Database of High-Yield FactsThe seventh edition of First Aid for the USMLE Step 2 CK contains a revised and expanded database of clinical material that student authors and faculty have identified as high yield for boards review. The facts are organized according to subject matter, whether medical specialty (e.g., Cardiovascular, Renal) or high-yield topic (e.g., Ethics) in medicine. Each subject is then divided into smaller subsections of related facts. Individual facts are generally presented in a logical approach, from basic definitions and epidemiology to History/Physical Exam, Diagnosis, and Treatment. Lists, mnemonics, and tables are used when helpful in forming key associations.
The content is mostly useful for reviewing material already learned. This section is not ideal for learning complex or highly conceptual material for the first time. Black-and-white images appear throughout the text. In some cases, reference is made to the “clinical image” section at the end of Section 2, which contains full-color glossy plates of histology and patient pathology by topic. At the end of Section 2, we also feature a Rapid Review chapter of key facts and classic associations to cram a day or two before the exam.
The Database of High-Yield Facts is not comprehensive. Use it to complement your core study material and not as your primary study source. The facts and notes have been condensed and edited to emphasize the essential material. Work with the material, add your own notes and mnemonics, and recognize that not all memory techniques work for all students.
We update Section 2 biannually to keep current with new trends in boards content as well as to expand our database of high-yield information. However, we must note that inevitably many other high-yield entries and topics are not yet included in our database.
We actively encourage medical students and faculty to submit entries and mnemonics so that we may enhance the database for future students. We also solicit recommendations of additional tools for study that may be useful in preparing for the examination, such as diagrams, charts, and computer-based tutorials (see How to Contribute, p. xv).
The entries in this section reflect student opinions of what is high yield. Owing to the diverse sources of material, no attempt has been made to trace or reference the origins of entries individually. We have regarded mnemonics as essentially in the public domain. All errors and omissions will be gladly corrected if brought to the attention of the authors, either through the publisher or directly by e-mail.
To evaluate patients for cardiac abnormalities, methodically assess the ECG for rate, rhythm, axis, intervals, waveforms, and chamber enlargement (see Figures 2.1-1 and 2.1-2).
The normal heart rate is 60–100 bpm. A rate < 60 bpm is bradycardia; > 100 bpm is tachycardia.
Look for sinus rhythm (P before every QRS and QRS after every P), irregular rhythms, junctional or ventricular rhythms (no P before a QRS), and ectopic beats.
Normal: An upright (positive) QRS in leads I and II (–30 degrees to +105 degrees).
Left-axis deviation: An upright QRS in lead I and a downward (negative) QRS in lead II (< –30 degrees).
Right-axis deviation: A downward QRS in lead I and an upright QRS in lead II (> +105 degrees).
II aVRI III aVL aVF V1 V2 V3 V4 V5 V6 F IGU R E 2.1 -1. Normal electrocardiogram from a healthy subject.
Quickly estimate heart rate by counting the number of large boxes subtended by two consecutive QRS complexes, as follows: 300-150-100-75-6050-30 bpm.
An upright QRS in leads I and ll—the “double thumbs-up” sign—signif es a normal axis.
Sinus rhythm is present with a heart rate of 75 bpm. The PR interval is 0.16 sec; the QRS interval (duration) is 0.08 sec; the QT interval is 0.36 sec; QTc is 0.40 sec; and the mean QRS axis is about +70 degrees. The precordial leads show normal R-wave progression with the transition zone (R wave = S wave) in lead V3. (Reproduced, with permission, from Fauci AS et al. Harrison’s Principles of Internal Medicine, 17th ed. New York: McGraw-Hill, 2008: Fig. 221-7.)
Time (s) 1.0 0.5 0 -0.5 0 0.2 0.4 0.6 P T S Q U Isoelectric line ST segment PR interval QT interval Potential (mV) Action potential QRS P T 0.2 0.4 0.6 Time (s)
SA node "pacemaker" inherent dominance with slow phase of upstroke AV node 100-msec delay atrioventricular delay
F IGU R E 2.1 -2.  Electrocardiogram measurements.WiLLiaM MaRRoW:W pattern of QRS in V1–V2 and M pattern of QRS in V3–V6 for LBBB
M pattern of QRS in V1–V2 and W pattern of QRS in V3–V6 for RBBB
Normal: PR interval between 120 and 200 msec and QRS < 100 msec.
Atrioventricular (AV) block: PR interval > 200 msec, or P with no QRS afterward.
Left bundle branch block (LBBB): QRS duration > 120 msec; no R wave in V1; wide, tall R waves in I, V5, and V6.
Right bundle branch block (RBBB): QRS duration > 120 msec; RSR′ complex (“rabbit ears”); qR or R morphology with a wide R wave in V1; QRS pattern with a wide S wave in I, V5, and V6.
Long QT syndrome: QTc > 440 msec. An underdiagnosed congenital disorder that predisposes to ventricular tachyarrhythmias.
Ischemia: Inverted T waves; poor R-wave progression in precordial leads; ST-segment changes (elevation or depression).
Transmural infarct: Significant Q waves (> 40 msec or more than one-third of the QRS amplitude). ST elevation; T-wave inversion; the presence of possible impending infarction based on plaque instability.
■Atrial hypertrophy: Right atrial abnormality if P-wave amplitude in lead II is < 2.5 mm; left atrial abnormality if P-wave width in lead II is > 120 msec, or if terminal negative defl ection in V1 is > 1 mm in amplitude and > 40 msec in duration.
F IGU R E 2.1 -3. Left ventricular hypertrophy.Shown are leads V1, V2, V5, and V6. S wave in V2 + R wave in V5 = 55 mm. Note ST changes and T-wave inversion in V5 and V6, suggesting strain. (Reproduced, with permission, from Gomella LG et al. Clinician’s Pocket Reference, 11th ed. New York: McGraw-Hill, 2006: Fig. 19-27.)
Left ventricular hypertrophy (LVH; see Figure 2.1-3):Cornell criteria: Amplitude of R in aVL + S in V3 > 28 mm in men or > 20 mm in women.
Sokolow-Lyon criteria: S in V1 + R in V5 or V6 > 35 mm.
Right ventricular hypertrophy (RVH): Right-axis deviation and an R wave in V1 > 7 mm.
Key exam findings that can narrow the differential include the following:
Jugular venous distention (JVD, > 7 cm above sternal angle): Suggests right heart failure, pulmonary hypertension, volume overload, tricuspid regurgitation, or pericardial disease.
Hepatojugular refl ux: Fluid overload; impaired right ventricular compliance.Kussmaul’s sign (↑ in JVP with inspiration): Right ventricular infarction, postoperative cardiac tamponade, tricuspid regurgitation, constrictive pericarditis.
Systolic murmurs:Aortic stenosis: Harsh systolic ejection murmur; radiation to carotids.Mitral regurgitation: Holosystolic murmur; radiation to axillae or to carotids.
Mitral valve prolapse: Midsystolic or late-systolic click.Flow murmur: Very common, and does not imply cardiac disease.
Diastolic murmurs: Always abnormal.Aortic regurgitation: Early decrescendo murmur.Mitral stenosis: Midto late, low-pitched murmur.Heart auscultation locations from the upper right sternal border, upper left sternal border, lower left sternal border, and apex: All (Aortic) People (Pulmonic) Try (Tricuspid) McDonald’s (Mitral).
Causes of CHF—Hypertension Endocrine Anemia Rheumatic heart disease Toxins Failure to take meds Arrhythmia Infection Lung (pulmonary
S3 gallop: Dilated cardiomyopathy (floppy ventricle), mitral valve disease; often normal in younger patients and in high-output states (e.g., pregnancy).
S4 gallop: Hypertension, diastolic dysfunction (stiff ventricle), aortic stenosis; often normal in younger patients and athletes.
Pulmonary: Left heart failure.Peripheral: Right heart failure and biventricular failure, peripheral venous disease, constrictive pericarditis, tricuspid regurgitation, hepatic disease, lymphedema; also nephrotic syndrome, hypoalbuminemia, and drugs.
Peripheral pulses: ■↑: Compensated aortic regurgitation, coarctation (arms > legs), patent ductus arteriosus. ■↓: Peripheral arterial disease.
Pulsus paradoxus (↓ systolic BP with inspiration): Pericardial tamponade; also asthma and COPD, tension pneumothorax, foreign body in airway.
Pulsus alternans (alternating weak and strong pulses): Cardiac tamponade, impaired left ventricular systolic function; poor prognosis.
Pulsus parvus et tardus (weak and delayed pulse): Aortic stenosis.
Table 2.1-1 outlines the etiologies, clinical presentation, and treatment of common bradyarrhythmias and conduction abnormalities.
Tables 2.1-2 and 2.1-3 outline the etiologies, clinical presentation, and treatment of common supraventricular and ventricular tachyarrhythmias.
Defined as a clinical syndrome caused by the inability of the heart to pump enough blood to maintain fluid and metabolic homeostasis. Risk factors include coronary artery disease (CAD), hypertension, cardiomyopathy, valvular heart disease, and diabetes. The American Heart Association/American College of Cardiology (AHA/ACC) guidelines classify heart failure according to clinical syndromes, but alternative classification systems include functional severity, left-sided vs. right-sided failure, and systolic vs. diastolic failure (see Tables 2.1-4 through 2.1-7).
T AB LE 2.1 -1. Bradyarrhythmias and Conduction AbnormalitiesSinus bradycardia Normal response to cardiovascular conditioning; can also result from sinus node dysfunction or from β-blocker or calcium channel blocker (CCB) excess. May be asymptomatic, but may also present with lightheadedness, syncope, chest pain, or hypotension. Ventricular rate < 60 bpm; normal P wave before every QRS complex. None necessary if asymptomatic; atropine may be used to ↑ heart rate; pacemaker placement is the def nitive treatment in severe cases. First-degree AV block Can occur in normal individuals; associated with ↑ vagal tone and with β-blocker or CCB use. Asymptomatic. PR interval > 200 msec. None necessary. Second-degree AV block (Mobitz I/ Wenckebach) Drug effects (digoxin, β-blockers, CCBs) or ↑ vagal tone; sinoatrial conduction disease; right coronary ischemia or infarction. Usually asymptomatic. Progressive PR lengthening until a dropped beat occurs; PR interval then resets. Stop the offending drug. Atropine or pacemaker placement as clinically indicated. Second-degree AV block (Mobitz II) Results from f brotic disease of the conduction system or from acute, subacute, or prior myocardial infarction (MI). Occasionally syncope; frequent progression to third-degree AV block. Unexpected dropped beat(s) without a change in PR interval. Pacemaker placement. Third-degree AV block (complete) No electrical communication between the atria and ventricles. Syncope, dizziness, acute heart failure, hypotension, cannon A waves. No relationship between P waves and QRS complexes. Pacemaker placement. Sick sinus syndrome (SSS)/ tachycardia-bradycardia syndrome A heterogeneous disorder consisting of abnormalities in supraventricular impulse generation and conduction that lead to intermittent supraventricular tachy-and bradyarrhythmias. 2° to tachycardia or bradycardia; may include syncope, palpitations, dyspnea, chest pain, TIA, and stroke. The most common indication for pacemaker placement.
T AB LE 2.1 -2.  Supraventricular TachyarrhythmiasAtrial Sinus tachycardia Normal physiologic response to fear, pain, and exercise. Can also be 2° to hyperthyroidism, volume contraction, infection, or pulmonary embolism. Palpitations, shortness of breath. Ventricular rate > 100 bpm; normal P waves before every QRS complex. Treat the underlying cause. Atrial f brillation (AF) Acute AF—   PIRATES: Pulmonary disease Ischemia Rheumatic heart disease Anemia/Atrial myxoma Thyrotoxicosis Ethanol Sepsis Chronic AF— hypertension, CHF. Often asymptomatic, but may present with shortness of breath, chest pain, or palpitations. Physical exam reveals irregularly irregular pulse. No discernible P waves, with variable and irregular QRS response.
Estimate risk of stroke using CHAD2 score.Anticoagulation if > 48 hours (to prevent CVA); rate control (CCBs, β-blockers, digoxin, amiodarone).
Initiate cardioversion only if new onset (< 48 hours) or if transesophageal echocardiogram (TEE) shows no left atrial clot, or after 3–6 weeks of warfarin treatment with satisfactory INR (2–3). See the Hematology chapter for more information on warfarin.
T AB LE 2.1 -2.  Supraventricular Tachyarrhythmias (continued)Atrioventricular Circular movement Palpitations, shortness of breath, angina, A retrograde P Same as that for reciprocating of an impulse syncope, lightheadedness. wave is often AVNRT. tachycardia between the AV
Atrial f utter Circular movement of electrical activity around the atrium at a rate of 300 times per minute. Usually asymptomatic, but can present with palpitations, syncope, and lightheadedness. Regular rhythm; “sawtooth” appearance of P waves can be seen. Atrial rate is usually 240–320 bpm with varying degrees of blockade. Anticoagulation and rate control. Cardiovert according to AF criteria. Multifocal atrial tachycardia Multiple atrial pacemakers or reentrant pathways; COPD, hypoxemia. May be asymptomatic. Three or more unique P-wave Treat the underlying morphologies; or β-blockers for rate > 100 bpm. rate control and disorder; verapamil suppression of atrial pacemakers (not very effective). AV junction reentry tachycardia depolarizes Atrioventricular A reentry circuit Palpitations, shortness of breath, angina, Rate 150–250 Carotid massage, nodal (AVNRT) in the AV node the atrium and ventricle nearly simultaneously. syncope, lightheadedness. bpm; P wave is often buried Valsalva, or adenosine in QRS or shortly after. arrhythmia. Cardiovert can stop the if hemodynamically unstable.
seen after a (AVRT) node and the normal QRS. atrium through a bypass tract. Seen in Wolff-Parkinson-White syndrome.
Paroxysmal atrial tachycardia Rapid ectopic pacemaker in the atrium (not sinus node). Palpitations, shortness of breath, angina, syncope, lightheadedness. Rate > 100 bpm; P wave with an unusual axis before each normal QRS. Adenosine can be used to unmask underlying atrial activity.
T AB LE 2.1 -3.  Ventricular TachyarrhythmiasPremature ventricular contraction (PVC) Ectopic beats arise from ventricular foci. Associated with hypoxia, electrolyte abnormalities, and hyperthyroidism. Usually asymptomatic, but may lead to palpitations. Early, wide QRS not preceded by a P wave. PVCs are usually followed by a compensatory pause. Treat the underlying cause. If symptomatic, give β-blockers or occasionally other antiarrhythmics. Ventricular tachycardia (VT) Can be associated with CAD, MI, and structural heart disease. Nonsustained VT is often asymptomatic; sustained ventricular tachycardia can lead to palpitations, hypotension, angina, and syncope. Can progress to VF. Three or more consecutive PVCs; wide QRS complexes in a regular rapid rhythm; AV dissociation. Cardioversion and antiarrhythmics (e.g., amiodarone, lidocaine, procainamide). Ventricular f brillation (VF) Associated with CAD and structural heart disease. Also associated with cardiac arrest (together with asystole). Syncope, absence of blood pressure, pulselessness. Totally erratic wide-complex tracing. Immediate electrical cardioversion and ACLS protocol. Torsades de pointes Associated with long QT syndrome, proarrhythmic response to medications, hypokalemia, and congenital deafness. Can present with sudden cardiac death; typically associated with palpitations, dizziness, and syncope. Polymorphous QRS; VT with rates between 150 and 250 bpm. Correct hypokalemia; withdraw offending drugs. Give magnesium initially and cardiovert if unstable.
T AB LE 2.1 -4.  AHA/ACC Classifcation and Treatment of CHF
A B Patients with structural heart disease (e.g., a history of MI, left ventricular systolic dysfunction, or valvular disease) who have never had symptoms of CHF. ACEIs, β-blockers. Patients with structural heart disease who have prior or current symptoms of CHF (shortness of breath, fatigue, ↓ exercise tolerance). Treatment includes diuretics, ACEIs, β-blockers, digitalis, and dietary salt restriction. Patients with marked symptoms of CHF at rest despite maximal medical therapy. C D
Patients who are at high risk of developing CHF because of the presence of risk factors, but who have no identifed structural or functional abnormalities and no signs or symptoms of CHF.
Manage treatable risk factors (hypertension, smoking, hyperlipidemia, obesity, exercise, alcohol abuse). ACEIs can be used in patients with atherosclerotic vascular disease, DM, or hypertension.
Treatment options include mechanical assist devices, heart transplantation, continuous IV inotropic drugs, and hospice care for end-stage patients.
T AB LE 2.1 -5.  NYHA Functional Classifcation of CHF
T AB LE 2.1 -6. Left-Sided vs. Right-Sided Heart Failure
TAB LE 2.1 -7. Comparison of Systolic and Diastolic Dysfunction
Patient age Often < 65 years of age. Often > 65 years of age. Comorbidities Dilated cardiomyopathy, valvular heart disease. Restrictive or hypertrophic cardiomyopathy; renal disease or hypertension. Physical exam Displaced PMI, S3 gallop. Sustained PMI, S4 gallop. CXR Pulmonary congestion, cardiomegaly. Pulmonary congestion, normal heart size. ECG/echocardiography Q waves, ↓ EF (< 40%). LVH, normal EF (> 55%).
The most common cause of right-sided heart failure is left-sided heart failure.
Diuretics are for symptomatic relief only and confer no mortality benef t.
Heart failure caused by systolic dysfunction is defined as a ↓ EF (< 50%) and left ventricular end-diastolic volumes. It is caused by inadequate left ventricular contractility or ↑ afterload. The heart compensates for low EF and preload through hypertrophy and ventricular dilation (Frank-Starling law), but the compensation ultimately fails, leading to ↑ myocardial work and worsening systolic function.
Exertional dyspnea is the earliest and most common presenting symptom and progresses to orthopnea, paroxysmal nocturnal dyspnea (PND), and finally rest dyspnea.
Chronic cough, fatigue, lower extremity edema, nocturia, Cheyne-Stokes respirations, and/or abdominal fullness may be seen.
Look for signs to distinguish leftfrom right-sided heart failure (see Table 2.1-6).
CHF is a clinical syndrome whose diagnosis is based on signs and symptoms.
Exam reveals parasternal lift, an elevated and sustained left ventricular impulse, and an S3/S4 gallop.
CXR: Cardiomegaly, cephalization of pulmonary vessels, pleural effusions, vascular plumpness, and prominent hila.
Echocardiogram: ↓ EF and ventricular dilation.Lab abnormalities: BNP > 500, ↑ creatinine, ↓ sodium.ECG: Usually nondiagnostic, but MI or AF may precipitate acute exacerbations.
Correct underlying causes such as arrhythmias, myocardial ischemia, and drugs (e.g., CCBs, antiarrhythmics, NSAIDs, alcohol, thyroid and valvular disease, high-output states).
Diurese aggressively with loop and thiazide diuretics (see Table 2.1-8).
TABLE 2.1-8.  Types of DiureticsLoop diuretics Furosemide, ethacrynic acid, bumetanide, torsemide Loop of Henle ↓ Na+/K+/2Cl− cotransporter; ↓ urine concentration; ↑ Ca2+ excretion. Ototoxicity, hypokalemia, hypocalcemia, dehydration, gout. Thiazide diuretics HCTZ, chlorothiazide, chlorthalidone Early distal tubule ↓ NaCl reabsorption leading to ↓ diluting capacity of nephron; ↓ Ca2+ excretion. Hypokalemic metabolic alkalosis, hyponatremia, hyperglycemia, hyperlipidemia, hyperuricemia, hypercalcemia. K+-sparing agents Spironolactone, triamterene, amiloride Cortical collecting tubule Spironolactone is an aldosterone receptor antagonist; triamterene and amiloride block Na+ channels. Hyperkalemia, gynecomastia, hirsutism, sexual dysfunction. Carbonic anhydrase inhibitors Acetazolamide Proximal convoluted tubule NaHCO3 diuresis ↓ total body NaHCO3. Hyperchloremic metabolic acidosis, neuropathy, NH3 toxicity, sulfa allergy. Osmotic agents Mannitol Proximal tubule Creates ↑ tubular f uid osmolarity, leading to ↑ urine f ow. Pulmonary edema, dehydration. Contraindicated in anuria and CHF.
Give ACEIs to all patients who can tolerate them. If a patient cannot tolerate ACEIs, consider an angiotensin receptor blocker (ARB). β-blockers should not be used during decompensated CHF but should be started once the patient is euvolemic.
Treat acute pulmonary congestion with LMNOP (see mnemonic).Control comorbid conditions (e.g., diabetes, hypertension, obesity) and limit dietary sodium and fl uid intake.
Long-term β-blockers and ACEIs/ARBs together help prevent neurohormonal remodeling of the heart. All of these agents ↓ mortality for New York Heart Association (NYHA) class II–IV patients.
Daily ASA and a statin are recommended for ischemic heart disease to prevent further ischemic events.
Chronic diuretic therapy (loop diuretics +/– thiazide) can prevent volume overload.
Low-dose spironolactone ↓ mortality risk when given with ACEIs and loop diuretics in patients with left ventricular systolic dysfunction and NYHA class III–IV heart failure. Monitor for hyperkalemia.
Anticoagulate patients with AF and those with a history of previous embolic events or a mobile left ventricular thrombus. Consider an implantable biventricular cardiac defibrillator (ICD) in patients with both an EF < 30% and CAD.
Loops lose calcium, whereas thiazides save it.■CHF that is unresponsive to maximal medical therapy may require a mechanical left ventricular assist device or cardiac transplantation.
Defined by ↓ ventricular compliance with normal systolic function. The ventricle has either impaired active relaxation (2° to ischemia, aging, and/or hypertrophy) or impaired passive filling (scarring from prior MI; restrictive cardiomyopathy). Left ventricular end-diastolic pressure ↑, cardiac output remains essentially normal, and EF is normal or ↑.
Associated with stable and unstable angina, shortness of breath, dyspnea on exertion, arrhythmias, MI, heart failure, and sudden death.
Diuretics are first-line therapy (see Table 2.1-8).Maintain rate and BP control via β-blockers, ACEIs, ARBs, or CCBs.
Digoxin is not useful in these patients.Myocardial disease; categorized as dilated, hypertrophic, or restrictive (see Table 2.1-9).
The most common cardiomyopathy. Left ventricular dilation and systolic dysfunction (low EF) must be present for diagnosis. Most cases are idiopathic, but known 2° causes include alcohol, myocarditis, postpartum status, drugs (doxorubicin, AZT, cocaine), endocrinopathies (thyroid dysfunction, acromegaly, pheochromocytoma), infection (coxsackievirus, HIV, Chagas’ disease, parasites), genetic factors, and nutritional disorders (wet beriberi). The two most common causes of 2° dilated cardiomyopathy are ischemia and long-standing hypertension.
T AB LE 2.1 -9. Differential Diagnosis of CardiomyopathiesMajor abnormality Impaired contractility Impaired relaxation Impaired elasticity Left ventricular cavity size (end diastole) ↑↑ ↓ ↑ Left ventricular cavity size (end systole) ↑↑ ↓↓ ↑ Ejection fraction (EF) ↓↓ ↑ or ↔ ↓ or ↔ Wall thickness ↓, variable ↑↑ ↑, variable
Often presents with gradual development of CHF symptoms.Exam often reveals displacement of the left venticular impulse, JVD, an S3/S4 gallop, or mitral/tricuspid regurgitation.
Echocardiography is diagnostic.ECG may show nonspecific ST-T changes, low-voltage QRS, sinus tachycardia, and ectopy. LBBB is common.
CXR shows an enlarged, balloon-like heart and pulmonary congestion.Address the underlying etiology (e.g., stop all alcohol use, treat endocrine disorders).
Treat symptoms of CHF with diuretics, and prevent disease progression with ACEIs, β-blockers, and aldosterone antagonists. Consider anticoagulation to ↓ thrombus risk only if AF or an intraventricular thrombus is present. Digoxin is a second-line agent; avoid CCBs in CHF.
Consider an ICD if EF < 35%.LVH results in impaired left ventricular relaxation and filling (diastolic dysfunction). Hypertrophy frequently involves the interventricular septum, leading to left ventricular outflow tract obstruction and impaired ejection of blood. The congenital form, hypertrophic obstructive cardiomyopathy (HOCM), is inherited as an autosomal-dominant trait in 50% of HOCM patients and is the most common cause of sudden death in young, healthy athletes in the United States. Other causes of marked hypertrophy include hypertension and aortic stenosis.
Patients may be asymptomatic but may also present with syncope, dyspnea, palpitations, angina, or sudden cardiac death.
Exam often reveals a sustained apical impulse, an S4 gallop, and a systolic ejection crescendo-decrescendo murmur that ↑ with ↓ preload (e.g., Valsalva maneuver, squatting).
Obstruction is worsened by ↑ myocardial contractility or by ↓ left ventricular filling (e.g., exercise, Valsalva maneuvers, vasodilators, dehydration).
Echocardiography is diagnostic and shows an asymmetrically thickened left ventricular wall and dynamic obstruction of blood fl ow.
ECG may show signs of LVH.CXR may reveal left atrial enlargement (LAE) 2° to mitral regurgitation.
■β-blockers are initial therapy for symptomatic relief; CCBs are second-line agents.
An S3 gallop signif es the end of rapid ventricular f lling in the setting of f uid overload and is associated with dilated cardiomyopathy.
Hypertrophic cardiomyopathy is the most common cause of sudden death in young, healthy athletes in the United States.
An S4 gallop signif es a stiff, noncompliant ventricle and associated with hypertrophic cardiomyopathy.
Surgical options for HOCM include dual-chamber pacing, partial excision or catheter ablation of the myocardial septum, ICD placement, and mitral valve replacement.
Patients should avoid intense athletic competition and training.Defined as ↓ elasticity of myocardium leading to impaired diastolic filling without significant systolic dysfunction (a normal or near-normal EF). It is caused by infiltrative disease (amyloidosis, sarcoidosis, hemochromatosis) or by scarring and fibrosis (2° to radiation or doxorubicin).
Signs and symptoms of left-sided and right-sided heart failure occur, but symptoms of right-sided heart failure (JVD, peripheral edema) often predominate.
CXR, MRI, and cardiac catheterization may be helpful, but echocardiography is key to diagnosis and reveals rapid early filling with a normal or near-normal EF.
Cardiac biopsy may reveal fibrosis or evidence of infiltration.ECG frequently shows LBBB.Therapeutic options are limited and generally are palliative only. Medical treatment includes cautious use of diuretics for fluid overload, vasodilators to ↓ filling pressure, and anticoagulation if not contraindicated.
Major risk factors for CAD include age, male gender, hyperlipidemia, DM, hypertension, obesity, a family history, and smoking.
The classic triad of angina consists of substernal chest pain that is provoked by exertion and relieved by rest or nitrates.
Clinical manifestations of CAD include stable and unstable angina, shortness of breath, dyspnea on exertion, arrhythmias, MI, heart failure, and sudden death. Risk factors include DM, a family history of premature CAD, smoking, dyslipidemia, abdominal obesity, hypertension, and male gender.
Substernal chest pain 2° to myocardial ischemia (O2 supply and demand mismatch). Prinzmetal’s (variant) angina mimics angina pectoris but is caused by vasospasm of coronary vessels. It classically affects young women at rest in the early morning and is associated with ST-segment elevation in the absence of cardiac enzyme elevation.
The classic triad consists of substernal chest pain or pressure (often described as a heaviness or pressure without pain), usually precipitated by stress or exertion and relieved by rest or nitrates.
Pain can radiate to the left arm, jaw, and neck and may be associated with shortness of breath, nausea/vomiting, diaphoresis, or lightheadedness.
Examination of patients experiencing stable angina is generally unremarkable. Look for carotid and peripheral bruits suggesting atherosclerosis and hypertension.
Rule out pulmonary, GI, or other cardiac causes of chest pain.
Angina may be diagnosed from the history alone, but significant ST-segment changes on exercise stress test with ECG monitoring is diagnostic of CAD.
Women and diabetics classically experience “silent” ischemic events and present “atypically”; for this reason, it is necessary to maintain a high index of suspicion in this patient population.
Treat acute symptoms with ASA, O2 and/or IV nitroglycerin, and IV morphine, and consider IV β-blockers. The efficacy of nondihydropyridine CCBs (diltiazem, verapamil) and ACEIs has also been validated.
Patients with a suspected MI must be admitted and monitored until acute MI is ruled out by serial cardiac enzymes.
Treat chronic symptoms with nitrates, ASA, and β-blockers; CCBs are second-line agents for symptomatic control only.
Initiate risk factor reduction (e.g., smoking, cholesterol, hypertension). Hormone replacement therapy is not protective in postmenopausal women.
Women, diabetics, the elderly, and post–heart transplant patients may have atypical, clinically silent MIs.
Only ASA and β-blockers have been shown to have a mortality benef t in the treatment of angina.
A spectrum of clinical syndromes caused by plaque disruption or vasospasm that leads to acute myocardial ischemia.
Unstable angina describes chest pain that is new onset, is accelerating (i.e., occurs with less exertion, lasts longer, or is less responsive to medications), or occurs at rest; it is distinguished from stable angina by patient history. It signals the presence of possible impending infarction based upon plaque instability. In contrast, NSTEMI indicates myocardial necrosis marked by elevations in troponin I, troponin T, or CK-MB.
Patients should be risk stratified according to the TIMI (Thrombolysis in Myocardial Infarction study) criteria to determine the likelihood of adverse cardiac events (see Table 2.1-10).
Unstable angina is not associated with elevated cardiac markers, but ST changes may be seen on ECG and are indicative of high-risk occlusions.
NSTEMI is diagnosed by serial cardiac enzymes and ECG.Acute treatment of symptoms is the same as that for stable angina. Clopidogrel, unfractionated heparin or enoxaparin, and glycoprotein IIb/IIIa inhibitors (e.g., eptifibatide, tirofiban, abciximab) should also be considered.
Patients with chest pain refractory to medical therapy, a TIMI score of ≥ 3, a troponin elevation, or ST changes > 1 mm should be given heparin and scheduled for angiography and possible revascularization (percutaneous coronary intervention [PCI] or CABG).
Think unstable angina if chest pain is new onset, accelerating, or occurring at rest.
T AB LE 2.1 -1 0. TIMI Risk Score for Unstable Angina/NSTEMI
DEATH, MI, OR URGENT CHARACTERISTICS POINT RISK SCORE DEATH OR MI REVASCULARIZATION
History Age ≥ 65 years 1 0/1 3 5 ≥ 3 CAD risk factors (family history, DM, tobacco, hypertension, ↑ cholesterol) 1 2 3 8 Known CAD (stenosis > 50%) 1 3 5 13 ASA use in past seven days 1 4 7 20 Presentation 5 12 26 Severe angina (≥ 2 episodes within 24 hours) 1 6/7 19 41 ST deviation ≥ 0.5 mm 1 + cardiac marker 1 Risk score—total points (0–7)
Higher-risk patients (risk score ≥ 3) beneft more from enoxaparin (vs. unfractionated heparin), glycoprotein IIb/IIIa inhibitors, and early angiography.
Defined as ST-segment elevations and cardiac enzyme release 2° to prolonged cardiac ischemia and necrosis.
Presents with acute-onset substernal chest pain, commonly described as a pressure or tightness that can radiate to the left arm, neck, or jaw.
Associated symptoms may include diaphoresis, shortness of breath, lightheadedness, anxiety, nausea/vomiting, and syncope.
Physical exam may reveal arrhythmias, new mitral regurgitation (ruptured papillary muscle), hypotension (cardiogenic shock), and evidence of new CHF (rales, peripheral edema, S3 gallop).
The best predictor of survival is left ventricular EF.■ECG: Look for ST-segment elevations or new LBBB. ST-segment depressions in leads V1–V2 can also be reciprocal change indicating infarction in the posterior wall.
Sequence of ECG changes: Peaked T waves → ST-segment elevation → Q waves → T-wave inversion → ST-segment normalization → T-wave normalization over several hours to days.
Cardiac enzymes: Troponin I is most sensitive; CK-MB is more specific. Both can take up to six hours to rise after the onset of chest pain (see Figure 2.1-4).
ST-segment abnormalities:ST-segment elevation in leads II, III, and aVF is consistent with an inferior MI involving the RCA/PDA and LCA (see Figure 2.1-5).
ST-segment elevation in leads V1–V4 usually indicates an anterior MI involving the LAD and diagonal branches (see Figure 2.1-6).
ST-segment elevation in leads I, aVL, and V5–V6 points to a lateral MI involving the LCA.
ST-segment depression in leads V1–V2 can be “reciprocal change” indicative of an acute infarct in the posterior wall.
Six key medications should be considered: ASA, β-blockers, clopidogrel, morphine, nitrates, and O2.
If the patient is in heart failure or in cardiogenic shock, do not give β-blockers; instead, give ACEIs, provided that the patient is not hypotensive.
Emergent angiography and PCI should be performed; if possible, the patient should undergo PCI for the lesion thought to be responsible for STEMI.
Common causes of chest pain include GERD, angina, esophageal pain, musculoskeletal disorders (costochondritis, trauma), and pneumonia.
Other causes of ST-segment elevation (often diffuse across multiple leads) include acute pericarditis, LVH, LBBB, and a normal variant (e.g., “early repolarization”).
F IGU R E 2.1 -4. Typical pattern of serum marker elevation after an acute MI.
CK-MB = creatine kinase, MB isoenzyme; cTnI = cardiac troponin I; cTnT = cardiac troponin T; LD1 = lactate dehydrogenase isoenzyme 1; MLC = myosin light chain. (Reproduced, with permission, from Tintinalli JE et al. Tintinalli’s Emergency Medicine: A Comprehensive Study Guide, 6th ed. New York: McGraw-Hill, 2004: Fig. 49-1.)
FIGURE 2.1-5. Inferior wall MI.In this patient with acute chest pain, the ECG demonstrated acute ST-segment elevation in leads II, III, and aVF with reciprocal ST-segment depression and T-wave flattening in leads I, aVL, and V4–V6. (Reproduced, with permission, from Stobo J et al. The Principles and Practice of Medicine, 23rd ed. Stamford, CT: Appleton & Lange, 1996: 20.)
FIGURE 2.1-6. Anterior wall MI.This patient presented with acute chest pain. The ECG showed acute ST-segment elevation in leads aVL and V1–V6, and hyperacute T waves. (Reproduced, with permission, from Stobo J et al. The Principles and Practice of Medicine, 23rd ed. Stamford, CT: Appleton & Lange, 1996: 19.)
If the patient presents within three hours, PCI cannot be performed within 90 minutes, and there are no contraindications to thrombolysis (e.g., a history of hemorrhagic stroke or recent ischemic stroke, severe heart failure, or cardiogenic shock), thrombolysis with tPA, reteplase, or streptokinase should be performed instead of PCI.
In the setting of three-vessel disease, left main coronary artery disease, discrete lesions not amenable to PCI, or diffuse disease with good target vessels, PCI should be attempted immediately for the lesion thought to be responsible for STEMI; the patient is a candidate for CABG afterward.
Long-term treatment includes ASA, ACEIs, β-blockers, high-dose statins, and clopidogrel (if PCI was performed). Modify risk factors with dietary changes, exercise, and tobacco cessation.
Arrhythmia is the most common complication and cause of death following acute MI; lethal arrhythmia is the most common cause of death following acute MI.
Less common complications include reinfarction, left ventricular wall rupture, VSD, pericarditis, papillary muscle rupture (with mitral regurgitation), left ventricular aneurysm or pseudoaneurysm, and mural thrombi.
Dressler’s syndrome, an autoimmune process occurring 2–10 weeks post-MI, presents with fever, pericarditis, pleural effusion, leukocytosis, and ↑ ESR.
A timeline of common post-MI complications is as follows:First day: Heart failure (treat with nitroglycerin and diuretics).2–4 days: Arrhythmia, pericarditis (diffuse ST elevation with PR depression).
5–10 days: Left ventricular wall rupture (acute pericardial tamponade causing electrical alternans, pulseless electrical activity), papillary muscle rupture (severe mitral regurgitation).
Weeks to months: Ventricular aneurysm (CHF, arrhythmia, persistent ST elevation, mitral regurgitation, thrombus formation).
Unable to perform PCI (diffuse disease)Stenosis of left main coronary artery Triple-vessel diseaseTotal cholesterol > 200 mg/dL, LDL > 130 mg/dL, triglycerides > 500 mg/ dL, and HDL < 40 mg/dL are risk factors for CAD. Etiologies include obesity, DM, alcoholism, hypothyroidism, nephrotic syndrome, hepatic disease, Cushing’s disease, OCP use, high-dose diuretic use, and familial hypercholesterolemia.
Most patients have no specific signs or symptoms.Patients with extremely high triglyceride or LDL levels may have xanthomas (eruptive nodules in the skin over the tendons), xanthelasmas (yellow fatty deposits in the skin around the eyes), and lipemia retinalis (creamy appearance of retinal vessels).
Dyslipidemia: ■Conduct a fasting lipid profile for patients > 20 years of age and repeat ev ery five years or sooner if elevated.
■Total serum cholesterol > 200 mg/dL on two different occasions is diagnostic of hypercholesterolemia.
T AB LE 2.1 -1 1. ATP III Guidelines for Risk Stratifcation of Hypercholesterolemia
CAD or CAD risk equivalentsa < 100 mg/dL (or < 70) > 100 mg/dL > 130 mg/dL 2+ risk factorsb < 130 mg/dL > 130 mg/dL > 160 mg/dL 0–1 risk factorb < 160 mg/dL > 160 mg/dL > 190 mg/dL a CAD risk equivalents = symptomatic carotid artery disease, peripheral arterial disease, abdominal aortic aneurysm, diabetes. b Risk factors = cigarette smoking, hypertension, low HDL (< 40 mg/dL), a family history of premature CAD, and age (men > 45 years; women > 55 years). An HDL > 60 mg/dL counts as a “negative” risk factor and removes one risk factor from the total score.
■LDL > 130 mg/dL or HDL < 40 mg/dL, even if total serum cholesterol is < 200 mg/dL, is diagnostic of dyslipidemia.
Based on risk stratification (see Table 2.1-11). Risk factors include diabetes (considered a CAD risk equivalent), smoking, hypertension, HDL < 40 mg/dL, age > 45 (males), age > 55 (females), and early CAD in first-degree relatives (males < 55 and females < 65).
The first intervention should be a 12-week trial of diet and exercise in a patient with no known atherosclerotic vascular disease. Commonly used lipid-lowering agents are listed in Table 2.1-12.
The BP goal in uncomplicated hypertension is < 140/< 90. For diabetics or patients with renal disease, the goal is < 130/< 80.
Defined as a systolic BP > 140 mmHg and/or a diastolic BP > 90 based on three measurements separated in time (see Table 2.1-13). Classified as 1° or 2°.
Hypertension with no identifiable cause. Represents 95% of cases of hypertension. Risk factors include a family history of hypertension or heart disease, a high-sodium diet, smoking, obesity, race (blacks > whites), and advanced age.
Hypertension is asymptomatic until complications develop.Patients should be evaluated for end-organ damage to the brain (stroke, dementia), eye (cotton-wool exudates, hemorrhage), heart (LVH), and kidney (proteinuria, chronic kidney disease). Renal bruits may signify renal artery stenosis as the cause of hypertension.
Conduct cardiovascular, neurologic, ophthalmologic, and abdominal exams.Obtain a UA, BUN/creatinine, CBC, and electrolytes to assess the extent of end-organ damage.
T AB LE 2.1 -1 2.  Lipid-Lowering AgentsHMG-CoA reductase inhibitors (statins) Atorvastatin, simvastatin, lovastatin, pravastatin, rosuvastatin Inhibit the rate-limiting step in cholesterol synthesis. ↓ LDL, ↓ triglycerides ↑ LFTs, myositis, warfarin potentiation. Lipoprotein lipase stimulators (f brates) Gemf brozil ↑ lipoprotein lipase, leading to ↑ VLDL and triglyceride catabolism. ↓ triglycerides, ↑ HDL GI upset, cholelithiasis, myositis, ↑ LFTs. Cholesterol absorption inhibitors Ezetimibe (Zetia) ↓ absorption of cholesterol at the small intestine brush border. ↓ LDL Diarrhea, abdominal pain. Can cause angioedema. Niacin Niaspan ↓ fatty acid release from adipose tissue; ↓ hepatic synthesis of LDL. ↑ HDL, ↓ LDL Skin fushing (can be prevented with ASA), paresthesias, pruritus, GI upset, ↑ LFTs. Bile acid resins Cholestyramine, colestipol, colesevelam Bind intestinal bile acids lead to ↓ bile acid stores and ↑ catabolism of LDL from plasma. ↓ LDL Constipation, GI upset, LFT abnormalities, myalgias. Can ↓ absorption of other drugs from the small intestine.
T AB LE 2.1 -1 3.  JNC-7 Classifcation and Management of Hypertension
Normal < 120 and < 80 Encourage Prehypertension 120–139 or 80–89 Yes No antihypertensive drug indicated. Stage 1 hypertension 140–159 or 90–99 Yes Thiazide diuretics for most patients; ACEIs, ARBs, β-blockers, CCBs, or a combination may be considered. Stage 2 hypertension ≥ 160 or ≥ 100 Yes Two-drug combination for most patients (usually a thiazide diuretic plus an ACEI, an ARB, a β-blocker, or a CCB).
Hypertensive crises are diagnosed on the basis of the extent of end-organ damage, not BP measurement.
Rule out 2° causes of hypertension, particularly in younger patients.
Begin with lifestyle modifications (e.g., weight loss, smoking cessation, salt reduction). Weight loss is the single most effective lifestyle modification. The BP goal in otherwise healthy patients is < 140/< 90. The goal in diabetics or patients with renal disease with proteinuria is < 130/< 80.
Diuretics (which are inexpensive and particularly effective in African-Americans), ACEIs, and β-blockers (which are beneficial for patients with CAD) have been shown to ↓ mortality in uncomplicated hypertension. They are first-line agents unless a comorbid condition requires another medication (see Table 2.1-14).
Periodically test for end-organ complications, including renal (BUN, creatinine, urine protein-to-creatinine ratio) and cardiac (ECG evidence of hypertrophy) complications.
Hypertension 2° to an identifiable organic cause. See Table 2.1-15 for the diagnosis and treatment of common causes.
A spectrum of clinical presentations in which elevated BPs lead to end-organ damage.
Presents with end-organ damage revealed by chest pain (ischemia or MI), back pain (aortic dissection), or changes in mental status (hypertensive encephalopathy).
Hypertensive urgency: Diagnosed on the basis of an elevated BP with only mild to moderate symptoms (headache, chest pain, syncope) and without end-organ damage.
Hypertensive emergency: Diagnosed by a significantly elevated BP with signs or symptoms of impending end-organ damage such as ARF, intracra-
T AB LE 2.1 -1 4. Treatment of 1° Hypertension with Comorbid Conditions
Heart failure Thiazide diuretics, β-blockers, ACEIs, ARBs, aldosterone antagonists. Post-MI β-blockers, ACEIs, aldosterone antagonists. High CVD risk Thiazide diuretics, β-blockers, ACEIs, CCBs. Diabetes Thiazide diuretics, β-blockers, ACEIs, ARBs, CCBs. Chronic kidney disease ACEIs, ARBs. Recurrent stroke prevention Thiazide diuretics, ACEIs.
T AB LE 2.1 -1 5. Common Causes of 2° Hypertension 1° renal disease Often unilateral renal parenchymal disease. Treat with ACEIs, which slow the progression of renal disease. Renal artery stenosis Especially common in patients < 25 and > 50 years of age with recent-onset hypertension. Etiologies include f bromuscular dysplasia (usually in younger patients) and atherosclerosis (usually in older patients). Diagnose with MRA or renal artery Doppler ultrasound. May be treated with angioplasty or stenting. Consider ACEIs as adjunctive or temporary therapy in unilateral disease. (In bilateral disease, ACEIs can accelerate kidney failure by preferential vasodilation of the efferent arteriole.) Open surgery is a second option if angioplasty is not effective or feasible. OCP use Common in women > 35 years of age, obese women, and those with long-standing use. Discontinue OCPs (effect may be delayed). Pheochromocytoma An adrenal gland tumor that secretes epinephrine and norepinephrine, leading to episodic headache, sweating, and tachycardia. Diagnose with urinary metanephrines and catecholamine levels or plasma metanephrine. Surgical removal of tumor after treatment with both α-blockers and β-blockers. Conn’s syndrome (hyperaldosteronism) Most often 2° to an aldosterone-producing adrenal adenoma. Causes the triad of hypertension, unexplained hypokalemia, and metabolic alkalosis. Surgical removal of tumor. Cushing’s syndrome Due to an ACTH-producing pituitary tumor, an ectopic ACTH-secreting tumor, or cortisol secretion by an adrenal adenoma or carcinoma. (See the Endocrinology chapter for more details.) Surgical removal of tumor. Coarctation of the aorta See the Pediatrics chapter. Surgical repair.
nial hemorrhage, papilledema, or ECG changes suggestive of ischemia or pulmonary edema.
■Malignant hypertension: Diagnosed on the basis of progressive renal failure and/or encephalopathy with papilledema.
Hypertensive urgencies: Can be treated with oral antihypertensives (e.g., β-blockers, clonidine, ACEIs) with the goal of gradually lowering BP over 24–48 hours (see Tables 2.1-16 and 2.1-17).
Hypertensive emergencies: Treat with IV medications (labetalol, nitroprusside, nicardipine) with the goal of lowering mean arterial pressure by no more than 25% over the first two hours to prevent cerebral hypoperfusion or coronary insufficiency.
T AB LE 2.1 -1 6. Major Classes of Antihypertensive Agents
Diuretics Thiazide, loop, K+ sparing ↓ extracellular fuid volume and thereby ↓ vascular resistance. Hypokalemia (not with K+ sparing), hyperglycemia, hyperlipidemia, hyperuricemia, azotemia. β-adrenergic blockers (β-blockers) Propranolol, metoprolol, nadolol, atenolol, timolol, carvedilol, labetalol ↓ cardiac contractility and renin release. Bronchospasm (in severe active asthma), bradycardia, CHF exacerbation, impotence, fatigue, depression. Centrally acting adrenergic agonists Methyldopa, clonidine Inhibit the sympathetic nervous system via central α2-adrenergic receptors. Somnolence, orthostatic hypotension, impotence, rebound hypertension. α1-adrenergic blockers Prazosin, terazosin, phenoxybenzamine Cause vasodilation by blocking actions of norepinephrine on vascular smooth muscle. Orthostatic hypotension. CCBs Dihydropyridines (nifedipine, felodipine, amlodipine), nondihydropyridines (diltiazem, verapamil) ↓ smooth muscle tone and cause vasodilation; may also ↓ cardiac output. Dihydropyridines: Headache, fushing, peripheral edema. Nondihydropyridines: ↓ contractility. Vasodilators Hydralazine, minoxidil ↓ peripheral resistance by dilating arteries/arterioles. Hydralazine: Headache, lupus-like syndrome. Minoxidil: Orthostasis, hirsutism. Captopril, enalapril, fosinopril, benazepril, lisinopril Block aldosterone formation, reducing peripheral resistance and salt/water retention. Cough, rashes, leukopenia, hyperkalemia. Losartan, valsartan, irbesartan Block aldosterone effects, reducing peripheral resistance and salt/water retention. Rashes, leukopenia, and hyperkalemia but no cough. ACEIs ARBs
Results from acute or chronic pericardial insults; may lead to pericardial effusion.
Inflammation of the pericardial sac. Can compromise cardiac output via tamponade or constrictive pericarditis. Most commonly idiopathic, although known etiologies include viral infection, TB, SLE, uremia, drugs, radiation, and neoplasms. May also occur after MI (either within days after MI or as a delayed phenomenon, i.e., Dressler’s syndrome) or open heart surgery.
TABLE 2.1-17. Antihypertensive Agents for Specifc Patient PopulationsDiabetes with proteinuria ACEIs or ARBs. CHF β-blockers, ACEIs or ARBs, diuretics (including spironolactone). Isolated systolic hypertension Diuretics are preferred; long-acting dihydropyridines. MI β-blockers without intrinsic sympathomimetic activity; ACEIs. Osteoporosis Thiazide diuretics. BPH α1-adrenergic blockers.
May present with pleuritic chest pain, dyspnea, cough, and fever.
Chest pain tends to worsen in the supine position and with inspiration.
Exam may reveal a pericardial friction rub, elevated JVP, and pulsus paradoxus (a ↓ in systolic BP > 10 mmHg on inspiration).
CXR, ECG, and echocardiogram to rule out MI and pneumonia.
ECG changes include diffuse ST-segment elevation and PR-segment depressions followed by T-wave inversions (see Figure 2.1-7).
Pericardial thickening or effusion may be evident on echocardiography.Address the underlying cause (e.g., corticosteroids/immunosuppressants for SLE, dialysis for uremia) or symptoms (e.g., ASA for post-MI pericarditis, ASA/NSAIDs for viral pericarditis). Avoid corticosteroids within a few days after MI, as they can predispose to ventricular wall rupture.
Pericardial effusions without symptoms can be followed, but evidence of tamponade requires pericardiocentesis, with continuous drainage as needed.
Excess fluid in the pericardial sac, leading to compromised ventricular filling and ↓ cardiac output. The condition is more closely related to the rate of fl uid formation than to the size of the effusion. Risk factors include pericarditis, malignancy, SLE, TB, and trauma (commonly stab wounds medial to the left nipple).
■Presents with fatigue, dyspnea, anxiety, tachycardia, and tachypnea that can rapidly progress to shock and death.
Causes of pericarditis—Beck’s triad can diagnose acute cardiac tamponade:F IGU R E 2.1 -7.  Acute pericarditis.Diffuse ST-segment elevations in multiple leads not consistent with any discrete coronary vas cular territory and PR-segment depressions. (Reproduced, with permission, from Gomella LG et al. Clinician’s Pocket Reference, 11th ed. New York: McGraw-Hill, 2006: Fig. 19-34.) ■Examination of a patient with acute tamponade may reveal Beck’s triad (hypotension, distant heart sounds, and JVD), a narrow pulse pressure, pulsus paradoxus, and Kussmaul’s sign (JVD on inspiration).
Echocardiogram shows right atrial and right ventricular diastolic collapse. CXR shows an enlarged, globular heart.
If present on ECG, electrical alternans is diagnostic.Aggressive volume expansion with IV fl uids.Urgent pericardiocentesis (aspirate will be nonclotting blood).Decompensation may warrant balloon pericardiotomy and pericardial window.Until recently, rheumatic fever (which affects the mitral valve more often than the aortic valve) was the most common cause of valvular heart disease in U.S. adults; the leading cause is now mechanical degeneration. Subtypes are listed in Table 2.1-18 along with their etiologies, presentation, diagnosis, and treatment.
Aortic aneurysms are most commonly associated with atherosclerosis. Most are abdominal, and > 90% originate below the renal arteries.
Usually asymptomatic and discovered incidentally on exam or radiologic study.
Risk factors include hypertension, high cholesterol, other vascular disease, a family history, smoking, gender (males > females), and age.
Exam demonstrates a pulsatile abdominal mass or abdominal bruits.Ruptured aneurysm leads to hypotension and severe, tearing abdominal pain that radiates to the back.
Abdominal ultrasound for diagnosis or to follow an aneurysm over time. CT may be useful to determine the precise anatomy.
In asymptomatic patients, monitoring is appropriate for lesions < 5 cm.
Surgical repair is indicated if the lesion is > 5.5 cm (abdominal), > 6 cm (thoracic), or smaller but rapidly enlarging.
Emergent surgery for symptomatic or ruptured aneurysms.A transverse tear in the intima of a vessel that results in blood entering the media, creating a false lumen and leading to a hematoma that propagates longitudinally. Most commonly 2° to hypertension. The most common sites of origin are above the aortic valve and distal to the left subclavian artery. Most often occurs at 40–60 years of age, with a greater frequency in males than in females.
Aortic aneurysm is most often associated with atherosclerosis, while aortic dissection is commonly linked to hypertension.
TABLE 2.1-18. Types of Valvular Heart DiseaseAortic stenosis Most often seen in the elderly. Unicuspid and bicuspid valves can lead to symptoms in childhood and adolescence. May be asymptomatic for years despite signif cant stenosis. Once symptomatic, usually progresses from angina to syncope to CHF to death within f ve years. Cx (also indications for valve replacements): ACS—Angina, CHF, Syncope. PE: Pulsus parvus et tardus (weak, delated carotid upstroke) and a single or paradoxically split S2 sound; systolic murmur radiating to the carotids. Dx: Echocardiography. Valve replacement. Balloon valvuloplasty can bridge patients to aortic valve replacement but is not def nitive treatment. Aortic regurgitation Acute: Infective endocarditis, aortic dissection, chest trauma. Chronic: Valve malformations, rheumatic fever, connective tissue disorders. Causes: CREAM—  Congenital Rheumatic damage, Endocarditis, Aortic dissection/ Aortic root dilatation, Marfan’s syndrome. Acute: Rapid onset of pulmonary congestion, cardiogenic shock, and severe dyspnea. Chronic: Slowly progressive onset of dyspnea on exertion, orthopnea, and PND. PE: Blowing diastolic murmur at the left sternal border, mid-diastolic rumble (Austin Flint murmur), and midsystolic apical murmur. Widened pulse pressure causes de Musset’s sign (head bob with heartbeat), Corrigan’s sign (water-hammer pulse), and Duroziez’s sign (femoral bruit). Dx: Echocardiography. Vasodilator therapy (dihydropyridines or ACEIs) for isolated aortic regurgitation until symptoms become severe enough to warrant valve replacement. Mitral valve stenosis The most common etiology continues to be rheumatic fever. Symptoms range from dyspnea, orthopnea, and PND to infective endocarditis and arrhythmias. PE: Opening snap and mid-diastolic murmur at apex; pulmonary edema. Dx: Echocardiography. Antiarrhythmics (digoxin, β-blockers) for symptomatic relief; mitral balloon valvotomy and valve replacement are effective for severe cases. Mitral valve regurgitation Primarily 2° to rheumatic fever or chordae tendineae rupture after MI. Patients present with dyspnea, orthopnea, and fatigue. PE: Holosystolic murmur radiating to axillae. Dx: Echocardiography will demonstrate regurgitant f ow; angiography can assess the severity of disease. Antiarrhythmics if necessary (AF is common with LAE; nitrates and diuretics to ↓ preload).
Sudden tearing/ripping pain in the anterior chest in ascending dissection; interscapular back pain in descending dissection.
The patient is typically hypertensive. If a patient is hypotensive, consider pericardial tamponade, hypovolemia from blood loss, or acute MI from involvement of the coronary arteries.
Asymmetric pulses and BP measurements are indicative of aortic dissection.
Signs of pericarditis or pericardial tamponade may be seen; a murmur of aortic regurgitation may be heard if the aortic valve is involved with a proximal dissection. Neurologic deficits may be seen if the aortic arch or spinal arteries are involved.
ECG, CXR (shows widening of the mediastinum, cardiomegaly, or new left pleural effusion). CT angiography is the gold standard of imaging.
TEE can provide details of the thoracic aorta, the proximal coronary arteries, the origins of arch vessels, the presence of a pericardial effusion, and aortic valve integrity.
There are two systems of classification for aortic dissection:DeBakey system: Classifies dissections as involving both the ascending and descending aorta (type I), confined to the ascending aorta (type II), or confined to the descending aorta (type III).
Stanford system: Classifies dissection of the ascending aorta as type A and all others as type B.
Monitor and medically manage BP and heart rate as necessary.
Do not give thrombolytics.If the dissection involves the ascending aorta, it is a surgical emergency; descending dissections can often be managed with BP and heart rate control.
Ascending aortic dissections are surgical emergencies, but descending dissections can often be treated medically.
Clot formation in the large veins of the extremities or pelvis. The classic Virchow’s triad of risk factors includes venous stasis (e.g., from plane fl ights, bed rest, or incompetent venous valves in the lower extremities), endothelial trauma (injury to the lower extremities), and hypercoagulable states (e.g., malignancy, pregnancy, OCP use).
Presents with unilateral lower extremity pain, erythema, and swelling.Homans’ sign is calf tenderness with passive foot dorsiflexion (poor sensitivity and specificity for DVT).
Doppler ultrasound; spiral CT or V/Q scan may be used to evaluate for pulmonary embolism (see Figure 2.1-8).
Virchow’s triad: hemostasis, trauma (endothelial damage), hypercoagulability.A negative D-dimer test can be used to rule out the possibility of pulmonary embolism in low-risk patients.
F IGU R E 2.1 -8. Algorithm for diagnostic imaging of DVT and PE.
(Reproduced, with permission, from Fauci AS et al. Harrison’s Principles of Internal Medicine, 17th ed. New York: McGraw-Hill, 2008: Fig. 256-1.)
Initial anticoagulation with IV unfractionated heparin or SQ lowmolecular-weight heparin followed by PO warfarin for a total of 3–6 months.
Consider an IVC filter in patients with contraindications to anticoagulation.
Hospitalized patients should receive DVT prophylaxis consisting of exercise as tolerated, anti-thromboembolic stockings, and SQ unfractionated heparin or low-molecular-weight heparin.
Occlusion of the blood supply to the extremities by atherosclerotic plaque. The lower extremities are most commonly affected. Clinical manifestations depend on the vessels involved, the extent and rate of obstruction, and the presence of collateral blood fl ow.
Presents with intermittent claudication (reproducible leg pain that occurs with walking and is always relieved with rest). As the disease progresses, pain occurs at rest and affects the distal extremities. Dorsal foot ulcerations may develop 2° to poor perfusion. A painful, cold, numb foot is characteristic of critical limb ischemia.
Aortoiliac disease: Associated with Leriche’s syndrome (buttock claudication, ↓ femoral pulses, male impotence).
Femoropopliteal disease: Calf claudication; pulses below the femoral artery are absent.
Acute ischemia: Most often caused by embolization from the heart; acute occlusions commonly occur at bifurcations distal to the last palpable pulse. May also be 2° to cholesterol atheroembolism (“blue toe syndrome”).
■Severe chronic ischemia: Lack of blood perfusion leads to muscle atrophy, pallor, cyanosis, hair loss, and gangrene/necrosis.
Carefully palpate pulses and auscultate for bruits.Measurement of ankle and brachial systolic BP (ankle-brachial index, or ABI) can provide objective evidence of atherosclerosis (rest pain usually occurs with an ABI < 0.4). A high ABI can indicate calcification of the arteries.
Doppler ultrasound helps identify stenosis and occlusion. Doppler ankle systolic pressure readings that are > 90% of brachial readings are normal.
Arteriography and digital subtraction angiography are necessary for surgical evaluation.
Control underlying conditions (e.g., DM, other cardiac risk factors); eliminate tobacco and institute careful hygiene and foot care. Exercise helps develop collateral circulation.
ASA, cilostazol, and thromboxane inhibitors may improve symptoms; anticoagulants may prevent clot formation.
Angioplasty and stenting have a variable success rate that is dependent on the area of occlusion.
Surgery (arterial bypass) or amputation can be employed when conservation treatment fails.
Avoid β-blockers in peripheral arterial disease 2° to B2-mediated peripheral vasoconstriction.
Disruption of the lymphatic circulation that results in peripheral edema and chronic infection of the extremities. Often a complication of surgery involving lymph node dissection. In underdeveloped countries, parasitic infection can lead to lymphatic obstruction, resulting in edema. Congenital malformations of the lymphatic system, such as Milroy’s disease, can present with lymphedema in childhood.
Postmastectomy patients present with unexplained swelling of the upper extremity.
Immigrants present with progressive swelling of the lower extremities bilaterally with no cardiac abnormalities (i.e., filariasis).
Children present with progressive, bilateral swelling of the extremities.Diagnosis is clinical. Rule out other causes of edema, such as cardiac and metabolic disorders.
Directed at symptom management, as no curative treatment exists. Agents such as diuretics are ineffective and relatively contraindicated.
Exercise, massage therapy, and pressure garments to mobilize and limit fluid accumulation may be of help.
■Maintain vigilance for cellulitis with prompt gram-antibiotic coverage for infection.
Cardiac syncope is associated with one-year sudden cardiac death rates of up to 40%.
A sudden, temporary loss of consciousness and postural tone 2° to cerebral hypoperfusion. Etiologies are either cardiac or noncardiac:
Cardiac: Valvular lesions, arrhythmias, pulmonary embolism, cardiac tamponade, aortic dissection.
Noncardiac: Orthostatic/hypovolemic hypotension, neurologic (TIA, stroke), metabolic abnormalities, neurocardiogenic syndromes (e.g., vasovagal/micturition syncope), psychiatric.
Rule out many potential etiologies. Triggers, prodromal symptoms, and associated symptoms should be investigated.
Cardiac causes of syncope are typically associated with very brief or absent prodromal symptoms, a history of exertion, lack of association with changes in position, and/or a history of cardiac disease.
Depending on the suspected etiology, Holter monitors or event recorders (arrhythmias), echocardiograms (structural abnormalities), and stress tests (ischemia) can be useful diagnostic tools.
Tailored to the etiology.Layers of the Skin 75 Common Terminology 75 Allergic and Immune-Mediated Disorders 75
The skin consists of three layers: the epidermis, the dermis, and subcutaneous tissue (see Figure 2.2-1). Table 2.2-1 describes pertinent components of the epidermis, the dermis, and the various skin appendages.
Table 2.2-2 outlines terms frequently used to describe common manifestations of dermatologic disease.
Table 2.2-3 outlines the types and mechanisms of hypersensitivity reactions. Descriptions of common allergic and immune-mediated disorders follow.
A relapsing inflammatory skin disorder that is common in infancy and presents differently in different age groups. It is characterized by pruritus that leads to lichenification (see Figure 2.2-2).
Eczema is the “itch that rashes.”Atopic dermatitis is commonly associated with asthma and allergic rhinitis.
Patients are at ↑ risk of 2° bacterial and viral infection.
Triggers include climate, food, contact with allergens or physical or chemical irritants, and emotional factors.
FIGURE 2.2-1. Layers of the skin.(Adapted, with permission, from Hardman JG et al. Goodman and Gilman’s The Pharmacological Basis of Therapeutics, 10th ed. New York: McGraw-Hill, 2001: 1805.)
TABLE 2.2-1. Components of Skin LayersKeratinocytes Melanocytes Langerhans cells Merkel cells Fibroblasts (synthesize collagen, elastin, and ground substance) Mast cells Monocytes/macrophages Vessels/lymphatics Nerves Smooth muscle
Nails (nail matrix, nail fold, nail plate, nail bed)Hair complex (hair follicles, sebaceous glands, apocrine glands)T AB LE 2.2-2. Common Terms Used to Describe Skin Lesions
Macule A fat lesion that differs in color from surrounding skin (< 1 cm in diameter). Papule An elevated solid lesion that is generally small (< 5 mm in diameter). Patch A small, circumscribed area differing in color from the surrounding surface (> 1 cm in diameter). Plaque An elevated solid lesion (> 5 mm in diameter). Cyst An epithelial-lined sac containing fuid or semisolid material. Vesicle A f uid-flled, very small (< 0.5-mm), elevated lesion. Bulla A large vesicle (> 5 mm). Wheal (or hive) An area of localized edema that follows vascular leakage and usually disappears within hours. Erosion A circumscribed, superfcial depression resulting from the loss of some or all of the epidermis. Ulcer A deeper depression resulting from destruction of the epidermis and upper dermis. Scale Abnormal shedding or accumulation of stratum corneum in f akes. Crust A hardened deposit of dried serum, blood, or purulent exudates. Lichenifcation Thickening of the epidermis. Scar A healing defect of the dermis (the epidermis alone heals without a scar).
T AB LE 2.2-3. Types and Mechanisms of Hypersensitivity Reactions
Type I Anaphylactic and atopic: Antigen cross-links IgE on presensitized mast cells and basophils, triggering the release of vasoactive amines (i.e., histamine). Reaction develops rapidly after antigen exposure as a result of preformed antibody. Examples include anaphylaxis, asthma, urticarial drug reactions, and local wheal and f are. First and Fast (anaphylaxis). Types I, II, and III are all antibody, or B-cell, mediated. Type II Cytotoxic: IgM and IgG bind to antigen on an “enemy” cell, leading to lysis (by complement) or phagocytosis. Examples include autoimmune hemolytic anemia, Rh disease (erythroblastosis fetalis), Goodpasture’s syndrome, and rheumatic fever. Cy-2-toxic. Antibody and complement lead to membrane attack complex (MAC). Type III Immune complex: Antigen-antibody complexes activate complement, which attracts neutrophils; neutrophils release lysosomal enzymes. Examples include polyarteritis nodosa, immune complex glomerulonephritis, SLE, and rheumatoid arthritis. Serum sickness: An immune complex disease (type III) in which antibodies to the foreign proteins are produced (takes f ve days). Immune complexes form and are deposited in membranes, where they fx complement (leading to tissue damage). More common than Arthus reaction. Arthus reaction: A local subacute antibody-mediated hypersensitivity (type III) reaction. Intradermal injection of antigen induces antibodies, which form antigen-antibody complexes in the skin. Characterized by edema, necrosis, and activation of complement. Examples include hypersensitivity pneumonitis and thermophilic actinomycetes. Imagine an immune complex as three things stuck together: antigen-antibody complement. Includes many glomerulonephritides and vasculitides. Most serum sickness is now caused by drugs (not serum). Fever, urticaria, arthralgias, proteinuria, and lymphadenopathy occur 5–10 days after antigen exposure. Antigen-antibody complexes cause the Arthus reaction. Type IV Delayed (cell-mediated) type: Sensitized T lymphocytes encounter antigen and then release lymphokines (leading to macrophage activation). Examples include TB skin tests, transplant rejection, and contact dermatitis (e.g., poison ivy, poison oak). 4th and last—delayed. Cell mediated, not antibody mediated; therefore, it is not transferable by serum.
Clinical manifestations by age group are as follows:Infants: Erythematous, weeping, pruritic patches on the face, scalp, and diaper area.
Children: Dry, scaly, pruritic, excoriated patches in the fl exural areas and neck.
Adults: Lichenification and dry, fissured skin, often limited to the hands.
FIGURE 2.2-2.  Atopic dermatitis.Erythema toxicum of the newborn resembles eczema, presenting with red papules/ vesicles with surrounding erythema. ↑ eosinophils will be seen on biopsy. This typically benign rash rarely appears after f ve days of age and is usually gone in 7–14 days; treatment is typically observation.
Hyperpigmentation, lichenification, and scaling are seen in the antecubital fossae. (Courtesy of Robert Swerlick, MD, as published in Fauci AS, Braunwald E, Kasper DL, et al. Harrison’s
Principles of Internal Medicine, 17th ed. New York: McGraw-Hill, 2008.)
Diagnosis is made clinically. Patients may have mild eosinophilia and ↑ IgE. Rule out seborrheic dermatitis, contact dermatitis, pityriasis rosea, drug eruption, and cutaneous T-cell lymphoma.
Prophylactic measures include use of nondrying soaps, application of moisturizers, and avoidance of known triggers.
Treat with topical corticosteroids (avoid systemic steroids in light of their side effect profile), PUVA, and topical immunomodulators (e.g., tacrolimus, pimecrolimus).
Topical corticosteroids should not be used for longer than 2–3 weeks.
A type IV hypersensitivity reaction that results from contact with an allergen to which the patient has previously been exposed and sensitized. Dermatitis develops when the patient is reexposed to the allergen or to a cross-reactive compound. More common in adults than in children.
Commonly presents with pruritus and rash, but can also present with edema, fever, and lymphadenopathy.
Frequently implicated allergens include poison ivy, poison oak, nickel, soaps, detergents, cosmetics, and rubber products containing latex (e.g., gloves and elastic bands in clothing).
Characteristic distributions involve areas where makeup, clothing, perfume, nickel jewelry, and plants come into contact with the skin.
The dermatitis begins in the area of contact with the antigen, with its appearance varying with the acuity of the lesion.
Acute: Approximately 24–48 hours after an allergic contact, the skin becomes erythematous, presenting with tiny blisters followed by scale and crusts. Lesions are intensely pruritic.
Subacute: Results from episodic exposure or a weak allergen. Lesions are less “angry appearing” than those of an acute infl ammatory rash, and some lichenification is seen.
Chronic: Results from extended exposure to an allergen. Characterized by erythema and lichenification with fissuring, often with superimposed acute dermatitis.
The overall shape of the rash often mimics that of the exposing object (see Figure 2.2-3), but it can also spread over the body via transfer of allergen by the hands or via circulating T lymphocytes. Patients are at ↑ risk of 2° infection.
Diagnosed by clinical impression. A patch test can be used to establish the causative allergen after the acute-phase rash has been treated. The differential includes atopic dermatitis, seborrheic dermatitis, impetigo, HSV, herpes zoster, and fungal infection.
Prophylaxis consists of avoidance of the offending allergen.Treat with topical or systemic corticosteroids as needed and with cool, wet compresses to relieve and debride the skin.
The pathogenesis of contact dermatitis involves allergenic molecules that are passed through the epidermis and taken up by Langerhans cells, which carry them to the lymph nodes and expose them to T lymphocytes.
FIGURE 2.2-3.  Contact dermatitis.Shown above are erythematous papules and vesicles with serous weeping localized to areas of contact with the offending agent. (Reproduced, with permission, from Hurwitz RM. Pathology of the Skin: Atlas of Clinical-Pathological Correlation, 2nd ed. Stamford, CT: Appleton & Lange, 1998: 3.)
Suspect HIV in a young person with severe seborrheic dermatitis.
A common disease that may be caused by Pityrosporum ovale, a generally harmless yeast found in sebum and hair follicles. It has a predilection for areas with oily skin such as the scalp, eyebrows, nasolabial folds, and midchest.
The appearance of rash varies with age:Infants: Presents as a severe, red diaper rash with yellow scale, erosions, and blisters. A thick crust (“cradle cap”) may be seen on the scalp.
Children/adults: Red, scaly patches are seen around the ears, eyebrows, nasolabial fold, midchest, and scalp. The rash is more localized and less dramatic than that seen in infants.
Patients with HIV/AIDS can develop severe seborrheic dermatitis or an overlapping syndrome of severe seborrheic dermatitis, psoriasis, psoriatic arthritis, and even Reiter’s syndrome.
Diagnosed by clinical impression. Rule out contact dermatitis and psoriasis.
Treatment consists of selenium sulfide or zinc pyrithione shampoos for the scalp, and topical antifungals and/or topical corticosteroids for other areas. Low-concentration coal tar shampoos are still available despite concerns about carcinogenicity.
A T-cell-mediated inflammatory dermatosis characterized by erythematous patches and silvery scales due to dermal inflammation and epidermal hyperplasia. Five percent of patients also have a seronegative arthritis. The condition usually starts in puberty or young adulthood, and its incidence is 2–4%.
The typical lesion is a round, sharply bordered erythematous patch with silvery scales (see Figure 2.2-4A).
Lesions are classically found on the extensor surfaces, including the elbows, knees, scalp, and lumbosacral regions.
Lesions may initially appear very small (guttate) but may slowly enlarge and become confluent. Psoriatic nails feature pitting, “oil spots,” and onycholysis, or lifting of the nail plate (see Figure 2.2-4B).
Psoriatic lesions can be provoked by local irritation or by trauma (Koebner’s phenomenon). Streptococcal infection can lead to cutaneous immune complex deposition, which triggers guttate psoriasis. Some medications, such as β-blockers, lithium, and ACEIs, can also induce psoriasis.
Psoriatic arthritis usually begins in the hands with “sausage digits,” but the knees, wrists and ankles as well as the lumbosacral region may also be affected. Arthritic patients with spinal involvement are usually HLAB27 .
When pustular psoriasis, a less common form, is generalized, it can be life threatening, presenting with fever, electrolyte abnormalities, and loss of serum proteins.
AB FIGURE 2.2-4. Psoriasis.(A) Skin changes. The classic sharply demarcated plaques with silvery scales are commonly located on the extensor surfaces (e.g., elbows, knees). (B) Nail changes. Note the pitting, onycholysis, and “oil spots.” (Reproduced, with permission, from Hur witz RM. Pathology of the Skin: Atlas of Clinical-Pathological Correlation, 2nd ed. Stamford, CT: Appleton & Lange, 1998: 15, 18.)
Clinical impression is usually sufficient for diagnosis.Classically presents with the Auspitz sign (bleeding when scale is scraped), but biopsy can be useful.
Histology classically shows a thickened epidermis, elongated rete ridges, an absent granular cell layer, preservation of nuclei, and a sterile neutrophilic infiltrate (Munro’s microabscess) in the stratum corneum.
Treat with topical steroids combined with keratolytic agents, tar, or anthralin along with UV therapy, including PUVA. Methotrexate may be used for severe cases. Retinoids (vitamin A derivatives) may also be used.
Arthritis should be treated first with NSAIDs and then with methotrexate if necessary. Systemic corticosteroids should be avoided, as tapering can induce psoriatic fl ares.
Recently, biologic agents such as TNF-α inhibitors have proven effective in severe psoriatic arthritis and psoriasis.
Urticaria is characterized by superficial, intense edema in a localized area. It is usually acute but can also be chronic (lasting > 6 weeks). The condition results from the release of vasoactive substances (histamine, prostaglandins) from mast cells in a type I hypersensitivity response.
■Hives can range in severity from a few itchy bumps to life-threatening anaphylaxis.
The typical lesion is an elevated papule or plaque that is reddish or white and variable in size. Lesions are widespread and last a few hours.
In severe allergic reactions, extracutaneous manifestations can include tongue swelling, angioedema (deeper, more diffuse swelling), asthma, GI symptoms, joint swelling, and fever.
Acute urticaria is a response to a trigger that may be a food, drug, virus, insect bite, or physical stimulus. Chronic urticaria is usually idiopathic.
Diagnosed by clinical impression and patient report. Biopsy demonstrates perivascular edema. It can often be difficult to determine the cause.
Treat with systemic antihistamines. Topical medications are of no benefit.
Maintain a high suspicion for a cutaneous drug reaction in patients who are hospitalized and develop rashes. Such reactions can take many forms, including urticarial, lupus-like, vasculitic, purpuric, lichenoid, and vesicular. Drugs can cause all four types of hypersensitivity reactions, and sometimes the same drug may cause different types of reactions in different patients.
Eruptions occur 7–14 days after exposure, so if a patient reacts within a day or two of starting a new drug (i.e., a drug they have never taken before), that drug is probably not the causative agent.
Eruptions are generally widespread, relatively symmetrical, and pruritic. Most are relatively short-lived, disappearing within 1–2 weeks following removal of the offending agent.
The exception is fixed drug eruption, which consists of reddish macules or papules that develop in the same area (usually the genitalia, face, or extremities) each time the patient is exposed to the triggering agent. After these lesions resolve, there is often a persistent brown pigmentation.
Extreme complications of drug eruptions include erythroderma and toxic epidermal necrolysis (TEN).
Diagnosed by clinical impression. Patients may have eosinophilia and eosinophils on histopathology.
Discontinue the offending agent; treat symptoms with antihistamines.A cutaneous reaction pattern with classic targetoid lesions that has many triggers and is often recurrent. Although some cases are idiopathic, many are triggered by recurrent HSV infection of the lip. Other common triggers are drugs (e.g., sulfa drugs, anticonvulsants, barbiturates, penicillin, NSAIDs) and mycoplasmal infections.
The characteristic lesion has a target appearance (see Figure 2.2-5), but other types of lesions may be seen as well.
The disease can occur on mucous membranes, where erosions are seen. Typically, lesions start as erythematous macules that become centrally clear and then develop a blister. The palms and soles are often affected.
May be associated with systemic symptoms, including fever, myalgias, headache, and arthralgias (these symptoms may precede eruption).
In its minor form, the disease is uncomplicated and localized to the skin. However, severe erythema multiforme can lead to TEN or Stevens-Johnson syndrome, in which patients are very ill with involvement of at least two mucosal surfaces.
Diagnosed by clinical impression. A history of recurrent labial herpes should be sought in all cases with multiple recurrences.
Symptomatic treatment is all that is necessary; systemic corticosteroids are of no benefit.
Minor cases can be treated with antipruritics; major cases should be treated as burns. In patients with HSV, suppressive acyclovir may ↓ the frequency of rashes.
FIGURE 2.2-5.  Erythema multiforme.Evolving erythematous plaques and papules are seen with a target appearance consisting of a dull red center, a pale zone, and a darker outer ring. (Reproduced, with permission, from Hurwitz RM. Pathology of the Skin: Atlas of Clinical-Pathological Correlation, 2nd ed. Stamford, CT: Appleton & Lange, 1998: 24.)
SJS and TEN may be confused with staphylococcal scalded-skin syndrome (SSSS), another condition in which patients lose widespread sheets of skin. SSSS is usually seen in children < 6 years of age and has an infectious etiology. SJS/TEN is generally seen in adults and is usually caused by a drug reaction.
Patients with erythema nodosum may have a falseVDRL (as in SLE).
SJS and TEN constitute two different points on the spectrum of life-threatening exfoliative mucocutaneous diseases that are often caused by a drug-induced immunologic reaction. The epidermal separation of SJS involves < 10% of body surface area (BSA), whereas TEN involves > 30% of BSA. Involvement of 10–30% of BSA is often considered SJS/TEN overlap.
May be preceded by erythema multiforme, a flulike prodrome, skin tenderness, a maculopapular drug rash, or painful mouth lesions.
Often associated with a history of exposure to new drugs, such as penicillin, sulfonamides, seizure medications (e.g., phenytoin, carbamazepine), quinolones, cephalosporins, allopurinol, corticosteroids, or NSAIDs.
Exam reveals severe mucosal erosions with widespread erythematous, cutaneous macules or atypical targetoid lesions. The epidermal lesions often become confluent and show a  Nikolsky’s sign and epidermal detachment.
Mucous membranes of the eyes, mouth, and genitals often become eroded and hemorrhagic as well.
SJS: Biopsy shows degeneration of the basal layer of the epidermis and perivascular mononuclear infiltrate with some eosinophils in the papillary dermis. Subepidermal blisters may also be seen.
TEN: Biopsy shows full-thickness eosinophilic epidermal necrosis with cell-poor infiltrate; there is a sparse perivascular lymphocytic infiltrate.
TEN vs. SSSS: On biopsy, TEN demonstrates full-thickness epidermal damage, whereas SSSS shows only superficial damage.
The differential also includes graft-versus-host reaction (usually after bone marrow transplant), radiation therapy, and burns.
Patients have the same complications as burn victims, including thermoregulatory difficulties, electrolyte disturbances, and 2° infections. Treatment includes skin coverage and maintenance of fluid and electrolyte balance. Controversial treatments include systemic corticosteroids in the early stages of SJS/ TEN or IVIG. There is a high risk of mortality.
A panniculitis whose triggers include infection (e.g., Streptococcus, Coccidioides, Yersinia, TB), drug reactions (e.g., sulfonamides, various antibiotics, OCPs), and chronic infl ammatory diseases (e.g., sarcoidosis, Crohn’s disease, ulcerative colitis, Behçet’s disease).
Painful, erythematous nodules appear on the patient’s lower legs (see Figure 2.2-6) and slowly spread, turning brown or gray. Patients may present with fever and joint pain.
FIGURE 2.2-6.  Erythema nodosum.Erythematous plaques and nodules are commonly located on pretibial areas. Lesions are pain ful and indurated but heal spontaneously without ulceration. (Reproduced, with permission, from Hurwitz RM. Pathology of the Skin: Atlas of Clinical-Pathological Correlation, 2nd ed.
Stamford, CT: Appleton & Lange, 1998: 132.)Diagnosed by clinical impression. Histology shows nonspecific septal panniculitis.Workup should include an ASO titer, a PPD test in patients who are high risk, a CXR to rule out sarcoid, and a small bowel series to rule out IBD in patients with GI symptoms.
Remove the triggering factor and treat the underlying disease where possible. NSAIDs can be used but may lead to erythema multiforme.
A life-threatening autoimmune condition characterized by an intraepidermal blister leading to widespread painful erosions of the skin and mucous membranes. Antibodies are directed against desmoglein molecules responsible for keratinocyte adherence, leading to loss of cellular attachment. Patients are generally middle-aged (40–60).
Initial presentation is with mucous membrane involvement, typically mouth ulcers, with progression to skin involvement. Rarely, an intact blister may be seen, but generally presents only with erosions, often accompanied by crusting, weeping, and 2° infections.
Along with the clinical picture, a  Nikolsky’s sign (the ability to produce a blister by rubbing skin adjacent to a natural blister) and skin biopsy with immunofl uorescence confirm the diagnosis.
Biopsy shows acantholysis (intraepidermal split with free-fl oating keratinocytes in the blister). Immunofl uorescence and ELISA are confirmatory for antidesmoglein antibodies.
Long-term treatment is generally required. Initially, systemic corticosteroids are used at high doses in combination with steroid-sparing agents introduced early to ↓ corticosteroid side effects.
Steroid-sparing agents include mycophenolate mofetil and azathioprine. Recently, rituximab and IVIG have been successfully used for recalcitrant disease.
An acquired blistering disease that leads to separation at the epidermal basement membrane. It is most commonly seen in patients 60–80 years of age. Its pathogenesis involves antibodies that are developed against the bullous pemphigoid antigen, which lies superficially in the basement membrane zone (BMZ). Antigen-antibody complexes activate complement and eosinophil degranulation that provoke an inflammatory reaction and lead to
F IGU R E 2.2-7.  Bullous pemphigoid.Multiple tense serous and partially hemorrhagic bullae can be seen. (Reproduced, with permission, from Fitzpatrick TB. Color Atlas & Synopsis of Clinical Dermatology, 4th ed. New York: McGraw-Hill, 2001: 100.) separation at the BMZ. The blisters are stable because their roof consists of nearly normal epidermis.
Presents with firm, stable blisters that arise on erythematous skin, often preceded by urticarial lesions. Nikolsky’s sign is . The blisters form crusts and erosions (see Figure 2.2-7). Mucous membranes are less commonly involved than is the case in pemphigus.
Diagnosed according to the clinical picture. Skin biopsy shows a subepidermal blister, often with an eosinophil-rich infiltrate. Immunofl uorescence demonstrates linear IgG and C3 immunoglobulin and complement at the dermal-epidermal junction.
Systemic corticosteroids. Topical corticosteroids can help prevent blister formation when applied to early lesions.
A painful, recurrent vesicular eruption of the mucocutaneous surfaces due to infection with HSV. HSV-1 usually produces oral-labial lesions, whereas HSV-2 usually causes genital lesions. The virus spreads through epidermal cells, causing them to fuse into giant cells. The local host infl ammatory response leads to erythema and swelling.
The initial infection is passed by direct contact, after which the herpesvirus remains dormant in local nerve ganglia. 1° episodes are generally longer and more severe than recurrences.
Onset is preceded by prodromal tingling, burning, or pain but can also present with lymphadenopathy, fever, discomfort, malaise, and edema of involved tissue.
Recurrences are limited to mucocutaneous areas innervated by the involved nerve.
Recurrent oral herpes (HSV-1): Typically consists of the common “cold sore,” which presents as a cluster of crusted vesicles on an erythematous base (see Figure 2.2-8A). It is often triggered by sun and fever.
Recurrent genital herpes (HSV-2): Unilateral and characterized by a cluster of blisters on an erythematous base, but with less pain and systemic involvement than the 1° infection.
Diagnosed primarily by the clinical picture. Multinucleated giant cells on Tzanck smear (see Figure 2.2-8B) yield a presumptive diagnosis.
VZV has the same appearance on Tzanck, so culture or direct fl uorescent antibody staining is needed for definitive diagnosis.
Dermatitis herpetiformis differs from HSV, consisting of pruritic papules and vesicles on the elbows, knees, buttocks, neck, and scalp. Granular IgA is seen on dermal papillae. The condition is associated with celiac disease (15–25% of celiac patients may have it). Treat with dapsone and a gluten-free diet.
AB FIGURE 2.2-8.  Herpes simplex.(A) 1° infection. Grouped vesicles on an erythematous base on the patient’s lips and oral mucosa may progress to pustules before resolving. (B) Tzanck smear. The multinucleated giant cells from vesicular fluid provide a presumptive diagnosis of HSV infec tion. The Tzanck smear cannot distinguish between HSV and VZV infection. (Reproduced, with permission, from Hurwitz
RM. Pathology of the Skin: Atlas of Clinical-Pathological Correlation, 2nd ed. Stamford, CT: Appleton & Lange, 1998: 145.)
Oral or IV acyclovir (IV for severe cases or for immunocompromised patients) ↓ both the frequency and the severity of recurrences. Daily acyclovir, valacyclovir, or famciclovir suppressive therapy may be used in patients with > 6 outbreaks per year or for those with erythema multiforme.
Acyclovir ointment is somewhat effective in reducing the duration of viral shedding but does not prevent recurrence.
In AIDS patients, HSV can persist, with ulcers remaining resistant to antiviral therapy. Symptomatic HSV infection lasting > 1 month can be considered an AIDS-defining illness.
VZV causes two different diseases, varicella and herpes zoster—with transmission occurring via respiratory droplet or by direct contact. VZV has an incubation period of 10–20 days, with contagion beginning 24 hours before the eruption appears and lasting until lesions have crusted.
A prodrome consisting of malaise, fever, headache, and myalgia occurs 24 hours before the onset of the rash.
Pruritic lesions appear in crops over a period of 2–3 days, evolving from red macules to grouped central vesicles (“dewdrop on a rose petal”) and then crusting over.
At any given time, patients have all stages of lesions over their entire body. The trunk, face, scalp, and mucous membranes are involved, but the palms and soles are spared.
In adults, chickenpox is often more severe, with systemic complications such as pneumonia and encephalitis.
Herpes zoster represents the recurrence of VZV in a specific nerve, with lesions cropping up along the nerve’s dermatomal distribution. Outbreaks are usually preceded by intense local pain and then arise as grouped blisters on an erythematous base (see Figure 2.2-9).
In immunocompromised patients, zoster can lead to severe local disease, disseminated cutaneous disease, and systemic diseases that mimic varicella. Older patients with severe zoster may develop postherpetic neuralgia.
Diagnosed by the clinical picture.Varicella is self-limited in healthy children. A vaccine is available for infants, children, and adults and is routinely used for disease prevention.
Adults should be treated with systemic acyclovir.Although acyclovir may speed the cutaneous course of zoster, pain control is most important for patients with this disease.
A poxvirus infection that is most common in young children and in AIDS patients. It is spread by physical contact.
■The rash is composed of tiny waxy papules, frequently with central umbilication. In children, lesions are found on the trunk, extremities, or face If you see giant molluscum (see Figure 2.2-10). In adults, they are commonly found on the genitalia contagiosum, think HIV.
and in the perineal region.FIGURE 2.2-9.  Varicella zoster.The unilateral dermatomal distribution of the grouped vesicles on an erythematous base is characteristic.
FIGURE 2.2-10.  Molluscum contagiosum.The dome-shaped, fleshy, umbilicated papule on the child’s eyelid is characteristic. (Repro duced, with permission, from Hurwitz RM. Pathology of the Skin: Atlas of Clinical-Pathological
Correlation, 2nd ed. Stamford, CT: Appleton & Lange, 1998: 149.)
In AIDS patients, lesions often appear on the face and can become quite large.
Lesions are asymptomatic unless they become inflamed or irritated.Diagnosed by the clinical picture, and confirmed by expressing and staining the contents of the papules. Giemsa or Wright’s stain allows for the identification of large inclusion or molluscum bodies.
Any local destructive method is effective, including curetting, freezing, or applying trichloroacetic acid to the lesions. Lesions resolve spontaneously over months to years and are often left untreated in children.
Warts are caused by many different types of HPV and can occur on skin, mucous membranes, and other epithelia. Although usually benign, some subtypes of HPV (especially 16 and 18) lead to squamous malignancies. Spread is by direct contact. HPV leads to hyperproliferation of infected cells.
Common warts are the most prevalent HPV infection. Although most often seen on the hands, they can occur anywhere. On plantar and palmar surfaces, warts tend to grow downward into the skin rather than outward, giving them a fl atter appearance.
The classic genital wart is a cauliflower-like papule or nodule appearing on the glans penis, the vulva, or the perianal region. Warts on mucous membranes are generally velvety and white, appearing on oral, genital, and even laryngeal mucosa. Laryngeal warts are transmitted to infants by mothers with genital HPV.
Diagnosed by the clinical picture. Acetowhitening can be helpful in visualizing mucosal lesions. There is a long latency period, with children sometimes acquiring HPV at birth and not manifesting any lesions until years later.
Treatment centers on destruction of the tissue by curettage, cryotherapy, or acid keratolytics. Genital warts are treated locally with podophyllin, trichloroacetic acid, imiquimod, or 5-FU. HPV lesions on the cervix must be monitored cytologically and histologically for evidence of malignancy.
A superficial, weeping local infection that primarily occurs in children and is caused by both group A streptococcal and staphylococcal organisms. It is transmitted by direct contact.
There are two types:Common type: Characterized by pustules and honey-colored crusts on an erythematous base; generally appears on the face (see Figure 2.211).
Bullous type: Usually acral; characterized by large stable blisters.Bullous impetigo is almost always caused by S. aureus and can evolve into SSSS. Streptococcal impetigo can be complicated by acute streptococcal glomerulonephritis.
FIGURE 2.2-11. Impetigo.What is another skin condition caused by group A strep? Erysipelas, which presents as a small red patch on the cheek that turns into a painful raised, shiny red plaque. Patients often have a history of trauma or pharyngitis. Treat with penicillin.
Dried pustules with a superficial golden-brown crust are most commonly found around the nose and mouth. (Reproduced, with permission, from Hurwitz RM. Pathology of the Skin: Atlas of Clinical-Pathological Correlation, 2nd ed. Stamford, CT: Appleton & Lange, 1998: 165.)
Scarlet fever: “Sunburn with goosebumps” appearance; strawberry tongue. Caused by S. pyogenes. Treatment: Penicillin.
Salmonella typhi: Small pink papules on the trunk (“rose spots”) in groups of 10–20  plus gallbladder disease. Treatment: Cholecystectomy for chronic carrier state.
Ludwig’s angina is a bilateral cellulitis of the submaxillary/ sublingual spaces that usually results from an infected tooth. It presents with dysphagia, drooling, fever, and a red, warm mouth and can lead to death from asphyxiation.
Diagnosed by the clinical picture.Treat with antibiotics with antistaphylococcal activity. Topical antibiotics are often sufficient, but systemic agents can hasten recovery and prevent spread to other patients.
An infection caused by Corynebacterium, presenting as brownish-red patches with fine scales that characteristically appear along major skin folds. It is more common among diabetics.
Wood’s light exam reveals coral-red fl uorescence of lesions. Gram staining reveals gram-, filamentous rods.
Treat with erythromycin. (Remember: erythrasma is treated with erythromycin.)A deep, local infection involving the connective tissue, subcutaneous tissue, or muscle in addition to the skin. It is commonly caused by staphylococci or group A streptococci originating from an area of damaged skin or from a systemic source of infection. Community-acquired MRSA is an increasingly common cause. Risk factors include diabetes, IV drug use, venous stasis, and immune compromise.
Presents with red, hot, swollen, tender skin. Fever and chills are also common.
Diagnosed by the clinical picture; wound culture may aid in diagnosis and help determine antibiotic sensitivities for treatment. Blood cultures should be obtained when bacteremia is suspected. Culture and sensitivities are important in case of MRSA. Rule out abscess, urticaria, contact dermatitis, osteomyelitis, and necrotizing fasciitis.
Treat with 7–10 days of oral antibiotics for mild cases or with IV antibiotics if there is evidence of systemic toxicity, comorbid conditions, DM, extremes of age, hand or orbital involvement, or other concerns.
Deep infection along a fascial plane causing severe pain followed by anesthesia. Infection is caused by S. pyogenes or Clostridium perfringens. A history of trauma or a recent surgery to the affected area is often but not always elicited.
Presents with sudden onset of pain and swelling at the site of trauma or recent surgery. Pain often progresses to anesthesia.
An area of erythema quickly spreads over the course of hours to days. Margins move out into normal skin, and skin becomes dusky or purplish near the site of insult, ultimately leading to necrosis.
Necrosis can initially have the appearance of undermining of the skin and subcutaneous layer; if the skin is open, gloved fingers can easily pass between the two layers to reveal yellow-green necrotic fascia (infection spreads quickly in deep fascia).
The most important signs are tissue necrosis, a putrid discharge, bullae, severe pain, gas production, rapid burrowing through fascial planes, lack of classical tissue inflammatory signs, and intravascular volume loss.
Local radiographs or CT scans show air in tissue. Biopsy from the edge of the lesion can be diagnostic.
A surgical emergency. Early and aggressive surgical debridement is critical.
If Streptococcus is the principal organism involved, penicillin G is the drug of choice. Clindamycin is second line.
For anaerobic coverage, give metronidazole or a third-generation cephalosporin.Inflammation of the hair follicle. Although typically caused by infection with Staphylococcus, Streptococcus, and gram-bacteria, folliculitis may occasionally be caused by yeast such as Candida albicans or Pityrosporum ovale. It may also be mechanical, arising from ingrown hairs (most common in patients with curly hair).
Presents as a tiny pustule that appears at the opening of a hair follicle and usually has a hair penetrating it. When the infection is deeper, a furuncle, or hair follicle abscess, develops.
Furuncles are larger and more painful than folliculitic lesions and may disseminate to adjacent follicles to form a carbuncle. Patients with diabetes or immunosuppression are at ↑ risk.
Folliculitis can be a critical problem in AIDS patients, in whom the disease is intensely pruritic and resistant to therapy.
Diagnosed by the clinical picture.Fournier gangrene is a form of necrotizing fasciitis that is localized to the scrotum and perineal area.
leads to “hot tub folliculitis.”Ironically, erythromycin does not cause erythema with sun exposure. It is tetracycline and doxycycline that can cause serious photosensitivity!
Topical antibiotics can be used to treat mild disease, but severe cases require systemic antibiotics. Large lesions must be incised, drained, and cultured to rule out MRSA. Patients who are prone to ingrown hairs should be advised not to shave.
An endogenous skin disease that is common among adolescents. The pathogenesis involves hormonal activation of sebaceous glands, the development of the comedo or plugged sebaceous follicle, and involvement of Propionibacterium acnes in the follicle, causing inflammation. Comedones may be caused by medications (e.g., lithium, corticosteroids) or by topical occlusion (e.g., cosmetics).
There are three stages of acne lesions:Comedo: May be open (“blackheads”) or closed (“whiteheads”); present in large quantities but with little infl ammation.
Infl ammatory: The comedo ruptures, creating a pustule that can be large and nodular.
Scar: As the infl ammation heals, scars may develop. Picking at papules exacerbates scarring.
Two types of cysts can occur in acne: inflammatory cysts, which are large, fluctuant pustules, and epidermoid cysts, which develop along the eyebrows and behind the ears.
Acne first develops at puberty and typically persists for several years. Males are more likely to have severe, cystic acne than are females. Women in their 20s tend to have a variant that flares cyclically with menstruation, featuring fewer comedones and more painful lesions on the chin. Androgenic stimulation may contribute to these lesions.
Diagnosed by the clinical picture.Treat comedones with topical tretinoin (Retin-A) and benzoyl peroxide.Inflammatory lesions should be treated with topical antibiotics (e.g., erythromycin, clindamycin) or systemic agents (e.g., tetracycline, erythromycin).
Isotretinoin (Accutane) leads to marked improvement in > 90% of acne patients and has greatly improved the treatment of severe acne.
Isotretinoin is, however, a teratogen and may cause transient elevations in cholesterol, triglycerides, and LFTs, and it may also be associated with depression.
Patients on isotretinoin are thus carefully monitored and are required to get monthly blood tests to check quantitative serum β-hCG (to rule out pregnancy), LFTs, cholesterol, and triglycerides. Monthly refills are contingent on completion of blood testing and evaluation by a dermatologist.
Abscesses in the sacrococcygeal region that usually occur near the top of the natal cleft. Their name may not be appropriate, as not all such cysts contain hair, and not all are true cysts. Repetitive trauma to the region plays a role. The condition is thought to start as a folliculitis that becomes an abscess complicated by perineal microbes, especially Bacteroides. It most commonly occurs between the ages of 20 and 40, affecting men more often than women.
Patients present with an abscess at the natal cleft that can be tender, fl uctuant, warm, and indurated and is sometimes associated with purulent drainage or cellulitis. Systemic symptoms are uncommon, but cysts may develop into perianal fistulas.
Risk factors include deep and hairy natal clefts, obesity, and a sedentary lifestyle.
Diagnosed by the clinical picture. Rule out perirectal and anal abscess.
Treatment consists of incision and drainage of the abscess under local anesthesia followed by sterile packing of the wound. Abscesses should be allowed to heal by 2° intention.
Antibiotics are not needed unless cellulitis is present; if they are prescribed, both aerobic and anaerobic coverage is required.
Good local hygiene and shaving of the sacrococcygeal skin can help prevent recurrence. Patients should follow up with a surgeon.
Caused by Malassezia furfur, a yeast that is part of the normal skin fl ora (morphologic variants are Pityrosporum ovale and Pityrosporum orbiculare). It is unclear what leads the organism to overgrow on the skin surface and become a pathogen, but humid and sweaty conditions as well as host factors such as oily skin can contribute. Cushing’s syndrome and immunosuppression are also risk factors.
Patients present with small, scaly patches of varying color, usually on the chest or back.
Lesions may be hypopigmented as a result of interference with melanin production, or they may be hyperpigmented by virtue of thickened scale.
Diagnosed by clinical impression, and confirmed by potassium hydroxide (KOH) preparation of scale that reveals a “spaghetti and meatballs” pattern of hyphae and spores.
Treat lesions with topical selenium sulfide daily for one week, followed by application once weekly for prophylaxis.
Commonly called “yeast infection” or “thrush,” candidiasis can be caused by any Candida species but is most commonly caused by C. albicans. In immune-competent patients, it typically presents as a superficial infection of the skin or mucous membranes in moist areas such as skin folds, armpits, the vagina, and below the breasts. Oral thrush is not uncommon among children, but in adults it is often a sign of a weakened immune system.
Patients often have a history of antibiotic use, steroid use, or diabetes.
Symptoms vary according to the site affected:Oral candidiasis: Presents with painless white plaques that cannot easily be scraped off.
Candidiasis of the skin: Presents as pink, circular, erythematous macules that converge, with smaller satellite lesions seen nearby, often in skin folds.
In infants, infection can often be seen in the diaper area and along the inguinal folds.
Diagnosed by the clinical picture.Confirmed by KOH preparation of a scraping or swab of the affected area. KOH dissolves the skin cells but leaves the Candida untouched such that candidal hyphae and pseudospores become visible.
Oral candidiasis: Oral fluconazole; nystatin swish and swallow.Superficial (skin) candidiasis: Topical antifungals; keep skin clean and dry.
Diaper rash: Topical nystatin.Dermatophytes live only in tissues with keratin (i.e., the skin, nails, and hair) and are a common cause of infection. Causative organisms include Microsporum, Trichophyton, and Epidermophyton. The immune response to the dermatophyte, rather than the organism itself, is responsible for many of the symptoms. Pets are a reservoir for Microsporum. Other risk factors include diabetes, ↓ peripheral circulation, immune compromise, and chronic maceration of skin (e.g., from athletic activities).
Presentation varies according to subtype: ■ Tinea corporis: Presents as a scaly, pruritic eruption with a sharp, irregular border, often with central clearing. May be seen in immunocompromised patients or in children following contact with infected pets.
Tinea pedis/manuum: Presents as chronic interdigital scaling with erosions between the toes (“athlete’s foot”) or as a thickened, scaly skin on the soles. Asymmetric involvement of the hands is typical.
Tinea cruris (“jock itch”): A chronic infection of the groin (typically sparing the scrotum) that is usually associated with tinea pedis.
Tinea capitis (“ringworm”): A diffuse, scaly scalp eruption similar to seborrheic dermatitis.
Diagnosed by the clinical picture; confirmed by scales prepared in KOH showing hyphae.
Patients can be treated with topical or systemic antifungals. Tinea capitis must be treated with systemic drugs.
Lice live off blood and on specific parts of the body, depending on their species. The head louse lives on the scalp and lays its eggs as nits attached to hair; the body louse lives in clothing and bites only the body. The pubic louse lives on pubic hair. Lice are spread through body contact or by the sharing of bedclothes and other garments. They secrete local toxins that lead to pruritus.
Patients with lice often experience severe pruritus, and 2° bacterial infection of the excoriations is a risk. Classroom epidemics of head lice are common.
Body lice are seen in people with inadequate hygiene or in those with crowded living conditions. Pubic lice (called “crabs” because of their squat, crablike body shape) contain anticoagulant in their saliva, so their bites often turn blue.
Lice can be seen on hairs or in clothes.Head lice: Treat with OTC pyrethrin (RID) and mechanical removal of nits.
Body lice: Wash body, clothes, and bedding thoroughly. Treating the body with topical permethrin or pyrethrin may also be required.
Pubic lice: Treat with RID.Caused by Sarcoptes scabiei, a tiny arthropod that mates on the skin surface, after which the female digs a passage into the stratum corneum and lays her eggs. The burrowing leads to pruritus that ↑ in intensity once an allergy to
Other ulcers (all can be treated with specialized wound dressings): ■Venous stasis ulcers: Found near the lateral or medial malleolus, often in association with lower extremity edema. Treat with compression (Unna boots or compression stockings) and elevation.
■Arterial insufficiency ulcers: Found on the heel and tips of toes. Typically very painful.
■Neuropathic ulcers: Found on the underside of the foot and toes, usually at pressure points. Typically painless.
the mite or its products develops. Scabies mites are spread through close contact.
Patients present with intense pruritus, especially at night and after hot showers.
The most commonly affected sites are the hands, axillae, and genitals.
On exam, the mite’s track can sometimes be seen along with erythematous, excoriated papules. 2° bacterial infection is common.
A history of pruritus in several family members is suggestive. The mite may be identifiable by scraping an intact tunnel and looking under the microscope, but this is often difficult.
Patients should be treated overnight with 1–2 applications of 5% permethrin from the neck down, and their contacts should be treated as well. Oral ivermectin is also effective. Pruritus may persist for two weeks after treatment, so symptomatic treatment should be provided.
Result from ischemic necrosis following continuous pressure on an area of skin that restricts microcirculation to the area. Ulcers are most commonly seen in bedridden patients who lie in one spot for too long. An underlying bony prominence or lack of fat ↑ the likelihood of ulcer formation. Patients who lack mobility or cutaneous sensation are also at ↑ risk. Incontinence of urine or stool may macerate the skin, facilitating ulceration.
Ulcers are graded by degree of damage:Grade I: Characterized by persistent redness.Grade II: Marked by ulceration.Grade III: Involves destruction of structures beneath the skin such as muscle or fat.
Diagnosed by the history and clinical appearance.Prevention is key and involves routinely moving bedridden patients and using special beds that distribute pressure. Once an ulcer has developed, low-grade lesions can be treated with routine wound care, including hydrocolloid dressings. High-grade lesions require surgical debridement.
Defined as necrosis of body tissue. There are three subtypes: dry, wet, and gas. The presence of one subtype does not exclude the others. Etiologies are as follows:
Dry gangrene: Due to insufficient blood flow to tissue, typically from atherosclerosis.
Wet gangrene: Involves bacterial infection, usually with skin fl ora.
Gas gangrene: Due to Clostridium perfringens infection.Dry gangrene: Early signs are a dull ache, cold, and pallor of the fl esh. As necrosis sets in, the tissue (usually a toe) becomes bluish-black, dry, and shriveled. Diabetes, vasculopathy, and smoking are risk factors.
Wet gangrene: The tissue appears bruised, swollen, or blistered with pus.
Gas gangrene: Typically occurs at a site of recent injury or surgery, presenting with swelling around the injury and with skin that turns pale and then dark red. Bacteria are rapidly destructive of tissue, producing gas that separates healthy tissue and exposes it to infection. A medical emergency.
Diagnosed by clinical impression.Surgical debridement, with amputation if necessary, is the mainstay of treatment. Antibiotics alone do not suffice by virtue of inadequate blood flow, but they should be given as an adjuvant to surgery.
Gas gangrene can be treated with hyperbaric oxygen, which is toxic to the anaerobic C. perfringens. Susceptible patients should maintain careful foot care and should avoid trauma.
A condition in which the skin in the intertriginous zones (genital and axillary regions and especially the nape of the neck) is hyperkeratotic and hyperpigmented with a velvety appearance (see Figure 2.2-12).
Associated with DM, Cushing’s disease, HAIR-AN syndrome, and obesity. May also be a paraneoplastic sign of underlying adenocarcinoma (usually GI).
Dx: Clinical appearance.Tx: May be treated with topical retinoids, but typically not treated. Patients should be encouraged to lose weight.
A chronic inflammatory dermatosis involving the skin and mucous membranes. The condition is intensely pruritic, can be induced by drugs, and can be associated with HCV infection.
Presents with violaceous, flat-topped, polygonal papules. Lesions may have Wickham’s striae (white stripes), especially on the mucous mem-
Lichen planus is the “P” disease: Planar, Purple, Pruritic, Persistent, Polygonal, Penile, Perioral, Puzzling, and Koebner’s Phenomenon.
FIGURE 2.2-12.  Acanthosis nigricans.Velvety, dark brown epidermal thickening of the armpit is seen with prominent skin fold and feathered edges. (Reproduced, with permission, from Wolff K et al. Fitzpatrick’s Color Atlas &
Synopsis of Clinical Dermatology, 5th ed. New York: McGraw-Hill, 2005: 87.) branes (see Figure 2.2-13), as well as prominent Koebner’s phenomena (lesions that appear at the site of trauma). The initial lesions often appear on the genitalia, where they are ulcerated.
■Although most cases resolve spontaneously over 6–18 months, those with oral involvement have a more chronic course.
Dx: Histology reveals a “lichenoid pattern”—i.e., a band of T lymphocytes at the epidermal-dermal junction with damage to the basal layer.
Tx: Mild cases can be treated with topical corticosteroids. For severe disease, systemic corticosteroids may be used. Tretinoin gel may be helpful on oral mucosa.
A chronic disorder of pilosebaceous units. The disorder has a female predominance and is more common among those with fair skin. Its etiology is unclear.
Patients are generally middle-aged and often have an abnormal fl ushing response to various substances.
Early in the disease, central facial erythema is seen with telangiectasias. Later, papules and pustules may develop.
Associated findings include ocular keratitis and rhinophyma (sebaceous gland hyperplasia of the nose).
FIGURE 2.2-13.  Lichen planus.Flat-topped, polygonal, sharply defined papules of violaceous color are grouped and confl uent.
The surface is shiny and reveals fine white lines (Wickham’s striae). (Reproduced, with permis sion, from Wolff K et al. Fitzpatrick’s Color Atlas & Synopsis of Clinical Dermatology, 5th ed.
New York: McGraw-Hill, 2005: 125.)Diagnosed by the clinical picture. Rosacea can be confused with acne but is not follicular in origin and involves an older age group.
In a high percentage of patients, ↑ numbers of Demodex mites (which normally live harmlessly in hair follicles, especially in the facial area) are found on the facial skin and can be seen by microscopic examination of skin scrapings.
Treat with low-potency topical corticosteroids or topical metronidazole. In more severe disease, systemic antibiotics may be used. Extremely severe cases can be treated with short-term oral metronidazole.
An acute dermatitis that is pink and scaly. Its etiology is unknown, but it has been hypothesized to represent a reaction to a viral infection with human herpesvirus (HHV) 6 or 7 because it tends to occur in mini-epidemics among young adults.
■The initial lesion is a herald patch that is several centimeters in diameter and erythematous with a peripheral scale.
Days to weeks later, a 2° exanthem appears, presenting with multiple tiny, symmetric papules with a fine “cigarette paper” scale (see Figure 2.2-14). Papules are arranged along skin lines, giving a classic “Christmas tree pattern” on the patient’s back.
Patients are generally asymptomatic, although the disease may be more extensive, pruritic, and chronic among African-Americans.
Diagnosed by clinical impression and confirmed by KOH exam to rule out fungus (the herald patch may be mistaken for tinea corporis). The differential also includes 2° syphilis (RPR should be ordered), guttate psoriasis, and drug eruptions.
Patients usually heal without treatment in 2–3 weeks, but skin lubrication, topical antipruritics, and systemic antihistamines may occasionally be necessary. Severe cases can be treated with a short course of systemic corticosteroids.
A disease of depigmentation whose pathogenesis is unknown. The mechanism may be autoimmune, neurologic, or both.
■ Patients develop small, sharply demarcated, depigmented macules or patches on otherwise normal skin, often on the hands, face, or genitalia.
FIGURE 2.2-14. Pityriasis rosea.The round to oval erythematous plaques are often covered with a fine white scale (“cigarette paper”) and are often found on the trunk and proximal extremities. Plaques are often preceded by a larger herald patch (arrow). (Reproduced, with permission, from Hurwitz RM. Pathology of the Skin: Atlas of Clinical-Pathological Correlation, 2nd ed. Stamford, CT: Appleton & Lange, 1998: 13.)
These spots then expand, sometimes in dermatomal patterns, to include large segments of skin.
The disease is usually chronic and progressive, with some patients becoming completely depigmented.
Many patients have serologic markers of autoimmune disease (e.g., antithyroid antibodies, DM, pernicious anemia) but seldom present with these diseases. Patients with malignant melanoma may develop an antimelanocyte immune response that leads to vitiligo.
Diagnosed by the history and clinical picture, with histology demonstrating total absence of melanocytes. Conditions to rule out include postinfl ammatory hypopigmentation, scleroderma, piebaldism, and toxic exposure (pheno-lated cleansers are toxic to melanocytes).
Topical or systemic psoralens and exposure to sunlight or PUVA may be helpful. Patients must wear sunscreen because depigmented skin lacks inherent sun protection. Dyes and makeup may be used to color the skin, or the skin may be chemically bleached to produce a uniformly white color.
A very common skin tumor, appearing in almost all patients after age 40. The etiology is unknown. When many seborrheic keratoses erupt suddenly, they may be part of a paraneoplastic syndrome due to tumor production of epidermal growth factors. Lesions have no malignant potential but may be a cosmetic problem.
Present as exophytic, waxy brown papules and plaques with prominent follicle openings (see Figure 2.2-15). Lesions often appear in great numbers and have a “stuck-on” appearance.
Lesions may become irritated either spontaneously or by external trauma, “Seborrheic keratoses, or especially in the groin, breast, or axillae. Irritated lesions are smoother and SKs, look StucK on.” redder.
Diagnosed by the clinical picture; can be confirmed by histology showing hyperplasia of benign, basaloid epidermal cells with horn pseudocysts (prominent follicular openings). Rule out actinic keratosis, lentigo (focal ↑ in melanocytes), squamous cell carcinoma (SCC), and basal cell carcinoma (BCC).
Cryotherapy or curettage is curative.A precursor of SCC in situ. Lesions are caused by exposure to sunlight.
FIGURE 2.2-15.  Seborrheic keratoses.Multiple brown, warty papules and nodules are seen on the back, characterized by a “stuck-on” appearance. (Reproduced, with permission, from Fitzpatrick TB. Color Atlas & Synopsis of
Clinical Dermatology, 4th ed. New York: McGraw-Hill, 2001: 195.)Lesions appear on sun-exposed areas (especially the face and arms) and primarily affect older patients, who rarely have a solitary lesion. They are erythematous with a light scale that can become thick and crusted (see Figure 2.2-16). Early lesions may be difficult to visualize and may be easier to find by palpation.
Diagnosed by clinical impression. Biopsy is seldom necessary but shows intraepidermal atypia over a sun-damaged dermis. The differential includes Bowen’s disease, a form of squamous cell carcinoma in situ.
Cryosurgery, topical 5-FU, or topical imiquimod can be used to destroy the lesion. If carcinoma is suspected, biopsy followed by excision or curettage is appropriate. Patients should be advised to use sun protection.
FIGURE 2.2-16.  Actinic keratosis.The discrete patch above has an erythematous base and a rough white scale. (Reproduced, with permission, from Hurwitz RM. Pathology of the Skin: Atlas of Clinical-Pathological Correlation, 2nd ed. Stamford, CT: Appleton & Lange, 1998: 359.)
The second most common skin tumor, with locally destructive effects as well as the potential for metastasis and death. UV light is the most common causative factor, but exposure to chemical carcinogens, prior radiation therapy, and the presence of chronically draining infectious sinuses (as in osteomyelitis) also predispose patients to developing SCC. Most SCCs occur in older adults with sun-damaged skin, arising from actinic keratoses.
■SCCs have a variety of forms, and a single patient will often have multiple variants (see Figure 2.2-17).
FIGURE 2.2-17. Squamous cell carcinoma.Note the crusting and ulceration of this erythematous plaque. Most lesions are exophytic nodules with erosion or ulceration. (Reproduced, with permission, from Hurwitz RM. Pathology of the Skin: Atlas of Clinical-Pathological Correlation, 2nd ed. Stamford, CT: Appleton & Lange, 1998: 360.)
Keratoacanthoma, a benign epithelial tumor, can look like SCC but develops more rapidly and may regress spontaneously. Treatment is usually similar to that of SCCs.
■SCCs that arise from actinic keratoses rarely metastasize, but those that arise on the lips and on ulcers are more likely to do so. SCC occurs on the lip far more commonly than does BCC.
Diagnosed by clinical suspicion and confirmed by biopsy, which is necessary for accurate diagnosis and appropriate therapeutic planning.
Histology shows intraepidermal atypical keratinocytes, with penetration of the basement membrane by malignant epidermal cells growing into the dermis. SCCs are graded histologically.
Surgical excision. Lesions with high metastatic potential may require additional radiation or chemotherapy.
The most common malignant skin tumor, BCC is slow growing and locally destructive but has virtually no metastatic potential. Chronic UV light exposure is the main risk factor. Multiple lesions on non-sun-exposed areas are suggestive of arsenic exposure or inherited basal cell nevus syndrome. Most lesions appear on the face and on other sun-exposed areas.
There are many types of BCC with varying degrees of pigmentation, ulceration, and depth of growth (see Figure 2.2-18).
FIGURE 2.2-18. Basal cell carcinoma.Seen above is an erythematous, fleshy, telangiectatic nodule with a translucent surface. (Reproduced, with permission, from Hurwitz RM. Pathology of the Skin: Atlas of Clinical-Pathological Correlation, 2nd ed. Stamford, CT: Appleton & Lange, 1998: 362.)
Diagnosed by clinical impression; confirmed by biopsy showing islands of proliferating epithelium resembling the basal layer of the epidermis. The differential includes benign tumors, hypopigmented melanocytic nevi, melanoma, dermatitis, psoriasis, and Paget’s disease.
Options include excision, curettage and electrodesiccation/cautery, deep cryotherapy, superficial radiation therapy, and Mohs’ surgery. Cure rates are > 95%.
The most common life-threatening dermatologic disease; incidence has been increasing throughout the world. Risk factors include short, intense bursts of sun exposure (especially in childhood and with intermittent exposure) and the presence of congenital melanocytic nevi, an ↑ number of nevi, or dysplastic nevi. Immunosuppression also ↑ risk. Some patients inherit a predisposition to melanoma with the familial atypical mole and melanoma (FAM-M) syndrome. There are several subtypes (see Table 2.2-4).
Malignant melanomas usually begin in the epidermal basal layer, where melanocytes are normally found.
The first growth phase is horizontal-intraepidermal, presenting with a lesion that is flat but increasing in diameter (typical of lentigo maligna or melanoma in situ). Later, there is a vertical growth phase with dermal invasion.
Lesion characteristics that are suggestive of melanoma include irregular pigment, irregular contour and border, nodule and ulcer formation, and changes in size/shape/color/contour/surface noted by the patient (see Figure 2.2-19).
TABLE 2.2-4.  Types of MelanomaLentigo maligna Arises in a lentigo. Usually found on sun-damaged skin of the face. Superfcial spreading Typically affects younger adults, presenting on the trunk in men and on the legs in women. A relatively prolonged horizontal growth phase helps identify the disease early, when it is still conf ned to the epidermis. Nodular Lesions have a rapid vertical growth phase and appear as a rapidly growing reddish-brown nodule with ulceration or hemorrhage. Acral lentiginous Begins on the hands and feet as a slowly spreading, pigmented patch. Type most commonly seen in Asians and African-Americans. Amelanotic Presents as a lesion without clinical pigmentation. Extremely diffcult to identify.
FIGURE 2.2-19. Melanoma.Note the asymmetry, border irregularity, color variation, and large diameter of this plaque.
(Reproduced, with permission, from Hurwitz RM. Pathology of the Skin: Atlas of Clinical-
Pathological Correlation, 2nd ed. Stamford, CT: Appleton & Lange, 1998: 432.) ■Malignant melanoma may metastasize, and 10% of patients with metastatic melanoma have no known 1° lesion. Metastasis may be local (to nearby skin), regional (between the original lesion and its regional lymph nodes), or distant (via lymphatic or hematogenous spread to almost every organ in the body).
Early recognition and treatment are essential. All adults should be examined for lesions that are suspicious for melanoma according to the ABCDE criteria, which identify dysplastic nevi and superficial spreading melanoma (see mnemonic).
The onset of pruritus is also an early sign of malignant change. An excisional biopsy should be performed on any suspicious lesion. Malignancy is determined histologically.
Malignant melanomas are staged by Breslow’s thickness (depth of invasion measured in millimeters) and by tumor-node-metastasis (TNM) staging (see Table 2.2-5). Clark’s level is another classification system linking melanoma depth to prognosis (see Table 2.2-6).
TABLE 2.2-5. TNM Staging of MelanomaT AB LE 2.2-6. Characterization of Melanoma by Clark’s Level
Lesions confined to the skin are treated by excision with margins. Lymph node dissection is useful for staging but does not ↑ survival. Chemotherapy and radiation therapy may be used but are not likely to be successful.
Malignant melanoma has the potential to relapse after several years; patients with early melanoma are at low risk for relapse but are at high risk for the development of subsequent melanomas. Patient surveillance is thus essential.
A vascular proliferative disease that has been attributed to a herpesvirus, HHV8, which is also called Kaposi’s sarcoma–associated herpesvirus (KSHV).
There are several types of KS:The classic variant is characterized by multicentric vascular macules and coalescent papules and plaques on the lower extremities. It usually occurs in the elderly, with a preponderance of cases in patients of Ashkenazi Jewish or Mediterranean descent.
More disseminated cases occur in African KS (endemic KS) and in immunocompromised patients.
Epidemic HIV-associated KS is an aggressive form of the disease, and although less common since the advent of HAART, it remains the most common HIV-associated malignancy.
Diagnosed by history and clinical impression, which are confirmed by biopsy showing spindle cells (elongated tumor cells) with  HHV-8 staining. The presence of the viral protein LANA in tumor cells can also be detected for diagnostic confirmation.
Treatment is technically palliative. Local lesions may be treated with radiation or cryotherapy; surgery is not recommended. Widespread or internal disease is treated with systemic chemotherapy (anthracyclines, paclitaxil, or IFN-α).
Not a fungus, but rather a slow, progressive neoplastic proliferation of T cells. Its pathogenesis is thought to be related to chronic immunostimulation that leads helper T cells to gather in the epidermis. Industrial exposure to irritating chemicals appears to ↑ risk. The disease is chronic and is more common in men than in women.
The early lesion is a nonspecific, psoriatic-appearing plaque that is palpable and often pruritic.
Stage I involves limited plaques, papules, and patches affecting < 10% BSA with no nodal involvement.
Stage II is characterized by limited or generalized skin involvement with palpable lymph nodes or one or more skin tumors with multicentric, often confluent reddish-brown nodules (see Figure 2.2-20). Rarely, patients skip the plaque stage and present directly with tumors.
Stage III is characterized by generalized erythroderma.FIGURE 2.2-20.  Mycosis fungoides.Massive nodular infiltration of the face leads to a leonine facies. (Reproduced, with permission, from Fitzpatrick TB. Color Atlas & Synopsis of Clinical Dermatology, 4th ed. New York: McGraw-Hill, 2001: 541.)
Stage IV is characterized by biopsy-lymph nodes or internal organ spread.
Patients may have dermatopathic lymphadenopathy without actual tumor involvement of the node. However, the internal organs can be involved, including the nodes, liver, and spleen.
Sézary’s syndrome is the leukemic phase of cutaneous T-cell lymphoma and is characterized by circulating Sézary cells in the peripheral blood, erythroderma, and lymphadenopathy.
Diagnosed by clinical features and histology, with immunologic characterization and electron microscopy showing the typical Sézary or Lutzner cells (cerebriform lymphocytes).
The early lesion is clinically indistinguishable from dermatitis, so histologic diagnosis is indicated for any dermatitis that is chronic and resistant to treatment.
Once clinical tumors have evolved, histology is useful for showing the type of cells present.
Stage I disease: Treat topically with steroids, retinoids, chemotherapy, or PUVA.
Stage II disease: Treat systemically with retinoids, interferon, monoclonal antibodies, or chemotherapy.
Photopheresis is the mainstay of treatment for many patients. For more extensive or advanced disease, radiation therapy is an effective option. Treatment modalities are often combined.
Disorders of Glucose Metabolism 114 TYPE 1 DIABETES MELLITUS 114 TYPE 2 DIABETES MELLITUS 115 METABOLIC SYNDROME 117
Due to autoimmune pancreatic β-cell destruction leading to insulin deficiency and abnormal fuel metabolism.
Classically presents with polyuria (especially nocturia), polydipsia, polyphagia, and rapid, unexplained weight loss. Patients may also present with ketoacidosis.
Usually affects nonobese children or young adults.Associated with HLA-DR3 and -DR4.At least one of the following is required to make the diagnosis:
A fasting (> 8-hour) plasma glucose of ≥ 126 mg/dL on two separate occasions.
A random plasma glucose of ≥ 200 mg/dL plus symptoms.
A two-hour postprandial glucose of ≥ 200 mg/dL after a glucose tolerance test on two separate occasions if the results of initial testing are equivocal.
Insulin (see Table 2.3-1) and self-monitoring of blood glucose in the normal range (80–120 mg/dL). Higher blood glucose levels (≥ 200 mg/dL) can be tolerated, particularly in the very young, in light of the ↑ risk of hypoglycemia.
Routine HbA1c testing (with a goal HbA1c < 8 in children), frequent BP checks, foot checks, annual dilated-eye exams, annual microalbuminuria screening, and a lipid profile every 2–5 years.
TABLE 2.3-1.  Types of InsulinRegular 30–60 minutes 2–4 hours 5–8 hours Humalog (lispro) 5–10 minutes 0.5–1.5 hours 6–8 hours NovoLog (aspart) 10–20 minutes 1–3 hours 3–5 hours Apidra (glulisine) 5–15 minutes 1.0–1.5 hours 1.0–2.5 hours NPH 2–4 hours 6–10 hours 18–28 hours Levemir (detemir) 2 hours No discernible peak 20 hours Lantus (glargine) 1–4 hours No discernible peak 20–24 hours a Combination preparations mix longer-acting and shorter-acting types of insulin together to provide immediate and extended coverage in the same injection (e.g., 70 NPH/30 regular = 70% NPH + 30% regular).
Table 2.3-2 outlines the acute, chronic, and treatment-related complications of DM.
A dysfunction in glucose metabolism that is best characterized as varying degrees of insulin resistance that may lead to β-cell burnout and insulin dependence.
TABLE 2.3-2.  Complications of DMComplications of treatment Dawn phenomenon Early-morning hyperglycemia caused by ↓ effectiveness of insulin and ↑ secretion of growth hormone (GH) and other hormones overnight. Move P.M. insulin closer to bedtime to treat. Acute complications Diabetic ketoacidosis (DKA) Hyperosmolar hyperglycemic state (HHS) Hyperglycemia-induced crisis that most commonly occurs in type 1 DM. Often precipitated by stress (including infections, MI, trauma, or alcohol) or by noncompliance with insulin therapy. May present with abdominal pain, vomiting, Kussmaul respirations, and a fruity, acetone breath odor. Patients are severely dehydrated with many electrolyte abnormalities and may also develop mental status changes. Treatment includes f uids, potassium, insulin, bicarbonate (if pH is < 7), and treatment of the initiating event or underlying disease process. Presents as profound dehydration, mental status changes, hyperosmolarity, and extremely high plasma glucose (> 600 mg/dL) without acidosis and with small or absent ketones. Occurs in type 2 DM; precipitated by acute stress (dehydration, infections) and often can be fatal. Treatment includes aggressive fluid and electrolyte replacement and insulin. Treat the initiating event. Chronic complications Retinopathy (nonproliferative, proliferative) Diabetic nephropathy Neuropathy Macrovascular complications Appears when diabetes has been present for at least 3–5 years. Preventive measures include control of hyperglycemia and hypertension, annual eye exams, and laser photocoagulation therapy for retinal neovascularization. Characterized by glomerular hyperfltration followed by microalbuminuria. Preventive measures include ACEIs or ARBs and BP/glucose control. Peripheral, symmetric, sensorimotor neuropathy leading to burning pain, foot trauma, infections, and diabetic ulcers. Treat with preventive foot care and analgesics. Late complications due to autonomic dysfunction include delayed gastric emptying, esophageal dysmotility, impotence, and orthostatic hypotension. Cardiovascular, cerebrovascular, and peripheral vascular disease. Cardiovascular disease is the most common cause of death in diabetic patients. The goal BP is < 130/< 75; ↓ LDL to < 100 mg/dL; ↓ triglycerides to < 150 mg/dL. Patients should also be started on low-dose ASA.
■Somogyi effect: Nocturnal hypoglycemia leading to a surge of counterregulatory hormones, leading in turn to hyperglycemia in the morning.
■Dawn phenomenon: Nocturnal secretion of GH leading to early-morning hyperglycemia.
Patients typically present with symptoms of hyperglycemia.Onset is more insidious than that of type 1 DM, and patients often present with complications.
Nonketotic hyperglycemia may be seen in the setting of poor glycemic control.
Usually occurs in older adults with obesity (often truncal); has a strong genetic predisposition.
Diagnostic criteria are the same as those for type 1 DM.
Follow-up testing:Patients with no risk factors: Test at 45 years of age; retest every three years.
Patients with impaired fasting glucose (> 110 mg/dL but < 126 mg/ dL): Follow up with frequent retesting.
The goal of treatment is tight glucose control—i.e., blood glucose levels ranging from 80 to 120 mg/dL and HbA1c levels < 7. Treatment measures include the following:
Diet, weight loss, and exercise.Oral agents (monotherapy or combination if uncontrolled):Sulfonylureas (glipizide, glyburide, and glimepiride): Insulin secretagogues. Hypoglycemia and weight gain are side effects.
Meglitinides (repaglinide and nateglinide): Short-acting agents whose mechanism of action is similar to that of sulfonylureas.
Metformin: Inhibits hepatic gluconeogenesis; ↑ peripheral sensitivity to insulin. Side effects include weight loss, GI upset, and, rarely, lactic acidosis. Contraindicated in the elderly (those > 80 years of age) and in patients with renal disease.
Thiazolidinediones (the “glitazones”): ↑ insulin sensitivity. Side effects include weight gain, edema, and potential hepatotoxicity.
α-glucosidase inhibitors: ↓ intestinal absorption of carbohydrates. Rarely used owing to the side effect of fl atulence.
DDP-4 inhibitors (sitagliptin): Inhibit the degradation of the endogenous enzyme that breaks down glucagon-like peptide 1 (GLP-1).
Insulin (alone or in conjunction with oral agents).Incretins (exenatide): GLP-1 agonists. Injected subcutaneously. Delay absorption of food; ↑ insulin secretion and ↓ glucagon secretion. Side effects include nausea and (rarely) pancreatitis.
Statins for hypercholesterolemia (goal LDL < 100); glucose control and fibric acid derivatives for hypertriglyceridemia.
Strict BP control to < 130/80; ACEIs/ARBs are usually first-line agents.
Antiplatelet agents (ASA) for patients at risk of cardiovascular disease or for those > 40 years of age.
Regular screening for cardiovascular disease, nephropathy, retinopathy, neuropathy, and smoking cessation.
See Table 2.3-2 for an outline of the complications of DM. Note that the presence of diabetes is equivalent to the highest risk for cardiovascular disease regardless of all other risk factors.
Also known as insulin resistance syndrome or syndrome X. Associated with an ↑ risk of CAD and mortality from a cardiovascular event.
Presents with abdominal obesity, high BP, impaired glycemic control, and dyslipidemia.
Three out of five of the following criteria must be met:
Abdominal obesity (↑ waist girth): > 40 inches in men and > 35 inches in women.
Triglycerides ≥ 150 mg/dL.HDL < 40 mg/dL in men and < 50 mg/dL in women.
BP ≥ 130/85 mmHg or administration of antihypertensive drugs.Fasting glucose ≥ 100 mg/dL.Intensive weight loss, aggressive cholesterol lowering, and BP control. Metformin has been shown to slow the onset of diabetes in this high-risk population.
Testing of Thyroid FunctionTFTs include the following (see also Table 2.3-3): ■TSH measurement: The single best test for assessing thyroid function. High TSH levels lead to 1° hypothyroidism; low TSH levels lead to thyrotoxicosis.
■Radioactive iodine uptake (RAIU) and scan: Determines the level of iodine uptake by the thyroid. Useful in differentiating thyrotoxic states, but has a limited role in determining malignancy.
T AB LE 2.3-3. Common Thyroid Function AbnormalitiesIn 1° endocrine disturbances, the gland itself is abnormal. In 2° endocrine disturbances, the HPA malfunctions.
1° hyperthyroidism ↓↑↑Graves’ disease, toxic multinodular goiter, toxic adenoma, amiodarone, molar pregnancy, postpartum thyrotoxicosis, postviral thyroiditis. 1° hypothyroidism ↑↓↓Hashimoto’s thyroiditis, hypothyroid phase of thyroiditis, iatrogenic factors (radioactive iodine thyroid ablation, excision with inadequate supplementation, external radiation, lithium, or amiodarone), iodine def ciency, inf ltrative disease.
Thyroid storm is an acute, life-threatening form of thyrotoxicosis that may present with atrial f brillation, fever, and delirium. Admit to intensive care.
TBG-elevating states that should not be treated include pregnancy, estrogen administration, infections, nephrotic syndrome, and anabolic steroid use.
Total T4 measurement: Not an adequate screening test. Ninety-nine percent of circulating T4 is bound to thyroxine-binding globulin (TBG). Total T4 levels can be altered by changes in levels of binding proteins.
T3 resin uptake (T3RU): Used with total T4 or T3 to correct for changes in TBG levels (e.g., the free thyroxine index = total T4 × T3RU).
Free T4 measurement: The preferred screening test for thyroid hormone levels; more useful for unstable thyroid states.
Refers to causes of thyrotoxicosis (↑ levels of T3/T4 due to any cause) in which the thyroid overproduces thyroid hormone, including Graves’ disease, toxic multinodular goiter (also called Plummer’s disease), and toxic adenomas.
Presents with weight loss, heat intolerance, nervousness, palpitations, ↑bowel frequency, insomnia, and menstrual abnormalities.
Exam reveals warm, moist skin, goiter, sinus tachycardia or atrial f brillation, fine tremor, lid lag, and hyperactive refl exes. Exophthalmos, pretibial myxedema, and thyroid bruits are seen only in Graves’ disease (see Figure 2.3-1).
The initial test of choice is serum TSH level, followed by T4 levels and, rarely, T3 (unless TSH is low and free T4 is not elevated). See Table 2.3-3.
AB F IGU R E 2.3-1. Physical signs of Graves’ disease.
(A) Graves’ ophthalmopathy. (B) Pretibial myxedema. (Figure 2.3-1A reproduced, with permission, from the Pathology Education Instructional Resource [PEIR] digital library [ http://peir.
at the University of Alabama, Birmingham. Figure 2.3-1B reproduced, with permission, from Greenspan FS, Strewler GJ. Basic and Clinical Endocrinology, 5th ed. Stamford, CT: Appleton & Lange, 1997.) 1° therapy is radioactive 131I thyroid ablation; antithyroid drugs (methimazole or propylthiouracil) may also be used if radioactive iodine is not indicated. Thyroidectomy is rarely indicated.
Give propranolol for adrenergic symptoms while awaiting the resolution of hyperthyroidism.
Administer levothyroxine to prevent hypothyroidism in patients who have undergone ablation or surgery.
Hashimoto’s thyroiditis is the most common cause of hypothyroidism (see Table 2.3-3). Anti-TPO antibodies are . The second most common cause is iatrogenic. Myxedema coma refers to severe hypothyroidism with ↓ mental status, hypothermia, and other parasympathetic symptoms. Mortality is 30–60%.
Presents with weakness, fatigue, cold intolerance, constipation, weight gain, depression, menstrual irregularities, and hoarseness. Exam may reveal dry, cold, puffy skin accompanied by edema, bradycardia, and delayed relaxation of DTRs.
See Table 2.3-3.Uncomplicated hypothyroidism (e.g., Hashimoto’s disease): Administer levothyroxine.Myxedema coma: Treat with IV levothyroxine and IV hydrocortisone (if adrenal insufficiency has not been excluded).
Inflammation of the thyroid gland. Common subtypes include subacute granulomatous, radiation-induced, autoimmune (lymphocytic, chronic, or Hashimoto’s), postpartum, and drug-induced (e.g., amiodarone) thyroiditis.
The subacute form presents with a tender thyroid accompanied by malaise and URI symptoms. Other forms are associated with painless goiter.
Thyroid dysfunction (typically thyrotoxicosis followed by hypothyroidism), with ↓ uptake on RAIU during the thyrotoxic phase.
β-blockers for hyperthyroidism; levothyroxine for hypothyroidism.Subacute thyroiditis is usually self-limited; treat with NSAIDs or with oral corticosteroids for severe cases.
TSH receptor antibodies are seen in patients with Graves’ disease.
The most Popular is Papillary:Check calcitonin levels if medullary cancer is suspected.Thyroid nodules are very common and show an ↑ incidence with age. Most are benign.
Usually asymptomatic on initial presentation.Hyperfunctioning nodules present with hyperthyroidism and local symptoms (dysphagia, dyspnea, cough, choking sensation) and are associated with a  family history (especially medullary thyroid cancer).
An ↑ risk of malignancy is associated with a history of neck irradiation, “cold” nodules on radionuclide scan, male sex, age < 20 or > 70, firm and fixed solitary nodules, a  family history (especially medullary thyroid cancer), and rapidly growing nodules with hoarseness.
Check for anterior cervical lymphadenopathy. Carcinoma (see Table 2.3 4) may be frm and f xed.
Medullary thyroid carcinoma is associated with multiple endocrine neoplasia (MEN) type 2 and familial medullary thyroid cancer.
The best method of assessing a nodule for malignancy is f ne-needle aspiration (FNA), which has high sensitivity and moderate specificity.
TFTs (TSH to exclude hyperfunction).Ultrasound determines if the nodule is solid or cystic; a radioactive scan determines whether it is hot or cold (cancers are usually cold and solid). Hot nodules are never cancerous and should not be biopsied.
TABLE 2.3-4. Types of Thyroid CarcinomaPapillary Represents 75–80% of thyroid cancers. The female-to-male ratio is 3:1. Slow growing; found in thyroid hormone–producing cells. Ninety percent of patients survive 10 years or more after diagnosis; the prognosis is worse in elderly patients or those with large tumors. Follicular Accounts for 17% of thyroid cancers; found in thyroid hormone– producing cells. Ninety percent of patients survive 10 years or longer after diagnosis; the prognosis is worse in elderly patients or those with large tumors. Medullary Responsible for 6–8% of thyroid cancers; found in calcitonin-producing C cells; the prognosis is related to degree of vascular invasion. Eighty percent of patients survive at least 10 years after surgery. Anaplastic Accounts for < 2% of thyroid cancers; rapidly enlarges and metastasizes. Ten percent of patients survive for > 3 years. a Tumors may contain mixed papillary and follicular pathologies.
Benign FNA: Follow with physical exam/ultrasound or a trial of levothyroxine suppression treatment.
Malignant FNA: Surgical resection is first-line treatment; adjunctive radioiodine ablation following excision is appropriate for follicular lesions.
Indeterminate FNA: Remove the nodule by surgical excision and wait for final pathology.
Medullary thyroid cancer has a poorer prognosis than papillary and follicular types. Anaplastic thyroid cancer has an extremely poor prognosis.
Associated with autosomal-dominant inheritance. Subtypes are as follows:MEN type 1 (Wermer’s syndrome): Pancreatic islet cell tumors (e.g., Zollinger-Ellison syndrome, insulinomas, VIPomas), parathyroid hyperplasia, and pituitary adenomas.
MEN type 2A (Sipple’s syndrome): Medullary carcinoma of the thyroid, pheochromocytoma or adrenal hyperplasia, parathyroid gland hyperplasia.
MEN type 2B: Medullary carcinoma of the thyroid, pheochromocytoma, oral and intestinal ganglioneuromatosis (mucosal neuromas), marfanoid habitus.
A common metabolic bone disease characterized by low bone mass and microarchitectural disruption, with bone mineral density > 2.5 SDs below normal peak bone mass. Most often affects thin, postmenopausal women (17%), especially Caucasians and Asians, with risk doubling (30%) after age 65.
Commonly asymptomatic even in the presence of a vertebral fracture.
Exam may reveal hip fractures, vertebral compression fractures (loss of height and progressive thoracic kyphosis), and/or distal radius fractures following minimal trauma (see Figure 2.3-2).
Bone pain unrelated to fracture is most likely osteomalacia rather than osteoporosis.
Smoking, excessive caffeine or alcohol intake, a history of estrogen-depleting conditions (e.g., amenorrhea, eating disorders), thyroid dysfunction, and steroid use are all associated with an ↑ risk.
DEXA: The gold standard; reveals significant osteopenia (bone mineral density < 2.5 SDs from normal peak level), most commonly in the vertebral bodies, proximal femur, and distal radius.
Labs: Markers of bone turnover (↑ urinary N-telopeptides and deoxypyridinoline) can facilitate diagnosis in equivocal cases but are not routinely used; rule out 2° causes with TFTs, CMP, serum 25-hydroxyvitamin D, CBC, and testosterone (in men).
X-rays: Global demineralization is apparent only after > 30% of bone density is lost.
Osteoporosis is the most common cause of pathologic fractures in elderly, thin women.
F IGU R E 2.3-2.  Radiographic findings in osteoporosis.compression). (Reproduced, with permission, from Kasper DL et al. Harrison’s Principles of
Internal Medicine, 16th ed. New York: McGraw-Hill, 2005: 2269.)Prevention with calcium supplementation and vitamin D.Smoking cessation and weight-bearing exercises help maintain bone density.Bisphosphonates (e.g., alendronate, risedronate, ibandronate, zoledronic acid), selective estrogen receptor modulators (e.g., raloxifene), and intranasal calcitonin may be used to prevent resorption and stabilize bone mineral density.
Estrogen replacement therapy may be indicated for short-term treatment in the symptomatic perimenopausal period.
Recombinant PTH may be used in patients with the highest level of risk.
Characterized by an ↑ rate of bone turnover. Causes both excessive resorption and excessive formation of bone, leading to a “mosaic” lamellar bone pattern. Suspected to be due to latent viral infection in genetically susceptible individuals. Found in roughly 4% of men and women > 40 years of age, and associated with 1° hyperparathyroidism in up to one-fifth of patients.
Usually asymptomatic, but may present with aching bone or joint pain, headaches, skull deformities, fractures, or nerve entrapment (leads to loss of hearing in 30–40% of cases).
Based on clinical history, characteristic radiographic changes (see Figure 2.33), and lab findings.
F IGU R E 2.3-3.  Radiographic findings in Paget’s disease.
Skull of a 58-year-old woman with Paget’s disease of bone. (Reproduced, with permission, from
Kasper DL et al. Harrison’s Principles of Internal Medicine, 16th ed. New York: McGraw-Hill, 2005: 2280.)
Imaging: Radionuclide bone scan is the most sensitive test.Labs: Abnormalities include ↑ serum alkaline phosphatase with normal calcium and phosphate levels; urinary pyridinolines may be helpful. Must be differentiated from metastatic bone disease.
The majority of patients are asymptomatic and require no treatment.
There is no cure for Paget’s disease. Bisphosphonates and calcitonin are used to slow osteoclastic bone resorption; NSAIDs and acetaminophen can be given for arthritis pain.
Pathologic fractures, cardiac complications, osteosarcoma (up to 1%).Eighty percent of 1° cases are due to a single adenoma and 15% to parathyroid hyperplasia. The most common 2° cause is phosphate retention in chronic kidney disease, which leads to renal osteodystrophy. 3° hyperparathyroidism occurs when chronic 2° hyperparathyroidism progresses to an unregulated state, resulting in hypercalcemia.
Most cases are asymptomatic, but signs and symptoms may be mild and include stones (nephrolithiasis), bones (bone pain, myalgias, arthralgias, fractures), abdominal groans (abdominal pain, nausea, vomiting, PUD, pancreatitis), and psychiatric overtones (fatigue, depression, anxiety, sleep disturbances).
Chronic renal insufficiency and gout are also associated with 1° hyperparathyroidism.
Relative surgical criteria for hyperparathyroidism include age < 50, markedly ↓ bone mass, nephrolithiasis/renal insuff ciency, profoundly elevated serum calcium or life-threatening hypercalcemia, and urine calcium > 400 mg in 24 hours.
Labs reveal hypercalcemia, hypophosphatemia, and hypercalciuria. Intact PTH is inappropriately ↑ relative to ionized calcium (see Table 2.3-5). Vitamin D deficiency may obscure mild cases.
A radionuclide parathyroid scan may help with localization of an adenoma, although localization is not always necessary.
Cancer is the most likely alternative diagnosis and must be ruled out, but with carcinoma PTH is usually < 25 pg/mL unless hyperparathyroidism is also present. Lithium and thiazides may exacerbate hyperparathyroidism.
Parathyroidectomy if the patient is symptomatic or if certain criteria are met. For acute hypercalcemia, give IV fuids (with a loop diuretic in the setting of renal or heart failure), IV bisphosphonate, and calcitonin.
Oral phosphate binders (aluminum hydroxide, calcium salts, sevelamer hydrochloride, and lanthanum carbonate) and dietary phosphate restriction are used in patients with 2° hyperparathyroidism regardless of dialysis status.
Cinacalcet ↓ PTH as well as calcium and phosphate and may be a helpful adjunct in end-stage renal disease.
Hypercalcemia is the most severe complication, presenting acutely with coma or altered mental status, bone disease, nephrolithiasis, and abdominal pain with nausea and vomiting.
The most common endogenous cause of Cushing’s syndrome is hypersecretion of ACTH from a pituitary adenoma (known as Cushing’s disease, or central hypercortisolism). Other endogenous causes include ectopic ACTH secretion from neoplasia (e.g., carcinoid tumor, small cell lung cancer) and excess adrenal secretion of cortisol (e.g., bilateral adrenal hyperplasia, adenoma, adrenal cancer). The condition is most commonly iatrogenic, resulting from treatment with exogenous corticosteroids.
T AB LE 2.3-5. Functions and Mechanisms of PTHChief cells of parathyroid ↑ bone resorption of calcium and phosphate. ↑ kidney resorption of calcium in the distal convoluted tubule. ↓ kidney resorption of phosphate. ↑ 1,25-(OH)2 vitamin D (cholecalciferol) production by stimulating kidney 1α-hydroxylase. PTH ↑ serum Ca2+, ↓ serum (PO4)3–, and ↑urine (PO4)3–. PTH stimulates both osteoclasts and osteoblasts. ↓ in free serum Ca2+ ↑ PTH secretion.
Presents with hypertension, central obesity, muscle wasting, thin skin with purple striae, psychological disturbances, hirsutism, moon facies, and “buffalo hump.”
Exam reveals depression, oligomenorrhea, growth retardation, proximal weakness, acne, excessive hair growth, symptoms of diabetes (2° to glucose intolerance), and ↑ susceptibility to infection. Headache or cranial nerve deficits are also seen with increasing size of the pituitary mass.
Diagnosis is as follows (see also Table 2.3-6):Begin with a screen: An elevated 24-hour free urine cortisol or evening salivary cortisol or a  overnight low-dose dexamethasone suppression test is considered abnormal if A.M. cortisol is persistently elevated following overnight suppression.
Distinguish ACTH-dependent from ACTH-independent causes: If late-afternoon ACTH levels are elevated, Cushing’s disease or ectopic ACTH is likely.
Hyperglycemia, glycosuria, and hypokalemia may also be present.Surgical resection of the hypersecretory source (pituitary, adrenal).Pituitary radiotherapy may also be considered.Blockers of adrenal steroidogenesis (e.g., ketoconazole, aminoglutethimide) may be of benefit.
Permanent hormone replacement therapy to correct deficiencies after treatment of the 1° lesion.
An adult condition due to a benign pituitary GH adenoma. Children with excess GH production present with gigantism.
■ Presents with enlargement of the jaw, hands, and feet and coarsening of facial features. May lead to carpal tunnel syndrome, diastolic dysfunction, hypertension, and arthritis.
T AB LE 2.3-6. Laboratory Findings in Cushing’s SyndromeFor unknown reasons, patients with DI prefer ice-cold beverages.Bitemporal hemianopia may result from compression of the optic chiasm by a pituitary adenoma.
Excess GH may also lead to glucose intolerance or diabetes.
Imaging: MRI of the pituitary shows a sellar lesion.Labs: Screen by measuring insulin-like growth factor 1 (IGF-1) levels (↑with acromegaly); confirm the diagnosis with an oral glucose suppression test (GH levels will remain elevated despite glucose suppression; baseline GH is not a reliable test).
Transsphenoidal surgical resection or external beam radiation of the tumor.
Octreotide can be used to suppress GH secretion.Pegvisomant can be used to block GH receptors in refractory cases.
Prolactinoma is the most common functioning pituitary tumor.Other pathologic causes include craniopharyngioma, irradiation, drugs (e.g., dopamine), and cirrhosis.
Hx/PE: Hypogonadism is manifested by infertility, oligomenorrhea, or amenorrhea. Galactorrhea, gynecomastia, or bitemporal hemianopia may be prominent.
Dx: The serum prolactin level is typically > 200 mg/mL.
Dopamine agonists (f rst-line therapy): Cabergoline or bromocriptine.Surgery: Should be considered when medical treatment has failed, when the patient desires future pregnancies, or in the setting of visual field defects.
Failure to concentrate urine as a result of central or nephrogenic ADH dysfunction. Subtypes are as follows:
Central DI: The posterior pituitary fails to secrete ADH. Causes include tumor, ischemia (Sheehan’s syndrome), traumatic cerebral injury, infection, and autoimmune disorders.
Nephrogenic DI: The kidneys fail to respond to circulating ADH. Causes include renal diseases and drugs (e.g., lithium, demeclocycline).
Presents with polydipsia, polyuria, and persistent thirst with dilute urine.
Patients may present with hypernatremia and dehydration, but if given unlimited access to water, they are typically normonatremic.
■ During a water deprivation test, patients excrete a high volume of dilute urine.
Desmopressin acetate (DDAVP), a synthetic analog of ADH, can be used to distinguish central from nephrogenic DI.
Central DI: DDAVP challenge will ↓urine output and ↑urine osmolarity.
Nephrogenic DI: DDAVP challenge will not significantly ↓ urine output.
MRI may show a pituitary or hypothalamic mass in central DI.
Treat the underlying cause.Central DI: Administer DDAVP intranasally or orally.Nephrogenic DI: Salt restriction and water intake are the 1° treatment. Thiazide diuretics are used to promote mild volume depletion and to stimulate proximal reabsorption of salt and water.
A common cause of euvolemic hyponatremia that results from stimulated ADH release independent of serum osmolality.
Associated with CNS disease (e.g., head injury, tumor), pulmonary disease (e.g., sarcoid, pneumonia), ectopic tumor production/paraneoplastic syndrome (e.g., small cell carcinoma), drugs (e.g., antipsychotics, antidepressants), or surgery.
Diagnose on the basis of a urine osmolality > 50–100 mOsm/kg with concurrent serum hyposmolarity in the absence of a physiologic reason for ↑ADH (e.g., CHF, cirrhosis, hypovolemia).
Urinary sodium ≥ 20 mEq/L demonstrates that the patient is not hypo-Fluid restriction is the volemic.
cornerstone of SIADH treatment.Restrict f uid and address the underlying cause.If hyponatremia is severe (< 110 mEq/L) or if the patient is significantly symptomatic (e.g., comatose, seizing), cautiously give hypertonic saline.
Demeclocycline can help normalize serum sodium by antagonizing the action of ADH in the collecting duct.
Chronic correction depends on treatment of the underlying disorder.Tolvaptan (a vasopressin agonist) can be used to treat refractory chronic cases.
May be 1° or 2°. Etiologies are as follows: ■ 1°: ■Most commonly caused by autoimmune adrenal cortical destruction (Addison’s disease), leading to deficiencies of mineralocorticoids and glucocorticoids. Autoimmune destruction may occur as part of a
The 4 S’s of adrenal crisis management:Salt: 0.9% salineSteroids: IV hydrocortisone 100 mg q 8 hSearch for the underlying illnessDo not delay in giving steroids when diagnosing a patient with AI.
polyglandular autoimmune syndrome (hypothyroidism, type 1 DM, vitiligo, premature ovarian failure, testicular failure, pernicious anemia).
■Other causes of 1° AI include congenital enzyme deficiencies, adrenal hemorrhage, TB, and other infections.
■ 2°: Caused by ↓ ACTH production by the pituitary; most often due to cessation of long-term glucocorticoid treatment.
Most symptoms are nonspecific.Weakness, fatigue, and anorexia with weight loss are common. GI manifestations, hypotension, and salt craving are also seen.
Hyperpigmentation (due to ↑ ACTH secretion) is seen in Addison’s disease, especially in areas of sun exposure or friction.
Labs show hyponatremia and eosinophilia (1° or 2°).Hyperkalemia is specific to 1° AI.Hypercalcemia is seen in up to one-third of cases.Diagnosis is confirmed with plasma cortisol levels:Low plasma cortisol levels (< 20 μg/dL) during a period of high physiologic stress is confirmatory.
A random plasma cortisol level > 20 μg/dL excludes the diagnosis.
Confrmatory test with synthetic ACTH stimulation test: A plasma cortisol level > 20 μg/dL excludes the diagnosis.
Glucocorticoid replacement, with mineralocorticoid replacement if 1°.In adrenal crisis, correct electrolyte abnormalities as needed; provide 50% dextrose to correct hypoglycemia; and initiate volume resuscitation.
■↑ steroids during periods of stress (e.g., major surgery, trauma, infection). Avoid 2° AI by tapering steroids slowly.
A tumor of chromaffin tissue found either in the adrenal medulla or in extra-adrenal sites that secrete catecholamines. May be associated with von Hippel–Lindau syndrome, neurofibromatosis, or MEN 2 syndromes.
Hx/PE: Presents with intermittent tachycardia, palpitations, chest pain, diaphoresis, hypertension, headache, tremor, and anxiety. Crises may be precipitated by anesthesia.
Dx: CT or MRI often demonstrates a suprarenal mass. Screen with plasma-free metanephrines (metanephrine and normetanephrine) or 24hour urine metanephrines. MIBG scan is sometimes helpful.
Tx: Surgical resection. Preoperatively, use α-adrenergic blockade f rst to control hypertension, followed by β-blockade to control tachycardia. Never give β-blockade first; otherwise, unopposed α-adrenergic stimulation will lead to refractory hypertension.
Results from excessive secretion of aldosterone from the zona glomerulosa of the adrenal cortex. It is usually due to adrenocortical hyperplasia (70%) but can also result from unilateral adrenal adenoma (Conn’s syndrome).
Presents with hypertension, headache, polyuria, and muscle weakness.Tetany, paresthesias, and peripheral edema are seen in severe cases.
Patients have diastolic hypertension without edema.Labs show hypokalemia, mild hypernatremia, metabolic alkalosis, hypomagnesemia, and an ↑aldosterone/plasma renin activity ratio (from hyposecretion of renin that fails to ↑ appropriately with volume depletion as well as from hypersecretion that does not suppress with volume expansion).
CT or MRI may reveal an adrenal mass.Laparoscopic or open adrenalectomy for adrenal tumors (after correcting BP and potassium).
Treat bilateral hyperplasia with spironolactone, an aldosterone receptor antagonist.A family of inherited disorders that lead to cortisol def ciency. Most cases are due to 21-hydroxylase defciency (autosomal recessive) that leads to ↓ cortisol production with elevated cortisol precursors (e.g., 17-OH progesterone). In severe cases, mineralocorticoid deficiency with salt wasting may develop. Other causes include 11and 17-hydroxylase deficiencies. Cortisol deficiency stimulates ACTH synthesis, leading to overproduction of adrenal androgens.
Presents with ambiguous genitalia in female infants and virilization when manifested later in life.
Also characterized by macrogenitosomia in male infants; precocious puberty (if manifested later in life); and hypertension (with 11and 17-hydroxylase deficiencies).
Diagnosed by high levels of cortisol precursors and androgens found in blood and urine.
Medical: Immediate fuid resuscitation and salt repletion. Administer cortisol to ↓ ACTH and adrenal androgens. Fludrocortisone is appropriate for severe 21-hydroxylase deficiency.
Surgical: May be required in the case of ambiguous genitalia in female infants.
Refer to the Gynecology chapter for information on the diagnosis and treatment of late-onset congenital adrenal hyperplasia.
Assessment of Disease Frequency 132Assessment of Diagnostic Studies 132Assessment of Risk 134Measures of Effect 135 Survival Curves 136 Treatment 136Screening Recommendations 141 Causes of Death 143 Reportable Diseases 144
The prevalence of a disease is the number of existing cases in the population at a specifc moment in time.
The incidence of a disease is the number of new cases in the disease-free population that develop over a period of time.
Prevalent cases are incident cases that have persisted in a population for various reasons:
Prevalence = Incidence × Average duration of diseaseA prevalence study is one in which people in a population are examined for the presence of a disease of interest at a given point in time.
The advantages of prevalence studies are as follows:They provide an effcient means of examining a population, allowing cases and noncases to be assessed all at once.
They can be used as a basis for diagnostic testing.
They can be used to plan which health services to offer and where.
Their disadvantages include the following:One cannot determine causal relationships because information is obtained only at a single point in time.
The risk or incidence of disease cannot be directly measured.
Physicians often use tests to try to ascertain a diagnosis, but because no test is perfect, a given result may be falsely or  (see Figure 2.4-1). When deciding whether to administer a test, one should thus consider both its sensitivity and its specif city.
■Sensitivity is the probability that a patient with a disease will have a test result. A sensitive test will rarely miss people with the disease and is therefore good at ruling people out.
Incidence is measured with a cohort study; prevalence is measured with a prevalence study.
As the mortality of a disease decreases, the prevalence of that disease increases (e.g., HIV infection).
Another name for a prevalence study is a cross-sectional study.
F IGU R E 2.4-1.  Sensitivity, specificity, PPV, and NPV.
■Specificity is the probability that a patient without a disease will have a test result. A specific test will rarely determine that someone has the disease when in fact they do not and is therefore good at ruling people in.
The ideal test is both sensitive and specifc, but a trade-off must often be made between sensitivity and specif city.
High sensitivity is particularly desirable when there is a signif cant penalty for missing a disease. It is also desirable early in a diagnostic workup, when it is necessary to reduce a broad differential. Example: An initial ELISA test for HIV infection.
High specificity is useful for confrming a likely diagnosis or for situations in which false-results may prove harmful. Example: A Western blot confrmatory HIV test.
Example: You search for your physician, Mary Adel, MD, in the local phone book.
Identifying all individuals named “Mary” would be a sensitive test, as anyone named Mary Adel would likely be included in the results. However, it is not specif c, as numerous other physicians would also be included. Remember the mnemonic “Snout”: High SENsitivity would allow one to rule out physicians not listed with this f rst name.
Identifying only individuals with the full name “Mary Lucy Adel IV” is very specifc, since individuals not named Mary Adel are especially likely to be declined. However, it is not sensitive, as she may be overlooked if she is not listed by her complete name. Remember the mnemonic “SPin”: High SPecifcity would allow one to rule in physicians listed with this full name.
Once a test has been administered and a patient’s result has been made available, that result must be interpreted through use of predictive values (or post-test probabilities):
The positive predictive value (PPV) is the probability that a patient with a  test result truly has the disease. The more specifc a test, the higher its PPV. The higher the disease prevalence, the higher the PPV of the test for that disease.
The negative predictive value (NPV) is the probability that a patient with a  test result truly does not have the disease. The more sensitive a test, the higher its NPV. The lower the disease prevalence, the higher the NPV of the test for that disease.
Another way to describe the performance of a diagnostic test involves the use of likelihood ratios (LRs), which express how much more or less likely a given test result is in diseased as opposed to nondiseased people:
Diseased people with a test result SensitivityNondiseased people with a test result 1 − specif city
SnOUT: Sensitive tests rule OUT disease. SpIN: Specific tests rule IN disease.
Because the predictive value of a test is affected by disease prevalence, it is advantageous to apply diagnostic tests to patients with an ↑ likelihood of having the disease being sought (i.e., an at-risk population).
If a test has an LR of 1, it does not change the pretest probability of disease. If the LR is 10, it makes disease 45% more likely. If the LR is 0.1, disease is 45% less likely.
Diseased people with a test result 1 − sensitivityNondiseased people with a test result Specif cityIf you see a set of COworkers being followed over time, think COhort study.
Cohort studies are also known as longitudinal studies or incidence studies.
Knowledge of risk factors may be used to predict future disease in a given patient. Risk factors may be causal (immediate or distant causes of disease) or disease markers (in which removing the risk factor does not necessarily ↓ the likelihood of disease). Risk factors can be diffcult to discover for a variety of reasons, including the following:
A disease may have a long latency period, with risky exposures remote and forgotten.
A risky exposure may be so common that its impact is hard to discern.
Disease incidence may be low, and it is hard to draw conclusions from infrequent events.
Risk associated with any individual exposure is small and hard to parse out.
There is seldom a close, constant relationship between a risk factor and a disease.
The best way to determine whether an exposure actually ↑ disease risk is with a prospective study. The ideal study for risk factor assessment would be an experiment in which the researcher controls risk exposure and then relates it to disease incidence. Doing so, however, may be unethical as well as prohibitively intrusive, time consuming, and expensive. Instead, observational studies such as cohort or case-control studies are used to determine risk.
In a cohort study, a group of people is assembled, none of whom have the outcome of interest (i.e., the disease), but all of whom could potentially experience that outcome. For each possible risk factor, the members of the cohort are classifed as either exposed or unexposed. All the cohort members are then followed over time, and rates of outcome events are compared in the two exposure groups.
Advantages of cohort studies are as follows:They follow the same logic as the clinical question (if people are exposed, will they get the disease?).
They are the only way to directly determine incidence.They can be used to assess the relationship of a given exposure to many diseases.
In prospective studies, exposure is elicited without bias from a known outcome.
The disadvantages of such studies include the following:They can be time consuming and expensive.Studies assess only the relationship of the disease to the few exposure factors recorded at the start of the study.
They require many subjects and are thus ineffcient and cannot be used to study rare diseases.
Cohort studies may be prospective—in which a cohort is assembled in the present and followed into the future—or they may be retrospective, in which a cohort is identifed from past records and followed to the present.
Case-control studies are essentially cohort studies in reverse. In such studies, a researcher selects two groups—one with disease (cases) and one without (controls)—and then looks back in time to measure the comparative frequency of exposure to a possible risk factor in the two groups.
The validity of a case-control study depends on appropriate selection of cases and controls, the manner in which exposure is measured, and the manner in which extraneous variables (confounders) are dealt with.
Cases and controls should be comparable in terms of opportunity for exposure (i.e., they should be members of the same base population with an equal opportunity of risk factor exposure).
Cases should be newly diagnosed using explicit criteria for diagnosis.
Exposures should be assessed in as unbiased a fashion as possible.
Confounding may be ↓ by matching subjects or through the stratif cation of subjects. Multivariable analysis may be helpful in this context.
Advantages of such studies are as follows:Studies use small groups, thereby reducing expense.They can be used to study rare diseases and can easily examine multiple risk factors.
Disadvantages include the following:Studies cannot calculate disease prevalence, incidence, or relative risk, because the numbers of subjects with and without a disease are determined artifcially by the investigator rather than by nature (an odds ratio can be used to estimate relative risk).
Retrospective data may be inaccurate owing to recall or survivorship biases.
If alcohol intake among individuals with breast cancer is compared with that of individuals without breast cancer, think case-control study.
Absolute risk: The number of finger injuries among hospital staff this week.
There are several ways to express and compare risk. These include the following:
Absolute risk: Defned as the incidence of disease.Attributable risk (or risk difference): The additional incidence of disease that is due to a risky exposure, on top of the background incidence from other causes.
Attributable risk = Incidence of disease in exposed – Incidence in unexposed
Relative risk (or risk ratio): Expresses how much more likely an exposed person is to get disease in comparison to an unexposed person. This indicates the strength of the association between exposure and disease, making it useful when one is considering disease etiology.
■ Odds ratio: An estimate of relative risk that is used in case-control studies. The odds ratio tells how much more likely it is that a person with a disease has been exposed to a risk factor than someone without the disease. The
Attributable risk: (number of injuries among staff who used scissors) – (number of injuries among staff who did not use scissors).
Relative risk: (number of injuries among staff who used scissors) ÷ (number of injuries among staff who did not use scissors).
F IGU R E 2.4-2. Relative risk (RR) vs. odds ratio (OR).
lower the disease incidence, the more closely it approximates relative risk (see Figure 2.4-2).
Odds that a diseased person is exposed Odds ratio = Odds that a nondiseased person is exposed
Odds ratio: (odds that injured staff used scissors) ÷ (odds that uninjured staff used scissors).
Once a diagnosis has been established, it is important to be able to describe the associated prognosis. Survival analysis is used to summarize the average time from one event (e.g., presentation, diagnosis, or start of treatment) to any outcome that can occur only once during follow-up (e.g., death or recurrence of cancer). The usual method is with a Kaplan-Meier curve (see Figure 2.4-3) describing the survival (or time-to-event if the measured outcome is not death) in a cohort of patients, with the probability of survival de
Probability of event creasing over time as patients die or drop out (are censored) from the study.
Odds = 1 − probability ofStudies are typically used to judge the best treatment for a disease. Although the gold standard for such evaluation is a randomized, double-masked controlled trial, other types of studies may be used as well (e.g., an observational
F IGU R E 2.4-3. Example of a Kaplan-Meier curve.
study, in which the exposure in question is a therapeutic intervention). In descending order of quality, published studies regarding treatment options include meta-analyses, randomized controlled trials, and case series/case reports.
A randomized controlled trial is an experimental, prospective study in which subjects are randomly assigned to a treatment or control group. Random assignment helps ensure that the two groups are truly comparable. The control group may be treated with a placebo or with the accepted standard of care. The study may be masked in one of two ways: single-masked, in which patients do not know which treatment group they are in, or double-masked, in which neither the patients nor their physicians know who is in which group. Double-masked studies are the gold standard for studying treatment effects.
Advantages of randomized controlled trials are as follows:They involve minimal bias.They have the potential to demonstrate causal relationships.Disadvantages include the following:They are costly and time intensive.Informed consent may be diffcult to obtain.Some interventions (e.g., surgery) are not amenable to masking.Ethical standards cannot allow all variables to be controlled.Def ned as any process that causes results to systematically differ from the truth. Good studies and data analyses seek to minimize potential bias. Types of bias include the following:
Selection bias: Occurs when samples or participants are selected that differ from other groups in additional determinants of outcome. Examples: A surgeon may select patients without signifcant comorbid conditions to receive surgery, resulting in unexpectedly positive outcomes compared to previous studies. Similarly, individuals concerned about a family history of breast cancer may be more likely to self-select in entering a mammography program, giving the impression of a prevalence that is higher than reality.
Measurement bias: Occurs when measurement or data-gathering methods differ between groups. Example: One group is assessed by CT while another group is assessed by MRI.
Confounding bias: Occurs when a third variable is associated with both the dependent variable and the independent variable (either positively or negatively), inducing a falseassociation (type I bias). Example: Fishermen in an area may experience a higher incidence of cataracts than the general population. However, becoming a fsherman will not in itself give you cataracts; rather, it is the sunlight to which those fshermen are exposed in their outdoor work.
Recall bias: Results from a difference between two groups in the retrospective recall of past factors or outcomes. Example: A patient with cancer may be more motivated than a healthy individual to recall past episodes of chemical exposure.
Lead-time bias: Results from earlier detection of disease, giving an appearance of prolonged survival when in fact the natural course is not altered. Example: A new and widely used screening test that detects cancer f ve
Randomization minimizes bias and confounding; double-blinded studies prevent observation bias.
Studies that are masked and randomized are better protected from the effects of bias, whereas observational studies are particularly susceptible to bias.
Confounding variables reduce the internal validity of a study.years earlier may give the impression that patients are living longer with the disease.
■ Length bias: Occurs when screening tests detect a disproportionate number of slowly progressive diseases but miss rapidly progressive ones, leading to overestimation of the beneft of the screen. Example: A better prognosis for patients with cancer is celebrated after implementation of a new screening program. However, this test disproportionally detects slow-growing tumors, which generally tend to be less aggressive.
Even with bias reduction, unsystematic random error is unavoidable owing to chance variation in studied data. Types of errors are as follows:
Type I (α) error:Defned as the probability of saying that there is a difference in treatment effects between groups when in fact there is not (i.e., a false-conclusion).
The p-value is an estimate of the probability that differences in treatment effects in a study could have happened by chance alone. Classically, differences associated with a p < 0.05 are statistically signif cant.
Type II (β) error:Defned as the probability of saying that there is no difference in treatment effects (i.e., a falseconclusion) when in fact a difference exists.
Power is the probability that a study will fnd a statistically signif cant difference when one is truly there. It relates directly to the number of subjects. Power (β) = 1 – type II error.
The confidence interval (CI) is a way of expressing statistical signif cance (p-value) that shows the size of the effect and the statistical power. CIs are interpreted as follows:
If one is using a 95% CI, there is a 95% chance that the interval contains the true effect size, which is likely to be closest to the point estimate near the center of the interval.
Example: You would like to estimate the percentage of women with a specifc disease. A 10% result from a sample of 3000 women would provide a 95% CI of 9%–11%, whereas a 10% f nding from a sample of 30 women would yield a CI of –1% of 21%. The frst case has more power because the sample size is larger, producing a narrow interval. In the latter case, you cannot state with 95% certainty that women in general even have the disease!
If the CI includes the value corresponding to a relative risk of 1.0 (i.e., zero treatment difference), the results are not statistically signif cant.
If the CI is wide, power is low.■There are three levels of prevention: 1° prevention: Includes measures to ↓ the incidence of disease.
2° prevention: Focuses on identifying the disease early, when it is asymptomatic or mild, and implementing measures that can halt or slow disease progression.
3° prevention: Includes measures that ↓ morbidity or mortality resulting from the presence of disease.
TABLE 2.4-1. Types of VaccinationsLive attenuated Measles, mumps, rubella, polio (Sabin), yellow fever, influenza (nasal spray). Inactivated (killed) Cholera, influenza, HAV, polio (Salk), rabies, influenza (injection). Toxoid Diphtheria, tetanus. Subunit HBV, pertussis, Streptococcus pneumoniae, HPV, meningococcus. Conjugate Hib, S. pneumoniae.
Prevention may be accomplished by a combination of immunization, chemoprevention, behavioral counseling, and screening. A good screening test has the following characteristics:
It has high sensitivity and specifcity.It has a high PPV.It is inexpensive, easy to administer, and safe.Treatment after screening is more effective than subsequent treatment without screening.
Vaccines work by mimicking infections and triggering an immune response in which memory cells are formed to recognize and fght any future infection. There are several different vaccine formulations, as indicated in Table 2.4-1.
Recommended vaccination schedules for children and adults are outlined in Figures 2.4-4 through 2.4-6.
1° prevention: A woman reduces dietary intake of fat or alcohol to reduce her risk of developing breast cancer.
2° prevention: A woman obtains a mammogram to screen for breast cancer.
3° prevention: A woman undergoes surgical intervention for breast cancer.
Diphtheria, Tetanus, PertussisRange of recommendedMeasles, Mumps, Rubella Varicella Hepatitis A MeningococcalF IGU R E 2.4-4. Recommended vaccinations for children 0–6 years of age.
(Reproduced from the Centers for Disease Control and Prevention, Atlanta, Georgia.)
F IGU R E 2.4-5. Recommended vaccinations for children 7–18 years of age.
Range of recommended ages (Reproduced from the Centers for Disease Control and Prevention, Atlanta, Georgia.)
VACCINE AGE GROUP 19–26 years 27–49 years 50–59 years 60–64 years >65 years Tetanus, diphtheria, pertussis (Td/Tdap)* Human papillomavirus (HPV)* Measles, mumps, rubella (MMR) * Influenza* Pneumococcal (polysaccharide) Hepatitis A* Hepatitis B* Meningococcal* Zoster Varicella * 3 doses 1 or more doses 2 doses 1 or 2 doses 1 dose 3 doses (females) Substitute 1-time dose ofTdap forTd booster; then boost withTd every 10 yrs 2 doses 1 or 2 doses 1 dose 1 dose *Covered by the Vaccine Injury Compensation Program. For all persons in this category who meet the age requirements and who lack evidence of immunity No recommendationRecommended if some other risk factor is present (e.g., on the basis of medical, 1 dose ann u all y Td booster every 10 yrs (e.g., lack documentation of vaccination or have occupational, lifestyle, or other indications) no evidence of prior infection)
F IGU R E 2.4-6. Recommended vaccinations for adults.(Reproduced from the Centers for Disease Control and Prevention, Atlanta, Georgia.)
T AB LE 2.4-2. Stages of Change in Behavioral Counseling
Precontemplation Denial or ignorance of the problem. A 51-year-old smoker has not even thought about cessation. Contemplation Ambivalence or conflicted emotions; assessing benefits and barriers to change. A 43-year-old crack cocaine addict considers treatment for her addiction. Preparation Experimenting with small changes; collecting information about change. A 28-year-old heroin addict visits his doctor to ask questions about quitting. Taking direct action toward achieving a goal. A 33-year-old enters a rehabilitation facility for treatment of addiction to prescription narcotics. Maintaining a new behavior; avoiding temptation. A 41-year-old continues to visit Alcoholics Anonymous meetings to gain support and reinforcement against relapse. Action Maintenance ■Live vaccines should not be administered to immunosuppressed patients. Such vaccines are also contraindicated in pregnant women owing to a theoretical risk of maternal-fetal transmission.
Defned as the use of drugs to prevent disease. Examples include supplementation of water and food with healthful vitamins and minerals; aspirin prophylaxis for heart disease; statin treatment for hypercholesterolemia; and perioperative β-blockade.
In offering counsel, physicians should tailor their education and suggestions to the individual patient as well as to his or her stage of change (see Table 2.4-2). Counseling is most likely to be successful when it accommodates the patient’s willingness to change or lack thereof.
Tables 2.4-3 and 2.4-4 outline recommended health care screening measures by age group and modality.
T AB LE 2.4-3. Health Screening Methods by AgeBirth–10 years Height and weight, BP, vision and hearing screening, hemoglobinopathy screen (at birth), phenylalanine level (at birth), TSH and/or T4 (at birth), lead level (at least one time before six years of age). 11–24 years Height and weight, BP, Pap test, gonorrhea and chlamydia (GC) screen (if sexually active), rubella serology or vaccination (women only); screen for risky behaviors, including substance abuse. 25–64 years Height and weight, BP (every two years), cholesterol (every five years), Pap test and bimanual pelvic exam, fecal occult blood test (FOBT) or fecal immunochemical test (FIT), sigmoidoscopy or colonoscopy, mammography, rubella serology or vaccination (women only); screen for alcohol abuse and depression. ≥ 65 years Height and weight, BP, FOBT or FIT, sigmoidoscopy or colonoscopy, Pap test, vision and hearing screening, osteoporosis (DEXA) scans for women; screen for alcohol abuse and depression.
T AB LE 2.4-4. Health Screening Methods by ModalityOnce every 10 years in patients ≥ 50 years of age (or ≥ 40 years of age for high-risk patients). The preferred modality if there is a known history of dysplasia. CT virtual colonoscopy is comparable to standard colonoscopy and can be used every five years as an initial screening exam.
Once every year within three years after onset of vaginal intercourse, but no later than age 21 up to age 30; once every two years with liquid-based Pap test. The interval can be ↑ to once every 2–3 years for women > 30 years of age with three  cytology tests.
Offer every three years to female patients in 20s and 30s, and every year to females 40 or more years of age (controversial).
a Different medical societies have various recommendations regarding cancer screening. Refer to the National Cancer Institute’s Web site for a recent summary of recommendations: www.nci.nih.gov/cancer_information/testing.
Colonoscopy Flexible sigmoidoscopy Once every five years in patients ≥ 50 years of age (or ≥ 40 years of age for high-risk patients). FOBT or FIT Once every year in patients ≥ 50 years of age (or ≥ 40 years of age for high-risk patients). Bimanual pelvic exam Once every 1–3 years in patients 20–40 years of age; once yearly in patients ≥ 40 years of age. Pap test Mammography Once every 1–2 years in patients ≥ 40 years of age; once yearly in patients ≥ 50 years of age (controversial). Endometrial tissue sampling Not recommended as a screening test; indicated for postmenopausal bleeding. CXR Not recommended as a screening test. Skin exam Insufficient evidence. DRE Offer every year to high-risk patients at 40 years and to others at 50 years of age (controversial). PSA Offer every year to high-risk patients at 40 years and to others at 50 years of age (controversial). Clinical breast exam
The leading cause of cancer mortality in the United States is lung cancer. Prostate and breast cancers are the most prevalent cancers in men and women, respectively, with lung and colorectal cancers ranking second and third most common in both sexes. Table 2.4-5 lists the principal causes of death in the United States by age group.
TABLE 2.4-5. Leading Causes of Death by Age GroupAll ages Heart disease, cancer, stroke, chronic lower respiratory disease, injuries, diabetes. < 1 year Congenital anomalies, disorders related to low birth weight, SIDS, maternal complications. 1–4 years Injuries, congenital anomalies, cancer, homicide, heart disease. 5–14 years Injuries, cancer, congenital anomalies, homicide, suicide, heart disease. 15–24 years Injuries, homicide, suicide, cancer, heart disease. 25–44 years Injuries, cancer, heart disease, suicide, HIV, homicide. 45–64 years Cancer, heart disease, injuries, stroke, diabetes, chronic lower respiratory disease. ≥ 65 years Heart disease, cancer, stroke, chronic lower respiratory disease, Alzheimer’s disease, diabetes. Adapted, with permission, from the National Center for Health Statistics, Department of Health and Human Services, www.cdc.gov/nchs.
By law, disease reporting is mandated at the state level, and the list of diseases that must be reported to public health authorities varies slightly by state. The CDC has a list of nationally notifable diseases that states voluntarily report to the CDC. These diseases include but are not limited to those listed in Table 2.4-6.
T AB LE 2.4-6.  Common Reportable DiseasesSTDs HIV, AIDS, syphilis, gonorrhea, chlamydia, chancroid, HCV. Tick-borne disease Lyme disease, ehrlichiosis, Rocky Mountain spotted fever. Potential bioweapons Anthrax, smallpox, plague. Vaccine-preventable disease Diphtheria, tetanus, pertussis, measles, mumps, rubella, polio, varicella, HAV, HBV, H. infl uenzae (invasive), meningococcal disease. Water-/food-borne disease Cholera, giardiasis, legionella, listeriosis, botulism, shigellosis, shiga toxin–producing E. coli, salmonellosis, trichinellosis, typhoid. Zoonoses Tularemia, psittacosis, brucellosis, rabies. Miscellaneous TB, leprosy, toxic shock syndrome, SARS, West Nile virus, VRSA, coccidioidomycosis, cryptosporidiosis.
Confidentiality 149 Conflict of Interest 149 Malpractice 150Respect for autonomy: Clinicians are obligated to respect patients as individuals and to honor their preferences in medical care. Example: A surgeon presents the risks and benefits of tumor resection to her patient before consent is given to proceed with the procedure.
Beneficence: Physicians have a responsibility to act in the patient’s best interest. As a fiduciary, the physician stands in a special relationship of trust and responsibility to patients. Respect for patient autonomy may confl ict with beneficence. Example: An elderly woman is adamant that she does not want to go to a rehabilitation facility and thus refuses amputation of a potentially gangrenous foot. The procedure is necessary to prevent life-threatening complications. The physician has a responsibility to act in the patient’s best interest.
Nonmaleficence: “Do no harm.” The responsibility to avert avoidable harms is a strong duty. However, if the potential benefits of an intervention outweigh the risks, an autonomous patient may make an informed decision to consent and proceed. Example: A patient may choose to undergo dialysis, accepting that his discomfort would be outweighed by the greater good of sustaining life.
Justice: With regard to individual patients, fairness is expressed as the notion that equal persons should be treated equally. Health care is an important resource, and access to quality health care gives individuals a greater chance for a healthy and productive life. Fair distribution of this resource is an ongoing challenge for health policy and in the clinical arena.
Defined as willing acceptance (without coercion) of a medical intervention by a patient after adequate discussion with a physician about the nature of the intervention along with its indications, risks, benefits, and potential alternatives (including no treatment).
Patients may change their minds at any time.Informed consent is required for significant procedures unless:Emergency treatment is required. Examples: An unconscious patient presents with cerebral edema after a motor vehicle collision, or a patient without previously indicated DNR/DNI status undergoes cardiac arrest.
Patients lack decision-making capacity (consent can be obtained from a surrogate decision maker). Examples: Patients may present with dementia or significant psychiatric disturbances. Minors generally require surrogate decision makers until they demonstrate adequate decision-making capacity or are of legal age.
Consent for treatment is implied in life-threatening situations when parents cannot be contacted.
Emancipated minors do not require parental consent for medical care. Minors are emancipated if they are married, in the armed services, or are financially independent of their parents and have sought legal emancipation.
Minors may consent to care for sexually transmitted infections without parental consent or knowledge. Rules concerning contraception, preg nancy, and abortion services and treatment for drug and alcohol dependency vary across the United States. (Some states leave the decision of informing parents about adolescent use of confidential services to the physician, based on the best interest of the patient. Other states limit disclosure.) ■Refusal of treatment: A parent has the right to refuse treatment for his/her child as long as those decisions do not pose a serious threat to the child’s well-being (e.g., refusing immunizations is not considered a serious threat). If a decision is not in the best interest of the child, a physician may seek a court order to provide treatment against parental wishes. In emergent situations, if withholding treatment jeopardizes the child’s safety, treatment can be initiated on the basis of legal precedent. Example: A physician provides blood transfusion to save the life of a six-year-old child seriously injured in a motor vehicle collision despite parental requests to withhold such a measure.
Minors may consent to care for sexually transmitted infections without parental consent or knowledge.
Competence: Refers to a person’s legal capacity to make decisions and be held accountable in a court of law. Competence is assessed by the courts and is often used interchangeably with the term decision-making capacity (see below).
Decision-making capacity: A medical term that refers to the ability of a patient to understand relevant information, appreciate the severity of the medical situation and its consequences, communicate a choice, and deliberate rationally about one’s values in relation to the decision being made. This can be assessed by the physician.
Decision-making capacity is best understood as varying with the complexity of the decision involved. Example: The level of capacity needed for a decision about liver transplantation is different from that needed to choose between two types of pain medication for fracture-related pain.
Incompetent patients, as assessed by the courts, or temporarily incapacitated patients cannot decide to accept or refuse treatment. Example: An intoxicated patient with altered mental status cannot refuse thiamine supplementation.
In general, patients who have decision-making capacity have the right to refuse or discontinue treatment. Example: Jehovah’s Witnesses can refuse blood products.
Living will: Addresses a patient’s wishes to maintain, withhold, or withdraw life-sustaining treatment in the event of terminal disease or a persistent vegetative state. Examples include DNR (do not resuscitate) and DNI (do not intubate) orders.
Durable power of attorney for health care (DPOAHC): Legally designates a surrogate health care decision maker if a patient lacks decision-making capacity. More fl exible than a living will. Surrogates should make decisions consistent with the person’s stated wishes.
If no living will or DPOAHC exists, decisions should be made by close family members (spouse, adult children, parents, and adult siblings), friends, or personal physicians, in that order.
In the absence of a living will or DPOA, the Spouse CHIPS in For the Person: Spouse, CHIldren, Parent, Sibling, Friend, Personal physician.
DNR/DNI orders do not mean “do not treat.”Patients cannot demand futile treatment from their physicians.A patient’s family cannot require that a doctor withhold information from the patient.
Withdrawal of CarePatients and their decision makers have the right to forgo or withdraw life-sustaining treatment.
No ethical distinction is considered to exist between withdrawing a treatment that offers no benefit and withholding one that is not indicated. This may include ventilation, fluids, nutrition, and medications such as antibiotics.
If the intent is to relieve suffering and medications administered are titrated for that purpose, then it is considered ethical to provide palliative treatment to relieve pain and suffering, even if it may hasten a patient’s death. Example: A physician prescribes midazolam to a patient who is expected to die within a day in order to offer relief from the acute distress of grand mal seizures and pain.
Euthanasia is the administration of a lethal agent with the intent to end life.
It is opposed by the AMA Code of Medical Ethics and is illegal in all states.
Patients who request euthanasia should be evaluated for inadequate pain control and comorbid depression.
Physician-assisted suicide is prescribing a lethal agent to a patient who will self-administer it to end his/her own life. This is currently illegal except in the state of Oregon.
Physicians are not ethically obligated to provide treatment and may refuse a family member’s request for further intervention on the grounds of futility under the following circumstances:
There is no pathophysiologic rationale for treatment.A given intervention has already failed.Maximal intervention is currently failing.Treatment will not achieve the goals of care.Patients have a right to know about their medical status, prognosis, and treatment options (full disclosure).
A patient’s family cannot require that a doctor withhold information from the patient.
A doctor may withhold information only if the patient requests not to be told or in the rare case when a physician determines that disclosure would severely harm the patient or undermine their informed decision-making capacity (therapeutic privilege).
Physicians are obligated to inform patients of mistakes made in their medical treatment.
If the specific error or series of errors is not known, the physician should communicate this with the family promptly and maintain contact with the patient as investigations reveal more facts.
Physicians are obligated to inform patients considering involvement in a clinical research protocol about the purpose of the research study and the entire study design as it will affect the patient’s treatment. This includes the possible risks, benefits, and alternatives to the research protocol.
An informed consent form approved by the overseeing research institutional review board (IRB) must be completed for participation in any clinical research protocol, describing the possible risks and benefits of involvement in the research study.
Information disclosed by a patient to his/her physician and information about a patient’s medical condition are confidential and cannot be divulged without expressed patient consent.
A patient may waive the right to confidentiality (e.g., with insurance companies).
It is ethically and legally necessary to override confidentiality in the following situations:
Patient intent to commit a violent crime (Tarasoff decision): Physicians have a duty to protect the intended victim through reasonable means (e.g., warn the victim, notify police).
Suicidal patients.Child and elder abuse.Reportable infectious diseases (duty to warn public officials and identifiable people at risk).
Gunshot and knife wounds (duty to notify the police).Impaired automobile drivers. Example: A patient begins to drive one week after hospitalization for seizures, although the department of motor vehicles in his state requires that licensed drivers be seizure free for at least three months.
Occurs when physicians find themselves having two interests in a given situation and their professional obligations are influenced by personal interest in another matter. Example: A physician may own stock in a pharmaceutical company (financial interest) that produces a drug he is prescribing to his patient (patient care interest).
Physicians should disclose existing conflicts of interest to affected parties (e.g., patients, institutions, audiences of journal articles or scientific meetings).
The essential elements of a civil suit under negligence include the four D’s:
The physician has a Duty to the patient.Dereliction of duty occurs.There is Damage to the patient.Dereliction is the Direct cause of damage.Unlike a criminal suit, in which the burden of proof is “beyond a reasonable doubt,” the burden of proof in a malpractice suit is “a preponderance of the evidence.”
Disorders of the Stomach and Duodenum 156 GASTRITIS 156 GASTRIC CANCER 157 PEPTIC ULCER DISEASE 157 ZOLLINGER-ELLISON SYNDROME 158
Disorders of the Small Bowel 159 DIARRHEA 159 MALABSORPTION 161 LACTOSE INTOLERANCE 162 CARCINOID SYNDROME 162 IRRITABLE BOWEL SYNDROME 162 SMALL BOWEL OBSTRUCTION 163 ILEUS 164 MESENTERIC ISCHEMIA 165 APPENDICITIS 166
Disorders of the Large Bowel 166 DIVERTICULAR DISEASE 166 LARGE BOWEL OBSTRUCTION 167 COLON AND RECTAL CANCER 167 ISCHEMIC COLITIS 170
Difficulty swallowing (dysphagia) or pain with swallowing (odynophagia) due to abnormalities of the oropharynx or esophagus.
Presentation varies according to the location:Oropharyngeal dysphagia: Presents with difficulty passing material from the oropharynx to the esophagus. Usually involves liquids more than solids. Causes can be neurologic or muscular and include stroke, Parkinson’s disease, myasthenia gravis, prolonged intubation, and Zenker’s diverticula.
Esophageal dysphagia: Usually involves solids more than liquids for most obstructive causes (strictures, Schatzki rings, webs, carcinoma) and is generally progressive. Motility disorders (achalasia, scleroderma, esophageal spasm) present with both liquid and solid dysphagia.
Examine for masses (e.g., goiter, tumor) and anatomic defects.Oropharyngeal dysphagia: Cine-esophagram.Esophageal dysphagia: Barium swallow followed by endoscopy, manometry, and/or pH monitoring. If an obstructive lesion is suspected, proceed directly to endoscopy with biopsy.
Odynophagia: Upper endoscopy.Etiology dependent.Table 2.6-1 outlines the etiology, diagnosis, and treatment of infectious esophagitis.
■A motility disorder in which normal peristalsis is periodically interrupted by high-amplitude nonperistaltic contractions of unknown etiology. Also known as nutcracker esophagus.
T AB LE 2.6-1. Causes of Infectious EsophagitisEsophageal webs are associated with iron deficiency anemia and glossitis (Plummer-Vinson syndrome).
Candidal esophagitis is an AIDS-defining illness.Candida albicans Oral thrush Yellow-white plaques adherent to the mucosa. Fluconazole PO HSV Oral ulcers Small, deep ulcerations; multinucleated giant cells with nuclear inclusions on biopsy. Acyclovir IV CMV Retinitis, colitis Large, superfcial ulcerations; intranuclear inclusions on biopsy. Ganciclovir IV
The musculature of the upper one-third of the esophagus is skeletal, whereas that of the lower two-thirds is smooth muscle.
Malignancy may mimic achalasia (pseudoachalasia).Hx/PE: Presents with chest pain, dysphagia, and odynophagia. Often precipitated by ingestion of hot or cold liquids; relieved by nitroglycerin.
Dx: Barium swallow may show a corkscrew-shaped esophagus. Esophageal manometry reveals high-amplitude, simultaneous contractions.
Tx: Nitrates and calcium channel blockers (CCBs) for symptomatic relief; surgery (esophageal myotomy) for severe, incapacitating symptoms.
A motor disorder of the esophagus characterized by impaired relaxation of the lower esophageal sphincter (LES) and loss of peristalsis in the distal two-thirds of the esophagus. Thought to result from the loss or absence of inhibitory ganglion cells in the myenteric (Auerbach’s) plexus.
Hx/PE: Progressive dysphagia, chest pain, regurgitation of undigested food, weight loss, and nocturnal cough are common symptoms.
Barium swallow reveals esophageal dilation with a “bird’s beak” tapering of the distal esophagus (see Figure 2.6-1).
Manometry shows ↑ resting LES pressure, incomplete LES relaxation upon swallowing, and ↓ peristalsis in the body of the esophagus.
Mechanical causes of obstruction must be ruled out by endoscopy.
Tx: Nitrates, CCBs, or endoscopic injection of botulinum toxin into the LES may provide short-term relief of symptoms. Pneumatic balloon dilation or surgical (Heller) myotomy are definitive treatment options.
FIGURE 2.6-1. Achalasia.Barium esophagram reveals esophageal dilation with a “bird’s beak” tapering of the distal esophagus. (Reproduced from Waters PF, DeMeester TR. Foregut motor disorders and their surgical management. Med Clin North Am 65: 1235, © 1981, with permission from Elsevier.)
The second most common esophageal motility disorder (after achalasia).Cervical outpouching through the cricopharyngeal muscle is called Zenker’s diverticulum. Diverticula can also occur in the middle and distal third of the esophagus.
Hx/PE: Patients complain of chest pain, dysphagia, halitosis, and regurgitation of undigested food.
Dx: Barium swallow will demonstrate outpouchings.Tx: If symptomatic, treat with surgical excision of the diverticulum. For Zenker’s diverticulum, myotomy of the cricopharyngeus is required to relieve the high-pressure zone.
Squamous cell carcinoma (SCC) is the most common type of esophageal cancer worldwide, while adenocarcinoma is most prevalent in the United States, Europe, and Australia. The latter is associated with Barrett’s esophagus (columnar metaplasia of the distal esophagus 2° to chronic GERD).
Alcohol use and smoking have been identified as major risk factors for SCC.
Hx/PE: Progressive dysphagia, initially to solids and later to liquids, is common. Weight loss, odynophagia, GERD, GI bleeding, and vomiting are also seen.
Dx: Barium study shows narrowing of the esophagus with an irregular border protruding into the lumen. EGD and biopsy confirm the diagnosis. CT and endoscopic ultrasound are used for staging.
Tx: Chemoradiation and surgical resection is the definitive treatment, but the prognosis is poor. Surgery is also offered for high-grade Barrett’s dysplasia. Patients who are not candidates for surgery may require an endoscopically placed esophageal stent for palliation and improved quality of life.
Symptomatic reflux of gastric contents into the esophagus, most commonly as a result of transient LES relaxation. Can be due to an incompetent LES, gastroparesis, or hiatal hernia.
Patients present with heartburn that commonly occurs 30–90 minutes after a meal, worsens with reclining, and often improves with antacids, sitting, or standing. Substernal chest pain can be difficult to distinguish from other causes.
Sour taste (“water brash”), globus, unexplained cough, and morning hoarseness can be clues.
Exam is usually normal unless a systemic disease (e.g., scleroderma) is present.
The history and clinical impression are important.An empiric trial of lifestyle modification and medical treatment is often attempted first. Studies may include barium swallow (to look for hiatal hernia), esophageal manometry, and 24-hour pH monitoring.
Squamous cell esophageal cancer is associated with tobacco and alcohol use.
Esophageal cancer metastasizes early because the esophagus lacks a serosa.
Risk factors for GERD include hiatal hernia and ↑ intra-abdominal pressure (e.g., obesity, pregnancy).
GERD can mimic cough-variant asthma.Patients with GERD should avoid caffeine, alcohol, chocolate, garlic, onions, mints, and nicotine.
Type A gastritis is associated with pernicious anemia due to the lack of intrinsic factor necessary for the absorption of vitamin B12.
■ EGD with biopsies should be performed in patients whose symptoms are unresponsive to initial empiric therapy, long-standing (to rule out Barrett’s esophagus and adenocarcinoma), or suggestive of complicated disease (e.g., anorexia, weight loss, dysphagia/odynophagia).
Lifestyle: Weight loss, head-of-bed elevation, reduction of meal size, and avoidance of nocturnal meals and substances that ↓ LES tone.
Pharmacologic: Start with antacids in patients with mild, intermittent symptoms; use H2 receptor antagonists (cimetidine, ranitidine) or PPIs (omeprazole, lansoprazole) in patients with chronic and frequent symptoms. PPIs are preferred for severe or erosive disease.
Surgical: For refractory or severe disease, Nissen fundoplication may offer significant relief.
Esophagitis, esophageal stricture, aspiration of gastric contents, upper GI bleeding, Barrett’s esophagus.
Herniation of a portion of the stomach upward into the chest through a diaphragmatic opening. There are two common types:
Sliding hiatal hernias (95%): The gastroesophageal junction and a portion of the stomach are displaced above the diaphragm.
Paraesophageal hiatal hernias (5%): The gastroesophageal junction remains below the diaphragm, while a neighboring portion of the fundus herniates into the mediastinum.
Hx/PE: May be asymptomatic. Those with sliding hernias may present with GERD.
Dx: Commonly an incidental finding on CXR; also frequently diagnosed by barium swallow or EGD.
Sliding hernias: Medical therapy and lifestyle modifications to ↓ GERD symptoms.
Paraesophageal hernias: Surgical gastropexy (attachment of the stomach to the rectus sheath and closure of the hiatus) is recommended to prevent gastric volvulus.
Inflammation of the stomach lining. Subtypes are as follows:Acute gastritis: Rapidly developing, superficial lesions that are often due to NSAID use, alcohol, H. pylori infection, and stress from severe illness (e.g., burns, CNS injury).
Chronic gastritis: ■Type A (10%): Occurs in the fundus and is due to autoantibodies to parietal cells. Causes pernicious anemia and is associated with other autoimmune disorders, such as thyroiditis. Also ↑ the risk of gastric adenocarcinoma.
■Type B (90%): Occurs in the antrum and may be caused by NSAID use or H. pylori infection. Often asymptomatic, but associated with ↑ risk of PUD and gastric cancer.
Patients may be asymptomatic or may complain of epigastric pain, nausea, vomiting, hematemesis, or melena.
Upper endoscopy can visualize the gastric lining.H. pylori infection can be detected by urease breath test, serum IgG antibodies (which indicate exposure, not current infection), H. pylori stool antigen, or endoscopic biopsy.
■↓ intake of offending agents. Antacids, sucralfate, H2 blockers, and/or PPIs may help.
Triple therapy (amoxicillin, clarithromycin, omeprazole) to treat H. pylori infection.
Give prophylactic H2 blockers or PPIs to patients at risk for stress ulcers (e.g., ICU patients).
This malignant tumor is the second most common cause of cancer-related death worldwide and is particularly common in Korea and Japan. Tumors are generally adenocarcinomas, which exhibit two morphologic types:
Intestinal type: Thought to arise from intestinal metaplasia of gastric mucosal cells. Risk factors include a diet high in nitrites and salt and low in fresh vegetables (antioxidants), H. pylori colonization, and chronic gastritis.
Diffuse type: Tends to be poorly differentiated and not associated with
H. pylori infection or chronic gastritis. Risk factors are largely unknown; signet ring cells are seen on pathology.
Hx/PE: Early signs are indigestion and loss of appetite. Advanced cases generally present with abdominal pain, weight loss, or upper GI bleeding.
Dx: Early gastric carcinoma is largely asymptomatic and is discovered serendipitously with endoscopic examination of high-risk individuals.
Tx: Successful treatment rests entirely on early detection and surgical removal of the tumor. Five-year survival is < 10% for advanced disease.
Damage to the gastric or duodenal mucosa caused by impaired mucosal defense and/or ↑ acidic gastric contents. H. pylori plays a causative role in > 90% of duodenal ulcers and 70% of gastric ulcers. Other risk factors include corticosteroid, NSAID, alcohol, and tobacco use. Males are affected more often than females.
■Classically presents with chronic or periodic dull, burning epigastric pain that improves with meals (especially duodenal ulcers), worsens 2–3 hours after eating, and can radiate to the back.
Gastric adenocarcinoma that metastasizes to the ovary is called a Krukenberg tumor.
Gastric cancer may present with Virchow’s node (an enlarged left supraclavicular lymph node).
After a meal, pain from a Gastric ulcer is Greater, whereas Duodenal pain Decreases.
Roughly 5–7% of lower GI bleeds are from an upper GI source.
Rule out Zollinger-Ellison syndrome with serum gastrin levels in cases of GERD and PUD that are refractory to medical management.
Misoprostol can help patients with PUD who require NSAID therapy (e.g., for arthritis).
Patients may also complain of nausea, hematemesis (“coffee-ground” emesis), or blood in the stool (melena or hematochezia).
Exam may reveal varying degrees of epigastric tenderness and, if there is active bleeding, a stool guaiac.
An acute perforation can present with a rigid abdomen, rebound tenderness, guarding, or other signs of peritoneal irritation.
AXR to rule out perforation (free air under the diaphragm); CBC to assess for GI bleeding (low or ↓ hematocrit).
Upper endoscopy with biopsy to confirm PUD and to rule out active bleeding or gastric adenocarcinoma (10% of gastric ulcers); barium swallow is an alternative.
H. pylori testing.In recurrent or refractory cases, serum gastrin can be used to screen for Zollinger-Ellison syndrome (patients must discontinue PPI use prior to testing).
Rule out active bleeding with serial hematocrits, a rectal exam with stool guaiac, and NG lavage.
Monitor the patient’s hematocrit and BP and treat with IV hydration, transfusion, IV PPIs, endoscopy, and surgery as needed for complications.
If perforation is likely, emergent surgery is indicated.Involves protecting the mucosa, decreasing acid production, and eradicating H. pylori infection.
Treat mild disease with antacids or with sucralfate, bismuth, and misoprostol (a prostaglandin analog) for mucosal protection. PPIs or H2 receptor antagonists may be used to ↓ acid secretion.
Patients with confirmed H. pylori infection should receive triple therapy (amoxicillin, clarithromycin, and omeprazole).
Discontinue use of exacerbating agents. Patients with recurrent or severe disease may require chronic symptomatic therapy.
Endoscopy and surgery:Patients with symptomatic gastric ulcers for > 2 months that are refractory to medical therapy should have either endoscopy or an upper GI series with barium to rule out gastric adenocarcinoma.
Refractory cases may require a surgical procedure such as parietal cell vagotomy (the most selective and preferred surgical approach).
Hemorrhage (posterior ulcers that erode into the gastroduodenal artery), gastric outlet obstruction, perforation (usually anterior ulcers), intractable pain.
■A rare condition characterized by gastrin-producing tumors in the duodenum and/or pancreas that lead to oversecretion of gastrin.
■↑ gastrin results in the production of high levels of gastric acid by the gastric mucosa, leading to recurrent/intractable ulcers in the stomach and duodenum (may occur more distally).
In 20% of cases, gastrinomas are associated with MEN 1 (pancreas, pituitary, and parathyroid tumors).
Hx/PE: Patients may present with unresponsive, recurrent gnawing, burning abdominal pain as well as with diarrhea, nausea, vomiting, fatigue, weakness, weight loss, and GI bleeding.
Dx: ↑ fasting serum gastrin levels are characteristic, as is ↑ gastrin following a secretin stimulation test. Octreotide scan can localize the tumor.
Requires ↓ acid production. H2 blockers are typically ineffective, but a moderateto high-dose PPI often controls symptoms.
In light of the malignant potential of the tumor, surgical resection should be attempted where possible.
Zollinger-Ellison syndrome is associated with MEN 1 syndrome in roughly 20% of cases.
Defined as the production of > 200 g of feces per day along with ↑ frequency or ↓ consistency of stool. Broadly, the four etiologic mechanisms are ↑ motility, ↑ secretion, ↑ luminal osmolarity, and inflammation (see also Table 2.6-2).
Acute diarrhea:Acute onset with < 2 weeks of symptoms; usually infectious and self-limited.
Causes include bacteria with preformed toxins (e.g., S. aureus, Bacillus cereus), noninvasive bacteria (e.g., enterotoxigenic E. coli, Vibrio cholerae, C. difficile), invasive bacteria (e.g., enteroinvasive E. coli, Salmonella, Shigella, Campylobacter, Yersinia), parasites (e.g., Giardia, Entamoeba histolytica), and opportunistic organisms (e.g., Cryptosporidium, Isospora, Microsporidium, CMV).
One of the most common causes of pediatric diarrhea is rotavirus infection (most common during winter).
Chronic diarrhea:Insidious onset with > 4 weeks of symptoms.Can be due to ↑ intestinal secretion (e.g., carcinoid, VIPomas), malabsorption/osmotic diarrhea (e.g., bacterial overgrowth, pancreatic insufficiency, mucosal abnormalities, lactose intolerance), inf ammatory bowel disease (IBD), or altered motility (e.g., IBS). ↑ stool osmotic gap and resolution of diarrhea with fasting suggest osmotic diarrhea. See Figure 2.6-2 for a diagnostic algorithm.
Acute diarrhea usually does not require laboratory investigation unless the patient has a high fever, bloody diarrhea, or diarrhea lasting > 4–5 days.
Send stool for fecal leukocytes, bacterial culture, C. difficile toxin, and O&P.
Consider sigmoidoscopy in patients with bloody diarrhea.Acute diarrhea:When bacterial infection is not suspected, treat with antidiarrheals (e.g., loperamide, bismuth salicylate) and oral rehydration solutions.
Acute diarrhea is generally infectious and self-limited.Organisms that cause bloody diarrhea include Salmonella, Shigella, E. coli, and Campylobacter.
Diarrhea after ingestion of raw eggs or dairy: thinkT AB LE 2.6-2. Causes of Infectious DiarrheaCampylobacter The most common etiology of infectious diarrhea. Ingestion of contaminated food or water. Affects young children and young adults. Generally lasts 7–10 days. Fecal RBCs and WBCs. Frequently bloody diarrhea. Rule out appendicitis and IBD. Erythromycin. Clostridium difficile Recent treatment with antibiotics (penicillins, cephalosporins, clindamycin). Affects hospitalized adult patients. Watch for toxic megacolon. Fever, abdominal pain, possible systemic toxicity. Fecal RBCs and WBCs. Most commonly causes colitis, but can involve the small bowel. Identify C. difficile toxin in the stool. Sigmoidoscopy shows pseudomembranes. Cessation of the inciting antibiotic. PO metronidazole or vancomycin; IV metronidazole if the patient cannot tolerate PO. Entamoeba histolytica Ingestion of contaminated food or water; history of travel in developing countries. Incubation period can last up to three months. Severe abdominal pain, fever. Fecal RBCs and WBCs. Chronic amebic colitis mimics IBD. Steroids can lead to fatal perforation. Treat with metronidazole. E. coli O157:H7 Ingestion of contaminated food (raw meat). Affects children and the elderly. Generally lasts 5–10 days. Severe abdominal pain, low-grade fever, vomiting. Fecal RBCs and WBCs. It is important to rule out GI bleed and ischemic colitis. HUS is a possible complication. Avoid antibiotic or antidiarrheal therapy, which ↑ HUS risk. Ingestion of contaminated poultry or eggs. Affects young children and elderly patients. Generally lasts 2–5 days. Prodromal headache, fever, myalgia, abdominal pain. Fecal WBCs. Sepsis is a concern, as 5–10% of patients become bacteremic. Sickle cell patients are susceptible to invasive disease leading to osteomyelitis. Treat bacteremia or at-risk patients (e.g., sickle cell patients) with oral quinolone or TMP-SMX. Extremely contagious; transmitted between people by the fecal-oral route. Affects young children and institutionalized patients. Fecal RBCs and WBCs. May lead to severe dehydration. Can also cause febrile seizures in the very young. Treat with TMP-SMX to ↓ person-to-person spread. Salmonella Shigella
Exclude: 1. Causes of acute diarrhea 2.Fecal leukocytesand occult blood Flexible sigmoidoscopy with biopsy Upper GI series, barium enema
HIGH-YIELD FACTS Inflammatory bowel disease Cancer Stool electrolytes, osmolality, weight/24 h, quantitative fat Increased osmotic gap Normal osmotic gap (Reproduced, with permission, from  McPhee SJ et al. Current Medical Diagnosis & Treatment, 48th ed. New York: McGraw-
Hill, 2009: Fig. 15-2.)If the patient has evidence of systemic infection (e.g., fever, chills, malaise), avoid antimotility agents and consider antibiotics after stool studies have been sent.
Chronic diarrhea: Identify the underlying cause and treat symptoms with loperamide, opioids, octreotide, or cholestyramine.
Pediatric diarrhea: For children who cannot take medication or PO fl uids—hospitalize, give IV fluids, replete electrolytes, and treat the underlying cause.
■Inability to absorb nutrients as a result of an underlying condition such as bile salt def ciency (e.g., bacterial overgrowth, ileal disease), short bowel syndrome, mucosal abnormalities (e.g., celiac disease, Whipple’s disease, tropical sprue), and pancreatic insuff ciency. The small bowel is most commonly involved.
Cutaneous fl ushing, diarrhea, wheezing, and cardiac valvular lesions are the most common manifestations of carcinoid tumors.
Half of all patients with IBS have comorbid psychiatric disturbances.
May result in ↓ absorption of protein, fat, carbohydrates, and micronutrients (folate/B12/iron).
Hx/PE: Presents with frequent, loose, watery stools and/or pale, foul-smelling, bulky stools associated with abdominal pain, f atus, bloating, weight loss, nutritional def ciencies, and fatigue.
Tx: Etiology dependent. Institute a gluten-free diet for patients with celiac sprue. Severely affected patients may receive TPN, immunosuppressants, and anti-infl ammatory medications.
Results from a defciency of lactase, a brush-border enzyme that hydrolyzes the disaccharide lactose into glucose and galactose.
Lactase deficiency is common among populations of African, Asian, and Native American descent. It may also occur transiently 2° to an acute episode of gastroenteritis or other disorders affecting the proximal small intestinal mucosa.
Hx/PE: Presents with abdominal bloating, f atulence, cramping, and watery diarrhea following milk ingestion.
Dx: Hydrogen breath test reveals ↑ breath hydrogen following ingestion of a lactose load (indicates metabolism of lactose by colonic bacteria). An empiric lactose-free diet that results in symptom resolution is highly suggestive of the diagnosis.
Tx: Avoidance of dairy products; lactase enzyme replacement.Due to liver metastasis of carcinoid tumors (hormone-producing enterochromaffin cells) that most commonly arise from the ileum and appendix and produce vasoactive substances such as serotonin and substance P. Prior to metastasis, most secreted hormones undergo first-pass metabolism by the liver and do not reach systemic circulation.
Hx/PE: Cutaneous fushing, diarrhea, abdominal cramps, wheezing, and right-sided cardiac valvular lesions are the most common manifestations. Symptoms usually follow eating, exertion, or excitement.
Dx: High urine levels of the serotonin metabolite 5-HIAA are diagnostic. Octreotide scan can localize the tumor.
Tx: Treatment includes octreotide (for symptoms) and debulking of tumor mass.
An idiopathic functional disorder that is characterized by changes in bowel habits that ↑ with stress as well as by abdominal pain that is relieved by bowel movements. It is most common in the second and third decades, but since the syndrome is chronic, patients may present at any age. Half of all IBS patients who seek medical care have comorbid psychiatric disorders (e.g., depression, anxiety, fibromyalgia).
■Patients present with abdominal pain, a change in bowel habits (diarrhea and/or constipation), abdominal distention, mucous stools, and relief of pain with a bowel movement.
IBS rarely awakens patients from sleep; vomiting, significant weight loss, and constitutional symptoms are also uncommon.
Exam is usually unremarkable except for mild abdominal tenderness.A diagnosis of exclusion based on clinical history.Tests to rule out other GI causes include CBC, TSH, electrolytes, stool cultures, abdominal films, and barium contrast studies.
Manometry can assess sphincter function.Psychological: Patients need reassurance from their physicians. They should not be told that their symptoms are “all in their head.”
Dietary: Fiber supplements (psyllium) may help.Pharmacologic: Treat with TCAs, antidiarrheals (loperamide), and antispasmodics (anticholinergics such as dicyclomine).
Defined as blocked passage of bowel contents through the small bowel. Fluid and gas can build up proximal to the obstruction, leading to fluid and electrolyte imbalances and significant abdominal discomfort. The obstruction can be complete or partial, and ischemia or necrosis of the bowel may occur. SBO may arise from adhesions from a prior abdominal surgery (60% of cases), hernias (10–20%), neoplasms (10–20%), intussusception, gallstone ileus, stricture due to IBD, or volvulus.
Patients typically experience cramping abdominal pain with a recurrent crescendo-decrescendo pattern at 5to 10-minute intervals.
Vomiting typically follows the pain; early emesis is bilious and nonfeculent if the obstruction is proximal but feculent if it is distal.
In partial obstruction, there is continued passage of flatus but no stool, whereas in complete obstruction, no flatus or stool is passed (obstipation).
Abdominal exam often reveals distention, tenderness, prior surgical scars, or hernias.
Bowel sounds are characterized by high-pitched tinkles and peristaltic rushes.
Peristalsis may disappear later in disease progression. Fever, hypotension, rebound tenderness, and tachycardia suggest peritonitis, a surgical emergency.
CBC may demonstrate leukocytosis if there is ischemia or necrosis of bowel.
Labs often refl ect dehydration and metabolic alkalosis due to vomiting. Lactic acidosis is particularly worrisome, as it suggests necrotic bowel and the need for emergent surgical intervention.
Abdominal films often demonstrate a stepladder pattern of dilated small-bowel loops, air-f uid levels (see Figure 2.6-3), and a paucity of gas in the colon. The presence of radiopaque material at the cecum is suggestive of gallstone ileus.
IBS is a diagnosis of exclusion.The leading cause of SBO in children is hernias. The leading cause of SBO in adults is adhesions.
Never let the sun rise or set on a complete SBO.
Anticholinergics, opioids, and hypokalemia slow GI motility.F IGU R E 2.6-3. Acute mechanical obstruction of the small intestine (upright film).
Note the air-fluid levels, marked distention of bowel loops, and absence of colonic gas. (Repro duced, with permission, from Kasper DL et al. Harrison’s Principles of Internal Medicine, 16th ed. New York: McGraw-Hill, 2005: 1804.)
For partial obstruction, supportive care may be sufficient and should include NPO status, NG suction, IV hydration, correction of electrolyte abnormalities, and Foley catheterization to monitor fl uid status.
Surgery is required in cases of complete SBO, vascular compromise (necrotic bowel), or symptoms lasting > 3 days without resolution.
Exploratory laparotomy may be performed with lysis of adhesions, resection of necrotic bowel, and evaluation for stricture, IBD, and hernias.
There is a 2% mortality risk for a nonstrangulated SBO; strangulated SBO is associated with up to a 25% mortality rate depending on the time between diagnosis and treatment.
A second-look laparotomy or laparoscopy may be performed 18–36 hours after initial surgical treatment to reevaluate bowel viability if ischemia is a concern.
Loss of peristalsis without structural obstruction. Risk factors include recent surgery/GI procedures, severe medical illness, immobility, hypokalemia or other electrolyte imbalances, hypothyroidism, DM, and medications that slow GI motility (e.g., anticholinergics, opioids).
Presenting symptoms include diffuse, constant, moderate abdominal discomfort; nausea and vomiting (especially with eating); and an absence of fatulence or bowel movements.
Exam may reveal diffuse tenderness and abdominal distention, no peritoneal signs, and ↓ or absent bowel sounds.
A rectal exam is required to rule out fecal impaction in elderly patients.
Diffusely distended loops of small and large bowel are seen on supine AXR with air-fluid levels on upright view.
A Gastrografin study can rule out partial obstruction; CT can rule out neo-In diagnosing ileus, look for plasms. air throughout the small and large bowel on AXR.
■↓ or discontinue the use of narcotics and any other drugs that reduce bowel motility.
Temporarily ↓ or discontinue oral feeds.Initiate NG suction/parenteral feeds as necessary.Replete electrolytes as needed.↓ mesenteric blood supply leading to insufficient perfusion to intestinal tissue and ischemic injury. Causes include acute arterial occlusion (usually involving the SMA) from thrombosis (due to atherosclerosis) or embolism (due to atrial fibrillation or ↓ ejection fraction); nonocclusive arterial disease (low cardiac output, arteriolar vasospasm); and venous thrombosis (due to hypercoagulable states).
Patients present with sudden onset of severe abdominal pain out of proportion to the exam.
A history of prior episodes of similar abdominal pain after eating (“intestinal angina”) may be present.
Other symptoms may include nausea, vomiting, diarrhea, and bloody stools.
Early abdominal exam is often unremarkable; later findings may include peritoneal signs (suggest bowel infarction).
Lab tests may show leukocytosis, metabolic acidosis with ↑ lactate, ↑ amylase, ↑ LDH, and ↑ CK.
AXR and CT may reveal bowel wall edema (“thumbprinting”) and air within the bowel wall (pneumatosis intestinalis).
Mesenteric angiography is the gold standard for arterial occlusive disease.
Volume resuscitation, broad-spectrum antibiotics, optimization of hemodynamics, and avoidance of vasoconstrictors.
Anticoagulation for arterial or venous thrombosis or embolism.The mortality rate for acute mesenteric ischemia is > 50%.
Diverticulosis is the most common cause of acute lower GI bleeding in patients > 40 years of age.
Diverticular disease must be distinguished from colon cancer with perforation.
Avoid fl exible sigmoidoscopy and barium enemas in the initial stages of diverticulitis because of perforation risk.
Early laparotomy for acute arterial occlusive disease or if evidence of peritonitis or clinical deterioration is present.
Angioplasty and thrombectomy +/– endovascular stenting for acute arterial thrombosis.
Embolectomy for acute arterial embolism.Resection of infarcted bowel.Sepsis/septic shock, multisystem organ failure, death.See the Emergency Medicine chapter.Outpouchings of mucosa and submucosa (false diverticula) that herniate through the colonic muscle layers in areas of high intraluminal pressure; most commonly found in the sigmoid colon. Diverticulosis is the most common cause of acute lower GI bleeding in patients > 40 years of age. Risk factors include a low-fber and high-fat diet, advanced age (65% occur in those > 80 years of age), and connective tissue disorders (e.g., Ehlers-Danlos syndrome). Diverticulitis is due to inflammation and, potentially, perforation of a diverticulum 2° to fecalith impaction.
Diverticulosis is often asymptomatic.Bleeding is painless and sudden, generally presenting as hematochezia with symptoms of anemia (fatigue, lightheadedness, dyspnea on exertion).
Diverticulitis presents with LLQ abdominal pain, fever, nausea, vomiting, and constipation. Perforation is a serious complication that leads to peritonitis and shock.
CBC may show leukocytosis.Diagnosis is based on AXR (to rule out free air, ileus, or obstruction), colonoscopy, or barium enema. Sigmoidoscopy/colonoscopy must be avoided in those with early diverticulitis due to the risk of perforation.
In patients with severe disease or in those who show lack of improvement, abdominal CT may reveal abscess or free air.
Uncomplicated diverticulosis: Patients can be followed and placed on a high-f ber diet or fiber supplements.
Diverticular bleeding: Bleeding usually stops spontaneously; transfuse and hydrate as needed. If bleeding does not stop, angiography with embolization or surgery is indicated.
Diverticulitis: Treat with bowel rest (NPO), NG tube placement, and broad-spectrum antibiotics (metronidazole and a fluoroquinolone or a secondor third-generation cephalosporin) if the patient is stable. Avoid barium enema and flexible sigmoidoscopy if diverticulitis is suspected.
■For perforation, perform immediate surgical resection of diseased bowel via a Hartmann’s procedure with a temporary colostomy.
Table 2.6-3 describes features that distinguish SBO from LBO. Figure 2.6-4 demonstrates the classic radiographic findings of LBO.
The second leading cause of cancer mortality in the United States after lung cancer. There is an ↑ incidence with age, with a peak incidence at 70– 80 years. There has also been an observed association between colon cancer
T AB LE 2.6-3. Characteristics of Small and Large Bowel Obstruction
History Moderate to severe acute abdominal pain; copious emesis. Cramping pain with distal SBO. Fever, signs of dehydration, and hypotension may be seen. Constipation/obstipation, deep and cramping abdominal pain (less intense than SBO), nausea/ vomiting (less than SBO but more commonly feculent). PE Abdominal distention (distal SBO), abdominal tenderness, visible peristaltic waves, fever, hypovolemia. Look for surgical scars/hernias; perform a rectal exam. High-pitched “tinkly” bowel sounds; later, absence of bowel sounds. Signif cant distention, tympany, and tenderness; examine for peritoneal irritation or mass; fever or signs of shock suggest perforation/peritonitis or ischemia/necrosis. High-pitched “tinkly” bowel sounds; later, absence of bowel sounds. Etiologies Adhesions (postsurgery), hernias, neoplasm, volvulus, intussusception, gallstone ileus, foreign body, Crohn’s disease, CF, stricture, hematoma. Colon cancer, diverticulitis, volvulus, fecal impaction, benign tumors. Assume colon cancer until proven otherwise. Differential LBO, paralytic ileus, gastroenteritis. SBO, paralytic ileus, appendicitis, IBD, Ogilvie’s syndrome (pseudo-obstruction). CBC, electrolytes, lactic acid, AXR (see Figure 2.6-3); contrast studies (determine if it is partial or complete), CT scan. CBC, electrolytes, lactic acid, AXR (see Figure 2.6-4), CT scan; water contrast enema (if perforation is suspected); sigmoidoscopy/colonoscopy if stable.
Hospitalize. Partial SBO can be treated conservatively with NG decompression and NPO status.
Patients with complete SBO should be managed aggressively with NPO status, NG decompression, IV fuids, electrolyte replacement, and surgical correction.
Hospitalize. Obstruction can be relieved with a Gastrografn enema, colonoscopy, or a rectal tube; however, surgery is usually required. Ischemic colon usually requires partial colectomy with a diverting colostomy.
Treat the underlying cause (e.g., neoplasm).TABLE 2.6-4.FIGURE 2.6-4. Large bowel obstruction.Barium study shows the “bird-beak” sign, with juxtaposed adjacent bowel walls in the dilated loop pointing toward the site of obstruction. (Reproduced, with permission, from Way LW. Current Surgical Diagnosis & Treatment, 10th ed. Stamford, CT: Appleton & Lange, 1994: 676.) and Streptococcus bovis bacteremia. Risk factors and screening protocols are summarized in Table 2.6-4.
■In the absence of screening, colon and rectal cancer typically present with symptoms only after a prolonged period of silent growth.
Hereditary syndromes—familial adenomatous polyposis (100% risk by age 40), Gardner’s disease, hereditary nonpolyposis colorectal cancer (HNPCC).
Family history.IBD—ulcerative colitis carries a higher risk than does Crohn’s disease.
Adenomatous polyps—villous polyps progress more often than tubular polyps and sessile more than pedunculated polyps. Lesions > 2 cm carry an ↑ risk.
Past history of colorectal cancer.High-fat, low-f ber diet.A DRE should be performed yearly for patients ≥ 50 years of age. Up to 10% of all lesions are palpable with DRE.
Stool guaiac should be performed every year for patients ≥ 50 years of age. Up to 50% of guaiac tests are due to colorectal cancer.
Colonoscopy every 10 years in those ≥ 50 years of age OR yearly FOBT with sigmoidoscopy every 5 years.
Colonoscopy should be performed every 10 years in patients ≥ 40 years of age who have a frst-degree relative with colorectal cancer or adenomatous polyps, or 10 years prior to the age at diagnosis of the youngest family member.
Although often asymptomatic, patients may present with unexplained anemia or vague abdominal pain. Other features depend on location:
Right-sided lesions: Often bulky, ulcerating masses that lead to anemia from chronic occult blood loss. Patients may complain of weight loss, anorexia, diarrhea, weakness, or vague abdominal pain. Obstruction is rare.
Left-sided lesions: Typically “apple-core” obstructing masses (see Figure 2.6-5). Patients complain of a change in bowel habits (e.g., ↓ stool caliber, constipation, obstipation), colicky abdominal pain, and/or blood-streaked stools. Obstruction is common.
Rectal lesions: Usually present with bright red blood per rectum, often with tenesmus and/or rectal pain. Can coexist with hemorrhoids, so rectal cancer must be ruled out in all patients with rectal bleeding.
Order a CBC (often shows microcytic anemia) and stool occult blood.
Perform sigmoidoscopy to evaluate rectal bleeding and all suspicious left-sided lesions.
Rule out synchronous right-sided lesions with colonoscopy. If colonoscopy is incomplete, rule out additional lesions with an air-contrast barium enema.
Determine the degree of invasion in rectal cancer with endorectal ultrasound.
Order a CXR, LFTs, and an abdominal/pelvic CT for metastatic workup. Metastases may arise from direct extension to local viscera, hematogenous spread (40–50% go to the liver, but spread may also occur to bone, lungs, and brain), or lymphatic spread (to pelvic lymph nodes).
Iron deficiency anemia in an elderly male is colorectal cancer until proven otherwise.
FIGURE 2.6-5.  Colon carcinoma.The encircling carcinoma appears as an “apple-core” filling defect in the descending colon on barium enema x-ray. (Reproduced, with permission, from Way LW. Current Surgical Diagnosis & Treatment, 10th ed. Stamford, CT: Appleton & Lange, 1994: 658.) ■Staging is based on the depth of tumor penetration into the bowel wall and the presence of lymph node involvement and distant metastases.
Ischemic colitis is a known complication of AAA repair due to sacrifice of the inferior mesenteric artery.
One unit of PRBCs should ↑ hemoglobin by 1 unit and hematocrit by 3–4 units.
Surgical resection of the 1° cancer is the treatment of choice. Regional lymph node dissection should be performed for staging purposes.
For rectal lesions, the resection technique depends on the proximity of the lesion to the anal verge (the junction between the anal canal and the anal skin).
Abdominoperineal resection: For distal lesions < 10 cm from the anal verge, when the sphincter cannot be preserved, the rectum and anus are resected and a permanent colostomy is placed.
Low anterior resection: For proximal lesions > 10 cm from the anal verge, a 1° anastomosis is created between the colon and rectum.
Wide local excision: For small, low-grade, well-differentiated tumors in the lower third of the rectum.
Adjuvant chemotherapy: Used in cases of colon cancer with lymph nodes. Can be considered for rectal cancers.
Follow with serial CEA levels (diagnostically nonspecific, but useful for monitoring recurrence), colonoscopy, LFTs, CXR, and abdominal CT (for metastasis).
Due to lack of arterial blood supply to the colon. Severity ranges from superficial mucosal involvement to full-thickness necrosis.
The most commonly affected site is the left colon, particularly the “watershed area” at the splenic fl exure. Incidence ↑ with age.
Hx/PE: Presents with crampy lower abdominal pain associated with bloody diarrhea. Fever and peritoneal signs suggest infarction.
CBC may reveal leukocytosis.Flexible sigmoidoscopy or colonoscopy to assess colonic mucosa.Supportive therapy with bowel rest, IV fluids, and broad-spectrum antibiotics.
Surgery with resection is indicated for infarction, fulminant colitis, or obstruction 2° to ischemic stricture.
Bleeding from the GI tract may present as hematemesis, hematochezia, and/or melena. Upper GI tract bleeding is defined as bleeding from lesions proximal to the ligament of Treitz (the anatomic boundary between the duodenum and jejunum). Table 2.6-5 presents the features of upper and lower GI bleeding.
Comprises Crohn’s disease and ulcerative colitis (see Figure 2.6-6). Most common in Caucasians and Ashkenazi Jews, appearing most frequently during the teens to early 30s or in the 50s. Table 2.6-6 summarizes the features of IBD.
T AB LE 2.6-5. Features of Upper and Lower GI Bleeding
HIGH-YIELD FACTS History/PE Hematemesis (”coffee-ground” emesis), melena > hematochezia, depleted volume status (e.g., tachycardia, lightheadedness, hypotension). Hematochezia > melena, but can be either. Diagnosis NG tube and NG lavage; endoscopy if stable. Rule out upper GI bleed with NG lavage. Anoscopy/sigmoidoscopy for patients < 45 years of age with small-volume bleeding. Colonoscopy if stable; arteriography or exploratory laparotomy if unstable. Etiologies PUD, esophagitis/gastritis, Mallory-Weiss tear, esophageal varices. Diverticulosis (60%), IBD, hemorrhoids/f ssures, neoplasm, AVM. Initial management Protect the airway (may need intubation). Stabilize the patient with IV fuids and PRBCs (hematocrit may be normal early in acute blood loss). Similar to upper GI bleed. Long-term management Endoscopy followed by therapy directed at the underlying cause (e.g., high-dose PPIs for PUD; octreotide and/or banding for varices). Depends on the underlying etiology. Endoscopic therapy (e.g., epinephrine injection), intra-arterial vasopressin infusion or embolization, or surgery for diverticular disease or angiodysplasia.
F IGU R E 2.6-6.  Inflammatory bowel disease.(A) Crohn’s disease. Barium enema x-ray reveals deep transverse fissures, ulcers, and edema of the bowel. (B) Ulcerative colitis. Barium enema x-ray demonstrates shortening of the colon, loss of haustra (“lead pipe” appearance), and fine serrations of the bowel edges from small ulcers. (Reproduced, with permission, from Stobo J et al. The Principles and Practice of Medicine, 23rd ed. Stamford, CT: Appleton & Lange, 1996: 135.)
T AB LE 2.6-6. Features of Ulcerative Colitis and Crohn’s Disease
Site of involvement The rectum is always involved. May extend proximally in a continuous fashion. Infammation and ulceration are limited to the mucosa and submucosa. May involve any portion of the GI tract, particularly the ileocecal region, in a discontinuous pattern (“skip lesions”). The rectum is often spared. Transmural infl ammation is seen. History/PE Bloody diarrhea, lower abdominal cramps, tenesmus, urgency. Exam may reveal orthostatic hypotension, tachycardia, abdominal tenderness, frank blood on rectal exam, and extraintestinal manifestations. Abdominal pain, abdominal mass, low-grade fever, weight loss, watery diarrhea. Exam may reveal fever, abdominal tenderness or mass, perianal fissures, fistulas, and extraintestinal manifestations. Extraintestinal manifestations Aphthous stomatitis, episcleritis/uveitis, arthritis, primary sclerosing cholangitis, erythema nodosum, and pyoderma gangrenosum. The same as ulcerative colitis, as well as gallstones, nephrolithiasis, and fstulas to the skin, bladder, or between bowel loops. Diagnosis CBC, AXR, stool cultures, O&P, stool assay for The same lab workup as ulcerative colitis. Upper GI
C. difficile.Colonoscopy can show diffuse and continuous rectal involvement, friability, edema, and pseudopolyps.
Defnitive diagnosis can be made with biopsy.5-ASA agents (e.g., sulfasalazine, mesalamine), topical or oral; corticosteroids and immunomodulating agents (e.g., azathioprine) for refractory disease.
Total proctocolectomy is curative for longstanding or fulminant colitis or toxic megacolon; it also ↓ cancer risk.
Markedly ↑ risk of colorectal cancer in longstanding cases (monitor with frequent fecal occult blood screening and yearly colonoscopy with multiple biopsies after eight years of disease).
series with small bowel follow-through.Colonoscopy may show aphthoid, linear, or stellate ulcers, strictures, “cobblestoning,” and “skip lesions.” “Creeping fat” may also be present during laparotomy.
Defnitive diagnosis can be made with biopsy.5-ASA agents; corticosteroids and immunomodulating agents (e.g., azathioprine, infiximab) are indicated if no improvement is seen.
Surgical resection may be necessary for suspected perforation, stricture, fstula, or abscess; may recur anywhere in the GI tract.
Incidence of 2° malignancy is lower than in ulcerative colitis, but greater than the general population.
Abnormal protrusions of abdominal contents (usually the small intestine) into the inguinal region through a weakness or defect in the abdominal wall. Defined as direct or indirect on the basis of their relationship to the inguinal canal.
■ Indirect: Herniation of abdominal contents through the internal and then external inguinal rings and eventually into the scrotum (in males).
The most common hernia in both genders.Due to a congenital patent processus vaginalis.Protrudes lateral to the inferior epigastric vessels.Direct: Herniation of abdominal contents through the fl oor of Hesselbach’s triangle.
Protrudes medial to the epigastric vessels.Hernial sac contents do not traverse the internal inguinal ring; they herniate directly through the abdominal wall and are contained within the aponeurosis of the external oblique muscle.
Most often due to an acquired defect in the transversalis fascia from mechanical breakdown that ↑ with age.
Because of the risk of incarceration and strangulation, surgical management (open or laparoscopic) is indicated unless specific contraindications are present.
Repair of a direct inguinal hernia involves correcting the defect in the transversalis fascia.
Indirect inguinal hernias are repaired by isolating and ligating the hernial sac and reducing the size of the internal inguinal ring to allow only the spermatic cord structures in males to pass through.
Hesselbach’s triangle is an area bounded by the inguinal ligament, the inferior epigastric artery, and the rectus abdominis.
Colic results from transient cystic duct blockage from impacted stones. Although risk factors include the 4 F’s—Female, Fat, Fertile, and Forty—the disorder is common and can occur in any patient. Flatulence can be thought of as a “5th F.” Other risk factors include OCP use, rapid weight loss, a family history, chronic hemolysis (pigment stones in sickle cell disease), small bowel resection, and TPN.
Patients present with postprandial abdominal pain (usually in the RUQ) that radiates to the right subscapular area or the epigastrium.
Pain is abrupt; is followed by gradual relief; and is often associated with nausea and vomiting, fatty food intolerance, dyspepsia, and fl atulence.
Gallstones may be asymptomatic in up to 80% of patients. Exam may reveal RUQ tenderness and a palpable gallbladder.
Plain x-rays are rarely diagnostic; only 10–15% of stones are radiopaque.
RUQ ultrasound is the imaging modality of choice (85–90% sensitive).
Table 2.6-7 contrasts lab findings with those of other forms of biliary disease.
Cholecystectomy is curative and can be performed electively for symptomatic gallstones. It is generally performed laparoscopically. Asymptomatic gallstones do not require any intervention.
Patients may require preoperative endoscopic retrograde cholangiopancreatography (ERCP) for common bile duct stones.
Treat nonsurgical candidates with dietary modif cation (avoid triggers such as fatty foods).
Pigmented gallstones result from hemolysis (black) or infection (brown).Most gallstones are precipitations of cholesterol and are not radiopaque.
TAB LE 2.6-7. Differential Diagnosis of Biliary DiseaseThe cystic artery usually passes through the anatomic triangle of Calot, comprising the common hepatic duct, the cystic duct, and the inferior border of the liver.
In patients with significant medical problems (including DM), delay cholecystectomy until acute infl ammation resolves.
Recurrent biliary colic, acute cholecystitis, choledocholithiasis, ascending cholangitis, gallstone ileus, gallstone pancreatitis.
Prolonged blockage of the cystic duct, usually by an impacted stone, that leads to obstructive distention, inflammation, superinfection, and possibly gangrene of the gallbladder (acute gangrenous cholecystitis). Acalculous cholecystitis occurs in the absence of cholelithiasis in patients who are chronically debilitated, those who are critically ill in the ICU or on TPN, and trauma or burn victims.
Patients present with RUQ pain, nausea, vomiting, and fever. Symptoms are typically more severe and of longer duration than those of biliary colic.
RUQ tenderness, inspiratory arrest during deep palpation of the RUQ (Murphy’s sign), low-grade fever, mild icterus, and possibly guarding or rebound tenderness may be present on exam.
Fever is often present, and CBC shows leukocytosis (see Table 2.6-7).
Ultrasound may demonstrate stones, bile sludge, pericholecystic fl uid, a thickened gallbladder wall, gas in the gallbladder, and an ultrasonic Murphy’s sign (see Figure 2.6-7).
Obtain a HIDA scan when ultrasound is equivocal (see Figure 2.6-8); nonvisualization of the gallbladder on HIDA scan suggests acute cholecystitis.
Hospitalize patients, administer broad-spectrum IV antibiotics and IV f u-ids, and replete electrolytes.
If diagnosed soon after onset, early cholecystectomy is indicated.For stable patients or those with significant medical problems, surgery can be delayed for 4–6 weeks.
F IGU R E 2.6-7. Acute cholecystitis, ultrasound.Note the sludge-filled, thick-walled gallbladder with a hyperechoic stone and acoustic shadow (arrow). (B) This patient exhibits sludge and pericholecystic fluid (arrow) but no gallstones. (Reproduced, with permission, from Grendell
Current Diagnosis & Treatment in Gastroenterology, 1st ed. Stamford, CT: Appleton & Lange, 1996: 212.)
Gangrene, empyema, perforation, emphysematous gallbladder (due to infection by gas-forming organisms), fistulization, gallstone ileus, sepsis, abscess formation.
■Gallstones in the common bile duct. Symptoms vary according to the degree of obstruction, the duration of the obstruction, and the extent of bacterial infection.
F IGU R E 2.6-8. Acute cholecystitis, HIDA scan.IV dye is taken up by hepatocytes and is conjugated and excreted into the common bile duct. The gallbladder is not visualized, although activity is present in the liver, common duct, and small bowel, suggesting cystic duct obstruction due to acute cholecystitis. (Reproduced, with permission, from Grendell J. Current Diagnosis & Treatment in Gastroenterology, 1st ed. Stamford, CT: Appleton & Lange, 1996: 217.)
Gallstone pancreatitis occurs when stones in the ampulla also obstruct the pancreatic duct.
Charcot’s triad consists of RUQ pain, jaundice, and fever/chills. Reynolds’ pentad consists of RUQ pain, jaundice, fever/chills, shock, and altered mental status.
Hx/PE: Although sometimes asymptomatic, it often presents with biliary colic, jaundice, fever, and pancreatitis.
Dx: The hallmark is ↑ alkaline phosphatase and total bilirubin, which may be the only abnormal lab values (see Table 2.6-7).
Tx: Management generally consists of ERCP with sphincterotomy followed by semielective cholecystectomy. Common bile duct exploration may be necessary.
An acute bacterial infection of the biliary tree that commonly occurs 2° to obstruction, usually from gallstones (choledocholithiasis) or primary sclerosing cholangitis (progressive inflammation of the biliary tree associated with ulcerative colitis). Other etiologies include bile duct stricture and malignancy (biliary or pancreatic). Gram-enterics (e.g., E. coli, Enterobacter, Pseudomonas) are commonly identified pathogens.
Charcot’s triad—RUQ pain, jaundice, and fever/chills—is classic and seen in 50–70% of cases.
Reynolds’ pentad—Charcot’s triad plus septic shock and altered mental status—may be present in acute suppurative cholangitis and suggests sepsis.
Look for leukocytosis, ↑ bilirubin, and ↑ alkaline phosphatase (see Table 2.6-7).
Obtain blood cultures to rule out sepsis. Ultrasound or CT may be a useful adjunct, but diagnosis is often clinical. Magnetic resonance cholangiopancreatography (MRCP) is a noninvasive test that may also be useful.
ERCP is both diagnostic and therapeutic (biliary drainage).Patients often require ICU admission for monitoring, hydration, BP support, and broad-spectrum IV antibiotic treatment.
Patients with acute suppurative cholangitis require emergent bile duct decompression via ERCP/sphincterotomy, percutaneous transhepatic drainage, or open decompression.
A mechanical obstruction resulting from the passage of a large (> 2.5-cm) stone into the bowel through a cholecystoduodenal fistula. Obstruction is often at the terminal ileum (TI)/ileocecal valve.
Hx/PE: Many patients have no previous history of biliary symptoms and present as an SBO. The classic presentation is that of a subacute SBO in an elderly woman.
Dx: Pneumobilia (gas in the biliary tree) seen on imaging can confirm, in addition to an upper GI series with small bowel follow-through showing a TI obstruction.
Tx: Laparotomy with stone extraction (enterolithotomy) or manipulation into the colon.
■An idiopathic disorder characterized by infl ammation, fibrosis, and strictures of extraand intrahepatic bile ducts. The disease usually presents in young men with IBD (most often ulcerative colitis).
Hx/PE: Presents with progressive jaundice, pruritus, and fatigue.Dx: is significantly associated with ■ Laboratory findings include ↑ alkaline phosphatase and ↑ bilirubin.
ulcerative colitis.MRCP/ERCP show multiple bile duct strictures with dilatations between strictures.
Liver biopsy reveals periductal sclerosis (“onion skinning”).Tx: High-dose ursodeoxycholic acid; endoscopic dilation and short-term stenting of bile duct strictures; liver transplantation. Patients are at ↑ risk for cholangiocarcinoma.
Liver diseases can be divided into distinct patterns based on LFT results:
Hepatocellular injury: ↑ AST and ALT.Cholestasis: ↑ alkaline phosphatase and bilirubin.Isolated hyperbilirubinemia: ↑ bilirubin; normal aminotransferases and alkaline phosphatase.Jaundice, which can be seen in any of the patterns outlined above, is a clinical sign that arises when excess bilirubin (> 2.5 mg/dL) is circulating in the blood. Figures 2.6-9 and 2.6-10 summarize the clinical approaches toward cholestasis and isolated hyperbilirubinemia. Hepatocellular injury is described in the section that follows.
Inflammation of the liver leading to liver cell injury and necrosis. The causes of acute hepatitis include viruses (e.g., HAV, HBV, HCV, HDV, HEV) and drug-induced disease (e.g., alcohol, acetaminophen, INH, methyldopa). The
Ductal dilation?FIGURE 2.6-9. Approach to cholestasis.HCV is Chronic. Eighty percent of patients with HCV infection will develop chronic hepatitis.
An AST/ALT ratio > 2 suggests alcoholic hepatitis—you’re toASTed.causes of chronic hepatitis include viruses (e.g., HBV, HCV, HDV), alcoholic hepatitis, autoimmune hepatitis, ischemic hepatitis, and hereditary etiologies (e.g., Wilson’s disease, hemochromatosis, α1-antitrypsin deficiency).
HAV and HEV are transmitted by the fecal-oral route.HBV and HCV are transmitted by bodily fluids, although the risk of acquiring HCV sexually is very low.
Acute hepatitis often starts with a viral prodrome of nonspecific symptoms (e.g., malaise, fever, joint pain, fatigue, URI symptoms, nausea, vomiting, changes in bowel habits) followed by jaundice and RUQ tenderness.
Exam often reveals jaundice, scleral icterus, tender hepatomegaly, possible splenomegaly, and lymphadenopathy.
Chronic hepatitis usually gives rise to symptoms indicative of chronic liver disease (jaundice, fatigue, hepatosplenomegaly). At least 80% of those infected with HCV and 10% of those with HBV will develop chronic hepatitis.
Dramatically ↑ ALT and AST and ↑ bilirubin/alkaline phosphatase are present in the acute form.
In chronic hepatitis, ALT and AST are ↑ for > 6 months with a concurrent ↑ in alkaline phosphatase/bilirubin and hypoalbuminemia. In severe cases, PT will be prolonged, as all clotting factors except factor VIII are produced by the liver.
The diagnosis of viral hepatitis is made by hepatitis serology (see Table 2.6-8 and Figure 2.6-11 for a description and timing of serologic markers) and by liver biopsy in chronic or severe cases.
ANA, anti–smooth muscle antibody, and antimitochondrial antibody point to autoimmune hepatitis. Iron saturation (hemochromatosis) and ceruloplasmin (Wilson’s disease) can identify other causes.
Treatment is etiology specific; monitor for resolution of symptoms over time.
Steroids for severe alcoholic hepatitis.Immunosuppression with steroids and other agents (azathioprine) for autoimmune hepatitis.
T AB LE 2.6-8. Key Hepatitis Serologic MarkersHBsAg Antigen found on the surface of HBV; continued presence indicates carrier state.    HBsAb Antibody to HBsAg; provides immunity to HBV. HBcAg Antigen associated with core of HBV.    HBcAb Antibody to HBcAg; during the window period. IgM HBcAb is an indicator of recent disease. HBeAg A second, different antigenic determinant in the HBV core. An important indicator of transmissibility (BEware!). IgM HAVAb IgM antibody to HAV; the best test to detect active hepatitis A. HBeAb Antibody to e antigen; indicates low transmissibility.
IFN-α, lamivudine (3TC), or adefovir for chronic HBV infection; peginterferon and ribavirin for chronic HCV infection.
Liver transplantation is the treatment of choice for patients with end-stage liver failure.
ICU management and emergent transplant for fulminant hepatic failure.Important diagnostic tests Incubation Prodrome,The sequelae of chronic hepatitis include cirrhosis, liver failure, and hepatocellular carcinoma.
Level of detectionF IGU R E 2.6-1 1. Time course of hepatitis B with serologic markers.
Alcoholism, chronic hepatitis, and other chronic liver diseases lead to cirrhosis.
Gut, butt, and caput—the three anastomoses commonly seen in cirrhosis.
Cirrhosis, liver failure, hepatocellular carcinoma (3–5%).Defined as f brosis and nodular regeneration resulting from hepatocellular injury. Etiologies include causes of chronic hepatitis, biliary tract disease (e.g., primary biliary cirrhosis, primary sclerosing cholangitis), right-sided heart failure, constrictive pericarditis, and Budd-Chiari syndrome (hepatic vein thrombosis 2° to hypercoagulability).
Presents with jaundice, ascites, spontaneous bacterial peritonitis, hepatic encephalopathy (e.g., asterixis, altered mental status), gastroesophageal varices, coagulopathy, and renal dysfunction. Weakness, anorexia, and weight loss are also seen in advanced disease.
Exam may reveal an enlarged, palpable, or firm liver. Stigmata of portal hypertension and signs of liver failure may be present (see Figures 2.6-12 and 2.6-13).
Lab studies show ↓ albumin, ↑ PT/PTT, and ↑ bilirubin. Anemia or thrombocytopenia (2° to hypersplenism) may also be seen.
Abdominal ultrasound with Doppler can assess liver size, the presence of ascites, and the patency of splenic and hepatic veins. The etiology of ascites can be established through measurement of the serum-ascites albumin gradient (SAAG = serum albumin – ascites albumin); see Table 2.6-9.
Obtain hepatitis serologies and autoimmune hepatitis studies.Serum ferritin, ceruloplasmin, and α1-antitrypsin may help identify additional causes, such as hemochromatosis, Wilson’s disease, and α1antitrypsin deficiency, respectively.
Liver biopsy showing bridging fibrosis and nodular regeneration.Effects of portal hypertensionEffects of liver cell failureLoss of sexual hairF IGU R E 2.6-1 2. Presentation of cirrhosis/portal hypertension.
(Adapted, with permission, from Chandrasoma P, Taylor CE. Concise Pathology, 3rd ed. Stamford, CT: Appleton & Lange, 1998: 654.)
Superior mesenteric v. Gastroesophageal vv. Superior-middle/inferior rectal vv. Gastrorenal-splenorenal vv. Paraumbilical v. IVC Systemic venousPortal venousPortal v. L. gastric v. Retro-peritoneal paravertebral v Splenic v. 1 2 3 4 5 v.
F IGU R E 2.6-1 3.  Portosystemic anastomoses.1. Left gastric–azygos → esophageal varices. 2. Superior–middle/inferior rectal → hemorrhoids.
3. Paraumbilical–inferior epigastric → caput medusae (navel). 4. Gastrorenal-splenorenal.5. Retroperitoneal paravertebral.Aimed at ameliorating the complications of cirrhosis/portal hypertension.Sodium restriction and diuretics (furosemide and spironolactone). Noncirrhotic causes of
Rule out infectious and neoplastic causes; perform paracentesis to ob- tain SAAG, cell count with differential, and cultures.
If possible, treat underlying liver disease. right heart failure, splenic
Spontaneous bacterial peritonitis: vein thrombosis, andPresents with fever, abdominal pain, and altered mental status.Check peritoneal fluid if there is a possibility of infection. The fl uid is if there are > 250 PMNs/mL or > 500 WBCs.
Treat with IV antibiotics (e.g., third-generation cephalosporin) to cover both gram-(Enterococcus) and gram-(E. coli, Klebsiella) organisms until a causative organism is identified.
T AB LE 2.6-9.  Serum-Ascites Albumin GradientSAAG > 1.1 SAAG < 1.1Ascites is due to protein leakage: ■Nephrotic syndrome ■Tuberculosis ■Malignancy (e.g., ovarian cancer)
Ascites is related to portal hypertension:Presinusoidal: Splenic or portal vein thrombosis, schistosomiasisSinusoidal: Cirrhosis, massive hepatic metastasesPostsinusoidal: Right heart failure, constrictive pericarditis, Budd-Chiari syndromeSpontaneous bacterial peritonitis is diagnosed by > 250 PMNs/mL or > 500 WBCs in the ascitic fl uid.
Primary biliary cirrhosis is an autoimmune disease that presents with jaundice and pruritus in middle-aged women.
Complications of hepatocellular carcinoma include GI bleeding, liver failure, and metastasis.
Hepatorenal syndrome: A diagnosis of exclusion; difficult to treat and often requires dialysis.
Hepatic encephalopathy:Due to ↓ clearance of ammonia.Often precipitated by dehydration, infection, electrolyte abnormalities, and GI bleeding.
Treat with dietary protein restriction, lactulose, and rifaximin.Esophageal varices:Monitor for GI bleeding; treat medically (β-blockers, octreotide), endoscopically (band ligation), or surgically (portocaval shunt).
Consider liver transplantation for patients with advanced disease.An autoimmune disorder characterized by destruction of intrahepatic bile ducts. The disease most commonly presents in middle-aged women with other autoimmune conditions.
Hx/PE: Presents with progressive jaundice, pruritus, and malabsorption of the fat-soluble vitamins (A, D, E, K).
Dx: Laboratory findings include ↑ alkaline phosphatase, ↑ bilirubin, antimitochondrial antibody, and ↑ cholesterol.
Tx: Ursodeoxycholic acid (slows progression of disease); cholestyramine for pruritus; liver transplantation.
One of the most common cancers worldwide despite its relatively low incidence in the United States. 1° risk factors for the development of hepatocellular carcinoma in the United States are cirrhosis and chronic hepatitis (HCV). In developing countries, af atoxins (in various food sources) and HBV infection are also major risk factors.
Patients commonly present with RUQ tenderness, abdominal distention, and signs of chronic liver disease such as jaundice, easy bruisability, and coagulopathy. Cachexia and weakness may be present.
Exam may reveal tender enlargement of the liver.Often suggested by the presence of a mass on ultrasound or CT as well as by abnormal LFTs and significantly elevated α-fetoprotein (AFP) levels.
Liver biopsy for definitive diagnosis.For small tumors that are detected early, aggressive tumor resection or orthotopic liver transplantation may be successful.
Chemotherapy and radiation are generally not effective, although they may be used to shrink large tumors prior to surgery (neoadjuvant therapy).
Monitor tumor recurrence with serial AFP levels. Prevent exposure to hepatic carcinogens and vaccinate against hepatitis in high-risk individuals.
Caused by hyperabsorption of iron with parenchymal hemosiderin accumulation in the liver, pancreas, heart, adrenals, testes, pituitary, and kidneys. It is an autosomal-recessive disease that usually occurs in males of northern European descent and is rarely recognized before the fifth decade. 2° hemochromatosis may occur with iron overload and is common in patients receiving chronic transfusion therapy (e.g., for α-thalassemia) as well as in alcoholics (alcohol ↑ iron absorption).
Patients may present with abdominal pain or symptoms of DM, hypogonadism, arthropathy of the MCP joints, heart failure, or cirrhosis.
Exam may reveal bronze skin pigmentation, pancreatic dysfunction, cardiac dysfunction (CHF), hepatomegaly, and testicular atrophy.
■↑ serum iron, percent saturation of iron, and ferritin with ↓ serum transferrin.
Fasting transferrin saturation (serum iron divided by transferrin level) > 45% is the most sensitive diagnostic test.
Glucose intolerance and mildly elevated AST and alkaline phosphatase can be present.
Perform a liver biopsy (to determine hepatic iron index), hepatic MRI, or HFE gene mutation screen.
Weekly phlebotomy; when serum iron levels ↓, perform maintenance phlebotomy every 2–4 months.
Deferoxamine can be used for maintenance therapy.Cirrhosis, hepatocellular carcinoma, cardiomegaly leading to CHF and/or conduction defects, DM, impotence, arthropathy, hypopituitarism.
■↓ ceruloplasmin and excessive deposition of copper in the liver and brain due to a deficient copper-transporting protein. Linked to an autosomalrecessive defect on chromosome 13. Usually occurs in patients < 30 years of age; 50% of patients are symptomatic by age 15.
Hx: Patients with present hemolytic anemia, liver abnormalities (jaundice 2° to hepatitis/cirrhosis), and neurologic (loss of coordination, tremor, dysphagia) as well as psychiatric (psychosis, anxiety, mania, depression) abnormalities.
PE: May reveal Kayser-Fleischer rings in the cornea (green-to-brown deposits of copper in Descemet’s membrane) as well as jaundice, hepatomegaly, asterixis, choreiform movements, and rigidity.
Dx: ↓ serum ceruloplasmin, ↑ urinary copper excretion, ↑ hepatic copper.
Tx: Dietary copper restriction (avoid shellfish, liver, legumes), penicillamine (a copper chelator that ↑ urinary copper excretion; administer with pyridoxine), and possibly oral zinc (↑ fecal excretion).
Wilson’s disease— ABCD Asterixis Basal ganglia deterioration Ceruloplasmin ↓, Cirrhosis, Copper ↑, Carcinoma (hepatocellular), Choreiform movements Dementia
Table 2.6-10 outlines the important features of acute and chronic pancreatitis. Table 2.6-11 lists Ranson’s criteria for predicting mortality associated with acute pancreatitis.
T AB LE 2.6-1 0. Features of Acute and Chronic Pancreatitis
Treatment Prognosis Complications Can have chronic pain and pancreatic exocrine and endocrine dysfunction. Chronic pain, malnutrition/weight loss, pancreatic cancer.
Pathophysiology Leakage of pancreatic enzymes into pancreatic and peripancreatic tissue, often 2° to gallstone disease or alcoholism. Irreversible parenchymal destruction leading to pancreatic dysfunction. Time course Abrupt onset of severe pain. Persistent, recurrent episodes of severe pain. Risk factors Gallstones, alcoholism, hypercalcemia, hypertriglyceridemia, trauma, drug side effects (thiazide diuretics), viral infections, post-ERCP, scorpion bites. Alcoholism (90%), gallstones, hyperparathyroidism, hypercholesterolemia, cystic f brosis. May also be idiopathic. History/PE Severe epigastric pain (radiating to the back); nausea, vomiting, weakness, fever, shock. Flank discoloration (Grey Turner’s sign) and periumbilical discoloration (Cullen’s sign) may be evident on exam. Recurrent episodes of persistent epigastric pain; anorexia, nausea, constipation, f atulence, steatorrhea, weight loss, DM. Diagnosis ↑ amylase, ↑ lipase, ↓ calcium if severe; “sentinel ↑ or normal amylase and lipase, ↓ stool elastase, Removal of the offending agent if possible. Standard supportive measures: IV f uids/electrolyte replacement, analgesia, bowel rest, NG suction, nutritional support, O2, “tincture of time.” IV antibiotics, respiratory support, and surgical debridement if necrotizing pancreatitis is present.
loop” or “colon cutoff sign” on AXR.Abdominal ultrasound or CT may show an enlarged pancreas with stranding, abscess, hemorrhage, necrosis, or pseudocyst.
Roughly 85–90% are mild and self-limited; 10– 15% are severe, requiring ICU admission. Mortality may approach 50% in severe cases.
Pancreatic pseudocyst, fistula formation, hypocalcemia, renal failure, pleural effusion, chronic pancreatitis, sepsis. Mortality 2° to acute pancreatitis can be predicted with Ranson’s criteria (see Table 2.6-11).
glycosuria, pancreatic calcifications, and mild ileus on AXR and CT (“chain of lakes”).
Analgesia, exogenous lipase/trypsin and medium-chain fatty-acid diet, avoidance of causative agents (EtOH), celiac nerve block, surgery for intractable pain or structural causes.
TABLE 2.6-11. Ranson’s Criteria for Acute Pancreatitisa a The risk of mortality is 20% with 3–4 signs, 40% with 5–6 signs, and 100% with ≥ 7 signs.
Roughly 75% are adenocarcinomas in the head of the pancreas. Risk factors include smoking, chronic pancreatitis, a first-degree relative with pancreatic cancer, and a high-fat diet. Incidence rises after age 45; slightly more common in men.
Presents with abdominal pain radiating toward the back, as well as with obstructive jaundice, loss of appetite, nausea, vomiting, weight loss, weakness, fatigue, and indigestion.
Often asymptomatic, and thus presents late in the disease course.
Exam may reveal a palpable, nontender gallbladder (Courvoisier’s sign) or migratory thrombophlebitis (Trousseau’s sign).
Use CT to detect a pancreatic mass, dilated pancreatic and bile ducts, the extent of vascular involvement (particularly the SMA, SMV, and portal vein), and metastases (hepatic).
If a mass is not visualized, use ERCP or endoscopic ultrasound for better visualization.
CA-19-9 is often elevated, but this measure lacks sensitivity and specificity.
Most patients present with metastatic disease, and treatment is palliative.
Some 10–20% of pancreatic head tumors have no evidence of metastasis or major vessel involvement and may be resected using the Whipple procedure (pancreaticoduodenectomy).
Chemotherapy with 5-FU and gemcitabine may improve short-term survival, but long-term prognosis is poor (5–10% five-year survival).
The classic presentation of pancreatic cancer is painless, progressive obstructive jaundice.
Neutropenia 210 Eosinophilia 211 Transplant Medicine 212 Diseases Associated with Neoplasms 213
Bleeding disorders due to platelet dysfunction usually manifest as petechiae, whereas disorders of coagulation factors cause other symptoms, such as hemarthroses.
Hemostasis requires the interaction of blood vessels, platelets, monocytes, and coagulation factors. This activates the clotting cascade, as shown in Figure 2.7-1.
Heparin: ↑ PTT, activates antithrombin III and affects the intrinsic pathway, and ↓ fibrinogen levels; protamine sulfate is the antidote.
Warfarin: ↑ PT, inhibits vitamin K and affects the extrinsic pathway, and is teratogenic, since its small size allows it to cross the placenta. Vitamin K is the antidote. Goal INR of 2.0–3.0 (2.5–3.5 in patients with mechanical valves).
Enoxaparin (low-molecular-weight heparin [LMWH]): Inhibits factor Xa and does not have to be monitored; dosing is once or twice daily.
Heparin-to-warfarin conversion is necessary because warfarin inhibits proteins C and S before other vitamin K–dependent factors (II, VII, IX, and X), leading to a transient period of paradoxical hypercoagulability before proper anticoagulation.
Intrinsic pathway—measured by PTT            (initiated by exposure of             collagen following vascular             trauma)
Hemophilia B is characterized by factor IX deficiency. 2 Hemophilia A is characterized by factor VIII deficiency. 3 Thrombin is inactivated by antithrombin III. The rate of inactivation increases in the presence of heparin.
* Vitamin K–dependent clotting factors (II, VII, IX, X). Their synthesis is inhibited by warfarin.
FIGURE 2.7-1.  Coagulation cascade.A defciency of a clotting factor that leads to a bleeding diathesis. Subtypes are distinguished on the basis of which factor is lacking (see Table 2.7-1). The condition is usually hereditary but may be acquired through the development of an antibody to a clotting factor. This may occur in patients with autoimmune or lymphoproliferative disease, postpartum, or following a blood transfusion. Patients are nearly always male and may have a  family history.
Presents with spontaneous hemorrhage into the tissues and joints that, if left untreated, can lead to arthropathy and joint destruction.
Spontaneous intracerebral hemorrhages, renal and retroperitoneal bleeding, and GI bleeding may also be seen.
Mild cases may have major hemorrhage after surgery or trauma but are otherwise asymptomatic.
Evaluate for suspected clotting factor def ciency:PT: Usually normal, but isolated elevations are seen in congenital factor VII deficiency.
aPTT: Prolonged (the more prolonged, the more severe the hemophilia).
Thrombin time, fbrinogen, bleeding time: Usually normal.Conduct a mixing study: Mix the patient’s plasma with normal plasma; if this corrects the aPTT, a factor deficiency is likely. If the aPTT does not correct, the patient may have a clotting factor inhibitor.
Obtain factor assays: Specific factor assays should then be performed for factors VII, VIII, IX, XI, and XII. Hemophilia is characterized according to factor level as follows:
Mild: > 5% of normal.Moderate: 1–3% of normal.Severe: ≤ 1% of normal.■Treat bleeding episodes with immediate transfusion of clotting factors (or cryoprecipitate) to at least 40% of normal concentration. Factor VIII has a half-life of 12 hours, so patients should be dosed BID to maintain ad-
TABLE 2.7-1.  Types of HemophiliaThe classic case of hemophilia is the boy (X-linked) from the Imperial Russian family (Recessive) who presents with hemarthroses following minimal or no trauma.
Cryoprecipitate consists of factors VIII and XIII, vWF, fibrinogen, and fibronectin.
Hemophilia B (factor IX defciency) (9%) X-linked inheritance. Hemophilia C (factor XI defciency) (< 1%) Most common in Ashkenazi Jews. Hemophilia A (factor VIII defciency) (90%) X-linked inheritance; the most common severe congenital clotting def ciency. Factor VII defciency (< 1%) Presents in a milder, likely heterozygous form.
DDAVP helps the body release extra factor VIII.ASA ↑ the risk of bleeding in patients with von Willebrand’s disease.
Ristocetin cofactor assay measures the ability of vWF to agglutinate platelets in vitro in the presence of ristocetin.
Suspect pulmonary embolism in a patient with rapid onset of hypoxia, hypercapnia, tachycardia, and an ↑ alveolar-arterial oxygen gradient without another obvious explanation.
equate levels. Factor IX has a half-life of 24 hours, so daily transfusion is needed.
The length of treatment varies with the lesion, extending up to several weeks after orthopedic surgery.
Mild hemophiliacs may be treated with desmopressin (DDAVP); if so, they should be f uid restricted to prevent the side effect of hyponatremia.
It may be necessary to transfuse RBCs, depending on the degree of blood loss.
Fifteen percent of patients who are treated for hemophilia A develop neutralizing IgG antibodies to factor VIII, which precludes further treatment with replacement factor.
An autosomal-dominant condition in which patients have deficient or defective von Willebrand’s factor (vWF) with low levels of factor VIII, which is carried by vWF. Symptoms are due to platelet dysfunction and to deficient factor
VIII. The disease is milder than hemophilia. vWD is the most common inherited bleeding disorder (1% of the population is affected).
Presents with easy bruising, mucosal bleeding (e.g., epistaxis, oral bleeding), menorrhagia, and postincisional bleeding. Platelet dysfunction is not severe enough to produce petechiae. Symptoms worsen with ASA use.
Look for a family history of bleeding disorders.Platelet count and PT are normal, but a prolonged aPTT may be seen as a result of factor VIII deficiency.
A ristocetin cofactor assay of patient plasma can measure the capacity of vWF to agglutinate platelets.
Bleeding episodes can be treated with DDAVP; menorrhagia can be controlled with OCPs.
Avoid ASA and other inhibitors of platelet function.Also called thrombophilias or prothrombotic states, hypercoagulable states is an all-inclusive term describing conditions that ↑ a patient’s risk of developing thromboembolic disease. Causes are multiple and may be genetic, acquired, or physiologic (see Table 2.7-2). Acquired causes are usually 2° to an underlying clinical condition, disease process, or lifestyle. Inherited causes are collectively called hereditary thrombotic disease, of which factor V Leiden (a polymorphism in factor V, rendering it resistant to inactivity by activated protein C, or APC) is the most common.
■ Presents with recurrent thrombotic complications, including DVT, pulmonary embolism, arterial thrombosis, MI, and stroke. Women may have recurrent miscarriages.
T AB LE 2.7 -2. Causes of Hypercoagulable States ■Although patients may have no recognizable predisposing factors, they usually have one or more of the causative factors outlined in Table 2.7-2. They may also have a  family history.
Under ideal circumstances, patients should be diagnosed before they are symptomatic, but this rarely occurs.
Prior to workup for hereditary causes, acquired causes of abnormal coagulation values should be ruled out. Confrmation of a hereditary abnormality requires two abnormal values that are obtained while the patient is asymptomatic and untreated, with similar values obtained in two other family members.
Workup for hypercoagulability includes lupus antigen/antiphospholipid syndrome, antithrombin III deficiency, protein C and S deficiencies, APC resistance, homocysteine elevation, and prothrombin G20210A mutation.
Treatment should address the type of thrombotic event as well as the area of thrombosis.
Treat DVT and pulmonary embolism with heparin (unfractionated or LMWH) followed by 3–6 months of oral warfarin anticoagulation for the first event, 6–12 months for the second, and lifelong anticoagulation for subsequent events.
Heparin-to-warfarin conversion is necessary (see the “Coagulation Cascade” discussion above).
A common disorder among hospitalized patients, second only to liver disease as a cause of acquired coagulopathy. It is caused by deposition of f brin in small blood vessels, leading to thrombosis and end-organ damage. Depletion of clotting factors and platelets leads to a bleeding diathesis. May be associated with almost any severe illness.
■Disorders commonly associated with DIC include obstetric complications, infections with septicemia, neoplasms, acute promyelocytic leukemia, pan-
DIC is characterized by both thrombosis and hemorrhage.Petechiae suggest Platelet deficiency.Bleeding into body Cavities or joints suggests Clotting factor deficiency.
The three causes of microangiopathic hemolytic anemia are HUS, TTP, and DIC.
creatitis, intravascular hemolysis, vascular disorders (e.g., aortic aneurysm), massive tissue injury and trauma, drug reactions, acidosis, and ARDS.
■Presentation varies according to whether the disease is acute or chronic:
Acute: Presents with generalized bleeding out of venipuncture sites into organs, with ecchymoses and petechiae. Patients who are in shock may have acral cyanosis.
Chronic: Presents with bruising and mucosal bleeding, thrombophlebitis, renal dysfunction, and transient neurologic syndromes.
Diagnosed as outlined in Table 2.7-3.DIC may be confused with severe liver disease, but unlike liver disease, factor VIII is depressed.
Treatment of the underlying illness often results in spontaneous reversal. Patients often require RBC transfusion and shock management. Platelets should be transfused in the event of hemorrhage with a platelet count < 20,000.
Part of a spectrum of diseases that includes hemolytic-uremic syndrome (HUS) and HELLP syndrome (see the Obstetrics chapter); thought to be due to platelet microthrombi that block off small blood vessels, leading to end-organ ischemia and dysfunction. RBCs are fragmented by contact with the microthrombi, leading to hemolysis (microangiopathic hemolytic anemia). The cause of initial microthrombus formation is unknown but may be infectious (bacterial toxins), drug related, autoimmune, or idiopathic.
A clinical syndrome characterized by f ve signs/symptoms: low platelet count, microangiopathic hemolytic anemia, neurologic changes (delirium, seizure, stroke), impaired renal function, and fever.
Diagnosis is largely clinical.It is rare for all signs to be present, but the presence of schistocytes (broken RBCs) on peripheral smear with low platelets and rising creatinine is highly suggestive. Nucleated RBCs are also often seen in the peripheral smear.
Hemolytic anemia labs include elevated indirect bilirubin, LDH, and AST along with low haptoglobin. Coagulation factors are normal.
TABLE 2.7-3. Laboratory Values in DICOverlapping conditions are HUS, HELLP syndrome, and DIC.HUS: Characterized by renal failure, hemolytic anemia, and low platelets. Severe elevations in creatinine are more typical of HUS than of TTP.
HELLP syndrome: Affects pregnant women, often occurring in conjunction with preeclampsia (see the Obstetrics chapter).
DIC: Distinguished from TTP by prolonged PT and aPTT.Treat with corticosteroids to ↓ the formation of microthrombi along with plasma replacement and plasmapheresis (the mainstay of severe cases). Rarely, splenectomy is performed with mixed results. Platelet transfusions are contraindicated.
A relatively common cause of thrombocytopenia. IgG antibodies are formed against the patient’s platelets. Bone marrow production of platelets is ↑, with ↑ megakaryocytes in the marrow. The most common immunologic disorder in women of childbearing age. May be acute or chronic.
Patients often feel well and present with no systemic symptoms. They may have minor bleeding, easy bruising, petechiae, hematuria, hematemesis, or melena. Bleeding is mucocutaneous. Usually there is no splenomegaly.
ITP is associated with a range of conditions, including lymphoma, leukemia, SLE, HIV, and HCV.
The clinical presentation is as follows:Acute: Abrupt onset of hemorrhagic complications following a viral illness. Commonly affects children 2–6 years of age, with males and females affected equally.
Chronic: Insidious onset that is unrelated to infection. Most often affects adults 20–40 years of age; women are three times more likely to be affected than men.
A diagnosis of exclusion, as the test for platelet-associated antibodies is a poor one.
Once other causes of thrombocytopenia have been ruled out, a diagnosis can be made on the basis of the history and physical, a CBC, and a peripheral blood smear showing normal RBC morphology. Most patients do not require bone marrow biopsy, which would show ↑ megakaryocytes as the only abnormality.
Most patients with acute childhood ITP spontaneously remit, but this is rarely the case in chronic ITP.
Treatment is reserved for patients with symptomatic bleeding. Those with platelet counts > 20,000 are generally asymptomatic.
Platelet transfusions are of no benefit, as patients’ IgG levels will also lead to destruction of platelets.
The main therapies are corticosteroids, high-dose gamma globulin (IVIG), and splenectomy. Most patients respond to corticosteroids, but if
Anti-D (Rh) immunoglobulin and rituximab are emerging therapies for ITP.
Anti-D (Rh) immunoglobulin and IVIG act as “decoys” so that WBCs will recognize them they cannot be tapered after 3–6 months, splenectomy should be considered.
An emerging therapy is anti-D (Rh) immunoglobulin, which binds to RBCs so that they are destroyed instead of the patient’s platelets. Patients will have a drop in their hematocrit. Rhand splenectomized patients should not receive this treatment.
In pregnant patients, severe thrombocytopenia may occur in the fetus.
instead of IgG on platelets.Figure 2.7-2 illustrates the various blood cell categories and lineages.
Anemia is a disorder of low hematocrit and hemoglobin. There are several subtypes, which are classified according to red cell morphology (MCV, RDW, color, shape) and reticulocyte count (see Figure 2.7-3). Once anemia has been diagnosed by a low hemoglobin/hematocrit, the approach starts with the MCV. An MCV < 80 fL indicates microcytic anemia; between 80 fL and 100 fL is normocytic; and > 100 fL is macrocytic.
A condition in which iron loss exceeds intake. May occur when dietary intake is insuff cient for the patient’s needs (e.g., when needs are ↑ by growth or pregnancy) or in the setting of chronic blood loss, usually 2° to menstruation or GI bleeding. Toddlers, adolescent girls, and women of childbearing age are most commonly affected.
F IGU R E 2.7 -2. Blood cell differentiation.CBC, reticulocyte countRetic < 2.5 Retic > 2.5Iron deficiency anemia in an elderly patient could be due to colorectal cancer and needs to be evaluated to rule out malignancy.
Iron deficiency anemia can be due to a hookworm infection.
FIGURE 2.7-3.  Anemia algorithm.Symptoms include fatigue, weakness, brittle nails, and pica. If the anemia develops slowly, patients are generally asymptomatic.
Physical findings include glossitis, angular cheilitis, and koilonychia (“spoon nails”).
Bone marrow biopsy looking for evidence of iron stores is the gold standard but is seldom performed.
Iron deficiency is often confused with anemia of chronic disease, in which iron use by the body is impaired. Labs can help differentiate the two conditions (see Table 2.7-4).
Peripheral blood smear shows hypochromic and microcytic RBCs with a low reticulocyte count.
Low serum ferritin reflects low body stores of iron and confirms the diagnosis. However, ferritin is also an acute-phase reactant and may thus obscure evidence of iron deficiency.
Treat with replacement iron for 4–6 months. Oral iron sulfate may lead to nausea, constipation, diarrhea, and abdominal pain. Antacids may interfere with iron absorption.
If necessary, IV iron dextran can be administered but is associated with a 10% risk of serious side effects, including anaphylaxis. Hence, this is usually done only by a hematologist.
T AB LE 2.7 -4.  Iron Defciency Anemia vs. Anemia of Chronic Disease
Most macrocytic anemias are caused by processes that interfere with normal DNA synthesis and replication.
B12 deficiency can be due to infection by a tapeworm,
Diphyllobothrium latum.Causes of oxidative stress in G6PD deficiency include infection, metabolic acidosis, fava beans, antimalarials, dapsone, sulfonamides, and nitrofurantoin.
Vitamin B12 (cobalamin) and folate def ciency interfere with DNA synthesis, leading to a delay in blood cell maturation. Cobalamin deficiency is due to malabsorption, usually from pernicious anemia (destruction of parietal cells, which produce the intrinsic factor needed for cobalamin absorption). Folate deficiency results from insufficient dietary folate, malabsorption, alcoholism, or use of certain drugs. Drugs that interfere with DNA synthesis, including many chemotherapeutic agents, may lead to megaloblastic anemia.
Presents with fatigue, pallor, diarrhea, loss of appetite, headaches, and tingling/numbness of the hands and feet.
Cobalamin deficiency affects the nervous system, so patients lacking that vitamin may develop a demyelinating disorder and may present with symptoms of motor, sensory, autonomic, and/or neuropsychiatric dysfunction, known as subacute combined degeneration of the cord.
Peripheral smear shows RBCs with an elevated MCV. Hypersegmented (> 5) granulocytes can also be seen.
Bone marrow sample reveals giant neutrophils and hypersegmented mature granulocytes.
The Schilling test (ingestion of radiolabeled cobalamin both with and without added intrinsic factor) is classic for measuring absorption of cobalamin but is rarely performed.
Serum vitamin levels are poorly diagnostic of deficiencies and are thus used with adjunctive tests, including methylmalonic acid (MMA) and homocysteine levels:
B12 def ciency: Elevated MMA and homocysteine.Folate def ciency: Normal MMA; elevated homocysteine.Address the cause of the anemia, and correct the underlying cause.
Occurs when bone marrow production is unable to compensate for ↑ destruction of circulating blood cells. Etiologies include the following:
G6PD def ciency: An X-linked recessive disease that ↑ RBC sensitivity to oxidative stress.
Paroxysmal nocturnal hemoglobinuria: A disorder in which blood cell sensitivity to complement activation is ↑.
Hereditary spherocytosis: An abnormality of the RBC membrane.Autoimmune RBC destruction: Occurs 2º to EBV infection, mycoplasmal infection, CLL, rheumatoid disease, or medications.
Sickle cell disease: A recessive β-globin mutation (see the following section).
Microangiopathic hemolytic anemia: TTP, HUS, DIC.Mechanical hemolysis: Associated with mechanical heart valves.Other: Malaria, hypersplenism.Presents with pallor, fatigue, tachycardia, and tachypnea.Patients are typically jaundiced, with low haptoglobin and elevated indirect bilirubin and LDH. Urine is dark with hemoglobinuria, and there is ↑ excretion of urinary and fecal urobilinogen. Reticulocyte count is elevated.
Diagnosed by the history and clinical presentation. High LDH, elevated indirect bilirubin, and ↓ haptoglobin levels are consistent with a diagnosis of hemolytic anemia. Also obtain a reticulocyte count. A Coombs’ test is used to detect autoimmune hemolysis.
Treatment varies with the cause of hemolysis but typically includes corticosteroids to address immunologic causes and iron supplementation to replace urinary losses. Splenectomy may be helpful, and transfusion may be necessary to treat severe anemia.
A rare condition caused by failure of blood cell production due to destruction of bone marrow cells. It may be hereditary, as in Fanconi’s anemia; may have an autoimmune or a viral etiology (e.g., HIV, parvovirus B19); or may result from exposure to toxins (e.g., drugs, cleaning solvents) or radiation.
Patients are typically pancytopenic, with symptoms resulting from a lack of RBCs, WBCs, and platelets—e.g., pallor, weakness, a tendency to infection, petechiae, bruising, and bleeding.
The disease may be of sudden or sustained onset and may be of variable severity, depending on the patient’s blood counts.
Diagnosed by clinical presentation and CBC; verifed by a bone marrow biopsy revealing hypocellularity and space occupied by fat.
The differential includes megaloblastic anemia, as both diseases feature an elevated MCV.
The classic case of G6PD deficiency is an African-American male soldier in Vietnam who took quinine.
Indirect Coombs’ tests detect antibodies to RBCs in the patient’s serum. Direct Coombs’ tests detect sensitized erythrocytes.
Patients with Fanconi’s anemia may be identified on physical exam by café au lait spots, short stature, and radial/thumb hypoplasia/ aplasia.
SCD represents a qualitative defect in the β-globin chain.Patients with SCD classically get osteomyelitis with Salmonella. They are also at ↑ risk of avascular necrosis of the hip.
Blood transfusion and stem cell transplantation to replace absent cells; immunosuppression with cyclosporin A and antithymocyte globulin to prevent autoimmune destruction of marrow. Infections are a major cause of mortality and should be treated aggressively.
An autosomal-recessive disorder most commonly caused by a mutation of adult hemoglobin (the β chain has glu replaced by val). Signs and symptoms are due to ↓ red cell survival and a tendency of sickled cells to lead to vasoocclusion.
Asymptomatic during the first year or two of life; may first present with dactylitis in childhood. Later, hemolysis results in anemia, jaundice, cholelithiasis, ↑ cardiac output (murmur and cardiomegaly), and delayed growth.
Vaso-occlusion leads to ischemic organ damage, especially splenic infarction, which predisposes to pneumococcal sepsis, and acute chest syndrome (pneumonia and/or pulmonary infarction). Patients also experience painful crises of unknown etiology. Common triggers for a vaso-occlusive crisis (VOC) include cold temperatures, dehydration, and infection.
Other potential complications include splenic sequestration, which occurs in patients who have not infarcted their spleens, and aplastic crisis, which is usually 2° to infection with parvovirus B19.
The sickle cell screen is based on a blood smear with sickle cells and target cells. The gold standard is quantitative hemoglobin electrophoresis.
Treat with hydroxyurea, which stimulates the production of fetal hemoglobin (hydroxyurea is teratogenic, so it is contraindicated in pregnancy).
If hydroxyurea does not prove effective, chronic transfusion therapy, which carries the risk of iron overload, can be tried.
Treat cholelithiasis with cholecystectomy.VOCs must be treated with adequate pain management, O2 therapy, IV fluid rehydration, and antibiotics (if infection is suspected to be the trigger).
To prevent VOCs from progressing to acute chest syndrome, initiate aggressive hydration and incentive spirometry, and keep the sickle variant < 40%. This can be done with simple transfusions or, if necessary, exchange transfusion in an ICU setting.
Hereditary disorders involving ↓ or absent production of normal globin chains of hemoglobin. α-thalassemia is caused by a mutation of one or more of the four genes for α-hemoglobin; β-thalassemia results from a mutation of one or both of the two genes for β-hemoglobin.
Thalassemia is most common among people of African, Middle Eastern, and Asian descent. Disease presentation and prognosis vary with the number of genes missing (see Table 2.7-5).
Diagnosed by hemoglobin electrophoresis evaluation (but note that this is normal in α-thalassemia) and DNA studies.
Most patients do not require treatment, but those with β-thalassemia major and hemoglobin H disease are commonly transfusion dependent and should be given iron chelators (deferoxamine) to prevent overload.
Erythrocytosis (an abnormal elevation of hematocrit) may be either 1° (due to ↑ RBC production) or 2° (due to ↓ plasma volume and hemoconcentration).
T AB LE 2.7 -5. Differential Diagnosis of Thalassemias β-thalassemia major 0/2 β Patients develop severe microcytic anemia in the frst year of life and need chronic transfusions or marrow transplant to survive. β-thalassemia minor 1/2 β Patients are asymptomatic, but their cells are microcytic and hypochromic on peripheral smear. Hydrops fetalis 0/4 α Patients die in utero. Hemoglobin H disease 1/4 α Patients have severe hypochromic, microcytic anemia with chronic hemolysis, splenomegaly, jaundice, and cholelithiasis. The reticulocyte count elevates to compensate, and one-third of patients have skeletal changes due to expanded erythropoiesis. α-thalassemia trait 2/4 α Patients have low MCV but are usually asymptomatic. Silent carrier 3/4 α Patients have no signs or symptoms of disease.
True polycythemia vera is characterized by a high red cell mass.
Premedication with acetaminophen and diphenhydramine is sometimes used to prevent transfusion reactions.
Hemoglobinuria in hemolytic transfusion reaction may lead to acute tubular necrosis and subsequent renal failure.
Characterized by ↑ hematocrit, ↓ tissue blood flow and oxygenation, and ↑ cardiac work.
Patients present with “hyperviscosity syndrome,” which consists of easy bleeding/bruising, blurred vision, neurologic abnormalities, plethora, pruritus (especially after a warm bath), hepatomegaly, splenomegaly, and CHF.
1° erythrocytosis is associated with hypoxia (from lung disease, smoking, high altitudes, or a poor intrauterine environment), neoplasia (erythropoietin-producing tumors), or polycythemia vera (PCV), in which there is clonal proliferation of a pluripotent marrow stem cell.
2° erythrocytosis is associated with excessive diuresis, severe gastroenteritis, and burns.
Erythrocytosis is diagnosed clinically and by cell counts, with ABGs used to assess hypoxia or imaging to demonstrate neoplasia.
Patients with PCV have excess RBCs, WBCs, and platelets. Levels of erythropoietin may be useful in distinguishing PCV, in which levels are low, from other causes of polycythemia.
Phlebotomy relieves symptoms of erythrocytosis, but treatment should also address the underlying cause.
PCV can be treated with cytoreductive drugs such as hydroxyurea or interferon. Because PCV is prothrombotic, ASA should also be used. With treatment, survival is 7–10 years.
Blood transfusion is generally safe but may result in a variety of adverse reactions. Nonhemolytic febrile reactions and minor allergic reactions are the most common, each occurring in 3–4% of all transfusions. Etiologies are as follows:
Nonhemolytic febrile reactions: Involve cytokine formation during the storage of blood, and WBC antibodies.
Minor allergic reactions: Involve antibody formation (usually IgA) against donor proteins. Usually occur following transfusion of plasma-containing product.
Hemolytic transfusion reactions: Entail the development of antibodies against donor erythrocytes. Usually result from ABO incompatibility or from antibody against minor antigens.
Nonhemolytic febrile reactions: Present with fever, chills, rigors, and malaise. Symptom onset is 1–6 hours following transfusion.
Minor allergic reactions: Characterized by urticaria.Hemolytic transfusion reactions: Present with fever, chills, nausea, fl ushing, apprehension, back pain, burning at the IV site, tachycardia, tachypnea, and hypotension. Symptoms begin following the transfusion of only a small amount of blood.
Diagnosed by clinical impression.Nonhemolytic febrile reactions: Stop the transfusion and control fever with acetaminophen. Rule out infection.
Minor allergic reactions: Administer antihistamines. In the setting of a severe reaction, stop the transfusion and give epinephrine +/– steroids.
Hemolytic transfusion reactions: Stop the transfusion immediately. Replace donor blood with normal saline; administer vigorous IV fl uids; and maintain good urine output (diuretics and pressors may be used to ↑ renal blood fl ow).
The porphyrias are a group of inherited disorders that include acute intermittent porphyria, porphyria cutanea tarda, and erythropoietic porphyria. Some porphyrias are autosomal dominant (e.g., acute intermittent porphyria) and others autosomal recessive (e.g., erythropoietic porphyria). All involve abnormalities of heme production that lead to an accumulation of porphyrins.
Signs and symptoms vary with the type of porphyria. In general, however, porphyrias are characterized by a combination of photodermatitis, neuropsychiatric complaints, and visceral complaints that typically take the form of a colicky abdominal pain and seizures.
Physical exam reveals tachycardia, skin erythema and blisters, aref exia, and a nonspecifc abdominal exam.
Patients with the erythropoietic form present with hemolytic anemia. Acute attacks are associated with stimulants of ↑ heme synthesis such as fasting or chemical exposures; well-known triggers are alcohol, barbiturates, and OCPs. Urine may appear red or brown after an acute attack. Patients may have a  family history.
Diagnosed by a combination of the history and physical along with labs showing elevated blood, urine, and stool porphyrins. Enzyme assays may also be helpful.
Avoidance of triggers of acute attacks; symptomatic treatment during acute episodes.
High doses of glucose may be administered to ↓ heme synthesis during mild attacks, and IV hematin can be given for severe attacks (provides feedback to the heme synthetic pathway).
Heme is necessary for the production of hemoglobin, myoglobin, and cytochrome molecules.
The telltale sign of porphyria is pink urine.The classic case of porphyria involves a college student who consumes alcohol and barbiturates at a party, and then has an acute episode of abdominal pain and brown urine the next day.
Malignant proliferations of hematopoietic cells, categorized by the type of cell involved and their level of differentiation. Leukemias may be acute or chronic, lymphocytic or myelogenous.
The four oncologic emergencies: hypercalcemia, spinal cord compression, superior vena cava syndrome, and leukostasis.
Acute myelogenous and lymphocytic leukemias are clonal disorders of early hematopoietic stem cells. They are characterized by rapid growth of immature blood cells (blasts), which overwhelms the ability of bone marrow to produce normal cells.
Acute myelogenous leukemia (AML) and acute lymphocytic leukemia (ALL) affect children as well as adults. ALL is the most common childhood malignancy.
Disease onset and progression are rapid; patients present with signs and symptoms of anemia (pallor, fatigue) and thrombocytopenia (petechiae, purpura, bleeding). Medullary expansion and periosteal involvement may lead to bone pain (common in ALL).
On exam, patients may have hepatosplenomegaly and swollen/bleeding gums from leukemic infiltration and ↓ platelets. Leukemic cells also infiltrate the skin and CNS.
Based on examination of the patient’s bone marrow, obtained by biopsy and aspiration, or peripheral blood if circulating blasts are present. Marrow that is infiltrated with blast cells (> 20–30%) is consistent with a leukemic process. In AML, the leukemic cells are myeloblasts; in ALL they are lymphoblasts. These cells may be distinguished by examination of morphology, cytogenetics, cytochemistry, and immunophenotyping (see Table 2.7-6).
The WBC count is usually elevated, but the cells are dysfunctional, and patients may be neutropenic with a history of frequent infection. If the WBC is very high (> 100,000), there is a risk of leukostasis (blasts occluding the microcirculation, leading to pulmonary edema, CNS symptoms, ischemic injury, and DIC).
The type of acute leukemia is further classified according to the FAB system (ALL: L1–L3; AML: M0–M7) and karyotype analysis. Prognosis varies with leukemic cytogenetics.
T AB LE 2.7 -6. Myeloblasts vs. LymphoblastsSize Larger (2–4 times RBC) Smaller (1.5–3.0 times RBC) Amount of cytoplasm More Less Nucleoli Conspicuous Inconspicuous Granules Common, f ne Uncommon, coarse Auer rods Present in 50% of cases Absent Myeloperoxidase
ALL and AML are treated primarily with chemotherapeutic agents, although transfusions, antibiotics, and colony-stimulating factors are also used. Patients with unfavorable genetics or those who do not achieve remission may be candidates for bone marrow transplantation.
Prior to therapy, patients should be well hydrated, and if their WBC counts are high, they may be started on allopurinol to prevent hyperuricemia and renal insufficiency resulting from blast lysis (tumor lysis syndrome).
Leukostasis syndrome may be treated with hydroxyurea +/– leukapheresis to rapidly ↓ WBC count.
Indicators of a poor prognosis are as follows:ALL: Age < 1 year or > 10 years; an ↑ in WBC count to > 50,000; the presence of the Philadelphia chromosome t(9,22) (associated with B-cell cancer); CNS involvement at diagnosis; and L3 morphology (associated with Burkitt’s lymphoma).
AML: Age > 60 years, CD34+ or MDR1+ phenotype, elevated LDH, mutations in chromosomes 5 or 7, t(6,9), trisomy 8 or a more complex karyotype, FLT3 gene mutation, and FAB M7 (acute megakaryocytic variant).
AML type (FAB) M3—acute promyelocytic leukemia (APL)—has a good prognosis because it is responsive to all-trans-retinoic acid (ATRA) therapy. The mutation that causes this form of AML contains the retinoic acid receptor. ATRA is less toxic than conventional chemotherapy.
A malignant, clonal proliferation of functionally incompetent lymphocytes that accumulate in the bone marrow, peripheral blood, lymph nodes, spleen, and liver. The most common type of leukemia. A rare form of T-cell CLL exists, but almost all cases involve well-differentiated B lymphocytes. The etiology is unknown, although there is some genetic contribution, as first-degree relatives of patients with CLL are three times more likely than others to develop a lymphoid malignancy. Primarily affects older adults (median age 65); the male-to-female ratio is 2:1.
Often asymptomatic, but many patients present with fatigue, malaise, and infection. Common physical findings are lymphadenopathy and splenomegaly.
Diagnosed by the clinical picture; may be confirmed by f ow cytometry demonstrating the presence of CD5—normally found only on T cells—on leukemic cells with the characteristic B-cell antigens CD20 and CD21.
CBC shows lymphocytosis (lymphocyte count > 5000) with an abundance of small, normal-appearing lymphocytes and ruptured smudge cells on peripheral smear. Granulocytopenia, anemia, and thrombocytopenia are common owing to marrow infiltration with leukemic cells. Abnormal function by the leukemic cells leads to hypogammaglobulinemia.
Bone marrow biopsy is rarely required for diagnosis or staging but may provide prognostic information and may help assess response to therapy.
A characteristic sign for AML type M3 (APL) is the
Auer rod.Eighty-five percent of children with ALL achieve complete remission with chemotherapy.
CLL may be complicated by autoimmune hemolytic anemia.The lymphoid equivalent of CLL is small lymphocytic lymphoma.The clinical stage correlates with expected survival (see Table 2.7-7).
Treatment is palliative. The degree of peripheral lymphocytosis does not correlate with prognosis, nor does it dictate when treatment should be initiated. Treatment is often withheld until patients are symptomatic—e.g., when they present with recurrent infection, severe lymphadenopathy or splenomegaly, anemia, and thrombocytopenia.
Treatment consists primarily of chemotherapy, especially with alkylating agents, although radiation may be useful for localized lymphadenopathy.
Although CLL is not curable, long disease-free intervals may be achieved with adequate treatment of symptoms.
Involves clonal expansion of myeloid progenitor cells, leading to leukocytosis with excess granulocytes and basophils and sometimes ↑ erythrocytes and platelets as well. To truly be CML, the BCR-ABL translocation must be present. In > 90% of patients, this is reflected by the Philadelphia chromosome t(9,22). CML primarily affects middle-aged patients.
With routine blood testing, many patients are diagnosed while asymptomatic. However, typical signs and symptoms are those of anemia.
Patients frequently have splenomegaly with LUQ pain and early satiety. Hepatomegaly may be present as well. Constitutional symptoms of weight loss, anorexia, fever, and chills may also be seen.
Patients with CML go through three disease phases:Chronic: Without treatment, typically lasts 3.5–5.0 years. Signs and symptoms are as described above. Infection and bleeding complications are rare.
Accelerated: A transition toward blast crisis, with an ↑ in peripheral and bone marrow blood counts. Should be suspected when the differential shows an abrupt ↑ in basophils and thrombocytopenia < 100,000.
Blast: Resembles acute leukemia; survival is 3–6 months.■Diagnosed by the clinical picture, including labs; cytogenetic analysis usually reveals the Philadelphia chromosome.
TAB LE 2.7 -7. Clinical Staging of CLL (Rai Staging)
CBwC shows a very high WBC—often > 100,000 at diagnosis, and sometimes reaching > 500,000. Differential shows granulocytes in all stages of maturation. Rarely, the WBC count will be so elevated as to cause a hyperviscosity syndrome.
Leukocyte alkaline phosphatase is low; LDH, uric acid, and B12 levels are elevated.
Varies with disease phase and is undergoing rapid change, particularly since the introduction of targeted therapies:
Chronic: Imatinib. Younger patients can be treated with allogeneic stem cell transplantation if a suitable matched sibling donor is available.
Blast: Therapy as for acute leukemia or dasatinib plus hematopoietic stem cell transplant or clinical trial.
A malignant disorder of well-differentiated B lymphocytes with an unclear cause. HCL is a rare disease that accounts for 2% of adult leukemia cases and most commonly affects older males.
Typically presents with pancytopenia, bone marrow infiltration, and splenomegaly.Patients complain of weakness, fatigue, petechiae and bruising, infection (especially with atypical mycobacteria such as Mycobacterium avium– intracellulare), abdominal pain, early satiety, and weight loss. Symptoms are similar to those of CLL except that patients rarely have lymphadenopathy.
Diagnosed by the history, physical exam, and labs; confirmed through the identification of hairy cells in the blood, marrow, or spleen.
Tartrate-resistant acid phosphatase (TRAP) staining of hairy cells, electron microscopy, and f ow cytometry (quantification of fl uorescence on cells with fluorescent-labeled monoclonal antibodies bound to cell-specific antigens) are helpful in distinguishing the pathognomonic hairy cells.
CBC usually demonstrates leukopenia (making the name leukemia a misnomer); roughly 85% of the time, a peripheral smear shows hairy cells, or mononuclear cells with abundant pale cytoplasm and cytoplasmic projections.
Ten percent of patients have a benign course and never require therapy, but the remainder develop progressive pancytopenia and splenomegaly. The median survival without treatment is five years.
Treatment begins when patients are symptomatic or extremely cytopenic. Nucleoside analogs are currently the initial treatment of choice, and effectively induce remission. Other treatment options include splenectomy, which may improve blood counts, and IFN-α.
Imatinib (Gleevec) is a selective inhibitor of the BCR-ABL tyrosine kinase.
The treatment of high-grade NHL may be complicated by tumor lysis syndrome, in which rapid cell death releases intracellular contents and leads to hyperkalemia, hyperphosphatemia, hyperuricemia, and hypocalcemia.
Malignant transformations of lymphoid cells residing primarily in lymphoid tissues, especially the lymph nodes. Classically organized into Hodgkin’s and non-Hodgkin’s varieties.
NHL represents a progressive clonal expansion of B cells, T cells, and/or natural killer (NK) cells stimulated by chromosomal translocations, most commonly t(14,18); by the inactivation of tumor suppressor genes; or by the introduction of exogenous genes by oncogenic viruses (e.g., EBV, HTLV-1, HCV). There is a strong association between H. pylori infection and MALT gastric lymphoma. Most NHLs (almost 85%) are of B-cell origin. NHL is the most common hematopoietic neoplasm and is five times more common than Hodgkin’s lymphoma.
The median patient age is > 50 years, but NHL may also be found in children, who tend to have more aggressive, higher-grade disease. Patient presentation varies with disease grade (see Table 2.7-8).
Excisional lymph node biopsy is necessary for diagnosis; the disease may first present at an extranodal site, which should be biopsied for diagnosis as well.
A CSF exam should be done in patients with HIV, neurologic signs or symptoms, or 1° CNS lymphoma. Disease staging (Ann Arbor classif cation) is based on the number of nodes and on whether the disease crosses the diaphragm.
■Treatment is based on histopathologic classification rather than on stage. Symptomatic patients are treated with radiation and chemotherapy
T AB LE 2.7 -8. Presentation of Non-Hodgkin’s LymphomaPainless peripheral adenopathy. Cytopenia from bone marrow involvement. Fatigue and weakness. Peripheral adenopathy, splenomegaly, hepatomegaly. Adenopathy. Extranodal disease (GI, GU, skin, thyroid, CNS). B symptoms (temperature > 38.5°C, night sweats, weight loss). Mass formation (e.g., abdominal mass with bowel obstruction in Burkitt’s lymphoma; mediastinal mass and SVC syndrome in lymphoblastic lymphoma). Bulky adenopathy, splenomegaly, hepatomegaly. Masses (abdominal, testicular, mediastinal). Skin f ndings. Low Intermediate to high (CHOP: cyclophosphamide [Cytoxan], Adriamycin, Oncovin [vincristine], and prednisone).
■The rule of thumb is for low-grade, indolent NHL to be treated with a palliative approach in symptomatic patients, and for high-grade, aggressive NHL to be treated aggressively with a curative approach.
A predominantly B-cell malignancy with an unclear etiology. There is a possible association with EBV. HD has a bimodal age distribution, peaking first in the third decade (primarily the nodular sclerosing type) and then in the elderly at around age 60 (mainly the lymphocyte-depleted type). It has a male predominance in childhood.
HD commonly presents as cervical adenopathy, although it may also present as a mediastinal mass; it is usually found above the diaphragm, with infradiaphragmatic involvement suggesting more widely disseminated disease.
Patients also have systemic B symptoms, pruritus, and hepatosplenomegaly. Pel-Ebstein fevers (1–2 weeks of high fever alternating with 1–2 afebrile weeks) and alcohol-induced pain at nodal sites are rare signs that are specific for HD.
Fine-needle biopsy is usually nondiagnostic, so diagnosis is usually made by excisional lymph node biopsy, which is examined for the classic Reed-Sternberg (RS) cells (giant abnormal B cells with bilobar nuclei and huge, eosinophilic nucleoli, which create an “owl’s-eye” appearance) and for abnormal nodal morphology.
Histologic types, in descending order of frequency, include nodular sclerosing, mixed cellularity, lymphocyte predominant, and lymphocyte depleted. Staging is based on the number of nodes, the presence of B symptoms, and whether the disease crosses the diaphragm; staging laparotomy is not recommended.
Treatment is stage dependent, involving chemotherapy and/or radiation. Radiation is directed toward the involved lymph node area plus the next contiguous region. Chemotherapy regimens used include ABVD (Adriamycin, bleomycin, vinblastine, dacarbazine) and MOPP (mechlorethamine, Oncovin [vincristine], procarbazine, and prednisone).
Five-year survival rates are very good and are 90% for stage I and II disease (nodal disease limited to one side of the diaphragm), 84% for stage III, and 65% for stage IV.
Chemotherapy and radiation can lead to 2° neoplasms such as AML, NHL, breast cancer, and thyroid cancer.
Clonal proliferation of malignant plasma cells at varying stages of differentiation, with excessive production of monoclonal immunoglobulins or immunoglobulin fragments (kappa/lambda light chains). It is commonly believed
The combination of anemia and bone pain must always raise suspicion of multiple myeloma.
Bone pain at rest should raise concern for malignancy.Hypercalcemia manifests in symptoms of polyuria, constipation, confusion, nausea, vomiting, and lethargy.
Because multiple myeloma is an osteoclastic process, a bone scan, which detects osteoblastic activity, may be .
to be a disease of the elderly, with a peak incidence in the seventh decade. Risk factors for disease development include radiation; monoclonal gammopathy of undetermined significance (MGUS); and, possibly, petroleum, pesticides, and other chemicals.
Patients present with anemia, plasmacytosis of the bone marrow, lytic bone lesions, hypercalcemia, and renal abnormalities. They are prone to infection and have elevated monoclonal (M) proteins in the serum and/or urine.
The classic triad of diagnostic criteria are > 10% plasma cells in the bone marrow and/or histologically proven plasma cell infiltration, M protein in serum or urine, and evidence of lytic bone lesions.
The presence of M proteins alone is insuffcient for the diagnosis of multiple myeloma; MGUS is relatively common. Other lymphoproliferative diseases may also result in M proteins, including CLL, lymphoma, Waldenström’s macroglobulinemia, and amyloidosis.
Patients should be evaluated with a skeletal survey, a bone marrow biopsy, serum and urine protein electrophoresis, and CBC.
Treat with chemotherapy.Common initial treatment involves a combination of melphalan (an oral alkylating agent) and prednisone and other agents. Myeloma cells tend to become resistant to drugs by an MDR gene mechanism, and autologous stem cell transplantation may be used to support more intensive doses of chemotherapy.
A clonal disorder of B cells that leads to a malignant monoclonal gammopathy. Elevated levels of IgM result in hyperviscosity syndrome, coagulation abnormalities, cryoglobulinemia, cold agglutinin disease (leading to autoimmune hemolytic anemia), and amyloidosis. Tissue is infiltrated by IgM and neoplastic plasma cells. A chronic, indolent disease of the elderly.
Presents with nonspecific symptoms of lethargy and weight loss along with Raynaud’s phenomenon from cryoglobulinemia. Patients complain of neurologic problems ranging from mental status changes to sensorimotor peripheral neuropathy and blurry vision. Organomegaly and organ dysfunction affecting the skin, GI tract, kidneys, and lungs are also seen.
As with multiple myeloma, MGUS is a precursor to disease.
Labs show elevated ESR, uric acid, LDH, and alkaline phosphatase.
Bone marrow biopsy and aspirate are required to establish the diagnosis. Marrow shows abnormal plasma cells, classically with Dutcher bodies (PASIgM deposits around the nucleus). Serum and urine protein electrophoresis and immunofixation are also used.
Excess immunoglobulin is removed with plasmapheresis; underlying lymphoma is treated with chemotherapy.
A generic term referring to extracellular deposition of protein fibrils. There are many different kinds of amyloidosis, involving different types of deposited fibrils with varying etiologies (see Table 2.7-9). Classically a disease of the elderly.
The clinical presentation depends on the type of precursor protein, tissue distribution, and the amount of amyloid deposition. In the two most common forms of systemic amyloidosis, 1° (AL) and 2° (AA), the major sites of clinically important amyloid deposition are in the kidneys, heart, and liver.
In some disorders, clinically important amyloid deposition is limited to one organ (e.g., the brain in Alzheimer’s disease).
Diagnosed by the clinical picture; confirmed by tissue biopsy with Congo red staining showing apple-green birefringence under polarized light.
1° amyloidosis is treated with experimental chemotherapy to reduce protein burden; in 2° amyloidosis, the underlying condition should be addressed. Transplantation is also used; kidney transplantation may cure dialysis-related amyloid, and liver transplantation may cure heritable amyloid.
TABLE 2.7-9.  Types of AmyloidosisAL A plasma cell dyscrasia, with deposition of monoclonal light-chain fragments. Associated with multiple myeloma and Waldenstr’s macroglobulinemia. AA Deposition of the acute-phase reactant serum amyloid A. Associated with chronic infammatory diseases (e.g., rheumatoid arthritis), infections, and neoplasms. Dialysis-related Deposition of β2 microglobulin, which accumulates in patients on long-term dialysis. Heritable Deposition of abnormal gene products (e.g., transthyretin, aka prealbumin). A heterogeneous group of disorders. Senile-systemic Deposition of otherwise normal transthyretin.
An absolute neutrophil count (ANC) < 1500, where ANC = (WBC count) (% bands + % segmented neutrophils) (0.01). Neutropenia may be due to a combination of ↓ production, sequestration to marginated or tissue pools, and ↑ destruction or utilization. It may be acquired or intrinsic (see Table 2.7-10).
Patients are at ↑ risk of infection, which varies inversely with neutrophil count.
Acute neutropenia: Associated with S. aureus, Pseudomonas, E. coli, Proteus, and Klebsiella sepsis.
Chronic and autoimmune neutropenia: Presents with recurrent sinusitis, stomatitis, gingivitis, and perirectal infections rather than sepsis. Some chronic neutropenias are accompanied by splenomegaly (e.g., Felty’s syndrome, Gaucher’s disease, sarcoidosis).
The history and physical exam are the cornerstones of diagnosis.
CBC with ANC may be used to follow neutropenia. If thrombocytopenia or anemia is present, bone marrow biopsy and aspirate should be performed.
Serum immunologic evaluation, ANA levels, and a workup for collagen vascular disease may be merited.
T AB LE 2.7 -1 0. Acquired vs. Intrinsic Neutropenia
HEMATOLOGY/ONCOLOGY Acquired Drug induced (e.g., chemotherapy, ethanol, antibiotics, NSAIDs), usually by marrow suppression. Marrow-inf ltrating disorders. Postinfectious. HIV infection. Benign familial leukopenia (seen in Yemenite Jews, West Indians, and people of African descent; due to genetic variation). Chronic idiopathic neutropenia (occurs in infancy and childhood; thought to be due to production of antineutrophil IgG). Autoimmune neutropenia (isolated or 2° to rheumatoid arthritis or SLE). Nutritional def ciency (B12/folate or thiamine def ciency). Metabolic disease (ketoacidosis, hyperglycinuria, orotic aciduria, MMA, hypothyroidism, Gaucher’s disease). Intrinsic Dyskeratosis congenita (X-linked, with integument abnormalities and hypocellular marrow). Kostmann’s syndrome (aka infantile agranulocytosis). Shwachman-Diamond-Oski syndrome (neutropenia, metaphyseal dysplasia, and pancreatic insuff ciency). Chédiak-Higashi syndrome (oculocutaneous albinism, neurologic impairment, and giant granules in cells). Fanconi’s anemia.
■Infection management is most important; patients may not be able to mount an inflammatory response to infection owing to their lack of neutrophils.
Fever in the context of neutropenia should be treated immediately with broad-spectrum antibiotics. Suspected fungal infections should be treated by fungemia. appropriately as well.
Hematopoietic stem cell factors such as G-CSF can be used to shorten the duration of neutropenia. In some instances, IVIG and allogeneic bone marrow transplantation may be used.
Absolute eosinophil count = (WBC) (% eosinophils) (0.01). Normal levels do not exceed 350. Eosinophilia can be triggered by the overproduction of one or more of three eosinophilopoietic cytokines (IL-3, IL-5, and GM-CSF) or by chemokines that stimulate the migration of eosinophils into peripheral blood and tissues. Eosinophilia may be a 1° disorder, but it usually occurs 2° to another cause (see Table 2.7-11).
A travel, medication, atopic, and diet history should be elicited along with a history of symptoms relating to lymphoma/leukemia.
Physical exam findings vary. Patients with hypereosinophilic syndrome (HES) may present with fever, anemia, and prominent cardiac findings (emboli from mural thrombi, abnormal ECGs, CHF, murmurs). Other affected organs include the lung, liver, spleen, skin, and nervous system (due to eosinophilic infiltration).
■In addition to a history and physical, a CBC and differential should be obtained, and CSF should be analyzed for eosinophilia, which is suggestive
T AB LE 2.7 -1 1.  Etiologies of Eosinophilia 1° Hypereosinophilic syndrome: Unknown etiology. Hereditary eosinophilia: Autosomal-dominant inheritance; rare. Eosinophilia-myalgia syndrome: Results from abnormal tryptophan metabolism. 2°
Allergic states with elevated serum IgE: The most common cause in the United
States. Parasitic diseases: The most common cause worldwide. Other:Coccidioidomycosis. Vasculitis (e.g., Churg-Strauss syndrome). Benign or malignant hematologic disorders; also solid tumors. Collagen vascular diseases (e.g., dermatomyositis, PAN). Drug induced (e.g., sulfonamides, iodides, ASA, phenytoin).
of a drug reaction or infection with a coccidioidomycosis or a helminth. Hematuria with eosinophilia may be a sign of schistosomiasis.
■Imaging of the lungs, abdomen, pelvis, and brain may demonstrate a focal defect that may be helpful in narrowing down the potential causes.
Medication should be tailored to the cause of the eosinophilia. HES is treated with corticosteroid and cytotoxic agents to ↓ the eosinophilia.
Tissue transplantation is increasingly used to treat a variety of diseases. Types of transplantation include the following:
Autologous: Transplantation from the patient to him/herself.Allogeneic: Transplantation from a donor to a genetically different patient.
Syngeneic: Transplantation between identical twins (i.e., from a donor to a genetically identical patient).
With allogeneic donation, efforts are made to ABO and HLA match the donor and recipient. Even with antigenic matching and immunosuppression, however, transplants may be rejected. There are three types of rejection: hyperacute, acute, and chronic (see Table 2.7-12).
Graft-versus-host disease (GVHD) is a complication specific to allogeneic bone marrow transplantation in which donated T cells attack host tissues. It may be acute (occurring < 100 days post-transplant) or chronic (occurring > 100 days afterward).
Minor histocompatibility antigens are thought to be responsible for GVHD, which typically presents with skin changes, cholestatic liver dysfunction, obstructive lung disease, or GI problems.
Patients are treated with high-dose corticosteroids.T AB LE 2.7 -1 2. Types of Transplant Rejection
Timing after transplant Within minutes. Five days to three months. Months to years. Pathomechanism Preformed antibodies. T-cell mediated. Chronic immune reaction causing f brosis. Tissue fndings Vascular thrombi; tissue ischemia. Laboratory evidence of tissue destruction such as ↑ GGT, alkaline phosphatase, LDH, BUN, or creatinine. Gradual loss of organ function. Prevention Check ABO compatibility. N/A N/A Treatment Cytotoxic agents. Confrm with sampling of transplanted tissue; treat with corticosteroids, antilymphocyte antibodies (OKT3), tacrolimus, or mycophenolate mofetil (MMF). No treatment; biopsy to rule out treatable acute reaction.
The typical regimen after transplant can include these commonly used drugs: prednisone, MMF, FK506 (tacrolimus), TMP-SMX, ganciclovir, and ketoconazole.
A variant of GVHD is the graft-versus-leukemia effect, in which leukemia patients who are treated with an allogeneic bone marrow transplant have significantly lower relapse rates than those treated with an autologous transplant. This difference is thought to be due to a reaction of donated T cells against leukemic cells.
Table 2.7-13 outlines conditions that are commonly associated with neoplasms.
T AB LE 2.7 -1 3. Disorders Associated with Neoplasms
Down syndrome ALL (“We will ALL go Down together”). Xeroderma pigmentosum Squamous cell and basal cell carcinomas of the skin. Chronic atrophic gastritis, pernicious anemia, postsurgical gastric remnants Gastric adenocarcinoma. Tuberous sclerosis (facial angiofbroma, seizures, mental retardation) Astrocytoma and cardiac rhabdomyoma. Actinic keratosis Squamous cell carcinoma of the skin. Barrett’s esophagus (chronic GI ref ux) Esophageal adenocarcinoma. Plummer-Vinson syndrome (atrophic glossitis, esophageal webs, anemia; all due to iron def ciency) Squamous cell carcinoma of the esophagus. Cirrhosis (alcoholic, HBV or HCV) Hepatocellular carcinoma. Ulcerative colitis Colonic adenocarcinoma. Paget’s disease of bone 2° osteosarcoma and f brosarcoma. AIDS Aggressive malignant NHLs and Kaposi’s sarcoma. Autoimmune diseases (e.g., myasthenia gravis) Benign and malignant thymomas. Acanthosis nigricans (hyperpigmentation and epidermal thickening) Visceral malignancy (stomach, lung, breast, uterus). Dysplastic nevus Malignant melanoma. Immunodefciency states Malignant lymphomas.
Infections of the Eyes and Ears 248 INFECTIOUS CONJUNCTIVITIS 248 ORBITAL CELLULITIS 248 OTITIS EXTERNA 249
Some common causes of pneumonia are outlined in Table 2.8-1.
May present classically or atypically.Classic symptoms: Sudden onset, fever, productive cough (purulent yellow-green sputum or hemoptysis), dyspnea, night sweats, pleuritic chest pain.
Atypical symptoms: Gradual onset, dry cough, headaches, myalgias, sore throat.
Lung exam may show ↓ or bronchial breath sounds, rales, wheezing, dullness to percussion, egophony, and tactile fremitus.
Elderly patients as well as those with COPD, diabetes, or immunocompromised status may have minimal or atypical signs on physical exam.
Workup includes physical exam, CXR, CBC, sputum Gram stain and culture (see Figures 2.8-1 and 2.8-2), nasopharyngeal aspirate, blood culture, and ABG.
Tests for specifc pathogens include the following:Legionella: Urine Legionella antigen test (detects only serogroup 1), sputum staining with direct fuorescent antibody (DFA), culture.
Chlamydia pneumoniae: Serologic testing, culture, PCR.TABLE 2.8-1. Common Causes of PneumoniaAtypical Nosocomial (hospital acquired) Immunocompromised Mycoplasma, Legionella, Chlamydia Gramrods (GNRs), Staphylococcus, anaerobes Staphylococcus, gramrods, fungi, viruses, Pneumocystis jiroveci (with HIV), mycobacteria Aspiration Anaerobes Alcoholics/IV drug users S. pneumoniae, Klebsiella, Staphylococcus Cystic fbrosis (CF) Pseudomonas, Burkholderia, S. aureus, mycobacteria COPD H. infl uenzae, Moraxella catarrhalis, S. pneumoniae Postviral Staphylococcus, H. influenzae Neonate Group B streptococci (GBS), E. coli Recurrent Obstruction, bronchogenic carcinoma, lymphoma, Wegener’s granulomatosis, immunodefciency, unusual organisms (e.g., Nocardia, Coxiella burnetii, Aspergillus, Pseudomonas) Viruses (RSV) Mycoplasma Chlamydia pneumoniae Streptococcus pneumoniae Mycoplasma C. pneumoniae S. pneumoniae S. pneumoniae H. infl uenzae Anaerobes Viruses Mycoplasma S. pneumoniae Viruses Anaerobes H. infl uenzae Gram-rods Special groups:
An adequate sputum Gram stain sample has many PMNs (> 25 cells/hpf) and few epithelial cells (< 25 cells/hpf).
FIGURE 2.8-1. S. aureus.These clusters of gramcocci were isolated from the sputum of a patient who developed pneumonia while hospitalized.
Mycoplasma: Usually clinical. Serum cold agglutinins and serum Mycoplasma antigen may also be used.
Streptococcus pneumoniae: Urine pneumococcal antigen test, culture.Viral: Nasopharyngeal aspirate, rapid tests for pathogens (e.g., inf uenza, RSV), DFA, viral culture.
FIGURE 2.8-2. S. pneumoniae.Sputum sample from a patient with pneumonia. Note the characteristic lancet-shaped gramdiplococci.
Table 2.8-2 summarizes the recommended initial treatment for pneumonia.Outpatient treatment with oral antibiotics is recommended only in uncomplicated cases.
In-hospital treatment with IV antibiotics is recommended for patients > 65 years of age and in those with comorbidity (alcoholism, COPD, diabetes, malnutrition), immunosuppression, unstable vitals or signs of respiratory failure, altered mental status, and/or multilobar involvement.
For patients with obstructive diseases (e.g., CF or bronchiectasis), consider adding pseudomonal, staphylococcal, or anaerobic coverage.
Infection due to Mycobacterium tuberculosis. Initial infection usually leads to latent TB infection (LTBI) that is asymptomatic. Most symptomatic cases (i.e., cases of active disease) are due to reactivation of latent infection rather
TABLE 2.8-2.  Treatment of PneumoniaThe PORT criteria (i.e., pneumonia severity index) risk-stratifies patients with pneumonia on the basis of age, comorbidity, and presentation. Note: The PORT criteria do not apply to AIDS patients.
Outpatient community-acquired pneumonia, patients ≤ 65 years of age, otherwise healthy S. pneumoniae, Mycoplasma pneumoniae, C. pneumoniae, H. infl uenzae, viral. Macrolide (azithromycin), doxycycline, or f uoroquinolone. Patients > 65 years of age or with comorbidity (COPD, heart failure, renal failure, diabetes, liver disease, EtOH abuse) S. pneumoniae, H. infl uenzae, aerobic GNRs (E. coli, Enterobacter, Klebsiella), S. aureus, Legionella, viruses. Macrolide or f uoroquinolone. Consider adding a second-generation cephalosporin or β-lactam to the macrolide. Community-acquired pneumonia requiring hospitalization S. pneumoniae, H. infl uenzae, anaerobes, aerobic GNRs, Legionella, Chlamydia. Extended-spectrum cephalosporin, β-lactam/β-lactamase inhibitor, or fuoroquinolone. Add a macrolide if atypical organisms are suspected. Community-acquired pneumonia requiring ICU care S. pneumoniae, H. infl uenzae, anaerobes, aerobic GNRs, Mycoplasma, Legionella, Pseudomonas. Fluoroquinolone or extended-spectrum cephalosporin or β-lactam/β-lactamase inhibitor + macrolide. Institution-/hospital-acquired pneumonia—patients hospitalized > 48 hours or in a long-term care facility > 14 days GNRs (including Pseudomonas and Acinetobacter), S. aureus, Legionella, mixed f ora. Extended-spectrum cephalosporin or β-lactam with antipseudomonal activity or carbapenem. Consider adding an aminoglycoside or a f uoroquinolone for coverage of resistant organisms (Pseudomonas) until lab sensitivities identify the best single agent. Patients who are critically ill or worsening over 24–48 hours on initial antibiotic therapy Methicillin-resistant S. aureus (MRSA). Add vancomycin or linezolid; broader gram-coverage.
TB almost always presents with an extended duration (> 3 weeks) of symptoms.
than to 1° exposure. Pulmonary TB is most common, but disseminated or extrapulmonary TB should be considered as well.
TB can infect almost any organ system, including the lungs, CNS, GU tract, bone, and GI tract.
Risk factors for active disease (i.e., reactivation) include immunosuppression (HIV), alcoholism, preexisting lung disease, diabetes, and advancing age. Risk factors for TB exposure include homelessness and crowded living conditions (e.g., prison), immigration/travel from developing nations, working in an allied health profession, and interacting with known TB contacts.
Presents with cough, hemoptysis, dyspnea, weight loss, fatigue, night sweats, fever, cachexia, hypoxia, tachycardia, lymphadenopathy, an abnormal lung exam, and a prolonged (> 3-week) symptom duration. TB is a common cause of fever of unknown origin (FUO). HIV patients can present with atypical signs and symptoms and have higher rates of extrapulmonary TB.
■ Active disease: Mycobacterial culture of sputum (or blood/tissue for extrapulmonary disease) is the gold standard but can take weeks to obtain. A sputum acid-fast stain (see Figure 2.8-3) can yield rapid preliminary results but lacks sensitivity.
Three A.M. sputum samples for AFB stain and a mycobacterial culture are advised. If the results of the stain are but there is a high degree of clinical suspicion, proceed to bronchoscopy with bronchoalveolar lavage or biopsy. HIV patients have a high rate of  sputum stains (i.e., a
AFB smear accompanied by a culture).The most common fnding among typical hosts is a cavitary inf ltrate in the upper lobe on CXR. HIV patients or those with 1° TB may show lower lobe infltrates with or without cavitation. Multiple f ne nodular
F IGU R E 2.8-3. TB organisms are identifed by their red color (“red snappers”) on acid-fast staining.
(Reproduced, with permission, from the Pathology Education Instructional Resource Digital Library [ http://peir.net] at the University of Alabama, Birmingham.) densities distributed throughout both lungs are typical of miliary TB, which represents hematologic or lymphatic dissemination.
■LTBI (i.e., previous exposure): Diagnose with a PPD test (see Figure 2.8-4). Immunocompromised individuals with LTBI may not mount a PPD (anergy). Interferon-gamma release assays are now available to diagnose LTBI as well. All cases of LTBI should be evaluated (e.g., with a CXR) to rule out active disease.
All cases should be reported to local and state health departments. Respiratory isolation should be instituted if TB is suspected. Treatment is as follows:
Active TB: Directly observed multidrug therapy with a four-drug regimen (INH, pyrazinamide, rifampin, ethambutol) × 2 months, followed by four months with INH and rifampin.
Administer vitamin B6 (pyridoxine) with INH to prevent peripheral neuritis.
Latent TB: For conversion of PPD without signs/symptoms of active disease, initiate therapy with INH × 9 months. Alternative regimens include INH × 6 months or rifampin × 4 months.
Viral causes are more common (90% in adults), but it is important to identify streptococcal pharyngitis (group A β-hemolytic Streptococcus pyogenes). Etiologies are as follows:
Bacterial: Group A streptococci (GAS), Neisseria gonorrhoeae, Corynebacterium diphtheriae, M. pneumoniae.
Viral: Rhinovirus, coronavirus, adenovirus, HSV, EBV, CMV, inf uenza virus, coxsackievirus, acute HIV infection.
Typical of streptococcal pharyngitis: Fever, sore throat, pharyngeal erythema, tonsillar exudate, cervical lymphadenopathy, soft palate petechiae, headache, vomiting, scarlatiniform rash (indicates scarlet fever).
Atypical of streptococcal pharyngitis: Coryza, hoarseness, rhinorrhea, cough, conjunctivitis, anterior stomatitis, ulcerative lesions, GI symptoms.
Rifampin turns body fl uids orange. Ethambutol can cause optic neuritis. INH causes peripheral neuritis and hepatitis.
PPD is injected intradermally on the volar surface of the forearm. The diameter of induration is measured at 48–72 hours. BCG vaccination typically renders a patient PPD  but should not preclude prophylaxis as recommended for unvaccinated individuals. The size of induration that indicates a test is interpreted as follows: ≥ 5 mm: HIV or risk factors, close TB contacts, CXR evidence of TB.  ≥ 10 mm: Indigent/homeless, residents of developing nations, IV drug use, chronic illness, residents of health and correctional institutions, and health care workers.  ≥ 15 mm: Everyone else, including those with no known risk factors.
A reaction with  controls implies anergy from immunosuppression, old age, or malnutrition and thus does not rule out TB.
FIGURE 2.8-4.  PPD interpretation.The Centor criteria for identifying streptococcal pharyngitis are fever, tonsillar exudate, tender anterior cervical lymphadenopathy, and lack of cough (three of four are required).
It is important to identify and treat streptococcal pharyngitis in order to prevent rheumatic fever, but overdiagnosis and overtreatment may lead to ↑ cost and antibiotic resistance.
Always consider occult sinusitis in febrile ICU patients.Diagnosed by clinical evaluation, rapid GAS antigen detection, and throat culture. With three out of four of the Centor criteria, the sensitivity of rapid antigen testing is > 90%.
If GAS is suspected, begin empiric antibiotic therapy with penicillin × 10 days. Cephalosporins, amoxicillin, and azithromycin are alternative options. Symptom relief can be attained with fuids, rest, antipyretics, and salt-water gargles.
Nonsuppurative: Acute rheumatic fever (see the Cardiovascular chapter), poststreptococcal glomerulonephritis.
Suppurative: Cervical lymphadenitis, mastoiditis, sinusitis, otitis media, retropharyngeal or peritonsillar abscess, and, rarely, thrombophlebitis of the jugular vein (Lemierre’s syndrome) due to Fusobacterium, an oral anaerobe.
Peritonsillar abscess may present with odynophagia, trismus (“lockjaw”), a muffed voice, unilateral tonsillar enlargement, and erythema, with the uvula and soft palate deviated away from the affected side. Culture abscess fuid and localize the abscess via intraoral ultrasound or CT. Treat with antibiotics and surgical drainage.
Refers to infammation of the paranasal sinuses. The maxillary sinuses are most commonly affected. Can be classifed by site, organism, or chronicity. Subtypes include the following:
Acute sinusitis (symptoms lasting < 1 month): Most commonly associated with viruses, S. pneumoniae, H. infl uenzae, and M. catarrhalis. Bacterial causes are rare and are characterized by symptoms lasting < 1 week.
Chronic sinusitis (symptoms persisting > 3 months): Represents a chronic infammatory process. Often due to obstruction of sinus drainage and ongoing low-grade anaerobic infections. In diabetic patients, mucormycosis should be considered.
Presents with fever, facial pain/pressure, headache, nasal congestion, and discharge. Exam may reveal tenderness, erythema, and swelling over the affected area.
High fever, leukocytosis, and a purulent nasal discharge are suggestive of acute bacterial sinusitis.
A clinical diagnosis. Culture and radiography are generally not required for acute sinusitis but may guide the management of chronic cases.
Transillumination shows opacifcation of the sinuses (low sensitivity).CT is the test of choice for sinus imaging (see Figure 2.8-5) but is usually necessary only if symptoms persist after treatment. MRI is useful for differentiating soft tissue (as in a tumor) from mucus.
FIGURE 2.8-5. Sinusitis.Compare the opacifed left maxillary sinus and normal air-flled right sinus on this coronal CT scan. (Reproduced, with permission, from Lalwani AK. Current Diagnosis & Treatment in Oto laryngology: Head and Neck Surgery, 2nd ed. New York: McGraw-Hill, 2008: Fig. 14-2.) ■Bacterial culture by sinus tap is the gold standard for diagnosis but is not routinely performed because of discomfort. Endoscopically guided cultures from the middle meatus are gaining popularity.
Most cases of acute sinusitis are viral and/or self-limited and can thus be treated with symptomatic therapy (decongestants, antihistamines, pain relief).
Acute bacterial sinusitis (usually < 7 days): Consider amoxicillin/clavulanate 500 mg PO TID × 10 days or, alternatively, clarithromycin, azithromycin, TMP-SMX, fuoroquinolone, or a second-generation cephalosporin × 10 days.
Chronic sinusitis (4–12 weeks): Adjuvant therapy with intranasal corticosteroids, decongestants, and antihistamines may be useful in combating the allergic/infammatory component of the disease. Antibiotics given are similar to those used for acute disease, although a longer course (3–6 weeks) may be necessary. Surgical intervention may also be required.
A pulmonary fungal infection endemic to the southwestern United States (e.g., San Joaquin Valley, California). Can present as an acute or subacute pneumonia or as a fulike illness, and may involve extrapulmonary sites, including bone, CNS, and skin. The incubation period is 1–4 weeks after exposure. Filipino, African-American, pregnant, and HIV-patients are at ↑ risk.
Potential complications of sinusitis include meningitis, frontal bone osteomyelitis, cavernous sinus thrombosis, and abscess formation.
Consider coccidioidomycosis in the HIV-, Filipino, African-American, or pregnant patient from the southwestern United States with respiratory infection.
Patients present with fever, anorexia, headache, chest pain, cough, dyspnea, arthralgias, and night sweats. Disseminated infection can present with meningitis, bone lesions, and soft tissue abscesses.
Obtain bronchoalveolar lavage along with fungal cultures of sputum, wound exudate, or other affected tissue.
Identify Coccidioides immitis spherules on H&E or other special stains of sputum or tissue.
Precipitin antibodies (IgM) ↑ within two weeks and disappear after two months; complement fxation antibodies (IgG) ↑ at 1–3 months. Titers > 1:16 indicate disseminated infection.
CXR fndings may be normal or may show infltrates, nodules, cavity, mediastinal or hilar adenopathy, or pleural effusion.
Consider bronchoscopy, fne-needle biopsy, open lung biopsy, or pleural biopsy if serology is indeterminate.
Acute: IV therapy is rarely necessary; however, consider IV amphotericin B for severe or protracted 1° pulmonary infection and disseminated disease. PO fuconazole or itraconazole may be used for mild infection or continuation therapy once the patient is stable.
Chronic: No treatment is needed for asymptomatic chronic pulmonary nodules or cavities. Progressive cavitary or symptomatic disease usually requires surgery plus long-term azole therapy for 8–12 months.
A highly contagious orthomyxovirus transmitted by droplet nuclei. There are three types of infuenza: A, B, and C. Subtypes of infuenza A (e.g., H5N1, H1N1) are classifed on the basis of glycoproteins (hemagglutinin and neuraminidase). Relevant terms are as follows:
Antigenic drift: Refers to small, gradual changes in surface proteins through point mutations. These small changes are suffcient to allow the virus to escape immune recognition, accounting for the fact that individuals can be infected with infuenza multiple times.
Antigenic shift: Refers to an acute, major change in the infuenza A subtype (signifcant genetic reassortment) circulating among humans; leads to pandemics.
In the United States, the typical infuenza season begins in November and lasts until March. Vaccination with inactivated infuenza virus is recommended for patients > 50 years of age, children 6 months to 19 years of age, patients of any age with chronic medical problems (e.g., diabetes, heart disease, renal failure, HIV), pregnant women, nursing home residents, and contacts of high-risk groups (e.g., health care workers).
Patients typically present with abrupt onset of fevers, myalgias, chills, cough, coryza, and weakness. Elderly patients may have atypical presentations characterized only by confusion.
Leukopenia is a common fnding. Rapid infuenza tests of viral antigens from nasopharyngeal swabs are available. More defnitive diagnosis can be made with DFA tests or viral culture.
Symptomatic care with analgesics and cough medicine. Antivirals such as oseltamivir or zanamivir are most effective when used within two days of onset and may shorten the course of infection by 1–2 days.
Severe 1° viral pneumonia, 2° bacterial pneumonia, sinusitis, bronchitis, and exacerbation of COPD and asthma can occur.
Reye’s syndrome, or fatty liver encephalopathy, has been associated with ASA use in children with viral infections, including inf uenza.
A live attenuated, nasally delivered infl uenza vaccine is available for healthy people 2–49 years of age who are not pregnant or severely immunocompromised.
Risk factors for meningitis include recent ear infection, sinusitis, immunodef ciencies, recent neurosurgical procedures, and sick contacts. Causes are listed in Table 2.8-3.
Patients present with fever, malaise, headache, neck stiffness, photophobia, altered mental status, nausea/vomiting, seizures, or signs of meningeal irritation ( Kernig’s and Brudzinski’s signs).
Obtain blood cultures.LP for CSF Gram stain and culture; obtain glucose, protein, WBC count plus differential, RBC count, and opening pressure (in the absence of papilledema or focal neurologic def cits).
Viral PCRs (e.g., HSV); cryptococcal antigen (for HIV patients).CT or MRI to rule out other diagnoses. CBC may reveal leukocytosis; CSF fndings vary (see Table 2.8-4).
TAB LE 2.8-3.  Causes of Meningitisa,bGBS E. coli/GNRs Listeria S. pneumoniae Neisseria meningitidis H. infl uenzae type b Enteroviruses N. meningitidis Enteroviruses S. pneumoniae HSV S. pneumoniae GNRs Listeria N. meningitidis a Causes in HIV include Cryptococcus, CMV, HSV, VZV, TB, toxoplasmosis (brain abscess), and JC virus (PML). b Note: The incidence of H. infl uenzae meningitis has ↓ greatly with the introduction of the H. infl uenzae vaccine in the last 10–15 years.
TABLE 2.8-4.  CSF Prof lesNormal < 10 < 5 ∼2/3 of serum 15–45 10–20 Clear 3–12 Bacterial meningitis ↔ ↑ (> 1000 PMNs) ↓ ↑ ↑ Cloudy ↔ or ↑ Viral meningitis ↔ ↑ (monos/ lymphs) ↔ ↔ or ↑ ↔ or ↑ Most often clear ↔ or ↑ Aseptic meningitis ↔ ↑ ↔ ↔ or ↑ ↔ Clear ↔ SAH ↑↑ ↑ ↔ ↑ ↔ or ↑ Yellow/red ↔ or ↑ Guillain-Barré syndrome ↔ ↔ ↔ or ↑ ↑↑ ↔ Clear or yellow (high protein) ↔ MS ↔ ↔ or ↑ ↔ ↔ ↔ Clear ↑↑ Pseudotumor cerebri ↔ ↔ ↔ ↔ ↑↑↑ Clear ↔
Antibiotics should be administered rapidly (see Table 2.8-5) and may be given empirically up to two hours before an LP is performed.
Some cases of viral meningitis can be treated with supportive care and close follow-up.
Close contacts of patients with meningococcal meningitis should receive rifampin, ciprofoxacin, or ceftriaxone prophylaxis.
T AB LE 2.8-5. Empiric Treatment of Bacterial Meningitis < 1 month GBS, E. coli/GNRs, Listeria. Ampicillin + cefotaxime or gentamicin. 1–3 months Pneumococci, meningococci, H. infl uenzae. Vancomycin IV + ceftriaxone or cefotaxime. 3 months – adulthood Pneumococci, meningococci. Vancomycin IV + ceftriaxone or cefotaxime. > 60 years/alcoholism/ chronic illness Pneumococci, gram-bacilli, Listeria, meningococci. Ampicillin + vancomycin + cefotaxime or ceftriaxone.
■ Dexamethasone may be benefcial in bacterial meningitis, especially S. pneumoniae, if given 15–20 minutes before antibiotics.
Cerebral edema: Visible on CT/MRI. Presents with loss of oculocephalic refex. Treat with IV mannitol.
Subdural effusions: May be seen on CT scan. Occur in 50% of infants with H. infl uenzae meningitis. No treatment is necessary.
Ventriculitis/hydrocephalus: Presents as a worsening clinical picture with improved CSF fndings. Requires ventriculostomy and possibly intraventricular antibiotics.
Seizures: Treat with benzodiazepines and phenytoin.Hyponatremia: Administer fuids and monitor sodium concentration.Subdural empyema: Presents with intractable seizures. Requires surgical evacuation.Other: Cranial nerve palsies, sensorineural hearing loss, coma, death.HSV and arboviruses are the most common causes of encephalitis. Rarer etiologies include CMV, toxoplasmosis, West Nile virus, VZV, Borrelia, Rickettsia, Legionella, enterovirus, Mycoplasma, and cerebral malaria. Children and the elderly are the most vulnerable.
Presents with altered consciousness, headache, fever, and seizures. Lethargy, confusion, coma, and focal neurologic defcits (cranial nerve def cits, accentuated DTRs) may also be present.
The differential includes brain abscess or malignancy, toxic-metabolic encephalopathy, subdural hematoma, and SAH.
CSF shows lymphocytic pleocytosis and moderately ↑ protein. RBCs without evidence of trauma suggest HSV encephalitis. The glucose level is low in tuberculous, fungal, bacterial, and amebic infections.
Obtain a CSF Gram stain (bacteria), acid-fast stain (mycobacteria), India ink (Cryptococcus), wet preparation (free-living amebae), and Giemsa stain (trypanosomes). PCR for HSV, CMV, EBV, VZV, and enterovirus.
MRI may demonstrate a contrast-enhancing lesion in the temporal lobe (in HSV).
HSV encephalitis requires immediate IV acyclovir. CMV encephalitis is treated with IV ganciclovir +/– foscarnet. Give doxycycline for suspected Rocky Mountain spotted fever, Lyme disease, or ehrlichiosis.
A focal, suppurative infection of the brain parenchyma, usually with a “ringenhancing” appearance due to fbrous capsule. The most common infective organisms are streptococci, staphylococci, and anaerobes; multiple organisms are often implicated (80–90% of cases are polymicrobial). Nonbacterial
Although other medications may be used, rifampin is the frequently tested prophylaxis of choice for close contacts of patients with meningococcal meningitis.
The presence of RBCs in CSF without a history of trauma indicates HSV encephalitis.
HSV encephalitis is associated with high morbidity. PCR is highly sensitive and specific. A full course of IV acyclovir is mandatory.
The classic clinical triad of headache, fever, and a focal neurologic deficit is present in 50% of cases of brain abscess.
When fever is absent, 1° and metastatic brain tumors become the major differential diagnoses.
In general, do not LP a patient with a mass lesion in the brain.
Some commonly tested AIDS-defining illnesses: causes include Toxoplasma, Aspergillus, and Candida; zygomycosis should be contemplated in immunocompromised hosts, and neurocysticercosis should be considered in relevant epidemiologic settings. Modes of transmission include the following:
Direct spread: Due to paranasal sinusitis (10% of cases; frequently affects young males; often due to Streptococcus milleri), otitis media or mastoiditis (33%), or dental infection (2%).
Direct inoculation: Affects patients with a history of head trauma or neurosurgical procedures.
Hematogenous spread (25% of cases): Often shows an MCA distribution with multiple abscesses that are poorly encapsulated and located at the gray-white junction.
Headache, drowsiness, inattention, confusion, and seizures are early symptoms, followed by signs of increasing ICP and then a focal neurologic def cit.
Headache is the most common symptom and is often dull, constant, and refractory to treatment. ↑ ICP leads to CN III and CN VI def cits.
CT scan will show a ring-enhancing lesion with a low-density core. MRI has higher sensitivity for early abscesses and posterior fossa lesions.
CSF analysis is not necessary and may precipitate a herniation syndrome.
Lab values may show peripheral leukocytosis, ↑ ESR, and ↑ CRP.
Initiate broad-spectrum IV antibiotics and surgical drainage (aspiration or excision) if necessary for diagnostic and/or therapeutic purposes. Lesions < 2 cm can often be treated medically.
Administer a third-generation cephalosporin + metronidazole +/– vancomycin; give IV therapy for 6–8 weeks followed by 2–3 weeks PO. Obtain serial CT/MRIs to follow resolution.
Dexamethasone with taper may be used in severe cases to ↓ cerebral edema; IV mannitol may be used to ↓ ICP.
CNS lymphoma, toxoplasmosis, or PMLP. jiroveci pneumonia or recurrent bacterial pneumoniaA retrovirus that targets and destroys CD4+ T lymphocytes. Infection is characterized by a progressively high rate of viral replication that leads to a progressive decline in CD4+ count (see Figure 2.8-6).
CD4+ count: Indicates the degree of immunosuppression; guides therapy and prophylaxis and helps determine prognosis.
Viral load: May predict the rate of disease progression; provides indications for treatment and gauges response to antiretroviral therapy.
■In acute HIV (acute infection/seroconversion, acute retroviral syndrome), the initial infection is often asymptomatic, but patients may also present with mononucleosis-like or f ulike symptoms (e.g., fever, lymphadenop
ACUTE LATENT IMMUNODEFICIENCY Acute symptoms Opportunistic infections and malignancies CD4 lymphocytes Anti-p24 antibodies Anti-gp120 antibodies Virus, p24 antigen
FIGURE 2.8-6. Time course of HIV infection.(Adapted, with permission, from Levinson W, Jawetz E. Medical Microbiology and Immunol ogy: Examination & Board Review, 6th ed. New York: McGraw-Hill, 2000: 276.) athy, maculopapular rash, pharyngitis, diarrhea, nausea/vomiting, weight loss, headache).
■HIV may later present as night sweats, weight loss, thrush, recurrent infections, or opportunistic infections. Complications are inversely correlated with CD4+ count (see Figure 2.8-7).
F IGU R E 2.8-7. Relationship of CD4+ count to development of opportunistic infections.
(Reproduced, with permission, from McPhee SJ et al. Current Medical Diagnosis & Treatment, 48th ed. New York: McGraw-Hill, 2009: Fig. 31-1.)
The homozygous CCR5 mutation may confer resistance to HIV infection.
HIVpatients who are pregnant should avoid efavirenz. If the patient is not on antiretroviral therapy at the time of delivery, she should be treated with zidovudine (AZT) intrapartum. Infants should receive AZT for six weeks after birth.
MMR is the only live vaccine that should be given to HIV patients. Do not give oral polio vaccine to HIV-patients or their contacts.
The Major Pathogens Concerning Complete T-Cell CollapseELISA test (high sensitivity, moderate specifcity): Detects anti-HIV antibodies in the bloodstream (can take up to six months to appear after exposure).
Western blot (low sensitivity, high specif city): Conf rmatory.Rapid HIV tests are now available.Baseline evaluation should include HIV RNA PCR (viral load), CD4+ cell count, CXR, PPD skin testing, Pap smear, VDRL/RPR, and serologies for CMV, hepatitis, toxoplasmosis, and VZV.
Evaluation for acute retroviral syndrome (acute HIV) should include HIV RNA PCR (viral load); ELISA may be .
Initiate antiretroviral therapy for the following: (1) symptomatic patients (i.e., those with AIDS-defning illness) regardless of CD4+ count or viral load; (2) asymptomatic patients with a CD4+ count < 350; (3) pregnant patients; and (4) those with specifc HIV-related conditions (e.g., HIV-associated nephropathy).
The initial regimen should generally consist of some combination of two nucleoside/nucleotide reverse transcriptase inhibitors (RTIs) plus either one non-nucleoside RTI (NNRTI) or one protease inhibitor. The most important principle is to select multiple medications (usually at least three) in order to achieve durable treatment response and limit the emergence of resistance.
The choice of regimen depends on drug-drug interactions, drug tolerance, patient adherence, and comorbid conditions (e.g., hyperlipidemia, refux). Monotherapy/dual therapy should not be used.
The goal of therapy is viral suppression (< 50 copies), which usually occurs more rapidly than immune reconstitution. CD4+ count and viral load should thus be carefully monitored.
An HIV genotype should be obtained before the initiation of therapy and when resistance is suspected, as such testing can provide mutation information and identify resistance to specif c antiretrovirals.
Table 2.8-6 outlines prophylactic measures against opportunistic infections.Figure 2.8-8 illustrates the microscopic appearance of some common opportunistic organisms.
Risk factors include xerostomia, antibiotic use, denture use, and immunosuppressed states (e.g., HIV, leukemias, lymphomas, cancer, diabetes, corticosteroid inhaler use, immunosuppressive treatment).
Hx/PE: Presents with soft white plaques that can be rubbed off, with an erythematous base and possible mucosal burning. The differential includes oral hairy leukoplakia (lateral borders of the tongue; not easily rubbed off). Odynophagia is characteristic of candidal esophagitis.
Dx: Usually clinical. KOH or Gram stain shows budding yeast and/or pseudohyphae.
Tx: Treat thrush with local therapy (e.g., nystatin suspension or clotrimazole tablets, or a PO azole such as fuconazole). Treat candidal esophagitis with PO azole therapy.
T AB LE 2.8-6. Prophylaxis for HIV-Related Opportunistic InfectionsP. jiroveci pneumonia CD4+ < 200/mm3, prior P. jiroveci infection, unexplained fever × 2 weeks, or HIV-related oral candidiasis. Single-strength TMP-SMX or dapsone +/– pyrimethamine. Discontinue prophylaxis when CD4+ is > 200 for ≥ 3 months. Mycobacterium avium complex (MAC) CD4+ < 50–100/mm3. Weekly azithromycin or daily clarithromycin. Discontinue prophylaxis when CD4+ is > 100/mm3 for > 6 months. Toxoplasma gondii CD4+ < 100/mm3 + IgG serologies. Double-strength TMP-SMX. — M. tuberculosis PPD > 5 mm or “high risk” (see TB section). Sensitive: INH × 9 months (+ pyridoxine) or rifampin +/– pyrazinamide × 2 months. Include pyridoxine with INH-containing regimens. Candida Multiple recurrences. Esophagitis: Fluconazole. Oral: Nystatin swish and  swallow. — HSV Multiple recurrences. Acyclovir, famciclovir, or valacyclovir. — All patients. Pneumovax. Give every fve years or when CD4+ is < 200. All patients. Infuenza vaccine annually. — S. pneumoniae Inf uenza
Pseudohyphae + budding yeasts Rare fruiting bodies45° angle branching septate hyphae 5–10 μm yeasts with wide capsular halo Narrow-based unequal budding Germ tubes at 37°C Irregular broad (empty-looking) nonseptate hyphae, wide-angle branching
F IGU R E 2.8-8. Common opportunistic organisms.The CSF antigen test for cryptococcal meningitis is highly sensitive and specific.
Risk factors include AIDS and exposure to pigeon droppings.Hx/PE: Presents with headache, fever, impaired mentation, and absent meningismus. The differential includes toxoplasmosis, lymphoma, TB meningitis, AIDS dementia complex, PML, HSV encephalitis, and other fungal disease.
Dx: LP (↓ CSF glucose; ↑ protein; ↑ leukocyte count with monocytic predominance, ↑↑ opening pressure); CSF cryptococcal antigen test, India ink stain, and fungal culture.
Tx: ■IV amphotericin B + f ucytosine × 2 weeks; then give f uconazole 400 mg × 8 weeks. Lifelong maintenance therapy should be administered with fuconazole 200 mg QD, or until CD4+ is > 200 for > 6 months.
■↑ opening pressure may require serial LPs or VP shunt for management.
Risk factors include AIDS, spelunking, and exposure to bird or bat excrement, especially in the Ohio and Mississippi river valleys.
1° exposure is often asymptomatic or causes a f ulike illness.
Presentation may range from no symptoms to fulminant disease with pulmonary or extrapulmonary manifestations.
Fever, weight loss, hepatosplenomegaly, lymphadenopathy, nonproductive cough, and pancytopenia indicate disseminated infection (most often within 14 days).
The differential includes atypical bacterial pneumonias, blastomycosis, coccidioidomycosis, TB, sarcoidosis, pneumoconiosis, and lymphoma.
CXR shows diffuse nodular densities, focal infltrate, cavity, or hilar lymphadenopathy (chronic infection is usually cavitary).
The urine and serum polysaccharide antigen test is the most sensitive test for making the initial diagnosis, monitoring response to therapy, and diagnosing relapse. Culture is also diagnostic (blood, sputum, bone marrow, CSF).
The yeast form is seen with silver stain on biopsy (bone marrow, lymph node, liver) or bronchoalveolar lavage.
Depends on the severity of disease and the host:Mild pulmonary disease or stable nodules: Treat supportively in the immunocompromised host.
Chronic cavitary lesions: Give itraconazole for > 1 year.Severe acute pulmonary disease or disseminated disease: Amphotericin B or amphotericin B liposomal × 3–10 days followed by itraconazole × 12 weeks or longer. Maintenance therapy with daily itraconazole.
Formerly known as Pneumocystis carinii pneumonia, or PCP. Risk factors include impaired cellular immunity and AIDS.
Presents with dyspnea on exertion, fever, nonproductive cough, tachypnea, weight loss, fatigue, and impaired oxygenation.
Can also present as disseminated disease or as local disease in other organ systems.
The differential includes TB, histoplasmosis, and coccidioidomycosis.Diagnosed by cytology of induced sputum or bronchoscopy specimen with silver stain and immunofuorescence. Obtain an ABG to check PaO2.
CXR may show diffuse, bilateral interstitial infltrates with a ground-glass appearance, but any presentation is possible.
Treat with high-dose TMP-SMX × 21 days. Clindamycin and primaquine constitute an alternative regimen for patients with sulfa allergy.
A prednisone taper should be used in patients with moderate to severe hypoxemia (PaO2 < 70 mm or an arterial-alveolar oxygen gradient > 35).
Most 1° CMV infections are asymptomatic; serious reactivation generally occurs only in immunocompromised patients. Seventy percent of adults in the United States have been infected. Transmission occurs via sexual contact, in breast milk, via respiratory droplets in nursery or day care facilities, and through blood transfusions. Risk factors for reactivation include the f rst 100 days status post tissue or bone marrow transplant and HIV positivity with a CD4+ < 100 or a viral load > 10,000.
Systemic infection may resemble EBV mononucleosis (see the discussion of infectious mononucleosis).
Specifc manifestations are as follows:CMV retinitis: Has a high rate of retinal detachment (“pizza pie” retinopathy), and presents with foaters and visual feld changes (CD4+ < 50).
GI and hepatobiliary involvement: Can present with multiple nonspecifc GI symptoms, including bloody diarrhea. CMV, microsporidia, and cryptosporidia have been implicated in the development of AIDS cholangiopathy.
CMV pneumonitis: Presents with cough, fever, and sparse sputum production; associated with a high mortality rate. Much more common in patients with hematologic malignancies and transplant patients than in those with AIDS.
CNS involvement: Can include polyradiculopathy, transverse myelitis, and subacute encephalitis (CD4+ < 50; periventricular calcif cations).
Suspect P. jiroveci pneumonia in any HIV patient who presents with nonproductive cough and dyspnea.
Treat CMV infection with ganciclovir.Virus isolation, culture, tissue examination, serum PCR.Treat with ganciclovir or foscarnet. Treat underlying disease if the patient is immunocompromised.
Ubiquitous organisms causing pulmonary and disseminated infection in several demographic groups. The 1° form occurs in apparently healthy nonsmokers (Lady Windermere syndrome); a 2° pulmonary form affects patients with preexisting pulmonary disease such as COPD, TB, or CF. Disseminated infection occurs in AIDS patients with a CD4+ < 50. There is no evidence that behavioral change affects exposure.
Disseminated M. avium infection in AIDS is associated with fever, weakness, and weight loss in patients who are not on HAART or chemoprophylaxis for MAC.
Hepatosplenomegaly and lymphadenopathy are occasionally seen.Adrenal insuffciency is possible in the setting of infltration into the adrenals.
Obtain mycobacterial blood cultures ( in 2–3 weeks).Labs show anemia, hypoalbuminemia, and ↑ serum alkaline phosphatase and LDH.
Biopsy of bone marrow, intestine, or liver reveals foamy macrophages with acid-fast bacilli. Typical granulomas may be absent in immunocompromised patients.
Treat with clarithromycin and ethambutol +/– rifabutin and HAART. Continue for > 12 months and until CD4+ is > 100 for > 6 months.
Weekly azithromycin for those with a CD4+ < 50 or AIDS-def ning opportunistic infection.
Risk factors include ingesting raw or undercooked meat and changing cat litter. Worldwide, exposure is highest in France.
1° infection is usually asymptomatic.Reactivated toxoplasmosis occurs in immunosuppressed patients and may present in specif c organs (brain, lung, and eye > heart, skin, GI tract, and liver).
■Encephalitis is common in seropositive AIDS patients. Classically, CNS lesions present with fever, headache, altered mental status, seizures, and focal neurologic def cits.
Serology, PCR (indicates exposure and risk for reactivation); tissue examination for histology, isolation of the organism in mice, or tissue culture.
In the setting of CNS involvement, obtain a CT scan (can show multiple isodense or hypodense, ring-enhancing mass lesions) or an MRI (predilection for basal ganglia; more sensitive).
Induction with high-dose PO pyrimethamine + sulfadiazine and leukovorin × 4–8 weeks; maintenance with low-dose pyrimethamine + sulfadiazine and leukovorin until the disease has resolved clinically and radio-graphically.
TMP-SMX (Bactrim DS) or pyrimethamine + dapsone can be used for prophylaxis in patients with a CD4+ < 100 and a toxoplasmosis IgG.
The two most likely differential diagnoses of ring-enhancing lesions in AIDS patients are toxoplasmosis and CNS lymphoma.
The most common bacterial STD in the United States. Caused by Chlamydia trachomatis, which can infect the genital tract, urethra, anus, and eye. Risk factors include unprotected sexual intercourse, new or multiple partners, and frequent douching. Often coexists with or mimics N. gonorrhoeae infection (known as nongonococcal urethritis when gonorrhea is absent). LGV serovars of Chlamydia cause lymphogranuloma venereum, an emerging cause of proctocolitis.
Infection is often asymptomatic but may present with urethritis, mucopurulent cervicitis, or PID.
Exam may reveal cervical/adnexal tenderness in women or penile discharge and testicular tenderness in men.
The differential includes gonorrhea, endometriosis, PID, orchitis, vaginitis, and UTI.
Lymphogranuloma venereum presents in its 1° form as a painless, transient papule or shallow ulcer. In its 2° form, it presents as painful swelling of the inguinal nodes, and in its 3° form it can present as an “anogenital syndrome” (anal pruritus with discharge, rectal strictures, rectovaginal f stula, and elephantiasis).
Diagnosis is usually clinical.Culture is the gold standard.Urine tests (PCR or ligase chain reaction) are a rapid means of detection, while DNA probes and immunofuorescence (for gonorrhea/chlamydia) take 48–72 hours.
Gram stain of urethral or genital discharge may show PMNs but no bacteria (intracellular).
Chlamydia infection is a common cause of nongonococcal urethritis in men.
Chlamydia species cause arthritis, neonatal conjunctivitis, pneumonia, nongonococcal urethritis/ PID, and lymphogranuloma venereum.
Treat for gonorrhea and chlamydia in light of the high prevalence of coinfection.
Syphilis is the “great imitator” because its dermatologic findings resemble those of many other diseases.
Doxycycline 100 mg PO BID × 7 days or azithromycin 1 g PO × 1 day. Use erythromycin in pregnant patients. Treat sexual partners, and maintain a low threshold to treat for N. gonorrhoeae. LGV serovars require prolonged therapy for 21 days.
Chronic infection and pelvic pain, Reiter’s syndrome (urethritis, conjunctivitis, arthritis), Fitz-Hugh–Curtis syndrome (perihepatic inf ammation and f brosis).
Ectopic pregnancy/infertility can result from PID (in women) and epididymitis (in men).
A gramintracellular diplococcus that can infect almost any site in the female reproductive tract. Infection in men tends to be limited to the urethra.
Presents with a greenish-yellow discharge, pelvic or adnexal pain, and swollen Bartholin’s glands. Men experience a purulent urethral discharge, dysuria, and erythema of the urethral meatus.
The differential includes chlamydia, endometriosis, pharyngitis, PID, vaginitis, UTI, salpingitis, and tubo-ovarian abscess.
Gram stain and culture is the gold standard for any site (i.e., pharynx, cervix, urethra, or anus). Nucleic acid amplif cation tests can be sent on penile/vaginal tissue or from urine.
Disseminated disease may present with monoarticular septic arthritis, rash, and/or tenosynovitis.
Ceftriaxone IM or cefepime PO × 1 dose. Also treat for presumptive chlamydia coinfection (doxycycline × 7 days or macrolide × 1 dose). Condoms are effective prophylaxis. Treat the sexual partner or partners if possible. Fluoroquinolones should not be used because of emerging resistance.
Disseminated disease requires IV ceftriaxone for at least 24 hours.
Persistent infection with pain; infertility; tubo-ovarian abscess with rupture; disseminated gonococcal infection (see Figure 2.8-9).
Caused by Treponema pallidum, a spirochete. AIDS can accelerate the course of disease progression.
■1° (10–90 days after infection): Presents with a painless ulcer (chancre; see Figure 2.8-10).
F IGU R E 2.8-9. Disseminated gonococcal infection.Hemorrhagic, painful pustules on erythematous bases. (Reproduced, with permission, from
Wolff K et al. Fitzpatrick’s Color Atlas & Synopsis of Clinical Dermatology, 5th ed. New York:
McGraw-Hill, 2005: Fig. 27-17.) 2° (4–8 weeks after chancre): Presents with low-grade fever, headache, malaise, and generalized lymphadenopathy with a diffuse, symmetric, asymptomatic (nonpruritic) maculopapular rash on the soles and palms. Highly infective 2° eruptions include mucous patches or condylomata lata (see Figure 2.8-11). Meningitis, hepatitis, nephropathy, and eye involvement may also be seen.
Early latent (period from resolution of 1° or 2° syphilis to end of f rst year of infection): No symptoms;  serology.
Late latent (period of asymptomatic infection beyond the f rst year): No symptoms; or  serology. One-third progress to 3° syphilis.
FIGURE 2.8-10.  1° syphilis.The chancre is an ulcerated papule with a smooth, clean base; raised, indurated borders; and scant discharge. (Reproduced, with permission, from Bondi EE. Dermatology: Diagnosis and Therapy, 1st ed. Stamford, CT: Appleton & Lange, 1991: 394.)
FIGURE 2.8-11.  Condylomata lata.Typical appearance of the verrucous heaped-up lesions of condylomata lata. (Reproduced, with permission, from Wolff K et al. Fitzpatrick’s Color Atlas & Synopsis of Clinical Dermatology, 5th ed. New York: McGraw-Hill, 2005: Fig. 27-27.) ■ 3° (late manifestations appearing 1–20 years after initial infection): Presents with destructive, granulomatous gummas. Neurosyphilis includes tabes dorsalis (posterior column degeneration), meningitis, and Argyll Robertson pupil (constricts with accommodation but not reactive to light). Cardiovascular fndings include dilated aortic root, aortitis, aortic root aneurysms, and aortic regurgitation.
■See Table 2.8-7. VDRL false positives are seen with Viruses (mononucleosis, HSV, HIV, hepatitis), Drugs/IV drug use, Rheumatic fever/Rheumatoid arthritis, and SLE/Leprosy.
TABLE 2.8-7.Dark-f eld microscopy Identifes motile spirochetes (only 1° and 2° lesions). VDRL/RPR Rapid and cheap, but sensitivity is only 60–75% in 1° disease. Many false positives. FTA-ABS Sensitive and specifc. Used as a 2° diagnostic test. TPPAa Sensitivity and specifcity similar to FTA-ABS but easier to use. Becoming the 2° test of choice.
a TPPA = T. pallidum particle agglutination test.■Neurosyphilis should be suspected and ruled out in any AIDS patient with neurologic symptoms and a RPR.
1°/2°: Benzathine penicillin IM × 1 day. Tetracycline or doxycycline × 14 days may be used for patients with penicillin allergies.
Latent infection: Treat with benzathine penicillin once weekly × 3 weeks.
Neurosyphilis: Treat with penicillin IV; penicillin-allergic patients should be desensitized prior to therapy.
See Table 2.8-8 for a description of common sexually transmitted genital lesions along with an outline of their diagnosis and treatment.
Remember that treatment of syphilis can result in an acute fl ulike illness known as the Jarisch-Herxheimer reaction.
Affect females more frequently than males, and E. coli cultures are obtained in 80% of cases. See the mnemonic SEEKS PP for other pathogens. Risk factors include the presence of catheters or other urologic instrumentation, anatomic abnormalities (e.g., BPH, vesicoureteral ref ux), previous UTIs or pyelonephritis, diabetes mellitus (DM), recent antibiotic use, immunosuppression, and pregnancy.
Present with dysuria, urgency, frequency, suprapubic pain, and possibly hematuria. Children may present with bed-wetting, poor feeding, recurrent fevers, and foul-smelling urine. The differential includes vaginitis, STDs, urethritis or acute urethral syndrome, and prostatitis.
Diagnosed by clinical symptoms. In the absence of symptoms, treatment is warranted only for children, those with anatomical GU tract anomalies, pregnant women, those with instrumented urinary tracts, patients scheduled for GU surgery, and renal transplant patients.
Urine dipstick/UA: ↑ leukocyte esterase (a marker of WBCs) is 75% sensitive and up to 95% specif c. ↑ nitrites (a marker of bacteria), ↑ urine pH (Proteus infections), and hematuria (seen with cystitis) are also commonly seen.
Microscopic analysis: Pyuria (> 5 WBCs/hpf) and bacteriuria (1 organism/hpf = 106 organisms/mL) are suggestive.
Urine culture: The gold standard is > 105 CFU/mL.Uncomplicated UTI: Treat on an outpatient basis with PO TMP-SMX or a f uoroquinolone × 3 days, or nitrofurantoin × 7 days. Note that resistance to TMP-SMX and fuoroquinolones has been increasing.
Complicated UTI (urinary obstruction, men, renal transplant, catheters, instrumentation): Administer the same antibiotics as above, but for 7–14 days.
Common UTI bugs— SEEKS PP Serratia E. coli Enterobacter Klebsiella pneumoniae S. saprophyticus Pseudomonas Proteus mirabilis
T AB LE 2.8-8. Sexually Transmitted Genital LesionsLesion Papule becomes a beefy-red ulcer with a characteristic rolled edge of granulation tissue Papule or pustule (chancroid; see Figure 2.8-12) Vesicle (3–7 days postexposure) Papule (condylomata acuminata; warts) Papule (chancre) Appearance Raised red lesions with a white border Irregular, deep, well demarcated, necrotic Regular, red, shallow ulcer Irregular, pink or white, raised; caulif ower Regular, red, round, raised Number 1 or multiple 1–3 Multiple Multiple Single Size 5–10 mm 10–20 mm 1–3 mm 1–5 mm 1 cm Pain No Yes Yes No No Concurrent signs and symptoms Granulomatous ulcers Inguinal lymphadenopathy Malaise, myalgias, and fever with vulvar burning and pruritus Pruritus Regional adenopathy Clinical exam, biopsy (Donovan bodies) Diffcult to culture; diagnosis is made on clinical grounds Tzanck smear shows multinucleated giant cells; viral cultures; DFA or serology Clinical exam; biopsy for conf rmation Spirochetes seen under dark-f eld microscopy; T. pallidum identifed by serum antibody test Doxycycline (100 mg BID) or azithromycin (1 g weekly) × 3 weeks Doxycycline (100 mg BID) or azithromycin (1 g weekly) × 3 weeks Acyclovir or valacyclovir for 1° infection Cryotherapy; topical agents such as podophyllin, trichloroacetic acid, or 5-FU cream Penicillin IM Diagnosis Treatmentd a Previously known as Calymmatobacterium granulomatis. b Some 85% of genital herpes lesions are caused by HSV-2. c HPV serotypes 6 and 11 are associated with genital warts; types 16, 18, and 31 are associated with cervical cancer. d For all, treat sexual partners.
FIGURE 2.8-12. Chancroid.Multiple, painful ulcers. (Reproduced, with permission, from Wolff K et al. Fitzpatrick’s Color
Atlas & Synopsis of Clinical Dermatology, 5th ed. New York: McGraw-Hill, 2005: Fig. 27-31.)
Pregnant patients: Treat asymptomatic bacteruria or symptomatic UTI with nitrofurantoin or cephalosporin × 3–7 days. Avoid f uoroquinolones. Confrm clearance with a repeat culture post-treatment.
Patients with urosepsis should be hospitalized and initially treated with IV antibiotics. Consider broader coverage to include resistant GNRs or enterococcus.
Prophylactic antibiotics may be given to women with uncomplicated recurrent UTIs. Check for prostatitis in men.
Nearly 85% of community-acquired cases of pyelonephritis result from the same pathogens that cause cystitis. Cystitis and pyelonephritis have similar risk factors.
■Signs and symptoms are similar to those of cystitis but show evidence of upper urinary tract disease.
■ Symptoms include f ank pain, fever/chills, and nausea/vomiting. Dysuria, frequency, and urgency are also possible.
■UA and culture: Results are similar to those of cystitis, but with WBC casts. Send blood cultures to rule out urosepsis.
Pyelonephritis is the most common serious medical complication of pregnancy. Twenty to thirty percent of patients with untreated bacteriuria will develop pyelonephritis.
When in doubt, admit a patient with pyelonephritis and administer IV antibiotics.
Urosepsis must be considered in any elderly patient with altered mental status.
SIRS = two or more of the following: 1.Temperature: Either < 36°C or > 38°C (i.e., hypothermia or fever).
Tachypnea: > 20 breaths per minute or PaCO2 < 32 mmHg on ABG.
Tachycardia: HR > 90 bpm.Leukocytosis/leukopenia: WBC < 4000 cells/mm3 or > 12,000 cells/mm3.CBC: Reveals leukocytosis.Imaging: In general, imaging is not necessary. Ultrasound can be used to rule out obstruction and calculi and can often confrm the diagnosis noninvasively, but CT is becoming the test of choice in patients with adequate renal function who are not responding to therapy. In recurrent cases, IVP may demonstrate renal scarring.
For mild cases, patients may be treated on an outpatient basis for 10–14 days. Fluoroquinolones are frst-line therapy. Encourage ↑ PO f uids and monitor closely.
Admit and administer IV antibiotics to patients who have serious medical complications or systemic symptoms, are pregnant, present with severe nausea and vomiting, or have suspected bacteremia. Fluoroquinolones, thirdor fourth-generation cephalosporins, β-lactam/β-lactamase inhibitors, and carbapenem may be used depending on disease severity.
Defned as the presence of systemic infammatory response syndrome (SIRS) with a documented infection, induced by microbial invasion or toxins in the bloodstream. Severe sepsis refers to sepsis with end-organ dysfunction due to poor perfusion. Septic shock refers to sepsis with hypotension and organ dysfunction from vasodilation. Examples include the following:
Gram-shock (e.g., staphylococci and streptococci) 2° to f uid loss caused by exotoxins.
Gram-shock (e.g., E. coli, Klebsiella, Proteus, and Pseudomonas) 2° to vasodilation caused by endotoxins (lipopolysaccharide).
Neonates: GBS, E. coli, Listeria monocytogenes, H. infl uenzae.Children: H. infl uenzae, pneumococcus, meningococcus.Adults: Gramcocci, aerobic grambacilli, anaerobes (dependent on the presumed site of infection).
IV drug users/indwelling lines: S. aureus, coagulase-Staphylococcus species.Asplenic patients: Pneumococcus, H. infl uenzae, meningococcus (encapsulated organisms).Presents with abrupt onset of fever and chills, altered mental status, tachycardia, and tachypnea. Severe sepsis is seen in end-organ dysfunction. Hypotension occurs in cases of septic shock.
Septic shock is typically a warm shock with warm skin and extremities. This contrasts with cardiogenic shock, which typically presents with cool skin and extremities.
Petechiae, ecchymoses, or abnormal coagulation tests suggest DIC (2–3% of cases).
A clinical diagnosis.Labs show leukocytosis or leukopenia with ↑ bands, thrombocytopenia (50% of cases), evidence of ↓ tissue perfusion (↑ creatinine, ↑ LFTs), and abnormal coagulation studies (↑ INR).
It is critical to obtain cultures of all appropriate sites (e.g., blood, sputum, CSF, wound, urine).
Imaging (CXR, CT) may aid in establishing the etiology or site of infection.
ICU admission may be required. Treat aggressively with IV f uids, pressors, and empiric antibiotics (based on the likely source of infection).
Treat underlying factors (e.g., remove Foley catheter or infected lines).
The 1° goal is to maintain BP and perfusion to end organs.
A protozoal disease caused by four strains of the genus Plasmodium (P. falciparum, P. vivax, P. ovale, and P. malariae) and transmitted by the bite of an infected female Anopheles mosquito. P. falciparum has the highest morbidity and causes the largest number of deaths, occasionally within 24 hours of symptom onset. Recent outbreaks have occurred in parts of the southern and eastern United States and in Europe, mainly through the arrival of infected travelers and immigrants from endemic areas. Travelers to endemic areas should take chemoprophylaxis and use mosquito repellent and bed nets to minimize exposure.
Patients have a history of exposure in a malaria-endemic area, with periodic attacks of sequential chills, fever (> 41°C), and diaphoresis occurring over 4–6 hours. Splenomegaly often appears four or more days after onset of symptoms. Patients are often asymptomatic between attacks, which recur every 2–3 days, depending on the Plasmodium strain.
Severely ill patients may present with hyperpyrexia, prostration, impaired consciousness, agitation, hyperventilation, and bleeding. The presence of rash, lymphadenopathy, neck stiffness, or photophobia suggests a different or additional diagnosis.
Timely diagnosis of the correct strain is essential because P. falciparum can be fatal and is often resistant to standard chloroquine treatment.
Giemsa-or Wright-stained thick and thin blood f lms should be sent for expert microscopic evaluation to determine the strain as well as the degree of parasitemia. Specimens should be obtained at eight-hour intervals for three days, including during and between febrile periods.
CBC usually demonstrates normochromic, normocytic anemia with reticulocytosis.If resources allow, more sensitive serologic tests are available, including rapid antigen detection methods, fuorescent antibody methods, and PCR.
Malaria should be considered in the differential for any patient who has emigrated from or recently traveled to tropical locations and presents with fever.
P. vivax, P. ovale, andP. malariae can all cause symptoms months to years after initial infection.
Obtain a finger stick in a patient with malaria and mental status changes to rule out hypoglycemia.
■Uncomplicated malarial infection can be treated orally, with the choice of medication determined by the Plasmodium strain. Chloroquine has been the standard antimalarial medication, but increasing resistance has led to
A young adult who presents with the triad of fever, sore throat, and lymphadenopathy may have infectious mononucleosis.
The lymphocytosis in EBV infection is predominantly due to B-cell proliferation, but the atypical cells are T lymphocytes.
the use of other medications, including quinine with clindamycin or doxycycline, atovaquone, mefoquine, artesunate, and halofantrine.
The life cycles of P. vivax and P. ovale strains include dormant liver hypnozoite forms, which are resistant to treatment with chloroquine. Thus, in cases of P. vivax, P. ovale, or an unknown strain, primaquine is added to eradicate the hypnozoites in the liver.
Severe infections can be treated with parenteral antimalarial medications (IV quinidine) with transition to oral regimens as tolerated. Newer combinations such as proguanil/atovaquone (Malarone) eliminate the need for multiple medications. Symptoms can be treated with supportive care.
Cerebral malaria: Headache, change in mental status, neurologic signs, retinal hemorrhages, convulsions, delirium, coma.
Severe hemolytic anemia: Usually associated with P. falciparum infection.Acute tubular necrosis and renal failure: Associated with blackwater fever (dark urine due to hemoglobinuria).
Noncardiogenic pulmonary edema: Often precipitated by overly rapid re-hydration.Other: Additional complications include grambacteremia, acute hepatopathy, hypoglycemia, cardiac dysrhythmias, secretory diarrhea, lactic acidosis, DIC, and a low birth rate in children of infected mothers.
Most commonly occurs in young adult patients; usually due to acute EBV infection. Transmission most often occurs through exchange of body f uids, including saliva.
Presents with fever and pharyngitis. Fatigue invariably accompanies initial illness and may persist for 3–6 months. Exam may reveal low-grade fever, generalized lymphadenopathy (especially posterior cervical), tonsillar exudate and enlargement, palatal petechiae, a generalized maculopapular rash, splenomegaly, and bilateral upper eyelid edema.
Patients who present with pharyngitis as their 1° symptom may be misdiagnosed as having streptococcal pharyngitis (30% of patients with infectious mononucleosis are asymptomatic carriers of group A strep in their oropharynx).
Treatment of patients with ampicillin (for streptococcal pharyngitis) during acute EBV infection can cause a prolonged, pruritic, drug-related maculopapular rash. This rash does not portend future sensitivity to β-lactams and will remit with discontinuation of ampicillin.
The differential also includes CMV, toxoplasmosis, HIV, HHV-6, other causes of viral hepatitis, and lymphoma.
Diagnosed by the heterophil antibody (Monospot) test (may be in the frst few weeks after symptoms begin). The EBV-infected proliferating B cells produce a characteristic antibody that agglutinates the horse and sheep RBCs that are the basis for the Monospot test.
EBV-specif c antibodies can be ordered in patients with suspected mono nucleosis and a  Monospot test. Infectious mononucleosis syndromes that are Monospot  and EBV-antibody are most often due to CMV infection. Acute HIV and other viral etiologies should be considered.
CBC with differential often reveals mild thrombocytopenia with relative lymphocytosis and > 10% atypical T lymphocytes.
CMP usually reveals mildly elevated transaminases, alkaline phosphatase, and total bilirubin.
Treatment is mostly supportive, as there is no effective antiviral therapy. Corticosteroids are indicated for airway compromise due to tonsillar enlargement, severe thrombocytopenia, or severe autoimmune hemolytic anemia.
CNS infection: Can present as aseptic meningitis, encephalitis, meningoencephalitis, cranial nerve palsies (particularly CN VII), optic and peripheral neuritis, transverse myelitis, or Guillain-Barré syndrome.
Splenic rupture: Occurs in < 0.5% of cases. More common in males, and presents with abdominal pain, referred shoulder pain, or hemodynamic compromise.
Upper airway obstruction: Treat with steroids.Bacterial superinfection: Ten percent of patients develop streptococcal pharyngitis secondarily.
Fulminant hepatic necrosis: More common in males; the most common cause of death in affected males.
Autoimmune hemolytic anemia: Occurs in 2% of patients during the f rst two weeks. Coombs . Mild anemia lasts 1–2 months. Treat with corticosteroids if severe.
Other: Rare complications associated with acute EBV infection include hepatitis (which can be fulminant), myocarditis or pericarditis with electrocardiographic changes, pneumonia with pleural effusion, interstitial nephritis, genital ulcerations, and vasculitis.
About one-third of patients with infectious mononucleosis have coexisting streptococcal pharyngitis that requires treatment.
Fever of Unknown Origin (FUO)A temperature of > 38.3°C of at least three weeks’ duration that remains undiagnosed following three outpatient visits or three days of hospitalization.
Presents with fever, headache, myalgia, and malaise. The differential includes the following:
Infectious: TB, endocarditis (e.g., HACEK organisms; see the discussion of infective endocarditis), occult abscess, osteomyelitis, catheter infections. In HIV patients, consider MAC, histoplasmosis, CMV, or lymphoma.
Neoplastic: Lymphomas, leukemias, hepatic and renal cell carcinomas.Autoimmune: Still’s disease, SLE, cryoglobulinemia, polyarteritis nodosa, connective tissue disease, granulomatous disease (including sarcoidosis).
Miscellaneous: Pulmonary emboli, alcoholic hepatitis, drug fever, familialMediterranean fever, factitious fever. ■ Undiagnosed (10–15%).Overall, infections and cancer account for the majority of cases of FUO (> 60%). Autoimmune diseases account for ~15%. In the elderly, rheumatic diseases account for one-third of cases.
FUO patients without other symptoms do not require empiric antibiotic therapy.
With fever and rash, think—Lyme disease is the most common vector-borne disease in North America.
Labs: Confrm the presence of fever and take a detailed history (including family, social, sexual, occupational, dietary, exposures [pets/animals], and travel); obtain a CXR, CBC with differential, ESR, multiple blood cultures, sputum Gram stain and culture, UA and culture, and PPD. Specifc tests (ANA, RF, viral cultures, viral serologies/antigen tests) can be obtained if an infectious or autoimmune etiology is suspected.
Imaging: CT of the chest and abdomen should be done early in the workup of a true FUO. Rule out drug fever. Invasive testing (marrow/liver biopsy) is generally low yield. Laparoscopy and colonoscopy are higher yield as second-line tests (after CT).
Stop unnecessary medications. Give empiric antibiotics to severely ill patients until the etiology has been determined. Stop antibiotics if there is no response.
Defned as a single oral temperature of ≥ 38.3°C (101°F) or a temperature of ≥ 38.0°C (100.4°F) for ≥ 1 hour in a neutropenic patient (i.e., an absolute neutrophil count of < 500 cells/mm3).
Hx/PE: Common in cancer patients undergoing chemotherapy (neutropenic nadir 7–10 days postchemotherapy). Infammation may be minimal or absent.
Send appropriate cultures, including blood, urine, sputum, and wound. Consider testing for viruses, fungi, and mycobacteria.
Conduct a thorough physical exam, but avoid a rectal exam in light of the bleeding risk if the patient is thrombocytopenic.
Obtain a CBC with differential, serum creatinine, BUN, and transaminases; order blood, urine, lesion, and stool cultures.
CXR for patients with respiratory symptoms; CT scan to evaluate for abscesses or other occult infection.
Tx: Empiric antibiotic therapy (see Figure 2.8-13). Routine use of colony-stimulating factors is not indicated. If fevers persist after 72 hours despite antibiotic therapy, start antifungal treatment.
A tick-borne disease caused by the spirochete Borrelia burgdorferi. Usually seen during the summer months, and carried by Ixodes ticks on white-tailed deer and white-footed mice. Endemic to the Northeast, northern Midwest, and Pacif c coast.
Hx/PE: Presents with the onset of rash with fever, malaise, fatigue, headache, myalgias, and/or arthralgias. Infection usually occurs after a tick feeds for > 18 hours.
■1° (early localized disease): Erythema migrans begins as a small erythematous macule or papule that is found at the tick-feeding site and expands slowly over days to weeks. The border may be macular or raised, often with central clearing (“bull’s eye”).
Fever (≥ 38.3°C) + Neutropenia (< 500 neutrophils/mm3) PO IV (outpatient) Vancomycin not needed Reassess after 3–5 days Vancomycin needed Intermediate/High Risk High-dose chemo? Hematologic malignancy? Neutropenia > 14 days? Combination Therapy: Aminoglycosides + antipseudomonal, penicillin, cefepime, ceftazidime, or carbapenem Vancomycin + cefepime, ceftazidime, or carbapenem ± aminoglycoside Monotherapy: Cefepime, ceftazidine, or carbapenem Ciprofloxacin + amoxicillin/clavulanate (adults only) Low Risk Solid tumors treated as outpatient with conventional chemotherapy? Minimal comorbidity? Neutropenia < 7 days?
F IGU R E 2.8-1 3. Empiric treatment algorithm for a neutropenic fever patient.
2° (early disseminated disease): Presents with migratory polyarthropathies, neurologic phenomena (e.g., Bell’s palsy), meningitis and/or myocarditis, and conduction abnormalities (third-degree heart block).
3° (late disease): Arthritis and subacute encephalitis (memory loss and mood change).
Dx: Clinical diagnosis of erythema migrans is as follows:ELISA and Western blot: Use the Western blot to conf rm a or indeterminate ELISA. A ELISA denotes exposure but is not specif c for active disease. Western blots sent without ELISA have high rates of false positives.
Tissue culture/PCR: Extremely diffcult to obtain; not routinely done.Tx: Treat early disease with doxycycline and more advanced disease (e.g., CNS or arthritic disease) with ceftriaxone. Consider empiric therapy for patients with the characteristic rash, arthralgias, or a tick bite acquired in an endemic area. Prevent with tick bite avoidance.
A disease caused by Rickettsia rickettsii and carried by the American dog tick (Dermacentor variabilis). The organism invades the endothelial lining of capillaries and causes small vessel vasculitis.
Hx/PE: Presents with headache, fever, malaise, and rash. The characteristic rash is initially macular (beginning on the wrists and ankles) but becomes petechial/purpuric as it spreads centrally (see Figure 2.8-14). Altered mental status or DIC may develop in severe cases.
Dx: Clinical diagnosis should be confrmed with indirect immunof uorescence of rash biopsy.
Tx: Doxycycline or chloramphenicol (for multidrug-resistant organisms).Lyme arthritis can be very subtle and minimally infl ammatory and can wax and wane.
Rocky Mountain spotted fever starts on the wrists and ankles and then spreads centrally.
FIGURE 2.8-14. Rocky Mountain spotted fever.These erythematous macular lesions will evolve into a petechial rash that will spread centrally. (Courtesy of Daniel Noltkamper, MD, as published in Knoop KJ et al. Atlas of Emergency Medicine, 2nd ed. New York: McGraw-Hill, 2002: 382.)
The condition can be rapidly fatal if left untreated. If clinical suspicion is high, begin treatment while awaiting testing. Prevent by avoiding tick bites.
Causes of red eye:A common complaint in the emergency room setting, inf ammation of the conjunctiva is most often bacterial or viral but can also be fungal, parasitic, allergic, or chemical. It is essential to differentiate potentially vision-threatening infectious etiologies from allergic or other causes of conjunctivitis, as well as to identify other vision-threatening conditions that may mimic conjunctivitis. See Table 2.8-9 for the common etiologies of infectious conjunctivitis.
Commonly due to infection of the paranasal sinuses; can lead to endophthalmitis and blindness. Usually caused by streptococci, staphylococci (including MRSA), and H. infl uenzae (in children). In diabetic and immunocompromised patients, mucormycosis and Rhizopus are in the differential.
Hx/PE: Presents with acute-onset fever, proptosis, ↓ EOM, ocular pain, and ↓ visual acuity. Look for a history of ocular trauma or sinusitis. Pala
T AB LE 2.8-9. Common Causes of Infectious ConjunctivitisBacterial Staphylococci, streptococci, Haemophilus, Pseudomonas, Moraxella Foreign body sensation, purulent discharge. Gram stain and culture if severe. Antibiotic drops/ ointment. N. gonorrhoeae An emergency! Corneal involvement can lead to perforation and blindness. Gram stain shows gram-intracellular diplococci. IM ceftriaxone, PO ciprofoxacin or of oxacin. Inpatient treatment if complicated. C. trachomatis A–C Recurrent epithelial keratitis in childhood, trichiasis, corneal scarring, and entropion. The leading cause of preventable blindness worldwide. Giemsa stain, chlamydial cultures. Azithromycin, tetracycline, or erythromycin × 3–4 weeks. Viral Adenovirus (most common) Copious watery discharge, severe ocular irritation, preauricular lymphadenopathy. Occurs in epidemics. Contagious; self-limited. Topical corticosteroids with supervision of an ophthalmologist.
tal or nasal mucosal ulceration with coexisting maxillary and/or ethmoid sinusitis suggests mucormycosis or Rhizopus.
Dx: Mostly clinical. Blood and tissue fuid culture; CT scan (to rule out orbital abscess and intracranial involvement).
Tx: Admit. Immediate IV antibiotics; request an ophthalmologic/ENT consult. Abscess formation may necessitate surgery. Diabetic and immunocompromised patients should be treated with amphotericin B and surgical debride ment (often associated with cavernous sinus thrombosis) if Mucor or Rhizopus is diagnosed.
An inf ammation of the external auditory canal, also known as “swimmer’s ear.” Pseudomonas (from poorly chlorinated pools) and Enterobacteriaceae are the most common etiologic agents. Both grow in the presence of excess moisture.
Hx/PE: Presents with pain, pruritus, and possible purulent discharge. Exam reveals pain with movement of the tragus/pinna (unlike otitis media) and an edematous and erythematous ear canal. See the Pediatrics chapter for a discussion of otitis media.
Dx: A clinical diagnosis. Gram stain and culture are helpful if a fungal etiology is suspected. CT scan if the patient is toxic appearing.
Neisseria conjunctivitis is an ocular emergency often requiring inpatient parenteral antibiotic therapy.
Diabetics are at risk for malignant otitis externa.■ Tx: Antibiotic and steroid eardrops. Use systemic antibiotics in patients with severe disease. Diabetics are at risk for malignant otitis externa and osteomyelitis of the skull base and thus require hospitalization and IV antibiotics.
pain with movement of the tragus/pinna.Infection of the endocardium, usually 2° to bacterial or other infectious causes. Most commonly affects the heart valves, especially the mitral valve. Risk factors include rheumatic, congenital, or valvular heart disease; prosthetic heart valves; IV drug abuse; and immunosuppression. Etiologies are as follows:
S. aureus (both methicillin-sensitive and methicillin-resistant): The causative agent in > 80% of cases of acute bacterial endocarditis in patients with a history of IV drug abuse.
Viridans streptococci: The most common pathogens for left-sided sub-acute bacterial endocarditis.
Coagulase-Staphylococcus: The most common infecting organism in prosthetic valve endocarditis.
Streptococcus bovis: S. bovis endocarditis is associated with coexisting GI malignancy.
Candida and Aspergillus species: Account for most cases of fungal endocarditis. Predisposing factors include long-term indwelling IV catheters, malignancy, AIDS, organ transplantation, and IV drug use. Table 2.8-10 lists the causes of endocarditis.
Constitutional symptoms are common (fever/FUO, weight loss, fatigue).Exam reveals a heart murmur. The mitral valve is more commonly affected than the aortic valve in non–IV drug users; more right-sided involvement is found in IV drug users (tricuspid valve > mitral valve > aortic valve).
Osler’s nodes (small, tender nodules on the f nger and toe pads), Janeway lesions (small peripheral hemorrhages; see Figure 2.8-15), splinter hemorrhages (subungual petechiae; see Figure 2.8-16), Roth’s spots (retinal hemorrhages), focal neurologic defcits from embolic stroke, and other embolic phenomena are also seen.
TABLE 2.8-10.  Causes of EndocarditisS. aureus (IV drug abuse) S. pneumoniae N. gonorrhoeae Viridans streptococci (native valve) Enterococcus S. epidermidis (prosthetic valve) S. bovis (GI insult) Fungi Cancer (poor prognosis). Mets seed valves; emboli can cause cerebral infarcts. Haemophilus parainfl uenzae Actinobacillus Cardiobacterium Eikenella Kingella Coxiella burnetii Brucella Bartonella Libman-Sacks endocarditis (autoantibody to valve)
FIGURE 2.8-15.  Janeway lesions.Peripheral embolization to the sole leads to a cluster of erythematous macules known as Janeway lesions. (Courtesy of the Department of Dermatology, Wilford Hall USAF Medical Center and Brooke Army Medical Center, San Antonio, TX, as published in Knoop KJ et al. Atlas of Emergency Medicine, 2nd ed. New York: McGraw-Hill, 2002: 384.)
Diagnosis is guided by risk factors, clinical symptoms, and the Duke criteria (see Table 2.8-11).
CBC with leukocytosis and left shift; ↑ ESR and CRP.
■Early empiric IV antibiotic treatment includes vancomycin or nafcillin + gentamicin. Ampicillin/sulbactam or ceftriaxone are alternative choices depending on the suspected organism. Tailor antibiotics once the causative agent is known. Acute valve replacement is sometimes necessary. The
FIGURE 2.8-16.  Splinter hemorrhages.Note the splinter hemorrhages along the distal aspect of the nail plate, due to emboli from sub-acute bacterial endocarditis. (Courtesy of the Armed Forces Institute of Pathology, Bethesda, MD, as published in Knoop KJ et al. Atlas of Emergency Medicine, 2nd ed. New York: McGraw-Hill, 2002: 384.)
T AB LE 2.8-1 1. Duke Criteria for the Diagnosis of Endocarditis
Endocarditis: indications for surgery—Suppurative local complications with conduction abnormalitiesResection of mycotic aneurysmIneffective antimicrobial therapy (e.g., vs. fungi)The anthrax-associated pruritic papule forms an ulcer with an edematous halo and then a black eschar.
At least two separate blood cultures for a typical organism, persistent bacteremia with any organism, or a single culture of Coxiella burnetii. Evidence of endocardial involvement (via transesophageal echocardiography or new murmur).
Predisposing risk factors. Fever ≥ 38.3°C. Vascular phenomena: Septic emboli, septic infarcts, mycotic aneurysm,
Janeway lesions. Immunologic phenomena: Glomerulonephritis, Osler’s nodes. Roth’s spots. Microbiological evidence that does not meet major criteria.
prognosis for prosthetic valve endocarditis is poor. See the mnemonic PUS RIVER for indications for surgery.
■Give antibiotic prophylaxis before dental work in patients with high-risk valvular disease (e.g., those with previous endocarditis or a prosthetic valve).
Caused by the spore-forming gram-bacterium Bacillus anthracis. Its natural incidence is rare, but infection is an occupational hazard for veterinarians, farmers, and individuals who handle animal wool, hair, hides, or bone meal products. Also a biological weapon. B. anthracis can cause cutaneous (most common), inhalation (most deadly), or GI anthrax.
Cutaneous: Presents 1–7 days after skin exposure and penetration of spores. The lesion begins as a pruritic papule that enlarges to form an ulcer surrounded by a satellite bulbus/lesion with an edematous halo and a round, regular, and raised edge. Regional lymphadenopathy is also characteristic. The lesion evolves into a black eschar within 7–10 days.
Inhalational: Presents with fever, dyspnea, hypoxia, hypotension, or symptoms of pneumonia (1–3 days after exposure), classically due to hemorrhagic mediastinitis.
GI: Occurs after the ingestion of poorly cooked, contaminated meat; can present with dysphagia, nausea/vomiting, bloody diarrhea, and abdominal pain.
CXR is the most sensitive test for inhalational disease (widened mediastinum, pleural effusions, infltrates). Aerobic culture and Gram stain of ulcer exudate show nonmotile short chains of bacilli. Antibody tests are also useful in confrming the diagnosis.
■ Ciprof oxacin or doxycycline plus one or two additional antibiotics for at least 14 days are frst-line therapy for inhalational disease or cutaneous disease of the face, head, or neck. Many strains express β-lactamases that confer resistance to penicillin; therefore, penicillin and amoxicillin are no longer recommended as single agents for inhalational disease.
■For cutaneous disease, treat for 7–10 days. Postexposure prophylaxis (ciprof oxacin) to prevent inhalation anthrax should be continued for 60 days.
Bone or bone marrow infection 2° to direct spread from a soft tissue infection (80% of cases) is most common in adults, whereas infection due to hematogenous seeding (20% of cases) is more common in children (metaphyses of the long bones) and IV drug users (vertebral bodies). Common pathogens are outlined in Table 2.8-12.
Presents with localized bone pain and tenderness along with warmth, swelling, erythema, and limited motion of the adjacent joint. Systemic symptoms (fevers, chills) and purulent drainage may be present.
Labs: ↑ WBC count, ESR (> 100), and CRP levels. Blood cultures may be .
X-rays are often  initially but may show periosteal elevation within 10–14 days. Bone scans are also used and are sensitive for osteomyelitis but lack specif city.
MRI (test of choice) will show ↑ signal in the bone marrow and associated soft tissue infection.
Defnitive diagnosis is made by bone aspiration with Gram stain and culture. Clinical diagnosis made by probing through the soft tissue to bone is usually suffcient, as aspiration carries a risk of infection.
T AB LE 2.8-1 2. Common Pathogens in OsteomyelitisPenicillin and amoxicillin are no longer recommended as single agents for the treatment of disseminated anthrax. Treat with ciprofl oxacin plus one or two other antibiotics.
Osteomyelitis is associated with peripheral vascular disease, diabetes, penetrating soft tissue injuries, chronic decubitus ulcers, and IV drug abuse.
Most people S. aureus IV drug user S. aureus or Pseudomonas Sickle cell disease Salmonella Hip replacement S. epidermidis Foot puncture wound Pseudomonas Chronic S. aureus, Pseudomonas, Enterobacteriaceae Diabetic Polymicrobial, Pseudomonas, S. aureus, streptococci, anaerobes
Diabetic osteomyelitis should be treated with antibiotics targeting gramorganisms and anaerobes.
Surgical debridement of necrotic, infected bone followed by IV antibiotics × 4–6 weeks. Empiric antibiotic selection is based on the suspected organism and Gram stain.
Consider clindamycin + ciprofoxacin, ampicillin/sulbactam, or oxacillin/ nafcillin (for methicillin-sensitive S. aureus); vancomycin (for MRSA); or ceftriaxone or ciprofoxacin (for gram-bacteria).
Chronic osteomyelitis, sepsis, septic arthritis. Long-standing chronic osteomyelitis with a draining sinus tract may eventually lead to squamous cell carcinoma (Marjolin’s ulcer).
Table 2.9-1 outlines the presentation and treatment of orthopedic injuries that commonly affect adults.
Volkmann’s contracture of the wrist and f ngers is caused by compartment syndrome due to supracondylar fractures.
Phalen’s maneuver: placing the wrists in f exion reproduces aching and numbness in < 60 seconds.
Tinel’s sign: tapping over the median nerve at the wrist elicits tingling in the median nerve distribution.
■↑pressure within a confined space that compromises nerve, muscle, and soft tissue perfusion. Occurs primarily in the anterior compartment of the lower leg and forearm 2° to trauma (fracture or muscle injury) to the affected compartment.
Hx/PE: Presents with pain out of proportion to physical findings; pain with passive motion of the fingers and toes; and paresthesias, pallor, poikilothermia, pulselessness, and paralysis. Pulselessness occurs late.
Dx: Measure compartment pressures (usually ≥ 30 mmHg); measure delta pressures (diastolic pressure – compartment pressure).
Tx: Immediate fasciotomy to ↓ pressures and ↑ tissue perfusion.
Entrapment of the median nerve at the wrist caused by ↓ size or space of the carpal tunnel, leading to paresthesias, pain, and occasionally paralysis. Can be precipitated by overuse of wrist flexors, diabetes mellitus, or thyroid dysfunction. Commonly occurs in pregnant and middle-aged women.
Presents with aching over the thenar area of the hand and proximal forearm. Pain may extend to the shoulder.
Paresthesia or numbness is seen in a median nerve distribution.
Symptoms worsen at night or when the wrists are held in flexion or extension.
Patients may report frequently dropping objects or inability to open jars.
Exam shows thenar atrophy (if CTS is long-standing).Phalen’s maneuver and Tinel’s sign are .A clinical diagnosis, although EMG testing can be used to confirm.
Splint the wrist in a neutral position at night and during the day if possible. Administer NSAIDs.
Conservative treatment can include corticosteroid injection of the carpal canal.
Work-related CTS may benefit from ergonomic aids.CTS of pregnancy usually resolves after delivery.Surgical release of the carpal tunnel is a widely accepted treatment, particularly for fixed sensory loss, thenar weakness, or intolerable symptoms.
Permanent loss of sensation, hand strength, and fine motor skills.
T AB LE 2.9-1. Common Adult Orthopedic InjuriesShoulder dislocation Anterior dislocation: Most common; the axillary artery and nerve are at risk. Patients hold the arm in slight abduction and external rotation. Posterior dislocation: Rare; associated with seizure and electrocutions; can injure the radial artery. Patients hold the arm in adduction and internal rotation. Reduction followed by a sling and swath. Recurrent dislocations may need surgical repair. Hip dislocation Posterior dislocation: Most common (> 90%); occurs via a posteriorly directed force on an internally rotated, fexed, adducted hip (“dashboard injury”). Associated with a risk of sciatic nerve injury and avascular necrosis (AVN). Anterior dislocation: Can injure the obturator nerve. Closed reduction followed by abduction pillow/ bracing. Evaluate with CT scan after reduction. Colles’ fracture Involves the distal radius. Often results from a fall onto an outstretched hand, leading to a dorsally displaced, dorsally angulated fracture. Commonly seen in the elderly (osteoporosis) and children. Closed reduction followed by application of a long-arm cast; open reduction if the fracture is intra-articular. Scaphoid fracture The most commonly fractured carpal bone. May take two weeks for radiographs to show the fracture. Assume a fracture if there is tenderness in the anatomical snuff box. Thumb spica cast. If displacement or navicular nonunion is present, treat with open reduction. With proximal third scaphoid fractures, AVN may result from disruption of blood f ow. Boxer’s fracture Fracture of the ffth metacarpal neck. Due to forward trauma of a closed fst (e.g., punching a wall). Closed reduction and ulnar gutter splint; percutaneous pinning if the fracture is excessively angulated. If skin is broken, assume infection by human oral pathogens and treat with surgical irrigation, debridement, and IV antibiotics (covering Eikenella). Humerus fracture Direct trauma. May have radial nerve palsy leading to wrist drop and loss of thumb abduction (see Figure 2.9-1). Hanging-arm cast vs. coaptation splint and sling. Functional bracing. “Nightstick fracture” Ulnar shaft fracture resulting from self-defense with the arm against a blunt object. Open reduction and internal fxation (ORIF) if signif cantly displaced. Monteggia’s fracture Diaphyseal fracture of the proximal ulna with subluxation of the radial head. ORIF of the shaft fracture (due to poor fracture diaphyseal blood supply) and closed reduction of the radial head.
T AB LE 2.9-1. Common Adult Orthopedic Injuries (continued)Femoral fracture Direct trauma. Beware of fat emboli, which present with fever, change in mental status, dyspnea, hypoxia, petechiae, and ↓ platelets. Intramedullary nailing of the femur. Irrigate and debride open fractures. Tibial fracture Direct trauma. Watch for compartment syndrome. Casting vs. intramedullary nailing. Open fractures An orthopedic emergency; patients must be taken to the OR in < 6 hours owing to ↑ infection risk. OR emergently to repair fracture. Treat with antibiotics and tetanus prophylaxis. Achilles tendon rupture Presents with a sudden “pop” like a rif e shot. More likely with ↓ physical conditioning. Exam shows limited plantar f exion and a  Thompson’s test (pressure on the gastrocnemius leading to absent foot plantar f exion). Treat surgically followed by long leg cast for six weeks. Knee injuries
Diaphyseal fracture of the radius with dislocation of the distal radioulnar joint. Results from a direct blow to the radius. ORIF of the radius and casting of the fractured forearm in supination to reduce the distal radioulnar joint.
↑ risk with osteoporosis. Presents with a shortened and externally rotated leg.
Displaced femoral neck fractures: Associated with an ↑ risk of AVN, nonunion, and DVTs.
Present with knee instability, edema, and hematoma.Results from a noncontact twisting mechanism, forced hyperextension, or impact to an extended knee.
anterior drawer and Lachman tests.Rule out a meniscal or MCL injury.Results from forced hyperextension.posterior drawer test.Meniscal tears:Result from an acute twisting injury or a degenerative tear in elderly patients.
Clicking or locking may be present.Exam shows joint line tenderness and a McMurray’s test.ORIF with parallel pinning of the femoral neck. Displaced fractures in elderly patients may require a hip hemiarthroplasty.
Anticoagulate to ↓ the likelihood of DVTs.Treatment of MCL/LCL and meniscal tears is usually conservative.Treatment of ACL injuries is generally surgical with graft from the patellar or hamstring tendons.
Operative PCL repair is reserved for highly competitive athletes.Operative meniscal repair is for younger patients with signifcant tears or older patients whose symptoms do not respond to conservative treatment.
F IGU R E 2.9-1. Lateral condyle fracture of the humerus.
(Reproduced, with permission, from Skinner HB. Current Diagnosis & Treatment in Orthopedics, 2nd ed. Stamford, CT: Appleton & Lange, 2000: 572.)
Inf ammation of the bursa by repetitive use, trauma, infection, or systemic inf ammatory disease. A bursa is a fl attened sac filled with a small amount of synovial fluid that serves as a protective buffer between bones and overlapping muscles. Common sites of bursitis include subacromial, olecranon, trochanteric, prepatellar, and infrapatellar bursae. Septic bursitis is more common in superficial bursae (olecranon, prepatellar, and infrapatellar bursae).
Presents with localized tenderness, ↓ range of motion (ROM), edema, and erythema; patients may have a history of trauma or infl ammatory disease.
Needle aspiration is indicated if septic bursitis is suspected; no labs or imaging is needed.
Conservative treatment includes rest, heat and ice, elevation, and NSAIDs.
Intrabursal corticosteroid injection can be considered (contraindicated if septic bursitis is suspected).
Septic bursitis should be treated with 7–10 days of antibiotics.
Oral f uoroquinolones areAn inf ammatory condition characterized by pain at tendinous insertions associated with an ↑ risk of into bone associated with swelling or impaired function. It commonly occurs tendon rupture and tendinitis.
Most lower back pain is mechanical; bed rest is contraindicated.
Red f ags for lower back pain include age > 50, > 6 weeks of pain, previous cancer history, severe pain, constitutional symptoms, and loss of anal sphincter tone.
in the supraspinatus, biceps, wrist extensor, patellar, iliotibial band, posterior tibial, and Achilles tendons. Overuse is the most common cause and includes work-related activities or an ↑ in activity level.
Presents with pain at a tendinous insertion that worsens with repetitive stress and resisted strength testing of the affected muscle group.
Wrist flexor tendinitis (lateral epicondylitis, or tennis elbow) worsens with resisted dorsiflexion of the wrist.
A clinical diagnosis. Consider a radiograph if there is a history of trauma.
Treat with rest and NSAIDs; apply ice for the first 24–48 hours.
Consider splinting or immobilization.Begin strengthening exercises once pain has subsided.If conservative treatment fails, consider peritendinous injection of lidocaine and corticosteroids. Never inject the Achilles tendon in view of the ↑ risk of rupture. Avoid repetitive injection.
Table 2.9-2 outlines the motor, reflex, and sensory deficits with which low back pain is associated.
Causes include degenerative changes, trauma, or neck/back strain or sprain. Most common (95%) in the lumbar region, especially at L4–L5 and L5–S1.
Presents with sudden onset of severe, electricity-like LBP, usually preceded by several months of aching, “discogenic” pain.
Common among middle-aged and older men.Exacerbated by ↑ intra-abdominal pressure or Valsalva (e.g., coughing).Associated with sciatica, paresthesias, muscle weakness, atrophy, contractions, or spasms.
T AB LE 2.9-2. Motor and Sensory Deficits in Back Pain
L4 L5 S1 Foot dorsifexion (tibialis anterior) Patellar Medial aspect of the lower leg. Big toe dorsifexion (extensor hallucis longus), foot eversion (peroneus muscles) None Dorsum of the foot and lateral aspect of the lower leg. Plantar fexion (gastrocnemius/soleus), hip extension (gluteus maximus). Achilles Plantar and lateral aspects of the foot.
A passive straight leg raise ↑pain (highly sensitive but not specific).
A crossed straight leg raise ↑ pain (highly specific but not sensitive). Large midline herniations can cause cauda equina syndrome.
Obtain an ESR and a plain radiograph if other causes of back pain are suspected (e.g., infection, trauma, compression fracture).
Order a stat MRI for cauda equina syndrome or for a severe or rapidly progressing neurologic deficit.
Order an MRI if symptoms are refractory to conservative management. MRI may show disk herniation (see Figure 2.9-2).
NSAIDs in scheduled doses, physical therapy, and local heat lead to resolution within four weeks in 80% of cases.
Epidural or nerve block may be of benefit.Severe or rapidly evolving neurologic deficits and cauda equina syndrome are indications for discectomy.
Narrowing of the lumbar or cervical spinal canal, leading to compression of the nerve roots. Most commonly due to degenerative joint disease; typically occurs in middle-aged or elderly patients.
■Presents with neck pain, back pain that radiates to the buttocks and legs, and leg numbness/weakness.
Lung, breast, and prostate cancer can metastasize to the vertebrae and cause back pain.
Bowel or bladder dysfunction (urinary overf ow incontinence), impotence, and saddle-area anesthesia are consistent with cauda equina syndrome, which is a surgical emergency.
FIGURE 2.9-2.  Disk herniation.MRI reveals herniations of L4–L5 and L5–S1. (Reproduced, with permission, from Skinner HB. Current Diagnosis & Treatment in Orthopedics, 1st ed. Stamford, CT: Appleton & Lange, 1995: 186.)
The most common benign bone tumor is osteochondroma.Leg cramping is worse at rest, with standing, and with walking (pseudoor neurogenic claudication).
Symptoms improve with fexion at the hips and bending forward.
Radiographs show degenerative changes that include disk space narrowing, facet hypertrophy, and spondylolisthesis, leading to a narrowed spinal canal.
MRI or CT shows spinal stenosis.Mild to moderate: NSAIDs and abdominal muscle strengthening.Advanced: Epidural corticosteroid injections can provide relief.Refractory: Surgical laminectomy may achieve significant short-term success, but many patients will have a recurrence of symptoms.
The second most common 1° malignant tumor of bone (after multiple myeloma). Tends to occur in the metaphyseal regions of the distal femur, proximal tibia, and proximal humerus; often metastasizes to the lungs. Some cases are preceded by Paget’s disease. Risk factors include male gender and age 20– 30.
Presents as progressive and eventually intractable pain that is worse at night.
Constitutional symptoms such as fever, weight loss, and night sweats may be present.
Erythema and enlargement over the site of the tumor may be seen.
See the Endocrinology chapter for a discussion of osteosarcoma vs. Paget’s disease.
Radiographs show Codman’s triangle (periosteal new bone formation at the diaphyseal end of the lesion) or a “sunburst pattern” of the osteosarcoma (see Figure 2.9-3)—in contrast to multilayered “onion skinning,” which is classic for Ewing’s sarcoma.
MRI and CT facilitate staging (soft tissue and bony invasion) and planning for surgery.
Limb-sparing surgical procedures and preand postoperative chemotherapy (e.g., methotrexate, doxorubicin, cisplatin, ifosfamide).
Amputation may be necessary.A common, chronic, noninfl ammatory arthritis of the synovial joints. Characterized by deterioration of the articular cartilage and osteophyte bone formation at the joint surfaces. Risk factors include a  family history, obesity, and a history of joint trauma.
FIGURE 2.9-3.  Osteosarcoma.“Sunburst” appearance of neoplastic bone formation in the femur of a 15-year-old girl. Amputation was required owing to the size of the tumor. (Reproduced, with permission, from Skinner HB. Current Diagnosis & Treatment in Orthopedics, 2nd ed. Stamford, CT: Appleton & Lange, 2000: 272.)
Presents with crepitus, ↓ ROM, and initially pain that worsens with activity and weight bearing but improves with rest. Morning stiffness lasts for < 30 minutes. Stiffness is also experienced after periods of rest (“gelling”).
Radiographs show joint space narrowing, osteophytes, subchondral sclerosis, and subchondral bone cysts (see Figure 2.9-4). Radiograph severity does not correlate with symptomatology.
Synovial fluid shows straw-colored fluid, normal viscosity, and a WBC count < 2000 cells/μL.
Physical therapy, weight reduction, and NSAIDs. Intra-articular corticosteroid injections may provide temporary relief. Consider joint replacement (e.g., total hip/knee arthroplasty) in advanced cases.
FIGURE 2.9-4.  Osteoarthritis.Plain radiographs show joint space narrowing, osteophytes, and subchondral degenerative cysts involving the DIP and PIP joints, with sparing of the MCP. (Reproduced, with permission, from USMLERx.com.)
A pain syndrome accompanied by loss of function and autonomic dysfunction, usually occurring after trauma. Formerly known as refl ex sympathetic dystrophy. The disease has three phases: acute sympathetic denervation and underactivity → dystrophic phase → atrophic phase.
Diffuse pain occurs out of proportion to the initial injury, often in a nonanatomic distribution.
Pain can occur at any time relative to the initial injury.
Loss of function of the affected limb is seen.Sympathetic dysfunction occurs and may be documented by skin, soft tissue, or blood fl ow changes.
Skin temperature, hair growth, and nail growth may ↑ or ↓. Edema may be present.
A clinical diagnosis, but objective evidence of changes in skin temperature, hair growth, or nail growth may be present.
Medications include NSAIDs, corticosteroids, low-dose TCAs, gabapentin, pregabalin, and calcitonin (no oral medications are consistently effective).
Physical therapy modalities such as heat, ice, desensitization techniques, and gentle ROM exercises may be helpful.
Chemical sympathetic blockade may relieve symptoms.Referral to a chronic pain specialist is appropriate for complicated cases.
A centrally mediated chronic pain disorder characterized by soft tissue and axial skeletal pain in the absence of joint pain. Inflammation is notably absent.
Hx/PE: Most common in women 30–50 years of age; associated with depression, anxiety, sleep disorders, IBS, and cognitive disorders (“fibro fog”).
Dx: Multiple (≥ 11 of 18), diffuse tender points over all four body quadrants and the axial skeleton must be present for diagnosis (see Figure 2.9-5). The presence of < 11 of 18 tender points or non-fibromyalgiaassociated tender points is known as myofascial pain syndrome.
Tx: Antidepressants (an SSRI/TCA combination has proven efficacy), gabapentin, pregabalin, muscle relaxants, and physical therapy (stretching, heat application, hydrotherapy). Avoid narcotics.
Recurrent attacks of acute monoarticular arthritis resulting from intra-articular deposition of monosodium urate crystals due to disorders of urate metabolism. Risk factors include male gender, obesity, and postmenopausal status in females.
■Presents with excruciating joint pain of sudden onset that can awaken the patient from sleep.
F IGU R E 2.9-5. Tender points characteristic of fibromyalgia.
Gout crystals appear yeLLow when paraLLel to the condenser.Causes of hyperuricemia: ↑ cell turnover (hemolysis, blast crisis, tumor lysis, myelodysplasia, psoriasis)
Cyclosporine Dehydration Diabetes insipidus Diet (e.g., ↑ red meat,Colchicine inhibits neutrophil chemotaxis and is most effective when used early during a gout f are (use is limited by a narrow therapeutic window).
Most commonly affects the frst MTP joint (podagra) and the midfoot, knees, ankles, and wrists; the hips and shoulders are generally spared.
Joints are erythematous, swollen, and exquisitely tender.Tophi (urate crystal deposits in soft tissue) may be seen with chronic disease.
Joint fluid aspirate shows needle-shaped, negatively birefringent crystals (see Table 2.9-3 and Clinical Images).
An elevated WBC count in the joint aspirate or peripheral blood may be seen during fl ares.
Serum uric acid is usually ↑ (≥ 7.5), but patients may have normal levels.
Punched-out erosions with overhanging cortical bone (“rat-bite” erosions) are seen in advanced gout.
Acute attacks: High-dose NSAIDs (e.g., indomethacin), colchicine, and/ or steroids.
Maintenance therapy: Allopurinol for overproducers, those with contraindications to probenecid treatment (tophi, renal stones, chronic renal failure), and refractory cases; probenecid for undersecretors.
Weight loss and avoidance of triggers of hyperuricemia will prevent recurrent attacks in many patients.
A chronic inflammatory disease of the spine and pelvis that causes sacroiliitis leading to fusion of the affected joints. Strongly associated with HLA-B27. Risk factors include male gender and a  family history.
Typical onset is in the late teens and early 20s. Presents with fatigue, intermittent hip pain, and LBP that worsens with inactivity and in the mornings.
■↓ spine fl exion ( Schober test), loss of lumbar lordosis, hip pain and stiffness, and ↓ chest expansion are seen as the disease progresses.
Anterior uveitis and heart block may occur.Other forms of seronegative spondyloarthropathy must be ruled out, including the following:
Reactive arthritis (formerly known as Reiter’s syndrome): A disease of young men. The characteristic arthritis, uveitis, conjunctivitis, and urethritis usually follow an infection with Campylobacter, Shigella, Salmonella, Chlamydia, or Ureaplasma.
Psoriatic arthritis: An oligoarthritis that can include the DIP joints.
TABLE 2.9-3. Gout vs. PseudogoutAssociated with psoriatic skin changes and sausage-shaped digits (dactylitis).■Enteropathic spondylitis: An ankylosing spondylitis–like disease characterized by sacroiliitis that is usually asymmetric and is associated with IBD.
HLA-B27 is found in 85–95% of cases.Radiographs may show fused sacroiliac joints, squaring of the lumbar vertebrae, development of vertical syndesmophytes, and bamboo spine.
ESR or CRP is ↑ in 75% of cases.RF; ANA.NSAIDs (e.g., indomethacin) for pain; exercise to improve posture and breathing.
Tumor necrosis factor (TNF) inhibitors or sulfasalazine can be used in refractory cases.
Polymyositis is a progressive, systemic connective tissue disease characterized by immune-mediated striated muscle infl ammation. Dermatomyositis presents with symptoms of polymyositis plus cutaneous involvement, although the pathogenesis is different. Most often affect patients 50–70 years of age; the male-to-female ratio is 1:2. African-Americans are affected more often than Caucasians.
Distinguished as follows:Polymyositis: Presents with symmetric, progressive proximal muscle weakness, pain, and difficulty breathing or swallowing (advanced disease).
Dermatomyositis: Patients may have heliotrope rash (a violaceous periorbital rash), “shawl sign” (a rash involving the shoulders, upper chest, and back), and/or Gottron’s papules (a papular rash with scales located on the dorsa of the hands, over bony prominences).
Patients may also develop myocarditis and cardiac conduction deficits.Can be associated with an underlying malignancy, especially lung and breast carcinoma.
■↑serum CK and anti-Jo-1 antibodies are seen (see Table 2.9-4).
■Muscle biopsy reveals inflammation and muscle fibers in varying stages of necrosis and regeneration.
High-dose corticosteroids with taper after 4–6 weeks to ↓ the maintenance dose.
Azathioprine and/or methotrexate can be used as steroid-sparing agents.T AB LE 2.9-4. Common Antibodies and Their Disease Associations
ANA SLE Anti-CCP RA Anticentromere CREST syndrome Anti-dsDNA SLE Antihistone Drug-induced SLE Anti-Jo-1 Polymyositis/dermatomyositis Antimitochondrial Primary biliary cirrhosis Anti-Scl-70 Scleroderma Anti-Sm SLE Anti-TSHR Graves’ disease c-ANCA Vasculitis, especially Wegener’s p-ANCA Vasculitis, microscopic polyangiitis Rheumatoid factor RA U1RNP antibody Mixed connective tissue disease
Sjren’s syndrome (keratoconjunctivitis sicca) is a common ocular manifestation of rheumatoid arthritis.
Felty’s syndrome is characterized by rheumatoid arthritis, splenomegaly, and neutropenia.
A systemic autoimmune disorder characterized by chronic, destructive, inflammatory arthritis with symmetric involvement of both large and small joints that results in synovial hypertrophy and pannus formation, ultimately leading to erosion of adjacent cartilage, bone, and tendons. Risk factors include female gender, age 35–50, and HLA-DR4.
Presents with insidious onset of morning stiffness for > 1 hour along with painful, warm swelling of multiple symmetric joints (wrists, MCP joints, ankles, knees, shoulders, hips, and elbows) for > 6 weeks.
Fever, fatigue, malaise, anorexia, and weight loss may also be seen.
Ulnar deviation of the fingers is seen with MCP joint hypertrophy (see Figure 2.9-6).
Also presents with ligament and tendon deformations (e.g., swan-neck and boutonnière deformities), vasculitis, atlantoaxial subluxation (intubation risk), and keratoconjunctivitis sicca.
F IGU R E 2.9-6. Rheumatoid arthritis.Note the boutonnière deformities of the digits, ulnar deviation of the fingers, MCP joint hyper trophy, and severe involvement of the PIP joints. (Reproduced, with permission, from Chan drasoma P. Concise Pathology, 3rd ed. Stamford, CT: Appleton & Lange, 1998: 978.)
Labs: ■↑RF (IgM antibodies against Fc IgG) is seen in > 75% of cases.
The presence of anti-CCP (cyclic citrullinated peptide) is more spe cific than RF. ■↑ ESR may also be seen.
Anemia of chronic disease.Synovial fluid aspirate shows turbid fl uid, ↓ viscosity, and an ↑ WBC count (3000–50,000 cells/μL).
Early: Soft tissue swelling and juxta-articular demineralization.Late: Joint space narrowing and erosions.NSAIDs (can be reduced or discontinued following successful treatment with disease-modifying antirheumatic drugs [DMARDs]).
DMARDs should be started early and include hydroxychloroquine, sulfasalazine, and methotrexate. Second-line agents include TNF inhibitors, rituximab (anti-CD20), and lefl unomide.
Also called systemic sclerosis; characterized by inflammation that leads to progressive tissue fibrosis through excessive deposition of type I and type III collagen. Commonly manifests as CREST syndrome (limited form), but can also occur in a diffuse form involving the skin as well as the GI, GU, renal, pulmonary, and cardiovascular systems. Risk factors include female gender and age 35–50.
Exam may reveal symmetric thickening of the skin of face and/or distal extremities.
CREST syndrome involves Calcinosis, Raynaud’s phenomenon, Esophageal dysmotility, Sclerodactyly, and Telangiectasias.
(lupus cerebritis,Libman-Sacks endocarditis: noninfectious vegetations often seen on the mitral valve in association with SLE and antiphospholipid syndrome.
■The diffuse form can lead to pulmonary f brosis, cor pulmonale, acute renal failure, and malignant hypertension.
RF and ANA may be .Anticentromere antibodies are specific for CREST syndrome (see Table 2.9-4).
Anti-Scl-70 (antitopoisomerase 1) antibodies are associated with diffuse disease and a poor prognosis (see Table 2.9-4).
Eosinophilia may be seen.Corticosteroids for acute flares; penicillamine can be used for skin changes.
Calcium channel blockers for Raynaud’s phenomenon.ACEIs for renal disease and prevention of a scleroderma renal crisis.
Mortality is due to pulmonary hypertension and complications of pulmonary hypertension.
A multisystem autoimmune disorder related to antibody-mediated cellular attack and deposition of antigen-antibody complexes. African-American women are at highest risk. Usually affects women of childbearing age.
Presents with nonspecific symptoms such as fever, anorexia, weight loss, and symmetric joint pain.
The mnemonic DOPAMINE RASH summarizes the criteria for diagnosing SLE (see also Figure 2.9-7 and Clinical Images). Patients with four of the criteria are likely to have SLE (96% sensitive and specific).
A  ANA is highly sensitive but not specific. Anti-dsDNA and anti-Sm antibodies are highly specific but not as sensitive (see Table 2.9-4).
Drug-induced SLE: antihistone antibodies are seen in 100% of cases but are nonspecific.
Neonatal SLE: Associated with  anti-Ro antibodies transmitted from mother to neonate.
The following may also be seen:Antiphospholipid antibodies.Anemia, leukopenia, and/or thrombocytopenia.Proteinuria and/or casts.NSAIDs for mild joint symptoms.Corticosteroids for acute exacerbations.Corticosteroids, hydroxychloroquine, cyclophosphamide, and azathioprine for progressive or refractory cases.
F IGU R E 2.9-7. Systemic lupus erythematosus.Erythematous patches and plaques of SLE, predominantly in sun-exposed areas. Note the malar rash across the bridge of the nose. (Reproduced, with permission, from Hurwitz RM. Pathology of the Skin: Atlas of Clinical-Pathological Correlation, 2nd ed. Stamford, CT: Appleton & Lange, 1998: 39.)
Also called giant cell arteritis; due to subacute granulomatous infl ammation of the large vessels, including the aorta, external carotid (especially the temporal branch), and vertebral arteries. The most feared manifestation is blindness 2° to occlusion of the central retinal artery (a branch of the internal carotid artery). Risk factors include polymyalgia rheumatica (affects almost half of TA patients), age > 50, and female gender.
Presents with new headache (unilateral or bilateral); scalp pain and temporal tenderness; and jaw claudication.
Fever, permanent monocular blindness, weight loss, and myalgias/arthralgias (especially of the shoulders and hips) are also seen.
ESR > 50 (usually > 100).Ophthalmologic evaluation.Temporal artery biopsy: Look for thrombosis; necrosis of the media; and lymphocytes, plasma cells, and giant cells.
High-dose prednisone begun immediately to prevent ocular involvement (or involvement of the remaining eye after onset of monocular blindness). Obtain a biopsy, but do not delay treatment. Conduct a follow-up eye exam.
Risk factors include female gender and age > 50.Presents with pain and stiffness of the shoulder and pelvic girdle musculature with difficulty getting out of a chair or lifting the arms above the head.
Other symptoms include fever, malaise, and weight loss. Weakness is generally not appreciated on exam.
Dx: Labs reveal a markedly ↑ESR, often associated with anemia.
Tx: Low-dose prednisone (10–20 mg/day).Table 2.9-5 outlines the presentation and treatment of common pediatric orthopedic injuries.
An X-linked recessive disorder resulting from a deficiency of dystrophin, a cytoskeletal protein. Onset is usually at 3–5 years of age.
Affects axial and proximal muscles more than distal muscles.May present with progressive clumsiness, fatigability, difficulty standing or walking, difficulty walking on toes (gastrocnemius shortening), Gowers’ maneuver (using the hands to push off the thighs when rising from the floor), and waddling gait.
Pseudohypertrophy of the gastrocnemius muscles is also seen.Mental retardation is common.Table 2.9-6 outlines the differential diagnosis of DMD and Becker muscular dystrophy.
dystrophin immunostain; ↑ CK.EMG shows polyphasic potentials and ↑ recruitment.Muscle biopsy shows necrotic muscle fibers from degeneration and variation in fiber size with fibrosis from regeneration.
Physical therapy is necessary to maintain ambulation and to prevent contractures.
Liberal use of tendon release surgery may prolong ambulation.Mortality is due to pulmonary congestion caused by high-output cardiac failure; cardiac fibrosis → arrhythmias and weak skeletal muscles → cardiopulmonary complications → pneumonia and respiratory failure.
T AB LE 2.9-5. Orthopedic Injuries in ChildrenClavicular fracture The most commonly fractured long bone in children. May be birth related (especially in large infants) and can be associated with brachial nerve palsies. Usually involves the middle third of the clavicle, with the proximal fracture end displaced superiorly owing to the pull of the sternocleidomastoid. Figure-of-eight sling vs. arm sling. Greenstick fracture Incomplete fracture involving the cortex of only one side of the bone. Reduction with casting. Order flms at 10–14 days. Nursemaid’s elbow Radial head subluxation that typically occurs as a result of being pulled or lifted by the hand. Presents with pain and refusal to bend the elbow. Manual reduction by gentle supination of the elbow at 90 degrees of f exion. No immobilization. Torus fracture Buckling of the cortex of a long bone 2° to trauma. Usually occurs in the distal radius or ulna. Cast immobilization for 3–5 weeks. Supracondylar humerus fracture Tends to occur at 5–8 years of age. Proximity to the brachial artery ↑ the risk of Volkmann’s contracture (results from compartment syndrome of the forearm). Cast immobilization; closed reduction with percutaneous pinning if signif cantly displaced. Osgood-Schlatter disease Overuse apophysitis of the tibial tubercle. Causes localized pain, especially with quadriceps contraction, in active young boys. ↓ activity for 2–3 months or until asymptomatic. A neoprene brace may provide symptomatic relief. Salter-Harris fracture Fractures of the growth plate in children. Classifed by fracture location: ■ I: Physis (growth plate). ■ II: Metaphysis and physis. ■ III: Epiphysis and physis. ■ IV: Epiphysis, metaphysis, and physis. ■ V: Crush injury of the physis. Types I and II: Conservative. Types III–V: Surgical repair to prevent complications such as leg length inequality.
Developmental Dysplasia of the HipAlso called congenital hip dislocation; can result in subluxed, dislocatable, or dislocated femoral heads, leading to early degenerative joint disease of the hips. Dislocations result from poor development of the acetabulum and hip due to lax musculature and from excessive uterine packing in the fl exed and adducted position (e.g., breech presentation), leading to excessive stretching of the posterior hip capsule and adductor muscle contracture.
T AB LE 2.9-6. DMD vs. Becker Muscular DystrophyOnset 3–5 years. 5–15 years and beyond. Life expectancy Teens. 30s–40s. Mental retardation Common. Uncommon. Western blot Dystrophin is markedly ↓ or absent. Dystrophin levels are normal, but protein is abnormal.
Most commonly found in f rst-born females born in the breech position.
Barlow’s maneuver: Pressure is placed on the inner aspect of the abducted thigh, and the hip is then adducted, leading to an audible “clunk” as the femoral head dislocates posteriorly.
Ortolani’s maneuver: The thighs are gently abducted from the midline with anterior pressure on the greater trochanter. A soft click signifies reduction of the femoral head into the acetabulum.
Allis’ (Galeazzi’s) sign: The knees are at unequal heights when the hips and knees are flexed (the dislocated side is lower).
Asymmetric skin folds and limited abduction of the affected hip are also seen.
Early detection is critical to allow for proper hip development.
Ultrasound may be helpful, especially after 10 weeks of age.
Radiographs are unreliable until patients are > 4 months of age because of the radiolucency of the neonatal femoral head.
Begin treatment early.< 6 months: Splint with a Pavlik harness (maintains the hip fl exed and abducted). To prevent AVN, do not flex the hips > 60 degrees.
6–15 months: Spica cast.15–24 months: Open reduction followed by spica cast.Joint contractures and AVN of the femoral head.Without treatment, a significant defect is likely in patients < 2 years of age.
Idiopathic AVN of the femoral head (see Figure 2.9-8). Most commonly found in boys 4–10 years of age. Usually a self-limited disease, with symptoms lasting < 18 months.
F IGU R E 2.9-8  Legg-Calvé-Perthes disease.AVN of the femoral head. (Reproduced, with permission, from Skinner HB. Current Diagnosis & Treatment in Orthopedics, 2nd ed. Stamford, CT: Appleton & Lange, 2000: 543.)
Generally asymptomatic at first, but patients can develop a painless limp.
If pain is present, it can be in the groin or anterior thigh, or it may be referred to the knee.
Limited abduction and internal rotation; atrophy of the affected leg.
Usually unilateral (85–90%).Observation is sufficient if there is limited femoral head involvement or if full ROM is present.
If extensive or if there is ↓ ROM, consider bracing, hip abduction with a Petrie cast, or an osteotomy.
The prognosis is good if the patient is < 5 years of age and has full ROM, ↓ femoral head involvement, and a stable joint.
Separation of the proximal femoral epiphysis through the growth plate, leading to medial and posterior displacement of the femoral head (relative to the femoral neck). May be due to an imbalance between growth hormone and sex hormones. Risk factors include obesity, age 11–13, male gender, and African-American ethnicity. Associated with hypothyroidism and other endocrinopathies.
■Typically presents with acute or insidious thigh or knee pain and a painful limp.
Differential diagnosis of pediatric limp—Acute cases present with restricted ROM and, commonly, inability to bear weight.
Bilateral in 40–50% of cases.Characterized by limited internal rotation and abduction of the hip. Flex-ion of the hip results in an obligatory external rotation 2° to physical displacement that is observed as further loss of internal rotation with hip fl ex-ion.
Radiographs of both hips in AP and frog-leg lateral views reveal posterior and medial displacement of the femoral head (see Figure 2.9-9).
Rule out hypothyroidism with TSH.The disease is progressive, so treatment should begin promptly.No weight bearing should be allowed until the defect is surgically stabilized.
Gentle closed reduction is appropriate only in acute slips.F IGU R E 2.9-9. Slipped capital femoral epiphysis.AP x-ray. The medial displacement of the left femoral epiphysis is best seen with a line drawn up the lateral femoral neck. The abnormal epiphysis does not protrude beyond this line.
Frog-leg lateral x-ray. Posterior displacement of the femoral epiphysis is characteristic. (Reproduced, with permission, from Skinner HB. Current Diagnosis & Treatment in Orthopedics, 2nd ed. Stamford, CT: Appleton & Lange, 2000: 546.)
Chondrolysis, AVN of the femoral head, and premature hip osteoarthritis leading to hip arthroplasty.
A lateral curvature of the spine of > 10 degrees occurring in the thoracic and/or lumbar spine and associated with rotation of the vertebrae and sometimes excessive kyphosis or lordosis. Most commonly idiopathic, developing in early adolescence. Other etiologies are congenital or associated with neuromuscular, vertebral, or spinal cord disease. The male-to-female ratio is 1:7 for curves that progress and require treatment.
Idiopathic disease is usually identified during school physical screening.Vertebral and rib rotation deformities are accentuated by a forward bending test.
Radiographs of the spine (posterior, anterior, and full-length views).Close observation for < 20 degrees of curvature.Spinal bracing for 20–49 degrees of curvature. Curvature may progress even with bracing.
Surgical correction for > 50 degrees of curvature.Severe scoliosis can create restrictive lung disease.A nonmigratory, nonsuppurative monoand polyarthritis with bony destruction that occurs in patients ≤ 16 years of age and lasts > 6 weeks. Formerly known as juvenile rheumatoid arthritis. Approximately 95% of cases resolve by puberty. More common in girls than in boys.
Can be accompanied by fever, nodules, erythematous rashes, pericarditis, and fatigue.
Subtypes are as follows:Pauciarticular: An asymmetric arthritis that involves weight-bearing joints. Associated with an ↑ risk of iridocyclitis that leads to blindness if left untreated.
Polyarticular: Resembles RA with symmetric involvement of multiple (≥ 5) small joints. Systemic features are less prominent; carries a ↓ risk of iridocyclitis.
Acute febrile: The least common subtype; manifests as arthritis with daily high, spiking fevers and a maculopapular, evanescent, salmon-colored rash. Hepatosplenomegaly and serositis may also be seen. No iridocyclitis is present; remission may occur within one year. Occurs equally in girls and boys.
There is no diagnostic test for JIA.A RF is found in 15% of cases.ANA may be , especially in the pauciarticular subtype. ■↑ ESR, WBC count, and platelets.
Imaging: Soft tissue swelling and osteoporosis may be seen.NSAIDs or corticosteroids; methotrexate is second-line therapy.Disorders of the Neuromuscular Junction 300 MYASTHENIA GRAVIS 300 LAMBERT-EATON MYASTHENIC SYNDROME 301 MULTIPLE SCLEROSIS 301 GUILLAIN-BARRÉ SYNDROME 302 AMYOTROPHIC LATERAL SCLEROSIS 303
Tables 2.10-1 through 2.10-5 and Figure 2.10-1 outline critical aspects of clinical neuroanatomy, including cranial nerve functions; the clinical presentation of common facial nerve lesions; spinal cord anatomy and functions; UMN and LMN signs; and pertinent clinical refl exes.
Acute onset of focal neurologic deficits resulting from disruption of cerebral circulation. Many classifications exist, but the most common comparison involves
TABLE 2.10-1.  Cranial Nerve FunctionsStroke is the third most common cause of death and the leading cause of major disability in the United States.
Olfactory I Smell Sensory Some Optic II Sight Sensory Say Oculomotor III Eye movement, pupillary constriction, lens accommodation, eyelid opening Motor Marry Trochlear IV Eye movement Motor Money Trigeminal V Mastication, facial sensation (including orbits, sinuses, tongue, teeth, and buccal mucosa), intracranial sensation (including meninges and blood vessels) Both But Abducens VI Eye movement Motor My Facial VII Facial movement, taste from the anterior two-thirds of the tongue, lacrimation, salivation (submandibular and sublingual glands), eyelid closing Both Brother Vestibulocochlear VIII Hearing, balance Sensory Says Glossopharyngeal IX Taste from the posterior third of the tongue, oropharyngeal sensation, swallowing (stylopharyngeus), salivation (parotid gland), monitoring carotid body and sinus chemoand baroreceptors Both Big Vagus X Taste from the epiglottic region, swallowing, palatal elevation, talking, thoracoabdominal viscera, monitoring aortic arch chemoand baroreceptors. Both Brains Accessory XI Head turning, shoulder shrugging Motor Matter Hypoglossal XII Tongue movement Motor Most Adapted, with permission, from Le T, Bhushan V et al. First Aid for the USMLE Step 1 2009. New York: McGraw-Hill, 2009: 394.
TABLE 2.10-2.  Facial Nerve LesionsUMN lesion LMN lesion Bell’s palsy Lesion of the motor cortex or the connection between the cortex and the facial nucleus. Contralateral paralysis of the lower face only. Ipsilateral paralysis of the upper and lower face. Complete destruction of the facial nucleus itself or its branchial efferent fbers (facial nerve proper). Peripheral ipsilateral facial paralysis with inability to close the eye on the involved side. Can occur idiopathically; gradual recovery is seen in most cases. Seen as a complication in AIDS, Lyme disease, Sarcoidosis, Tumors, and Diabetes. ALexander Bell with STD: AIDS, Lyme, Sarcoid, Tumors, Diabetes. Adapted, with permission, from Le T, Bhushan V et al. First Aid for the USMLE Step 1 2009. New York: McGraw-Hill, 2009: 397. Upperdivision Lower division Face area of motor cortex Cortico-bulbar tract (UMN lesion = central facial) Facial nucleus LMN lesion CN VII (LMN lesion = Bell´s palsy)
TABLE 2.10-3.ischemic (80%) vs. hemorrhagic (20%). Table 2.10-6 contrasts modifiable and nonmodifiable risk factors associated with stroke. Etiologies are as follows:
Atherosclerosis of the extracranial vessels (internal/common carotid, basilar, and vertebral arteries).
Lacunar infarcts in regions supplied by perforating vessels (result from hypertension, hypercholesterolemia, or diabetes).
Cardiac or aortic emboli: Thromboemboli (AF, ventricular hypokinesis, prosthetic valves, marantic endocarditis), atheroemboli (aortic arch atherosclerosis), infectious emboli (bacterial endocarditis), paradoxical emboli (via patent foramen ovale).
Hypercoagulable states: Include those associated with antiphospholipid antibodies, activated protein C resistance, malignancy, and OCPs in the context of smoking.
Craniocervical dissection: Trauma, fibromuscular dysplasia (young females), infl ammatory/infectious diseases.
Lateral corticospinal Movement of contralateral limbs Pyramidal, at the cervicomedullary junction 1° motor cortex Fine touch, vibration, conscious proprioception Arcuate fbers at the medulla Pacini’s and Meissner’s tactile disks, muscle spindles, and Golgi tendon organs Pain, temperature Ventral white commissure at spinal cord level Free nerve endings, pain f bers Dorsal column medial lemniscus Spinothalamic
Adapted, with permission, from Le T, Bhushan V et al. First Aid for the USMLE Step 1 2009. New York: McGraw-Hill, 2009: 105.
TABLE 2.10-4. UMN vs. LMN SignsPattern of weakness Pyramidal (arm extensors, leg f exors) Variable Tone Spastic (↑); initially f accid (↓) Flaccid (↓) DTRs ↑ (initially ↓ or normal) ↓Miscellaneous signs Babinski’s, other CNS signs Atrophy, fasciculations ■ Other causes: Venous sinus thrombosis, sickle cell anemia, vasculitis (e.g., giant cell arteritis).
Symptoms are dependent on the vascular territory affected:Middle cerebral artery (MCA): Aphasia (dominant hemisphere), neglect (nondominant hemisphere), contralateral paresis and sensory loss in the face and arm, gaze preference toward the side of the lesion, homonymous hemianopia.
Anterior cerebral artery (ACA): Contralateral paresis and sensory loss in the leg; cognitive or personality changes.
Posterior cerebral artery (PCA): Homonymous hemianopia, memory deficits, dyslexia/alexia.Basilar artery: Coma, “locked-in” syndrome, cranial nerve palsies (e.g., diplopia), apnea, visual symptoms, drop attacks, dysphagia, dysarthria, vertigo, “crossed” weakness and sensory loss affecting the ipsilateral face and contralateral body.
Lacunar: Pure motor or sensory stroke, dysarthria–clumsy hand syndrome, ataxic hemiparesis.
TIA: A transient neurologic deficit that lasts < 24 hours (most last < 1 hour) and is determined to be of ischemic etiology. Many TIAs (~30–50%) are associated with small, asymptomatic strokes on diffusion-weighted MRI.
■Emergent head CT without contrast (see Figure 2.10-2) to differentiate ischemic from hemorrhagic stroke and to identify potential candidates for thrombolytic therapy.
TABLE 2.10-5.  Clinical Refl exesMCA stroke can cause CHANGes:Contralateral paresis and sensory loss in the face and arm the side of the lesion
Biceps = C5 nerve root. Triceps = C7 nerve root. Patella = L4 nerve root. Achilles = S1 nerve root. Babinski––dorsifexion of the big toe and fanning of other toes; sign of UMN lesion, but normal refex in the frst year of life. Refexes count up in order. S1, 2 L3, 4 C5, 6 C7, 8 C5, 6 L3, 4 C7, 8 S1, 2
Adapted, with permission, from Le T, Bhushan V et al. First Aid for the USMLE Step 1 2009. New York: McGraw-Hill, 2009: 392.
FIGURE 2.10-1.  Spinal cord lesions.(Reproduced, with permission, from Le T, Bhushan V et al. First Aid for the USMLE Step 1 2009. New York: McGraw-Hill, 2009: 389.)
MRI to identify early ischemic changes (e.g., diffusion-weighted MRI is sensitive for acute stroke).
ECG and an echocardiogram if embolic stroke is suspected.Vascular studies of intracranial and extracranial disease include carotid ultrasound, transcranial Doppler, MRA, and angiography (see Figure 2.10-3).
T AB LE 2.1 0-6.  Modifiable and Nonmodifiable Risk Factors for Stroke
FAME: Family history of MI or stroke Age > 60 Male gender Ethnicity (African-American, Hispanic, Asian) “Live the way a COACH SHoulDD”: CAD Obesity Atrial f brillation Carotid stenosis Hypercholesterolemia Smoking Hypertension Diabetes Drug use (cocaine or IV drugs)
F IGU R E 2.1 0-2.  CT/MRI findings in ischemic stroke in the right MCA territory.
(A) CT shows low density and effacement of cortical sulci (between arrowheads) and compression of the anterior horn of the lateral ventricle (arrow). (B) T1-weighted MRI shows loss of sulcal markings (between arrowheads) and compression of the anterior horn of the lateral ventricle (arrow). (C) T2-weighted MRI scan shows increased signal intensity (between arrowheads) and ventricular compression (arrow). (Reproduced, with permission, from Aminoff MJ. Clinical Neurology, 3rd ed. Stamford, CT: Appleton & Lange, 1996: 275.)
F IGU R E 2.1 0-3. Vascular studies preand postendarterectomy.
Contraindications to tPA therapy—Stroke or head trauma within the last three monthsAnticoagulation with INR > 1.7 or prolonged PTTLow platelet count (< 100,000/mm3)Elevated BP: Systolic > 185 or diastolic BP > 110
Surgery in the past 14 daysTIA (mild symptoms or rapid improvement of symptoms)GI or urinary bleeding in the past 21 daysSeizures present at the onset of stroke (A) Carotid arteriogram showing stenosis of the proximal internal carotid artery. (B) Postop erative arteriogram with restoration of the normal luminal size following endarterectomy.
(Reproduced, with permission, from Way LW. Current Surgical Diagnosis & Treatment, 10th ed. Stamford, CT: Appleton & Lange, 1994: 763.) ■Screen for hypercoagulable states with a history of thrombosis, in the setting of a first stroke, or in patients < 50 years of age.
■ Acute:Ischemic stroke: tPA is indicated if administered within three hours of symptom onset, but first rule out contraindications. Be aware of potential bleeding or angioedema. Intra-arterial thrombolysis can be used for select patients within six hours of major stroke from MCA occlusion if such patients are not suitable candidates for IV tPA.
Hemorrhagic stroke: See the discussion of parenchymal hemorrhage.ICU admission should be considered, especially for comatose patients or for those who are unable to protect their airways for possible intubation.
Monitor for signs and symptoms of brain swelling, ↑ ICP, and herniation. Serial CTs are helpful in the evaluation of deteriorating patients. As a temporizing measure, treat with mannitol and hyperventilation.
ASA is associated with ↓ morbidity and mortality in acute ischemic stroke presenting ≤ 48 hours from onset.
Allow permissive hypertension and hypoxemia to maintain perfusion of ischemic cerebral tissue. However, in the setting of severe hypertension (SBP > 220 or DBP >120) or hemorrhagic stroke, treat with IV labetalol or nicardipine infusion. Additionally, to administer tPA, SBP must be < 185 and DBP < 110.
Treat fever and hyperglycemia, as both are associated with worse prognoses in the setting of acute stroke.
Prevent and treat post-stroke complications such as aspiration pneumonia, UTI, and DVT.
Immediate labs to be obtained include CBC with platelets, cardiac enzymes and troponin, electrolytes, BUN, creatinine, serum glucose, PTT, PT, INR, lipid profile, and oxygen saturation.
Prevention and long-term treatment:ASA, clopidogrel: If stroke is 2° to small vessel disease or thrombosis, or if anticoagulation is contraindicated.
Carotid endarterectomy: If stenosis is > 70% in symptomatic patients or > 60% in asymptomatic patients (contraindicated in 100% occlusion).
Anticoagulation: In new AF or hypercoagulable states, the target INR is 2–3. In cases involving a prosthetic valve, the target INR is 3–4 or add an antiplatelet agent.
Management of hypertension, hypercholesterolemia, and diabetes (hypertension is the single greatest risk factor for stroke).
Etiologies of SAH include trauma, berry aneurysms, AVM, and trauma to the circle of Willis.
Aneurysmal SAH presents with an abrupt-onset, intensely painful “thunderclap” headache, often followed by neck stiffness and other signs of meningeal irritation, including photophobia, nausea/vomiting, and meningeal stretch signs. Rapid development of obstructive hydrocephalus or seizures often leads to ↓ arousal or frank coma and death in the absence of neurosurgical intervention.
More than one-third of patients will give a history of a “sentinel bleed” days to weeks earlier marked by an abrupt-onset headache, often with nausea/vomiting, or transient diplopia that completely resolved in a matter of minutes to hours.
Immediate head CT without contrast (see Figure 2.10-4) to look for blood in the subarachnoid space. Sensitivity is > 95% in those with severe SAH but is much lower in patients with normal mental status.
Immediate LP if CT is to look for RBCs, xanthochromia (yellowish CSF due to breakdown of RBCs), ↑ protein (from the RBCs), and ↑ ICP. Note that LP results can be falsely  in the first 6–12 hours (because xanthochromia has not yet developed) and after the first 24–28 hours (because xanthochromia has resolved).
Four-vessel angiography (or equivalent noninvasive angiography such as CT angiography with 3-D reconstructions) should be performed once SAH is confirmed. Noninvasive angiography is warranted in high-risk cases and in those with high clinical suspicion even if CT and LP are unrevealing.
Call neurosurgery.Prevent rebleeding (most likely to occur in the first 48 hours) by maintaining systolic BP < 150 until the aneurysm is clipped or coiled.
Prevent vasospasm and associated neurologic deterioration (most likely to occur 5–7 days after SAH) by administering calcium channel blockers (CCBs), IV fluids, and pressors to maintain BP. Give phenytoin for seizure prophylaxis.
■↓ ICP by raising the head of the bed and instituting hyperventilation.
Treat hydrocephalus through a lumbar drain or serial LPs.CN III palsy with pupillary involvement is associated with berry aneurysms.
Conditions associated with berry aneurysms that can MAKE an SAH more likely: dominant, polycystic) Ehlers-Danlos syndrome Sickle cell anemia Atherosclerosis History (familial)
The characteristic “worst headache of my life” of SAH comes on quickly, in contrast to migraine (peak intensity > 30 minutes).
F IGU R E 2.1 0-4.  Subarachnoid hemorrhage.Mental status changes associated with an expanding epidural hematoma occur within minutes to hours and classically have a lucid interval. With a subdural hematoma, mental status changes can occur within days to weeks.
(A) CT scan without contrast reveals blood in the subarachnoid space at the base of the brain (arrows). (B) A normal CT scan without contrast shows no density in this region (arrows).
(Reproduced, with permission, from Aminoff MJ. Clinical Neurology, 3rd ed. Stamford, CT:
Appleton & Lange, 1996: 78.) ■ Surgical clipping is the defnitive treatment for aneurysms. Endovascular coiling is an option for poor surgical candidates.
Risk factors include hypertension, tumor, amyloid angiopathy (in the elderly), anticoagulation, and vascular malformations (AVMs, cavernous hemangiomas).
Hx/PE: Presents with focal motor and sensory defcits that often worsen as the hematoma expands. Severe headache of sudden onset, nausea/ vomiting, seizures, lethargy, or obtundation may also be seen.
Dx: Immediate noncontrast head CT (see Figure 2.10-5). Look for mass effect or edema that may predict herniation.
Tx: Similar to that of SAH. Elevate the head of the bed and institute anti-seizure prophylaxis. Surgical evacuation may be necessary if mass effect is present. Several types of herniation may occur, including central, uncal, subfalcine, and tonsillar (see Figure 2.10-6 and Table 2.10-7).
Typically occurs following head trauma (usually falls or assaults), leading to rupture of bridging veins and accumulation of blood between the dura and arachnoid membranes. Common in the elderly and alcoholics.
Hx/PE: Presents with headache, changes in mental status, and contra-lateral hemiparesis. Changes may be subacute or chronic. May present as pseudodementia in the elderly.
F IGU R E 2.1 0-5.  Intraparenchymal hematoma.Head CT without contrast reveals the irregularly shaped hyperdensity with midline shift of the choroid plexus. (Reproduced, with permission, from Saunders CE. Current Emergency Diagno sis & Treatment, 4th ed. Stamford, CT: Appleton & Lange, 1992: 248.)
Dx: CT demonstrates a crescent-shaped, concave hyperdensity acutely (isodense subacutely, hypodense chronically) that does not cross the mid-line (see Figure 2.10-7A).
Tx: Surgical evacuation if symptomatic. Subdural blood may regress spontaneously if it is chronic.
3. Uncal herniation 4. Cerebellar tonsillar herniation into the Tentorium foramen magnum
Coma and death result when these herniations compress the brain stem
F IGU R E 2.1 0-6. Sites of herniation syndromes.
(Adapted, with permission, from Simon RP et al. Clinical Neurology, 4th ed. Stamford, CT: Appleton & Lange, 1999: 314.)
TAB LE 2.1 0-7. Clinical Presentation of Herniation SyndromesCingulate herniation Occurs 2° to mass lesions of the frontal lobes. No specifc signs or symptoms; frequently seen on head CT. Downward transtentorial (central) herniation Occurs when large supratentorial mass lesions push the midbrain inferiorly. Presents with a rapid change in mental status; bilaterally small and reactive pupils; Cheyne-Stokes respirations; and fexor or extensor posturing. Uncal herniation Occurs 2° to mass lesions of the middle fossa. CN III becomes entrapped, leading to a fxed and dilated ipsilateral pupil followed by an eye that is deviated “down and out.” Ipsilesional hemiparesis (“false localizing”) results from compression of the cerebral peduncle (opposite the mass lesion) against the tentorial edge. Cerebellar tonsillar herniation into the foramen magnum Occurs 2° to posterior fossa mass lesions. Tonsillar herniation → medullary compression → respiratory arrest. Usually rapidly fatal.
Usually a result of a lateral skull fracture leading to a tear of the middle meningeal artery.
Hx/PE: Obvious, severe trauma induces an immediate loss of consciousness followed by a lucid interval (minutes to hours). Uncal herniation
F IGU R E 2.1 0-7. Subdural vs. epidural hematoma.
(A) Subdural hematoma. Note the crescent shape and the mass effect with midline shift. (B) Epidural hematoma with classic biconvex lens shape. (Reproduced, with permission, from Aminoff MJ. Clinical Neurology, 3rd ed. Stamford, CT: Appleton & Lange, 1996: 296.) leads to coma with a “blown pupil” (fixed and dilated ipsilateral pupil) and ultimately ipsilateral hemiparesis.
■Dx: CT shows a lens-shaped, convex hyperdensity limited by the sutures (see Figure 2.10-7B).
■ Tx: Emergent neurosurgical evacuation. May quickly evolve to brain her- niation and death 2° to the arterial source of bleeding.
Causes of headache include the following:Acute (new; onset seconds to minutes): New migraine/cluster headache, aneurysmal SAH, acutely ↑ ICP (e.g., colloid cyst, obstructive hydrocephalus), acute ocular disease (e.g., angle-closure glaucoma), cerebral venous thrombosis, cavernous sinus thrombosis, craniocervical dissection, pituitary apoplexy, acute severe hypertension (e.g., pheochromocytoma), angina (rare), ischemic stroke/intraparenchymal hemorrhage (headache is usually not the presenting manifestation).
Subacute (new; onset hours to days): New migraine/tension-type headache or viral syndrome vs. meningitis, other cranial infections (acute sinusitis, dental infections, orbital infections, cavernous sinus infections, otitis media/mastoiditis), temporal arteritis, subacutely ↑ ICP (e.g., large tumor, progressive hydrocephalus, altitude sickness, pseudotumor cerebri), sub-acute ocular disease (e.g., keratitis, iritis, scleritis, orbital infection), sub-acute severe hypertension (e.g., hypertensive encephalopathy, eclampsia), intracranial hypotension (e.g., spontaneous, post-LP), subdural hematoma, carbon monoxide, lead poisoning in children (rare), encephalitis.
Chronic/episodic: Migraine, cluster headache, tension-type headache, medication overuse headaches (e.g., caffeine withdrawal, “rebound” headaches from NSAID or analgesic overuse), trigeminal or other neuralgias (e.g., glossopharyngeal, postherpetic), TMJ disease, cervical arthritis, chronic sinusitis.
Conduct full general and neurologic exams, including a funduscopic exam.
Evaluate the following:Chronicity: Recent or recently changed headaches warrant immediate workup if they are not clearly migraines or other 1° headache disorders.
Intensity: Severe headaches are more likely to be dangerous, but not all dangerous headaches are severely intense (e.g., temporal arteritis).
Location: Posterior headaches are less likely to be benign, especially in children.
Duration: Headaches lasting > 72 hours are not migraines.Diurnal variation: Cluster headaches and those from elevated ICP usually occur or worsen at night.
Triggers: Examples include chocolate and red wine.Provocative factors: Lying down may make high-ICP headaches worse; standing up may make low-ICP headaches worse.
Palliative factors: Sleep clears migraines.Recent-onset headaches warrant immediate workup! If headache is associated with focal neurologic def cits, rule out more serious etiologies with CT or MRI. Rule out SAH with a CT and LP if symptoms are abrupt in onset; then consider other causes typically missed by CT (e.g., dural thrombosis, dissection, or apoplexy).
If a 20-year-old female develops headaches after drinking red wine, think migraine.
Associated symptoms/signs: Significant findings include fever or rash (consider meningitis or other infectious causes), jaw claudication (specific for temporal arteritis), or constitutional symptoms such as weight loss (associated with neoplastic, inflammatory, or infectious conditions). Photophobia, nausea, and vomiting are associated with migraine, aneurysmal SAH, and meningitis, but neck stiffness is more likely to accompany the latter two.
Neurologic sequelae: Look for diplopia, mental status changes or associated symptoms (numbness, weakness, dizziness, ataxia, visual disturbances), papilledema, or pupillary abnormalities (partial CN III palsy or Horner’s syndrome).
Patient risk factors: High-risk patients are > 50 years of age, immunocompromised, or with preexisting malignancy.
If SAH is suspected, obtain a head CT without contrast.
If CT is , LP is mandatory.Obtain a CBC.If temporal arteritis is suspected, obtain ESR.A CT/MRI is needed for suspected SAH, ↑ ICP, or focal neurologic findings. Use CT without contrast to evaluate acute hemorrhage.
Affects females more often than males; may be familial. Associated with vascular and brain neurotransmitter (serotonin) changes. Pain is ultimately linked to trigeminal nucleus activation in the brain stem.
Auras appear to result from a different pathomechanism (electrical spreading depression in the brain, possibly linked to ion channel dysfunction) and may occur with or without the pain of migraine headache. Onset usually occurs by the early 20s.
Triggers include certain foods (e.g., red wine), fasting, stress, menses, OCPs, bright light, and disruptions in normal sleep patterns.
Presents with a throbbing headache (> 2 hours but usually < 24 hours, and almost always < 72 hours in duration) that is associated with nausea, vomiting, photophobia, and noise sensitivity. Headache is usually relieved by sleep and darkness.
Classic migraines: Often unilateral and preceded by a visual aura in the form of either scintillating scotomas (bright or flashing lights) or visual field cuts.
Common migraines: May be bilateral and periorbital without preceding auras.
Dx: Based on history.Avoid known triggers.Abortive therapy includes triptans (first line after OTC NSAIDs have failed), metoclopramide, and various analgesics. Consider symptomatic treatment for nausea.
Prophylaxis for frequent or severe migraines includes anticonvulsants (e.g., gabapentin, topiramate), TCAs (e.g., amitriptyline), β-blockers (propranolol), and CCBs.
Males are affected more often than females; average age of onset is 25.
Presents as a brief, excruciating, unilateral periorbital headache that lasts 30 minutes to three hours, during which the patient tends to be extremely restless.
Attacks tend to occur in clusters, affecting the same part of the head at the same time of day (commonly during sleep) and in a certain season of the year.
Associated symptoms include ipsilateral lacrimation of the eye, conjunctival injection, Horner’s syndrome, and nasal stuffiness.
Dx: Classic presentations with a history of repeated attacks over an extended period of time require no evaluation. First episodes require a workup to exclude disorders associated with Horner’s syndrome (e.g., carotid artery dissection or cavernous sinus infection).
Acute therapy: High-fl ow O2 (100% non-rebreather), dihydroergotamine, octreotide, sumatriptan or zolmitriptan.
Prophylactic therapy: Transitional (prednisone, ergotamine), maintenance (verapamil, methysergide, lithium, valproic acid, topiramate).
Considered by some to be a milder form of migraine headache. More common in females than in males.
Hx/PE: Presents with tight, bandlike pain that is not associated with sensory phobia, nausea/vomiting, or auras and is brought on by fatigue or stress. Nonspecific symptoms (e.g., anxiety, poor concentration, difficulty sleeping) may also be seen. May be generalized or most intense in the frontal, occipital, and neck regions. Usually occurs at the end of the day.
Dx: A diagnosis of exclusion. Be particularly aware of giant cell arteritis in patients > 50 years of age with new headaches; always obtain an ESR even if headaches are mild and unassociated with constitutional or vascular symptoms. There are no focal neurologic signs.
Tx: Relaxation, massage, hot baths, and avoidance of exacerbating factors. NSAIDs and acetaminophen are first-line abortive therapy, but trip-tans may also be considered.
The usual etiology involves a suppurative process of the orbit, nasal sinuses, or central face that leads to septic thrombosis of the cavernous sinus. Non-septic thrombosis is rare; S. aureus is the most common causative agent. The syndrome can also be seen with nonbacterial agents, particularly fungi (Mucor or Aspergillus species). Current antibiotics have greatly ↓ both incidence and mortality.
Headache is the most common presenting symptom.Patients may present with orbital pain, edema, diplopia (2° to oculomotor, abducens, or trochlear nerve involvement), or visual disturbances and may describe a recent history of sinusitis or facial infection. On exam, they typically appear ill and have a fever.
If a 25-year-old male wakes up repeatedly during the night with unilateral periorbital pain associated with ipsilateral lacrimation, think cluster headache.
If a 30-year-old female complains of headaches at the end of the day that worsen with stress and improve with relaxation or massage, think tension-type headache.
Tension-type headaches are the most common type of headache diagnosed in adults.
Additional signs may include red eye, proptosis, ptosis, or ophthalmoplegia of the affected eye (partial or complete). Diminished pupillary constriction (CN III) and/or dilation (Horner’s) may also be present.
Changes in mental status such as confusion, drowsiness, or coma suggest spread to the CNS or sepsis. Late findings include meningismus or systemic signs of sepsis.
Lab studies show an ↑ WBC count.Blood cultures reveal the causative agent in up to 50% of cases.
CSF exam may reveal ↑ protein consistent with a parameningeal reaction unless there is frank meningitis.
MRI (with gadolinium, pituitary protocol) is the principal means of confirming the anatomic diagnosis; MR or CT venography may be important adjuncts.
Biopsy of paranasal sinuses or other affected tissue is often necessary in fungal cases for organism identification by histology and culture.
Treat aggressively and empirically with a penicillinase-resistant penicillin (nafcillin or oxacillin) plus a thirdor fourth-generation cephalosporin (e.g., ceftriaxone or cefepime) to provide broad-spectrum coverage pending blood culture results. Potential anaerobic infection from sinus or dental sources should be covered with metronidazole. Vancomycin can be added to address potential MRSA involvement. Antifungal therapy is required for fungal cases.
IV antibiotics are recommended for at least 3–4 weeks.Paroxysmal events associated with aberrant electrical activity in the brain detectable by EEG, leading to changes in neurologic perception or behavior. An aura is experienced by 50–60% of patients with epilepsy. See Table 2.10-8 for common etiologies by age. To further narrow down the etiology of a seizure, assess the following:
Determine whether the patient has a history of epilepsy (i.e., a history of unprovoked and recurrent seizures). Other seizures may be self-limited and may resolve once an underlying medical condition has been treated. Elevated serum prolactin levels are consistent with an epileptic seizure in the immediate postictal period.
TABLE 2.10-8. Causes of Seizure by Age GroupNon-neurologic etiologies include hypoglycemia, hyponatremia, hypocalcemia, hyperosmolar states, hepatic encephalopathy, uremia, porphyria, drug overdose (cocaine, antidepressants, neuroleptics, methylxanthines, lidocaine), drug withdrawal (alcohol and other sedatives), eclampsia, hyperthermia, hypertensive encephalopathy, head trauma, and cerebral hypoperfusion.
Seizures with a focal onset (or focal postictal deficit) suggest focal CNS pathology. They may be the presenting sign of a tumor, stroke, AVM, infection, hemorrhage, or developmental abnormality.
First seizures that resolve after a single episode are frequently left untreated when the underlying cause is unknown.
Arise from a discrete region, or an “epileptogenic focus,” in one cerebral hemisphere and do not lead to loss of consciousness unless they secondarily generalize.
Simple partial seizures: May include motor features (e.g., jacksonian march, or the progressive jerking of successive body regions) as well as sensory, autonomic, or psychic features (e.g., fear, déjà vu, hallucinations) without alteration of consciousness. A postictal focal neurologic deficit (e.g., hemiplegia/hemiparesis, or Todd’s paralysis) is possible and usually resolves within 24 hours. Often confused with acute stroke (ruled out by MRI).
Complex partial seizures: Typically involve the temporal lobe (70–80%) with bilateral spread of the aberrant electrical discharge. Characterized by an impaired level of consciousness, auditory or visual hallucinations, déjà vu, automatisms (e.g., lip smacking, chewing, or even walking), and postictal confusion/disorientation and amnesia.
Obtain an EEG.Rule out systemic causes with a CBC, electrolytes, calcium, fasting glucose, LFTs, a renal panel, RPR, ESR, and a toxicology screen.
A focal seizure implies a focal brain lesion. Rule out a mass by MRI or CT with contrast.
Treat the underlying cause.Recurrent partial seizures: Phenytoin, oxcarbazepine, carbamazepine (Tegretol), phenobarbital, and valproic acid can be administered as mono-therapy. In children, phenobarbital is the first-line anticonvulsant.
Intractable temporal lobe seizures: Consider anterior temporal lobectomy.Primarily idiopathic. Partial seizures can evolve into secondarily generalized tonic-clonic seizures.
If a patient presents wth progressive jerking of successive body regions and hallucinations but without loss of consciousness, think simple partial seizures.
If a patient presents with an episode of lip smacking associated with an impaired level of consciousness and followed by confusion, think complex partial seizures.
Both simple partial and complex partial seizures may evolve into 2° generalized tonic-clonic (grand mal) seizures.
If a patient presents with clonic movements associated with loss of consciousness and incontinence, think tonicclonic (grand mal) seizures.
If a child is brought from school to her pediatrician after experiencing f ve-second episodes of staring into space, think absence (petit mal) seizures.
Presents with sudden onset of loss of consciousness with tonic extension of the back and extremities, continuing with 1–2 minutes of repetitive, symmetric clonic movements.
Marked by incontinence and tongue biting. Patients may appear cyanotic during the ictal period. Consciousness is slowly regained in the postictal period, but patients are confused and may prefer to sleep; muscle aches and headaches may be present.
EEG typically shows 10-Hz activity during the tonic phase and slow waves during the clonic phase.
Protect the airway.Treat the underlying cause if known.1° generalized tonic-clonic seizures: Phenytoin, fosphenytoin, or valproate constitutes first-line therapy. Lamotrigine or topiramate may be used as adjunctive therapy.
Secondarily generalized tonic-clonic seizures: Treatment is the same as that for partial seizures.
Begin in childhood; subside before adulthood. Often familial.Hx/PE: Present with brief (5to 10-second), often unnoticeable episodes of impaired consciousness occurring up to hundreds of times per day. Patients are amnestic during and immediately after seizures and may appear to be daydreaming or staring. Eye fluttering or lip smacking is common.
Dx: EEG shows classic three-per-second spike-and-wave discharges.Tx: Ethosuximide is the first-line agent.A medical emergency consisting of prolonged (> 10-minute) or repetitive seizures that occur without a return to baseline consciousness. May be either convulsive (the more medically urgent form) or nonconvulsive.
Common causes include anticonvulsant withdrawal/noncompliance, anoxic brain injury, EtOH/sedative withdrawal or other drug intoxication, metabolic disturbances (e.g., hyponatremia), head trauma, and infection.
Death usually results from the underlying medical condition and may occur in 10% of cases of status epilepticus.
Determine the underlying cause with pulse oximetry, CBC, electrolytes, calcium, glucose, ABGs, LFTs, BUN/creatinine, ESR, antiepileptic drug levels, and a toxicology screen.
Obtain an EEG and brain imaging, but defer testing until the patient is stabilized.
Obtain a stat head CT to evaluate for intracranial hemorrhage.
Obtain an LP in the setting of fever or meningeal signs, but only after having done a CT scan to assess the safety of the LP.
Maintain ABCs; consider rapid intubation for airway protection.Administer thiamine, glucose, and naloxone to presumptively treat potential etiologies.
Give IV benzodiazepine (lorazepam or diazepam) plus a loading dose of fosphenytoin.
If seizures continue, intubate and load with phenobarbital. Consider an IV sedative (midazolam or pentobarbital) and initiate continuous EEG monitoring.
Initiate a meticulous search for the underlying cause.A form of generalized epilepsy that typically begins within six months of birth. May be idiopathic or 2° to a variety of conditions, including PKU, perinatal infections, hypoxic-ischemic injury, and tuberous sclerosis.
Affects males more often than females; associated with a  family history.
Hx/PE: Presents with tonic, bilateral, symmetric jerks of the head, trunk, and extremities that tend to occur in clusters of 5–10; arrest of psycho-motor development occurs at the age of seizure onset. The majority of patients have mental retardation.
Dx: Look for an abnormal interictal EEG characterized by hypsarrhythmia.
Tx: Hormonal therapy with ACTH, prednisone, and clonazepam or valproic acid. Medications may treat the spasms but have little impact on patients’ long-term prognosis.
Treatment of status epilepticus: First ABCs, Then Begin Giving Naloxone: Fosphenytoin, ABCs, Thiamine, Benzodiazepine, Glucose, Naloxone.
If a male infant is brought to the hospital with muscular jerks and an uncle who had the same problem, think infantile spasms (West syndrome).
A common cause of recurrent peripheral vertigo resulting from a dislodged otolith that leads to disturbances in the semicircular canals (95% posterior, 5% horizontal).
Hx/PE: Patients with posterior canal BPPV present with transient, episodic vertigo (lasting < 1 minute) and mixed upbeat-torsional nystagmus triggered by changes in head position (classically while turning in bed, getting in/out of bed, or reaching overhead). Some patients complain of nonvertiginous feelings of dizziness or lightheadedness. Nausea and vomiting are uncommon owing to the short-lived stimulus.
Have the patient turn his or her head 45 degrees right or left and go from a sitting to a supine position while quickly turning the head to the side (Dix-Hallpike maneuver). If vertigo and the typical nystagmus (upbeat and toward the affected shoulder) are reproduced, BPPV is the likely diagnosis.
Nystagmus that persists for > 1 minute, gait disturbance, or nausea/ vomiting that is out of proportion to nystagmus should raise concern for a central lesion.
Some 80% of cases can be resolved at the bedside using the modified Epley maneuver (a 270-degree head rotation from the Dix-Hallpike testing position).
With BPPV, it’s all in the name:Benign = otolith (not a tumor).Paroxysmal = sudden, temporary episodes lasting < 1 minute.Positional = starts while turning in bed or reaching overhead.
Vertigo = vertigo or dizziness is the main symptom.If you see a 27-year-old male who presents with vertigo and vomiting for one week after having been diagnosed with a viral infection, think acute vestibular neuritis.
■The condition usually subsides spontaneously in weeks to months but often recurs months or years later. Antivertigo medications (e.g., meclizine) are generally contraindicated, as they tend to inhibit central compensation, which may lead to chronic unsteadiness and falls in the elderly.
Typically a diagnosis of exclusion once the more serious causes of vertigo (e.g., cerebellar stroke) have been ruled out.
Hx/PE: Presents with acute onset of severe vertigo, head-motion intolerance, and gait unsteadiness accompanied by nausea, vomiting, and nystagmus. Auditory or aural symptoms (“labyrinthitis”) may include unilateral tinnitus, ear fullness, or hearing loss. Without auditory or aural symptoms (more common), the condition is known as “vestibular neuritis.”
Acute peripheral vestibulopathy demonstrates the following:An abnormal vestibulo-ocular reflex (VOR) as determined by a bedside head impulse test (i.e., rapid head rotation from lateral to center while staring at the examiner’s nose).
A predominantly horizontal nystagmus that always beats in one direction, opposite the lesion.
No vertical eye misalignment by alternate cover testing.If patients are “high risk” (i.e., if they have atypical eye findings or any neurologic symptoms or signs, cannot stand independently, have head or neck pain, are > 50 years of age, or have one or more stroke risk factors), they should be imaged by MRI with diffusion-weighted imaging.
For low-risk patients, consider caloric testing as ancillary support for the diagnosis.
Labyrinthitis (with auditory symptoms) is mimicked by lateral pontine/ cerebellar stroke (AICA arterial territory). Vestibular neuritis (without auditory symptoms) is mimicked by lateral medullary/cerebellar stroke (PICA arterial territory).
Tx: Acute treatment consists of corticosteroids given < 72 hours after symptom onset and vestibular sedatives (e.g., meclizine). The condition usually subsides spontaneously within weeks to months. Once the hyperacute stage has passed, cautious engagement in normal physical activities and exercise should be encouraged.
A cause of recurrent vertigo with auditory symptoms that affects at least 1 in 500 in the United States. More common among females.
Hx/PE: Presents with recurrent episodes of severe vertigo, hearing loss, tinnitus, or ear fullness, often lasting hours to days. Nausea and vomiting are typical. Patients progressively lose low-frequency hearing over years and may become deaf on the affected side.
Dx: Diagnosis is made clinically and is based on a thorough history and physical exam. Two episodes (lasting 20 minutes or more) with remission of symptoms between episodes, hearing loss documented at least once with audiometry, and tinnitus or aural fullness are needed to make the diagnosis once other causes (e.g., TIA, otosyphilis) have been ruled out. A brain
MRI with vascular imaging (e.g., MRA) may help assess potential intracranial pathology, particularly cerebrovascular disease.
■ Tx: Classically, a low-sodium diet and diuretic therapy were first-line treatments. As theories of pathogenesis have shifted, many clinicians have begun to treat patients with “migraine” diets, other lifestyle changes, prophylactic antimigraine medications, and occasionally benzodiazepines or antiemetics. For severe unilateral cases, ablative therapies (e.g., intratympanic gentamicin to damage the labyrinth, vestibular nerve section) have been used with some success.
A cause of recurrent vertigo (usually without auditory symptoms) that affects roughly 10% of migraine sufferers. More common among females. Its pathogenesis may be related to intermittent electrical (ion channel) dysfunction in the cerebellum.
Hx/PE: Presents with recurrent episodes of mild dizziness to severe vertigo lasting minutes to days. Nausea, vomiting, and photophobia are common; headaches are variably present and may be mild or severe. Patients are left with no substantial deficits in between spells, although balance may deteriorate over decades.
The diagnosis is usually made clinically on the basis of a thorough history and physical exam to exclude other causes.
Patients who would otherwise qualify for a diagnosis of Ménière’s save the absence of auditory symptoms and documented hearing loss are likely to have vestibular migraine. A history of photoor phonophobia during the episode, particularly if dizziness is associated with headache, is highly suggestive in such patients.
The diagnosis is one of exclusion, and care should be taken to ensure that patients do not have intermittent dizziness due to TIA. In patients < 50 years of age, a history of recent trauma or of severe, abrupt-onset, or persistent pain (> 72 hours) should raise concern for vertebral artery dissection with TIAs.
A brain MRI with vascular imaging (e.g., MRA) is sometimes indicated to assess potential intracranial pathology, particularly cerebrovascular disease.
Episodic ataxia type 2 can be corroborated by genetic testing.
Tx: Can usually be prevented through migraine medication, diet, or lifestyle changes. Benzodiazepines or antiemetics may be tried. Surgical therapies are not indicated.
One of the most common causes of loss of consciousness 2° to an abrupt drop in cerebral perfusion. Etiologies include cardiac arrhythmias and cardiac outflow obstruction, vasovagal syncope, orthostatic hypotension, micturition-related syncope, basilar TIAs, and idiopathic causes. Presyncope is described as a feeling of imminent loss of consciousness without actual fainting. Commonly confused with seizures.
Patients may report a trigger (e.g., standing for long period of time, fear/sight of blood, Valsalva maneuver).
Ménière’s disease consists of recurrent episodes, but unlike BPPV, these usually last hours to days.
Unlike Ménière’s, vestibular migraine usually has no associated auditory or aural symptoms.
Rule out vertebral artery dissection in those with persistent head or neck pain and intermittent isolated dizziness or vertigo.
■Typically follows a prodrome of lightheadedness or dizziness, muff ed sounds, constricting vision, diffuse weakness, diaphoresis, or pallor. Leads to loss of consciousness and muscle tone for < 30 seconds and recovery within seconds.
Structural CNS causes (e.g., basilar TIA, intermittent obstructive hydrocephalus) are rare among patients who return to normal mental status and have a normal neurologic examination after a brief loss of consciousness.
Seizures are more likely if limb jerking is unilateral or lasts > 30 seconds; if there is prolonged confusion after the episode; or if the patient bites the lateral aspect of their tongue.
Unless there is a clear vasovagal faint in a young patient without cardiac disease or risk factors, place all patients on telemetry or Holter monitoring to evaluate for arrhythmia, and rule out myocardial is chemia with an ECG and cardiac enzymes. Obtain an EEG to rule out seizures. Consider an echocardiogram, a tilt-table test, or neuroimaging, especially vascular.
Tx: Treat the underlying cause; avoid triggers.An autoimmune disorder caused by antibodies that bind to postsynaptic acetylcholine (ACh) receptors located at the neuromuscular junction. Most often affects young adult females, and can be associated with thyrotoxicosis, thymoma, and other autoimmune disorders.
Presents with fl uctuating fatigable ptosis or double vision, bulbar symptoms (e.g., dysarthria, dysphagia), and proximal muscle weakness. Symptoms typically worsen as the day progresses but f uctuate dramatically.
Patients may report difficulty climbing stairs, rising from a chair, brushing their hair, and swallowing.
Myasthenic crisis is rare but includes the potentially lethal complications of respiratory compromise and aspiration.
Edrophonium (Tensilon test): Anticholinesterase leads to rapid amelioration of symptoms. Rarely used today owing to the risk of bradycardia.
Ice test: Place a pack of ice on one eye for five minutes; ptosis resolves transiently.
An abnormal single-f ber EMG and/or a decremental response to repetitive nerve stimulation can yield additional confirmation.
ACh antibodies are  in 80% of patients; anti–muscle-specific kinase (anti-MuSK) antibodies are in 5%.
Chest CT is used to evaluate for thymoma. Eighty-five percent of patients with thymoma have  antibodies against striated muscle.
Follow serial FVCs to determine the need to intubate.Anticholinesterases (pyridostigmine) are used for symptomatic treatment.Prednisone and other immunosuppressants (e.g., azathioprine, cyclosporine, mycophenolate) are the mainstays of treatment.
In severe cases, plasmapheresis or IVIG may provide temporary relief (days to weeks).
Resection of thymoma can be curative.Avoid giving certain antibiotics (e.g., aminoglycosides) and drugs (e.g., β-blockers) to patients with myasthenia gravis.
An autoimmune disorder caused by antibodies directed toward presynaptic calcium channels in the neuromuscular junction. Small cell lung carcinoma is a significant risk factor (60% of cases).
Hx/PE: Presents with weakness and fatigability of proximal muscles along with depressed or absent DTRs. Extraocular, respiratory, and bulbar muscles are typically spared.
Dx: Repetitive nerve stimulation reveals a characteristic incremental response. Also diagnosed by autoantibodies to presynaptic calcium channels and a chest CT indicative of a lung neoplasm.
Tx: Treat small cell lung carcinoma; tumor resection may reverse symptoms. 3,4-diaminopyridine or guanidine can be given; acetylcholinesterase inhibitors (pyridostigmine) can be added to either regimen. Corticosteroids and azathioprine can be combined or used alone for immunosuppression.
Although the pathogenesis of MS is unclear, there is evidence of an autoimmune etiology in genetically susceptible individuals who are exposed to environmental triggers such as viral infections. Such potential etiologies are thought to be T-cell mediated. The female-to-male ratio is 3:2, and onset is typically between 20 and 40 years of age. MS becomes more common as one moves farther away from the equator. Subtypes are relapsing-remitting, primary progressive, secondary progressive, and progressive relapsing (see Table 2.10-9).
Presents with multiple neurologic complaints that are separated in time and space and are not explained by a single lesion. As the disease progresses, permanent deficits may accumulate.
Limb weakness, optic neuritis, paresthesias, diplopia, vertigo, nystagmus, gait unsteadiness, urinary retention, sexual and bowel dysfunction, depression, and cognitive impairment are also seen. Symptoms classically worsen transiently with hot showers.
Attacks are unpredictable but on average occur every 1.5 years, lasting for 6–8 weeks.
Neurologic symptoms can come and go or be progressive. The prognosis is best with a relapsing and remitting history.
Lhermitte’s sign, demonstrated by sharp pain traveling up or down the neck and back with flexion, generally suggests the presence of cervical myelitis.
Repetitive nerve stimulation reveals a characteristic incremental response in Lambert-Eaton myasthenic syndrome, and a decremental response in myasthenia gravis.
The classic triad in MS is scanning speech, intranuclear ophthalmoplegia, and nystagmus.
Pregnancy may be associated with a ↓ in symptoms of MS.
T AB LE 2.1 0-9. Subtypes of Multiple SclerosisRelapses Yes. No acute episodes. Yes. Yes. Progression None. From onset. Not at onset; begins to progress later. From onset. Course of symptoms Full recovery, or def cits may remain after each episode. Minor remissions and plateaus may take place during progression. Relapses, minor remissions, and plateaus may take place during progression. Full recovery, or progressive def cits may remain after each episode. 66% 19% Develops after relapsing-remitting type. 15% Best. Worse. Worse. Worse. Percentage of cases at onset Prognosis
For optic neuritis, give IV, not oral, corticosteroids.MRI shows multiple, asymmetric, often periventricular white matter lesions (Dawson’s fingers), especially in the corpus callosum. Active lesions enhance with gadolinium.
CSF reveals mononuclear pleocytosis (> 5 cells/μL), an ↑ IgG index, or oligoclonal bands (nonspecific).
Abnormal somatosensory or visual evoked potentials may also be present.
Corticosteroids should be given during acute exacerbations.Immunomodulators alter relapse rates in relapsing-remitting MS and include interferon-β1a (Avonex/Rebif), interferon-β1b (Betaseron), and copolymer-1 (Copaxone).
Mitoxantrone can be given for worsening relapsing/remitting or progressive MS.
Alternative treatments include cyclophosphamide, IVIG, and plasmapheresis.Symptomatic therapy is crucial and includes baclofen for spasticity; cholinergics for urinary retention; anticholinergics for urinary incontinence; carbamazepine or amitriptyline for painful paresthesias; and antidepressants for clinical depression.
An acute, rapidly progressive, acquired demyelinating autoimmune disorder of the peripheral nerves that results in weakness. Also known as acute infl ammatory demyelinating polyneuropathy. Associated with recent Campylobacter jejuni infection, viral infection, or influenza vaccination. Approximately 85% of patients make a complete or near-complete recovery (may take up to one year). The mortality rate is < 5%.
Classically presents with progressive (over days), symmetric, ascending paralysis (distal to proximal) involving the trunk, diaphragm, and cranial nerves. Atypical presentations are common, including variants that begin with cranial involvement or progress unpredictably to involve the respiratory muscles.
Autonomic dysregulation, areflexia, and dysesthesias may be present.Evidence of diffuse demyelination is seen on EMG and nerve conduction studies, which show ↓ nerve conduction velocity.
Supported by a CSF protein level > 55 mg/dL with little or no pleocytosis (albuminocytologic dissociation).
Admit to the ICU for impending respiratory failure.Plasmapheresis and IVIG are first-line treatments. Corticosteroids are not indicated.
Aggressive physical rehabilitation is imperative.A chronic, progressive degenerative disease of unknown etiology characterized by loss of upper and lower motor neurons. Also known as Lou Gehrig’s disease. ALS has an unrelenting course and almost always progresses to respiratory failure and death, usually within five years of diagnosis. Males are more commonly affected than females, and onset is generally between ages 40 and 80.
Presents with asymmetric, slowly progressive weakness (over months to years) affecting the arms, legs, diaphragm, and lower cranial nerves. Some patients initially present with fasciculations. Weight loss is common.
Associated with UMN and/or LMN signs (see Table 2.10-4). Eye movements and sphincter tone are generally spared. Tongue atrophy and fasciculation may be apparent.
Emotional lability is a common feature.The clinical presentation is usually diagnostic.Involvement of the tongue (CN XII) or oropharyngeal muscles (CN IX, X), known as “bulbar” involvement, suggests pathology above the foramen magnum and generally excludes the most common differential, cervical spondylosis with compressive myelopathy, as a cause.
EMG/nerve conduction studies reveal widespread denervation and fibrillation potentials. Such studies are principally performed to exclude other demyelinating motor neuropathies.
CT/MRI of the cervical spine is done to exclude structural lesions, particularly in those without bulbar involvement.
A 55-year-old male presents with slowly progressive weakness in his left upper extremity and later his right, associated with fasciculations but without bladder disturbance and with a normal cervical MRI. Think ALS.
Supportive measures and patient education.A chronic, progressive, global decline in multiple cognitive areas (see the mnemonic the 5 A’s of dementia). Alzheimer’s disease accounts for 60–80% of cases. The differential diagnosis is described in the mnemonic DEMENTIAS. Take care not to confuse delirium and dementia (see the Psychiatry chapter).
Risk factors for AD include age, female gender, a family history, Down syndrome, and low educational status. Pathology involves neurof brillary tangles, neuritic plaques with amyloid deposition, amyloid angiopathy, and neuronal loss.
Amnesia for newly acquired information is usually the first presenting sign, followed by language deficits, acalculia, depression, agitation, psychosis, and apraxia (inability to perform skilled movements).
Mild cognitive impairment may precede AD by 10 years. Survival is 5–10 years from the onset of symptoms, with death usually occurring 2° to aspiration pneumonia or other infections. Except for the mental state, the physical exam is generally normal.
A diagnosis of exclusion that can be defnitively diagnosed only on autopsy; suggested by clinical features and by an insidiously progressive cognitive course without substantial motor impairment.
MRI or CT may show atrophy and can rule out other causes, particularly vascular dementia, normal pressure hydrocephalus, and chronic subdural hematoma. PET imaging shows nonspecific bilateral temporoparietal hypometabolism. CSF is normal.
Neuropsychological testing can help distinguish dementia from depression. Hypothyroidism, vitamin B12 deficiency, and neurosyphilis should be ruled out in atypical cases.
Prevention of associated symptoms:Provide supportive therapy for the patient and family.Treat depression, agitation, sleep disorders, hallucinations, and delusions.Prevention of disease progression: Cholinesterase inhibitors (donepezil, rivastigmine, galantamine, and tacrine) are first-line therapy. Tacrine is associated with hepatotoxicity and is less often used. Memantine, an NMDA receptor antagonist, may slow decline in moderate to severe disease.
Dementia associated with a history of stroke and cerebrovascular disease is the second most common type of dementia. Risk factors include age, hypertension, diabetes, embolic sources, and a history of stroke.
Criteria for the diagnosis of vascular dementia include the presence of dementia and two or more of the following:
Focal neurologic signs on exam.Symptom onset that was abrupt, stepwise, or related to stroke.
Brain imaging showing evidence of old infarctions or extensive deep white matter changes 2° to chronic ischemia.
Protocols for the prevention and treatment of vascular dementia are the same as those for stroke.
A rare, progressive form of dementia characterized by atrophy of the frontal and temporal lobes. Round intraneuronal inclusions known as Pick bodies are the classic pathologic finding.
Patients present with signifcant changes in behavior and personality early in the disease. Other symptoms include speech disturbance, inattentiveness, and occasionally extrapyramidal signs. Unlike Parkinson’s disease, frontotemporal dementia rarely begins after age 75.
The diagnosis is suggested by clinical features and by evidence of circumscribed frontotemporal atrophy revealed by MRI or CT.
Treatment is symptomatic only; no curative therapy has yet been made available.
A potentially treatable form of dementia that is thought to arise from impaired CSF outflow from the brain.
Symptoms include the classic triad of dementia, gait apraxia, and urinary incontinence. Headaches and other signs of ↑ ICP (e.g., papilledema) typically do not appear, although continuous ICP monitoring may reveal spikes of elevated pressure.
If a patient shows abrupt changes in symptoms over time rather than a steady decline, think vascular dementia.
If a patient presents with rapid cognitive decline over the course of weeks to months, think CJD.
The diagnosis is suggested by clinical features. The gait is classically described as “magnetic” or with “feet glued to the floor,” as the forefoot is not completely dorsally extended.
LP or continuous lumbar CSF drainage for several days reveals normal pressure but may cause clinically significant improvement of the patient’s symptoms.
CT or MRI shows ventricular enlargement out of proportion to sulcal atrophy.
Surgical CSF shunting is the treatment of choice.Although it is the most common prion disease, CJD remains an extremely rare form of dementia. CJD is a member of the transmissible spongiform encephalopathies, all of which are characterized by spongy degeneration, neuronal loss, and astrocytic proliferation. In CJD, an abnormal protease-resistant prion protein accumulates in the brain.
CJD causes a subacute dementia with ataxia or myoclonic jerks with rapid clinical decline that is noted weeks to months after symptom onset.
Suggested by clinical features.The differential diagnosis often includes viral encephalitis, Hashimoto’s (steroid-responsive) encephalopathy, and toxic encephalopathy (e.g., lithium or bismuth).
EEG shows pyramidal signs and periodic sharp waves.MRI with diffusion-weighted imaging may show ↑ T2 and FLAIR intensity in the putamen and the head of the caudate and is also used to exclude structural brain lesions.
CSF is usually normal.Definitive diagnosis can be made only by brain biopsy or autopsy. Specimens must be handled with special precautions to avoid transmission.
Currently, there is no effective treatment. Most patients die within one year of symptom onset.
A rare, hyperkinetic, autosomal-dominant disease involving multiple abnormal CAG triplet repeats (< 29 is normal) within the HD gene on chromosome 4. The number of repeats typically expands in subsequent generations, leading to earlier expression and more severe disease (anticipation). Life expectancy is 20 years from the time of diagnosis.
Presents at 30–50 years of age with gradual onset of chorea (sudden onset of purposeless, involuntary dancelike movements), altered behavior, and dementia (begins as irritability, clumsiness, fidgetiness, moodiness, and antisocial behavior). Weight loss and depression may also be seen.
A clinical diagnosis confirmed by genetic testing.CT/MRI show cerebral atrophy (especially of the caudate and putamen). Molecular genetic testing is conducted to determine the number of CAG repeats.
There is no cure, and disease progression cannot be halted. Treat symptomatically.
Reserpine or tetrabenazine can be given to minimize unwanted movements. Psychosis should preferably be treated with atypical antipsychotics to reduce the risk of extrapyramidal side effects or tardive dyskinesia. SSRIs are first-line therapy for depression.
Genetic counseling should be offered to offspring.An idiopathic hypokinetic disorder that usually begins after age 50–60 and is attributable to dopamine depletion in the substantia nigra. It is characterized pathologically by Lewy bodies, which are intraneuronal eosinophilic inclusions.
The “Parkinson’s tetrad” consists of the following:Resting tremor (e.g., “pill rolling”).Rigidity: “Cogwheeling” due to the combined effects of rigidity and tremor.
Bradykinesia: Slowed movements and difficulty initiating movements. Festinating gait (a wide leg stance with short accelerating steps) without arm swing is also seen.
Postural instability: Stooped posture, impaired righting refl exes, freezing, falls.
Other manifestations include masked facies, memory loss, and micrographia.Parkinsonism is the broader clinical phenotype of bradykinesia and rigidity (with or without substantial tremor). It is often caused by disorders other than idiopathic Parkinson’s disease, most commonly multiple subcortical infarcts (“vascular parkinsonism”).
Nonidiopathic causes of parkinsonism include viral encephalitis (postencephalitic parkinsonism), trauma (dementia pugilistica), and numerous toxins (e.g., manganese, MPTP [designer drugs], and, iatrogenically, neuroleptics [tardive dyskinesia]). Some of these disorders are diagnosed on the basis of failure of levodopa/carbidopa to produce a clinical response.
Other idiopathic dementias may mimic Parkinson’s disease and include progressive supranuclear palsy and multiple system atrophy.
If a 43-year-old male patient presents with sudden onset of chorea, irritability, and antisocial behavior and his father experienced these symptoms at a slightly older age, think Huntington’s disease.
A signif cant difference between gait abnormalities in Parkinson’s and that of NPH is preservation of arm swing in NPH.
There are four PaRTS to Parkinson’s: Postural instability, Rigidity (cogwheeling), Tremor (“pill rolling”), and Slowed movements (bradykinesia).
A side effect associated with pramipexole is uncontrolled gambling.Most CNS tumors are metastatic. The most common 1° CNS tumors in adults are glioblastoma multiforme and meningioma. The most common 1° CNS tumors in children are medulloblastomas and astrocytomas.
Liver and Skin Go to the BRain: Liver, Skin, GI, Breast, Renal.
Two-thirds of 1° brain tumors in adults are supratentorial. One-third of those in children are supratentorial.
Levodopa and carbidopa, both of which are dopamine precursors, are the mainstays of therapy.
Dopamine agonists (ropinirole, pramipexole, bromocriptine) can be used for treatment in early disease. Apomorphine is another dopamine agonist that can be used for rescue therapy if a sudden additional dose is needed.
Selegiline (an MAO-B inhibitor) may be neuroprotective and may ↓ the need for levodopa.
Catechol-O-methyltransferase (COMT) inhibitors (entacapone or tolcapone) are not given alone but ↑ the availability of levodopa to the brain and may ↓ motor fl uctuations.
Amantadine has mild antiparkinsonian activity and may improve akinesia, rigidity, and tremor. It can be used for temporary, short-term monotherapy early in the course of the disease.
If medical therapy fails, surgical pallidotomy or chronic deep brain stimulation may produce clinical benefit.
Intracranial neoplasms may be 1° (30%) or metastatic (70%).Of all 1° brain tumors, 40% are benign, and these rarely spread beyond the CNS.
Metastatic tumors are most often from 1° lung, breast, kidney, and GI tract neoplasms and melanoma. They occur at the gray-white junction; may be multiple discrete nodules; and are characterized by rapid growth, invasiveness, necrosis, and neovascularization.
More common in males than in females, except for meningiomas.
Symptoms depend on tumor type and location (see Table 2.10-10), local growth and resulting mass effect, cerebral edema, or elevated ICP 2° to ventricular obstruction. Although headaches are often thought of as the main presenting symptom, only 31% of patients present with headache at diagnosis and only 8% have headache as the sole presenting feature.
Seizures or slowly progressive focal motor deficits are the most common presenting features. When ↑ ICP is the presenting feature, symptoms include headache, nausea/vomiting, and diplopia (false localizing CN VI palsies). However, in the era of neuroimaging, it is relatively rare for patients to present with ↑ ICP.
Hemispheric tumors often produce visual field abnormalities and neuropsychiatric symptoms, including personality changes, lethargy, syncope, cognitive decline, aphasia, apraxia, and depression. Parasellar lesions usually present with visual loss and/or diplopia. Posterior fossa lesions tend to present with gait ataxia or cranial nerve deficits and/or ↑ ICP from obstructive hydrocephalus.
Metastases that tend to present with intracranial hemorrhage include renal cell carcinoma, thyroid cancer, choriocarcinoma, and melanoma.
■Contrast CT and MRI with and without gadolinium to localize and determine the extent of the lesion. Gadolinium-enhanced MRI is generally better for visualizing soft tissue tumors and vascularity, but CT is better for
TABLE 2.10-10.  Common 1° NeoplasmsAstrocytoma Arises in brain parenchyma. Low-grade astrocytomas are relatively uncommon. Presents with seizures, focal defcits, or headache. Has a protracted course. Has a better prognosis than glioblastoma multiforme (see below). Resection if possible; radiation. Glioblastoma multiforme (grade IV astrocytoma) High mitotic activity and either endothelial proliferation or necrosis in tumor, leading to ring-enhancing lesions on MRI. There is a major difference between grade III and grade IV. The most common 1° brain tumor. Presents with headache and ↑ seizures, focal def cits, or headache. Progresses rapidly and has a poor prognosis (< 1 year from the time of prognosis). Surgical removal/resection. Radiation and chemotherapy have variable results. Meningioma Originates from the dura mater or arachnoid. Presentation depends on location; often related to cranial neuropathy or is an incidental f nding. Good prognosis. Incidence ↑ with age. Imaging may reveal dural tail. Surgical resection; radiation for unresectable tumors. Acoustic neuroma (schwannoma) Derived from Schwann cells. Presents with ipsilateral tinnitus, hearing loss, vertigo, and late signs of CN V–VII or brain stem compression. Surgical removal. A primitive neuroectodermal tumor. Arises from the fourth ventricle and causes ↑ ICP. Common in children. Highly malignant; may seed the subarachnoid space. May cause obstructive hydrocephalus. Surgical resection coupled with radiation and chemotherapy. May arise from the ependyma of a ventricle (commonly the fourth) or the spinal cord. Common in children; low grade. May cause obstructive hydrocephalus. Surgical resection; radiation. Medulloblastoma Ependymoma evaluating skull base lesions and for emergencies (e.g., obstructive hydrocephalus) when an MRI cannot be rapidly acquired.
■Histologic diagnosis via CT-guided biopsy or surgical tumor debulking/ removal.
Resection (if possible), radiation, and chemotherapy.Therapy is highly dependent on tumor type, histology, progression, and site (see Table 2.10-10).
Corticosteroids can be used to ↓ vasogenic edema and ↓ ICP. Management is often palliative.
Seizure prophylaxis can be used in patients who have had a seizure.
Symptoms of ↑ ICP:Headache that is worse in the morning or with recumbency
In NF1, you— spots) NN (2 Neurof bromas) OT (OpTic glioma) FAI (Freckling, Axillary relative with NF1)
NF1 and NF2 are clinically evident by ages 15 and 20, respectively.
If you see infantile spasms in the setting of a hypopigmented lesion on the child’s trunk, consider tuberous sclerosis.
The most common neurocutaneous disorder. There are two major types: neurofibromatosis 1 (NF1, or von Recklinghausen’s syndrome) and neurofibromatosis 2 (NF2). Both obey autosomal-dominant inheritance. The NF genes are located on chromosome 17 and 22, respectively, for NF1 and NF2.
Diagnostic criteria for NF1 include two or more of the following:
Six café au lait spots (each ≥ 5 mm in children or ≥ 15 mm in adults).
Two neurofibromas of any type.Freckling in the axillary or inguinal area.Optic glioma.Two Lisch nodules (pigmented iris hamartomas).Bone abnormality (e.g., kyphoscoliosis).A f rst-degree relative with NF1.Diagnostic criteria for NF2 are as follows:Bilateral acoustic neuromas or a first-degree relative with NF2 and either unilateral acoustic neuromas or two of any of the following: neurofibromas, meningiomas, gliomas, or schwannoma.
Other features include seizures, skin nodules, and café au lait spots.
MRI of the brain, brain stem, and spine with gadolinium.
Obtain a complete dermatologic exam, ophthalmologic exam, and family history. Auditory testing is recommended.
There is no cure; treatment is symptomatic (e.g., surgery for kyphoscoliosis or debulking of tumors).
Acoustic neuromas and optic gliomas can be treated with surgery or radio-surgery. Meningiomas may be resected.
Affects many organ systems, including the CNS, skin, heart, retina, and kidneys. Obeys autosomal-dominant inheritance.
Presents with convulsive seizures (infantile spasms in infants),“ash-leaf” hypopigmented lesions on the trunk and extremities, and mental retardation (↑ likelihood with early age of onset).
Other skin manifestations include sebaceous adenomas (small red nodules on the nose and cheeks in the shape of a butterfly) and a shagreen patch (a rough papule in the lumbosacral region with an orange-peel consistency).
Two retinal lesions are recognized: (1) mulberry tumors, which arise from the nerve head; and (2) phakomas, which are round, flat, gray lesions located peripherally in the retina.
Symptoms are 2° to small benign tumors that grow on the face, eyes, brain, kidney, and other organs.
Mental retardation and CHF from cardiac rhabdomyoma may also be seen.
Renal involvement may include hamartomas, angiomyolipomas, or, rarely, renal cell carcinoma.
Diagnosis is usually clinical.Skin lesions are enhanced by a Wood’s UV lamp.Head CT: Reveals calcified tubers within the cerebrum in the periventricular area. Lesions may on rare occasion transform into malignant astrocytomas.
ECG: Evaluate for rhabdomyoma of the heart, especially in the apex of the left ventricle (affects > 50% of patients).
Renal ultrasound: May reveal renal hamartomas, masses, or polycystic disease.
Renal CT: May show angiomyolipomas (causing cystic or fibrous pulmonary changes).
CXR: May reveal pulmonary lesions or cardiomegaly 2° to rhabdomyoma.
Treatment should be based on symptoms (e.g., cosmetic surgery for adenoma sebaceum).
Simple partial or complex partial seizures can be controlled with oxcarbazepine or carbamazepine; lamotrigine can be given for generalized seizures. Treat infantile spasms with ACTH or vigabatrin.
Surgical intervention may be indicated in the setting of ↑ ICP or for seizures associated with an epileptogenic focus or severe developmental delay.
A general term for speech and language disorders. Usually results from insults (e.g., strokes, tumors, abscesses) to the “dominant hemisphere” (the left hemisphere in > 95% of right-handed people and 60–80% of left-handed people).
■ A disorder of language production, including writing, with intact comprehension. Due to an insult to Broca’s area in the posterior inferior fron
Broca’s aphasia is also known tal gyrus. Often 2° to a left superior MCA stroke. Also known as motor aphasia.
Hx/PE: Presents with impaired repetition, frustration with awareness of aphasia. deficits, arm and facial hemiparesis, hemisensory loss, and apraxia of the oral muscles. Speech is described as “telegraphic” and agrammatical with frequent pauses.
Tx: Speech therapy (varying outcomes with intermediate prognosis).Wernicke’s Aphasia Wernicke’s aphasia is also known as f uent or receptive ■ A disorder of language comprehension with intact yet nonsensical production. Also known as sensory aphasia. aphasia.
BROca’s is BROken and Wernicke’s is Wordy.Due to an insult to Wernicke’s area in the left posterior superior temporal (perisylvian) gyrus. Often 2° to left inferior/posterior MCA embolic stroke.
Hx/PE: Presents with preserved f uency of language with impaired repetition and comprehension, leading to “word salad.” Patients are unable to follow commands; make frequent use of neologisms (made-up words) and paraphasic errors (word substitutions); show lack of awareness of deficits; and exhibit right upper homonymous quadrantanopia 2° to involvement of Meyer’s loop.
Tx: Treat the underlying etiology and institute speech therapy.A state of unconsciousness marked by a profound suppression of responses to external and internal stimuli (i.e., a state of unarousable unresponsiveness). Lesser states of impaired arousal are known as “obtundation” or “stupor.” Coma is due to either catastrophic structural CNS injury or diffuse metabolic dysfunction. Coma indicates bilateral dysfunction of both cerebral hemispheres or the brain stem (pons or higher); when structural, coma usually results from bilateral pathology. Causes include the following:
Diffuse hypoxic/ischemic encephalopathy (e.g., postcardiac arrest).Diffuse axonal injury from high-acceleration trauma (e.g., MVA).Brain herniation (e.g., cerebral mass lesion, SAH with obstructive hydrocephalus).
Widespread infection (e.g., viral encephalitis or advanced bacterial meningitis).Massive brain stem hemorrhage or infarction (e.g., pontine myelinolysis).Electrolyte disturbances (e.g., hypoglycemia).Exogenous toxins (e.g., opiates, benzodiazepines, EtOH, other drugs).Generalized seizure activity or postictal states.Endocrine (e.g., severe hypothyroidism) or metabolic dysfunction (e.g., thiamine deficiency).
Obtain a complete medical history from witnesses, including current medications (e.g., sedatives).
Conduct thorough medical and neurologic exams, including assessments of mental status, spontaneous motor activity, muscular tone, breathing pattern, funduscopy, pupillary response, eye movements (including the doll’seye maneuver if the neck has been cleared from fracture), corneal refl ex, cold-water caloric testing, gag reflex, and motor or autonomic responses to noxious stimuli applied to limbs, trunk and face (e.g., retromandibular pressure, nasal tickle).
Typically made by a combination of the history/physical and laboratory tests or neuroimaging.
Check glucose, electrolytes, calcium, a renal panel, LFTs, ABG, a toxicology screen, and blood and CSF cultures. Other metabolic tests (e.g., TSH) may be performed based on the clinical index of suspicion.
Obtain a head CT without contrast before other imaging to evaluate for hemorrhage or structural changes. Imaging should precede LP in light of the risk of herniation.
Obtain an MRI to exclude structural changes and ischemia (e.g., brain stem). EEG may be both diagnostic and prognostic.
Rule out catatonia, hysterical or conversion unresponsiveness, “locked-in” syndrome, or persistent vegetative state (PVS), all of which can be confused with true coma (see Table 2.10-11).
“Locked-in” syndrome: Patients are awake and alert but can move only their eyes and eyelids. Associated with central pontine myelinolysis, brain stem stroke, and advanced ALS.
PVS: Characterized by normal wake-sleep cycles but lack of awareness of self or the environment. The most common causes are trauma with diffuse cortical injury or hypoxic ischemic injury.
Initial treatment should consist of the following measures:Stabilize the patient: Attend to ABCs.Reverse the reversible: Administer DONT—Dextrose, Oxygen, Naloxone, and Thiamine.Identify and treat the underlying cause and associated complications.Prevent further damage.Table 2.10-12 describes the neurologic symptoms commonly associated with nutritional deficiencies.
Figure 2.10-8 illustrates common visual field defects and the anatomic areas with which they are associated.
T AB LE 2.1 0-1 1. Differential Diagnosis of Coma
Alertness Wakeful and alert with retained cognitive abilities. Wakefulness without awareness. Unconscious; no sleep-wake cycles. Unconscious; no sleep-wake cycles. Most common causes Central pontine myelinolysis, brain stem stroke, advanced ALS. Diffuse cortical injury or hypoxic ischemic injury. See above. Same as coma. Voluntary motor ability Eyes and eyelids. None. None. None. Respiratory drive Yes. Yes. Yes. None.
T AB LE 2.1 0-1 2. Neurologic Syndromes Associated with Nutritional Deficiencies
Thiamine (vitamin B1) Wernicke’s encephalopathy Korsakoff’s dementia The classic triad consists of encephalopathy (disorientation, inattentiveness, confusion, coma), ophthalmoplegia (nystagmus, lateral rectus palsy, conjugate gaze palsy, vertical gaze palsy), and ataxia (polyneuropathy; cerebellar and vestibular dysfunction leading to problems standing or walking). Above, plus anterograde and retrograde amnesia, horizontal nystagmus, and confabulations. Alcoholics, hyperemesis, starvation, renal dialysis, AIDS. Can be brought on or exacerbated by high-dose glucose administration. Same as above. Usually occurs in the “resolution” phase of Wernicke’s syndrome that was treated late or inadequately. Reversible almost immediately with thiamine administration. Always give thiamine before glucose. Irreversible. Cyanocobalamin (vitamin B12)a Combined system disease (CSD) or subacute combined degeneration of the posterior and lateral columns of the spinal cord (see the discussion of clinical neuroanatomy); peripheral neuropathy. Gradual, progressive onset. Symmetric paresthesias, stocking-glove sensory neuropathy, leg stiffness, spasticity, paraplegia, bowel and bladder dysfunction, sore tongue. Dementia. Patients with pernicious anemia; strict vegetarians; status post gastric or ileal resection; ileal disease (e.g., Crohn’s); alcoholics or others with malnutrition. B12 injections or large oral doses. Folatea Folate def ciency Irritability; personality changes without the neurologic symptoms of CSD. Alcoholics; patients with pernicious anemia. Reversible if corrected early. a Associated with ↑ homocysteine and ↑ risk of vascular events.
In the eye, aqueous humor is produced by the ciliary body on the iris, travels through the pupil into the anterior chamber, and is then drained via the trabecular meshwork in the angle of the anterior chamber.
■Any process that disrupts this natural fl ow can ↑ intraocular pressure (IOP), damaging the optic nerve and causing visual field deficits. Glaucoma is the result of such damage to the nerve.
Left hemianopia with macular sparingFIGURE 2.10-8. Visual field defects.Defect in visual field of Lt. eye  Rt. eye 1 2 3 4 Optic chiasm Optic nerve Optic tract loop Calcarine fissure Visual cortex 1 5 3 2 Dorsal optic radiation Lt. Rt. Lateral geniculatebody ■Open-angle glaucoma is much more common in the United States than closed-angle glaucoma.
Occurs when the iris dilates and pushes against the lens of the eye, disrupting flow of aqueous humor into the anterior chamber. Pressure in the posterior chamber then pushes the peripheral iris forward and blocks the angle.
Risk factors include family history, older age, Asian ethnicity, hyperopia, prolonged pupillary dilation (prolonged time in a dark area, stress, medications), anterior uveitis, and lens dislocation.
Hx/PE: Classically presents with extreme eye pain, blurred vision, headache, nausea, and vomiting. A hard, red eye is seen (from acute closure of a narrow anterior chamber angle); the pupil is dilated and nonreactive to light. IOP is ↑. If it resolves spontaneously prior to presentation (e.g., with pupillary constriction in sunlight), ophthalmologic examination may reveal narrow angles in one or both eyes.
Dx: Diagnosis is based on clinical history and examination. Those that resolve may mimic a migraine headache with blurred vision; the distinction is that the headaches and blurred vision are more likely to be triggered by darkness (due to pupillary dilation) rather than by bright lights (migraine).
Tx: This is a medical emergency that can cause blindness. Treatment to ↓ IOP may include eyedrops (timolol, pilocarpine, apraclonidine) or systemic medications (oral or IV acetazolamide, IV mannitol). Laser peripheral iridotomy, which creates a hole in the peripheral iris, is curative and may be performed prophylactically.
generally occurs bilaterally, ■Flow of aqueous humor through the trabecular meshwork is limited, in- creasing IOP. A diseased trabecular meshwork obstructs proper drainage of the eye, leading to a gradual ↑ in pressure and progressive vision loss. occurs unilaterally.
In the United States, macular degeneration is the leading cause of permanent bilateral visual loss in the elderly.
Risk factors include age > 40 years, African-American ethnicity, diabetes, and myopia.
Hx/PE: Usually asymptomatic until late in the clinical course, when patients may begin to notice visual deficits. Should be suspected in patients > 35 years of age who need frequent lens changes and have mild headaches, visual disturbances, and impaired adaptation to darkness. The earliest visual defect is seen in the peripheral nasal fields. Cupping of the optic nerve head is seen on funduscopic exam.
Dx: Tonometry, ophthalmoscopic visualization of the optic nerve, and visual field testing are most important. A diseased trabecular meshwork obstructs proper drainage of the eye, gradually increasing pressure and leading to progressive vision loss.
Tx: Treat with topical β-blockers (timolol, betaxolol) to ↓ aqueous humor production or with pilocarpine to ↑ aqueous outflow. Carbonic anhydrase inhibitors may also be used. If medication fails, laser trabeculoplasty or a trabeculectomy can improve aqueous drainage.
More common among Caucasians, females, smokers, and those with a family history.
Presents with painless loss of central vision.Atrophic (“dry”) macular degeneration: Responsible for 80% of cases. Causes gradual vision loss.
Exudative or neovascular (“wet”) macular degeneration: Much less common, but associated with more rapid and severe vision damage.
Funduscopy by an ophthalmologist reveals drusen and/or pigmentary changes in patients with atrophic AMD. Hemorrhage and subretinal fluid are suggestive of exudative AMD.
Atrophic AMD:No treatment is currently available, although a combination of vitamins (vitamin C, vitamin E, beta-carotene, and zinc) has been found to slow disease progression.
An ↑ mortality rate from high doses of vitamin E and an elevated lung cancer incidence among individuals on beta-carotene supplementation may require modification of this regimen for smokers.
Exudative AMD:VEGF inhibitors have been shown to improve vision (ranibizumab, bevacizumab) or slow visual loss (pegaptanib) in patients with exudative AMD.
Photodynamic therapy with verteporfin, which involves use of a laser to selectively target retinal vessels, may be useful in conjunction with VEGF inhibitors.
Occurs in elderly patients and is often idiopathic.Central retinal artery occlusion: Presents with sudden, painless, unilateral blindness. The pupil reacts to a near stimulus but is sluggishly reactive to direct light. Patients present with a cherry-red spot on the fovea, retinal swelling (whitish appearance to the nerve fiber layer), and retinal arteries that may appear bloodless.
Central retinal vein occlusion: Characterized by rapid, painless vision loss of variable severity. A choked, swollen optic disk with hemorrhages, venous stasis retinal hemorrhages, cotton-wool spots, and edema of the macula may be seen on funduscopic exam.
Central retinal artery occlusion: Intra-arterial thrombolysis of the ophthalmic artery within eight hours of onset of symptoms may produce benefit in some patients, although evidence remains controversial. Other treatments applied but of unclear benefit include increasing IOP through drainage of the anterior chamber or IV acetazolamide. If implemented, treatments should be applied immediately before irreversible retinal infarction and permanent blindness ensue.
Central retinal vein occlusion: Laser photocoagulation has variable results.Physiology of Normal Pregnancy 321 THE BASICS OF PREGNANCY 321 NORMAL PHYSIOLOGY OF PREGNANCY 321
Teratology 325 Maternal-Fetal Infections 326 Spontaneous Abortion  328 Elective Termination of Pregnancy 329 Normal Labor and Delivery 329
Medical Complications of Pregnancy 336 HYPEREMESIS GRAVIDARUM 336 DIABETES IN PREGNANCY 338 GESTATIONAL AND CHRONIC HYPERTENSION 340 PREECLAMPSIA AND ECLAMPSIA 340 ANTEPARTUM HEMORRHAGE 342
Obstetric Complications of Pregnancy 342 ECTOPIC PREGNANCY 342 INTRAUTERINE GROWTH RESTRICTION 344 FETAL MACROSOMIA 345 POLYHYDRAMNIOS 345 OLIGOHYDRAMNIOS 345 Rh ISOIMMUNIZATION 345 GESTATIONAL TROPHOBLASTIC DISEASE 346 MULTIPLE GESTATIONS 348 Abnormal Labor and Delivery 348 SHOULDER DYSTOCIA 348 FAILURE TO PROGRESS 348 RUPTURE OF MEMBRANES 349 PRETERM LABOR 350 FETAL MALPRESENTATION 351 INDICATIONS FOR CESAREAN SECTION 351 EPISIOTOMY 353
The Basics of PregnancyThe following terms and concepts are central to an understanding of the physiologic processes of pregnancy (see also Figure 2.11-1).
Gravidity: The number of times a woman has been pregnant.
Parity: The number of pregnancies that led to a birth beyond 20 weeks’ gestational age or an infant weighing > 500 g.
Developmental age (DA): The number of weeks and days since fertilization. Typically used only in research, as the exact date of fertilization is not commonly known.
Gestational age (GA): The number of weeks and days measured from the frst day of the last menstrual period (LMP). GA can also be determined by:
Fundal height: At 20 weeks, the uterus is at the umbilicus and grows approximately 1 cm/week.
Quickening, or appreciation of fetal movement: Typically occurs at 17–18 weeks.
Fetal heart tones: Can be heard at 10–12 weeks by Doppler.
Ultrasound: Measures fetal crown-rump length (CRL) at 5–12 weeks and measures biparietal diameter (BPD), femur length (FL), and abdominal circumference (AC) from 13 weeks. Ultrasound measurement of GA is most reliable during the f rst trimester.
Normal Physiology of PregnancyThe normal physiologic changes that occur during pregnancy are graphically illustrated according to system in Figures 2.11-2 and 2.11-3.
Nägele’s rule: due date = last menstrual period + nine months + seven days.
F IGU R E 2.1 1 -1. Perinatal nomenclature by date.
(Reproduced, with permission, from DeCherney AH, Nathan L. Current Diagnosis & Treatment: Obstetrics & Gynecology, 10th ed. New York: McGraw-Hill, 2007: Fig. 9-1.) (Reproduced, with permission, from Gardner DG, Shoback D. Greenspan’s Basic & Clinical Endocrinology, 8th ed. New York: McGraw-Hill, 2007: Fig. 17-2A.)
The goal of prenatal care is to prevent, diagnose, and treat conditions that can lead to adverse outcomes in pregnancy. Expected weight gain, nutrition, and exercise recommendations are outlined in Table 2.11-1.
Get a quantitative β-hCG:To diagnose and follow ectopic pregnancy.To monitor trophoblastic disease.To screen for fetal aneuploidy.Still UNDERage at 18: trisomy 18 = ↓ AFP, ↓ estriol, ↓β-hCG, ↓ inhibin A.
Table 2.11-2 outlines a typical prenatal diagnostic testing schedule by week. The sections that follow describe each recommended screening modality in further detail.
The standard for diagnosing pregnancy.Produced by the placenta; peaks at 100,000 mIU/mL by 10 weeks of gesta tion. ■↓ throughout the second trimester; levels off in the third trimester.
hCG levels double approximately every 48 hours during early pregnancy. This is often used to diagnose ectopic pregnancy when doubling is abnormal.
Maternal serum α-fetoprotein (MSAFP), which is produced by the fetus, crosses the placenta in small amounts and enters the maternal circulation. Measurement results are reported as multiples of the median (MoMs) and depend on accurate gestational dating.
Elevated MSAFP (> 2.5 MoMs): Associated with open neural tube defects (anencephaly, spina bifda), abdominal wall defects (gastroschisis, omphalocele), multiple gestation, incorrect gestational dating, fetal death, and placental abnormalities (e.g., placental abruption).
Decreased MSAFP (< 0.5 MoM): Associated with trisomy 21 and 18, fetal demise, and inaccurate gestational dating.
MSAFP is now rarely performed alone because its sensitivity for detecting chromosomal abnormalities is ↑ by adding inhibin A to estriol, β-hCG, and MSAFP (quad screening). Results of quad screening are as follows: gradually increases an addi   tional 10% by 28 weeks.
Peripheral venous Progressive increase to term. distentionPeripheral vascular Progressive decrease to term. +40 resistance +30Pulmonary Respiratory rate Unchanged. +20Respiratory rate, vital capacityTidal volume Increases by 30–40%.Expiratory reserve Gradual decrease.Vital capacity Unchanged. +10Respiratory minute Increases by 40%.   volumeElectrolytesElectrolytes Unchanged. 0 second trimester. +20Hematocrit Decreases slightly. +10Fibrinogen Increases.
Gastrointestinal Sphincter tone Decreases.0 Gastric emptying Increases. time (Reproduced, with permission, from Gardner DG, Shoback D. Greenspan’s Basic & Clinical Endocrinology, 8th ed. New York: McGraw-Hill, 2007: Fig. 17-2B.)
TABLE 2.11-1.  Standard Prenatal CareWeight gain Guidelines for weight gain in pregnancy: ■Recommended gain: An additional 100–300 kcal/day; 500 kcal/day during breastfeeding. ■Excessive gain: > 1.5 kg/mo. ■Inadequate gain: < 1 kg/mo. Guidelines according to prepregnancy body mass index (BMI): ■Underweight (BMI < 19.8): 12–18 kg gain. ■Acceptable (BMI 19.8–26.0): 11–16 kg gain. ■Overweight (BMI 26.1–29.0): 7–11 kg gain. ■Severely overweight (BMI > 29.0): 7 kg gain. Nutrition Guidelines for nutritional supplementation: ■Folic acid supplements (↓ neural tube defects for all reproductive-age women): 0.4 mg/day, or 4 mg/day for women with a history of neural tube defects in prior pregnancies. ■Iron: Starting at the frst visit, 30 mg/day of elemental iron (or 150 mg of iron sulfate). ■Calcium: 1300 mg/day for women < 19 years of age; 1000 mg/day for those > 19 years of age. Additional guidelines for complete vegetarians: ■Vitamin D: 10 μg or 400 IU/day. ■Vitamin B12: 2 μg/day. Exercise Thirty minutes of moderate exercise daily is recommended.
Trisomy 18: All four are ↓.Trisomy 21: ↓ AFP and estriol; ↑ β-hCG and inhibin A.
2 up, 2 down: trisomy 21 = ↓ AFP, ↓ estriol, ↑β-hCG, ↑ inhibin A.
Recommended at weeks 9–14.Pregnancy-associated plasma protein A (PAPP-A) + ultrasound-determined nuchal transparency (a measure of fuid in the fetal neck) + free β-hCG can detect ~85% of cases of Down syndrome and ~97% of cases of trisomy 18.
Advantages: Screen of low-risk pregnant women (< 35 years of age); available earlier and less invasive than chorionic villus sampling (see below).
Recommended at weeks 10–12.Involves transcervical or transabdominal aspiration of placental (chorionic villi) tissue.
Advantages: Has a diagnostic accuracy comparable to that of amniocentesis; available at 10–12 weeks’ gestation.
Disadvantages: Carries a risk of fetal loss (1–2%); cannot detect open neural tube defects.
Limb defects have been associated with CVS performed at ≤ 9 weeks.
T AB LE 2.1 1 -2. Prenatal Diagnostic Testing Schedule
Prenatal visits Weeks 0–28: Every four weeks. Weeks 29–35: Every two weeks. Weeks 36–birth: Every week. Initial visit 9–14 weeks Offer PAPP-A + nuchal transparency + free β-hCG +/– CVS. 15–20 weeks Offer MSAFP or quad screen (AFP, estriol, β-hCG, and inhibin A) +/– amniocentesis. 18–20 weeks Ultrasound for full anatomic screen. 24–28 weeks One-hour glucose challenge test for gestational diabetes screen.
Heme: CBC, Rh factor, type and screen. Infectious disease: UA and culture, rubella antibody titer, HBsAg, RPR/VDRL, cervical gonorrhea and chlamydia, PPD, HIV, Pap smear (to check for dysplasia). If indicated: HbA1c, sickle cell screening. Discuss genetic screening: Tay-Sachs, CF.
Recommended at 15–20 weeks.Consists of transabdominal aspiration of amniotic fuid using an ultrasound-guided needle and evaluation of fetal cells for genetic studies.
Advantages: Detects ~80% of open neural tube defects, ~85% of cases of Down syndrome, and ~60% of cases of trisomy 18.
Disadvantages: Risks include premature rupture of membranes (PROM), chorioamnionitis, and fetal-maternal hemorrhage, which can result in fetal loss (0.5%).
Indicated for the following:In women who will be > 35 years of age at the time of delivery.
In conjunction with an abnormal quad screen.In Rh-sensitized pregnancy to obtain fetal blood type or to detect fetal hemolysis.
To evaluate fetal lung maturity via a lecithin-to-sphingomyelin ratio ≥ 2.5 or to detect the presence of phosphatidylglycerol (done during the third trimester).
Major defects are apparent in about 3% of births and in roughly 4.5% of children by f ve years of age. Table 2.11-3 lists FDA risk classif cations of pharmaceutical products for use during pregnancy. Table 2.11-4 outlines common teratogenic agents.
T AB LE 2.1 1 -3.  FDA Risk Classifcation of Drugs for Use During Pregnancy
Category A Adequate and well-controlled studies in women fail to demonstrate a risk to the fetus in the frst trimester (and there is no risk in later trimesters). The possibility of fetal harm seems remote. Vitamin B6, vitamin E, folic acid (within the recommended daily allowances). Category B Either animal reproduction studies have not demonstrated risk to the fetus but no adequate and well-controlled studies in pregnant women have been reported, or animal reproduction studies have shown an adverse effect that was not confrmed in controlled studies in women in the frst trimester (and there is no evidence of risk in later trimesters). Ampicillin, acetaminophen, bupropion. Category C Either studies in animals have revealed adverse effects on the fetus but no controlled studies in women have been reported, or studies in women and animals are not available. Drugs should be given only if the potential benef t justifes the potential risk to the fetus. Diphenhydramine, rifampin, zidovudine (AZT). Category D Positive evidence of human fetal risk exists, but the benefts from use in pregnant women may be acceptable despite the risk. Alcohol, phenytoin, tetracycline. Category X Studies in animals or humans have demonstrated fetal abnormalities, or evidence exists of fetal risk based on human experience, or both, and the risk in pregnant women clearly outweighs any possible benef t. Isotretinoin, thalidomide, warfarin.
Pregnant women should not change the cat’s litterbox.First-trimester toxoplasmosis infection is less common but more severe. Third-trimester infection is more common but less severe.
May occur at any time during pregnancy, labor, and delivery. Common sequelae include premature delivery, CNS abnormalities, anemia, jaundice, hepatosplenomegaly, and growth retardation. The most common pathogens can be remembered through use of the mnemonic TORCHeS (see also Table 2.11-5):
Toxoplasmosis: Transplacental transmission, with 1° infection occurring via consumption of raw meat or contact with cat feces. Specif c f ndings include hydrocephalus, intracranial calcifications, chorioretinitis, and ring-enhancing lesions on head CT.
Other: Parvovirus, varicella, Listeria, TB, malaria, fungi.Rubella: Transplacental transmission in the frst trimester. Specif c f ndings include a purpuric “blueberry muffin” rash, cataracts, mental retardation, hearing loss, and patent ductus arteriosus (PDA).
CMV: The most common congenital infection; primarily transmitted transplacentally. Specif c fndings include a petechial rash (similar to “blueberry muffn” rash) and periventricular calcifications.
Herpes: Intrapartum transmission if the mother has active lesions. Can cause skin, eye, and mouth infections or life-threatening CNS/systemic infection.
HIV: Transmission can occur in utero, at the time of delivery, or via breast milk. Occurs in 13–39% of births to infected mothers. The combination of AZT treatment (prenatally, intrapartum, and neonatally for the f rst six weeks of life) and cesarean delivery can lower transmission to 2%. Newborns with congenitally acquired HIV are often asymptomatic. Failure to
T AB LE 2.1 1 -4. Common Teratogenic Agents and Their Associated Defects
ACEIs Fetal renal tubular dysplasia and neonatal renal failure, oligohydramnios, intrauterine growth restriction (IUGR), lack of cranial ossif cation. Alcohol Fetal alcohol syndrome (growth restriction before and after birth, mental retardation, midfacial hypoplasia, renal and cardiac defects). Consumption of > 6 drinks per day is associated with a 40% risk of fetal alcohol syndrome. Androgens Virilization of females; advanced genital development in males. Carbamazepine Neural tube defects, fngernail hypoplasia, microcephaly, developmental delay, IUGR. Cocaine Bowel atresias; congenital malformations of the heart, limbs, face, and GU tract; microcephaly; IUGR; cerebral infarctions. Diethylstilbestrol (DES) Clear cell adenocarcinoma of the vagina or cervix, vaginal adenosis, abnormalities of the cervix and uterus or testes, possible infertility. Lead ↑ spontaneous abortion (SAB) rate; stillbirths. Lithium Congenital heart disease (Ebstein’s anomaly). Methotrexate ↑ SAB rate. Organic mercury Cerebral atrophy, microcephaly, mental retardation, spasticity, seizures, blindness. Phenytoin IUGR, mental retardation, microcephaly, dysmorphic craniofacial features, cardiac defects, f ngernail hypoplasia. Radiation Microcephaly, mental retardation. Medical diagnostic radiation delivering < 0.05 Gy to the fetus has no teratogenic risk. Streptomycin and kanamycin Hearing loss; CN VIII damage. Tetracycline Permanent yellow-brown discoloration of deciduous teeth; hypoplasia of tooth enamel. Thalidomide Bilateral limb defciencies, anotia and microtia, cardiac and GI anomalies. Trimethadione and paramethadione Cleft lip or cleft palate, cardiac defects, microcephaly, mental retardation. Valproic acid Neural tube defects (spina bifda); minor craniofacial defects. Vitamin A and derivatives ↑ SAB rate, microtia, thymic agenesis, cardiovascular defects, craniofacial dysmorphism, microphthalmia, cleft lip or cleft palate, mental retardation. Warfarin (wages war on the fetus) Nasal hypoplasia and stippled bone epiphyses, developmental delay, IUGR, ophthalmologic abnormalities.
T AB LE 2.1 1 -5. Diagnosis and Treatment of Common Congenital Infections
Toxoplasmosis Serologic testing Pyrimethamine + sulfadiazine Avoid exposure to cat feces during pregnancy. Spiramycin prophylaxis for the third trimester. Rubella Serologic testing Immunize before pregnancy; vaccinate the mother after delivery if serologic titers remain . CMV Urine culture, PCR of amniotic f uid Postpartum ganciclovir HSV Serologic testing Acyclovir Perform a C-section if lesions are present at delivery. ELISA, Western blot AZT or nevirapine in pregnant women with HIV; perform elective C-section if viral load is > 1000; treat infants with prophylactic AZT; avoid breastfeeding. Dark-f eld microscopy, VDRL/RPR, FTA-ABS Penicillin Penicillin in pregnant women who test . HIV Syphilis thrive, bacterial infections with common organisms, and an ↑ incidence of upper and lower respiratory diseases may appear early or may be delayed for months to years. HIV-mothers should be counseled not to breastfeed their infants.
Syphilis: Primarily intrapartum transmission. Specif c fndings include a maculopapular skin rash, lymphadenopathy, hepatomegaly, “snuffl es” (mucopurulent rhinitis), and osteitis. In childhood, late congenital syphilis is characterized by saber shins, saddle nose, CNS involvement, and Hutchinson’s triad: peg-shaped upper central incisors, deafness, and interstitial keratitis (photophobia, lacrimation).
Defned as loss of products of conception (POC) prior to the 20th week of pregnancy. Approximately 60% of chemically evident pregnancies and 15– 20% of clinically diagnosed pregnancies terminate in a SAB. More than 80% will occur in the frst trimester. Risk factors are as follows:
Chromosomal abnormalities: A factor in approximately 50% of SABs in the frst trimester, 20–30% in second-trimester losses, and 5–10% in third-trimester losses.
Maternal factors:Maternal trauma, ↑ maternal age, infection, dietary def ciencies.Inherited thrombophilias: Factor V Leiden, prothrombin, antithrombin, proteins C and S, methylene tetrahydrofolate reductase (hyperhomocysteinemia).
Immunologic issues: Antiphospholipid antibodies, alloimmune factors.Anatomic issues: Uterine abnormalities, incompetent cervix, cervical conization or loop electrosurgical excision procedure (LEEP), cervical injury, DES exposure, anatomical abnormalities of the cervix.
Endocrinologic issues: Diabetes mellitus (DM), hypothyroidism, progeste rone def ciency.
Environmental factors: Tobacco (with > 14 cigarettes/day, the risk is twofold), alcohol, caffeine (> 500 mg caffeine/day), toxins, drugs, radiation.
Fetal factors: Anatomic malformation.See Table 2.11-6 for types of SAB.■↓ levels of hCG.Can identify the gestational sac 5–6 weeks from the LMP, a fetal pole at six weeks, and fetal cardiac activity at 6–7 weeks.
With accurate dating, a small, irregular intrauterine sac without a fetal pole on transvaginal ultrasound is diagnostic of an abnormal pregnancy.
Maternal Rh type should be determined and RhoGAM given if the type is Rh .
It has been estimated that 50% of all pregnancies in the United States are unintended. Some 25% of all pregnancies end in elective abortion. Options for elective abortion depend on GA and patient preferences (see Table 2.11-7).
Leopold’s maneuvers are used to determine fetal lie (longitudinal or transverse) and, if possible, fetal presentation (breech or cephalic).
Cervical examination:Evaluate dilation, effacement, station, cervical position, and cervical consistency. Use the Bishop score (see Table 2.11-8) to evaluate the favorability of delivery and the probability of succeeding with an induction. Scoring is interpreted as follows: 0–4: Indicates a 45–50% chance of failure. Give prostaglandins for induction.
5–9: Points to a 10% chance of failure. Give pitocin for induction.
10–13: Associated with a very high probability of success. There is no need for intervention for induction.
Confrm or determine fetal presentation.Determine fetal position through palpation of the fetal sutures and fontanelles.
Conduct a sterile speculum exam if rupture of membranes (ROM) is suspected.
Table 2.11-9 and Figure 2.11-4 depict the normal stages of labor.
FHR monitoring is the most common obstetric procedure and is used in 85% of live births in the United States. It may be performed with an electrode at
T AB LE 2.1 1 -6. Types of Spontaneous Abortion
Complete POC is expelled. Pain ceases, but spotting may persist. Closed os. Ultrasound shows an empty uterus. POC should be sent to pathology to conf rm fetal tissue. None. Incomplete Some POC is expelled. Bleeding/mild cramping. Visible tissue on exam. Open os. Ultrasound shows retained fetal tissue. Manual uterine aspiration (MUA) or D&C. Threatened No POC is expelled. Uterine bleeding +/– abdominal pain. Closed os + intact membranes + fetal cardiac motion on ultrasound. Pelvic rest for 24–48 hours and follow-up ultrasound to assess the viability of conceptus. Inevitable No POC is expelled. Uterine bleeding and cramps. Open os +/− ROM. MUA, D&C, misoprostol, or expectant management. Missed No POC is expelled. No fetal cardiac motion. No uterine bleeding. Brownish vaginal discharge. Closed os. No fetal cardiac activity; retained fetal tissue on ultrasound. MUA, D&C, or misoprostol. Septic Endometritis leading to septicemia. Maternal mortality is 10–15%. Hypotension, hypothermia, ↑ WBC count. MUA, D&C, and IV antibiotics. Intrauterine fetal demise Absence of fetal cardiac activity. Uterus small for GA; no fetal heart tones or movement on ultrasound. Induce labor; evacuate the uterus (D&E) to prevent DIC at GA > 16 weeks. Recurrenta If early in pregnancy, often due to chromosomal abnormalities. If later in pregnancy, often due to hypercoagulable states (e.g., SLE, factor V Leiden, protein S def ciency). Incompetent cervix should be suspected with a history of painless dilation of the cervix and delivery of a normal fetus between 18 and 32 weeks. Karyotyping of both parents. Hypercoagulability workup of mother. Evaluate for uterine abnormalities. Surgical cerclage procedures to suture the cervix closed until labor or ROM occurs with subsequent removal prior to delivery. Restriction of activities. a Defned as two or more consecutive SABs or a total of three SABs in one year.
tached to the fetal scalp (a method that yields more precise results), or external monitoring can be conducted using Doppler ultrasound (a less invasive option). However, continuous electronic FHR monitoring has not been shown to be more effective than appropriate intermittent monitoring.
TABLE 2.11-7. Elective Termination of PregnancyFirst trimester (90% therapeutic abortions [TABs]) Medical management: ■Oral mifepristone (low dose) + oral/vaginal misoprostol ■IM/oral methotrexate + oral/vaginal misoprostol ■Vaginal or sublingual or buccal misoprostol (high dose), repeated up to three times Surgical management: ■ Manual aspiration ■D&C with vacuum aspiration Up to: 49 days’ GA 49 days’ GA 56 days’ GA Up to 13 weeks’ GA Second trimester (10% TABs) Obstetric management: Induction of labor (typically with prostaglandins, amniotomy, and oxytocin) Surgical management: D&E 13–24 weeks’ GA (depending on state laws) Same as above
Patients without complications: Review FHR tracings every 30 minutes in the frst stage of labor and every 15 minutes in the second stage of labor.
Patients with complications: Review FHR tracings every 15 minutes in the frst stage of labor and every 5 minutes in the second stage of labor.
Rate (normal = 110–160 bpm):FHR < 110 bpm: Bradycardia. Can be caused by congenital heart malformations or severe hypoxia (2° to uterine hyperstimulation, cord prolapse, or rapid fetal descent).
FHR > 160 bpm: Tachycardia. Can be caused by hypoxia, maternal fever, or fetal anemia.
Variability (normal beat-to-beat variability = 6–25 bpm): See Figures 2.11-5 and 2.11-6.
Undetectable variability: Indicates severe fetal distress.TABLE 2.11-8.  Bishop ScoreTABLE 2.11-9.  Stages of LaborFirst Latent Active Onset of labor to 3–4 cm dilation 4 cm to complete cervical dilation (10 cm) 6–11 hrs 4–6 hrs (1.2 cm/hr) 4–8 hrs 2–3 hrs (1.5 cm/hr) Prolongation seen with excessive sedation and hypertonic uterine contractions. Prolongation seen with cephalopelvic disproportion. Second Complete cervical dilation to delivery of infant 0.5–3.0 hrs 5–30 min Baby goes through all cardinal movements of delivery. Third Delivery of infant to delivery of placenta 0–0.5 hr 0–0.5 hr Uterus contracts and placenta separates to establish hemostasis.
Minimal variability: < 6 bpm. Indicates fetal distress or the effects of opioids or magnesium.
Normal variability: 6–25 bpm.Marked variability: > 25 bpm. May indicate fetal distress; may occur before a ↓ in variability.
Sinusoidal variability: Points to serious fetal anemia; may also occur during maternal meperidine use.
FIGURE 2.11-4. Stages of labor.Cervical dilation, level of descent, and orientation of occipitoanterior presentation during various stages of labor. (Reproduced, with permission, from DeCherney AH. Current Obstetric & Gynecologic Diagnosis & Treatment, 8th ed. Stamford, CT: Appleton & Lange, 1994: 211.)
F IGU R E 2.1 1 -5. Varying (variable) fetal heart rate decelerations.
Deceleration B exhibits “shoulders” of acceleration compared with deceleration A. (Reproduced, with permission, from Cunningham FG et al. Williams Obstetrics, 22nd ed. New York: McGraw-Hill, 2005: Fig. 18-21.)
F IGU R E 2.1 1 -6. Late fetal heart rate decelerations.
Late decelerations due to uteroplacental insuffciency resulting from placental abruption. Immediate cesarean delivery was performed. Umbilical artery pH was 7.05 and PO2 was 11 mmHg. (Reproduced, with permission, from Cunningham FG et al. Williams Obstetrics, 22nd ed. New York: McGraw-Hill, 2005: Fig. 18-17.)
Accelerations: Onset of an ↑ in FHR to a peak in < 30 seconds. Reassuring because they indicate fetal ability to appropriately respond to the environment.
Decelerations: See Table 2.11-10.In general, antepartum fetal surveillance is used in pregnancies in which the risk of antepartum fetal demise is ↑. Testing is initiated in most at-risk patients
TABLE 2.11-10. Types of Fetal DecelerationEarly A visually apparent, gradual (onset to nadir in > 30 sec) ↓ in FHR with a return to baseline that mirrors the uterine contraction. Head compression from the uterine contraction (normal). Late A visually apparent, gradual (onset to nadir in > 30 sec) ↓ in FHR with return to baseline whose onset, nadir, and recovery occur after the beginning, peak, and end of uterine contraction, respectively. Uteroplacental insuff ciency and fetal hypoxemia. Variable An abrupt (onset to nadir in < 30 sec), visually apparent ↓ in FHR below baseline lasting ≥ 15 sec but < 2 min. Umbilical cord compression. Illustrations reproduced, with permission, from Cunningham FG et al. Williams Obstetrics, 22nd ed. New York: McGraw-Hill, 2005: Figs.18-14, 18-16, and 18-18.
at 32–34 weeks (or 26–28 weeks if there are multiple worrisome risk factors present). The following assessments are made:
Fetal movement assessment: Assessed by the mother as the number of fetal movements over one hour. The average time to obtain 10 movements is 20 minutes. Maternal reports of ↓ fetal movements should be evaluated by means of the tests described below.
Nonstress test (NST): Performed with the mother resting in the lateral tilt position (to prevent supine hypotension). FHR is monitored externally by Doppler along with a tocodynamometer to detect uterine contractions. Acoustic stimulation may be used.
“Reactive” (normal response): Two accelerations of ≥ 15 bpm above baseline lasting for at least 15 seconds over a 20-minute period (see Figure 2.11-7).
“Nonreactive”: Fewer than two accelerations over a 20-minute period. Perform further tests (e.g., a biophysical profle). Lack of FHR accelerations may occur with any of the following: GA < 32 weeks, fetal sleeping, fetal CNS anomalies, and maternal sedative or narcotic administration.
Contraction stress test (CST): Performed in the lateral recumbent position. FHR is monitored during spontaneous or induced (via nipple stimulation or oxytocin) contractions. Reactivity is determined from fetal heart monitoring, as with the NST. The procedure is contraindicated in women with preterm membrane rupture or known placenta previa; women with a history of uterine surgery; and women who are at high risk for preterm labor.
FIGURE 2.11-7. Reactive nonstress test.(Reproduced, with permission, from Cunningham FG et al. Williams Obstetrics, 22nd ed. New York: McGraw-Hill, 2005: Fig. 15-7.)
A negative CST is good; a positive one is bad.
When performing a BPP, remember to–Test the Baby, MAN!“Positive” CST: Defned by late decelerations following 50% or more of contractions in a 10-minute window; raises concerns about fetal compromise. Delivery is usually warranted.
“Negative” CST: Defned as no late or signifcant variable decelerations within 10 minutes and at least three contractions. Highly predictive of fetal well-being in conjunction with a normal NST.
“Equivocal” CST: Def ned by intermittent late decelerations or significant variable decelerations.
Biophysical profile (BPP): Uses real-time ultrasound to assign a score of 2 (normal) or 0 (abnormal) to fve parameters: fetal tone, breathing, movement, amniotic fuid volume, and NST. Scoring is as follows: 8–10: Reassuring for fetal well-being.
6: Considered equivocal. Term pregnancies are usually delivered with this prof le.
0–4: Extremely worrisome for fetal asphyxia; strong consideration should be given to immediate delivery if no other explanation is found.
Modified biophysical profile (mBPP): Combines the NST with the amniotic fuid index (AFI, or the sum of the measurements of the deepest cord-free amniotic fuid measured in each of the abdominal quadrants). The test is considered normal with a reactive NST and an AFI > 5 cm.
Umbilical artery Doppler velocimetry: With IUGR, there is reduction and even reversal of umbilical artery diastolic fow. The test is of benef t only when IUGR is suspected.
Oligohydramnios (AFI < 5 cm) always warrants further workup.Uterine contractions and cervical dilation result in visceral pain (T10–L1). Descent of the fetal head and pressure on the vagina and perineum result in somatic pain (pudendal nerve, S2–S4). In the absence of a medical contraindication, maternal request is a suffcient medical indication for pain relief during labor. Absolute contraindications to regional anesthesia (epidural, spinal, or combination) include the following (see also Table 2.11-11):
Maternal use of a once-daily dose of low-molecular-weight heparin (LMWH) within 12 hours
Skin infection over the site of needle placement ■↑ ICP caused by a mass lesion
If “morning sickness” persists after the f rst trimester, think hyperemesis gravidarum.
Persistent vomiting not related to other causes, acute starvation (usually large ketonuria), and weight loss (usually at least a 5% ↓ from prepregnancy weight). Occurs in 0.5–2.0% of pregnancies. More common in f rst pregnancies, multiple gestations, and molar pregnancies. ↑β-hCG and ↑ estradiol have been implicated in its pathophysiology.
T AB LE 2.1 1 -1 1. Available Methods of Anesthesia and Analgesia
Nonpharmacologic (social support, massages, breathing, aromatherapy, ambulation and repositioning) No known  side effects. Works by increasing coping with pain rather than eliminating pain. Limited pain relief. Opioids Provide an adequate level of pain relief for some women without the risks associated with regional anesthesia. Local block (lidocaine) Excellent anesthesia before episiotomy and during repair of lacerations; can be used to perform a pudendal block. Rarely, may cause seizures, hypotension, and cardiac arrhythmias. Epidural The most effective form of pain relief; can also be used for cesarean delivery or postpartum tubal ligation. Can result in pruritus, fever, hypotension, and transient FHR deceleration. Spinal Rapid-onset analgesia that provides excellent pain relief for procedures of limited duration (30–250 minutes). Limited duration; puts patients at risk for hypotension, postdural puncture headache, and transient neurologic symptoms. Combined spinal epidural General
Offers rapid onset of spinal analgesia combined with the ability to prolong the duration of analgesia with continuous epidural infusion.
Used in emergent cesarean delivery and indicated in some cases of FHR abnormality; can be useful in cases where regional anesthesia is absolutely contraindicated or fails.
The sedative effect of opioids ↓ FHR variability and ↑ the possible need for neonatal naloxone administration and f ve-minute Apgar scores < 7.
Carries the risks of both procedures; may ↑ the risk of bradycardia and emergent cesarean delivery over epidural analgesia alone.
Requires airway control; carries a signif cant risk of maternal aspiration and neonatal depression (inhaled anesthetic agents readily cross the placenta); associated with higher maternal morbidity rates than epidural anesthesia.
Distinguish from “morning sickness,” acid refux, gastroenteritis, hyperthyroidism, and neurologic conditions.
Rule out molar pregnancy: Check β-hCG level and ultrasound.Determine severity: Evaluate for ketonemia, ketonuria, hyponatremia, and hypokalemic, hypochloremic metabolic alkalosis. Measure liver enzymes, serum bilirubin, and serum amylase/lipase.
The f rst step in the diagnosis of hyperemesis gravidarum is to rule out molar pregnancy with ultrasound +/– β-hCG.
The f rst step in the management of hyperemesis gravidarum is vitamin B6 and doxylamine if not severe or antiemetics and IV f uids if severe.
Gestational diabetes is typically asymptomatic, so the f rst step in diagnosis is a one-hour glucose challenge at 24–28 weeks. If ≥ 140 mg/dL, perform a three-hour glucose challenge test.
Keys to the management of gestational diabetes: (1) the ADA diet; (2) insulin if needed; (3) ultrasound for fetal growth; and (4) NST beginning at 30–32 weeks.
First step: Administer vitamin B6.Second step: Doxylamine (an antihistamine) PO.Third step: Promethazine or dimenhydrinate PO/PR.If severe: Metoclopramide, ondansetron, prochlorperazine, or promethazine IM/PO.If dehydrated: IV fuids, IV nutritional supplementation, and dimenhydrinate IV.
Diabetes in pregnancy is divided into two categories: gestational diabetes, in which onset occurs during pregnancy, and pregestational diabetes. The White classif cation (see Table 2.11-12) is commonly used to classify women according to the nature of their diabetes and the associated risk.
Carbohydrate intolerance of variable severity that is frst diagnosed during pregnancy. Occurs in 3–5% of all pregnancies, usually in late pregnancy.
Typically asymptomatic. Edema, polyhydramnios, or a large-for-GA infant (> 90th percentile) may be warning signs.
First step: One-hour 50-g glucose challenge test; venous plasma glucose is measured one hour later (at 24–28 weeks). Values ≥ 140 mg/dL are considered abnormal.
Next step: Confrm with an oral three-hour (100-g) glucose tolerance test showing any two of the following: fasting > 95 mg/dL; one hour > 180 mg/ dL; two hours > 155 mg/dL; three hours > 140 mg/dL.
First step: Start with the ADA diet, regular exercise, and strict glucose monitoring (four times a day). Tight maternal glucose control (fasting glucose < 100; oneto two-hour postprandial glucose < 150) improves outcomes.
Next step: Add insulin if dietary control is insuff cient.
Give intrapartum insulin and dextrose to maintain tight control during delivery.
Obtain periodic ultrasound and NSTs to assess fetal growth and wellbeing.
It may be necessary to induce labor at 39–40 weeks.
More than 50% of patients go on to develop glucose intolerance and/or type 2 DM later in life.
T AB LE 2.1 1 -1 2.  White Classifcation of Diabetes in Pregnancy
A1 Gestational diabetes; insulin not required. A2 Gestational diabetes; insulin required. B Age of onset 20 years or older or duration < 10 years. C Age of onset 10–19 years or duration 10–19 years. D Age of onset < 10 years or duration > 20 years. F Nephropathy. H Cardiomyopathy. R Proliferating retinopathy. RF Retinopathy and nephropathy. T Renal transplant.
Observed in 1% of all pregnancies. Insulin requirements may ↑ as much as threefold. Poorly controlled DM is associated with an ↑ risk of congenital malformations, fetal loss, and maternal/fetal morbidity during labor and delivery.
Renal, ophthalmologic, and cardiac evaluation to assess for end-organ damage.
Strict glucose control (with diet, exercise, insulin therapy, and frequent self-monitoring for type 1 and type 2 DM) to minimize fetal defects.
Fasting morning: ≤ 90 mg/dL.Two-hour postprandial: < 120 mg/dL.Fetus: 18–20 weeks: Ultrasound to determine fetal age and growth; evaluate for cardiac anomalies and polyhydramnios; quad screen to screen for developmental anomalies.
32–34 weeks: Close fetal surveillance (e.g., NST, CST, BPP). Admit if maternal DM has been poorly controlled or fetal parameters are a concern. Serial ultrasounds for fetal growth.
Delivery and postpartum:Maintain normoglycemia (80–100 mg/dL) during labor with an IV insulin drip and hourly glucose measurements.
Consider early delivery in the setting of poor maternal glucose control, preeclampsia, macrosomia, or evidence of fetal lung maturity.
Cesarean delivery should be considered for an estimated fetal weight (EFW) > 4500 g.
Greater than eight, investigate! If HbA1c is > 8%, look for congenital abnormalities.
If UA before 20 weeks reveals glycosuria, think pregestational diabetes.
Hyperglycemia in the f rst trimester suggests preexisting diabetes and should be managed as pregestational diabetes.
Encourage breastfeeding with an appropriate ↑ in caloric intake.Continue glucose monitoring postpartum. Insulin needs rapidly ↓ after delivery.
See Table 2.11-13.Distinguished as follows:Gestational hypertension (formerly known as pregnancy-induced hypertension): Idiopathic hypertension without signif cant proteinuria (< 300 mg/L) that develops at > 20 weeks’ gestation. As many as 25% of patients may go on to develop preeclampsia.
Chronic hypertension: Present before conception and at < 20 weeks’ gestation, or may persist for > 12 weeks postpartum. Up to one-third of patients may develop superimposed preeclampsia.
Tx: Monitor BP closely and treat with appropriate antihypertensives (e.g., methyldopa, labetalol, nifedipine). Do not give ACEIs or diuretics, as ACEIs are known to lead to uterine ischemia, and diuretics can aggravate low plasma volume to the point of uterine ischemia.
Cx: Complications are similar to those of preeclampsia (see below).
Distinguished as follows:Preeclampsia: New-onset hypertension (SBP ≥ 140 mmHg or DBP ≥ 90 mmHg) and proteinuria (> 300 mg of protein in a 24-hour period) occurring at > 20 weeks’ gestation.
Eclampsia: New-onset grand mal seizures in women with preeclampsia.HELLP syndrome (hemolytic anemia, elevated liver enzymes, and low platelets): A variant of preeclampsia with a poor prognosis.
■The etiology is unknown, but clinical manifestations are explained by vasospasm leading to hemorrhage and organ necrosis.
T AB LE 2.1 1 -1 3. Complications of Pregestational Diabetes Mellitus macrosomia) and need for C-section Preterm labor Infection Polyhydramnios Postpartum hemorrhage Maternal mortality Macrosomia or IUGR Cardiac and renal defects Neural tube defects (e.g., sacral agenesis) Hypocalcemia Polycythemia Hyperbilirubinemia IUGR Hypoglycemia from hyperinsulinemia Respiratory distress syndrome (RDS) Birth injury (e.g., shoulder dystocia) Perinatal mortality ■Risk factors include nulliparity, African-American ethnicity, extremes of age (< 20 or > 35), multiple gestation, molar pregnancy, renal disease (due to SLE or type 1 DM), a family history of preeclampsia, and chronic hypertension.
See Table 2.11-14 for the signs and symptoms of preeclampsia and eclampsia.
The only cure for preeclampsia/eclampsia is delivery of the fetus.
If the patient is close to term or preeclampsia worsens, induce delivery with IV oxytocin, prostaglandin, or amniotomy.
If far from term, treat with modifed bed rest and expectant management.
Severe preeclampsia:First step: Control BP with labetalol and/or hydralazine (goal < 160/110 with a DBP of 90–100 to maintain fetal blood f ow).
Second step: Prevent seizures with continuous magnesium sulfate drip. Watch for signs of magnesium toxicity (loss of DTRs, respiratory paralysis, coma). Continue seizure prophylaxis for 24 hours postpartum. Treat magnesium toxicity with IV calcium gluconate.
Third step: Deliver by induction or C-section when mother is stable.
First step: ABCs with supplemental O2.Second step: Seizure control/prophylaxis with magnesium. If seizures recur, give IV diazepam. Monitor magnesium blood levels and magnesium toxicity; monitor fetal status. Control BP (labetalol and/or hydralazine). Limit fuids; Foley for strict I/Os.
T AB LE 2.1 1 -1 4. Presentation of Preeclampsia and Eclampsia
Signs of severe preeclampsia are persistent headache or other cerebral or visual disturbances, persistent epigastric pain, and hyperreactive ref exes.
Mild preeclampsia Usually asymptomatic. BP ≥ 140/90 on two occasions > 6 hours apart. Proteinuria (> 300 mg/24 hrs or 1–2 urine dipsticks). Edema. Severe preeclampsia BP > 160/110 on two occasions > 6 hours apart. Renal: Proteinuria (> 5 g/24 hrs or 3–4 urine dipsticks) or oliguria (< 500 mL/24 hrs). Cerebral changes: Headache, somnolence. Visual changes: Blurred vision, scotomata. Hyperactive ref exes/clonus. RUQ pain. Hemolysis, elevated liver enzymes, thrombocytopenia (HELLP syndrome). Eclampsia The most common signs preceding an eclamptic attack are headache, visual changes, and RUQ/epigastric pain. Seizures are severe if not controlled with anticonvulsant therapy.
With third-trimester bleeding, think anatomically:Vagina: bloody show, traumaCervix: cervical cancer, cervical/vaginal lesionPlacenta: placental abruption, placenta previaFetus: fetal bleedingThe classic triad of ectopic pregnancy PAVEs the way for diagnosis: ■Third step: Initiate delivery if the patient is stable and convulsions are controlled. Postpartum management is the same as that for preeclampsia. Seizures may occur antepartum (25%), intrapartum (50%), or postpartum (25%); most occur within 48 hours after delivery.
Preeclampsia: Prematurity, fetal distress, stillbirth, placental abruption, seizure, DIC, cerebral hemorrhage, serous retinal detachment, fetal/ maternal death.
Eclampsia: Cerebral hemorrhage, aspiration pneumonia, hypoxic encephalopathy, thromboembolic events, fetal/maternal death.
Defned as any bleeding that occurs after 20 weeks’ gestation.
Complicates 3–5% of pregnancies (prior to 20 weeks, bleeding is referred to as threatened abortion).
The most common causes are placental abruption and placenta previa (see Table 2.11-15 and Figure 2.11-8). Other causes include other forms of abnormal placentation (e.g., placenta accreta), ruptured uterus, genital tract lesions, and trauma.
Most often tubal, but can be abdominal, ovarian, or cervical.
Presents with abdominal pain and vaginal spotting/bleeding, although some patients are asymptomatic.
Associated with etiologies that cause scarring to the fallopian tubes, including a history of PID, pelvic surgery, DES use, or endometriosis.
The differential includes surgical abdomen, abortion, ovarian torsion, PID, and ruptured ovarian cyst.
Approach a woman of reproductive age presenting with abdominal pain as a ruptured ectopic pregnancy until proven otherwise. Proceed as follows:
First step: pregnancy test and a transvaginal ultrasound showing an empty uterus.
Second step: Confrm with a serial hCG without appropriate hCG doubling.
Medical treatment (methotrexate) is suffcient for small, unruptured tubal pregnancies.
Surgical options for salpingectomy or salpingostomy with evacuation (laparoscopy vs. laparotomy).
Tubal rupture and hemoperitoneum (an obstetric emergency).T AB LE 2.1 1 -1 5. Placental Abruption vs. Placenta Previa
Premature (before delivery) separation of normally implanted placenta. Abnormal placental implantation: ■ Total: Placenta covers the cervical os. ■ Marginal: Placenta extends to the margin of the os. ■ Low-lying: Placenta is in close proximity to the os. 1 in 100. 1 in 200. Risk factors Hypertension, abdominal/pelvic trauma, tobacco or cocaine use, previous abruption, rapid decompression of an overdistended uterus, excessive stimulation. Prior C-sections, grand multiparity, advanced maternal age, multiple gestation, prior placenta previa. Symptoms Painful, dark vaginal bleeding that does not spontaneously cease. Abdominal pain, uterine hypertonicity. Fetal distress. Painless, bright red bleeding that often ceases in 1–2 hours with or without uterine contractions. Usually no fetal distress. Diagnosis Primarily clinical. Transabdominal/transvaginal ultrasound sensitivity is only 50%; look for retroplacental clot; most useful for ruling out previa. Transabdominal/transvaginal ultrasound sensitivity is > 95%; look for an abnormally positioned placenta. Pathophysiology Incidence
Stabilize patients with mild abruption and a premature fetus; manage expectantly (hospitalize; start IV and fetal monitoring; type and cross blood; bed rest).
Moderate to severe abruption: Immediate delivery (vaginal delivery with amniotomy if mother and fetus are stable and delivery is expected soon; C-section for maternal or fetal distress).
No vaginal exam! Stabilize patients with a premature fetus; manage expectantly.
Give tocolytics.Serial ultrasound to assess fetal growth; resolution of partial previa.
Give betamethasone to help with fetal lung maturity.Deliver by C-section. Indications for delivery include labor, life-threatening bleeding, fetal distress, documented fetal lung maturity, and 36 weeks’ GA.
Hemorrhagic shock. ↑ risk of placenta accreta. Coagulopathy: DIC in 10%. Vasa previa (fetal vessels crossing the internal os). Recurrence risk is 5–16% and rises to 25% after Preterm delivery, PROM, IUGR, congenital two previous abruptions. anomalies. Fetal hypoxia. Recurrence risk is 4–8%.
F IGU R E 2.1 1 -8.  Placental implantation.(A) Normal placenta. (B) Low implantation. (C) Partial placenta previa. (D) Complete placenta previa. (Adapted, with permis sion, from DeCherney AH. Current Obstetric & Gynecologic Diagnosis & Treatment, 8th ed. Stamford, CT: Appleton & Lange, 1994: 404.)
Defned as an EFW less than the 10th percentile for GA.
Affected infants are commonly born to women with systemic diseases that lead to uteroplacental insuffciency (intrauterine infection, hypertension, anemia).
Other risk factors include maternal substance abuse, placenta previa, and multiple gestations.
First step: Diagnose by confrming serial fundal height measurements with ultrasound.
Second step: Ultrasound the fetus for EFW (although as pregnancy advances, ultrasound fetal weight estimates become increasingly unreliable).
First step: Explore the underlying etiology and correct if possible.
If near due date: Administer steroids (e.g., betamethasone) to accelerate fetal lung maturity.
Then: Perform fetal monitoring with NST, CST, BPP, and umbilical artery Doppler velocimetry. A nonreassuring status near term may prompt delivery.
↑ perinatal morbidity and mortality.Defned as a birth weight > 90th percentile. A common sequela of gestational diabetes.
Dx: Diagnose by weighing the newborn at birth (prenatal diagnosis is imprecise).
Tx: Planned cesarean delivery may be considered for an EFW > 5000 g in women without diabetes and for an EFW > 4500 g in women with diabetes.
Cx: ↑ risk of shoulder dystocia (leading to brachial plexus injury and Erb-Duchenne palsy) as birth weight ↑.
Defned as an AFI > 20 on ultrasound. May be present in normal pregnancies, but fetal chromosomal developmental abnormalities must be considered.
Etiologies include maternal DM, multiple gestation, isoimmunization, pulmonary abnormalities (e.g., cystic lung malformations), fetal anomalies (e.g., duodenal atresia, tracheoesophageal fstula, anencephaly), and twin-twin transfusion syndrome.
Hx/PE: Usually asymptomatic.Dx: Fundal height greater than expected. Evaluation includes ultrasound for fetal anomalies, glucose testing for DM, and Rh screen.
Tx: Etiology specif c.Cx: Preterm labor, fetal malpresentation, cord prolapse.An AFI < 5 cm on ultrasound. Usually asymptomatic, but IUGR or fetal distress may be present. Etiologies include fetal urinary tract abnormalities (e.g., renal agenesis, GU obstruction), chronic uteroplacental insuff ciency, and ROM.
Dx: The sum of the deepest amniotic fuid pocket in all four abdominal quadrants on ultrasound.
Tx: Rule out inaccurate gestational dates. Treat the underlying cause if possible.
Cx: Associated with a 40-fold ↑ in perinatal mortality. Other complications include musculoskeletal abnormalities (e.g., clubfoot, facial distortion), pulmonary hypoplasia, umbilical cord compression, and IUGR.
In this condition, fetal RBCs leak into the maternal circulation, and maternal anti-Rh IgG antibodies form that can cross the placenta, leading to hemolysis of fetal Rh RBCs (erythroblastosis fetalis). There is an ↑ risk among an Rh-women who have had a previous SAB or TAB as well as among those who have undergone a previous delivery with no RhoGAM given.
Sensitized Rhmothers with titers > 1:16 should be closely monitored with serial ultrasound and amniocentesis for evidence of fetal hemolysis.
In severe cases, initiate preterm delivery when fetal lungs are mature. Prior to delivery, intrauterine blood transfusions may be given to correct a low fetal hematocrit.
If the mother is Rh at 28 weeks and the father is Rh  or unknown, give RhoGAM (Rh immune globulin).
If the baby is Rh , give RhoGAM postpartum.Give RhoGAM to Rh-mothers who undergo abortion or who have had an ectopic pregnancy, amniocentesis, vaginal bleeding, or placenta previa/ placental abruption. Type and screen is critical; follow β-hCG closely and prevent pregnancy for one year.
Hydrops fetalis occurs when fetal hemoglobin drops to < 7 g/dL.
Other complications include fetal hypoxia and acidosis, kernicterus, prematurity, and death.
A range of proliferative trophoblastic abnormalities that can be benign or malignant.
Complete moles: Usually result from sperm fertilization of an empty ovum; 46,XX (paternally derived).
Incomplete (partial) moles: Occur when a normal ovum is fertilized by two sperm (or a haploid sperm that duplicates its chromosomes); usually 69,XXY and contain fetal tissue.
Presents with f rst-trimester uterine bleeding (most common), hyperemesis gravidarum, preeclampsia/eclampsia at < 24 weeks, and uterine size greater than dates.
Risk factors include extremes of age (< 20 or > 40 years) and a diet def cient in folate or beta-carotene.
No fetal heartbeat is detected. Pelvic exam may reveal enlarged ovaries (bilateral theca-lutein cysts) or expulsion of grapelike molar clusters into the vagina.
Labs show markedly ↑ serum β-hCG (usually > 100,000 mIU/mL), and pelvic ultrasound reveals a “snowstorm” appearance with no gestational sac or fetus present (see Figure 2.11-9).
CXR may show lung metastases; D&C reveals “cluster-of-grapes” tissue (see Figure 2.11-10).
FIGURE 2.11-9.  Molar pregnancy.Transvaginal ultrasound shows a large, complex intrauterine mass with cystic regions that have the characteristic appearance of grapes.(Reproduced, with permission, from Tintinalli JE et al. Tintinalli’s Emergency Medicine: A Comprehensive Study Guide, 6th ed. New York: McGraw-Hill, 2004: Fig. 113-27.)
Evacuate the uterus and follow with weekly β-hCG. Treat malignant disease with chemotherapy (methotrexate or dactinomycin) and residual uterine disease with hysterectomy; chemotherapy and irradiation are highly effective for metastases.
F IGU R E 2.1 1 -1 0. Gross specimen of hydatidiform mole.
A complete or classical hydatidiform mole is characterized grossly by an abundance of edematous enlarged chorionic villi but no fetus or fetal membranes. There are theca-lutein cysts in both ovaries (arrows). (Reproduced, with permission, from Cunningham FG et al. Williams Obstetrics, 22nd ed. New York: McGraw-Hill, 2005: Fig.11-1.)
Molar pregnancy may progress to malignant GTD, including invasive moles (10–15%) and choriocarcinoma (2–5%) with pulmonary or CNS metastases. Trophoblastic pulmonary emboli may also be seen.
Affect 3% of all live births.Since 1980, there has been a 65% ↑ in the frequency of dizygotic (fraternal) twins and a 500% ↑ in triplet and high-order births (most due to the advent of assisted reproductive technology). The incidence of monozygotic (identical) twins has remained steady.
Hx/PE: Characterized by rapid uterine growth, excessive maternal weight gain, and palpation of three or more large fetal parts on Leopold’s maneuvers.
Dx: Ultrasound; hCG, HPL, and MSAFP are elevated for GA.
Tx: Multifetal reduction and selective fetal termination is an option for higher-order multiple pregnancies; antepartum fetal surveillance for IUGR. Management by a high-risk specialist is recommended.
Maternal: Patients are six times more likely to be hospitalized with complications—e.g., preeclampsia, preterm labor, preterm PROM (PPROM), placental abruption, pyelonephritis, and postpartum hemorrhage.
Fetal: Complications include twin-to-twin transfusion syndrome, IUGR, and preterm labor.
Affects 0.6–1.4% of all deliveries in the United States. Risk factors include obesity, diabetes, a history of a macrosomic infant, and a history of prior shoulder dystocia.
Diagnosed by a prolonged second stage of labor, recoil of the perineum (“turtle sign”), and lack of spontaneous restitution.
In the event of dystocia, be the mother’s HELPER:Help reposition.Leg elevated (McRoberts’ maneuver).Pressure (suprapubic).Enter the vagina and attempt rotation (Wood’s screw).Reach for the fetal arm.Failure to ProgressAssociated with chorioamnionitis, occiput posterior position, nulliparity, and elevated birth weight.
First-stage protraction or arrest: Labor that fails to produce adequate rates of progressive cervical change.
Prolonged second-stage arrest:Nulliparous: Inadequate cervical dilation after > 3 hours with regional anesthesia; > 2 hours without.
Multiparous: Inadequate cervical dilation after > 2 hours with regional anesthesia; > 1 hour without.
See Table 2.11-16.Chorioamnionitis leads to fetal infection, pneumonia, and bacteremia.Some 10% of those affected have permanent injury, 11% have a risk of postpartum hemorrhage, and 3.8% are at risk of fourth-degree laceration.
Rupture of Membranes (ROM)Distinguished as follows:Spontaneous ROM: Occurs > 1 hour before onset of labor. May be precipitated by vaginal or cervical infections, abnormal membrane physiology, or cervical incompetence.
PPROM: Rupture of membranes occurring at < 37 weeks’ gestation.
Prolonged ROM: Defned as rupture > 18 hours prior to delivery. Risk factors include low socioeconomic status (SES), young maternal age, smoking, and STDs.
Patients often report a “gush” of clear or blood-tinged amniotic fl uid. Uterine contractions may be present.
TABLE 2.11-16.  Failure to ProgressFirst Latent Active Failure to have progressive cervical change: ■Prima: > 20 hours ■Multi: > 14 hours ■Prima: > 2 hrs ■Multi: > 2 hrs after reaching 3–4 cm Second Arrest of fetal descent: ■Prima: > 2 hrs; > 3 hours with epidural ■Multi: > 1 hr; > 2 hrs with epidural Close observation with ↓ in epidural rate and continued oxytocin. Assisted vaginal delivery (forceps or vacuum). C-section.
Therapeutic rest via parenteral analgesia; oxytocin; amniotomy; cervical ripening.Amniotomy; oxytocin; C-section if the previous interventions are ineffective.a Augmentation with oxytocin should be considered when contraction frequency is < 3 in a 10-minute period or intensity of contraction is < 25 mmHg above baseline.
To minimize the risk of infection, do not perform digital vaginal exams on women with PROM.
Preterm labor = regular uterine contractions + concurrent cervical change at < 37 weeks’ gestation.
First step:A sterile speculum exam reveals pooling of amniotic fuid in the vaginal vault.
Nitrazine paper test is  (paper turns blue, indicating alkaline pH of amniotic f uid).
Fern test is (a ferning pattern is seen under a microscope after amniotic fuid dries on a glass slide).
Second step: Ultrasound to assess amniotic f uid volume.If unsure: Ultrasound-guided transabdominal instillation of indigo carmine dye to check for leakage (unequivocal test).
Minimize infection risk; do not perform digital vaginal exams on women who are not in labor or for whom labor is not planned immediately.
Check fetal heart tracing, maternal temperature, WBC count, and uterine tenderness for evidence of chorioamnionitis.
Depends on GA and fetal lung maturity.Term: First check GBS status and fetal presentation; then labor may be induced or the patient can be observed for 24–72 hours.
> 34–36 weeks’ gestation: Labor induction may be considered.< 32 weeks’ gestation: Expectant management with bed rest and pelvic rest.
Antibiotics: Given to prevent infection and to prolong the latency period in the absence of infection.
Antenatal corticosteroids (e.g., betamethasone or dexamethasone × 48 hours): Can be given to promote fetal lung maturity in the absence of intra-amniotic infection prior to 32 weeks’ GA.
If signs of infection or fetal distress develop, give antibiotics (ampicillin and gentamicin) and induce labor.
Preterm labor and delivery, chorioamnionitis, placental abruption, cord prolapse.Defned as onset of labor between 20 and 37 weeks’ gestation.
Occurs in > 10% of all U.S. pregnancies and is the 1° cause of neonatal morbidity and mortality.
Risk factors include multiple gestation, infection, PROM, uterine anomalies, previous preterm labor or delivery, polyhydramnios, placental abruption, poor maternal nutrition, and low SES. Most patients have no identifiable risk factors.
Patients may have menstrual-like cramps, onset of low back pain, pelvic pressure, and new vaginal discharge or bleeding.
■ Requires regular uterine contractions (≥ 3 contractions of 30 seconds each over a 30-minute period) and concurrent cervical change at < 37 weeks’ gestation.
Assess for contraindications to tocolysis (e.g., infection, nonreassuring fetal testing, placental abruption).
Perform a sterile speculum exam to rule out PROM.Obtain an ultrasound to rule out fetal or uterine anomalies, verify GA, and assess fetal presentation and amniotic f uid volume.
Obtain cultures for chlamydia, gonorrhea, and GBS. Obtain a UA and urine culture.
Hydration and bed rest.Unless contraindicated, begin tocolytic therapy (β-mimetics, MgSO4, CCBs, PGIs) and give steroids to accelerate fetal lung maturation. Give penicillin or ampicillin for GBS prophylaxis if preterm delivery is likely.
RDS, intraventricular hemorrhage, PDA, necrotizing enterocolitis, retinopathy of prematurity, bronchopulmonary dysplasia, death.
Defned as any presentation other than vertex (i.e., head closest to birth canal, chin to chest, occiput anterior). Risk factors include prematurity, prior breech delivery, uterine anomalies, polyor oligohydramnios, multiple gestations, PPROM, hydrocephalus, anencephaly, and placenta previa.
Breech presentations are the most common form (affect 3% of all deliveries) and involve presentation of the fetal lower extremities or buttocks into the maternal pelvis (see Figure 2.11-11). Subtypes include the following:
Frank breech (50–75%): The thighs are fexed and the knees are extended.
Footling breech (20%): One or both legs are extended below the buttocks.
Complete breech (5–10%): The thighs and knees are f exed.
Follow: Up to 75% spontaneously change to vertex by week 38.
External version: If the fetus has not reverted spontaneously, a version may be attempted by applying directed pressure to the maternal abdomen to turn the infant to vertex. The success rate is roughly 50%. Risks of version are placental abruption and cord compression, so be prepared for an emergency C-section if needed.
Trial of breech vaginal delivery: Attempt only if delivery is imminent; otherwise contraindicated. Complications include cord prolapse and/or head entrapment.
Elective C-section: Recommended given the lower risk of fetal morbidity.
Breech presentation is the most common fetal malpresentation.See Table 2.11-17 for indications. For both elective and indicated cesarean delivery, sodium citrate should be used to ↓ gastric acidity and prevent acid aspiration syndrome.
FIGURE 2.11-11. Types of breech presentations.(Reproduced, with permission, from DeCherney AH. Current Obstetric & Gynecologic Diagnosis & Treatment, 8th ed. Stamford, CT: Appleton & Lange, 1994: 411.)
TABLE 2.11-17. Indications for Cesarean SectionSurgical extension of the vaginal opening into the perineum.There are two types: median (midline) and mediolateral.Complications include extension to the anal sphincter (third degree) or rectum (fourth degree), which is more common with midline episiotomy, as well as bleeding, infection, dyspareunia, and, in rare cases, rectovaginal fstula formation or maternal death.
Routine use of episiotomy is not recommended.Defned as a loss of > 500 mL of blood for vaginal delivery or > 1000 mL for C-section occurring before, during, or after delivery of the placenta. Table 2.11-18 summarizes common causes.
Complications include acute blood loss (potentially fatal), anemia due to chronic blood loss (predisposes to puerperal infection), and Sheehan’s syndrome (pituitary ischemia and necrosis; the 1° cause of anterior pituitary insuffciency in adult females, most commonly presenting as failure to lactate).
T AB LE 2.1 1 -1 8. Common Causes of Postpartum Hemorrhage
Risk factors Uterine overdistention (multiple gestation, macrosomia, polyhydramnios). Exhausted myometrium (rapid or prolonged labor, oxytocin stimulation). Uterine infection. Conditions interfering with contractions (anesthesia, myomas, MgSO4). Precipitous labor. Operative vaginal delivery (forceps, vacuum extraction). Large infant. Inadequate episiotomy repair. Placenta accreta/increta/percreta. Placenta previa. Uterine leiomyomas. Preterm delivery. Previous C-section/ curettage. Diagnosis Palpation of a soft, enlarged, “boggy” uterus. The most common cause of postpartum hemorrhage (90%). Manual and visual inspection of the lower genital tract for any laceration > 2 cm long. Manual and visual inspection of the placenta and uterine cavity for missing cotyledons. Ultrasound may also be used to inspect the uterus. Treatmenta Bimanual uterine massage (usually successful). Oxytocin infusion. Methergine (methylergonovine) if not hypertensive. Prostaglandin (PGF2a). Surgical repair of the physical defect. Manual removal of remaining placental tissue. Curettage with suctioning (take care not to perforate the uterine fundus). a For all uterine causes, when bleeding persists after conventional therapy, uterine/internal iliac artery ligation or hysterectomy can be lifesaving.
Postpartum endometritis:The 7 W’s of postpartum fever (10 days postdelivery):Womb (endomyometritis) Wind (atelectasis, pneumonia) Water (UTI) Walk (DVT, pulmonary embolism) Wound (incision, episiotomy)
Weaning (breast engorgement, abscess, mastitis)Breastfeeding is contraindicated in maternal HIV infection, active hepatitis, and use of certain medications.
Characterized by a temperature ≥ 38°C for at least two of the first ten postpartum days (not including the first 24 hours).
Risk factors for postpartum endometritis include emergent C-section, PROM, prolonged labor, multiple intrapartum vaginal exams, intrauterine manipulations, delivery, low SES, young age, prolonged ruptured membranes, bacterial colonization, and corticosteroid use.
For endometritis, hospitalize and give broad-spectrum empiric IV antibiotics (e.g., clindamycin and gentamicin) until patients have been afebrile for 48 hours (24 hours for chorioamnionitis). Add ampicillin for complicated cases.
For persistent postpartum fever that is not responsive to broad-spectrum antibiotics, think septic pelvic thrombophlebitis, in which pelvic infection leads to infection of the vein wall and intimal damage, leading in turn to thrombogenesis. The clot is then invaded by microorganisms. Suppuration follows, with liquefaction, fragmentation, and, finally, septic embolization.
Presents with abdominal and back pain and a picket-fence fever curve (“hectic” fevers) with wide swings from normal to as high as 41°C (105.8°F).
Diagnose with blood cultures and CT looking for a pelvic abscess.
Treat with broad-spectrum antibiotics and anticoagulation with heparin × 7–10 days.
Defned as pituitary ischemia and necrosis that leads to anterior pituitary insuffciency 2° to massive obstetric hemorrhage and shock.
The 1° cause of anterior pituitary insuffciency in adult females. The most common presenting syndrome is failure to lactate (due to ↓ prolactin levels).
Other symptoms include weakness, lethargy, cold insensitivity, genital atrophy, and menstrual disorders.
Dx: The diagnosis is established with provocative hormonal testing and MRI of the pituitary and hypothalamus to rule out tumor or other pathology.
Tx: Treatment consists of the replacement of all defcient hormones. However, some patients may recover TSH and even gonadotropin function after cortisol replacement alone.
During pregnancy, ↑ estrogen and progesterone result in breast hypertrophy and inhibition of prolactin release. After delivery of the placenta, hormone levels ↓ markedly and prolactin is released, stimulating milk production. Periodic infant suckling leads to further release of prolactin and oxytocin, which stimulate myoepithelial cell contraction and milk ejection (“let-down ref ex”).
Colostrum (“early breast milk”) contains protein, fat, secretory IgA, and minerals. Within one week postpartum, mature milk with protein, fat, lactose, and water is produced.
High IgA levels in colostrum provide passive immunity for the infant and protect against enteric bacteria.
Other benef ts include ↓ incidence of infant allergies, early upper respiratory tract infections, and GI infections; facilitation of mother-child bonding; and maternal weight loss.
Contraindications to breastfeeding include HIV infection, active HBV and HCV infection, and use of certain medications (e.g., tetracycline, chloramphenicol, warfarin).
Cellulitis of the periglandular tissue caused by nipple trauma from breastfeeding coupled with the introduction of bacteria, usually S. aureus, from the infant’s pharynx into the nipple ducts. Affects 2–3% of nursing women.
Symptoms often begin 2–4 weeks postpartum.Breast symptoms are usually unilateral and include breast tenderness, a palpable mass, erythema, edema, warmth, and possible purulent nipple drainage. Signifcant fever, chills, and malaise may also be seen.
Differentiate from simple breast swelling.Infection is suggested by focal symptoms, a  breast milk culture, an ↑ WBC count, and fever.
■ First step: Continued breastfeeding to prevent the accumulation of infected material (or use of a breast pump in patients who are no longer
The treatment of mastitis breastfeeding) and PO antibiotics (dicloxacillin, cephalexin, amoxicillin/ clavulanate, azithromycin, clindamycin).
■ Next step: If abscess is present, treat with incision and drainage. continued breastfeeding.
Menarche and Normal Female Development  359 Normal Menstrual Cycle 359 Menopause 360 Contraception 361 Sexual Assault 361 Abnormalities of the Menstrual Cycle 364
Breast development (thelarche) precedes menarche and usually begins between the ages of 8 and 11.
Menarche usually occurs between the ages of 10 and 16.
Figure 2.12-1 graphically illustrates the stages of normal female development.
The progression of a normal menstrual cycle is as follows (see also Figure 2.12-2):
Follicular phase (days 1–13): Typically lasts about 13 days but may vary. ↑ FSH → growth of follicles → ↑ estrogen production. Results in the development of straight glands and thin secretions of the uterine lining (proliferative phase).
Ovulation (day 14):LH and FSH spike results in rupture of the ovarian follicle and release of a mature ovum.
Ruptured follicular cells involute and create the corpus luteum.Luteal phase (days 15–28): This phase is the length of time (14 days) that the corpus luteum can survive without further LH stimulation.
HEIGHT SPURT GROWTH RATE AGE RANGE PEAK Height 3 in/y Weight 17.5 lb/y 11.5–16.5 yWeight 6 lb/y AGE RANGE 10-16.5 y MENARCHE
Average Height 62.5 in (158.5 cm) Average Weight 106 lb (48 kg)
RATING PUBIC HAIR Initial hair is straight and fine. AGE RANGE 8–14 years Pubic hair becomes coarse, darkens, and spreads. Hair looks like an adult’s but limited in area. Inverted triangular pattern is established. AGE RANGE 12.5–16.5 years
F IGU R E 2.1 2-1. Normal female development.(Reproduced, with permission, from Hay WW Jr et al. Current Diagnosis & Treatment: Pediatrics, 19th ed. New York: McGraw-Hill, 2008: Fig. 3-4.)
Currently, HRT is not recommended as f rst-line treatment for menopausal symptoms.
(Reproduced, with permission, from Fauci AS et al. Harrison’s Principles of Internal Medicine, 17th ed. New York: McGraw-Hill, 2008: Fig. 341-8.)
The corpus luteum produces estrogen and progesterone, allowing the endometrial lining to develop thick endometrial glands with thick secretions (secretory phase).
In the absence of implantation, the corpus luteum cannot be sustained, and the endometrial lining sloughs off.
Cessation of menses for a minimum of 12 months as a result of cessation of follicular development. Average age of onset is 51. “Premature menopause” is defned as ovarian failure and menstrual cessation before age 40.
The mnemonic HAVOC lists prominent features of menopause.Other symptoms include insomnia, anxiety/irritability, vaginal bleeding, poor concentration, mood changes, dyspareunia, and loss of libido.
Labs f rst show ↑ FSH and then show ↑ LH.
DEXA scan to follow bone density for osteoporosis.Lipid prof le (↑ total cholesterol, ↓ HDL).■ Vasomotor symptoms: ■HRT (combination estrogen and progestin):HRT has been shown to ↑ cardiovascular morbidity and mortality and may ↑ the incidence of breast and endometrial cancers. For this reason, clinicians should thoroughly review the risks and benef ts of HRT before initiating treatment.
Posthysterectomy patients do not need progestin. Unopposed estrogen in patients with a uterus predisposes to endometrial cancer.
Contraindications to HRT include vaginal bleeding, suspected or known breast cancer, endometrial cancer, and a history of thromboembolism, chronic liver disease, or hypertriglyceridemia.
Non-HRT: Venlafaxine and, less commonly, clonidine can be given to ↓ the frequency of hot f ashes.
Vaginal atrophy:Long term: Estradiol vaginal ring.Short term: Estrogen vaginal cream will relieve symptoms. Once a woman is
Osteoporosis: Treat with daily calcium supplementation and exercise; pos postmenopausal, she should sibly bisphosphonates.
■Of women who are sexually active and do not use a contraceptive method, 85% will become pregnant within one year.
Absolute contraindications to various methods are as follows:Estrogen-containing hormonal methods (OCPs, NuvaRing, “the patch”):A history of CAD or DVTMirena and Copper T IUDs:PID that is active (within three months) or recurrentA Pap smear with squamous intraepithelial lesions or two atypical Pap smears
A history of heart valve replacement or artif cial joints
Copper T alone: Copper intolerance (allergy to copper, Wilson’s disease); severe dysmenorrhea and/or menorrhagia.
Mirena alone: Levonorgestrel allergy, breast cancer, acute liver disease or liver tumor, or a history of BRCA.
Table 2.12-1 describes the effectiveness of contraceptive methods along with their relative advantages and disadvantages.
Emergency contraception (EC) methods prevent pregnancy after unprotected sex or contraceptive failure. Table 2.12-2 describes the various methods of EC.
More than one sexual partner and nulliparity are not absolute contraindications to IUD use.
The most effective methods of contraception are longer-term methods that ↓ user error.
Combined hormonal methods of contraception protect against endometrial, ovarian, and breast cancer.
Sexual assault is the most frequently unreported crime in the United States. Physicians are often required to evaluate rape victims and collect evidence. Most rape victims are women; however, men may also be victims of rape.
■Take a full history, including contraceptive use, last time of coitus, condom use prior to the assault, drug or alcohol use, history of STDs, history of mental illness or defciency, description of the assailant, location and
T AB LE 2.1 2-1.  Contraceptive MethodsMost effective: > 99% (1 in 100 women will become pregnant using these methods) Implanon (“the implant”): Progestin-only implant Lasts up to three years. Immediate fertility with removal. Safe with breastfeeding. Associated with weight gain, depression, irregular bleeding (no period; spotting; heavier, more frequent periods). Intrauterine device with progestin (Mirena): Inf ammation from foreign body; cervical thickening and endometrial decidualization with progesterone Effective for up to f ve years. Lighter periods; less cramping. Immediate fertility with removal. Safe with breastfeeding. Spotting (up to six months). Associated with acne. Risk of uterine puncture (1/1000). Intrauterine device— ParaGard (Copper T): Infammation from foreign body; copper exerts a spermicidal effect Effective for up to 10 years. Immediate fertility with removal. Safe with breastfeeding. ↑ cramping and bleeding (5–10%). Risk of uterine puncture (1/1000). Surgical sterilization (vasectomy, tubal ligation) Permanently effective. Safe with breastfeeding. Tubal ligation: Irreversible; ↑ ectopic pregnancy. Vasectomy: Most failures are due to not waiting for two semen samples.  Very effective: 90–99% (1–10 in 100 women will become pregnant using these methods) Depo-Provera (medroxy-progesterone): IM injection every three months Lighter or no periods. Each shot works for three months. Safe with breastfeeding. Associated with irregular bleeding and weight gain. Decreases in bone mineral density (reversible). Delayed fertility after discontinuation (one shot can last 10 months). Ortho Evra (“the patch”): Combined weekly estrogen and progestin dermal patch Can make periods more regular. Not administered daily. Risk of thromboembolism (especially for smokers and those > 35 years of age). NuvaRing (“the ring”): Combined low-dose progestin and an estrogen vaginal ring Can make periods more regular. Can improve acne. Used continuously for three weeks; then one week without the ring. Safe to use continuously to skip periods. May ↑ vaginal discharge. Spotting occurs in the frst 1–2 months.
T AB LE 2.1 2-1.  Contraceptive Methods (continued)Oral contraceptive pills (combination estrogen and progestin): Inhibit FSH/LH, suppressing ovulation; thicken cervical mucus; decidualize endometrium ↓ risk of ovarian and endometrial cancers.a Predictable, lighter, less painful menses. Often improve acne. Immediate fertility upon cessation. Require daily compliance. Breakthrough bleeding (10–30%). Risk of thromboembolism (especially for smokers and those > 35 years of age). Progestin-only “minipills”: Thicken cervical mucus Safe with breastfeeding. Requires strict compliance (taking pill at the same time each day). Moderately effective: 75–90% (up to 10–25 women in 100 will become pregnant using these methods) Male condoms: A latex sheath covers the penis The only method that effectively protects against pregnancy and STDs, including HIV. Possible allergy to latex or spermicides. Diaphragm with spermicide Some protection against STDs. Must be ftted by provider. Female condom Some protection against STDs. Can be clumsy and diff cult. Fertility awareness methods No side effects. Often used by women who have a cultural, religious, or personal preference for “natural” contraception. Requires partner’s participation. No STD/HIV protection. Less effective: 68–74% (26–32 women in 100 will become pregnant using these methods) Withdrawal No side effects. No STD/HIV protection. Spermicide Frequent use may protect against HIV. May be used as a 2° method. Not recommended as a 1° method. a Other combined hormonal methods (e.g., patch, ring) may also protect against endometrial, breast, and ovarian cancer; however, data are still lacking given their relatively recent introduction.
time of the assault, circumstances of the assault (e.g., penile penetration, use of condoms, extragenital acts, use or display of weapons), and the patient’s actions since the assault (e.g., douching, bathing, brushing teeth, urination/defecation, changing clothes).
■Conduct a complete physical exam, making note of any signs of trauma, along with a detailed pelvic exam, including a survey of the external genitals, vagina, cervix, and anus.
Saline prep for sperm.Gonorrhea and chlamydia smear/culture (including rectal if appropriate).T AB LE 2.1 2-2.  Emergency Contraceptive Methods “Morning-After Pill”—used within 120 hours of unprotected sex Combined estrogen/progestin (75% effective) Progestin only (80% effective) Available over the counter. Does not disrupt embryo postimplantation. Can be used as bridge contraception. Safe for all women. Same as above. Fewer nausea/vomiting side effects than combined EC. Nausea, vomiting, fatigue, headache, dizziness, breast tenderness. No protection against STDs. Same as above. Copper T IUD—used within 7 days of unprotected sex (99% effective) Can be used as EC and continued for up to 10 years of contraception. High initial cost of insertion. Must be inserted by provider. No protection against STDs.
Serologic testing for HIV, syphilis, HSV, HBV, and CMV.Serum pregnancy test.Blood alcohol level; urine toxicology screen.STD treatment (ceftriaxone plus doxycycline).HIV risk assessment and possible postexposure prophylaxis.EC for pregnancy prevention.Refer for psychological counseling.Arrange for follow-up with the same physician or with another provider if more appropriate.
Follow-up should include repeat screening for STDs, repeat screening for pregnancy, and a discussion of coping methods with appropriate referrals for psychiatric care if needed.
Pediatric vaginal discharge is caused by a variety of factors and may be normal, but STDs resulting from sexual abuse must be ruled out.
Etiologies of vaginal discharge in pediatric patients include the following:
Infectious vulvovaginitis:May present with a malodorous, yellow-green, purulent discharge; most often caused by group A streptococcus.
May also be caused by any STD resulting from sexual abuse (STDs must be ruled out and, if found, reported to child protective services).
Foreign objects.Candidal infection: May be associated with diabetes; measure glucose and/or check for glycosuria.
Sarcoma botryoides (rhabdomyosarcoma): A malignancy with lesions that have the appearance of “bunches of grapes” within the vagina.
Onset of 2° sexual characteristics before the age of eight. Subtypes are as follows (see also Table 2.12-3):
Central precocious puberty: Results from early activation of hypothalamic GnRH production. Most commonly idiopathic (also known as constitutional or true); may be related to obesity. May also be caused by CNS tumors.
Peripheral precocious puberty: Also called pseudo-precocious puberty. Results from nonhypothalamic GnRH production.
Signs of estrogen excess (breast development and possibly vaginal bleeding) point to ovarian cysts or tumors.
Signs of androgen excess (pubic and/or axillary hair, enlarged clitoris, acne, and/or ↑ body odor) suggest adrenal tumors or congenital adrenal hyperplasia (CAH).
First step: Obtain a radiograph of the wrist and hand to determine bone age.
If bone age is within one year of chronological age, puberty has not started or has just recently begun.
If bone age exceeds chronological age by > 2 years, puberty has been present for at least one year or is progressing rapidly.
Next step: Conduct a GnRH agonist (leuprolide) stimulation test.Central precocious puberty: If LH response is , obtain a cranial MRI to look for CNS tumors.
In girls 6–8 years of age with signs of precocious puberty, the incidence of CNS tumor is 2% in the absence of other CNS signs.
If CNS tumors are ruled out, constitutional precocious puberty is the likely etiology.
Peripheral precocious puberty: If LH response is , order the following:
Ultrasound of the ovaries and/or adrenals: To look for ovarian or adrenal cysts/tumors.
Estradiol: Levels will be ↑ in ovarian cysts or tumors.
T AB LE 2.1 2-3. Causes of Precocious Pubertal Development
If onset of 2° sexual characteristics is seen by age eight, work up for precocious puberty by determining bone age and conducting a GnRH stimulation test to distinguish central from peripheral precocious puberty.
Constitutional (idiopathic) Hypothalamic lesions (hamartomas, tumors, congenital malformations) Dysgerminomas Hydrocephalus CNS infections CNS trauma/irradiation Pineal tumors (rare) Neurofbromatosis with CNS involvement Tuberous sclerosis Congenital adrenal hyperplasia Adrenal tumors McCune-Albright syndrome (polyostotic f brous dysplasia) Gonadal tumors Exogenous estrogen, oral (OCPs) or topical Ovarian cysts (females)
Surgery is not required for the treatment of ambiguous genitalia in congenital adrenal hyperplasia; it is always cosmetic and may be deferred.
Androgen (DHEA, DHEAS): Especially critical in the setting of advanced bone age or signs of adrenarche.
17-OH progesterone: To screen for advanced bone age or adrenarche.
Central precocious puberty: Leuprolide is frst-line therapy. With treatment, physical changes regress or cease to progress.
Peripheral precocious puberty: Treat the cause.Ovarian cysts: No intervention is necessary, as cysts will usually regress spontaneously.
CAH: Treat with glucocorticoids. Surgery is not required for the treatment of ambiguous genitalia.
Adrenal or ovarian tumors: Require surgical resection.McCune-Albright syndrome: Antiestrogens (tamoxifen) or estrogen synthesis blockers (ketoconazole or testolactone) may be effective.
1° amenorrhea is def ned as the absence of menses by age 16 with 2° sexual development present, or the absence of 2° sexual characteristics by age 14.
Absence of 2° sexual characteristics (no estrogen production): Etiologies are as follows:
Constitutional growth delay: The most common cause.1° ovarian insuff ciency: Most commonly Turner’s syndrome. Look for a history of radiation and chemotherapy.
Central hypogonadism: May be caused by a variety of factors, including the following:
Undernourishment, stress, prolactinemia, or exercise.CNS tumor or cranial irradiation.Kallmann’s syndrome (isolated gonadotropin def ciency) associated with anosmia.Presence of 2° sexual characteristics (evidence of estrogen production but other anatomic or genetic problems): Etiologies include the following:
Mlerian agenesis: Absence of two-thirds of the vagina; uterine abnormalities.
Imperforate hymen: Presents with hematocolpos (blood in the vagina) that cannot escape, along with a bulging hymen. Requires surgical opening.
Complete androgen insensitivity: Patients present with breast development (aromatization of testosterone to estrogen) but are amenorrheic and lack pubic hair.
First step: Get a pregnancy test.Next step: Obtain a radiograph to determine if bone age is consistent with pubertal onset (> 12 years in girls).
■If the patient is of short stature (bone age < 12 years) with normal growth velocity, constitutional growth delay (the most common cause of 1° amenorrhea) is the probable cause.
■If bone age is > 12 years but there are no signs of puberty, obtain LH/ FSH and consider where the problem is on the HPA axis (see Figure 2.12-3).
■↓ GnRH, ↓ LH/FSH, ↓ estrogen/progesterone at prepuberty levels: Points to constitutional growth delay (puberty has not yet started).
■↓ GnRH, ↓ LH/FSH, ↓ estrogen/progesterone: Hypogonadotropic hypogonadism. Suggests a hypothalamic or pituitary problem.
■↑ GnRH, ↑ LH/FSH, ↓ estrogen/progesterone: Hypergonadotropic hypogonadism. Points to a condition in which the ovaries fail to produce estrogen.
■↑ GnRH, ↑ LH/FSH, high estrogen or testosterone: Suggests PCOS or a problem with estrogen receptors.
■Normal pubertal hormone levels: Indicates an anatomic problem (menstrual blood can’t get out).
Constitutional growth delay: ↓ GnRH, ↓ LH/FSH, ↓ E/P at prepuberty levels (↓ GnRH, ↓ LH/FSH, ↓ E/P): (↓ GnRH, ↓ LH/FSH, ↓ E/P): Gonadotropin-releasing hormone (GnRH) Anorexia, excess exercise, weight loss, stress (GnRH deficiency)
Sheehan’s syndrome Hypothalamus -Tumors, infection, trauma,Anorexia, excess exercise,Pituitary gland Hyperprolactinemia     weight loss, stress HypothyroidismLuteinizing hormone (LH) Follicle-stimulating hormone (FSH) Adrenal—CAH, Cushing’s Adrenal syndrome, Addison’s disease Pancreas gland Thyroid Other endocrine glands (↑ GnRH, ↑ LH/FSH, ↓ E/P): (chemotherapy, radiation, idiopathic) (gonadotropin-resistant (↑ GnRH, ↑ LH/FSH, ↓ E/P):  ovary syndrome) Premature ovarian failure; 40(↑ GnRH, ↑ LH/FSH): -Menopause-Androgen insensitivity Chemotherapy with (↑ testosterone, ↑ estrogen) alkylating agents-PCOS (↑ estrogen, androgen) hydroxylase or aromatase) Primary anatomic: Secondary anatomic: Anovulatory problem: Normal hormone levels Normal hormone levels PCOS -Transverse vaginal septum  to endometritis, scarring -Vaginal and/or cervical  after delivery, or D&C agenesis Cervical stenosis
F IGU R E 2.1 2-3. Causes of primary and secondary amenorrhea.
Ultrasound may be needed to evaluate the ovaries.Normal breast development and no uterus: Obtain a karyotype to evalu-
The f rst step in the workup of 1° or 2° amenorrhea is a pregnancy test!
ate for androgen insensitivity syndrome.Stigmata of Turner’s syndrome: Obtain a karyotype.Normal breast development and uterus: Measure prolactin and obtain a cranial MRI.
Constitutional growth delay: No treatment is needed.Hypogonadism: Begin HRT with estrogen alone at the lowest dose. Twelve to eighteen months later, begin cyclic estrogen/progesterone therapy (if the uterus is present).
Anatomic: Generally requires surgical intervention.Defned as the absence of menses for six consecutive months in women who have passed menarche.
First step: Get a pregnancy test.Second step: β-hCG: Measure TSH and prolactin. ■↑ TSH: Indicates hypothyroidism. ■↑ prolactin (inhibits the release of LH and FSH): Points to a thy roid pathology. Order an MRI of the pituitary to rule out tumor. ■↑↑ prolactin: Suggests a prolactin-secreting pituitary adenoma.
Normal β-hCG: Initiate a progestin challenge (10 days of progestin).
progestin challenge (withdrawal bleed): Indicates anovulation that is likely due to noncyclic gonadotropin secretion, pointing to PCOS or idiopathic anovulation. Check LH levels, and if LH is moderately high, the etiology is likely PCOS. Marked elevation of LH can indicate premature menopause.
progestin challenge (no bleed): Indicates uterine abnormality or estrogen defciency. Check FSH levels. ■↑ FSH: Indicates hypergonadotropic hypogonadism/ovarian fail ure.
■↓ FSH: Obtain a cyclic estrogen/progesterone test. A withdrawal bleed points to hypogonadotropic hypogonadism; a withdrawal bleed suggests an endometrial or anatomic problem.
Signs of hyperglycemia (polydipsia, polyuria) or hypotension: Conduct a 1-mg overnight dexamethasone suppression test to distinguish CAH, Cushing’s syndrome, and Addison’s syndrome.
If clinical virilization is present: Measure testosterone, DHEAS, and 17–hydroxyprogesterone.
Mild pattern: PCOS, CAH, or Cushing’s syndrome.Moderate to severe pattern: Look for an ovarian or adrenal tumor.
■ Hypothalamic: Reverse the underlying cause and induce ovulation with gonadotropins.
Tumors: Excision; medical therapy for prolactinomas (e.g., bromocriptine, cabergoline).Premature ovarian failure (age < 40 years): If the uterus is present, treat with estrogen plus progestin replacement therapy.
Menstrual pain associated with ovulatory cycles in the absence of pathologic f ndings. Caused by uterine vasoconstriction, anoxia, and sustained contractions mediated by an excess of prostaglandin (PGF2α).
Presents with low, midline, spasmodic pelvic pain that often radiates to the back or inner thighs.
Cramps occur in the frst 1–3 days of menstruation and may be associated with nausea, diarrhea, headache, and f ushing.
There are no pathologic fndings on pelvic exam.A diagnosis of exclusion. Rule out 2° dysmenorrhea (see workup below).
NSAIDs; topical heat therapy; combined OCPs, Mirena IUD.Menstrual pain for which an organic cause exists. Common causes include endometriosis and adenomyosis, tumors, fbroids, adhesions, polyps, and PID.
Look for pathology. Patients may have a palpable uterine mass, cervical motion tenderness, adnexal tenderness, a vaginal or cervical discharge, or visible vaginal pathology (mucosal tears, masses, prolapse). However, normal abdominal and pelvic exams do not rule out pathology.
See Table 2.12-4 for distinguishing features of endometriosis vs. adenomyosis.
First step: Obtain a β-hCG to exclude ectopic pregnancy.Second step: Order the following:A CBC with differential to rule out infection or neoplasm.
UA to rule out UTI.Gonococcal/chlamydial swabs to rule out STDs/PID.Stool guaiac to rule out GI pathology.Third step: Look for pelvic pathology causing pain (see Table 2.12-4).
Treatment is etiology specif c.T AB LE 2.1 2-4. Endometriosis vs. AdenomyosisDef nition Functional endometrial glands and stroma outside the uterus. Endometrial tissue in the myometrium of the uterus. History/PE Presents with cyclical pelvic and/or rectal pain and dyspareunia (painful intercourse). Presents with the classic triad of noncyclical pain, menorrhagia, and an enlarged uterus. Diagnosis Requires direct visualization by laparoscopy or laparotomy. Classic lesions have a blue-black (“raspberry”) or dark brown (“powder-burned”) appearance. Ovaries may have endometriomas (the characteristic “chocolate cysts”). Ultrasound is useful but cannot distinguish between leiomyoma and adenomyosis. MRI can aid in diagnosis but is costly. Treatment Pharmacologic: Inhibit ovulation. Combination OCPs are frst line; other options include GnRH analogs (leuprolide) and danazol. Conservative surgical treatment: Excision, cauterization, or ablation of the lesions and lysis of adhesions. Twenty percent of patients can become pregnant subsequent to treatment. Defnitive surgical treatment: TAH/BSO +/– lysis of adhesions. Pharmacologic: Largely symptomatic relief. NSAIDs (frst line) plus OCPs or progestins. Conservative surgical treatment: Endometrial ablation or resection using hysteroscopy. Complete eradication of deep adenomyosis is diffcult and results in high treatment failure. Defnitive surgical treatment: Hysterectomy is the only def nitive treatment. Complications Infertility (the most common cause among menstruating women > 30 years of age). Rarely, can progress to endometrial carcinoma.
Pregnancy is the most common cause of abnormal uterine bleeding and amenorrhea. Always check a pregnancy test!
Normal menstrual bleeding ranges from two to seven days. Vaginal bleeding that occurs six or more months following the cessation of menstrual function is cancer related until proven otherwise.
Assess the extent of bleeding:Menorrhagia: ↑ amount of fow (> 80 mL of blood loss per cycle) or prolonged bleeding (fow lasting > 8 days); may lead to anemia.
Oligomenorrhea: An ↑ length of time between menses (35–90 days between cycles).
Polymenorrhea: Frequent menstruation (< 21-day cycle); anovular.Metrorrhagia: Bleeding between periods.Menometrorrhagia: Excessive and irregular bleeding.Pelvic exam: Look for an enlarged uterus, a cervical mass, or polyps to assess for myomas, pregnancy, or cervical cancer.
First step: Obtain a β-hCG to rule out ectopic pregnancy.
Second step: Order a CBC to rule out anemia.Third step:Pap smear to rule out cervical cancer (which can present with bleeding).
TFTs to rule out hyper-/hypothyroidism and hyperprolactinemia.Obtain platelet count, bleeding time, and PT/PTT to rule out von Willebrand’s disease and factor XI def ciency.
Order an ultrasound to evaluate the ovaries, uterus, and endometrium. Look for uterine masses, polycystic ovaries, and thickness of the endometrium.
If the endometrium is ≥ 4 mm in a postmenopausal woman, obtain an endometrial biopsy. An endometrial biopsy should also be obtained if the patient is > 35 years of age, obese (BMI > 35), and diabetic.
Heavy bleeding: Since heavy or prolonged uterine bleeding has likely denuded the endometrial cavity, estrogen is needed to rapidly promote endometrial growth.
First step: For hemorrhage, high-dose estrogen IV stabilizes the endometrial lining and stops bleeding within one hour.
Next step: If bleeding is not controlled within 12–24 hours, a D&C is indicated.
Ovulatory bleeding: The goal is to ↓ blood loss.First step: NSAIDs to ↓ blood loss.Next step: If the patient is hemodynamically stable, treat with OCPs or a Mirena IUD to thicken the endometrium and control the bleeding. If this is not effective within 24 hours, look for an alternative diagnosis.
Anovulatory bleeding: The goal is to convert proliferative endometrium to secretory endometrium.
Give progestins × 10 days to stimulate withdrawal bleeding.For young patients with anovulatory bleeding who may also have a bleeding disorder, give desmopressin followed by a rapid ↑ in von Willebrand’s factor and factor VIII (lasts roughly six hours).
If medical management fails, options include the following:D&C: An appropriate diagnostic/therapeutic option.Hysteroscopy: Can help identify endometrial polyps as well as aid in the performance of directed uterine biopsies.
Hysterectomy or endometrial ablation: Appropriate in women who fail or do not want hormonal treatment, have symptomatic anemia, and/or experience a disruption in their quality of life from persistent, unscheduled bleeding.
First-line treatment of abnormal uterine bleeding consists of NSAIDs to ↓ blood loss!
OCPs and the Mirena IUD are highly effective treatment options for menorrhagia.
Complications of abnormal uterine bleeding are anemia and endometrial hyperplasia +/− carcinoma.
A 21-hydroxylase defciency that can present in its most severe, classic form as a newborn female infant with ambiguous genitalia and life-threatening salt wasting (see the Endocrinology chapter for a discussion of early-onset CAH). Milder forms present later in life. 11β-hydroxylase defciency is a less common cause of adrenal hyperplasia.
Presents with excessive hirsutism, acne, amenorrhea and/or abnormal uterine bleeding, infertility, and, rarely, a palpable pelvic mass.
Hirsutism = male hair pattern.Virilization = frontal balding, muscularity, clitoromegaly, and deepening of the voice.
Defeminization = ↓ breast size; loss of feminine adipose tissue.
The most severe form of PCOS is HAIR-AN syndrome: HyperAndrogenism, Insulin Resistance, and Acanthosis Nigricans.
■↑ androgens (testosterone > 2 ng; DHEAS > 7 μg/mL): Rule out adrenal or ovarian neoplasm. ■↑ serum testosterone: Suspect an ovarian tumor. ■↑ DHEAS: Suspect an adrenal source (adrenal tumor, Cushing’s syn drome, CAH). ■↑ 17-OH progesterone levels (either basally or in response to ACTH stimulation).
■Table 2.12-5 outlines the differential diagnosis of hyperandrogenism.Glucocorticoids (e.g., prednisone). Medical therapy for adrenal and ovarian disorders prevents new terminal hair growth but does not resolve hirsutism. Laser ablation, electrolysis, or conventional hair removal techniques must be used to remove unwanted hair.
One of the most common endocrine disorders in reproductive women, with a prevalence of 6–10% among U.S. women of reproductive age. Also known as Stein-Leventhal syndrome. Diagnosis requires two of the following three criteria: 1.
Clinical or biochemical evidence of hyperandrogenismT AB LE 2.1 2-5. Differential Diagnosis of HyperandrogenismPCOS Irregular menses, slow-onset hirsutism, obesity, infertility, hypertension, a family history of PCOS or DM. Fasting glucose, insulin/lipid prof le, BP, ultrasound for ovarian cysts. 21-hydroxylase def ciency—nonclassic (late-onset) CAH Severe hirsutism or virilization, a strong family history of CAH, short stature, signs of defeminization. More common among Ashkenazi Jews. 17-hydroxyprogesterone (17-HP) levels before and after ACTH stimulation test > 10 ng/dL; CYP21 genotype. 21-hydroxylase def ciency—classic (congenital) CAH Same as above but with congenital virilization. 17-HP levels > 30 ng/dL. Hypothyroidism Fatigue, weight gain, amenorrhea. TSH. Hyperprolactinemia Amenorrhea, galactorrhea, infertility. Prolactin. Androgen-secreting neoplasm Pelvic mass, rapid-onset hirsutism or virilization, > 30 with onset of symptoms. Pelvic ultrasound or abdominal/pelvic CT. Cushing’s syndrome Hypertension, buffalo hump, purple striae, truncal obesity. Elevated BP plus dexamethasone suppression test.
High BP.BMI > 30 (obesity).Stigmata of hyperandrogenism or insulin resistance (menstrual cycle disturbances, hirsutism, obesity, acne, androgenic alopecia, acanthosis nigricans).
Women with PCOS are also at ↑ risk for the following:
Metabolic syndrome—insulin resistance, obesity, atherogenic dyslipidemia, and hypertensionBiochemical hyperandrogenemia: ↑ testosterone (total +/− free); DHEAS, DHEA.Exclude other causes of hyperandrogenism:TSH, prolactin.17-OH progesterone to rule out nonclassical CAH.Consider screening in the setting of clinical signs of Cushing’s syndrome (e.g., moon facies, buffalo hump, abdominal striae) or acromegaly (e.g., ↑ head size).
Evaluate for metabolic abnormalities:Two-hour oral glucose tolerance test.Fasting lipid and lipoprotein levels (total cholesterol, HDL, LDL, triglycerides).
Optional tests:Ultrasound: Look for > 8 small, subcapsular follicles forming a “pearl necklace” sign (see Figure 2.12-4). Seen in roughly two-thirds of women with PCOS.
Gonadotropins: ↑ LH/FSH ratio (> 2:1).Fasting insulin levels.24-hour urine for free cortisol: Adult-onset CAH or Cushing’s syndrome.
F IGU R E 2.1 2-4. Polycystic ovary with prominent multiple cysts.
(Reproduced, with permission, from DeCherney AH. Current Obstetric & Gynecologic Diagnosis & Treatment, 8th ed. Stamford, CT: Appleton & Lange, 1994: 747.) ↓ the risk of endometrial hyperplasia/carcinoma among women with PCOS.
Women who are not attempting to conceive: Treat with a combination of OCPs, progestin, and metformin (or other insulin-sensitizing agents).
Women who are attempting to conceive: Clomiphene +/− metformin is frst-line treatment for ovulatory stimulation.
Symptom-specif c treatment:Hirsutism: Combination OCPs are frst line; antiandrogens (spironolactone, f nasteride) and metformin may also be used.
Cardiovascular risk factors and lipid levels: Diet, weight loss, and exercise plus potentially lipid-controlling medication (e.g., statins).
↑ risk of early-onset type 2 DM; ↑ risk of miscarriages; ↑ long-term risk of breast and endometrial cancer due to unopposed estrogen secretion.
Defned as inability to conceive after 12 months of normal, regular, unprotected sexual activity. 1° infertility is characterized by no prior pregnancies; 2° infertility occurs in the setting of at least one prior pregnancy. Etiologies are shown in Figure 2.12-5 and Table 2.11-6.
Cyst and Abscess of Bartholin’s DuctObstruction of the gland leads to pain, swelling, and abscess formation.
Infertility14% of reproductive aged women 5 million couples in the U.S. Female causes 58% Male causes 25% Unexplained 17% Amenorrhea/ ovulatory dysfunction 46% Hypothalamic/ pituitary causes 51% Polycystic ovary syndrome 30% Premature ovarian failure 12% Tubal defect 38% Primary hypogonadism ( FSH) 30–40% Secondary hypogonadism ( FSH, LH) 2% Disordered sperm transport 10–20% Unknown 40–50% Endometriosis 9% Other 7% Uterine or outflow tract disorders 7%
FIGURE 2.12-5. Causes of infertility.(Reproduced, with permission, from Fauci AS et al. Harrison’s Principles of Internal Medicine, 17th ed. New York: McGraw-Hill, 2008: Fig. 341-9.)
TABLE 2.12-6.  Infertility WorkupMale causes Testicular injury or infection Medications (corticosteroids, cimetidine, spironolactone) Thyroid or liver disease Signs of hypogonadism Varicocele TSH Prolactin Karyotype (to rule out Klinefelter’s syndrome) Semen analysis Treatment of hormonal def ciency Intrauterine insemination (IUI) Donor insemination In vitro fertilization (IVF) Intracytoplasmic sperm injection Ovulatory factors Age (incidence ↑ with age) Symptoms of hyper-/ hypothyroidism Galactorrhea Menstrual cycle abnormalities Basal body temperature Ovulation predictor Midluteal progesterone Early follicular FSH +/– estradiol level (ovarian reserve) TSH, prolactin, androgens Ovarian sonography (antral follicle count) Endometrial biopsy (luteal phase defect) Treatment depends on the etiology (e.g., levothyroxine, dopamine) Induction of ovulation with clomiphene, gonadotropins, and pulsatile GnRH IUI IVF Tubal/ pelvic factors History of PID, appendicitis, endometriosis, pelvic adhesions, tubal surgery Hysterosalpingogram, endometrial biopsy Laparoscopic resection or ablation of endometriomas or f broids IVF Cervical factors Abnormal Pap smears, postcoital bleeding, cryotherapy, conization, or DES exposure in utero Pap smear Physical exam Antisperm antibodies IUI with washed sperm IVF
Presents with periodic painful swelling on either side of the introitus and dyspareunia.
A fuctuant swelling 1–4 cm in diameter is seen in the inferior portion of either labium minus.
Tenderness is evidence of active infection.Asymptomatic cysts do not require therapy. Frequent warm soaks may be helpful.
If an abscess develops, treat with aspiration or incision and drainage. Culture for Chlamydia and other pathogens.
Antibiotics are unnecessary unless cellulitis is present.A spectrum of conditions that cause vulvovaginal symptoms such as itching, burning, irritation, and abnormal discharge. The most common causes are bacterial vaginosis, vulvovaginal candidiasis, and trichomoniasis (see Table 2.12-7).
Presents with a change in discharge, malodor, pruritus, irritation, burning, swelling, dyspareunia, and dysuria.
Normal secretions are as follows:Midcycle estrogen surge: Clear, elastic, mucoid secretions.Luteal phase/pregnancy: Thick and white secretions; adhere to the vaginal wall.
TABLE 2.12-7.  Causes of Vaginitis 15–50% (most common). 5–50%. 15–30%. Refects a shift in vaginal f ora. Protozoal f agellates (an STD). Usually Candida albicans. Risk factors Pregnancy, > 1 sexual partner, female sexual partner, frequent douching. An STD. Unprotected sex with multiple partners. DM, broad-spectrum antibiotic use, pregnancy, corticosteroids, HIV, OCP use, IUD use, young age at f rst intercourse, ↑ frequency of intercourse. History Odor, ↑ discharge. ↑ discharge, odor, pruritus, dysuria. Pruritus, dysuria, burning, ↑ discharge. Exam Mild vulvar irritation. “Strawberry petechiae” in the upper vagina/cervix (rare). Erythematous, excoriated vulva/ vagina. Discharge Homogenous, grayish-white, f shy/stale odor. Profuse, malodorous, yellow-green, frothy. Thick, white, curdy texture without odor. Wet mounta “Clue cells” (epithelial cells coated with bacteria; see Figure 2.12-6); shift in vaginal f ora (↑ cocci, ↓ lactobacilli). Motile trichomonads (fagellated organisms that are slightly larger than WBCs). — KOH prep whiff test (fshy smell). — Hyphae (see Figure 2.12–6). Treatment PO or vaginal metronidazole or clindamycin. Single-dose PO metronidazole or tinidazole. Treat partners; test for other STDs. Topical azole or PO f uconazole. Complications Chorioamnionitis/endometritis, infection, preterm delivery, miscarriage, PID. Same as for bacterial vaginosis. Oral azoles should be avoided in pregnancy. a If there are many WBCs and no organism on saline smear, suspect Chlamydia. Incidence Etiology
AB FIGURE 2.12-6. Causes of vaginitis.(A) Candidal vaginitis. Candida albicans organisms are evident on KOH wet mount. (B) Gardnerella vaginalis. Note the granular epithelial cells (“clue cells”) and indistinct cell margins. (Image A reproduced, with permission, from Wolff K et al. Fitzpatrick’s Color Atlas & Synopsis of Clinical Dermatology, 5th ed. New York: McGraw-Hill, 2005: 717. Image B reproduced, with permission, from Kasper DL et al. Harrison’s Principles of Internal Medicine, 16th ed. New York: McGraw-Hill, 2005: 767.)
Conduct a thorough examination of the vulva, vaginal walls, and cervix.
If there are many WBCs and no organism on saline smear, suspect Chlamydia.
Samples from the speculum exam should be obtained for vaginal pH, amine (“whiff”) test, wet mount (with saline), and 10% hydroxide (KOH) microscopy.
To rule out cervicitis, DNA tests or cultures for Neisseria gonorrhoeae or Chlamydia trachomatis should be obtained in patients with a purulent discharge, numerous leukocytes on wet prep, cervical friability, and any symptoms of PID.
Treatment is etiology specifc (see Table 2.12-7).Infammation of the uterine cervix. Because the female genital tract is contiguous from the vulva to the fallopian tubes, there is some overlap between vulvovaginitis and cervicitis. Etiologies are as follows:
Infectious (most common): Chlamydia, gonococcus, Trichomonas, HSV, HPV.Noninfectious: Trauma, radiation exposure, malignancy.Hx/PE: Yellow-green mucopurulent discharge; cervical motion tenderness; absence of other signs of PID.
Dx/Tx: See the discussion of STDs in the Infectious Disease chapter.
Criteria for the clinical diagnosis of bacterial vaginosis (three of four are required):
Vaginal pH > 4.5Clue cells comprise > 20% of epithelial cells on wet mount
A polymicrobial infection of the upper genital tract that is associated with Neisseria gonorrhoeae (one-third of cases), Chlamydia trachomatis (one-third of cases), and endogenous aerobes/anaerobes. The lifetime risk is 1–3%. Risk IUDs do not ↑ PID risk.
The chandelier sign is def ned as severe cervical motion tenderness that makes the patient “jump for the chandelier” on exam.
Mild and subclinical PID is a major cause of tubal factor infertility, ectopic pregnancy, and chronic pelvic pain due to pelvic scarring.
factors include non-Caucasian ethnicity, douching, smoking, multiple sex partners, and prior STDs and/or PID.
Presents with lower abdominal pain, fever and chills, menstrual disturbances, and a purulent cervical discharge.
are also seen.Diagnosed by the presence of acute lower abdominal or pelvic pain plus one of the following:
A WBC count > 10,000 has poor positive and negative predictive value for PID.
Order a β-hCG and ultrasound to rule out pregnancy and to evaluate for the possibility of tubo-ovarian abscess.
Ultrasound is a noninvasive means of diagnosing PID. Look for:
Thickening or dilation of the fallopian tubesFluid in the cul-de-sacAntibiotic treatment should not be delayed while awaiting culture results. All sexual partners should be examined and treated appropriately.
Outpatient regimens:Regimen A: Of oxacin or levof oxacin × 14 days +/– metronidazole × 14 days.
Regimen B: Ceftriaxone IM × 1 dose or cefoxitin plus probenecid plus doxycycline × 14 days +/– metronidazole × 14 days.
Inpatient antibiotic regimens:Cefoxitin or cefotetan plus doxycycline × 14 days.Clindamycin plus gentamicin × 14 days.Drainage of a tubo-ovarian/pelvic abscess is appropriate if the mass persists after antibiotic treatment; the abscess is > 4–6 cm; or the mass is in the cul-de-sac in the midline and drainable through the vagina.
If the abscess is dissecting the rectovaginal septum and is fxed to the vaginal membrane, colpotomy drainage is appropriate.
If the patient’s condition deteriorates, perform exploratory laparotomy.Surgery may range from TAH/BSO with lysis of adhesions in severe cases to conservative surgery for women who desire to maintain fertility.
Some 25% of women with acute disease develop repeated episodes of infection, chronic pelvic pain, dyspareunia, ectopic pregnancy, or infertility.
RUQ pain (Fitz-Hugh–Curtis syndrome) may indicate an associated perihepatitis (abnormal liver function, shoulder pain).
The risk of infertility ↑ with repeated episodes of salpingitis and is esti mated to approach 10% after the frst episode, 25% after the second episode, and 50% after a third episode.
Caused by preformed S. aureus toxin (TSST-1); often occurs within f ve days of the onset of a menstrual period in women who have used tampons. The incidence in menstruating women is now 6–7:100,000 annually. Nonmenstrual cases are nearly as common as menstrual cases.
Presents with abrupt onset of fever, vomiting, and watery diarrhea, with fever 38.9°C (102°F) or higher.
A diffuse macular erythematous rash is also seen.Nonpurulent conjunctivitis is common.Desquamation, especially of the palms and soles, generally occurs during recovery within 1–2 weeks of illness.
Blood cultures are because symptoms result from preformed toxin and are not due to the invasive properties of the organism.
Rapid rehydration.Antistaphylococcal drugs (nafcillin, oxacillin); vancomycin for women with penicillin allergy.
Corticosteroids can reduce the severity of illness and ↓ fever.
Manage renal or cardiac failure.The mortality rate associated with TSS is 3–6%.Three major causes of death are ARDS, intractable hypotension, and hemorrhage 2° to DIC.
TSS is a rare but potentially fatal reaction to S. aureus toxin. Diagnosis is clinical because reaction is to the toxin produced by the bacteria, not to the bacterium itself. The f rst steps in treatment are rapid rehydration and antibiotic treatment.
Gynecologic cancers include uterine, endometrial, ovarian, cervical, and vulvar neoplasms. Ovarian cancer carries the highest mortality.
The most common benign neoplasm of the female genital tract. The tumor is discrete, round, frm, and often multiple and is composed of smooth muscle and connective tissue. Tumors are estrogen and progesterone sensitive, so they often ↑ in size during pregnancy and ↓ after menopause. Malignant transformation to leiomyosarcoma is rare (0.1–0.5%). Prevalence is 25% among Caucasian women and 50% among African-American women.
HISTORY/PE Uterine myomas are benignThe majority of cases are asymptomatic.Symptomatic patients may present with the following: menorrhagia.■Bleeding: Longer, heavier periods; anemia.If a uterine mass continues to grow after menopause, malignancy must be ruled out with a biopsy.
Eighty percent of women with endometrial carcinoma have vaginal bleeding, but only 5–10% of women with abnormal vaginal bleeding have endometrial cancer.
Pressure: Pelvic pressure and bloating; constipation and rectal pressure; urinary frequency or retention.
Pain: 2° dysmenorrhea, dyspareunia.Pelvic symptoms: A frm, nontender, irregular enlarged (“lumpybumpy”), or cobblestone uterus may be seen.
CBC: To look for anemia.Ultrasound: To look for uterine myomas; can also exclude ovarian masses.
MRI: Can delineate intramural and submucous myomas.Combined hormonal contraception.Medroxyprogesterone acetate or danazol to slow or stop bleeding.GnRH analogs (leuprolide or nafarelin) to ↓ the size of myomas, suppress further growth, and ↓ surrounding vascularity. Also used prior to surgery.
Surgery: Emergent surgery is indicated for torsion of a pedunculated myoma.
Women of childbearing years: Myomectomy or hysteroscopy with leiomyoma resection.
Women who have completed childbearing: Total or subtotal abdominal or vaginal hysterectomy.
Uterine artery embolization (~ 25% will need further invasive treatment).
Infertility may be due to a myoma that distorts the uterine cavity and plays a role similar to that of an IUD.
Type I endometrioid adenocarcinomas derive from atypical endometrial hyperplasia and are the most common female reproductive cancer in the United States (~35,000 cases/year). Type II cancers derive from serous or clear cell histology (see Table 2.12-8).
Type I: Vaginal bleeding (early fnding); pain (late fnding); metabolic syndrome.
Type II: No vaginal bleeding.Endometrial/endocervical biopsy.Vaginal ultrasound shows a thickened endometrium leading to hypertrophy and neoplastic change.
TYPE I: ENDOMETRIOID TYPE II: SEROUSTABLE 2.12-8. Types of Endometrial CancerEpidemiology 75% of endometrial cancers. 25% of endometrial cancers. Etiology Unopposed estrogen stimulation (e.g., tamoxifen use, exogenous estrogen-only therapy). Unrelated to estrogen; the p53 mutation is present in 90% of cases. Precursor lesion Hyperplasia and atypical hyperplasia. None. Mean age at diagnosis 55 years. 67 years. Prognosis Favorable. Poor.
Type I: High-dose progestins for women of childbearing age; TAH/BSO +/– radiation for postmenopausal women.
Type II: TAH/BSO with adjuvant chemotherapy for advanced-stage cancer.The upper third of the cervix is made up of columnar cells (similar to the lower uterine segment). The lower two-thirds of the cervix is made up of squamous cells (similar to the vagina). The exposure of columnar cells to an acidic vaginal pH results in metaplasia to squamous cells. The normal squamocolumnar junction (transformation zone) is located in the ectocervix and can be exposed to carcinogens, resulting in cervical intraepithelial neoplasia (CIN), an abnormal proliferation or overgrowth of the basal cell layer.
HPV DNA is found in 99.7% of all cervical carcinomas. HPV 16 is the most prevalent type in squamous cell carcinoma; HPV 18 is most prevalent in adenocarcinoma.
Additional risk factors for cervical cancer include immunosuppression, infection with HIV or a history of STDs, tobacco use, high parity, and OCPs.
The Gardasil vaccine may protect against HPV types 6, 11, 16, and 18 and may also prevent the development of cervical cancer.
Metrorrhagia, postcoital spotting, and cervical ulceration are the most common signs.
A bloody or purulent, malodorous, nonpruritic discharge may appear after invasion.
■Starting at age 21 or no more than three years after becoming sexually active, women should have a Pap smear with conventional cervical cytology on a yearly basis or liquid-based cervical cytology once every two years. Table 2.12-9 outlines the classifcation of Pap smear results.
Hormonal contraceptives are protective against endometrial cancer.Screening of asymptomatic women for endometrial cancer is not recommended.
Fifty percent of women with cervical cancer had not had a Pap smear in the three years preceding their diagnosis, and another 10% had not been screened in f ve years.
T AB LE 2.1 2-9.  Classifcation Systems for Pap Smears 1 Benign Benign Normal 2 Benign with inf ammation Benign with inf ammation Normal, atypical squamous cells (ASC) 3 Mild dysplasia CIN I LSIL 3 Moderate dysplasia CIN II HSIL 3 Severe dysplasia CIN II HSIL 4 Carcinoma in situ CIN II HSIL 5 Invasive cancer Invasive cancer Invasive cancer
Women ≥ 30 years of age who have had three consecutive normal tests may ↑ their screening interval to once every three years.
For women ≥ 30 years of age, HPV DNA testing for high-risk strands may be used for screening as well.
Screening should be discontinued for women ≥ 70 years of age who have had three or more normal Pap smears. Women with DES exposure and/or immunocompromised status (including HIV positivity) should continue as long as they do not have a life-limiting condition.
Women who have had the HPV vaccine should continue cervical cancer screening according to established guidelines.
Recent guidelines for the diagnosis and follow-up of cervical cancer distinguish women ≤ 21 from those > 21 years of age for all subtypes of cervical lesions except atypical glandular cells.
The diagnosis and follow-up of specifc subtypes of cervical lesions should thus proceed as follows:
Atypical glandular cells (AGC): < 35 years of age with no endometrial cancer risk factors: Proceed to colposcopy, endocervical curettage (ECC), and HPV DNA testing.
≥ 35 years of age, endometrial cancer factors, or abnormal bleeding: Add an endometrial biopsy.
Atypical squamous cells of undetermined signif cance (ASC-US): ≤ 21 years of age: Repeat Pap smear at 12 months. If Pap smear is or reveals ASC-US or LSIL, repeat at 12 months.
> 21 years of age: Immediate colposcopy, HPV DNA testing, and repeat Pap smear at 6 months.
Low-grade squamous intraepithelial lesions (LSIL): ≤ 21 years of age: Same as ASC-US.
> 21 years of age: Immediate colposcopy.High-grade squamous intraepithelial lesions (HSIL) or atypical squamous cells suspicious of high-grade dysplasia (ASC-H): Immediate colposcopy is indicated for all age groups.
■Treatment is based on fndings of colposcopy:If colposcopy is satisfactory, proceed to treatment based on f ndings.
If colposcopy is unsatisfactory, perform ECC and cervical biopsy and proceed to treatment based on f ndings.
Noninvasive disease: Treatment based on biopsy results for noninvasive lesions (stage 0 disease) is as follows (see Figure 2.12-7):
CIN I: ■Untreated CIN I will regress in 60% of patients, progress in 10%, and persist in 30%. Thus, the mainstay of treatment for CIN I is close observation.
For women > 21 years of age, Pap smear screening at 6 and 12 months and/or HPV DNA testing at 12 months is indicated. For women ≤ 21 years of age, HPV testing is not recommended.
After two  Pap smears or a DNA test, patients can be managed with routine annual follow-up.
Persistent CIN I can be treated with ablative (cryotherapy or laser ablation) or excisional therapy (loop electrosurgical excision procedure [LEEP]; laser and cold-knife conization).
CD F IGU R E 2.1 2-7. Cervical intraepithelial neoplasia.
(A) Colpophotograph illustrating a low-grade cervical intraepithelial neoplasia (CIN) in the transformation zone. (B)–(D).Histopathology of CIN I, II, and III. (Reproduced, with permission, from Kantarjian HM et al. MD Anderson Manual of Medical Oncology, 1st ed. New York: McGraw-Hill: Fig. 24-4.)
CIN II and III:Untreated CIN II will regress in 43% of patients, progress in 22%, and persist in 35%. Untreated CIN III will regress in 32% of patients, progress in 14%, and persist in 56%.
CIN II and III should be treated with ablative (cryotherapy or laser ablation) or excisional therapy (LEEP; laser and cold-knife conization).
Hysterectomy is a treatment option for recurrent CIN II or III.
Postablative or excisional therapy follow-up is as follows:CIN I, II, or III with margins: Pap smear at 12 months and/or HPV testing.
CIN II or III with margins: Pap smear at 6 months; consider repeat ECC.
If margins are unknown, obtain a Pap smear at 6 months and HPV DNA testing at 12 months.
■ Invasive disease: Treatment based on biopsy results for invasive carcinoma is as follows (for staging, see Figure 2.12-8):
Microinvasive carcinoma (stage IA1): Treat with cone biopsy and close follow-up or simple hysterectomy.
Stages IA2, IB1, and IIA: May be treated either with radical hysterectomy with concomitant radiation and chemotherapy or with radiation plus chemotherapy alone.
Stages IB2, IIB, III, and IV: Treat with radiation therapy plus concurrent cisplatin-based chemotherapy.
■The overall fve-year relative survival rate for carcinoma of the cervix is 68% in Caucasian women and 55% in African-American women.
FIGURE 2.12-8. Staging of cervical cancer.Anatomic display of the stages of cervix cancer, defned by location, extent of tumor, frequency of presentation, and f ve-year survival. (Reproduced, with permission, from Fauci AS et al. Harrison’s Principles of Internal Medicine, 17th ed. New York: McGraw-Hill, 2008: Fig. 93-1.)
Survival rates are inversely proportionate to the stage of cancer: ■Stage 0: 99–100%.
Stage IA: > 95%.Stage IB-IIA: 80–90%.Stage IIB: 65%.Stage III: 40%.Stage IV: < 20%.Almost two-thirds of patients with untreated carcinoma of the cervix die of uremia when ureteral obstruction is bilateral.
Responsible for 1–4% of gynecologic malignancies. Some 90–95% are squamous lesions occurring in women > 50 years of age, followed by melanoma, basal cell carcinoma, adenocarcinoma, sarcoma, Bartholin’s gland tumors, and metastatic disease. Risk factors include HPV (types 16, 18, and 31), lichen sclerosus, infrequent medical exams, diabetes, obesity, hypertension, cardiovascular disease, and immunosuppression.
Presents with pruritus, pain, or ulceration of the mass.Early: Lesions may appear white, pigmented, raised, thickened, nodular, or ulcerative.
Late: Presents with a large, caulifower-like or hard ulcerated area in the vulva.
The frst step is vulvar punch biopsy for any suspicious lesions.
Vulvar intraepithelial neoplasia (VIN) is considered precancerous and more commonly occurs in premenopausal women.
VIN I and II: Associated with mild and moderate dysplasia.
VIN III: Carcinoma in situ.Precancerous lesions: Reduce irritative or other predisposing causes. Topical corticosteroids (e.g., betamethasone, clobetasol) and crotamiton are particularly effective for pruritus.
High-grade VIN: Topical chemotherapy, laser ablation, wide local excision, skinning vulvectomy, and simple vulvectomy.
Invasive: Treated with (1) radical vulvectomy and regional lymphadenectomy or (2) wide local excision of the 1° tumor with inguinal lymph node dissection +/– preoperative radiation, chemotherapy, or both.
Accounts for 1–2% of all gynecologic malignancies. Squamous cell carcinoma usually occurs in postmenopausal woman, whereas other histologic types (rhabdosarcoma, endodermal sinus tumor, adenocarcinoma, and clear cell adenocarcinoma from DES) usually affect younger women. Risk factors include immunosuppression, chronic irritation (e.g., long-term pessary use or prolapse of female organs), low socioeconomic status, radiation for cervical cancer, hysterectomy for dysplasia, multiple sexual partners, and DES exposure.
Frequency of female genital tract cancers: endometrial > ovarian > cervical. Number of deaths: ovarian > endometrial > cervical.
Any palpable ovarian or adnexal mass in a premenarchal or postmenopausal patient is suggestive of an ovarian neoplasm.
Characterized by abnormal vaginal bleeding, an abnormal discharge, or postcoital bleeding.
Presents in the upper third of the vagina in 75% of patients.
Cytology, colposcopy, and biopsy.Local excision of involved areas when they are few and small.
Extensive involvement of the vaginal mucosa may require partial or complete vaginectomy.
Invasive disease requires radiation therapy or radical surgery.Most ovarian tumors are benign, but malignant tumors are the leading cause of death from reproductive tract cancer. Risk factors include the following:
Age, low parity, ↓ fertility, or delayed childbearing.A  family history. Patients with one affected frst-degree relative have a 5% lifetime risk. With two or more affected frst-degree relatives, the risk is 7%.
The BRCA1 mutation carries a 45% lifetime risk of ovarian cancer. The BRCA2 mutation is associated with a 25% lifetime risk.
Lynch II syndrome, or hereditary nonpolyposis colorectal cancer (HNPCC), is associated with an ↑ risk of colon, ovarian, endometrial, and breast cancer.
OCPs taken for fve years or more ↓ risk by 29%.
Both benign and malignant ovarian neoplasms are generally asymptomatic.Mild, nonspecifc GI symptoms or pelvic pressure/pain may be seen.
Early disease is typically not detected on routine pelvic exam.
Some 75% of woman present with advanced malignant disease, as evidenced by abdominal pain and bloating, a palpable abdominal mass, and ascites.
Table 2.12-10 differentiates the benign and malignant characteristics of pelvic masses.
Tumor markers (see Table 2.12-11): ↑ CA-125 is associated with epithelial cell cancer (90% of ovarian cancers) but is used only as a marker for progression and recurrence.
Premenopausal women: ↑ CA-125 may point to benign disease such as endometriosis.
Postmenopausal women: ↑ CA-125 (> 35 units) indicates an ↑ likelihood that the ovarian tumor is malignant.
Transvaginal ultrasound: Used to screen high-risk women.T AB LE 2.1 2-1 0. Benign vs. Malignant Pelvic Masses
Treatment of ovarian masses is as follows:Premenarchal women: Masses > 2 cm require exploratory laparotomy.Premenopausal women:Observation for 4–6 weeks is suffcient for asymptomatic, mobile, unilateral, simple cystic masses < 8–10 cm. Most resolve spontaneously.
Surgical evaluation is warranted for masses > 8–10 cm as well as for those that are unchanged on repeat pelvic exam and ultrasound.
Postmenopausal women:Asymptomatic, unilateral simple cysts < 5 cm in diameter with a normal CA-125 should be closely followed with ultrasound.
Palpable masses warrant surgical evaluation by exploratory laparotomy.Treatment of ovarian cancer is as follows:Surgical staging followed by TAH/BSO with omentectomy and pelvic and para-aortic lymphadenectomy.
TABLE 2.12-11.  Ovarian Tumor MarkersEpithelial CA-125 Endodermal sinus AFP Embryonal carcinoma AFP, hCG Choriocarcinoma hCG Dysgerminoma LDH Granulosa cell Inhibin ■Benign neoplasms warrant tumor removal or unilateral oophorectomy.
Postoperative chemotherapy is routine except for women with early-stage or low-grade ovarian cancer.
Radiation therapy is effective for dysgerminomas.Women with the BRCA1 gene mutation should be screened annually with ultrasound and CA-125 testing. Prophylactic oophorectomy is recommended by age 35 or whenever childbearing is completed.
OCP use ↓ risk.Risk factors for pelvic organ prolapse include vaginal birth (particularly with use of forceps), genetic predisposition, advancing age, prior pelvic surgery, connective tissue disorders, and ↑ intra-abdominal pressure associated with obesity or straining with chronic constipation.
Presents with the sensation of a bulge or protrusion in the vagina.
Urinary or fecal incontinence, a sense of incomplete bladder emptying, and dyspareunia are also seen.
The degree of prolapse can be evaluated by having the woman perform the Valsalva maneuver while in the lithotomy position.
Supportive measures include a high-fber diet and weight reduction in obese patients and limitation of straining and lifting.
Pessaries may temporarily reduce prolapse and are helpful in women who do not wish to undergo surgery or who are chronically ill.
The most common surgical procedure is vaginal or abdominal hysterectomy with vaginal vault suspension.
Defned as the involuntary loss of urine due to either bladder or sphincteric dysfunction.
Table 2.12-12 outlines the types of incontinence along with their distinguishing features and treatment (see also the mnemonic DIAPPERS).
Exclude fstula in cases of total incontinence. Look for neurologic abnormalities in cases of urge incontinence (spasticity, faccidity, rectal sphincter tone) or distended bladder in overf ow incontinence.
First step: Obtain a UA and urine culture to exclude UTI.
Next step: ■Voiding diary; possible urodynamic testing.Causes of urinary incontinence without specif c urogenital pathology—Excessive urinary output (hyperglycemia, hypercalcemia, CHF)TABLE 2.12-12.  Types of IncontinenceTotal Uncontrolled loss at all times and in all positions. Loss of sphincteric eff ciency (previous surgery, nerve damage, cancer inf ltration). Abnormal connection between the urinary tract and the skin (f stula). Surgery. Stress After ↑ intra-abdominal pressure (coughing, sneezing, lifting). Urethral sphincteric insuff ciency due to laxity of pelvic f oor musculature; common in multiparous women or after pelvic surgery. Kegel exercises and pessary. Vaginal vault suspension surgery. Strong, unexpected urge to void that is unrelated to position or activity. Detrusor hyperrefexia or sphincter dysfunction due to inf ammatory conditions or neurogenic disorders of the bladder. Anticholinergic medications or TCAs; behavioral training (biofeedback). Chronic urinary retention. Chronically distended bladder with ↑ intravesical pressure that just exceeds the outlet resistance, allowing a small amount of urine to dribble out. Placement of urethral catheter in acute settings. Treat underlying diseases. Timed voiding. a Etiologies include inhibited contractions, local irritation (cystitis, stone, tumor), and CNS causes. b Etiologies include physical agents (tumor, stricture), neurologic factors (lesions), and medications.
Serum creatinine to exclude renal dysfunction.Cystogram to demonstrate fstula sites and descensus of the bladder neck.
Table 2.12-12 outlines treatment options according to subtype.The most common of all benign breast conditions. Involves exaggerated stromal tissue response to hormones and growth factors. Findings include cysts (gross and microscopic), papillomatosis, adenosis, fbrosis, and ductal epithelial hyperplasia. Primarily affects women 30–50 years of age; rarely found in postmenopausal woman. Associated with trauma and caffeine use.
Presents with cyclic bilateral mastalgia and swelling, with symptoms most prominent just before menstruation.
Rapid f uctuation in the size of the masses is common.
Other symptoms include an irregular, bumpy consistency to the breast tissue (“oatmeal with raisins”).
The differential diagnosis of a breast mass includes f brocystic disease, f broadenoma, mastitis/ abscess, fat necrosis, and breast cancer.
Intraductal papilloma is a common cause of bloody nipple discharge.
See Figure 2.12-9 for an algorithm of a breast mass workup.
Mammography is of limited use. Ultrasound can help differentiate a cystic from a solid mass.
Fine-needle aspiration (FNA) of a discrete mass that is suggestive of a cyst is indicated to alleviate pain as well as to confrm the cystic nature of the mass.
Perform an excisional biopsy if no fuid is obtained or if the fuid is bloody on aspiration.
There is an ↑ risk of breast cancer if ductal epithelial hyperplasia or cellular atypia is present.
Dietary modifcations (e.g., caffeine restriction).Danazol may be given for severe pain but is rarely used in view of its side effects (acne, hirsutism, edema).
Consider use of OCPs, which ↓ hormonal f uctuations.A benign, slow-growing breast tumor with epithelial and stromal components. The most common breast lesion in women < 30 years of age. Cystosarcoma phyllodes is a large f broadenoma.
Suspicious mass: -Age > 35 -Family history -Firm, rigid -Axillary adenopathy -Skin changes FNA Excisional biopsy Excisional biopsy Follow-up monthly × 3 Clear fluid, mass disappears Bloody fluid Residual mass or thickening DCIS/cancer: Treat as indicated Mammography Core or excisional biopsy Negative: Reassure, routine follow-up Nonsuspicious mass: -Age < 35 -No family history -Movable, fluctuant -Size change w/cycle CystSolid Cytology Malignant Treatment Repeat FNA or open surgical biopsy Benign or inconclusive
FIGURE 2.12-9. Workup of a breast mass.Presents as a round or ovoid, rubbery, discrete, relatively mobile, non-tender mass 1–3 cm in diameter.
Usually solitary, although up to 20% of patients develop multiple f broadenomas.
Tumors do not change during the menstrual cycle.Does not occur after menopause unless the patient is on HRT.
Breast ultrasound can differentiate cystic from solid masses.Needle biopsy or FNA.Excision with pathologic exam if the diagnosis remains uncertain.Excision is curative, but recurrence is common.The most common cancer (affects one in eight women) and the second most common cause of cancer death in women (after lung cancer). Sixty percent occur in the upper outer quadrant. Risk factors include the following (most women have no risk factors):
Female gender, older age.A personal history of breast cancer.Breast cancer in a f rst-degree relative.BRCA1 and BRCA2 mutations (associated with early onset).A high-fat and low-f ber diet.A history of fbrocystic change with cellular atypia.■↑ exposure to estrogen (nulliparity, early menarche, late menopause, f rst full-term pregnancy after age 35).
Ninety percent of breast cancers are found by the patient. Clinical manifestations include the following:
Early f ndings: May present as a single, nontender, frm-to-hard mass with ill-defned margins or as mammographic abnormalities with no palpable mass.
Later f ndings: Skin or nipple retraction, axillary lymphadenopathy, breast enlargement, redness, edema, pain, fxation of the mass to the skin or chest wall.
Late f ndings:Ulceration; supraclavicular lymphadenopathy; edema of the arm; metastases to the bone, lung, and liver.
Prolonged unilateral scaling erosion of the nipple with or without discharge (Paget’s disease of the nipple).
Metastatic disease:Back or bone pain, jaundice, weight loss.A frm or hard axillary node > 1 cm.Axillary nodes that are matted or fxed to the skin (stage III); ipsilateral supraclavicular or infraclavicular nodes (stage IV).
↑ exposure to estrogen (early menarche, late menopause, nulliparity) ↑ the risk of breast cancer.
In a postmenopausal woman with a new breast lesion, maintain a high degree of clinical suspicion for breast cancer.
The f rst step in the workup of a suspicious mass in postmenopausal women and in those > 30 years of age is a mammogram. For premenopausal women < 30 years of age, get an ultrasound.
Breast cancer stages:Stage I: Tumor size < 2 cm.Stage II: Tumor size 2–5 cm.Stage III: Axillary node involvement.Stage IV: Distant metastasis.Diagnostic measures differ for postmenopausal and premenopausal women.Postmenopausal women: The frst step is mammography. Look for ↑ density with microcalcifcations and irregular borders. Mammography can detect lesions roughly two years before they become clinically palpable (see Figure 2.12-10A).
Premenopausal women: The frst step for women < 30 years of age is ultrasound, which can distinguish a solid mass from a benign cyst (see Figure 2.12-10B).
Additional measures include the following:Tumor markers for recurrent breast cancer: Include CEA and CA 15-3 or CA 27-29.
Receptor status of tumor: Determine estrogen receptor (ER), progesterone receptor (PR), and HER2/neu status.
Metastatic disease:Labs: ↑ ESR, ↑ alkaline phosphatase (liver and bone metastases), ↑ calcium.
Imaging: CXR; CT of the chest, abdomen, pelvis, and brain; bone scan.
All hormone receptor– patients should receive tamoxifen.ER-patients should receive chemotherapy.Trastuzumab, a monoclonal antibody that binds to HER2/neu receptors on the cancer cell, is highly effective in HER2/neu-expressive cancers.
Surgical options include the following:Partial mastectomy (lumpectomy) plus axillary dissection followed by radiation therapy.
Modifed radical mastectomy (total mastectomy plus axillary dissection).Contraindications to breast-conserving therapy include large tumor size, subareolar location, multifocal tumors, fxation to the chest wall, or involvement of the nipple or overlying skin.
Stage IV disease should be treated with radiotherapy and hormonal therapy; mastectomy may be required for local symptom control.
TNM staging (I–IV) is the most reliable indicator of prognosis.
ERand PRstatus is associated with a favorable course.Cancer localized to the breast has a 75–90% cure rate. With spread to the axilla, the fve-year survival is 40–50%.
Aneuploidy is associated with a poor prognosis.Pleural effusion occurs in 50% of patients with metastatic breast cancer; edema of the arm is common.
B F IGU R E 2.1 2-1 0. Palpable breast mass on mammography and ultrasound.
(A) Craniocaudal mammography of a palpable mass (arrows). (B) Ultrasound image demonstrating a solid mass with irregular borders (arrows) consistent with cancer. (Reproduced, with permission, from Brunicardi FC et al. Schwartz’s Principles of Surgery, 8th ed. New York: McGraw-Hill, 2005: Fig. 16-26.)
Also known as nonaccidental trauma; includes neglect as well as physical, sexual, and psychological maltreatment of children. Suspect abuse if the history is discordant with physical findings or if there is a delay in obtaining appropriate medical care. Certain injuries in children such as retinal hemorrhages and specific fracture types are pathognomonic for abuse.
Abuse or neglect in infants may present as apnea, seizures, feeding intolerance, excessive irritability or somnolence, or failure to thrive (FTT).
Neglect in older children may present as poor hygiene or behavioral abnormalities.
Exam findings may include the following:Injuries in atypical places (e.g., the face or thighs) or patterns (stockingglove burns, cigarette burns, belt marks).
Spiral fractures of the humerus and femur (strongly suggest abuse in children < 3 years of age) or epiphyseal/metaphyseal “bucket fractures,” which suggest shaking or jerking of the child’s limbs.
Posterior rib fractures.Genital trauma, bleeding, or discharge.Rule out conditions that mimic abuse—e.g., bleeding disorders or Mongolian spots (bruises), osteogenesis imperfecta (fractures), bullous impetigo (cigarette burns), and “coining” (an alternative treatment in certain cultures).
A skeletal survey and bone scan can show fractures in various stages of healing.
Test for gonorrhea, syphilis, chlamydia, and HIV if sexual abuse is suspected.
Rule out shaken baby syndrome (SBS) by performing an ophthalmologic exam for retinal hemorrhages and a noncontrast CT for subdural hematomas. Infants with SBS often do not exhibit external signs of abuse.
Consider an MRI to visualize white matter changes (diffuse axonal injury associated with violent shaking) and the extent of intraand extracranial bleeds. MRI often requires the young patient to be sedated and/or intubated, while CT usually does not.
Document injuries, including location, size, shape, color, and the nature of all lesions, bruises, or burns.
Notify child protective services (CPS) for evaluation and possible removal of the child from the home.
Hospitalize if necessary to stabilize injuries or to protect the child.
Consider abuse if the caretaker’s story and the child’s injuries don’t match.
Reporting any suspicion of child abuse is mandatory; you cannot be sued for doing so.
Intrauterine risk factors for congenital heart disease include maternal drug use (alcohol, lithium, thalidomide, phenytoin), maternal infections (rubella), and maternal illness (DM, PKU). Disease is classified by the presence or absence of cyanosis:
Transposition of the great vessels = two arteries switchedTetralogy of Fallot (four)VSD is the most common congenital heart defect.Acyanotic conditions (“pink babies”): Have left-to-right shunts in which oxygenated blood from the lungs is shunted back into the pulmonary circulation.
Cyanotic conditions (“blue babies”): Have right-to-left shunts in which deoxygenated blood is shunted into the systemic circulation.
A condition in which an opening in the ventricular septum allows blood to flow between ventricles. VSD is the most common congenital heart defect. It is more common among patients with Apert’s syndrome (cranial deformities, fusion of the fingers and toes), Down syndrome, fetal alcohol syndrome, TORCH syndrome (toxoplasmosis, other agents, rubella, CMV, HSV), cri du chat syndrome, and trisomies 13 and 18.
Small defects are usually asymptomatic at birth, but exam reveals a harsh holosystolic murmur heard best at the lower left sternal border.
Large defects can present with frequent respiratory infections, dyspnea, FTT, and CHF. If present, the holosystolic murmur is softer and more blowing but can be accompanied by a systolic thrill, crackles, a narrow S2 with an ↑ P1, and a mid-diastolic apical rumble refl ecting ↑ flow across the mitral valve.
Echocardiogram is diagnostic. ECG and CXR can demonstrate LVH with small defects and show both LVH and RVH with larger VSDs. CXR may show ↑ pulmonary vascular markings.
Most small VSDs close spontaneously; patients should be monitored via echocardiography.
Surgical repair is indicated in symptomatic patients who fail medical management, children < 1 year of age with signs of pulmonary hypertension, and older children with large VSDs that have not ↓ in size over time.
Treat existing CHF with diuretics, inotropes, and ACEIs; treat respiratory infections as needed.
A condition in which an opening in the atrial septum allows blood to fl ow between the atria, leading to left-to-right shunting. Associated with Holt-Oram syndrome (absent radii, ASD, first-degree heart block), fetal alcohol syndrome, and Down syndrome.
Ostium primum defects present in early childhood with findings of a murmur or fatigue with exertion. Ostium secundum defects (most common) tend to present in late childhood or early adulthood. Symptom onset and severity depend on the size of the defect.
Symptoms of easy fatigability, frequent respiratory infections, and FTT can be observed, but patients are frequently asymptomatic.
ASD has a f xed, widely split S2.■Exam reveals a right ventricular heave; a wide and fxed, split S2; and a systolic ejection murmur at the upper left sternal border (from ↑ fl ow across the pulmonary valve). There may also be a mid-diastolic rumble at the left lower sternal border.
Echocardiogram with color flow Doppler reveals blood flow between the atria (diagnostic), paradoxical ventricular wall motion, and a dilated right ventricle.
ECG most commonly shows right axis deviation and RVH, although other patterns are possible depending on the type of defect. PR prolongation is common.
CXR reveals cardiomegaly and ↑ pulmonary vascular markings.Most lesions are small defects that may close spontaneously and do not require treatment.
Surgical closure is indicated in infants with CHF and in patients with more than a 2:1 ratio of pulmonary to systemic blood flow. Early correction prevents complications such as arrhythmias, right ventricular dysfunction, and Eisenmenger’s syndrome.
Failure of the ductus arteriosus to close in the first few days of life, leading to a left-to-right shunt from the aorta to the pulmonary artery. Risk factors include maternal first-trimester rubella infection, prematurity, and female gender.
Typically asymptomatic; patients with large defects may present with FTT, recurrent lower respiratory tract infections, lower extremity clubbing, and CHF.
Exam reveals a wide pulse pressure; a continuous “machinery murmur” at the second left intercostal space at the sternal border; a loud S2; and bounding peripheral pulses.
A color flow Doppler demonstrating blood flow from the aorta into the pulmonary artery is diagnostic.
With larger PDAs, echocardiography shows left atrial and left ventricular enlargement.
ECG may show LVH, and CXR may show cardiomegaly if large lesions.
Give indomethacin unless the PDA is needed for survival (e.g., transposition of the great vessels, tetralogy of Fallot, hypoplastic left heart) or if indomethacin is contraindicated (e.g., intraventricular hemorrhage).
If indomethacin fails or if the child is > 6–8 months of age, surgical closure is required.
In Eisenmenger’s syndrome, left-to-right shunt leads to pulmonary hypertension and shunt reversal.
In infants presenting in a shocklike state within the f rst few weeks of life, look for: 1.
Inborn error of metabolism 3.Ductal-dependent congenital heart disease, usually left-sided lesions (as the ductus is closing) 4.
Come IN and CLOSE the door: give INdomethacin to CLOSE a PDA.
What maternally ingested drug is associated with Ebstein’s anomaly (tricuspid valve displacement into the right ventricle)? Lithium.
Coarctation is a cause of 2° hypertension in children.Coarctation of the AortaConstriction of a portion of the aorta, leading to ↑ flow proximal to and ↓ flow distal to the coarctation. Occurs just below the left subclavian artery in 98% of patients. The condition is associated with Turner’s syndrome, berry aneurysms, and male gender. More than two-thirds of patients have a bicuspid aortic valve.
Often presents in childhood with asymptomatic hypertension.Lower extremity claudication, syncope, epistaxis, and headache may be present.
The classic physical exam finding is a systolic BP that is higher in the upper extremities; the difference in BP between the left and right arm can indicate the point of coarctation.
Additional findings include weak femoral pulses, radiofemoral delay, a short systolic murmur in the left axilla, and a forceful apical impulse.
In infancy, critical coarctation requires a patent PDA for survival. Such infants may present in the first few weeks of life in a shocklike state when the PDA closes. Differential cyanosis may be seen with lower oxygen saturation in the left arm and lower extremities (postductal areas) as compared to the right arm (preductal area).
Echocardiography and color flow Doppler are diagnostic.CXR in young children may demonstrate cardiomegaly and pulmonary congestion.
In older children, the following compensatory changes may be seen: LVH on ECG; the “3” sign on CXR due to preand postdilatation of the coarctation segment with aortic wall indentation; and “rib notching” due to collateral circulation through the intercostal arteries.
If severe coarctation presents in infancy, the ductus arteriosus should be kept open with prostaglandin E1 (PGE1).
Surgical correction or balloon angioplasty (controversial).Monitor for restenosis, aneurysm development, and aortic dissection.Transposition of the Great VesselsThe most common cyanotic congenital heart lesion in the newborn. In this condition, the aorta is connected to the right ventricle and the pulmonary artery to the left ventricle, creating parallel pulmonary and systemic circulations. Without a septal defect or a PDA, it is incompatible with life. Risk factors include diabetic mothers and, rarely, DiGeorge syndrome (see the mnemonic CATCH 22).
■Critical illness and cyanosis typically occur immediately after birth. Reverse differential cyanosis may be seen if left ventricular outflow tract obstruction (e.g., coarctation, aortic stenosis) is also present.
■Exam reveals tachypnea, progressive hypoxemia, and extreme cyanosis. Some patients have signs of CHF, and a single loud S2 is often present. There may not be a murmur if no VSD is present.
CXR may show a narrow heart base, absence of the main pulmonary artery segment (“egg-shaped silhouette”), and ↑ pulmonary vascular markings.
Start IV PGE1 to maintain or open the PDA.If surgery is not feasible within the first few days of life or if the PDA cannot be maintained with prostaglandin, perform balloon atrial septostomy to create or enlarge an ASD.
Surgical correction (arterial or atrial switch).Tetralogy of FallotConsists of pulmonary stenosis, overriding aorta, RVH, and VSD. The most common cyanotic congenital heart disease in children. Early cyanosis results from right-to-left shunting across the VSD. As right-sided pressures ↓ in the weeks after birth, the shunt direction reverses and cyanosis may ↓. If the degree of pulmonary stenosis is severe, the right-sided pressures may remain high and cyanosis may worsen over time. Risk factors include maternal PKU and DiGeorge syndrome.
Presents in infancy or early childhood with dyspnea and fatigability. Cyanosis is often not present at birth but develops over the first two years of life; the degree of cyanosis often reflects the extent of pulmonary stenosis.
Infants are often asymptomatic until 4–6 months of age, when CHF may develop and may manifest as diaphoresis with feeding or tachypnea.
Children often squat for relief (↑ systemic vascular resistance) during hypoxemic episodes (“tet spells”).
Hypoxemia may lead to FTT or mental status changes.Exam reveals a systolic ejection murmur at the left upper sternal border (right ventricular outflow obstruction), a right ventricular heave, and a single S2.
Echocardiography and catheterization.CXR shows a “boot-shaped” heart with ↓ pulmonary vascular markings. Remember that a VSD may result in ↑ pulmonary vascular markings.
ECG shows right-axis deviation and RVH.Lesions with severe pulmonary stenosis or atresia require immediate PGE1 to keep the PDA open along with urgent surgical consultation.
Treat hypercyanotic “tet spells” with O2, propranolol, phenylephrine, knee-chest position, fluids, and morphine.
Temporary palliation can be achieved through the creation of an artificial shunt (e.g., balloon atrial septostomy) before definitive surgical correction (Blalock-Taussig shunt).
Coarctation in infancy may present with differential cyanosis, while transposition of the great arteries may present with reverse differential cyanosis.
Transposition of the great vessels is the most common cyanotic heart disease of newborns. Tetralogy of Fallot is the most common cyanotic heart disease of childhood.
Both transposition of the great vessels and tetralogy of Fallot are initially treated with PGE1 and are def nitively treated with surgical correction.
Table 2.13-1 highlights major developmental milestones. Commonly tested milestones appear in bold.
T AB LE 2.1 3-1.  Developmental Milestones 2 months Lifts head/chest when prone. Tracks past midline. Alerts to sound; coos. Recognizes parent; social smile. 4–5 months Rolls front to back, back to front (5 months). Grasps rattle. Orients to voice; begins to make consonant sounds; razzes. Enjoys looking around; laughs. 6 months Sits unassisted. Transfers objects; raking grasp. Babbles. Stranger anxiety. 9–10 months Crawls; pulls to stand. Uses three-finger (immature) pincer grasp. Says “mama/dada” (nonspecif c). Waves bye-bye; plays pat-a-cake. 12 months Cruises (11 months); walks alone. Uses two-finger (mature) pincer grasp. Says “mama/dada” (specif c). Imitates actions; separation anxiety. 15 months Walks backward. Uses cup. Uses 4–6 words. Temper tantrums. 18 months Runs; kicks a ball. Builds tower of 2–4 cubes. Names common objects. May start toilet training. 2 years Walks up/down steps with help; jumps. Builds tower of six cubes. Uses two-word phrases. Follows two-step commands; removes clothes. 3 years Rides tricycle; climbs stairs with alternating feet (3–4 years). Copies a circle; uses utensils. Uses three-word sentences. Brushes teeth with help; washes/dries hands. Hops. Copies a square. Knows colors and some numbers. Cooperative play; plays board games. Skips; walks backward for long distances. Ties shoelaces; knows left and right; prints letters. Uses f ve-word sentences. Domestic role playing; plays dress-up. 4 years 5 years a For premature infants < 2 years of age, chronological age must be adjusted for gestational age. For example, an infant born at seven months’ gestation (two months early) would be expected to perform at the four-month level at the chronological age of six months.
At each well-child check, height, weight, and head circumference are plotted on growth charts specific for gender and age:
Head circumference: Measured routinely in the first two years. ↑ head circumference can indicate hydrocephalus or tumor; ↓ head circumference can point to microcephaly (e.g., TORCH infections).
Height and weight: Measured routinely until adulthood. The pattern of growth is more important than the raw numbers. Infants may lose 5–10% of birth weight (BW) over the first few days but should return to their BW by 14 days. Infants can be expected to double their BW by 4–5 months, triple by one year, and quadruple by two years.
Failure to thrive: Persistent weight less than the 5th percentile for age or “falling off the growth curve” (i.e., crossing two major percentile lines on a growth chart). Classified as follows:
Organic: Due to an underlying medical condition such as cystic fibro-sis, congenital heart disease, celiac sprue, pyloric stenosis, chronic infection (e.g., HIV), and GERD.
Nonorganic: Primarily due to psychosocial factors such as maternal depression, neglect, or abuse.
A careful dietary history and close observation of maternal-infant interactions (especially preparation of formula and feeding) are critical to diagnosis.
Children should be hospitalized if there is evidence of neglect or severe malnourishment. Calorie counts and supplemental nutrition (if breastfeeding is inadequate) are mainstays of treatment.
Tanner staging: Performed to assess physical development in boys and girls. Stage 1 is preadolescent; stage 5 is adult. Increasing stages are assigned for testicular and penile growth in boys and breast growth in girls; pubic hair development is used for both stages.
Girls: The average age of puberty is 10.5 years. Generally the order of progression is thelarche (breast bud development) → pubarche (pubic hair development) → growth spurt → menarche (first menstrual bleeding). The average age of menarche in United States girls is 12.5 years.
Boys: The average age of puberty is 11.5 years. Generally the order of progression is gonadarche (testicular enlargement) → pubarche → adrenarche (axillary hair, facial hair, vocal changes) → growth spurt.
Variants of normal sexual development are as follows:Delayed puberty: No testicular enlargement in boys by age 14, or no breast development or pubic hair in girls by age 13.
Constitutional growth delay: A normal variant, and the most common cause of delayed puberty. The growth curve lags behind others of the same age but is consistent. There is often a  family history, and children ultimately achieve target height potential.
Pathological puberty delay: Rarely, due to systemic disease (e.g., IBD), malnutrition (e.g., anorexia nervosa), gonadal dysgenesis (e.g., Klinefelter’s syndrome, Turner’s syndrome), or endocrine abnormalities (e.g., hypopituitarism, hypothyroidism, Kallmann’s syndrome, androgen insensitivity syndrome, Prader-Willi syndrome)
Precocious puberty: Any sign of 2° sexual maturation in girls < 8 years or boys < 9 years of age. Often idiopathic; may be central or peripheral (see the Gynecology chapter).
Signs of autism include no babbling and/or gesturing by 12 months, no single words by 16 months, no two-word phrases by 24 months, failure to make eye contact, or any loss of language or social skills.
Infants with FTT will f rst fall off of the weight curve, then the height curve, and f nally the head circumference curve.
Tables 2.13-2 and 2.13-3 outline common genetic diseases and their associated abnormalities.
TABLE 2.13-2.  Genetic DiseasesDown syndrome Trisomy 21 (most common) or robertsonian translocation (higher risk of recurrence) The most common chromosomal disorder and cause of mental retardation. Associated with advanced maternal age. Presents with mental retardation, a fat facial profle, prominent epicanthal folds, and a simian crease. Associated with duodenal atresia, Hirschsprung’s disease, and congenital heart disease (the most common malformation is atrioventricular canal, which includes an ASD and VSD with mitral and tricuspid valve abnormalities due to endocardial cushion defects). Associated with an ↑ risk of acute lymphocytic leukemia (ALL), hypothyroidism, and early-onset Alzheimer’s. Edwards’ syndrome Trisomy 18 Presents with severe mental retardation, rocker-bottom feet, low-set ears, micrognathia, clenched hands, and a prominent occiput. Associated with congenital heart disease. May have horseshoe kidneys. Death usually occurs within one year of birth. Patau’s syndrome Trisomy 13 Presents with severe mental retardation, microphthalmia, microcephaly, cleft lip/palate, abnormal forebrain structures (holoprosencephaly), “punched-out” scalp lesions, and polydactyly. Associated with congenital heart disease. Death usually occurs within one year of birth. Klinefelter’s syndrome (male) 45,XXY Presence of an inactivated X chromosome (Barr body). One of the most common causes of hypogonadism in males. Presents with testicular atrophy, a eunuchoid body shape, tall stature, long extremities, and gynecomastia. Treat with testosterone (prevents gynecomastia; improves 2° sexual characteristics). Turner’s syndrome (female) 45,XO The most common cause of 1° amenorrhea; due to gonadal dysgenesis. No Barr body. Features include short stature, shield chest, widely spaced nipples, webbed neck, coarctation of the aorta, and/or bicuspid aortic valve. May present with lymphedema of the hands and feet in the neonatal period. May have horseshoe kidney. Double Y males 47,XYY Observed with ↑ frequency among inmates of penal institutions. Phenotypically normal; patients are very tall with severe acne and antisocial behavior (seen in 1–2% of XYY males).
TABLE 2.13-2.  Genetic Diseases (continued)Phenylketonuria (PKU) ↓ phenylalanine hydroxylase or ↓ tetrahydrobiopterin cofactor Screened for at birth; screening is valid only after the baby has had a protein meal (i.e., a normal breast or formula feed). Tyrosine becomes essential and phenylalanine builds up excess phenyl ketones. Presents with mental retardation, fair skin, eczema, and a musty or mousy urine odor. Blond-haired, blue-eyed infants. Associated with an ↑ risk of heart disease. Treat with ↓ phenylalanine and ↑ tyrosine in diet. A mother with PKU who wants to become pregnant must restrict her diet as above before conception. Fragile X syndrome An X-linked defect affecting the methylation and expression of the FMR1 gene The second most common cause of genetic mental retardation. Presents with macro-orchidism; a long face with a large jaw; large, everted ears; and autism. A triplet repeat disorder that may show genetic anticipation.
An autosomal-recessive disorder caused by mutations in the CFTR gene (chloride channel) on chromosome 7 and characterized by widespread exocrine gland dysfunction. CF is the most common severe genetic disease in the United States and is most frequently found in Caucasians.
Fifty percent of patients present with FTT or chronic sinopulmonary disease.
Characterized by recurrent pulmonary infections (especially with Pseudomonas and S. aureus) with subsequent cyanosis, digital clubbing, cough, dyspnea, bronchiectasis, hemoptysis, chronic sinusitis, rhonchi, rales, hyperresonance to percussion, and nasal polyposis.
Fifteen percent of infants present with meconium ileus. Patients usually have greasy stools and flatulence; other prominent GI symptoms include pancreatitis, rectal prolapse, hypoproteinemia, biliary cirrhosis, jaundice, and esophageal varices.
GI symptoms are more prominent in infancy, while pulmonary manifestations predominate thereafter.
Additional symptoms include type 2 DM, a “salty taste,” male infertility (agenesis of the vas deferens), and unexplained hyponatremia.
Patients are at risk for fat-soluble vitamin deficiency (vitamins A, D, E, and
K) 2° to malabsorption and may present with manifestations of these deficiencies.
Sweat chloride test > 60 mEq/L for those < 20 years of age and > 80 mEq/L in adults; DNA probe test.
Most states now perform mandatory newborn screening, but occasional false positives do occur, so children must be brought in for a sweat test to distinguish disease from a carrier state.
The sweat chloride test has traditionally been considered the gold standard for the diagnosis of CF, but conf rmatory genetic analysis is now routinely done.
T AB LE 2.1 3-3.  Lysosomal Storage DiseasesFabry’s disease Caused by a def ciency of α-galactosidase A that leads to accumulation of ceramide trihexoside in the heart, brain, and kidneys. Findings include renal failure and an ↑ risk of stroke and MI. X-linked recessive. Krabbe’s disease Absence of galactosylceramide and galactoside (due to galactosylceramidase defciency), leading to the accumulation of galactocerebroside in the brain. Characterized by optic atrophy, spasticity, and early death. Autosomal recessive. Gaucher’s disease Caused by a defciency of glucocerebrosidase that leads to the accumulation of glucocerebroside in the brain, liver, spleen, and bone marrow (Gaucher’s cells with characteristic “crinkled paper,” enlarged cytoplasm). May present with hepatosplenomegaly, anemia, and thrombocytopenia. Type 1, the more common form, is compatible with a normal life span and does not affect the brain. Autosomal recessive. Niemann-Pick disease A defciency of sphingomyelinase that leads to the buildup of sphingomyelin cholesterol in reticuloendothelial and parenchymal cells and tissues. Patients with type A die by the age of three. Autosomal recessive. No man PICKs (Niemann-PICK) his nose with his sphinger. Tay-Sachs disease An absence of hexosaminidase that leads to GM2 ganglioside accumulation. Infants may appear normal until 3–6 months of age, when weakness begins and development slows and regresses. Exaggerated startle response. Death occurs by the age of three. A cherry-red spot is visible on the macula. The carrier rate is 1 in 30 Jews of European descent (1 in 300 for others). Tay-SaX lacks heXosaminidase. Metachromatic leukodystrophy A defciency of arylsulfatase A that leads to the accumulation of sulfatide in the brain, kidney, liver, and peripheral nerves. Autosomal recessive. Hurler’s syndrome A def ciency of α-L-iduronidase that leads to corneal clouding and mental retardation. Autosomal recessive. Hunter’s syndrome A defciency of iduronate sulfatase. A mild form of Hurler’s with no corneal clouding and mild mental retardation. X-linked recessive. Hunters need to see (no corneal clouding) to aim for the X.
Pulmonary manifestations are managed with chest physical therapy, bronchodilators, corticosteroids, antibiotics, and DNase.
Administer pancreatic enzymes and fat-soluble vitamins A, D, E, and K for malabsorption.
Nutritional counseling and support with a high-calorie and high-protein diet are essential for health maintenance.
■Patients who have severe disease (but who can tolerate surgery) may be candidates for lung or pancreas transplants. Life expectancy was once around 20 years, but with newer treatments it is increasing to past age 30.
A condition in which one portion of the bowel invaginates or “telescopes” into an adjacent segment, usually proximal to the ileocecal valve (see Figure 2.131). The most common cause of bowel obstruction in the first two years of life (males > females); usually seen between three months and three years of age. The cause is often unknown. Risk factors include conditions with potential lead points, including Meckel’s diverticulum, intestinal lymphoma (> 6 years of age), Henoch-Schönlein purpura, parasites, polyps, adenovirus or rotavirus infection, celiac disease, and CF.
Presents with abrupt-onset, colicky abdominal pain in apparently healthy children, often accompanied by flexed knees and vomiting. The child may appear well in between episodes if intussusception is released.
The classic triad is abdominal pain, vomiting, and blood per rectum (affects only one in three patients).
Late signs include bloody mucus in stools (red “currant jelly” stool), lethargy, and fever. The condition may progress to shock as blood flow to the affected segment is compromised.
On exam, look for abdominal tenderness, a stool guaiac, and a palpable “sausage-shaped” RUQ abdominal mass.
FIGURE 2.13-1. Intussusception.A segment of bowel telescopes into an adjacent segment, causing obstruction. (Reproduced, with permission, from Way LW. Current Surgical Diagnosis & Treatment, 10th ed. Stamford, CT: Appleton & Lange, 1994: 1222.) enema is both diagnostic and therapeutic in most cases of intussusception.
The classic metabolic derangement in pyloric stenosis is hypochloremic, hypokalemic metabolic alkalosis (due to persistent emesis of HCl).
Meckel’s rule of 2’s—Most common in children under 2 2 times as common in males
Contains 2 types of tissue (pancreatic and gastric) 2 inches long Found within 2 feet of the ileocecal valve Occurs in 2% of the population
Correct any volume or electrolyte abnormalities and check CBC (for leukocytosis).
Abdominal plain films are often normal early in the disease, but later they may show small bowel obstruction, perforation, or a soft tissue mass. Ultrasound may show a “target sign.”
In the setting of high clinical suspicion, an air-contrast barium enema should be performed without delay, as it is diagnostic in > 95% of cases and curative in > 80%. If the child is unstable or has peritoneal signs or if enema reduction is unsuccessful, perform surgical reduction and resection of gangrenous bowel.
Hypertrophy of the pyloric sphincter, leading to gastric outlet obstruction. More common in firstborn males; associated with tracheoesophageal fistula and with a maternal history of pyloric stenosis.
Nonbilious emesis typically begins around three weeks of age and progresses to projectile emesis after most to all feedings.
Babies initially feed well but eventually suffer from malnutrition and dehydration.
Exam may reveal a palpable olive-shaped, mobile, nontender epigastric mass and visible gastric peristaltic waves.
Abdominal ultrasound is the imaging modality of choice and reveals a hypertrophic pylorus.
Barium studies reveal a narrow pyloric channel (“string sign”) or a pyloric beak.
Correct existing dehydration and acid-base/electrolyte abnormalities.Surgical correction with pyloromyotomy.Caused by failure of the omphalomesenteric (or vitelline) duct to obliterate. The most common congenital abnormality of the small intestine, affecting up to 2% of children. Most frequently occurs in children < 2 years of age.
Typically asymptomatic, and often discovered incidentally.Classically presents with sudden, painless rectal bleeding.Abdominal pain typically signifies complications such as diverticulitis, volvulus, and intussusception.
A Meckel scintigraphy scan (technetium-99m pertechnetate) is diagnostic; plain films have limited value but can be useful in diagnosing obstruction or perforation.
In the presence of active bleeding, treatment is excision of the diverticulum together with the adjacent ileal segment (ulcers frequently develop in adjacent ileum).
If the condition is asymptomatic but discovered intraoperatively, treatment is controversial but often involves excision.
Congenital lack of ganglion cells in the distal colon, leading to uncoordinated peristalsis and ↓ motility. Associated with male gender, Down syndrome, Waardenburg’s syndrome, and multiple endocrine neoplasia (MEN) type 2.
Neonates present with failure to pass meconium within 48 hours of birth, accompanied by bilious vomiting and FTT; children with less severe lesions may present later in life with chronic constipation.
Physical exam may reveal abdominal distention and explosive discharge of stool following rectal exam.
Barium enema is the imaging study of choice and reveals a narrowed distal colon with proximal dilation. Plain films reveal distended bowel loops with a paucity of air in the rectum.
Anorectal manometry detects a failure of the internal sphincter to relax after distention of the rectal lumen. It is typically used in atypical presentations or older children.
Full-thickness rectal biopsy confirms the diagnosis and reveals absence of the myenteric (Auerbach’s) plexus and submucosal (Meissner’s) plexus along with hypertrophied nerve trunks enhanced with acetylcholinesterase stain.
Traditionally a two-stage surgical repair is used involving the creation of a diverting colostomy at the time of diagnosis, followed several weeks later by a definitive “pull-through” procedure connecting the remaining colon to the rectum.
Malrotation with VolvulusCongenital malrotation of the midgut results in abnormal positioning of the small intestine (cecum in the right hypochondrium) and formation of fibrous bands (Ladd’s bands). Bands predispose to obstruction and constriction of blood fl ow.
Often presents in the newborn period with bilious emesis, crampy abdominal pain, distention, and the passage of blood or mucus in stool.
Postsurgical adhesions can lead to obstruction and volvulus at any point in life.
The def nitive diagnosis of Hirschsprung’s disease requires a full-thickness rectal biopsy.
Pneumatosis intestinalis on plain f lms is pathognomonic for necrotizing enterocolitis in neonates.
AXR may reveal the absence of intestinal gas but may also be normal.
If the patient is stable, an upper GI is the study of choice and shows an abnormal location of the ligament of Treitz. Ultrasound may be used, but sensitivity is determined by the experience of the ultrasonographer.
NG tube insertion to decompress the intestine.IV fl uid hydration.Surgical repair (emergent when volvulus is present).A condition in which a portion of the bowel undergoes necrosis. The most common GI emergency in neonates; most commonly occurs in premature infants but can occur in full-term infants as well.
Symptoms are nonspecific and include feeding intolerance, delayed gastric emptying, abdominal distention, and bloody stools.
Symptoms may rapidly progress to intestinal perforation, peritonitis, abdominal erythema, and shock. Maintain a high index of suspicion.
Lab findings are nonspecific and may show hyponatremia, metabolic acidosis, leukopenia or leukocytosis with left shift, thrombocytopenia, and coagulopathy (DIC with prolonged PT, aPTT, and a D-dimer).
Plain abdominal radiographs may show dilated bowel loops, pneumatosis intestinalis (intramural air bubbles representing gas produced by bacteria within the bowel wall), portal venous gas, or abdominal free air. Serial abdominal plain films should be taken every six hours.
Ultrasound may also be helpful in discerning free air, areas of loculation or walled-off abscesses, and bowel necrosis.
Initiate supportive measures, including NPO, an orogastric tube for gastric decompression, correction of dehydration and electrolyte abnormalities, TPN, and IV antibiotics.
Indications for surgery are perforation or radiographic worsening on serial abdominal plain films. An ileostomy with mucous fistula is typically performed, with a reanastomosis later.
Complications include formation of intestinal strictures and short-bowel syndrome.Congenital immunodeficiencies are rare and often present with chronic or recurrent infections (e.g., chronic thrush), unusual or opportunistic organisms, incomplete treatment response, or FTT. Categorization is based on the one immune system component that is abnormal (see also Table 2.13-4).
T AB LE 2.1 3-4.  Pediatric ImmunodeficienciesB cell X-linked agamma-globulinemia (Bruton’s) Common variable immunodef ciency IgA def ciency A B-cell def ciency in boys only. Immunoglobulin level drops in the 20s and 30s; usually a combined Band T-cell defect. Mild; the most common immunodef ciency. Life threatening; encapsulated Pseudomonas, Streptococcus pneumoniae, and Haemophilus infections after six months (passive immunity through maternal antibodies wanes). ↑ pyogenic upper and lower respiratory infections; ↑ risk of lymphoma and autoimmune disease. Usually asymptomatic; patients may develop recurrent respiratory or GI infections. Anaphylactic transfusion reaction due to anti-IgA antibodies is a common presentation. Quantitative immunoglobulin levels. If low, conf rm diagnosis with Band T-cell subsets (absent B cells; T cells are often high); absent tonsils and other lymphoid tissue may be a clue. Treat with prophylactic antibiotics and IVIG. Quantitative immunoglobulin levels; confrm with Band T-cell subsets; treat with IVIG. Quantitative IgA levels; treat infections. Do not give immunoglobulins (can lead to the production of anti-IgA antibodies). T cell Thymic aplasia (DiGeorge syndrome) See mnemonic. Presents with tetany (2° to hypocalcemia) in the f rst days of life. Variable risk of infection. ↑↑↑ infections with fungi and Pneumocystis jiroveci pneumonia (formerly P. carinii). Absolute lymphocyte count; mitogen stimulation response; delayed hypersensitivity skin testing. Treat with bone marrow transplantation and IVIG for antibody def ciency; PCP prophylaxis. Thymus transplantation is an alternative. Combined Ataxia-telangiectasia Severe combined immunodef ciency (SCID) Oculocutaneous telangiectasias and progressive cerebellar ataxia. Caused by a DNA repair defect. Severe lack of B and T cells. ↑ incidence of non-Hodgkin’s lymphoma, leukemia, and gastric carcinoma. Severe, frequent bacterial infections; chronic candidiasis; and opportunistic organisms. No specifc treatment; may require IVIG depending on the severity of the Ig def ciency. Treat with bone marrow transplant or stem cell transplant and IVIG for antibody def ciency. Needs PCP prophylaxis.
T AB LE 2.1 3-4.  Pediatric Immunodeficiencies (continued)Combined (continued) Wiskott-Aldrich syndrome An X-linked disorder with less severe Band T-cell dysfunction. Patients have eczema, ↑ IgE/IgA, ↓ IgM, and thrombocytopenia. The classic presentation involves bleeding, eczema, and recurrent otitis media. ↑↑ risk of atopic disorders, lymphoma/leukemia, and infection from S. pneumoniae, S. aureus, and H. infl uenzae type b. Phagocytic Chronic granulomatous disease (CGD) Leukocyte adhesion def ciency Chédiak-Higashi syndrome An X-linked (2/3) or autosomal-recessive (1/3) disease with def cient superoxide production by PMNs and macrophages. Anemia, lymphadenopathy, and hypergamma-globulinemia may be present. A defect in the chemotaxis of leukocytes. An autosomal-recessive disorder that leads to Chronic skin, pulmonary, GI, and urinary tract infections; osteomyelitis and hepatitis. Infecting organisms are catalase . ↑ risk of infection with Aspergillus. May have granulomas of the skin and GI/GU tracts. Recurrent skin, mucosal, and pulmonary infections. May present as omphalitis in the newborn period with delayed separation of the umbilical cord. ↑↑ incidence of overwhelming infections with S. pyogenes, a defect in neutrophil S. aureus, and Pseudomonas chemotaxis/microtubule species. polymerization.
The syndrome includes oculocutaneous albinism, neuropathy, and neutropenia.Treatment is supportive (IVIG and antibiotics). Patients rarely survive to adulthood. Patients with severe infections may be treated with a bone marrow transplant.
Absolute neutrophil count with neutrophil assays.The nitroblue tetrazolium test is diagnostic for CGD.Treat with daily TMP-SMX; judicious use of antibiotics during infections. IFN-γ can ↓ the incidence of serious infection. Bone marrow transplantation and gene therapy are new therapies.
No pus with minimal infammation in wounds (due to a chemotaxis defect). High WBCs in blood. Bone marrow transplantation is curative.
Look for giant granules in neutrophils. Bone marrow transplant is the treatment of choice.
T AB LE 2.1 3-4.  Pediatric Immunodeficiencies (continued)Complement C1 esterase def ciency (hereditary angioedema) Terminal complement def ciency (C5–C9) An autosomal-dominant disorder with recurrent episodes of angioedema lasting 2–72 hours and provoked by stress or trauma. Inability to form membrane attack complex (MAC). Can lead to life-threatening airway edema. Recurrent meningococcal or gonococcal infections. Rarely, lupus or glomerulonephritis.
Total hemolytic complement (CH50) to assess the quantity and function of complement. Purif ed C1 esterase and FFP can be used prior to surgery.
Meningococcal vaccine and appropriate antibiotics.B-cell def ciencies: Most common (50%). Typically present after six months of age with recurrent sinopulmonary, GI, and urinary tract infections with encapsulated organisms (H. infl uenzae, S. pneumoniae, Neisseria meningitidis). Treated with IVIF (except for IgA deficiencies).
T-cell def ciencies: Tend to present earlier (1–3 months) with opportunistic and low-grade fungal, viral, and intracellular bacterial infections (e.g., mycobacteria). 2° B-cell dysfunction may also be seen.
Phagocyte def ciencies: Characterized by mucous membrane infections, abscesses, and poor wound healing. Infections with catalaseorganisms (e.g., S. aureus), fungi, and gram-enteric organisms are common.
Complement def ciencies: Present in children with congenital asplenia or splenic dysfunction (sickle cell disease). Characterized by recurrent bacterial infections with encapsulated organisms.
A multisystemic acute vasculitis that primarily affects young children (80% are < 5 years of age), particularly those of Asian ancestry. Divided into acute, sub-acute, and chronic phases.
Acute phase: Lasts 1–2 weeks and presents with the following symptoms (fever plus four or more of the criteria below are required for diagnosis):
Fever (usually > 40°C) for at least f ve days.
Bilateral, nonexudative, painless conjunctivitis sparing the limbic area.Polymorphous rash (primarily truncal).Cervical lymphadenopathy (often painful and unilateral, with at least one node > 1.5 cm).
Diffuse mucous membrane erythema (e.g., “strawberry tongue”); dry, red, chapped lips.
Erythema of the palms and soles; indurative edema of the hands and feet; late desquamation of the fingertips (in the subacute phase).
Other manifestations include sterile pyuria, gallbladder hydrops, hepatitis, and arthritis.
Untreated Kawasaki disease can lead to coronary aneurysms and even myocardial infarction!
Conjunctivitis Rash Adenopathy Strawberry tongue Hands and feet (red, swollen, f aky skin) BURN (fever > 40°C for ≥ 5 days)
Subacute phase: Begins after the abatement of fever and typically lasts for an additional 2–3 weeks. Manifestations are thrombocytosis and elevated ESR. Untreated children may begin to develop coronary artery aneurysms (40%); all patients should be assessed by echocardiography at diagnosis.
Chronic phase: Begins when all clinical symptoms have disappeared; lasts until ESR returns to baseline. Untreated children are at risk of aneurysmal expansion and MI.
High-dose ASA (for inflammation and fever) and IVIG (to prevent aneurysms).
Low-dose ASA is then continued, usually for six weeks. Children who develop coronary aneurysms may require chronic anticoagulation with ASA or other antiplatelet medications.
Corticosteroids may be used in IVIG-refractory cases, but routine use is not recommended.
Referral to a pediatric cardiologist and routine follow-up echocardiograms to assess for progression of coronary artery aneurysms are important parts of ongoing management.
An autoimmune disorder manifesting as arthritis with “morning stiffness” and gradual loss of motion that is present for at least six weeks in a patient < 16 years of age. Formerly known as juvenile rheumatoid arthritis (JRA).
Pauciarticular (oligoarthritis): Most common; four or fewer joints are involved (usually weight-bearing); usually ANA and RF . Involves young females; uveitis is common and requires slit-lamp exam for evaluation. No systemic symptoms.
Polyarthritis: Involves five or more joints; symmetric. RF positivity is rare and indicates severe disease; younger children may be ANA  with milder disease. Systemic symptoms are rare.
Systemic-onset (Still’s disease): May present with recurrent high fever (usually > 39°C), hepatosplenomegaly, and a salmon-colored macular rash; usually RF and ANA .
NSAIDs and strengthening exercises.Corticosteroids and immunosuppressive medications (methotrexate; anti-TNF agents such as etanercept) are second-line agents.
Corticosteroids are used in the presence of carditis.A suppurative infection of the middle ear cavity that is common in children. Up to 75% of children have at least three episodes by the age of two. Common pathogens include S. pneumoniae, nontypable H. infl uenzae, Moraxella catarrhalis, and viruses such as influenza A, RSV, and parainfl uenza virus.
Symptoms include ear pain, fever, crying, irritability, difficulty feeding or sleeping, vomiting, and diarrhea. Young children may tug on their ears.
Signs on otoscopic exam reveal an erythematous tympanic membrane (TM), bulging or retraction of the TM, loss of TM light refl ex, and ↓ TM mobility (test with an insuffl ator bulb).
High-dose amoxicillin (80–90 mg/kg/day) × 10 days for empiric therapy. Resistant cases may require amoxicillin/clavulanic acid.
Complications include TM perforation, mastoiditis, meningitis, cholesteatomas, and chronic otitis media. Recurrent otitis media can cause hearing loss with resultant speech and language delay. Chronic otitis media may require tympanostomy tubes.
An acute inflammatory illness of the small airways that primarily affects infants and children < 2 years of age, often in the fall or winter months. RSV is the most common cause; others include parainfl uenza, infl uenza, and metapneumovirus. Progression to respiratory failure is a potentially fatal complication. For severe RSV, risk factors include age < 6 months, male gender, prematurity, heart or lung disease, and immunodeficiency.
Presents with low-grade fever, rhinorrhea, cough, and apnea (in young infants).
Exam reveals tachypnea, wheezing, intercostal retractions, crackles, prolonged expiration, expiratory wheezing, and hyperresonance to percussion.
Predominantly a clinical diagnosis; routine cases do not need blood work or a CXR.
CXR may be obtained to rule out pneumonia and may show hyperinfl ation of the lungs with flattened diaphragms, interstitial infiltrates, and atelectasis.
Nasopharyngeal aspirate to test for RSV is highly sensitive and specific but has little effect on management (infants should be treated for bronchiolitis regardless of whether RSV is or not).
Treatment is primarily supportive; treat mild disease with outpatient management using fluids and nebulizers if needed.
Hospitalize in the setting of marked respiratory distress, O2 saturation of < 92%, toxic appearance, dehydration/poor oral feeding, a history of prematurity (< 34 weeks), age < 3 months, underlying cardiopulmonary disease, or unreliable parents.
Treat inpatients with contact isolation, hydration, and O2. A trial of aerosolized albuterol may be attempted; continue albuterol therapy only if effective.
RSV is the most common cause of bronchiolitis.Ribavirin is an antiviral drug that has a controversial role in bronchiolitis treatment. It is sometimes used in high-risk infants with underlying heart, lung, or immune disease.
RSV prophylaxis with injectable polyor monoclonal antibodies (RespiGam or Synagis) is recommended in winter for high-risk patients ≤ 2 years of age (e.g., those with a history of prematurity, chronic lung disease, or congenital heart disease).
An acute viral inflammatory disease of the larynx, primarily within the subglottic space. Pathogens include parainf uenza virus type 1 (most common), 2, and 3; RSV; influenza; and adenovirus. Bacterial superinfection may progress to tracheitis.
Prodromal URI symptoms are typically followed by low-grade fever, mild dyspnea, inspiratory stridor that worsens with agitation, a hoarse voice, and a characteristic barking cough (usually at night).
Diagnosed by clinical impression; often based on the degree of stridor and respiratory distress.
AP neck film may show the classic “steeple sign” from subglottic narrowing (see Figure 2.13-2), but the finding is neither sensitive nor specif c.
Table 2.13-5 differentiates croup from epiglottitis and tracheitis.FIGURE 2.13-2. Croup.The x-ray shows marked subglottic narrowing of the airway (“steeple sign”). (Reproduced, with permission, from Saunders CE. Current Emergency Diagnosis & Treatment, 4th ed. Stamford, CT: Appleton & Lange, 1992: 448.)
T AB LE 2.1 3-5. Characteristics of Croup, Epiglottitis, and Tracheitis
Age group affected 3 months to 3 years 3–7 years 3 months to 2 years Incidence in children presenting with stridor 88% 8% 2% Pathogen Parainf uenza virus H. infl uenzae Often S. aureus Onset Prodrome (1–7 days) Rapid (4–12 hours) Prodrome (3 days) leading to acute decompensation (10 hours) Fever severity Low grade High grade Intermediate grade Associated symptoms Barking cough, hoarseness Muffed voice, drooling Variable respiratory distress Position preference None Seated, neck extended None Response to racemic epinephrine Stridor improves None None CXR fndings “Steeple sign” on AP flm “Thumbprint sign”’ on lateral f lm Subglottic narrowing
Mild cases: Outpatient management with cool mist therapy and fl uids.
Moderate cases: May require supplemental O2, oral and IM corticosteroids, and nebulized racemic epinephrine.
Severe cases (e.g., respiratory distress at rest, inspiratory stridor): Hospitalize and give nebulized racemic epinephrine.
A serious and rapidly progressive infection of supraglottic structures (e.g., the epiglottis and aryepiglottic folds). Prior to immunization, H. infl uenzae type b was the 1° pathogen. Common causes now include Streptococcus species,
Epiglottitis can lead to nontypable H. infl uenzae, and viral agents.
Presents with acute-onset high fever (39–40°C), dysphagia, drooling, a muffled voice, inspiratory retractions, cyanosis, and soft stridor.
Patients sit with the neck hyperextended and the chin protruding (“sniffing dog” position) and lean forward in a “tripod” position to maximize air entry.
Untreated infection can lead to life-threatening airway obstruction and respiratory arrest.
Diagnosed by clinical impression. The differential diagnosis must include diffuse and localized causes of airway obstruction (see Tables 2.13-5 and 2.13-6).
The airway must be secured before def nitive diagnosis. In light of potential laryngospasm and airway compromise, do not examine the throat unless an anesthesiologist or otolaryngologist is present.
Definitive diagnosis is made via direct fiberoptic visualization of a cherry-red, swollen epiglottis and arytenoids.
Lateral x-ray shows a swollen epiglottis obliterating the valleculae (“thumbprint sign”; see Figure 2.13-3).
This disease is a true emergency. Keep the patient (and parents) calm, call anesthesia, and transfer the patient to the OR.
Treat with endotracheal intubation or tracheostomy and IV antibiotics (ceftriaxone or cefuroxime).
Bacterial meningitis most often occurs in children < 3 years of age; common organisms include S. pneumoniae, N. meningitidis, and E. coli. Enteroviruses are the most common agents of viral meningitis and occur in children of all ages. Risk factors include sinofacial infections, trauma, and sepsis.
■Bacterial meningitis classically presents with the triad of headache, high fever, and nuchal rigidity.
T AB LE 2.1 3-6. Comparison of Retropharyngeal Abscess and Peritonsillar Abscess
Age group affected Six months to six years. Usually > 10 years of age. History/PE Muffed “hot potato” voice; trismus; drooling; cervical lymphadenopathy. Usually unilateral; may see mass in the posterior pharyngeal wall on visual inspection. Muffed “hot potato” voice; trismus; drooling; displacement of the affected tonsil medially and laterally. Pathogen Group A streptococcus (most common); S. aureus; Bacteroides. Group A streptococcus (most common); S. aureus; S. pneumoniae; anaerobes. Preferred position Supine with the neck extended (sitting up or fexing the neck worsens symptoms). None. Diagnosis On lateral neck x-ray, the soft tissue plane should be ≤ 50% of the width of the corresponding vertebral body. Contrast CT of the neck helps differentiate abscess from cellulitis. Usually clinical. Treatment Aspiration or incision and drainage of abscess; antibiotics. Incision and drainage +/− tonsillectomy; antibiotics.
FIGURE 2.13-3. Epiglottitis.The classic swollen epiglottis (“thumbprint sign”; arrow) and obstructed airway are seen on lateral neck x-ray. (Reproduced, with permission, from Saunders CE. Current Emergency Diag nosis & Treatment, 4th ed. Stamford, CT: Appleton & Lange, 1992: 447.)
Viral meningitis is typically preceded by a prodromal illness that includes fever, sore throat, and fatigue.
Kernig’s sign (pain on knee extension when the hip is flexed) and Brudzinski’s sign (pain with passive neck flexion) are nonspecific signs of meningeal irritation.
Additional physical exam findings may include signs of ↑ ICP (papilledema, cranial nerve palsies) or petechial rash (N. meningitidis). Signs in neonates include lethargy, hyperor hypothermia, poor tone, a bulging fontanelle, and vomiting.
Head CT to rule out ↑ ICP (risk of brain stem herniation).
Perform an LP; send cell count with differential, glucose and protein levels, Gram stain, and culture.
Empiric antibiotic therapy regimens (ceftriaxone, vancomycin, ampicillin) should be administered until bacterial meningitis can be excluded.
Neonates should receive ampicillin and cefotaxime or gentamicin. Consider acyclovir if there is concern for herpes encephalitis (e.g., if the mother had HSV lesions at the time of the infant’s birth).
Older children should receive ceftriaxone and vancomycin.A bacterial infection caused by Bordetella pertussis (whooping cough), a grambacillus. The DTaP vaccine (given in five doses in early childhood) is protective, but immunity wanes by adolescence. Adolescents and young adults serve as the primary reservoir for pertussis. Pertussis can be life threatening for young infants but is generally a milder infection in older children and adults.
Has three stages: (1) catarrhal (mild URI symptoms; lasts 1–2 weeks), (2) paroxysmal (paroxysms of cough with inspiratory whoop and post-tussive emesis; lasts 2–3 months), and (3) convalescent (symptoms wane).
Patients most often present in the paroxysmal stage but are most contagious in the catarrhal stage.
The classic presentation is an infant < 6 months of age with post-tussive emesis and apnea.
Labs show an elevated WBC count with lymphocytosis (often ≥ 70%).
Culture is the gold standard.Hospitalize infants < 6 months of age.Give erythromycin × 14 days to patients and close contacts (including day care contacts).
Patients should not return to school or day care until five days of antibiotics have been administered or until three weeks have elapsed if no therapy has been initiated.
Table 2.13-7 outlines the clinical presentation of common viral exanthems.
TABLE 2.13-7.  Viral ExanthemsErythema infectiosum (f fth disease) Parvovirus B19 Prodrome: None; fever is often absent or low grade. Rash: “Slapped-cheek,” erythematous rash. An erythematous, pruritic, maculopapular rash starts on the arms and spreads to the trunk and legs. Worsens with fever and sun exposure. Arthritis, hemolytic anemia, encephalopathy. Congenital infection is associated with fetal hydrops and death. Aplastic crisis may be precipitated in children with ↑ RBC turnover (e.g., sickle cell anemia, hereditary spherocytosis) or in those with ↓ RBC production (e.g., severe iron def ciency anemia). Measles Paramyxovirus Prodrome: Low-grade fever with Cough, Coryza, and Conjunctivitis (the “3 C’s”); Koplik’s spots (small irregular red spots with central gray specks) appear on the buccal mucosa after 1–2 days. Rash: An erythematous maculopapular rash spreads from the head toward the feet. Common: Otitis media, pneumonia, laryngotracheitis. Rare: Subacute sclerosing panencephalitis.
TABLE 2.13-7.  Viral Exanthems (continued)Rubella Rubella virus Prodrome: Asymptomatic or tender, generalized lymphadenopathy. Rash: Presents with an erythematous, tender maculopapular rash that also starts on the face and spreads distally. In contrast to measles, children with rubella often have only a low-grade fever and do not appear as ill. Polyarthritis may be seen in adolescents. Encephalitis, thrombocytopenia (a rare complication of postnatal infection). Congenital infection is associated with congenital anomalies. Roseola infantum HHV-6 Prodrome: Acute onset of high fever (> 40°C); no other symptoms for 3–4 days. Rash: A maculopapular rash appears as fever breaks (begins on the trunk and quickly spreads to the face and extremities) and often lasts < 24 hours. Febrile seizures may occur as a result of rapid fever onset. Varicella Varicella-zoster virus (VZV) Prodrome: Mild fever, anorexia, and malaise precede the rash by 24 hours. Rash: Generalized, pruritic, “teardrop” vesicular periphery; lesions are often at different stages of healing. Infectious from 24 hours before eruption until lesions crust over. Progressive varicella with meningoencephalitis and hepatitis occurs in immunocompromised children. Congenital infection is associated with congenital anomalies. Varicella zoster VZV Prodrome: Reactivation of varicella infection; starts as pain along an affected sensory nerve. Rash: Pruritic “teardrop” vesicular rash in a dermatomal distribution. Uncommon unless the patient is immunocompromised. Encephalopathy, aseptic meningitis, pneumonitis, TTP, Guillain-Barré syndrome, cellulitis, arthritis. Hand-foot-and-mouth disease Coxsackie A Prodrome: Fever, anorexia, oral pain. Rash: Oral ulcers; maculopapular vesicular rash on the hands and feet and sometimes on the buttocks. None (self-limited).
APGAR (0, 1, 2 in each category)Appearance (blue/pale, pink trunk, all pink) Pulse (0, < 100, > 100) Grimace with stimulation (0, grimace, grimace and cough)
Activity (limp, some, active) Respiratory effort (0, irregular, regular)Direct hyperbilirubinemia is always pathologic.A rapid scoring system that helps evaluate the need for neonatal resuscitation. Each of five parameters (see the mnemonic APGAR) is assigned a score of 0–2 at one and five minutes after birth.
Scores of 8–10: Typically reflect good cardiopulmonary adaptation.Scores of 4–7: Indicate the possible need for resuscitation. Infants should be observed, stimulated, and possibly given ventilatory support.
Scores of 0–3: Indicate the need for immediate resuscitation.Table 2.13-8 describes selected congenital malformations.An elevated serum bilirubin concentration (> 5 mg/dL) due to ↑ hemolysis or ↓ excretion. Subtypes are as follows:
Conjugated (direct) hyperbilirubinemia: Always pathologic.Unconjugated (indirect) hyperbilirubinemia: May be physiologic or pathologic. See Table 2.13-9 for differentiating characteristics.
Kernicterus: A complication of unconjugated hyperbilirubinemia that results from irreversible bilirubin deposition in the basal ganglia, pons, and cerebellum. It typically occurs at levels of > 25–30 mg/dL and can be fatal. Risk factors include prematurity, asphyxia, and sepsis.
The differential includes the following:Conjugated: Extrahepatic cholestasis (biliary atresia, choledochal cysts), intrahepatic cholestasis (neonatal hepatitis, inborn errors of metabolism, TPN cholestasis), Dubin-Johnson syndrome, Rotor’s syndrome, TORCH infections (see the Infectious Disease chapter).
Unconjugated: Physiologic jaundice, hemolysis, breast milk jaundice, ↑ enterohepatic circulation (e.g., GI obstruction), disorders of bilirubin metabolism, hemolysis, sepsis, Crigler-Najjar syndrome, Gilbert’s syndrome.
The history should focus on diet (breast milk or formula), intrauterine drug exposure, and family history (hemoglobinopathies, enzyme deficiencies, RBC defects).
Physical exam may reveal signs of hepatic or GI dysfunction (abdominal distention, delayed passage of meconium, light-colored stools, dark urine), infection, or hemoglobinopathies (cephalohematomas, bruising, pallor, petechiae, and hepatomegaly).
Kernicterus presents with lethargy, poor feeding, a high-pitched cry, hypertonicity, and seizures; jaundice may follow a cephalopedal progression as bilirubin concentrations ↑.
CBC with peripheral blood smear; blood typing of mother and infant (for ABO or Rh incompatibility); Coombs’ test and bilirubin levels.
Ultrasound and/or HIDA scan can confirm suspected cholestatic disease.T AB LE 2.1 3-8.  Selected Congenital MalformationsTracheoesophageal f stula Tract between the trachea and esophagus. Associated with defects such as esophageal atresia and VACTERL (Vertebral, Anal, Cardiac, Tracheal, Esophageal, Renal, Limb) anomalies. Presentation: Polyhydramnios in utero, ↑ oral secretions, inability to feed, gagging, aspiration pneumonia, respiratory distress. Diagnosis: CXR showing an NG tube coiled in the esophagus identifes esophageal atresia. The presence of air in the GI tract is suggestive; confrm with bronchoscopy. Treatment: Surgical repair. Congenital diaphragmatic hernia GI tract segments protrude through the diaphragm into the thorax; 90% are posterior left (Bochdalek). Presentation: Respiratory distress (from pulmonary hypoplasia and pulmonary hypertension); sunken abdomen; bowel sounds over the left hemithorax. Diagnosis: Ultrasound in utero; confrmed by postnatal CXR. Treatment: High-frequency ventilation or extracorporeal membrane oxygenation to manage pulmonary hypertension; surgical repair. Gastroschisis Herniation of the intestine only through the abdominal wall next to the umbilicus (usually on the right) with no sac. Presentation: Polyhydramnios in utero; often premature; associated with GI stenoses or atresia. Treatment: A surgical emergency! Single-stage closure is possible in only 10% of cases. Omphalocele Herniation of abdominal viscera through the abdominal wall at the umbilicus into a sac covered by peritoneum and amniotic membrane. Presentation/diagnosis: Polyhydramnios in utero; often premature; associated with other GI and cardiac defects. Seen in Beckwith-Wiedemann syndrome and trisomies. Treatment: C-section can prevent sac rupture; if the sac is intact, postpone surgical correction until the patient is fully resuscitated. Keep the sac covered/stable with petroleum and gauze. Intermittent NG suction to prevent abdominal distention. Duodenal atresia Complete or partial failure of the duodenal lumen to recanalize during gestational weeks 8–10. Presentation: Polyhydramnios in utero; bilious emesis within hours after frst feeding; associated with Down syndrome and other cardiac/GI anomalies (e.g., annular pancreas, malrotation, imperforate anus). Diagnosis: Abdominal radiographs show the “double-bubble” sign (air bubbles in the stomach and duodenum) proximal to the site of the atresia. Treatment: Surgical repair.
For direct hyperbilirubinemia, check LFTs, bile acids, blood cultures, sweat test, and tests for aminoacidopathies and α1-antitrypsin deficiency.
A jaundiced neonate who is febrile, hypotensive, and/or tachypneic needs a full sepsis workup and ICU monitoring.
Treat underlying causes (e.g., infection).Treat unconjugated hyperbilirubinemia with phototherapy (for mild elevations) or exchange transfusion (for severe elevations > 20 mg/dL). Start
T AB LE 2.1 3-9. Physiologic vs. Pathologic JaundiceRDS is the most common cause of respiratory failure in preterm infants.
An L/S ratio < 2:1 indicates a need for maternal glucocorticoid administration.
Not present until 72 hours after birth. Present in the frst 24 hours of life. Bilirubin ↑ < 5 mg/dL/day. Bilirubin ↑ > 0.5 mg/dL/hour. Bilirubin peaks at < 14–15 mg/dL. Bilirubin ↑ to > 15 mg/dL. Direct bilirubin is < 10% of total. Direct bilirubin is > 10% of total. Resolves by one week in term infants and two weeks in preterm infants. Persists beyond one week in term infants and two weeks in preterm infants.
phototherapy earlier (10–15 mg/dL) for preterm infants. Phototherapy with conjugated hyperbilirubinemia can lead to skin bronzing.
The most common cause of respiratory failure in preterm infants (affects > 70% of infants born at 28–30 weeks’ gestation); formerly known as hyaline membrane disease. Surfactant def ciency leads to poor lung compliance, alveolar collapse, and atelectasis. Risk factors include maternal DM, male gender, and the second born of twins.
Presents in the first 48–72 hours of life with a respiratory rate > 60/min, progressive hypoxemia, cyanosis, nasal flaring, intercostal retractions, and expiratory grunting.
Check ABGs, CBC, and blood cultures to rule out infection.
Diagnosis is based mainly on characteristic CXR findings:RDS: “Ground-glass” appearance, diffuse atelectasis, and air bronchograms on CXR.
Transient tachypnea of the newborn: Retained amniotic fl uid results in prominent perihilar streaking in interlobular fissures.
Meconium aspiration: Coarse, irregular infiltrates; hyperexpansion and pneumothoraces.Congenital pneumonia: Nonspecific patchy infiltrates; neutropenia, tracheal aspirate, and Gram stain suggest the diagnosis.
Continuous positive airway pressure (CPAP) or intubation and mechanical ventilation.
Artificial surfactant administration ↓ mortality.Pretreat mothers at risk for preterm delivery (< 30 weeks’ gestation) with corticosteroids; if > 30 weeks, monitor fetal lung maturity via a lecithin-to-sphingomyelin (L/S) ratio and the presence of phosphatidylglycerol in amniotic fl uid.
Persistent PDA, bronchopulmonary dysplasia, retinopathy of prematurity, barotrauma from positive pressure ventilation, intraventricular hemorrhage, and NEC are complications of treatment.
A range of nonhereditary, nonprogressive disorders of movement and posture; the most common movement disorder in children. Often results from perinatal neurologic insult, but in most cases the cause is unknown. Risk factors include low birth weight, intrauterine exposure to maternal infection, prematurity, perinatal asphyxia, trauma, brain malformation, and neonatal cerebral hemorrhage. Categories include the following:
Pyramidal (spastic): Spastic paresis of any or all limbs. Accounts for 75% of cases. Mental retardation is present in up to 90% of cases.
Extrapyramidal (dyskinetic): A result of damage to extrapyramidal tracts. Subtypes are ataxic (difficulty coordinating purposeful movements), choreoathetoid, and dystonic (uncontrollable jerking, writhing, or posturing). Abnormal movements worsen with stress and disappear during sleep.
May be associated with seizure disorders, behavioral disorders, hearing or vision impairment, learning disabilities, and speech deficits.
Affected limbs may show hyperreflexia, pathologic reflexes (e.g., Babinski), ↑ tone/contractures, weakness, and/or underdevelopment.
■Toe walking and scissor gait are common. Hip dislocations and scoliosis may be seen.
Diagnosed by clinical impression. Ultrasound or CT may be useful in infants to identify intracranial hemorrhage or structural malformations. MRI is diagnostic in older children. EEG may be useful in patients with seizures.
There is no cure for cerebral palsy. Special education, physical therapy, braces, and surgical release of contractures may help.
Treat spasticity with diazepam, dantrolene, or baclofen. Baclofen pumps and posterior rhizotomy may alleviate severe contractures.
Usually occur in children between six months and five years of age who have no evidence of intracranial infection or other causes. Risk factors include a rapid ↑ in temperature and a history of febrile seizures in a close relative. Febrile seizures recur in 30% of patients.
■Seizures usually occur during the onset of fever and may be the first sign of an underlying illness (e.g., otitis media, roseola).
The most common presenting symptom of cerebral palsy is delayed motor development.
Perform an LP if CNS infection is suspected in a patient with a febrile seizure.
Simple febrile seizures do not cause brain damage, usually do not recur, and do not lead to an ↑ risk of epilepsy.
ALL is the most common childhood malignancy, followed by CNS tumors and lymphomas.
■ Classified as simple or complex:Simple: A short-duration (< 15-minute), generalized seizure with one seizure in a 24-hour period. High fever (> 39°C) and fever onset within hours of the seizure are typical.
Complex: A long-duration (> 15-minute) or focal seizure, or multiple seizures in a 24-hour period. Low-grade fever for several days before seizure onset may be present.
Focus on finding a source of infection. LP is indicated if there are clinical signs of CNS infection (e.g., altered consciousness, meningismus, a tense/ bulging anterior fontanelle) after ruling out ↑ ICP.
No lab studies are needed if presentation is consistent with febrile seizures in children > 18 months of age. Infants < 12 months of age need a sepsis workup (CBC, UA, and blood, urine, and CSF culture).
For atypical presentations, obtain electrolytes, serum glucose, blood cultures, UA, and CBC with differential.
Use antipyretic therapy (acetaminophen; avoid ASA in light of the risk of Reye’s syndrome) and treat any underlying illness. Note that antipyretic therapy does not ↓ the recurrence of febrile seizures.
For complex seizures, perform a thorough neurologic evaluation, including an EEG and MRI. Chronic anticonvulsant therapy (e.g., diazepam or phenobarbital) may be necessary.
The risk of recurrence is < 30% and is highest within one year of the initial episode. For simple febrile seizures, there is no ↑ risk of developmental abnormalities or epilepsy.
Risk factors for the development of epilepsy include complex febrile seizures (~10% risk), a  family history of epilepsy, and an abnormal neurologic exam or developmental delay.
A hematopoietic malignancy of lymphocytic or myeloblastic origin. The most common childhood malignancy; 97% of cases are acute leukemias (ALL > AML). ALL is most common in male Caucasian children between two and five years of age; AML is seen most frequently in male African-American children throughout childhood. Associated with trisomy 21, Fanconi’s anemia, prior radiation, severe combined immunodeficiency, and congenital bone marrow failure states.
Symptoms are abrupt in onset. They are initially nonspecific (anorexia, fatigue) and are followed by bone pain with refusal to bear weight, fever (from neutropenia), anemia, ecchymoses, petechiae, and/or hepatosplenomegaly.
CNS metastases may be associated with headache, vomiting, and papilledema.
■AML can present with a chloroma, a greenish soft-tissue tumor on the skin or spinal cord.
CBC, coagulation studies, and peripheral blood smear (high numbers of blast cells). Peripheral smears show lymphoblasts in 90% of cases. WBC counts can be low, normal, or high.
Obtain a bone marrow aspirate for immunophenotyping (TdT assay and a panel of monoclonal antibodies to Tand B-cell antigens) and genetic analysis, which help confirm the diagnosis.
CXR to rule out a mediastinal mass.Chemotherapy based, including induction, consolidation, and maintenance phases.Tumor lysis syndrome (hyperkalemia, hyperphosphatemia, hyperuricemia) is common prior to and during the initiation of treatment. Treat with fl u-ids, diuretics, allopurinol, urine alkalinization, and reduction of phosphate syndrome at the onset of any intake.
chemotherapy regimen.An embryonal tumor of neural crest origin. More than half of patients are < 2 years of age, and 70% of patients have distant metastases at presentation. Associated with neurofibromatosis, Hirschsprung’s disease, and the N-myc oncogene.
Lesion sites are most commonly abdominal, thoracic, and cervical (in descending order).
Symptoms may vary with location and may include a nontender abdominal mass (may cross the midline), Horner’s syndrome, hypertension, or cord compression (from a paraspinal tumor).
Patients may have anemia, FTT, and fever.More than 50% of patients will have metastases at diagnosis. Signs include bone marrow suppression, proptosis, hepatomegaly, subcutaneous nodules, and opsoclonus/myoclonus.
CT scan; fine-needle aspirate of tumor. Histologically appears as small, round, blue tumor cells with a characteristic rosette pattern.
Elevated 24-hour urinary catecholamines (VMA and HVA).Bone scan and bone marrow aspirate.CBC, LFTs, coagulation panel, BUN/creatinine.Local excision plus postsurgical chemotherapy and/or radiation.Wilms’ tumor is associatedA renal tumor of embryonal origin that is most commonly seen in children 2–5 years of age. Associated with Beckwith-Wiedemann syndrome (hemihy-hemihypertrophy.
pertrophy, macroglossia, visceromegaly), neurofibromatosis, and WAGR syndrome (Wilms’, Aniridia, Genitourinary abnormalities, mental Retardation).
Presents as an asymptomatic, nontender, smooth abdominal mass.Abdominal pain, fever, hypertension, and microscopic or gross hematuria are seen.
CBC, BUN, creatinine, and UA.Abdominal ultrasound.CT scans of the chest and abdomen are used to detect metastases.
Local resection and nephrectomy with postsurgical chemotherapy and radiation depending on stage and histology.
It is critical to distinguish between Ewing’s sarcoma and osteosarcoma (see Table 2.13-10).
An important aspect of every well-child visit. Commonly tested advice includes the following:
T AB LE 2.1 3-1 0. Ewing’s Sarcoma vs. Osteosarcoma
Sarcoma (neuroectoderm); associated with chromosome 11:22 translocation. Osteoblasts (mesenchyme). Commonly seen in Caucasian male adolescents. Commonly seen in male adolescents. History/PE Local pain and swelling. Systemic symptoms (fever, anorexia, fatigue) are common. Local pain and swelling. Systemic symptoms are rare. Location Midshaft of long bones (femur, pelvis, f bula, humerus). Metaphyses of long bones (distal femur, proximal tibia, proximal humerus). Metastases to lungs in 20%. Leukocytosis, ↑ ESR. Lytic bone lesion with “onion skin” periosteal reaction on plain x-ray. ↑ alkaline phosphatase. “Sunburst” lytic bone lesions. Chest CT to rule out pulmonary metastases. Local excision, chemotherapy, and radiation. Local excision, chemotherapy. Origin Epidemiology Diagnosis Treatment
Keep the water heater at < 48.8°C (< 120ºF).Babies should sleep on their backs without any stuffed animals or other toys in the crib (to ↓ the risk of SIDS).
Car safety seats should be rear facing and should be placed in the back of the car (seats can face forward if the child is > 1 year of age and weighs > 20 lbs).
No solid foods should be given prior to six months; they should then be introduced gradually and one at a time. Do not give cow’s milk prior to 12 months.
Syrup of ipecac (an emetic) is no longer routinely recommended for accidental poisoning. Poison control should be contacted immediately for assistance.
Objective hearing screening (otoacoustic emissions and/or auditory brain stem response) for newborns prior to discharge is common.
Objective hearing screening is indicated for children with a history of meningitis, TORCH infections, measles and mumps, and recurrent otitis media or chronic middle ear infections.
The red reflex should be checked at birth. Leukocoria is the lack of a red refl ex.
Strabismus (ocular misalignment) is normal until three months of age; beyond three months, children should be evaluated by a pediatric ophthalmologist and may require corrective lenses, occlusion, and/or surgery to prevent amblyopia (suppression of retinal images in a misaligned eye, leading to permanent vision loss).
The Epidemiology chapter summarizes CDC-recommended vaccinations for the pediatric population. Contraindications and precautions in this population are as follows:
Severe allergy to a vaccine component or a prior dose of vaccine. Patients who are allergic to eggs may not receive MMR or infl uenza vaccine.
Encephalopathy within seven days of prior pertussis vaccination.Avoid live vaccines (oral polio vaccine, varicella, MMR) in immunocompromised and pregnant patients (exception: HIV patients may receive MMR and varicella).
Current moderate to severe illness (with or without fever).Prior reactions to pertussis vaccine (fever > 40.5°C, shocklike state, persistent crying for > 3 hours within 48 hours of vaccination, or seizure within three days of vaccination).
A history of receiving IVIG in the past year.The following are not contraindications to vaccination:Mild illness and/or low-grade fever.Current antibiotic therapy.Pneumococcal polysaccharide vaccine (PPV) should be administered to high-risk groups (sickle cell disease or splenectomy, immunodeficient).
Leukocoria indicates retinoblastoma, congenital cataracts, or retinopathy of prematurity.New evidence has shown impaired intelligence and neurodevelopmental outcomes among children exposed to lead levels as low as 10 μg/dL.
Most exposure in children is due to lead-contaminated household dust from leaded paint. Screening should be routinely performed at 12 and 24 months for patients living in high-risk areas (pre-1950s homes or zip codes with high percentages of elevated blood lead levels).
Presents with irritability, hyperactivity or apathy, anorexia, intermittent abdominal pain, constipation, intermittent vomiting, and peripheral neuropathy (wrist or foot drop).
Acute encephalopathy (usually with levels > 70 μg/dL) is characterized by ↑ ICP, vomiting, confusion, seizures, and coma.
Blood lead level.CBC and peripheral blood smear show microcytic, hypochromic anemia and basophilic stippling.
< 45 μg/dL and asymptomatic: Retest at 1–3 months; remove sources of lead exposure.
45–69 μg/dL: Chelation therapy (inpatient EDTA or outpatient oral succimer [DMSA]).
≥ 70 μg/dL: Chelation therapy (inpatient EDTA + BAL [IM dimercaprol]).
Buspirone is another drug, in addition to SSRIs, that should not be used with MAOIs.
Many OCD patients initially present to a nonpsychiatrist— e.g., they may consult a dermatologist with a skin complaint 2° to overwashing hands.
Uncontrollable, excessive anxiety or worry about activities or events in life that leads to signifcant impairment or distress.
The male-to-female ratio is 1:2; clinical onset is usually in the early 20s.
Hx/PE: Presents with anxiety on most days (six or more months) and with three or more somatic symptoms (restlessness, fatigue, diff culty concentrating, irritability, muscle tension, disturbed sleep).
Lifestyle changes, psychotherapy, medication. SSRIs, venlafaxine, and buspirone are most often used (see Table 2.14-1). Benzodiazepines may be used for immediate symptom relief.
Taper benzodiazepines as soon as long-term treatment is initiated (e.g., with SSRIs) in light of the high risk of tolerance and dependence. Do not stop benzodiazepines “cold turkey,” as patients may develop potentially lethal withdrawal symptoms similar to those of alcohol withdrawal.
Patient education is essential.Characterized by obsessions and/or compulsions that lead to signif cant distress and dysfunction in social or personal areas.
Typically presents in late adolescence or early adulthood; prevalence is equal in males and females. Often a chronic condition that is diff cult to treat.
Hx/PE: ■Obsessions: Persistent, unwanted, and intrusive ideas, thoughts, impulses, or images that lead to marked anxiety or distress (e.g., fear of contamination, fear of harm to oneself or to loved ones) and occur despite the patient’s attempts to prevent them.
T AB LE 2.1 4-1.  Anxiolytic MedicationsSSRIs (f uoxetine, sertraline, paroxetine, citalopram, escitalopram) First-line treatment for generalized anxiety disorder, OCD, and PTSD. Nausea, GI upset, somnolence, sexual dysfunction, agitation. Buspirone Generalized anxiety disorder, OCD, PTSD. Seizures with chronic use. No tolerance, dependence, or withdrawal. β-blockers Performance anxiety, PTSD. Bradycardia, hypotension. Benzodiazepines Anxiety, insomnia, alcohol withdrawal, muscle spasm, night terrors, sleepwalking. ↓ sleep duration; risk of abuse, tolerance, and dependence; disinhibition in young or old patients; confusion. Flumazenil (competitive antagonist at GABA receptor) Antidote to benzodiazepine intoxication. Resedation; nausea, dizziness, vomiting, and pain at the injection site.
Compulsions: Repeated mental acts or behaviors that neutralize anxiety from obsessions (e.g., hand washing, elaborate rituals for ordinary tasks, counting, excessive checking).
Patients recognize these behaviors as excessive and irrational products of their own minds (vs. obsessive-compulsive personality disorder, or OCPD; see Table 2.14-2). Patients wish they could get rid of the obsessions and/or compulsions.
Tx: Pharmacotherapy (SSRIs are frst-line pharmacologic treatment; see Table 2.14-1); cognitive-behavioral therapy (CBT) using exposure and desensitization relaxation techniques. Patient education is imperative.
Characterized by recurrent, unexpected panic attacks.Two to three times more common in females than in males. Agoraphobia is present in 30–50% of cases. The average age of onset is 25, but may occur at any age.
Panic attacks are def ned as discrete periods of intense fear or discomfort in which at least four of the following symptoms develop abruptly and peak within 10 minutes: tachypnea, chest pain, palpitations, diaphoresis, nausea, trembling, dizziness, fear of dying or “going crazy,” depersonalization, or hot f ashes.
Perioral and/or acral paresthesias, when present, are fairly specif c to panic attacks, which produce hyperventilation and low oxygen saturation.
Patients present with one or more months of concern about having additional attacks or signifcant behavior change as a result of the attacks—e.g., avoiding situations that may precipitate attacks.
Elucidate if a patient has panic disorder with or without agoraphobia so that agoraphobia can also be addressed in the treatment plan.
The differential should include the following:Medical conditions: Angina, MI, arrhythmias, hyperthyroidism, vitamin B12 def ciency, pheochromocytoma.
Psychiatric conditions: Substance-induced anxiety, generalized anxiety disorder, PTSD.CBT, pharmacotherapy (e.g., SSRIs, TCAs).Benzodiazepines (e.g., clonazepam) may be used for immediate relief, but long-term use should be avoided in light of the potential for addiction and tolerance (see Table 2.14-1).
Taper benzodiazepines as soon as long-term treatment is initiated (e.g., SSRIs).
Alprazolam (Xanax) is an SSRI that is sometimes used to treat panic disorder, but it has such a short half-life that patients can go into mild withdrawal within a day.
TABLE 2.14-2. OCD vs. OCPDCharacterized by obsessions and/or compulsions. Patients are excessively conscientious and inf exible. Patients recognize the obsessions/ compulsions and want to be rid of them (ego-dystonic). Patients do not recognize their behavior as problematic (ego-syntonic).
Agoraphobia is def ned as fear of being alone in public places. Literally translated, it means “fear of the marketplace.”
Top causes of PTSD in males are (1) rape and (2) combat. Top causes in females are (1) childhood abuse and (2) rape.
In patients with a history of substance abuse, benzodiazepines should be avoided in view of their high addictive potential.
Defned as follows:Social phobia: Characterized by marked fear provoked by social or performance situations in which embarrassment may occur. It may be specifc (e.g., public speaking, urinating in public) or general (e.g., social interaction) and often begins in adolescence.
Specific phobia: Anxiety is provoked by exposure to a feared object or situation (e.g., animals, heights, airplanes). Most cases begin in childhood.
Hx/PE: Presents with excessive or unreasonable fear and/or avoidance of an object or situation that is persistent and leads to signifcant distress or impairment in function. A related history of traumatic events or panic attacks may be present. Patients recognize that their fear is excessive.
Specific phobias: CBT involving desensitization through incremental exposure to the feared object or situation and relaxation techniques. Other options include supportive, family, and insight-oriented psychotherapy.
Social phobias: CBT, SSRIs, low-dose benzodiazepines, or β-blockers (for performance anxiety) may be used (see Table 2.14-1).
Follows exposure to an extreme, life-threatening traumatic event (e.g., assault, combat, witnessing a violent crime) that evoked intense fear, helplessness, or horror.
Characterized by reexperiencing of the event (e.g., nightmares), avoidance of stimuli associated with the trauma, numbed responsiveness (e.g., detachment, anhedonia), and ↑ arousal (e.g., hypervigilance, exaggerated startle) that lead to signifcant distress or impairment in functioning.
Symptoms must persist for > 1 month.Survivor guilt, irritability, poor concentration, amnesia, personality change, sleep disturbance, substance abuse, depression, and suicidality may be present.
Some controversy exists regarding the prevalence of PTSD, which some clinicians feel is overdiagnosed. It is therefore prudent to carefully consider other diagnoses in the differential—e.g., major depressive disorder, personality disorder, or adjustment disorder.
SSRIs are frst line; buspirone, TCAs, and MAOIs may be helpful (see Table 2.14-1).
Short-term agents targeting anxiety include β-blockers and α2-agonists (e.g., clonidine).
Benzodiazepines are also used but should be avoided in light of their addictive potential, as there is a high incidence of substance abuse among individuals with PTSD.
Psychotherapy and support groups are useful.Affect memory, orientation, judgment, and attention.An impairment in cognitive functioning with global deficits. Level of consciousness is stable. Prevalence is highest among those > 85 years of age. The course is persistent and progressive. The most common causes are Alzheimer’s disease (50%) and multi-infarct dementia (25%). Other causes are outlined in the mnemonic DEMENTIAS.
Diagnostic criteria include memory impairment and one or more of the following:
Aphasia: Language impairment.Apraxia: Inability to perform motor activities.Agnosia: Inability to recognize previously known objects.Impaired executive function (problems with planning, organizing, and abstracting) in the presence of a clear sensorium.
Personality, mood, and behavior changes are common (e.g., wandering and aggression).
A careful history and physical are critical. Serial mini-mental status exams should be performed.
Rule out treatable causes of dementia; obtain CBC, RPR, CMP, TFTs, HIV, B12/folate, ESR, UA, and a head CT or MRI.
n Table 2.14-3 outlines key characteristics distinguishing dementia from delirium.
TABLE 2.14-3. Delirium vs. DementiaCauses of dementia—Degenerative diseases (Parkinson’s, Huntington’s)Endocrine (thyroid, parathyroid, pituitary, adrenal)Metabolic (alcohol, electrolytes, vitamin B12 def ciency, glucose, hepatic, renal, Wilson’s disease)
Exogenous (heavy metals, carbon monoxide, drugs)Infection (meningitis, encephalitis, endocarditis, syphilis, HIV, prion diseases, Lyme disease)
Stroke/Structure (vascular dementia, ischemia, vasculitis, normal pressure hydrocephalus)Level of attention Impaired (f uctuating). Usually alert. Onset Acute. Gradual. Course Fluctuating from hour to hour. Progressive deterioration. Consciousness Clouded. Intact. Hallucinations Present (often visual or tactile). Occur in approximately 30% of patients in highly advanced disease. Prognosis Reversible. Largely irreversible, but up to 15% of cases are due to treatable causes and are reversible.
Major causes of delirium—It is common for delirium to be superimposed on dementia.
MDEs can be present in major depressive disorder or in bipolar disorder types I and II.
Provide environmental cues and a rigid structure for the patient’s daily life.
Cholinesterase inhibitors are used to treat. Low-dose antipsychotics may be used for agitation. Avoid benzodiazepines, which may worsen disinhibition and confusion.
Family, caregiver, and patient education and support are imperative.An acute disturbance of consciousness with altered cognition that develops over a short period of time (usually hours to days). Children, the elderly, and hospitalized patients (e.g., ICU psychosis) are particularly susceptible. Major causes are outlined in the mnemonic I WATCH DEATH. Symptoms are potentially reversible if the underlying cause can be treated.
Presents with acute onset of waxing and waning consciousness with lucid intervals and perceptual disturbances (hallucinations, illusions, delusions).
Patients may be combative, anxious, paranoid, or stuporous.Also characterized by a ↓ attention span and short-term memory, a reversed sleep-wake cycle, and ↑ symptoms at night (sundowning).
Check vitals, pulse oximetry, and glucose; perform physical and neurologic exams.
Note recent medications (narcotics, anticholinergics, steroids, or benzodiazepines), substance use, prior episodes, medical problems, signs of organ failure (kidney, liver), and infection (occult UTI is common in the elderly; check UA).
Order lab and radiologic studies to identify a possible underlying cause.
Treat underlying causes (delirium is often reversible).Normalize fuids and electrolytes.Optimize the sensory environment.Use low-dose antipsychotics (e.g., haloperidol) for agitation and psychotic symptoms.
Conservative use of physical restraints may be necessary to prevent harm to the patient or others.
Also known as affective disorders.A mood disorder characterized by one or more major depressive episodes (MDEs). The male-to-female ratio is 1:2; lifetime prevalence ranges from 15% to 25%. Onset is usually in the mid-20s; in the elderly, prevalence ↑ with age. Chronic illness and stress ↑ risk. Up to 15% of patients die by suicide.
Diagnosis requires depressed mood or anhedonia (loss of interest/pleasure) and five or more signs/symptoms from the SIG E CAPS mnemonic for a two-week period. Table 2.14-4 outlines the differential diagnosis of conditions that may be mistaken for depression. Selected depression subtypes include the following:
Psychotic features: Typically mood-congruent delusions/hallucinations.Postpartum: Occurs within one month postpartum; has a 10% incidence and a high risk of recurrence. Psychotic symptoms are common.
Atypical: Characterized by weight gain, hypersomnia, and rejection sensitivity.Seasonal: Depressive episodes tend to occur during a particular season, most commonly winter. Responds well to light therapy +/– antidepressants.
Double depression: MDE in a patient with dysthymia. Has a poorer prognosis than MDE alone.
Pharmacotherapy: Effective in 50–70% of patients. Allow 2–6 weeks to take effect; treat for ≥ 6 months (see Table 2.14-5).
Psychotherapy: Psychotherapy combined with antidepressants is more effective than either treatment alone.
Electroconvulsive therapy (ECT):Safe, highly effective, often lifesaving therapy that is reserved for refractory depression or psychotic depression, or if rapid improvement in mood is needed.
T AB LE 2.1 4-4. Differential Diagnosis of Major Depression
Symptoms of a depressive episode—Interest (loss of interest or pleasure in activities)Guilt (feelings of worthlessness or inappropriate guilt)Mood disorder due to a medical condition Hypothyroidism, Parkinson’s disease, CNS neoplasm, other neoplasm (e.g., pancreatic cancer), stroke (especially ACA stroke), dementias, parathyroid disorders. Substance-induced mood disorder Illicit drugs, alcohol, antihypertensives, corticosteroids, OCPs. Adjustment disorder with depressed mood A constellation of symptoms resembling an MDE but not meeting the criteria for MDE. Occurs within three months of an identif able stressor. Normal bereavement Occurs after the loss of a loved one. No severe impairment/suicidality; usually resolves in one year, but varies with cultural norms. May lead to major depressive disorder requiring treatment. Illusions/hallucinations of the deceased can be normal as long as the person recognizes them as such. Dysthymia Milder, chronic depression with depressed mood present most of the time for at least two years; often treatment resistant.
T AB LE 2.1 4-5. Indications and Side Effects of Common Antidepressants
SSRIs Fluoxetine, sertraline, paroxetine, citalopram, f uvoxamine Depression and anxiety. Sexual side effects, GI distress, agitation, insomnia, tremor, diarrhea. Serotonin syndrome (fever, myoclonus, mental status changes, cardiovascular collapse) can occur if SSRIs are used with MAOIs. Paroxetine can cause pulmonary hypertension in the fetus. Atypicals Bupropion, venlafaxine, mirtazapine, trazodone Depression, anxiety, and chronic pain. Bupropion: ↓ seizure threshold; minimal sexual side effects. Contraindicated in patients with eating disorders as well as in seizure patients. Venlafaxine: Diastolic hypertension. Mirtazapine: Weight gain, sedation. Trazodone: Highly sedating; priapism. Nortriptyline, desipramine, amitriptyline, imipramine Depression, anxiety disorder, chronic pain, migraine headaches, enuresis (imipramine). Lethal with overdose owing to cardiac conduction arrhythmias (e.g., long QRS). Monitor in the ICU for 3–4 days following an OD. Anticholinergic effects (dry mouth, constipation, urinary retention, sedation). Phenelzine, tranylcypromine, selegiline (patch form available) Depression, especially atypical. Hypertensive crisis if taken with high-tyramine foods (cheese, red wine). Sexual side effects, orthostatic hypotension, weight gain. TCAs MAOIs
Discontinue SSRIs at least two weeks before starting an MAOI. Wait f ve weeks if the patient was on f uoxetine.
Mixed states and mania are psychiatric emergencies 2° to impaired judgment and great risk of harm to self and others.
May also be used for mania and psychosis. Usually requires 6–12 treatments.
Adverse effects include postictal confusion, arrhythmias, headache, and anterograde amnesia.
■Contraindications include recent MI/stroke, intracranial mass, and high anesthetic risk (a relative contraindication).
Phototherapy: Effective for patients whose depression has a seasonal pattern.
Transcranial magnetic stimulation (TMS): Now approved for the treatment of major depression. TMS is about as effective as medications but is not as effective as ECT.
Prevalence is approximately 1% for type I and an additional 3% for type II; males and females are affected equally. A family history of bipolar illness signif cantly ↑ risk. Average age of onset is 20, and the frequency of mood episodes tends to ↑ with age. Up to 10–15% of those affected die by suicide. Subtypes are as follows: ■Bipolar I: At least one manic or mixed episode (usually requiring hospitalization).
Bipolar II: At least one MDE and one hypomanic episode (less intense than mania). Patients do not meet the criteria for full manic or mixed episodes.
Rapid cycling: Four or more episodes (MDE, manic, mixed, or hypo-manic) in one year.
Cyclothymic: Chronic and less severe, with alternating periods of hypo-mania and moderate depression for > 2 years.
The mnemonic DIG FAST outlines the clinical presentation of mania.
Patients may report excessive engagement in pleasurable activities (e.g., excessive spending or sexual activity), reckless behaviors, and/or psychotic features.
Antidepressant use may trigger manic episodes.A manic episode is one week or more of persistently elevated, expansive, or irritable mood plus three DIG FAST symptoms. Psychotic symptoms are common in mania.
Symptoms are not due to a substance or medical condition and lead to signifcant impairment socially, occupationally, or familially.
Hypomania is similar but does not involve marked functional impairment or psychotic symptoms and does not require hospitalization.
■ Mania: Give mood stabilizers for maintenance therapy (see Table 2.14-6) and antipsychotics in the acute phase (see the discussion of psychotic dis-
TABLE 2.14-6.  Mood StabilizersSymptoms of mania—Flight of ideas (or racing thoughts) Activities/psychomotor Agitation 439 Lithium First-line mood stabilizer. Used for acute mania (in combination with antipsychotics), for prophylaxis in bipolar disorders, and for augmentation in depression treatment. Thirst, polyuria, diabetes insipidus, tremor, weight gain, hypothyroidism, nausea, diarrhea, seizures, teratogenicity (if used in the frst trimester), acne, vomiting. Narrow therapeutic window (but blood level can be monitored). Lithium toxicity: > 1.5 mEq/L; presents with ataxia, dysarthria, delirium, and acute renal failure. Avoid lithium in patients with ↓ renal function. Carbamazepine Second-line mood stabilizer; anticonvulsant; trigeminal neuralgia. Nausea, skin rash, leukopenia, AV block. Rarely, aplastic anemia (monitor CBC biweekly). Stevens-Johnson syndrome. Bipolar disorder; anticonvulsant. GI (nausea, vomiting), tremor, sedation, alopecia, weight gain. Rarely, pancreatitis, thrombocytopenia, fatal hepatotoxicity, and agranulocytosis. Second-line mood stabilizer; anticonvulsant. Blurred vision, GI distress, Stevens-Johnson syndrome. ↑ dose slowly to monitor for rashes.
Characteristics of personality disorders— orders below). Benzodiazepines may be of beneft in refractory agitation.
Bipolar depression: Mood stabilizers +/– antidepressants. Start mood stabilizers first (see Table 2.14-6) to avoid inducing mania. ECT may be used to treat refractory cases.
In patients with severe depression or bipolar II with predominantly depressive features, antidepressant treatment can be augmented with low-dose lithium—e.g., at blood levels of 0.4–0.6 mEq/L.
Personality can be defned as an individual’s set of emotional and behavioral traits, which are generally stable and predictable. Personality disorders are defned when one’s traits become chronically rigid and maladaptive and affect most aspects of one’s life (see the mnemonic MEDIC). Onset occurs by early adulthood. Personality disorders are defned under Axis II in the DSM-IV (see defnition of axes on the following page). Specifc disorders are outlined in Table 2.14-7.
TAB LE 2.1 4-7. Signs and Symptoms of Personality Disorders
Distrustful, suspicious; interpret others’ motives as malevolent.Isolated, detached “loners.” Restricted emotional expression.Odd behavior, perceptions, and appearance. Magical thinking; ideas of reference.
Patients are suspicious and distrustful of psychiatrists, making it diffcult to form therapeutic relationships between patient and psychiatrist.
Be clear, honest, noncontrolling, and nondefensive.Unstable mood, relationships, and self-image; feelings of emptiness. Impulsive. History of suicidal ideation or self-harm.
Excessively emotional and attention seeking. Sexually provocative; theatrical.Grandiose; need admiration; have sense of entitlement. Lack empathy.Violate rights of others, social norms, and laws. Impulsive; lack remorse. Begins in childhood as conduct disorder.
Patients change the rules and demand attention. They are manipulative and demanding and will split staff members.
Be frm. Stick to the treatment plan.Be fair. Do not be punitive or derogatory.Be consistent. Do not change rules.Preoccupied with perfectionism, order, and control at the expense of eff ciency. Infexible morals, values.
Socially inhibited; rejection sensitive. Fear being disliked or ridiculed.Submissive, clingy; need to be taken care of. Diffculty making decisions. Feel helpless.
Patients are controlling and may sabotage their treatment. Words may be inconsistent with actions.
Avoid power struggles. Give clear recommendations, but do not push patients into decisions.
Ask about attitudes, mood variability, activities, and reaction to stress.
Patients have chronic problems dealing with responsibilities, roles, and stressors. They may also deny their behavior, have diff culty understanding the cause of their problems, have diffculty changing their behavior patterns, and frequently refuse psychiatric care.
Psychotherapy is the mainstay of therapy.Pharmacotherapy is reserved for cases with comorbid mood, anxiety, or psychotic signs/symptoms.
Characterized by hallucinations, delusions, disordered thoughts, behavioral disturbances, and disrupted social functioning with a clear sensorium.
Epidemiology: Prevalence is approximately 1%; males and females are affected equally. Peak onset is earlier in males (ages 18–25) than in females (ages 25–35), and has an ↑ incidence in those born in winter or early spring. Schizophrenia in frst-degree relatives also ↑ risk. Ten percent of those affected commit suicide.
Etiology: Etiologic theories focus on neurotransmitter abnormalities such as dopamine dysregulation (frontal hypoactivity; limbic hyperactivity; effcacy of dopamine antagonists) and brain abnormalities on CT and MRI (enlarged ventricles and ↓ cortical volume). Subtypes are as follows:
Paranoid: Delusions (often of persecution of the patient) and/or hallucinations are present. Cognitive function is usually preserved. Associated with the best overall prognosis.
Disorganized: Speech and behavior patterns are highly disordered and disinhibited with fat affect. The thought disorder is pronounced, and the patient has poor contact with reality. Carries the worst prognosis.
Catatonic: A rare form characterized by psychomotor disturbance with two or more of the following: excessive motor activity, immobility, extreme negativism, mutism, waxy fexibility, echolalia, or echopraxia.
Two or more of the following are present continuously for six or more months with social or occupational dysfunction: symptoms: Hallucinations (most often auditory), delusions, disorganized speech, bizarre behavior, and thought disorder.
symptoms: Flat affect, ↓ emotional reactivity, poverty of speech, lack of purposeful actions, and anhedonia.
The differential includes the following:Schizophreniform disorder: Symptoms of schizophrenia with a duration of < 6 months.
Schizoaffective disorder: Combines the symptoms of schizophrenia with a major affective disorder (major depressive disorder or bipolar disorder).
Five categories are used by the DSM-IV to classify the factors contributing to an individual’s mental state:
Axis I: Psychiatric disorders.Axis II: Personality disorders and mental retardation.Axis III: Physical and medical problems.Axis IV: Social and environmental problems/ stressors.Axis V: The Global Assessment of Functioning (GAF), which rates a patient’s overall level of social, occupational, and psychological functioning on a scale of 1 (nonfunctional) to 100 (extremely high functioning across several areas).
Antipsychotics (see Table 2.14-8); long-term follow-up.Supportive psychotherapy, training in social skills, vocational rehabilita tion, and illness education may help. Terms used to describe ■ symptoms may be more diffcult to treat.
components of psychosis:Delusion: A f xed false idiosyncratic belief.Hallucination: Perception of an object or event without an existing external stimulus.
Illusion: False perception of an actual external stimulus.A persistent pattern of excessive inattention and/or hyperactivity/impulsivity. More common in males; typically presents between ages 3 and 13. Often shows a familial pattern.
Diagnosis requires six or more symptoms from each category listed below for six or more months in at least two settings, leading to signifcant social and academic impairment. Some symptoms must be present in patients before age seven.
■Inattention: Poor attention span in schoolwork/play; poor attention to detail or careless mistakes; does not listen when spoken to; has difficulty
T AB LE 2.1 4-8.  Antipsychotic MedicationsTypical antipsychotics Haloperidol, droperidol, f uphenazine, thioridazine, chlorpromazine Atypical antipsychotics Clozapine, risperidone (also available in long-acting depot injection), quetiapine, olanzapine, ziprasidone, aripiprazole Currently frst-line treatment for schizophrenia given fewer EPS and anticholinergic effects. Clozapine is reserved for severe treatment resistance and severe tardive dyskinesia. Weight gain, type 2 DM, somnolence, sedation, and QTc prolongation. Agranulocytosis requiring weekly CBC monitoring (clozapine).
Psychotic disorders, acute agitation, acute mania, Tourette’s syndrome. Thought to be more effective for symptoms of schizophrenia; primarily block D2 dopamine receptors.
For patients in whom compliance is a major issue, consider antipsychotics that come in depot forms (haloperidol, f uphenazine).
(EPS; see Table 2.14-9), hyperprolactinemia.Anticholinergic effects (dry mouth, urinary retention, constipation).Seizures, hypotension, sedation, and QTc prolongation.(thioridazine). Neuroleptic malignant syndrome:Fever, muscle rigidity, autonomic instability, elevated CK, clouded consciousness. Stop medication; provide supportive care in the ICU; administer dantrolene or bromocriptine (see Table 2.14-9).
T AB LE 2.1 4-9. Extrapyramidal Symptoms and TreatmentAcute dystonia Involuntary muscle contraction or spasm (e.g., torticollis, oculogyric crisis). Anticholinergics (benztropine or diphenhydramine); some patients on antipsychotics who are prone to dystonic reactions may need regular prophylactic dosing of these. Akathisia Subjective/objective restlessness, which is perceived as being distressing. ↓ neuroleptic and try β-blockers (propranolol). Benzodiazepines or anticholinergics may help. Pseudoparkinsonism (e.g., shuffing gait, cogwheel rigidity). Give an anticholinergic (benztropine) or a dopamine agonist (amantadine). ↓ the dose of neuroleptic or discontinue (if tolerated). Stereotypic oral-facial movements. Likely from dopamine receptor sensitization. Often irreversible (50%). Discontinue or ↓ the dose of neuroleptic; attempt treatment with more appropriate drugs; and consider changing neuroleptic (e.g., to clozapine or risperidone). Giving anticholinergics or decreasing neuroleptics may initially worsen tardive dyskinesia.
following instructions or finishing tasks; loses items needed to complete tasks; is forgetful and easily distracted.
■ Hyperactivity/impulsivity: Fidgets; leaves seat in classroom; runs around inappropriately; cannot play quietly; talks excessively; does not wait turn; interrupts others.
Initial treatment may be nonpharmacologic (e.g., behavior modif cation). Sugar and food additives are not considered etiologic factors.
Pharmacologic treatment includes the following:Psychostimulants: Methylphenidate (Ritalin), dextroamphetamine (Dexedrine), mixed salts of dextroamphetamine and amphetamine (Adderall), atomoxetine (Strattera), pemoline (Cylert). Adverse effects include insomnia, irritability, ↓ appetite, tic exacerbation, and ↓ growth velocity (normalizes when medication is stopped).
Antidepressants (e.g., SSRIs, nortriptyline, bupropion) and α2-agonists (e.g., clonidine).More common in males. May be associated with tuberous sclerosis and fragile X syndrome. Symptom severity and IQ vary widely.
■Characterized by abnormal or impaired social interaction and communication together with restricted activities and interests, evident before age three.
Children must exhibit ADHD symptoms in two or more settings (e.g., home and school).
Conduct disorder is seen in Children. Antisocial personality disorder is seen in Adults.
Patients fail to develop normal social behaviors (e.g., social smile, eye contact) and lack interest in relationships.
The development of spoken language is delayed or absent.Children show stereotyped speech and behavior (e.g., hand f apping) and restricted interests (e.g., preoccupation with parts of objects).
Other pervasive developmental disorders include the following:Asperger’s syndrome: An autism-like disorder of social impairment and repetitive activities, behaviors, and interests without marked language or cognitive delays.
Rett’s disorder: A genetic neurodegenerative disorder of females with progressive impairment (e.g., language, head growth, coordination) after five months of normal development.
Childhood disintegrative disorder: Severe developmental regression after > 2 years of normal development (e.g., language, motor skills, social skills, bladder/bowel control, play).
Intensive special education, behavioral management, and symptom-targeted medications (e.g., neuroleptics for aggression; SSRIs for stereotyped behavior).
Family support and counseling are crucial.Include conduct disorder and oppositional def ant disorder.More common among males and in patients with a history of abuse.
Conduct disorder: A repetitive, persistent pattern of violating the basic rights of others or age-appropriate societal norms or rules for one year or more. Behaviors may be aggressive (e.g., rape, robbery, animal cruelty) or nonaggressive (e.g., stealing, lying, deliberately annoying people). May progress to antisocial personality disorder in adulthood.
Oppositional defiant disorder: A pattern of negativistic, defiant, disobedient, and hostile behavior toward authority fgures (e.g., losing temper, arguing) for six or more months. May progress to conduct disorder.
Tx: Individual and family therapy.Occur more frequently in males and in those of low socioeconomic status (SES); often exhibit a familial pattern.
Academic functioning is substantially lower than expected for age, intelligence, and education as measured by standardized test achievement in reading, mathematics, or written expression.
Learning problems signifcantly interfere with schooling and daily activities.Always rule out physical disorders (e.g., deafness) and social factors (e.g., non–English speakers).
Tx: Interventions include remedial classes or individualized learning strategies.Associated with male gender, chromosomal abnormalities, congenital infections, teratogens, inborn errors of metabolism, and alcohol/illicit substances during pregnancy.
Patients have signifcantly subaverage intellectual functioning (an IQ of < 70) with deficits in adaptive functioning (e.g., hygiene, social skills); onset is before the age of 18.
Levels of severity are mild (IQ 50–70; 85% of cases), moderate (IQ 35–49), severe (IQ 20–34), and profound (IQ < 20).
Tx: 1° prevention consists of educating the general public about possible causes of mental retardation and providing optimal prenatal screening and health care to mothers and their children.
Treatment measures include family counseling and support; speech and language therapy; occupational/physical therapy; behavioral intervention; educational assistance; and social skills training.
More common in males; shows a genetic predisposition. Associated with ADHD, learning disorders, and OCD.
Begins prior to age 18.Characterized by multiple motor (e.g., blinking, grimacing) and vocal (e.g., grunting, coprolalia) tics occurring many times per day, recurrently, for > 1 year with social or occupational impairment.
Tx: Treatments include dopamine receptor antagonists (haloperidol, pimozide) or clonidine. Behavioral therapy may be of beneft, and counseling can aid in social adjustment and coping. Stimulants can worsen or precipitate tics.
Fetal alcohol syndrome is the number one avoidable cause of mental retardation.
Coprolalia = repetition of obscene words.Features of substance dependence—Both substance abuse and substance dependence are maladaptive patterns of substance use that lead to clinically signifcant impairment. Substance abuse is distinguished from substance dependence as follows:
Substance abuse: Requires one or more of the following in one year:
Failure to fulfill responsibilities at work, school, or home.Use in physically hazardous situations (e.g., driving while intoxicated).Legal problems during the time of substance use.Continued substance use despite recurrent social or interpersonal problems 2° to the effects of such use (e.g., frequent arguments with spouse over the substance use).
Substance dependence: Requires three or more of the following in one year:
Tolerance and use of progressively larger amounts to obtain the same desired effect.
Withdrawal symptoms when not taking the substance.Failed attempts to cut down use or abstain from the substance.
Three or more of seven within a 12-month period:Harm (physical and psychosocial) with continued useDesire to cut down/ controlTime spent obtaining/ using the substance is ↑A diagnosis of substance dependence trumps a diagnosis of substance abuse.
Signifcant time spent obtaining the substance (e.g., visiting many doctors to obtain a prescription for pain pills).
Isolation from life activities.Taking greater amounts of the substance than intended.Continued substance abuse despite recurrent physical or psychological problems 2° to the effect of the substance use.
Substance use is often denied or underreported, so seek out collateral information from family and friends.
Check urine and blood toxicology screens, LFTs, and serum EtOH level.
The management of intoxication for selected drugs is described in Table 2.14-10.
T AB LE 2.1 4-1 0. Signs and Symptoms of Substance Abuse
Alcohol Disinhibition, emotional lability, slurred speech, ataxia, aggression, blackouts, hallucinations, memory impairment, impaired judgment, coma. Tremor, tachycardia, hypertension, malaise, nausea, seizures, DTs, agitation. Opioids Euphoria leading to apathy, CNS depression, constipation, pupillary constriction, and respiratory depression (life threatening in overdose). Naloxone/naltrexone will block opioid receptors and reverse effects (beware of antagonist clearing before opioids, particularly with long-acting opioids such as methadone). Dysphoria, insomnia, anorexia, myalgias, fever, lacrimation, diaphoresis, dilated pupils, rhinorrhea, piloerection, nausea, vomiting, stomach cramps, diarrhea, yawning. Opioid withdrawal is not life threatening, “hurts all over,” and does not cause seizures. Amphetamines Psychomotor agitation, impaired judgment, hypertension, pupillary dilation, tachycardia, fever, diaphoresis, anxiety, angina, euphoria, prolonged wakefulness/attention, arrhythmias, delusions, seizures, hallucinations. Haloperidol can be given for severe agitation and symptom-targeted medications (e.g., antiemetics, NSAIDs). Postuse “crash” with anxiety, lethargy, headache, stomach cramps, hunger, fatigue, depression/dysphoria, sleep disturbance, nightmares. Cocaine Psychomotor agitation, euphoria, impaired judgment, tachycardia, pupillary dilation, hypertension, paranoia, hallucinations, sudden death. ECG changes from ischemia are often seen (“cocaine chest pain”). Treat with haloperidol for severe agitation along with symptom-specifc medications (e.g., to control hypertension). Postuse “crash” with hypersomnolence, depression, malaise, severe craving, angina, suicidality, ↑ appetite, nightmares, “cocaine bugs.”
T AB LE 2.1 4-1 0. Signs and Symptoms of Substance Abuse (continued)
Phencyclidine hydrochloride (PCP) Assaultiveness, belligerence, psychosis, violence, impulsiveness, psychomotor agitation, fever, tachycardia, vertical/horizontal nystagmus, hypertension, impaired judgment, ataxia, seizures, delirium. Give benzodiazepines or haloperidol for severe symptoms; otherwise reassure. Acidifcation of urine or gastric lavage can help eliminate the drug. Recurrence of intoxication symptoms due to reabsorption in the GI tract; sudden onset of severe, random violence. LSD Marked anxiety or depression, delusions, visual hallucinations, fashbacks, pupillary dilation, impaired judgment, diaphoresis, tachycardia, hypertension, heightened senses (e.g., colors become more intense). Supportive counseling; traditional antipsychotics for psychotic symptoms; benzodiazepines for anxiety. Marijuana Euphoria, slowed sense of time, impaired judgment, social withdrawal, ↑ appetite, dry mouth, conjunctival injection, hallucinations, anxiety, paranoia, amotivational syndrome. Barbiturates Low safety margin; respiratory depression. Anxiety, seizures, delirium, life-threatening cardiovascular collapse. Benzodiazepines Interactions with alcohol, amnesia, ataxia, somnolence, mild respiratory depression. (Avoid using for insomnia in the elderly; can cause paradoxical agitation even in relatively low doses.) Rebound anxiety, seizures, tremor, insomnia, hypertension, tachycardia, death. Restlessness, insomnia, diuresis, muscle twitching, arrhythmias, tachycardia, fushed face, psychomotor agitation. Headache, lethargy, depression, weight gain, irritability, craving. Restlessness, insomnia, anxiety, arrhythmias. Irritability, headache, anxiety, weight gain, craving, bradycardia, diff culty concentrating, insomnia. Caffeine Nicotine
Occurs more often in males (4:1) and in those 21–34 years of age, although the incidence in females is rising. Also associated with a  family history.
Hx/PE: See Table 2.14-10 for the symptoms of intoxication and withdrawal. Look for palmar erythema or telangiectasias as well as for other signs and symptoms of end-organ complications.
Dx: Screen with the CAGE questionnaire. Monitor vital signs for evidence of withdrawal. Labs may reveal ↑ LFTs, LDH, and MCV.
Rule out medical complications; correct electrolyte abnormalities.Start a benzodiazepine taper for withdrawal symptoms. Add haloperidol for hallucinations and psychotic symptoms.
Pinpoint pupils are not always a reliable sign of opioid ingestion because coingestions can lead to normal or enlarged pupils. Also look for a ↓ respiratory rate, track marks, and ↓breath sounds.
CAGE questionnaire: 1.Have you ever felt the need to Cut down on your drinking?
Have you ever felt Annoyed by criticism of your drinking?
Have you ever felt Guilty about drinking?Have you ever had to take a morning Eye opener?
More than one “yes” answer makes alcoholism likely.There are two types of anorexia nervosa:Give multivitamins and folic acid; administer thiamine before glucose (which depletes thiamine) to prevent Wernicke’s encephalopathy.
Give anticonvulsants to patients with a seizure history.Group therapy, disulfram, or naltrexone can aid patients with dependence.
Long-term rehabilitative therapy (e.g., Alcoholic Anonymous).■ Cx:GI bleeding from gastritis, ulcers, varices, or Mallory-Weiss tears.Pancreatitis, liver disease, DTs, alcoholic hallucinosis, peripheral neuropathy, Wernicke’s encephalopathy, Korsakoff’s psychosis, fetal alcohol syndrome, cardiomyopathy, anemia, aspiration pneumonia, ↑ risk of sustaining trauma (e.g., subdural hematoma).
Risk factors include female gender, low self-esteem, and high SES. Also associated with OCD, major depressive disorder, anxiety, and careers such as modeling, gymnastics, ballet, and running.
Hx/PE: Diagnosed as follows (see also Table 2.14-11):Body weight is < 85% of that expected.Patients present with refusal to maintain normal body weight, an intense fear of weight gain, a distorted body image (patients perceive themselves as fat), and amenorrhea.
Patients restrict (e.g., fasting, excessive exercise) or binge and purge (through vomiting, laxatives, and diuretics).
Signs and symptoms include lanugo, dry skin, bradycardia, lethargy, hypotension, cold intolerance, and hypothermia (as low as 35°C).
Dx: Measure height and weight; check CBC, electrolytes, endocrine levels, and ECG. Perform a psychiatric evaluation to screen patients for co-morbid conditions.
Initially, monitor caloric intake to restore nutritional status and to stabilize weight; then focus on weight gain.
Hospitalize if necessary to restore nutritional status, rehydrate, and correct electrolyte imbalances.
Once the patient is medically stable, initiate individual, family, and group psychotherapy. Treat comorbid depression and anxiety.
Cx: Mitral valve prolapse, arrhythmias, hypotension, bradycardia, amenor-TABLE 2.14-11. Anorexia vs. BulimiaBody image Disturbed body image; use extensive measures to avoid weight gain (e.g., purging, excess exercise). Same. Binge eating May occur. Same. Patients are underweight (≥ 15% below expected weight). Patients are of normal weight or are overweight. Patients are typically not distressed by their illness and may thus be resistant to treatment. Patients are typically distressed about their symptoms and are thus easier to treat. Weight Attitude toward illness rhea (missing three consecutive cycles), nephrolithiasis, osteoporosis, multiple stress fractures, pancytopenia, thyroid abnormalities (see Table 2.1412). Mortality from suicide or medical complications is > 10%.
More common among women; associated with low self-esteem, mood disorders, and OCD.
Hx/PE: Diagnostic criteria are as follows (see also Table 2.14-11):
Patients have normal weight or are overweight. For at least two times a week for three or more months, patients have episodes of binge eating and compensatory behaviors that include purging or fasting.
Patients are usually ashamed and conceal their behaviors.Signs include dental enamel erosion, enlarged parotid glands, and scars on the dorsal hand surfaces (from inducing vomiting). Patients usually have normal body weight.
Tx: Psychotherapy focuses on behavior modifcation and body image. Antidepressants may be effective for both depressed and nondepressed patients.
Cx: See Table 2.14-12.Interest in sexual activity usually does not ↓ with aging.
Men usually require ↑ stimulation of the genitalia for longer periods of time to reach orgasm; intensity of orgasm ↓, and the length of the refractory period before the next orgasm ↑.
In women, estrogen levels ↓ after menopause, leading to vaginal dryness and thinning, which may result in discomfort during coitus. May be treated with HRT, estrogen vaginal suppositories, or other vaginal creams.
Preoccupation with or engagement in unusual sexual fantasies, urges, or behaviors for > 6 months with clinically signifcant impairment in one’s life. Includes criminal sex offenders (e.g., pedophilia); see Table 2.14-13. Found almost exclusively in men, and usually begins before or during puberty.
Sexual excitement is derived from unique exposures to certain situations, individuals, or objects.
T AB LE 2.1 4-1 2. Medical Complications of Eating Disorders be more disturbed by their behavior than anorexics and are more easily engaged in therapy. Anorexic patients deny health risks associated with their behavior, making them resistant to treatment.
Bupropion should be avoided in the treatment of patients with eating disorders, as it is associated with a ↓ seizure threshold.
Cachexia Hypothermia Fatigue Electrolyte abnormalities Arrhythmias Sudden death Hypotension Bradycardia Prolonged QT interval Dental erosions and decay Abdominal pain Delayed gastric emptying Amenorrhea Nephrolithiasis Dermatologic: Lanugo Hematologic: Leukopenia Neurologic: Seizures Musculoskeletal: Osteoporosis, stress fractures
T AB LE 2.1 4-1 3. Features of Common Paraphilias
Exhibitionism Sexual arousal from exposing one’s genitals to a stranger. Pedophilia Urges or behaviors involving sexual activities with children. Voyeurism Observing unsuspecting persons unclothed or involved in sex. Fetishism Use of nonliving objects (often clothing) for sexual arousal. Transvestic fetishism Cross-dressing for sexual arousal. Frotteurism Touching or rubbing one’s genitalia against a nonconsenting person (common in subways). Sexual sadism Sexual arousal from inficting suffering on sexual partner. Sexual masochism Sexual arousal from being hurt, humiliated, bound, or threatened.
■ Tx: Treatment includes insight-oriented psychotherapy and behavioral therapy. Antiandrogens (e.g., Depo-Provera) have been used for hypersexual paraphilic activity.
Strong, persistent cross-gender identification and discomfort with one’s assigned sex or gender role of the assigned sex in the absence of intersexual disorders. Patients may have a history of dressing like the opposite sex, taking sex hormones, or pursuing surgeries to reassign their sex.
More common in males than in females. Associated with depression, anxiety, substance abuse, and personality disorders, which may be addressed and treated.
Tx: Treatment is complex and includes educating the patient about culturally acceptable behavior patterns. Other options include sex-reassignment surgery or hormonal treatment (e.g., estrogen for males, testosterone for females). Supportive psychotherapy is helpful.
Problems in sexual arousal, desire, or orgasm or pain with sexual intercourse.
Prevalence is 30%; one-third of cases are attributable to biological factors and another third to psychological factors.
Tx: Treatment depends on the particular condition. Pharmacologic strategies include sildenafl (Viagra) and bupropion (Wellbutrin). Psychotherapeutic strategies include sensate focusing.
Up to one-third of all American adults suffer from some type of sleep disorder during their lives. The term dyssomnia describes any condition that leads to a disturbance in the normal rhythm or pattern of sleep. Insomnia is the most common example. Risk factors include female gender, the presence of mental and medical disorders, substance abuse, and advanced age.
Affects up to 30% of the general population; causes sleep disturbance that is not attributable to physical or mental conditions. Often exacerbated by anxiety, and patients may become preoccupied with getting enough sleep.
Dx: Patients present with a history of nonrestorative sleep or difficulty initiating or maintaining sleep that is present at least three times a week for one month.
First-line therapy includes the initiation of good sleep hygiene measures, which include the following:
Establishment of a regular sleep scheduleLimiting of caffeine intakeAvoidance of daytime napsWarm baths in the eveningUse of the bedroom for sleep and sexual activity only
Exercising early in the dayAvoidance of large meals near bedtimePharmacotherapy is considered second-line therapy and should be initiated with care for short periods of time (< 2 weeks). Pharmacologic agents include diphenhydramine (Benadryl), zolpidem (Ambien), zaleplon (Sonata), and trazodone (Desyrel).
Dx: Diagnosed when a patient complains of excessive daytime sleepiness or nighttime sleep that occurs for > 1 month. The excessive somnolence cannot be attributable to medical or mental illness, medications, poor sleep hygiene, insuffcient sleep, or narcolepsy.
First-line therapy includes stimulant drugs such as amphetamines.Antidepressants such as SSRIs may be useful in some patients.
May affect up to 0.16% of the population. Onset typically occurs by young adulthood, generally before the age of 30. Some forms of narcolepsy may have a genetic component.
Manifestations include excessive daytime somnolence and ↓REM sleep latency on a daily basis for at least three months. Sleep attacks are the classic symptom; patients cannot avoid falling asleep.
Factitious disorders and malingering are distinct from somatoform disorders in that they involve conscious and intentional processes.
■The characteristic excessive sleepiness may be associated with the following:
Cataplexy: Sudden loss of muscle tone that leads to collapse.
Hypnagogic hallucinations: Occur as the patient is falling asleep.Hypnopompic hallucinations: Occur as the patient awakens.Sleep paralysis: Brief paralysis upon awakening.■ Tx: Treat with a regimen of scheduled daily naps plus stimulant drugs such as amphetamines; give SSRIs for cataplexy.
Occurs 2° to disturbances in breathing during sleep that lead to excessive daytime somnolence and sleep disruption. Etiologies can be either central or peripheral.
Central sleep apnea (CSA): A condition in which both airf ow and respiratory effort cease. CSA is linked to morning headaches, mood changes, and repeated awakenings during the night.
Obstructive sleep apnea (OSA): A condition in which airf ow ceases as a result of obstruction along the respiratory passages. OSA is strongly associated with snoring. Risk factors include male gender, obesity, prior upper airway surgeries, a deviated nasal septum, a large uvula or tongue, and retrognathia (recession of the mandible).
In both forms, arousal results in cessation of the apneic event.
Associated with sudden death in infants and elderly, headaches, depression, ↑ systolic blood pressure, and pulmonary hypertension.
Dx: Sleep studies (polysomnography) document the number of arousals, obstructions, and episodes of ↓ O2 saturation; distinguish OSA from CSA; and identify possible movement disorders, seizures, or other sleep disorders.
OSA: Nasal continuous positive airway pressure (CPAP). Weight loss if obese. In children, most cases are due to tonsillar/adenoidal hypertrophy, which is corrected surgically.
CSA: Mechanical ventilation (e.g., BPAP) with a backup rate for severe cases.
A spectrum of disorders characterized by a misalignment between desired and actual sleep periods. Subtypes include jet-lag type, shift-work type, delayed sleep-phase type, and unspecif ed.
Jet-lag type usually resolves within 2–7 days without specific treatment.
Shift-work type may respond to light therapy.Oral melatonin may be useful if given 5½ hours prior to the desired bedtime.
Patients often present with medically unexplained somatic symptoms, generally with varying etiologies.
Somatoform disorders: Patients have no conscious control over symptoms. The fve main categories are outlined in Table 2.14-14.
Factitious disorders: Patients fabricate symptoms or cause self-injury to assume the sick role (1° gain). More common in males.
Munchausen’s syndrome: Common among health care workers.Munchausen’s syndrome by proxy: A “caregiver” makes someone else ill and enjoys taking on the role of concerned onlooker.
Malingering: Patients intentionally cause or feign symptoms for 2° gain of financial benefit or housing.
Most frequently affects women < 35 years of age who f ll the following criteria:
Are experiencing marital discord and are substance abusers or have a partner who is a substance abuser; or
Are pregnant, are of low SES, or have obtained a restraining order.
In malingering, patients intentionally simulate illness for personal gain.Sexual abusers are usually male and are often known to the victim (and are often family members).
TABLE 2.14-14.Somatization disorder Multiple, chronic somatic symptoms from different organ systems with multiple GI, sexual, neurologic, and pain complaints. Frequent clinical contacts and/or surgeries; signif cant functional impairment. The male-to-female ratio is 1:20; onset is usually before age of 30. Schedule regular appointments with the identifed 1° caregiver who maintains communication with consultants and specialists; psychotherapy. Conversion disorder Symptoms or defcits of voluntary motor or sensory function (e.g., blindness, seizure-like movements, paralysis) incompatible with medical processes. Close temporal relationship to stress or intense emotion. More common in young females and in lower socioeconomic and less educated groups. Usually resolves spontaneously, but psychotherapy may help. Hypochondriasis Preoccupation with or fear of having a serious disease despite medical reassurance, leading to signifcant distress/impairment. Often involves a history of prior physical disease. Men and women are equally affected. Onset is in adulthood. Manage with group therapy and schedule regular appointments with the patient’s 1° caregiver. Body dysmorphic disorder Preoccupation with an imagined physical defect or abnormality that leads to signif cant distress/impairment. Patients often present to dermatologists or plastic surgeons. Has a slight female predominance. May be associated with depression. SSRIs may be of benef t. Somatoform pain disorder Intensity or profle of pain symptoms is inconsistent with physiologic processes. Close temporal relationship with psychological factors. More common in females; peak onset is at 40–50 years of age. May be associated with depression. Treatment includes rehabilitation (e.g., physical therapy), psychotherapy, and behavioral therapy. Analgesia is usually not helpful. TCAs and SNRIs (venlafaxine and duloxetine) may be therapeutic.
Suicide is the third leading cause of death (after homicide and accidents) among 15to 24-year-olds in the United States.
Emergent inpatient hospitalization is required for patients with suicidal intentions.
Victims of childhood abuse are more likely to become adult victims of abuse.
Patients typically have multiple somatic complaints, frequent ER visits, and unexplained injuries with delayed medical treatment. They may also avoid eye contact or act afraid or hostile.
Children may exhibit precocious sexual behavior, genital or anal trauma, STDs, UTIs, and psychiatric problems.
Other clues include a partner who answers questions for the patient or refuses to leave the exam room.
Tx: Perform a screening assessment of the patient’s safety domestically and in their close personal relationships. Provide medical care, emotional support, and counseling; educate the patient about support services and refer appropriately. Documentation is crucial.
Accounts for 30,000 deaths per year in the United States; the eighth overall cause of death in the United States. One suicide occurs every 20 minutes.
Risk factors include male gender, age greater than 45 years, psychiatric disorders (major depression, presence of psychotic symptoms), a history of an admission to a psychiatric institution, a previous suicide attempt, a history of violent behavior, ethanol or substance abuse, recent severe stressors, and a family suicide history (see the mnemonic SAD PERSONS).
Women are more likely to attempt suicide, whereas men are more likely to succeed by virtue of their ↑ use of more lethal methods.
Perform a comprehensive psychiatric evaluation.Ask about family history, previous attempts, ambivalence toward death, and hopelessness.
Ask directly about suicidal ideation, intent, and plan, and look for available means.
Tx: A patient who endorses suicidality requires emergent inpatient hospitalization even against his will. Suicide risk may ↑ after antidepressant therapy is initiated because a patient’s energy to act on suicidal thoughts can return before the depressed mood lifts.
Neoplasms of the Lungs 469 LUNG NODULES 469 LUNG CANCER 470
Beware—all that wheezes is not asthma!Asthma should be suspected in children with multiple episodes of croup and URIs associated with dyspnea.
Characterized by airway narrowing, obstructive lung diseases restrict air movement and often cause air trapping. The etiologies of obstructive lung disease are described in the mnemonic ABCT. Figure 2.15-1 illustrates the role of lung volume measurements in the diagnosis of lung disease; Table 2.15-1 and Figure 2.15-2 contrast obstructive with restrictive lung disease.
Reversible airway obstruction 2° to bronchial hyperreactivity, airway infl ammation, mucous plugging, and smooth muscle hypertrophy.
Presents with cough, episodic wheezing, dyspnea, and/or chest tightness. Symptoms often worsen at night or early in the morning.
Exam reveals wheezing, prolonged expiratory duration (↓ I/E ratio), accessory muscle use, tachypnea, tachycardia, ↓ breath sounds (late sign), ↓O2 saturation (late sign), hyperresonance, and possible pulsus paradoxus.
■ABGs: Mild hypoxia and respiratory alkalosis. Normalizing PCO2, respiratory acidosis, and more severe hypoxia in an acute exacerbation warrant close observation, as they may indicate fatigue and impending respiratory failure.
F IGU R E 2.1 5-1. Lung volumes in the interpretation of pulmonary function tests.
(Reproduced, with permission, from Gomella LG et al. Clinician’s Pocket Reference, 11th ed. New York: McGraw-Hill, 2006: Fig. 18-1.)
T AB LE 2.1 5-1. Obstructive vs. Restrictive Lung Diseasea a FEV1 = forced expiratory volume in one second; FVC = forced vital capacity.
Spirometry/PFTs: ↓ FEV1/FVC; peak fow is diminished acutely; ↑ RV and total lung capacity (TLC).
CBC: Possible eosinophilia.CXR: Hyperinf ation.Methacholine challenge: Tests for bronchial hyperresponsiveness; useful when PFTs are normal but asthma is still suspected.
In general, avoid allergens or any potential triggers. Management is as follows (see also Tables 2.15-2 and 2.15-3):
Asthma triggers include allergens, URIs, cold air, exercise, drugs, and stress.
F IGU R E 2.1 5-2. Obstructive vs. restrictive lung disease.
Note: Obstructive lung volumes > normal (↑ TLC, ↑ FRC, ↑ RV); restrictive lung volumes < normal. In both obstructive and restrictive disease, FEV1 and FVC are reduced, but in obstructive disease, FEV1 is more dramatically reduced, resulting in a ↓FEV1/FVC ratio.
T AB LE 2.1 5-2. Common Asthma Medications and Their Mechanisms β2-agonists Albuterol: Relaxes bronchial smooth muscle (β2-adrenoceptors). Give during acute exacerbations. Salmeterol: Long-acting agent for prophylaxis. Corticosteroids Beclomethasone, prednisone: Inhibit the synthesis of virtually all cytokines; inactivate NF-κB, a transcription factor for TNF-α, among other infl ammatory agents. Inhaled corticosteroids are the first-line treatment for long-term control of asthma. Muscarinic antagonists Ipratropium: Competitively blocks muscarinic receptors, preventing bronchoconstriction. Methylxanthines Theophylline: Likely causes bronchodilation by inhibiting phosphodiesterase, thereby ↓ cAMP hydrolysis and ↑ cAMP levels. Usage is limited because of its narrow therapeutic-toxic index (cardiotoxicity, neurotoxicity). Cromolyn Prevents release of vasoactive mediators from mast cells. Useful for exercise-induced bronchospasm. Effective only for the prophylaxis of asthma; not effective during an acute asthmatic attack. Toxicity is rare. Antileukotrienes Zileuton: A 5-lipoxygenase pathway inhibitor. Blocks conversion of arachidonic acid to leukotrienes. Montelukast, zafirlukast: Blocks leukotriene receptors.
TABLE 2.15-3.Acute: O2, bronchodilating agents (short-acting inhaled β2-agonists are f rst-line therapy), ipratropium (never use alone for asthma), systemic corticosteroids, magnesium (for severe exacerbations). Maintain a low threshold for intubation in severe cases or acutely in patients with PCO2 > 50 mmHg or PO2 < 50 mmHg.
Chronic: Measure lung function (FEV1, peak fow, and sometimes ABGs) to guide management. Administer long-acting inhaled bronchodilators and/ or inhaled corticosteroids, systemic corticosteroids, cromolyn, or, rarely,
Medications for Chronic Treatment of AsthmaMild intermittent ≤ 2 days/week ≤ 2 nights/month ≥ 80% No daily medications. PRN short-acting bronchodilator. Mild persistent > 2/week but < 1/day > 2 nights/month ≥ 80% Daily low-dose inhaled corticosteroids. PRN short-acting bronchodilator. Moderate persistent Daily > 1 night/week 60–80% Lowto medium-dose inhaled corticosteroids + long-acting inhaled β2-agonists. Severe persistent Continual, frequent ≤ 60% High-dose inhaled corticosteroids + long-acting inhaled β2-agonists. Possible PO corticosteroids. PRN short-acting bronchodilator.
theophylline. Montelukast and other leukotriene antagonists are oral adjuncts to inhalant therapy.
A disease caused by cycles of infection and infammation in the bronchi/bronchioles that lead to permanent fbrosis, remodeling, and dilation of bronchi.
Presents with chronic cough accompanied by frequent bouts of yellow or green sputum production, dyspnea, and possible hemoptysis and halitosis.
Associated with a history of pulmonary infections (e.g., Pseudomonas, Haemophilus, TB), hypersensitivity (allergic bronchopulmonary aspergillosis), cystic f brosis, immunodefciency, localized airway obstruction (foreign body, tumor), aspiration, autoimmune disease (e.g., rheumatoid arthritis, SLE), or IBD.
Exam reveals rales, wheezes, rhonchi, purulent mucus, and occasional hemoptysis.
CXR: ↑ bronchovascular markings; tram lines (parallel lines outlining dilated bronchi as a result of peribronchial inf ammation and f brosis); areas of honeycombing.
High-resolution CT: Dilated airways and ballooned cysts at the end of the bronchus (mostly lower lobes). Spirometry shows a ↓ FEV1/FVC ratio.
Antibiotics for bacterial infections; consider inhaled corticosteroids.Maintain bronchopulmonary hygiene (cough control, postural drainage, chest physiotherapy).Consider lobectomy for localized disease or lung transplantation for severe disease.
Characterized by ↓ lung function with airfow obstruction. Generally 2° to chronic bronchitis or emphysema, which are distinguished as follows:
Chronic bronchitis: Productive cough for > 3 months per year for two consecutive years.
Emphysema: Terminal airway destruction and dilation that may be 2° to smoking (centrilobular) or to α1-antitrypsin deficiency (panlobular).
Symptoms are minimal or nonspecifc until the disease is advanced.
The clinical spectrum includes the following (most patients are a combination of the two phenotypes):
Emphysema (“pink puffer”): Dyspnea, pursed lips, minimal cough, ↓ breath sounds, late hypercarbia/hypoxia. Patients often have a thin, wasted appearance. Pure emphysematous patients tend to have few reactive episodes between exacerbations.
aspiration Or 2° to foreign bodies Necrotizing pneumonia Chemical corrosive smoking cessation, pneumococcal and infl uenza vaccines)
Dilators (β2-agonists, anticholinergics)In COPD patients with chronic hypercapnia, high concentrations of O2 may suppress patients’ hypoxic respiratory drive.
Supplemental oxygen titrated to > 90% SaO2 for > 15 hours a day and smoking cessation are the only interventions proven to improve survival in patients with COPD.
■Chronic bronchitis (“blue bloater”): Cyanosis with mild dyspnea; productive cough. Patients are often overweight with peripheral edema, rhonchi, and early signs of hypercarbia/hypoxia. Look for the classic barrel chest, use of accessory chest muscles, JVD, end-expiratory wheezing, and muffed breath sounds.
CXR: Hyperinfl ated lungs, ↓ lung markings with fat diaphragms, and a thin-appearing heart and mediastinum. Parenchymal bullae or subpleural blebs (pathognomonic of emphysema) are also seen (see Figure 2.15-3).
PFTs: ↓ FEV1/FVC; normal or ↓ FVC; normal or ↑ TLC (emphysema, asthma); ↓ DLCO (in emphysema).
ABGs: Hypoxemia with acute or chronic respiratory acidosis (↑ PCO2).
Blood cultures: Obtain if the patient is febrile.Gram stain and sputum culture: Consider in the setting of fever or productive cough, especially if infltrate is seen on CXR.
Acute exacerbations: O2, inhaled β-agonists (albuterol) and anticholinergics (ipratropium, tiotropium), IV +/− inhaled corticosteroids, antibiotics. Severe cases may beneft from noninvasive ventilation. Consider intubation in the setting of severe hypoxemia or hypercapnia, impending respiratory fatigue, or changes in mental status.
Chronic: Smoking cessation, supplemental O2 (if resting PaO2 is ≤ 55 mmHg or SaO2 is ≤ 89%, or in the setting of cor pulmonale, pulmonary hypertension, a hematocrit > 55%, or nocturnal hypoxia), inhaled β-agonists,
AB F IGU R E 2.1 5-3. Chronic obstructive pulmonary disease.
Note the hyperinfated and hyperlucent lungs, f at diaphragms, ↑ AP diameter, narrow mediastinum, and large upper bullae on (A) AP and (B) lateral CXRs. (Reproduced, with permission, from Stobo J et al. The Principles and Practice of Medicine, 23rd ed. Stamford, CT: Appleton & Lange, 1996: 135.) anticholinergics (tiotropium), systemic or inhaled corticosteroids. Give pneumococcal and fl u vaccines.
Characterized by a loss of lung compliance, restrictive lung diseases result in ↑ lung stiffness and ↓ lung expansion. Table 2.15-1 and Figure 2.15-2 contrast obstructive with restrictive lung disease. The etiologies of restrictive lung disease are shown in the mnemonic PAINT.
A heterogeneous group of disorders characterized by infl ammation and/or fibrosis of the interalveolar septum. In advanced disease, cystic spaces develop in the lung periphery (“honeycombing”). Causes include idiopathic interstitial pneumonias, collagen vascular disease, granulomatous disorders, drugs, hypersensitivity disorders, pneumoconiosis, and eosinophilic pulmonary syndromes.
Presents with shallow, rapid breathing; dyspnea with exercise; and a nonproductive cough. Patients may have cyanosis, inspiratory squeaks, fne or “Velcro-like” crackles, fnger clubbing, or right heart failure.
■ CXR: Reticular, nodular, or ground-glass pattern; “honeycomb” pattern (severe disease).
■↓TLC, ↓FVC, ↓DLCO (may be normal if the cause is extrapulmonary), normal FEV1/FVC. Serum markers of connective tissue diseases should be obtained if clinically indicated.
Supportive. Avoid exposure to causative agents. Some inf ammatory diseases respond to corticosteroids or other anti-inf ammatory/immunosuppressive agents.
A multisystem disease of unknown etiology characterized by noncaseating granulomas. Most commonly found in African-American females and northern European Caucasians; most often arises in the third or fourth decade of life.
Presents with fever, cough, malaise, weight loss, dyspnea, and arthritis. The lungs, liver, eyes, skin (erythema nodosum, violaceous skin plaques), nervous system, heart, and kidney may be affected. Symptoms may be GRUELING (see mnemonic).
Causes of restrictive lung disease—Pleural (fibrosis, effusions, empyema, pneumothorax)Alveolar (edema, hemorrhage, pus)Interstitial lung disease (idiopathic interstitial pneumonias), Infl ammatory (sarcoid, cryptogenic organizing pneumonitis), Idiopathic
Neuromuscular (myasthenia, phrenic nerve palsy, myopathy)Thoracic wall (kyphoscoliosis, obesity, ascites, pregnancy, ankylosing spondylitis)Medications that can cause or contribute to interstitial lung disease include busulfan, nitrofurantoin, amiodarone, bleomycin, radiation, and long-term high O2 concentration (e.g., ventilators).
CXR: Radiographic fndings are used to stage the disease.Biopsy: Lymph node biopsy or transbronchial/video-assisted thoracoscopic lung biopsy reveals noncaseating granulomas.
PFTs: Restrictive or obstructive pattern and ↓ diffusion capacity.Other findings: ↑serum ACE levels (neither sensitive nor specif c), hypercalcemia, hypercalciuria, ↑ alkaline phosphatase (with liver involvement), lymphopenia, cranial nerve defects, arrhythmias.
Systemic corticosteroids are indicated for constitutional symptoms, hypercalcemia, or extrathoracic organ involvement.
Risk factors include environmental exposure to antigens leading to alveolar thickening and granulomas. Types and etiologies are listed in Table 2.15-4.
Acute: Dyspnea, fever, malaise, shivering, and cough starting 4–6 hours after exposure.
Chronic: Patients present with progressive dyspnea; exam reveals f ne bilateral rales.
CXR is normal or shows miliary nodular infltrate (acute); fbrosis is seen in the upper lobes (chronic).
Avoid ongoing exposure to inciting agents; give corticosteroids to ↓ chronic inf ammation.
T AB LE 2.1 5-4. Antigens of Hypersensitivity PneumonitisFarmer’s lung Spores of actinomycetes from moldy hay. Bird fancier’s lung Antigens from feathers, excreta, serum. Mushroom worker’s lung Spores of actinomycetes from compost. Malt worker’s lung Spores of Aspergillus clavatus in grain. Grain handler’s lung Grain weevil dust. Bagassosis Spores of actinomycetes from sugarcane. Air conditioner lung Spores of actinomycetes from air conditioners.
Risk factors include prolonged occupational exposure and inhalation of small inorganic dust particles.
Table 2.15-5 outlines the f ndings and diagnostic criteria associated with common pneumoconioses.
Avoid triggers; supportive therapy and supplemental O2.The most common form of idiopathic interstitial pneumonia. Has an unrelenting progression, with death usually occurring within 5–10 years.
Exertional dyspnea and a nonproductive cough.Inspiratory crackles and/or clubbing on exam.T AB LE 2.1 5-5.  Diagnosis of PneumoconiosesUsual interstitial pneumonia is one of the most common forms of interstitial pneumonia.
Asbestosis Work involving manufacture of tile or brake linings, insulation, construction, demolition, or shipbuilding. Presents 15–20 years after initial exposure. CXR: Linear opacities at lung bases and interstitial fibrosis; calcified pleural plaques are indicative of benign pleural disease. ↑ risk of mesothelioma (rare) and lung cancer; risk of lung cancer is higher in smokers. Coal miner’s disease Work in underground coal mines. CXR: Small nodular opacities (< 1 cm) in upper lung zones. Spirometry: Consistent with restrictive disease. Progressive massive fibrosis. Work in mines or quarries or with glass, pottery, or silica. CXR: Small (< 1-cm) nodular opacities in upper lung zones. Eggshell calcifications. Spirometry: Consistent with restrictive disease. ↑ risk of TB; need annual TB skin test. Progressive massive fibrosis. Work in high-technology fields such as aerospace, nuclear, and electronics plants; ceramics industries; foundries; plating facilities; dental material sites; and dye manufacturing. CXR: Diffuse infiltrates; hilar adenopathy. Requires chronic corticosteroid treatment. Silicosis Berylliosis
High-resolution CT: Patchy opacities at the lung bases, often with honeycombing.
PFTs: Restrictive pattern.Surgical biopsy (usually required to confrm the diagnosis): Interstitial in-f ammation, fbrosis, and honeycombing.
Options include corticosteroids, cytotoxic agents (azathioprine, cyclophosphamide), antifbrotic agents (have not been shown to improve survival), and lung transplantation.
A diverse group of disorders characterized by eosinophilic pulmonary infiltrates and peripheral blood eosinophilia. Includes allergic bronchopulmonary aspergillosis, Löffl er’s syndrome, and acute eosinophilic pneumonia.
Presents with dyspnea, cough, and/or fever.CBC reveals peripheral eosinophilia; CXR shows pulmonary inf ltrates.Removal of the extrinsic cause or treatment of underlying infection if identifed. Corticosteroid treatment may be used if no cause is identif ed.
Causes include ventilation-perfusion (V/Q) mismatch, right-to-left shunt, hypoventilation, low inspired O2 content (important at altitudes), and diffusion impairment.
Findings depend on the etiology. ↓HbO2 saturation, cyanosis, tachypnea, shortness of breath, pleuritic chest pain, and altered mental status may be seen.
Pulse oximetry: Demonstrates ↓ HbO2 saturation.CXR: To rule out ARDS, atelectasis, or an infltrative process (e.g., pneumonia) and to look for signs of pulmonary embolism.
ABGs: To evaluate PaO2 and to calculate the alveolar-arterial (A-a) oxygen gradient ([(Patm − 47) × FiO2 − (PaCO2/0.8)] − PaO2). An ↑ A-a gradient suggests a V/Q mismatch or a diffusion impairment. Figure 2.15-4 summarizes the approach toward hypoxemic patients.
Is PaCO2 increased? Hypoventilation Yes Yes No No Is PAO2 − PaO2 increased?
Is PAO2 − PaO2 increased? Yes Yes NoNo Is low PO2 correctable with O2?
1. High altitude 2. ↓ FiO2HIGH-YIELD FACTS Hypoventilation plus another mechanism Shunt 1.  Alveolar collapse (asthma, COPD) 2.  Intra-alveolar filling (pneumonia,      pulmonary edema) 3.  Intracardiac shunt 4. Vascular shunt within lungs 1.  Airways disease (asthma, COPD) 2. Interstitial lung disease 3.  Alveolar disease 4.  Pulmonary vascular disease V/Q mismatch 1. ↓ respiratory drive 2.  Neuromuscular disease Hypoventilation alone
F IGU R E 2.1 5-4. Determination of the mechanism of hypoxia.
(Reproduced, with permission, from Kasper DL et al. Harrison’s Principles of Internal Medicine, 16th ed. New York: McGraw-
Hill, 2005.)Address the underlying etiology.Administer O2 before initiating evaluation.If the patient is on a ventilator, ↑ O2 saturation by increasing FiO2, positive end-expiratory pressure (PEEP), or the I/E ratio.
Hypercapnic patients: ↑ minute ventilation.Acute respiratory failure with refractory hypoxemia, ↓lung compliance, and noncardiogenic pulmonary edema. The pathogenesis is thought to be endothelial injury. Common triggers include sepsis, pneumonia, aspiration, multiple blood transfusions, inhaled/ingested toxins, and trauma. Overall mortality is 30–40%.
Presents with acute-onset (12–48 hours) tachypnea, dyspnea, and tachycardia +/− fever, cyanosis, labored breathing, diffuse high-pitched rales, and hypoxemia in the setting of one of the systemic infammatory causes or exposure. Additional fndings are as follows:
Phase 1 (acute injury): Normal physical exam; possible respiratory alkalosis.
Phase 2 (6–48 hours): Hyperventilation, hypocapnia, widening A-a oxygen gradient.
Phase 3: Acute respiratory failure, tachypnea, dyspnea, ↓ lung compliance, scattered rales, diffuse chest infltrates on CXR (see Figure 2.15-5).
F IGU R E 2.1 5-5. AP CXR showing a diffuse alveolar filling pattern 2° to ARDS.
(Reproduced, with permission, from Kasper DL et al. Harrison’s Principles of Internal Medicine, 16th ed. New York: McGraw-Hill, 2005: 1497.) ■ Phase 4: Severe hypoxemia unresponsive to therapy; ↑ intrapulmonary shunting; metabolic and respiratory acidosis.
The criteria for ARDS diagnosis (according to the American-European Consensus Conference defnition) are as follows:
Acute onset of respiratory distress.PaO2/FiO2 ratio ≤ 200 mmHg.Bilateral pulmonary infltrates on CXR.No evidence of cardiac origin (capillary wedge pressure < 18 mmHg or no clinical evidence of elevated left atrial pressure).
There is no standard treatment.Treat the underlying disease and maintain adequate perfusion to prevent end organ damage.
Minimize injury induced by mechanical ventilation by ventilating with low tidal volumes.
Use PEEP to recruit collapsed alveoli and titrate PEEP and FiO2 to achieve adequate oxygenation. Goal oxygenation is PaO2 > 60 mmHg or SaO2 > 90% on FiO2 ≤ 0.6.
Slowly wean patients from ventilation, and follow with extubation trials (see Table 2.15-6).
Pulmonary hypertension is defned as a mean pulmonary arterial pressure of > 25 mmHg (normal = 15 mmHg). It is classifed as either 1° (if the etiology
T AB LE 2.1 5-6. Criteria for Extubation from Mechanical Ventilationa a Patients who meet these criteria are typically given a weaning (T-piece) trial to determine if they are ready for extubation.
is unknown) or 2°. 1° pulmonary hypertension most often occurs in young or middle-aged women. The main causes of 2° pulmonary hypertension include the following: ■↑ pulmonary venous pressure from left-sided heart failure or mitral valve disease. ■↑ pulmonary blood fow 2° to congenital heart disease with left-to-right shunt.
Hypoxic vasoconstriction 2° to chronic lung disease (e.g., COPD).Thromboembolic disease.Remodeling of pulmonary vessels 2° to structural lung disease.Presents with dyspnea on exertion, fatigue, lethargy, syncope with exertion, chest pain, and symptoms of right-sided CHF (edema, abdominal distention, JVD).
Inquire about a history of COPD, interstitial lung disease, heart disease, sickle cell anemia, emphysema, and pulmonary emboli.
Exam reveals a loud, palpable S2 (often split), a systolic ejection murmur, an S4, or a parasternal heave.
CXR shows enlargement of central pulmonary arteries.ECG demonstrates RVH.Echocardiogram and right heart catheterization may show signs of right ventricular overload and may aid in the diagnosis of the underlying cause.
Supplemental O2, anticoagulation, vasodilators, and diuretics if symptoms of right-sided CHF are present. Treat underlying causes of 2° pulmonary hypertension.
Causes of pulmonary hypertension include left heart failure, mitral valve disease, and ↑ resistance in the pulmonary veins, including hypoxic vasoconstriction.
Other etiologies of embolic disease include postpartum status (amniotic f uid emboli), fracture (fat emboli), and cardiac surgery (air emboli).
Dyspnea, tachycardia, and a normal CXR in a hospitalized and/or bedridden patient should raise suspicion of pulmonary embolism.
Occlusion of the pulmonary vasculature by a blood clot. Ninety-f ve percent of emboli originate from DVTs in the deep leg veins. Often leads to pulmonary infarction, right heart failure, and hypoxemia. Virchow’s triad consists of the following:
Stasis: Immobility, CHF, obesity, surgery, ↑ central venous pressure.Endothelial injury: Trauma, surgery, recent fracture, previous DVT.Hypercoagulable states: Pregnancy/postpartum, OCP use, coagulation disorders (e.g., protein C/protein S defciency, factor V Leiden), malignancy, severe burns.
Presents with sudden-onset dyspnea, pleuritic chest pain, low-grade fever, cough, and, rarely, hemoptysis.
Pulmonary embolism:Hypoxia and hypocarbia with resulting respiratory alkalosis.Tachypnea, tachycardia, and fever.Exam may reveal a loud P2 and prominent jugular A waves with right heart failure.
Venous thrombosis: Unilateral swelling; cords on the calf.ABGs: Respiratory alkalosis (2° hyperventilation) with PO2 < 80 mmHg.
CXR: Usually normal, but may show atelectasis, pleural effusion, Hampton’s hump (a wedge-shaped infarct), or Westermark’s sign (oligemia in the affected lung zone).
ECG: Not diagnostic; most commonly reveals sinus tachycardia. The classic triad of S1Q3T3—acute right heart strain with an S wave in lead I, a Q wave in lead III, and an inverted T wave in lead III—is uncommon.
Helical (spiral) CT with IV contrast: Sensitive for pulmonary embolism.
V/Q scan: May reveal segmental areas of mismatch. Results are reported with a designated probability of pulmonary embolism (low, indeterminate, or high) and are interpreted in combination with clinical suspicion.
Angiogram: The gold standard, but more invasive and rarely done today (see Figure 2.15-6).
D-dimer: Sensitive but not specifc in patients at risk for DVT or pulmonary embolism (a useful “rule-out” test in patients with a low clinical suspicion, but it cannot rule out DVT or pulmonary embolism alone in patients with an intermediate or high clinical suspicion of clot).
Venous ultrasound of the lower extremity: Can detect a clot that may have given off the pulmonary embolism. Serial ultrasounds have high diagnostic specif city.
Heparin: Bolus followed by weight-based continuous infusion of unfractioned heparin or low-molecular-weight heparin (LMWH) SQ.
Warfarin: For long-term anticoagulation, usually given for at least six months unless the underlying predisposing factor persists (and is then given indefnitely). Follow INR (goal = 2–3).
IVC filter: Indicated for patients with documented DVT in a lower extremity if anticoagulation is contraindicated or if patients experience recurrent emboli while anticoagulated.
FIGURE 2.15-6.  Pulmonary embolus.A large flling defect in the pulmonary artery is evident on pulmonary angiogram.
Thrombolysis: Indicated only in cases of massive DVT or pulmonary embolism causing right heart failure and hemodynamic instability (contraindicated in patients with recent surgery or bleeding).
DVT prophylaxis: Treat all immobile patients; give SQ heparin, LMWH, intermittent pneumatic compression of the lower extremities (less effective), and early ambulation (most effective).
Often asymptomatic, or patients may present with chronic cough, dyspnea, and shortness of breath. Always inquire about smoking and exposure history.
Serial CXRs: Determine the location, progression, and extent of the nodule.
Chest CT: Determine the nature, extent, and infltrating nature of the nodule.
Characteristics favoring carcinoma: Age > 45–50; smoking history; history of malignancy; new or enlarging (unless very rapidly enlarging) lesions; absence of calcifcation or irregular calcifcation; size > 2 cm; irregular margins.
Lung nodule clues based on the history:Recent immigrant: Think TB.From the southwestern United States: Think coccidioidomycosis.From the Ohio River Valley: Think histoplasmosis.Squamous and Small cell cancers are Central lesions.■Characteristics favoring a benign lesion: Age < 35; no change from old flms; central/uniform/laminated/popcorn calcifcation; size < 2 cm; smooth margins.
Surgical resection is indicated for nodules at high risk for malignancy. Low-risk nodules can be followed with CXR or CT every three months for one year and then every six months for another year. An invasive diagnostic procedure is indicated if the size of the nodule ↑.
The leading cause of cancer death in the United States. Risk factors include tobacco smoke (except for bronchoalveolar carcinoma) and radon or asbestos exposure. Types are as follows:
Small cell lung cancer (SCLC):Highly correlated with cigarette exposure.Central location.Neuroendocrine origin; associated with paraneoplastic syndromes (see Table 2.15-7).Metastases are often found on presentation (intrathoracic and extrathoracic sites such as brain, liver, and bone).
Non–small cell lung cancer (NSCLC): Less likely to metastasize.TAB LE 2.1 5-7. Paraneoplastic Syndromes of Lung CancerAdenocarcinoma: The most common lung cancer; peripheral location. Includes bronchoalveolar carcinoma, which is associated with multiple nodules, interstitial infltration, and prolifc sputum production but is not associated with smoking.
Squamous cell carcinoma: Central location; 98% are seen in smokers.
Large cell/neuroendocrine carcinomas: Least common; associated with a poor prognosis.
Presents with cough, hemoptysis, dyspnea, wheezing, postobstructive pneumonia, chest pain, weight loss, and possible abnormalities on respiratory exam (crackles, atelectasis).
Other f ndings include Horner’s syndrome (miosis, ptosis, anhidrosis) in patients with Pancoast’s tumor at the apex of the lung; superior vena cava syndrome (obstruction of the SVC with supraclavicular venous engorgement); hoarseness (2° to recurrent laryngeal nerve involvement); and many paraneoplastic syndromes (see Table 2.15-7).
CXR or chest CT.Fine-needle aspiration (CT guided) for peripheral lesions and bronchoscopy (biopsy or brushing) for central lesions.
Thoracoscopic biopsy may be performed, with conversion to open thoracotomy if the lesion is found to be malignant.
■ SCLC: Unresectable. Often responds to radiation and chemotherapy initially but always recurs; has a lower median survival rate than NSCLC. Has usually metastasized at the time of diagnosis.
Chemotherapy is the mainstay ■NSCLC: Surgical resection in early stages (IA, IB, IIA, IIB, and possibly IIIA). The extent of resection is based on lesion size; the presence of me-of treatment for small cell tastases; and the patient’s age, general health, and lung function. Supple- lung cancer.
ment surgery with radiation or chemotherapy (depending on the stage). Palliative radiation and/or chemotherapy is appropriate for symptomatic but unresectable disease.
An abnormal accumulation of fluid in the pleural space. Classifed as follows:
Transudate: 2° to ↑ pulmonary capillary wedge pressure (PCWP) or ↓ oncotic pressure.
Exudate: 2° to ↑ pleural vascular permeability.Table 2.15-8 lists the possible causes of both transudates and exudates.
Presents with dyspnea, pleuritic chest pain, and/or cough. Exam reveals dullness to percussion and ↓breath sounds over the effusion. A pleural friction rub may be present.
TABLE 2.15-8. Causes of Pleural EffusionsCHF Cirrhosis Nephrotic syndrome Pneumonia (parapneumonic effusion) TB Malignancy Pulmonary embolism Collagen vascular disease (rheumatoid arthritis, SLE) Pancreatitis Trauma
Complicated parapneumonic effusions necessitate chest tube drainage.Presentation of pneumothorax:CXR shows costophrenic angle blunting.Thoracentesis is indicated for new effusions > 1 cm in decubitus view, except with bilateral effusions and other clinical evidence of CHF.
The effusion is an exudate if it meets Light’s criteria:
The ratio of pleural to serum protein is > 0.5 or
The ratio of pleural to serum LDH is > 0.6 or
Pleural fuid LDH is more than two-thirds the upper normal limit of serum LDH
A parapneumonic effusion is classifed as complicated in the setting of a  Gram stain or culture or a pH < 7.2 (normal is 7.6) or a glucose level of < 60. The presence of pus indicates an empyema.
Treatment is directed toward the underlying condition causing the effusion. Complicated parapneumonic effusions and empyemas require chest tube drainage in addition to antibiotic therapy.
A collection of air in the pleural space that can lead to pulmonary collapse. Subtypes are as follows: 1° spontaneous pneumothorax: 2° to rupture of subpleural apical blebs (usually found in tall, thin young males).
2° pneumothorax: 2° to COPD, TB, trauma, Pneumocystis jiroveci (formerly P. carinii) pneumonia, and iatrogenic factors (thoracentesis, subclavian line placement, positive-pressure mechanical ventilation, bronchoscopy).
Tension pneumothorax: A pulmonary or chest wall defect acts as a one-way valve, drawing air into the pleural space during inspiration but trapping air during expiration. Etiologies include penetrating trauma, infection, and positive-pressure mechanical ventilation. Shock and death result unless the condition is immediately recognized and treated.
Presents with acute onset of unilateral pleuritic chest pain and dyspnea.
Exam reveals tachypnea, diminished or absent breath sounds, hyperresoF IGU R E 2.1 5-7.  Tension pneumothorax.Note the hyperlucent lung feld, hyperexpanded lower diaphragm, collapsed lung, tracheal de viation, mediastinal shift, and compression of the opposite lung on AP CXR.
nance, ↓tactile fremitus, and JVD 2° to compression of the superior vena cava.
■Suspect tension pneumothorax in the presence of tracheal deviation, respiratory distress, falling O2 saturation, hypotension, and distended neck veins.
CXR shows the presence of a visceral pleural line and/or lung retraction from the chest wall (best seen in end-expiratory flms; see Figure 2.15-7).
Small pneumothoraces may resorb spontaneously. Supplemental O2 therapy is helpful.
Large, symptomatic pneumothoraces require chest tube placement.Tension pneumothorax requires immediate needle decompression (second intercostal space at the midclavicular line) followed by chest tube placement.
In hypernatremia, certain patients (e.g., infants, intubated patients, those with a change in mental status) may not drink enough free water to replace insensible losses.
Hypernatremia causes— The 6 D’s Diuresis Dehydration Diabetes insipidus Docs (iatrogenic) Diarrhea Disease (e.g., kidney, sickle cell)
Serum sodium > 145 mEq/L. Usually due to water loss rather than sodium gain.
Presents with thirst (due to hypertonicity) as well as with oliguria or polyuria (depending on the etiology).
Neurologic symptoms include mental status changes, weakness, focal neurologic deficits, and seizures.
Exam reveals “doughy” skin and signs of volume depletion.Assess volume status by conducting a clinical exam and measuring urine volume and osmolality.
Hypertonic Na+ gain: Due to hypertonic saline/tube feeds or ↑aldosterone (suppresses ADH).
Pure water loss: Due to central or nephrogenic diabetes insipidus; characterized by large volumes of dilute urine. Do not neglect dermal and respiratory insensible losses.
Hypotonic f uid loss: Due to ↓ intake, diuretics, intrinsic renal disease, GI losses (diarrhea), burns, and osmotic diuresis (mannitol, glucose in DKA, urea with high protein feeds).
A minimal volume (approximately 500 ml/day) of maximally concentrated urine (> 800 mOsm/kg) suggests adequate renal response without adequate free-water replacement.
Treat the underlying causes and replace free-water deficit with hypotonic saline, D5W, or oral water, depending on volume status.
Correction of chronic hypernatremia (> 36–48 hours) should be accomplished gradually over 48–72 hours (≤ 0.5 mEq/L/hr) to prevent neurologic damage 2° to cerebral edema.
Serum sodium < 135 mEq/L. Almost always due to ↑ ADH.
May be asymptomatic or may present with confusion, lethargy, muscle cramps, hyporeflexia, and nausea.
Can progress to seizures, coma, or brain stem herniation.Hyponatremia can be categorized according to serum and urine osmolality as well as by volume status (i.e., by clinical exam). Osmolality is classified as follows:
High (> 295 mEq/L): Hyperglycemia, hypertonic infusion (e.g., mannitol).Normal (280–295 mEq/L): Hypertriglyceridemia, paraproteinemia (pseudohyponatremia).Hypervolemic hyponatremia is caused by “nephrOSIS, cirrhOSIS, and cardiOSIS.” ■ Low (< 280 mEq/L): Applies to the majority of cases. Hypotonic etiolog ies are listed in Table 2.16-1.
Specific treatments are outlined in Table 2.16-1.Chronic hyponatremia (> 72 hours’ duration) should be corrected slowly (no more than 0.5 mEq/L/hr) in order to prevent central pontine myelinolysis (symptoms include paraparesis/quadriparesis, dysarthria, and coma).
Serum potassium > 5 mEq/L. Etiologies are as follows:Spurious: Hemolysis of blood samples, fist clenching during blood draws, delays in sample analysis, extreme leukocytosis or thrombocytosis.
■↓excretion: Renal insufficiency, drugs (e.g., spironolactone, triamterene, ACEIs, trimethoprim, NSAIDs), hypoaldosteronism, type IV renal tubular acidosis (RTA).
Cellular shifts: Cell lysis, tissue injury (rhabdomyolysis), insulin deficiency, acidosis, drugs (e.g., succinylcholine, digitalis, arginine, β-blockers), exercise.
May be asymptomatic or may present with nausea, vomiting, intestinal colic, aref exia, weakness, flaccid paralysis, and paresthesias.
Confirm hyperkalemia with a repeat blood draw. In the setting of extreme leukocytosis or thrombocytosis, check plasma potassium.
ECG findings include tall, peaked T waves; a wide QRS; PR prolongation; and loss of P waves (see Figure 2.16-1). Can progress to sine waves, ventricular fibrillation, and cardiac arrest.
T AB LE 2.1 6-1. Evaluation and Treatment of Hypotonic Hyponatremia
Consider using hypertonic saline only if a patient has seizures due to hyponatremia, and use it cautiously and brief y. In most instances, normal saline is the best replacement f uid.
What dreaded complication can arise from treating hyponatremia too rapidly? Central pontine myelinolysis.
Hypervolemic Renal failure, nephrotic syndrome, cirrhosis, CHF, hypothyroidism, 2° or 3° adrenal insuff ciency. Water restriction; consider diuretics; cortisol replacement with adrenal insuff ciency; thyroid replacement with hypothyroidism. Euvolemic SIADH, renal failure, drugs, psychogenic polydipsia, oxytocin use. Water restriction. Hypovolemic Diuretics (especially thiazides), vomiting, diarrhea, bleeding, third spacing, dehydration, DKA, 1° adrenal insuff ciency. Replete volume with normal saline.
FIGURE 2.16-1. Hyperkalemia on ECG.Hypokalemia is usually due to renal or GI lossesHypokalemia sensitizes the heart to digitalis toxicity because K+ and digitalis compete for the same sites on the Na+/K+ pump, so if a patient is on digitalis, potassium levels must be carefully monitored.
Electrocardiographic manifestations include peaked T waves, PR prolongation, and a widened
QRS complex. (Reproduced, with permission, from Cogan MG. Fluid and Electrolytes, 1st ed.
Stamford, CT: Appleton & Lange, 1991: 170.)Values of > 6.5 mEq/L or ECG changes (especially PR prolongation or wide QRS) require emergent treatment.
The mnemonic C BIG K summarizes the treatment of hyperkalemia.
First give calcium gluconate for cardiac cell membrane stabilization.Give bicarbonate and/or insulin and glucose to temporarily shift potassium into cells.
β-agonists (e.g., albuterol) promote cellular reuptake of potassium.Eliminate potassium from diet and IV fl uids.Kayexalate to remove potassium from the body.Dialysis is appropriate for patients with renal failure or for severe, refractory cases.
Serum potassium < 3.6 mEq/L. Etiologies are as follows:Transcellular shifts: Insulin, β2-agonists, alkalosis, familial hypokalemic periodic paralysis.GI losses: Diarrhea, chronic laxative abuse, vomiting, NG suction.Renal losses: Diuretics (e.g., loop or thiazide), 1° mineralocorticoid excess or 2° hyperaldosteronism, ↓ circulating volume, Bartter’s and Gitelman’s syndromes, drugs (e.g., gentamicin, amphotericin), DKA, hypomagnesemia, type I RTA (defective distal H+ secretion), polyuria.
Presents with fatigue, muscle weakness or cramps, ileus, hypotension, hyporeflexia, paresthesias, rhabdomyolysis, and ascending paralysis.
Twenty-four-hour or spot urine potassium may distinguish renal from GI losses.
ECG may show T-wave fattening, U waves (an additional wave after the T wave), and ST-segment depression, leading to AV block and subsequent cardiac arrest.
Consider RTA in the setting of metabolic acidosis.Treat the underlying disorder.Oral and/or IV potassium repletion. Do not exceed 20 mEq/L/hr.
Replace magnesium, as this deficiency complicates potassium repletion.Monitor ECG and plasma potassium levels frequently during replacement.Serum calcium > 10.2 mg/dL. The most common causes are hyperparathyroidism and malignancy (e.g., breast cancer, squamous cell carcinoma, multiple myeloma). Other causes are summarized in the mnemonic CHIMPANZEES.
Usually asymptomatic and discovered by routine labs, but may present with bones (osteopenia, fractures), stones (kidney stones), abdominal groans (anorexia, constipation), and psychiatric overtones (weakness, fatigue, altered mental status).
Order a total/ionized calcium, albumin, phosphate, PTH, parathyroid hormone–related peptide (PTHrP), vitamin D, and ECG (may show a short QT interval).
IV hydration followed by furosemide to ↑ calcium excretion.Calcitonin, bisphosphonates (e.g., pamidronate), glucocorticoids, calcimimetics, and dialysis are used for severe or refractory cases. Avoid thiazide diuretics, which ↑ tubular reabsorption of calcium.
Serum calcium < 8.5 mg/dL. Etiologies include hypoparathyroidism (postsurgical, idiopathic), malnutrition, hypomagnesemia, acute pancreatitis, vitamin D deficiency, and pseudohypoparathyroidism. In infants, consider DiGeorge’s syndrome (tetany shortly after birth; absence of thymic shadow).
Presents with abdominal muscle cramps, dyspnea, tetany, perioral and acral paresthesias, and convulsions.
Facial spasm elicited from tapping of the facial nerve (Chvostek’s sign) and carpal spasm after arterial occlusion by a BP cuff (Trousseau’s sign) are classic findings that are most commonly seen in severe hypocalcemia.
Order an ionized Ca2+, Mg+, PTH, albumin, and possibly calcitonin. If the patient is post-thyroidectomy, review the operative note to determine the number of parathyroid glands removed.
ECG may show a prolonged QT interval.Causes of hypercalcemia—Hyperthyroidism Iatrogenic (e.g., thiazides, parenteral (e.g., MEN 1) Excess vitamin A Excess vitamin D Sarcoidosis and other
Loops (furosemide) Lose calcium.A classic case of hypocalcemia is a patient who develops cramps and tetany following thyroidectomy.
Serum calcium may be falsely low in hypoalbuminemia; check ionized calcium.
Treat the underlying disorder.Magnesium repletion.Administer oral calcium supplements; give IV calcium for severe symptoms.
Serum magnesium < 1.5 mEq/L. Etiologies are as follows: ■↓intake: Malnutrition, malabsorption, short bowel syndrome, TPN.
■↑loss: Diuretics, diarrhea, vomiting, hypercalcemia, drugs (e.g., aminoglycosides, amphotericin), alcoholism, kidney losses (e.g., recovering ATN, postobstructive diuresis).
■ Miscellaneous: DKA, pancreatitis, extracellular fluid volume expansion.Symptoms are generally related to concurrent hypocalcemia and hypokalemia; they include anorexia, nausea, vomiting, muscle cramps, and weakness.
In severe cases, symptoms may also include hyperactive refl exes, tetany, paresthesias, irritability, confusion, lethargy, seizures, and arrhythmias.
Labs may show concurrent hypocalcemia and hypokalemia.ECG may reveal prolonged PR and QT intervals.IV and oral supplements.Hypokalemia and hypocalcemia will not correct without magnesium correction.See Figure 2.16-2 for a diagnostic algorithm of acid-base disorders.
A net ↓ in either tubular H+ secretion or HCO3 reabsorption that leads to a non–anion gap metabolic acidosis. There are three main types of RTA; type IV (distal) is the most common form (see Table 2.16-2).
An abrupt ↓ in renal function leading to the retention of creatinine and BUN.
↓ urine output (oliguria, defined as < 500 cc/day) is not required for ARF. ARF is categorized as follows (see also Table 2.16-3):
Prerenal: ↓ renal perfusion.Intrinsic: Injury within the nephron unit.Postrenal: Urinary outflow obstruction. Generally, both kidneys must be obstructed before one can see a significant ↑ in BUN and creatinine.
Alcoholics are the most common patient population with hypomagnesemia.Aspirin (salicylate) overdose can cause both a metabolic acidosis and a respiratory alkalosis.
If an asthmatic patient’s blood gas goes from alkalotic to normal, it can be a sign of respiratory muscle fatigue, which requires urgent intubation.
pH < 7.4 pH > 7.4 Acidosis AlkalosisRespiratory Metabolic Respiratory alkalosis acidosis acidosis with –Hyperventilation compensation –Aspirin ingestion (early) –Chronic lung disease –Opioids, narcotics, sedatives –Weakening of
F IGU R E 2.1 6-2. Diagnostic algorithm for acid-base disorders.
Metabolic alkalosis with compensation –Vomiting –Diuretic use –Antacid use –Hyperaldosteronism
Symptoms of uremia include malaise, fatigue, confusion, oliguria, anorexia, and nausea.
Exam may show a pericardial rub, asterixis, hypertension, ↓ urine output, and an ↑ respiratory rate (compensation of metabolic acidosis or from pulmonary edema 2° to volume overload)
Category-specific symptoms are as follows:Prerenal: Thirst, orthostatic hypotension, tachycardia, ↓ skin turgor, dry mucous membranes, reduced axillary sweating, stigmata of comorbid conditions.
Intrinsic: Associated with a history of drug exposure (aminoglycosides, NSAIDs), infection, or exposure to contrast media or toxins (e.g., myoglobin, myeloma protein). Hematuria or tea-colored urine, foamy urine (from proteinuria), hypertension, and/or edema may also be present.
Atheroemboli: Subcutaneous nodules, livedo reticularis, digital ischemia.Postrenal: Prostatic disease, ↓ urine output leading to suprapubic pain, distended bladder and fl ank pain.
Check serum electrolytes. Examine the urine for RBCs, WBCs, casts (see Table 2.16-4), and urine eosinophils.
An FeNa < 1%, a UNa < 20, a urine specifc gravity > 1.020, or a BUN/Cr ratio > 20 suggests a prerenal etiology.
A urinary catheter and renal ultrasound can help rule out obstruction. Ultrasound can also identify kidneys that are ↓ in size, as occurs with chronic kidney disease.
Patients with ARF may have a normal urine volume.An FeNa < 1% indicates that the kidneys are trying to conserve sodium, suggesting a prerenal etiology.
TABLE 2.16-2. Types of Renal Tubular AcidosisDefect H+ secretion HCO3 – reabsorption Aldosterone def ciency or resistance, leading to defects in Na+ reabsorption and H+ and K+ excretion Serum K+ Low Low High Urinary pH > 5.3 5.3 initially; < 5.3 once serum is acidic < 5.3 Etiologies (most common) Hereditary, cirrhosis, autoimmune disorders (Sjren’s syndrome, SLE), hypercalciuria, sickle cell disease, drugs (lithium, amphotericin) Hereditary (idiopathic or part of syndromes such as Fanconi’s syndrome or cystinosis), drugs (carbonic anhydrase inhibitors), multiple myeloma, amyloidosis, heavy metal poisoning, vitamin D def ciency 1° aldosterone def ciency, hyporeninemic hypoaldosteronism (e.g., from kidney disease, ACEIs, NSAIDs), drugs (e.g., amiloride, spironolactone, heparin), pseudohypoaldosteronism Potassium citrate Potassium citrate Furosemide, mineralocorticoid +/– glucocorticoid replacement, and low-potassium diet in patients with aldosterone def ciency Nephrolithiasis Rickets, osteomalacia Hyperkalemia Treatment Complications
TABLE 2.16-3. Causes of Acute Renal FailureAcute tubular necrosis (ATN) Acute/allergic interstitial nephritis Glomerulonephritis Thromboembolism Renovascular disease (HUS/TTP, scleroderma) Prostatic disease Nephrolithiasis Pelvic tumors Recent pelvic surgery Retroperitoneal f brosis
Hypovolemia (hemorrhage, dehydration, burns) Cardiogenic shock (↓ CO) Systemic vasodilation (sepsis, burns) Anaphylaxis Drugs (ACEIs, ARBs, NSAIDs) Renal artery stenosis Cirrhosis with ascites
T AB LE 2.1 6-4. Findings on Microscopic Urine Examination in Acute Renal Failure
Hyaline casts Normal fnding, but an ↑ amount suggests volume depletion Prerenal Red cell casts, dysmorphic red cells Glomerulonephritis Intrinsic White cells, eosinophils Allergic interstitial nephritis, atheroembolic disease Intrinsic Granular casts, renal tubular cells, “muddy-brown cast” ATN Intrinsic White cells, white cell casts Pyelonephritis Postrenal
In patients with oliguria, the FeNa can help identify prerenal failure and distinguish it from intrinsic renal disease.
Obtain a renal biopsy only when the cause of intrinsic renal disease is unclear.
Balance fluids and electrolytes; avoid nephrotoxic drugs.In acute or allergic interstitial nephritis, adjust or discontinue offending medications.
Dialyze if indicated (see the mnemonic AEIOU) using hemodialysis. Peritoneal dialysis should be considered only for long-term dialysis patients or for patients who are not hemodynamically stable.
Metabolic acidosis; hyperkalemia leading to arrhythmias.Hypertension (from renin hypersecretion).Volume overload leading to CHF and pulmonary edema.Chronic kidney disease may result, requiring dialysis to prevent the buildup of K+, H+, phosphate, and toxic metabolites.
Ingestions (salicylates, theophylline, methanol, barbiturates, lithium, ethylene glycol)Uremic symptoms (pericarditis, encephalopathy, bleeding, nausea, pruritus, myoclonus)Most commonly due to diabetes mellitus (DM), hypertension, and glomerulonephritis. Another commonly tested etiology is polycystic kidney disease (the autosomal-dominant form is more common and is adult onset; the autosomalrecessive form is seen in children).
Generally asymptomatic until GFR < 30, but patients gradually experience the signs and symptoms of uremia (anorexia, nausea, vomiting, uremic pericarditis, “uremic frost,” delirium, seizures, coma).
Common metabolic derangements include the following:Azotemia (↑ BUN and creatinine).Fluid retention (hypertension, edema, CHF, pulmonary edema).Metabolic acidosis.Anemia of chronic disease (↓ erythropoietin production).Hypocalcemia, hyperphosphatemia (↓ phosphate excretion; impaired vitamin D production leading to renal osteodystrophy).
ACEIs/ARBs and hypertension control have been shown to ↓ the progression of CKD.
Additional pharmacotherapy is as follows:Erythropoietin analogs for anemia of chronic disease.Fluid restriction; low Na+/K+/phosphate intake.Oral phosphate binders and calcitriol (1,25-OH vitamin D) for renal osteodystrophy.
Renal replacement therapy includes hemodialysis, peritoneal dialysis, and renal transplantation.
Table 2.16-5 and Figure 2.16-3 summarize the mechanisms of action and side effects of commonly used diuretics.
T AB LE 2.1 6-5. Mechanism of Action and Side Effects of Diuretics
Carbonic anhydrase inhibitors Acetazolamide Proximal convoluted tubule. Inhibit carbonic anhydrase, ↑ H+ reabsorption, block Na+/ H+ exchange. Hyperchloremic metabolic acidosis, sulfa allergy. Osmotic agents Mannitol, urea Entire tubule. ↑ tubular fuid osmolarity. Pulmonary edema due to CHF and anuria. Loop agents Furosemide, ethacrynic acid, bumetanide, torsemide Ascending loop of Henle. Inhibit Na+/K+/2Cl– transporter. Water loss, metabolic alkalosis, ↓ K+, ↓Ca2+, ototoxicity, sulfa allergy (except ethacrynic acid, hyperuricemia). Thiazide agents HCTZ, chlorothiazide Distal convoluted tubule. Inhibit Na+/Cl– transporter. Water loss, metabolic alkalosis, ↓Na+, ↓ K+, ↑ glucose, ↑Ca2+, ↑ uric acid, sulfa allergy, pancreatitis. K+-sparing agents Spironolactone, triamterene, amiloride Cortical collecting tubule. Aldosterone receptor antagonist (spironolactone); block sodium channel (triamterene, amiloride). Metabolic acidosis; ↑ K+; antiandrogenic effects, including gynecomastia (spironolactone).
Glomerulusconvoluted tubule Proximal straight tubule 1 Cortex Outer medulla Diuretics 1 Acetazolamide 2 Osmotic agents (mannitol) 3 Loop agents (e.g., furosemide) 4 Thiazides5 Aldosterone antagonists6 ADH antagonists2 2 2 3 4 5 6 Thin descending limbH2O H2O H2O (+ADH) Inner medulla Loop of Henle Thin ascending limbThick ascending limbNa+ K+ K+ 2Cl−Ca2+ Mg2+ tubule(+PTH) (+aldosterone) ? 4 F IGU R E 2.1 6-3. Overview of diuretics.
(Reproduced, with permission, from Katzung BG. Basic & Clinical Pharmacology, 10th ed. New York: McGraw-Hill, 2007: Fig. 15-1.)
A disorder of glomerular inflammation, also called glomerulonephritis. Proteinuria may be present but is usually < 1.5 g/day. Causes are summarized in Table 2.16-6.
The classic findings are oliguria, macroscopic/microscopic hematuria (teaor cola-colored urine), hypertension, and edema. the patient has hematuria, hypertension, and oliguria.
UA shows hematuria and possibly mild proteinuria.Patients have a ↓ GFR with elevated BUN and creatinine. Complement, ANA, ANCA, and anti-GBM antibody levels should be measured to determine the underlying etiology.
Renal biopsy may be useful for histologic evaluation.T AB LE 2.1 6-6. Causes of Nephritic SyndromeImmune complex Postinfectious glomerulonephritis IgA nephropathy (Berger’s disease) Classically associated with recent group A β-hemolytic streptococcal infection, but can be seen with any infection (usually 2–6 weeks prior). The most common type; associated with upper respiratory or GI infections. Commonly seen in young males; may be seen in Henoch-Schlein purpura. Oliguria, edema, hypertension, teaor cola-colored urine. Episodic gross hematuria or persistent microscopic hematuria. Low serum C3 that normalizes 6–8 weeks after presentation; ↑ASO titer; lumpy-bumpy immunofl uorescence. Normal C3. Supportive. Almost all children and most adults have a complete recovery. Glucocorticoids for select patients; ACEIs in patients with proteinuria. Some 20% of cases progress to end-stage renal disease (ESRD). Pauci-immune Wegener’s granulomatosis Granulomatous inf ammation of the respiratory tract and kidney with necrotizing vasculitis. Fever, weight loss, hematuria, hearing disturbances, respiratory and sinus symptoms. Cavitary pulmonary lesions bleed and lead to hemoptysis. Presence of c-ANCA (cell-mediated immune response). Renal biopsy shows segmental necrotizing glomerulonephritis with few immunoglobulin deposits on immunof uorescence. High-dose corticosteroids and cytotoxic agents. Patients tend to have frequent relapses. Anti-GBH disease Goodpasture’s syndrome Alport’s syndrome Rapidly progressing glomerulonephritis with pulmonary hemorrhage; peak incidence is in males in their mid-20s. Hereditary glomerulonephritis; presents in boys 5–20 years of age. Hemoptysis, dyspnea, possible respiratory failure. Asymptomatic hematuria associated with nerve deafness and eye disorders. Linear anti-GBM deposits on immunof uorescence; iron def ciency anemia; hemosiderin-f lled macrophages in sputum; pulmonary infltrates on CXR. GBM splitting on electron microscopy. Plasma exchange therapy; pulsed steroids. May progress to ESRD. Progresses to renal failure. Anti-GBM nephritis may recur after transplant.
Treat hypertension, fluid overload, and uremia with salt and water restriction, diuretics, and, if necessary, dialysis.
In some cases, corticosteroids are useful in reducing glomerular infl ammation.
Defined as proteinuria (≥ 3.5 g/day), generalized edema, hypoalbuminemia, and hyperlipidemia. Approximately one-third of all cases result from systemic diseases such as DM, SLE, or amyloidosis. Causes are summarized in Table 2.16-7.
TAB LE 2.1 6-7. Causes of Nephrotic SyndromeMinimal change disease The most common cause of nephrotic syndrome in children. Idiopathic etiology; 2° causes include NSAIDs and hematologic malignancies. Tendency toward infections and thrombotic events. Light microscopy appears normal; electron microscopy shows fusion of epithelial foot processes with lipid-laden renal cortices. Steroids; excellent prognosis. Focal segmental glomerulosclerosis Idiopathic, IV drug use, HIV infection, obesity. The typical patient is a young African-American male with uncontrolled hypertension. Microscopic hematuria; biopsy shows sclerosis in capillary tufts. Prednisone, cytotoxic therapy, ACEIs/ARBs to ↓ proteinuria. Membranous nephropathy The most common nephropathy in Caucasian adults. 2° causes includes solid tumor malignancies (especially in patients > 60 years of age) and immune complex disease. Associated with HBV, syphilis, malaria, and gold. “Spike-and-dome” appearance due to granular deposits of IgG and C3 at the basement membrane. Prednisone and cytotoxic therapy for severe disease. Diabetic nephropathy Two characteristic forms: diffuse hyalinization and nodular glomerulosclerosis (Kimmelstiel-Wilson lesions). Generally have long-standing, poorly controlled DM with evidence of retinopathy or neuropathy. Thickened GBM; ↑mesangial matrix. Tight control of blood sugar; ACEIs for type 1 DM and ARBs for type 2 DM.
TAB LE 2.1 6-7. Causes of Nephrotic Syndrome (continued)Lupus nephritis Classifed as WHO types I–VI. Both nephrotic and nephritic. The severity of renal disease often determines overall prognosis. Proteinuria or RBCs on UA may be found during evaluation of SLE patients. Mesangial proliferation; subendothelial and/or subepithelial immune complex deposition. Prednisone and cytotoxic therapy may slow disease progression. Renal amyloidosis 1° (plasma cell dyscrasia) and 2° (infectious or infammatory) are the most common. Patients may have multiple myeloma or a chronic inf ammatory disease (e.g., rheumatoid arthritis, TB). Nodular glomerulosclerosis; EM reveals amyloid f brils; apple-green birefringence with Congo red stain. Prednisone and melphalan. Bone marrow transplant may be used for multiple myeloma. Membrano-proliferative nephropathy Can also be nephritic syndrome. Type I is associated with HCV, cryoglobulinemia, SLE, and subacute bacterial endocarditis. Idiopathic form is present at 8–30 years of age. Slow progression to renal failure. “Tram-track,” double-layered basement membrane. Type I has subendothelial deposits and mesangial deposits; all three types have low serum C3; type II by way of C3 nephritic factor. Corticosteroids and cytotoxic agents may help.
Proteinuria, hypoalbuminemia, edema, hyperlipidemia, and hyperlipiduria in nephrotic syndrome are due to the initial ↑ in permeability of the glomerulus to protein.
Presents with generalized edema and foamy urine. In severe cases, dyspnea and ascites may develop.
Patients have ↑ susceptibility to infection as well as a predisposition to hypercoagulable states with an ↑ risk for venous thrombosis and pulmonary embolism.
UA shows proteinuria (≥ 3.5 g/day) and lipiduria.Blood chemistry shows ↓ albumin (< 3 g/dL) and hyperlipidemia.
Evaluation should include workup for 2° causes.Renal biopsy is used to definitively diagnose the underlying etiology.
■ Treat with protein and salt restriction, judicious diuretic therapy, and antihyperlipidemics.
Immunosuppressant medications may be useful for certain etiologies.ACEIs ↓ proteinuria and diminish the progression of renal disease in patients with renal scarring.
Vaccinate with 23-polyvalent pneumococcus vaccine (PPV23), as patients are at ↑ risk of Streptococcus pneumoniae infection.
Renal calculi. Stones are most commonly calcium oxalate but may also be calcium phosphate, struvite, uric acid, or cystine (see Table 2.16-8 and Figure 2.16-4). Risk factors include a  family history, low f uid intake, gout, medications (allopurinol, chemotherapy, loop diuretics), postcolectomy/ postileostomy, specific enzyme deficiencies, type I RTA (due to alkaline urinary pH and associated hypocitruria), and hyperparathyroidism. Most common in older males.
Presents with acute onset of severe, colicky f ank pain that may radiate to the testes or vulva and is associated with nausea and vomiting.
Patients are unable to get comfortable and shift position frequently (as opposed to those with peritonitis, who lie still).
UA may show gross or microscopic hematuria (85%) and an altered urine pH.
KUB (kidney/ureter/bladder radiography) identifies radiopaque stones but will miss the 10% of stones that are radiolucent.
TABLE 2.16-8.  Types of NephrolithiasisWhich bacteria are associated with “staghorn calculi”? Urease-producing organisms such as Proteus.
Calcium oxalate/ calcium phosphate 83% The most common causes are idiopathic hypercalciuria and 1° hyperparathyroidism. Alkaline urine. Radiopaque. Hydration, dietary sodium and protein restriction, thiazide diuretic. Avoid ↓calcium intake (can lead to hyperoxaluria and an ↑ risk of osteoporosis). Struvite (Mg-NH4 -PO4) or “triple phosphate” 9% Associated with urease-producing organisms (e.g., Proteus). Form staghorn calculi. Alkaline urine. Radiopaque. Hydration; treat UTI if present; surgical removal of staghorn stone. Uric acid 7% Associated with gout, xanthine oxidase defciency, and high purine turnover states (e.g., chemotherapy). Acidic urine (pH < 5.5). Radiolucent. Hydration; alkalinize urine with citrate, which is converted to HCO3 – in the liver; dietary purine restriction and allopurinol. Cystine 1% Due to a defect in renal transport of certain amino acids (COLA—cystine, ornithine, lysine, and arginine). Hexagonal crystals. Radiopaque. Hydration, dietary sodium restriction, alkalinization of urine, penicillamine.
FIGURE 2.16-4. Nephrolithiasis.KUB shows two dense 1-cm calcifications (arrows) projecting over the midportion of the left kidney, consistent with nephrolithiasis. (Reproduced, with permission, from Chen MY, Pope
TL Jr., Ott DJ. Basic Radiology, 1st ed. New York: McGraw-Hill, 2004: 243.)
Noncontrast abdominal CT scans are the gold standard for the diagnosis of kidney stones.
Consider a renal ultrasound to look for obstruction (ultrasound is also preferred for pregnant patients, in whom radiation from CT should be avoided).
An IVP can be used to confirm the diagnosis if there is a lack of contrast filling below the stone.
Hydration and analgesia are the initial treatment.Kidney stones < 5 mm in diameter can pass through the urethra; stones < 3 cm in diameter can be treated with extracorporeal shock-wave lithotripsy (ESWL), percutaneous nephrolithotomy, or retrograde ureteroscopy.
Preventive measures include hydration; additional prophylaxis is dependent on stone composition.
Characterized by the presence of progressive cystic dilation of the renal tubules, as well as by cysts in the spleen, liver, and pancreas. The two major forms are as follows: ■Autosomal dominant (ADPKD):
Most common.Usually asymptomatic until patients are > 30 years of age.
One-half of ADPKD patients will have ESRD requiring dialysis by age 60.
Associated with an ↑ risk of cerebral aneurysm, especially in patients with a  family history.
Autosomal recessive (ARPKD): Less common but more severe. Presents in infants and young children with renal failure, liver fibrosis, and portal hypertension; may lead to death in the first few years of life.
Pain and hematuria are the most common presenting symptoms. Sharp, localized pain may result from cyst rupture, infection, or passage of renal calculi.
Additional findings include hypertension, hepatic cysts, cerebral berry aneurysms, diverticulosis, and mitral valve prolapse.
Patients may have large, palpable kidneys on abdominal exam.Based on ultrasound (most common) or CT scan. Multiple bilateral cysts will be present throughout the renal parenchyma, and renal enlargement will be visualized. Genetic testing by DNA linkage analysis for ADPKD1 and ADPKD2 is available.
Prevent complications and ↓ the rate of progression to ESRD. Early management of UTIs is critical to prevent renal cyst infection. BP control (ACEIs, ARBs) is necessary to ↓ hypertension-induced renal damage.
Dialysis and renal transplantation are used to manage patients with ESRD.
If a patient with known ADPKD develops a sudden-onset, severe headache, you must rule out subarachnoid hemorrhage from a ruptured berry aneurysm!
Dilation of renal calyces. Usually occurs 2° to obstruction of the urinary tract. In pediatric patients, the obstruction is often at the ureteropelvic junction. In adults, it may be due to BPH, tumors, aortic aneurysms, or renal calculi. Can also be caused by high-output urinary flow and vesicoureteral refl ux.
May be asymptomatic, or may present with fl ank/back pain, ↓ urine output, abdominal pain, and UTIs.
■ Ultrasound or CT scan to detect dilation of the renal calyces and/or ureter. ■↑ BUN and creatinine provide evidence of 2° renal failure.
Surgically correct any anatomic obstruction; use laser or sound wave lithotripsy if calculi are causing obstruction.
Ureteral stent placement across the obstructed area of the urinary tract and/or percutaneous nephrostomy tube placement to relieve pressure may be appropriate if the urinary outflow tract is not sufficiently cleared of obstruction. Foley or suprapubic catheters may be required for lower urinary tract obstruction (e.g., BPH).
Left untreated, hydronephrosis resulting from urinary obstruction leads to hypertension, acute or chronic renal failure, or sepsis, and has a very poor prognosis.
A VCUG should be obtained in all boys presenting with their f rst UTI, girls < 3 years of age with their f rst UTI or < 5 years of age with febrile UTI, and older girls with pyelonephritis or recurrent UTIs.
Bringing the testes into the scrotum does not ↓ the risk of testicular cancer.
Retrograde projection of urine from the bladder to the ureters and kidneys. Often caused by insufficient tunneling of the ureters into submucosal bladder tissue, leading to ineffective restriction of retrograde urine flow during bladder contraction. May also be due to posterior urethral valves, urethral or meatal stenosis, or a neurogenic bladder. Classified as follows:
Mild refux (grades I–II): No ureteral or renal pelvic dilation. Often resolves spontaneously.
Moderate to severe refux (grade III–V): Ureteral dilation with associated caliceal blunting in severe cases.
Patients present with recurrent UTIs, typically in childhood. Prenatal ultrasound may identify hydronephrosis.
Obtain a voiding cystourethrogram (VCUG) to detect abnormalities at ureteral insertion sites and to classify the grade of refl ux.
Nuclear renal scan (DMSA or MAG-3) can be used to evaluate for renal function.
Treat infections aggressively. Treat mild reflux with daily prophylactic antibiotics (amoxicillin if < 2 months of age; otherwise TMP-SMX or nitrofurantoin) until refl ux resolves.
Surgery (ureteral reimplantation) is generally reserved for children with persistent high-grade (III to V) reflux or for those with breakthrough pyelonephritis while on prophylaxis. Inadequate treatment can lead to progressive renal scarring and ESRD.
Failure of one or both of the testes to fully descend into the scrotum. Low birth weight is a risk factor.
Bilateral cryptorchidism is associated with prematurity, oligospermia, congenital malformation syndromes (Prader-Willi, Noonan syndromes), and infertility. Associated with an ↑ risk of testicular malignancy.
The testes cannot be manipulated into the scrotal sac with gentle pressure (vs. retractile testes) and may be palpated anywhere along the inguinal canal or in the abdomen.
Orchiopexy by 6–12 months of age (most testes will spontaneously descend by 3 months).
If discovered later, treat with orchiectomy to avoid the risk of testicular cancer.
Table 2.16-9 outlines the etiologies, presentation, diagnosis, and treatment of scrotal swelling.
Found in 10–25% of middle-aged and elderly men. Classified as failure to initiate (e.g., psychological, endocrinologic, neurologic), failure to fill (e.g., arteriogenic), or failure to store (e.g., veno-occlusive dysfunction). Risk factors include DM, atherosclerosis, medications (e.g., β-blockers, SSRIs, TCAs, diuretics), hypertension, heart disease, surgery or radiation for prostate cancer, and spinal cord injury.
Because patients rarely volunteer this complaint, physicians should make a specific inquiry.
Ask about risk factors (diabetes, peripheral vascular disease), medication use, recent life changes, and psychological stressors.
The distinction between psychological and organic ED is based on the presence of nocturnal or early-morning erections (if present, it is nonorganic) and on situation dependence (i.e., occurring with only one partner).
T AB LE 2.1 6-9. Differential Diagnosis of Scrotal Swelling
Painless causes Hydrocele Varicocele Remnant of the processus vaginalis. Dilation of the pampiniform venous plexus (“bag of worms”).
Usually asymptomatic; transilluminates.Asymptomatic or presents with vague, aching scrotal pain. Affects the left testicle more often than the right.
May disappear in the supine position.Does not transilluminate.Lab and radiologic workups are rarely indicated.Obtain an ultrasound if there is concern for inguinal hernia or testicular cancer.
Typically none unless hernia is present or hydrocele persists beyond 12–18 months of age (indicates patent processus vaginalis, which leads to an ↑ risk for inguinal hernia).
If symptomatic or if testis makes up < 40% of total volume, may be treated surgically with a varicocelectomy or ligation, or through embolization via interventional radiology.
T AB LE 2.1 6-9. Differential Diagnosis of Scrotal Swelling (continued )
Infection of the epididymis, usually from STIs, prostatitis, and/or ref ux.
Twisting of the spermatic cord, leading to ischemia and possible testicular infarction.
Typically affects those > 30 years of age; presents with epididymal tenderness, tender/ enlarged testicle(s), fever, scrotal thickening, erythema, and pyuria.
Pain may ↓ with scrotal elevation ( Prehn’s sign).Typically affects those < 30 years of age; presents with intense, acute-onset scrotal pain that remains the same or ↑ with scrotal elevation ( Prehn’s sign).
Pain is often accompanied by nausea/vomiting and/or dizziness.Loss of cremasteric refex is also seen.UA, culture (pyuria). Culture often shows Neisseria gonorrhoeae, E. coli, or Chlamydia.
Doppler ultrasound shows normal to ↑blood fow to testes.Doppler ultrasound shows ↓blood f ow to testes.(If there is a high clinical suspicion for testicular torsion, do not wait for ultrasound and proceed immediately to surgery!)
Antibiotics (tetracycline, f uoroquinolones); NSAIDs; scrotal support for pain.Attempt manual detorsion.Immediate surgery to salvage testis (the testicle is often unsalvageable after six hours of ischemia).
Orchiopexy of both testes to prevent future torsion.“Point and Shoot”: The Parasympathetic nervous system mediates erection; the Sympathetic nervous system mediates ejaculation.
■ Evaluate for neurologic dysfunction (e.g., anal tone, lower extremity sensation) and for hypogonadism (e.g., small testes, loss of 2° sexual characteristics).
Testosterone and gonadotropin levels may be abnormal.Check prolactin levels, as elevated prolactin can result in ↓ androgen activity.
Patients with psychological ED may benefit from psychotherapy or sex therapy involving discussion and exercises with the appropriate partner.
Oral sildenafl (Viagra), vardenafl (Levitra), and tadalaf l (Cialis) are phosphodiesterase-5 (PDE5) inhibitors that result in prolonged action of cGMP-mediated smooth muscle relaxation and ↑ blood flow in the corpora cavernosa.
Testosterone is a useful therapy for patients with hypogonadism of testicular or pituitary origin; it is discouraged for patients with normal testosterone levels.
Vacuum pumps, intracavernosal prostaglandin injections, and surgical implantation of semirigid or inflatable penile prostheses are alternatives for patients who fail PDE5 therapy.
Enlargement of the prostate that is a normal part of the aging process and is seen in > 80% of men by age 80. Most commonly presents in men > 50 years of age. BPH can result in urinary retention, recurrent UTIs, bladder and renal calculi, hydronephrosis, and kidney damage over time.
Obstructive symptoms: Hesitancy, weak stream, intermittent stream, incomplete emptying, urinary retention, bladder fullness.
Irritative symptoms: Nocturia, daytime frequency, urge incontinence, opening hematuria.On DRE, the prostate is uniformly enlarged with a rubbery texture. If the prostate is hard or has irregular lesions, cancer should be suspected.
Conduct a DRE to screen for masses; if findings are suspicious, evaluate for prostate cancer.
Obtain a UA and urine culture to rule out infection and hematuria.
Measure creatinine levels to rule out obstructive uropathy and renal insufficiency.
PSA testing and cystoscopy are not recommended for longitudinal BPH monitoring.
Medical therapy includes α-blockers (e.g., terazosin), which relax smooth muscle in the prostate and bladder neck, as well as 5α-reductase inhibitors (e.g., finasteride), which inhibit the production of dihydrotestosterone.
Transurethral resection of the prostate (TURP) or open prostatectomy is appropriate for patients with moderate to severe symptoms.
The most common cancer in men and the second leading cause of cancer death in men (after lung cancer). Risk factors include advanced age and a family history.
Usually asymptomatic, but may present with obstructive urinary symptoms (e.g., urinary retention, a ↓ in the force of the urine stream) as well as with lymphedema due to obstructing metastases, constitutional symptoms, and back pain due to bone metastases.
DRE may reveal a palpable nodule or an area of induration. Early carcinoma is usually not detectable on exam.
A tender prostate suggests prostatitis.What drugs are an absolute contraindication to sildenaf l? Nitrates (the combined effect of ↓ BP can lead to myocardial ischemia).
BPH most commonly occurs in the central (periurethral) zone of the prostate and may not be detected on DRE.
The major side effect of α-blockers is orthostatic hypotension.Leading causes of cancer death in men: 1. Lung cancer 2. Prostate cancer 3. Colorectal cancer 4. Pancreatic cancer 5. Leukemia
An elevated PSA may be due to BPH, prostatitis, UTI, prostatic trauma, or carcinoma.
An annual DRE after age 50 is the recommended screening method for prostate cancer.
Suggested by clinical findings and/or a markedly ↑PSA (> 4 ng/mL).
Definitive diagnosis is made with ultrasound-guided transrectal biopsy, which typically shows adenocarcinoma.
Tumors are graded by the Gleason histologic system, which sums the scores (from 1 to 5) of the two most dysplastic samples (10 is the highest grade).
Look for metastases with CXR and bone scan (metastatic lesions show an osteoblastic or ↑ bone density). Fully 40% of patients present with metastatic disease at diagnosis.
Treatment is controversial, as many cases of prostate cancer are slow to progress. Treatment choice is based on the aggressiveness of the tumor and the patient’s mortality risk.
Watchful waiting may be the best approach for elderly patients with low-grade tumors.
Radical prostatectomy and radiation therapy (e.g., brachytherapy or external beam) are associated with an ↑ risk of incontinence and/or impotence.
PSA, while controversial as a screening test, is used to follow patients post-treatment to evaluate for disease recurrence.
Treat metastatic disease with androgen ablation (e.g., GnRH agonists, orchiectomy, flutamide) and chemotherapy.
All males > 50 years of age should have an annual DRE. Screening should begin earlier in African-American males and in those with a first-degree relative with prostate cancer.
Screening with PSA is common, but its utility remains controversial.
The second most common urologic cancer and the most frequent malignant tumor of the urinary tract; usually a transitional cell carcinoma. Most prevalent in males during the sixth and seventh decades. Risk factors include smoking, diets rich in meat and fat, schistosomiasis, chronic treatment with cyclophosphamide, and occupational exposure to aniline dye (a benzene derivative).
Gross hematuria is the most common presenting symptom.Other urinary symptoms, such as frequency, urgency, and dysuria, may also be seen, but most patients are asymptomatic in the early stages of disease.
Cystoscopy with biopsy is diagnostic.UA often shows hematuria (macroor microscopic); cytology may show dysplastic cells.
IVP can examine the upper urinary tract as well as defects in bladder filling.
■MRI, CT, and bone scan are important tools with which to define invasion and metastases.
Treatment depends on the extent of spread beyond the bladder mucosa.
Carcinoma in situ: Intravesicular chemotherapy.Superf cial cancers: Complete transurethral resection or intravesicular chemotherapy with mitomycin-C or BCG (the TB vaccine).
Large, high-grade recurrent lesions: Intravesicular chemotherapy.Invasive cancers without metastases: Radical cystectomy or radiotherapy for patients who are deemed poor candidates for radical cystectomy as well as for those with unresectable local disease.
Invasive cancers with distant metastases: Chemotherapy alone.An adenocarcinoma from tubular epithelial cells (~80–90% of all malignant tumors of the kidney). Tumors can spread along the renal vein to the IVC and can metastasize to lung and bone. Risk factors include male gender, smoking, obesity, acquired cystic kidney disease in ESRD, and von Hippel– Lindau disease.
Presenting signs include hematuria, f ank pain, and a palpable f ank mass. Metastatic disease can present with weight loss and malaise.
Many patients have fever or other constitutional symptoms. Left-sided varicocele may seen in males (due to tumor blockage of the left gonadal vein, which empties into the left renal vein; the right gonadal vein empties directly into the IVC).
Anemia is common at presentation, but polycythemia due to ↑ erythropoietin production may be seen in 5–10% of patients.
Ultrasound and/or CT to characterize the renal mass (usually complex cysts or solid tumor).
Surgical resection may be curative in localized disease.Response rates from radiation or chemotherapy are only 15–30%. Newer tyrosine kinase inhibitors (sorafenib, sunitinib), which ↓ tumor angiogenesis and cell proliferation, have shown promising results and have recently been approved by the FDA for the treatment of renal cell carcinoma.
The classic triad of renal cell carcinoma is hematuria, f ank pain, and a palpable f ank mass, but only 5–10% present with all three components of the triad.
A heterogeneous group of neoplasms. Some 95% of testicular tumors derive from germ cells, and virtually all are malignant. Cryptorchidism is associated with an ↑ risk of neoplasia in both testes. Klinefelter’s syndrome is also a risk factor. Testicular cancer is the most common malignancy in males 15–34 years of age.
β-hCG in men = choriocarcinoma.Patients most often present with painless enlargement of the testes.
Most testicular cancers occur between ages 15 and 30, but seminomas have a peak incidence between 40 and 50 years of age.
Testicular ultrasound.CXR and abdominal/pelvic CT to evaluate for metastasis.Tumor markers are useful for diagnosis and in monitoring treatment response.
β-hCG is always elevated in choriocarcinoma and is elevated in 10% of seminomas.
α-fetoprotein (AFP) is often elevated in nonseminomatous germ cell tumors, particularly endodermal sinus (yolk sac) tumors. It is also elevated in hepatocellular carcinoma, hepatoblastoma, and neuroblastoma.
Radical orchiectomy.Seminomas are exquisitely radiosensitive and also respond to chemotherapy.Platinum-based chemotherapy is used for nonseminomatous germ cell tumors.The steps underlying the acute management of a trauma patient can be remembered with the mnemonic ABCDE. Establishing airway patency takes precedence over all other treatment, followed by providing respiratory support and treating conditions that impair respiration, followed in turn by providing circulatory support and treating conditions that impair circulation.
Start with supplemental O2 by nasal cannula or face mask for conscious patients. Use a jaw-thrust maneuver to reposition the tongue in an unconscious patient. A chin-lift maneuver can be used as a last resort but should be avoided where possible, as it requires movement of the potentially unstable C-spine. An oropharyngeal or nasopharyngeal airway may facilitate bag-mask ventilation.
Perform intubation in patients with apnea, significantly depressed mental status (Glasgow Coma Scale [GCS] < 8), or impending airway compromise (e.g., significant maxillofacial trauma or inhalation injury in fires).
Perform a surgical airway (cricothyroidotomy) in patients who cannot be intubated or in whom there is significant maxillofacial trauma, making intubation impractical.
Maintain cervical spine stabilization/immobilization in trauma patients until the spine is appropriately cleared through exam and radiographic studies. However, never allow this concern to delay airway management.
Thorough cardiac and pulmonary exams will identify the five thoracic causes of immediate death: tension pneumothorax, cardiac tamponade, open pneumothorax, massive hemothorax, and airway obstruction.
If tension pneumothorax (absent breath sounds on the affected side in combination with shock and hypoxemia) is identified, immediate needle decompression is needed. This is accomplished by placing a 16to 18-gauge angiocatheter into the second intercostal space at the midclavicular line, followed by placement of a chest tube.
If open pneumothorax is identified, an occlusive dressing must be applied immediately. This must be secured on three sides only to prevent the development of tension pneumothorax.
Massive hemothorax is diagnosed through chest tube placement and is defined as > 1000 cc of immediate blood return or > 200/hour for > 2–4 hours. The treatment for massive hemothorax is volume resuscitation followed by surgery to repair the site of bleeding. The treatment for flail chest is supportive, followed by surgical fixation of the chest wall.
Apply direct pressure to any actively bleeding wounds.Place a 16-gauge IV in each antecubital fossa.Isotonic fluids (LR or NS) are repleted in a 3:1 ratio (fluid to blood loss). Start with a fluid bolus of 1–2 L in adults; then recheck vitals and continue repletion as indicated.
If the patient remains tachycardic or hypotensive after the first 2 L of isotonic fluid, transfusion with packed RBCs may be indicated.
To remember the Glasgow Coma Scale, think 4-eyes, Jackson-5, V6 engine. Four points can be assigned for eye response, five points for verbal response, and six points for motor response.
Patients with chest trauma and shock may have cardiac tamponade. The relevant signs are JVD, hypotension, and muffled heart sounds. This can be diagnosed with bedside ultrasound. If tamponade is diagnosed, an immediate pericardiocentesis is necessary.
Disability (CNS dysfunction) is assessed and quantified with the GCS.
Exposure requires that the patient be completely disrobed and assessed for injury and temperature status on both the front and back of the body. Hypothermia is a common problem in trauma and can worsen bleeding; once the exam is done, the patient should be covered with warm blankets.
Once the patient is stable, conduct a full examination.For unstable patients with suspected hemoperitoneum or tamponade, do a focused abdominal sonography for trauma (FAST) scan. Four spaces are checked for blood: between the right kidney and liver (Morrison’s pouch), between the left kidney and spleen (the splenorenal recess), posterior to the bladder (the pouch of Douglas), and in the pericardium. Hemoperitoneum requires immediate surgical consultation for operative management; hemopericardium requires immediate pericardiocentesis.
Radiology studies should be ordered on the basis of the patient assessment. A CXR is needed for all patients with thoracic trauma, and a head CT should be ordered for all patients with loss of consciousness or depressed mental status. A C-spine CT is needed for all patients with neck pain or tenderness, neurologic findings, or depressed mental status.
After urethral injury has been ruled out, place a Foley catheter if it is necessary to monitor urine output (e.g., in hemodynamically unstable patients, patients receiving fluid resuscitation, or patients undergoing major surgery).
Pertinent labs should be ordered based on the mechanism of injury, suspicion of intoxication or OD, and past medical history.
A rough estimate of SBP can be made on the basis of palpated pulses. Carotids correspond roughly to an SBP of 60 mmHg, femorals to an SBP of 70 mmHg, and radials to an SBP of 80 mmHg.
The evaluation and treatment of penetrating trauma depend on the location and extent of the injury.
Intubate early.Immediate surgical exploration is mandatory for patients with shock and active ongoing hemorrhage from neck wounds.
All wounds that violate the platysma are considered true penetrating neck trauma. The neck is divided into three zones, and treatment varies according to which zone is injured (see Figure 2.17-1).
Diagnostic workup is individualized based on the location of the wound, suspected injuries, and the preference of the trauma surgeon. Appropriate tests may include angiography of the aorta and carotid/cerebral arteries, CT scan of the neck with or without CT angiography, Doppler ultrasound, contrast esophagography, esophagoscopy, or bronchoscopy.
Immediately evaluate trauma patients for tension pneumothorax, cardiac tamponade, open pneumothorax, massive hemothorax, fl ail chest, and airway obstruction.
FIGURE 2.17-1. Zones of the neck.(Reproduced, with permission, from Way LW. Current Surgical Diagnosis & Treatment, 10th ed. Stamford, CT: Appleton & Lange, 1994: 223.)
Unstable patients with penetrating thoracic injuries require immediate intubation followed by assessment and treatment of the life-threatening injuries described above. Empiric placement of bilateral chest tubes may be needed if the precise nature of injury is unclear.
Open thoracotomy may be indicated for patients with penetrating chest trauma leading to cardiac arrest, provided that the patient arrested in the ED or shortly before arrival.
Leave any impaled objects in place until the patient is taken to the OR, as such objects may tamponade further blood loss.
Beware of tension pneumothorax, open pneumothorax, massive hemothorax, flail chest, cardiac tamponade, aortic disruption, diaphragmatic tear, and esophageal injury.
If a previously stable chest trauma patient suddenly dies, suspect air embolism.
A new diastolic murmur after chest trauma suggests aortic dissection.
The absence of pain does not rule out an abdominal injury.
Gunshot wounds usually require immediate exploratory laparotomy, although stable patients can be managed conservatively in select cases.
Stab wounds in a hemodynamically unstable patient or in a patient with peritoneal signs or evisceration require immediate exploratory laparotomy.
Stab wounds in a hemodynamically stable patient warrant a CT or FAST scan followed by close inpatient observation.
■Complete neurovascular assessment is critical; check pulses, motor function, and sensory function.
Arteriography and surgical management are required for patients with suspected vascular injuries.
Nerve injuries generally require surgical repair.Early wound irrigation and tissue debridement, not antibiotic therapy, are the most important steps in the treatment of contaminated wounds. However, do administer antibiotics and tetanus prophylaxis.
A rapid deceleration head injury causes coup-contrecoup injuries, in which a bleed is noted both at the site of impact and across from the point of impact.
Epidural hematomas: Lenticular in shape on head CT. Bleed is from the medial meningeal artery (the higher arterial pressure is able to push the dura away from the skull, causing the lens shape on imaging). These bleeds cannot cross suture lines but can expand rapidly and cause herniation and death. Patients classically have loss of consciousness immediately after the injury and then have a “lucid interval” after which they become comatose.
Subdural hematomas: Follow the curve of the skull and result from shearing of the dural bridging veins. These bleeds can cross suture lines. In a pediatric patient, a subdural hematoma coupled with retinal hemorrhages constitutes child abuse until proven otherwise. These bleeds accumulate more slowly than epidural hematomas but can still cause death. They may present acutely (immediate), subacutely (days), or chronically (weeks).
The classic cause is a rapid deceleration injury (e.g., high-speed motor vehicle accidents, ejection from vehicles, and falls from heights). Since complete aortic rupture is rapidly fatal (85% die at the scene), patients with aortic disruption who are seen in the ED usually have a contained hematoma within the adventitia. Laceration is most common just proximal to the ligamentum arteriosum.
Immediate CXR reveals a widened mediastinum (> 8 cm), loss of aortic knob, pleural cap, deviation of the trachea and esophagus to the right, and depression of the left main stem bronchus.
CT evaluation and/or transesophageal echocardiography (TEE) prior to surgery.Aortography is the gold standard for evaluation.Basic trauma management (ABCs); emergent surgery for defect repair.■Three or more adjacent ribs fractured at two points, causing paradoxical inward movement of the flail segment with inspiration.
Other signs of suspected child abuse are spiral fractures in the limbs, bucket-handle fractures, bruises, and rib fractures.
Marfan’s syndrome, syphilis, and Ehlers-Danlos syndrome all predispose to a weak aortic wall.
Aortic disruption is often associated with first and second rib, scapular, and sternal fractures.
Kehr’s sign: Referred shoulder pain due to diaphragmatic irritation (classically on the left due to spleen rupture).
Hx/PE: Presents with crepitus and abnormal chest wall movement. Abnormal chest wall movement may not be appreciated if the patient is splinting because of pain.
Dx: Primarily clinical, although CXR, O2 saturation, and blood gases may help.
Tx: O2, narcotic analgesia. Respiratory support, including intubation and mechanical ventilation, may be needed to treat hypoxemia in severe cases. Surgical fixation of the chest wall is generally needed.
Cx: Respiratory compromise is a complication due to underlying pulmonary contusion.
The spleen and liver are the most commonly injured organs following blunt abdominal trauma. Symptoms are consistent with signs of blood loss and include hypotension, tachycardia, and peritonitis. Suspect spleen or liver injury when lower rib fractures are present.
Pancreatic rupture should be suspected after a direct epigastric blow (handlebar injury).
Diaphragmatic rupture may occur with blunt or penetrating trauma. It is difficult to diagnose and often missed. Kehr’s sign may be present; radio-graphs may demonstrate abdominal viscera in the thorax.
The kidneys are the most commonly injured GU organ in trauma, with injuries including renal contusion, laceration, fracture, and pedicle injury.
In hemodynamically stable patients, abdominal blunt trauma can be diagnosed with FAST scan (see the 2° Survey section), CT scan, and serial abdominal exams.
In hemodynamically unstable patients, abdominal blunt trauma should be treated with immediate exploratory laparotomy to look for organ injury or intra-abdominal bleeding.
Most commonly occur after high-speed traumas such as motor vehicle accidents or falls from heights. Require immediate attention by the orthopedist owing to their life-threatening potential.
May present with an unstable pelvis upon compression.Pelvic x-rays may confirm the fracture; in a stable patient, a CT scan of the pelvis will better define the extent of injury.
If hypotension and shock are present, an exsanguinating hemorrhage is likely. In the field, MAST (military antishock trousers; rarely used today) can be used to maintain adequate BP and organ perfusion.
Consider embolization of bleeding vessels, emergent external pelvic fixation, or, in a hemodynamically stable patient, internal fixation. Give blood early. Hemorrhage results in death in 50% of patients.
Pelvic injuries can be associated with urethral injury. It is suggested by blood at the urethral meatus; a high-riding, “ballotable” prostate; or lack of a prostate.
If present, a retrograde urethrogram must be performed to rule out injury before a Foley catheter is placed.
Never explore a pelvic or retroperitoneal hematoma. Follow with serial hemoglobin and hematocrit.
Table 2.17-1 summarizes the basic management of cardiac arrhythmias in an acute setting.
T AB LE 2.1 7 -1. Management of Cardiac Arrhythmiasa,b
Updated in 2005, CPR is 30 compressions to every two breaths for all arrest victims after puberty.
Unsynchronized shock with 360 J → 360-J shock → epinephrine → 360-J shock →amiodarone or lidocaine → 360-J shock → epinephrine.
Vasopressin may be given in place of the frst or second dose of epinephrine. Amiodarone, lidocaine, procainamide, or sotalol may be used for stable ventricular tachycardia.
Epinephrine or vasopressin; simultaneously search for the underlying cause (see the 5 H’s and 5 T’s mnemonic) and provide empiric treatment. Give atropine for bradycardic PEA only.
If unstable, perform synchronized electrical cardioversion.If stable, control rate with vagal maneuvers (Valsalva maneuver, carotid sinus massage, or cold stimulus).
If resistant to maneuvers, give up to three doses of adenosine followed by other AV-nodal blocking agents (calcium channel blockers [CCBs] or β-blockers).
If unstable, perform synchronized electrical cardioversion starting at 100 J.
If stable, control rate with diltiazem or β-blockers and anticoagulate if duration is > 48 hours.
Elective cardioversion may be performed if duration is < 48 hours; otherwise, the clinician must anticoagulate or perform TEE prior to conversion.
Do not give nodal blockers if there is evidence of Wolff-Parkinson-White syndrome (δ waves) on ECG.
If symptomatic, give atropine and consider dopamine, epinephrine, and glucagon.
If Mobitz II or third-degree heart block is present, place transcutaneous pacemaker pads, and have atropine at the bedside. A temporary transvenous pacemaker may be required for hemodynamically unstable patients.
a In all cases, disruptions of CPR should be minimized. After a shock or administration of a drug, CPR should be resumed immedi ately, and fve cycles of CPR should be given before checking for a pulse or rhythm.
b Doses of electricity listed above assume a monophasic defbrillator. Maximum energy output on more modern biphasic def brilla tors is usually 150–200 J.
Asystole Epinephrine and atropine. Ventricular fbrillation or pulseless ventricular tachycardia Pulseless electrical activity (PEA) Supraventricular    tachycardia (SVT) Atrial f brillation/f utter Bradycardia
Possible causes of PEA—The 5 H’s and 5 T’sHypovolemia Hypoxia Hydrogen ion: Acidosis Hyper/Hypo: K+, other metabolic Hypothermia Tablets: Drug OD, ingestion Tamponade: Cardiac Tension pneumothorax Thrombosis: Coronary Thrombosis: Pulmonary
Acute-onset abdominal pain has many potential etiologies and may require immediate medical or surgical intervention. Sharp, focal pain generally implies a parietal (peritoneal) etiology; dull, diffuse pain is commonly of visceral (organ) origin. Figure 2.17-2 identifies the common causes of acute abdomen.
Obtain a complete history, including the elements indicated in the mnemonic OPQRST.
Obtain a full gynecologic history for females (including last menstrual period, pregnancy, and any STD symptoms). If a female has abdominal pain with cervical motion tenderness, there should be a low threshold to treat for pelvic inflammatory disease (PID).
Perforation leads to sudden onset of diffuse, severe pain, usually with abdominal rigidity on exam.
Obstruction leads to acute onset of severe, radiating, colicky pain. Patients may complain of obstipation or bilious emesis.
Infl ammation leads to gradual onset (over 10–12 hours) of constant, illdefined pain.
Associated symptoms include the following: ■Anorexia, nausea, vomiting, changes in bowel habits, hematochezia, and melena suggest GI etiologies.
Rapid onset of severe,Abrupt, excruciating pain ulcer Mesenteric thrombosis,Intermittent, colicky pain,Gradual, steady pain crescendo with free intervalsAcute cholecystitis, acute cholangitis,Small bowelAppendicitis,FIGURE 2.17-2.  Acute abdomen.The location and character of pain are helpful in the differential diagnosis of the acute abdomen. (Reproduced, with permission, from Way LW. Current Surgical Diagnosis & Treatment, 10th ed. Stamford, CT: Appleton & Lange, 1994: 444.)
Fever and cough suggest pneumonia.Hematuria, pyuria, and costovertebral angle tenderness point to a GU etiology.
If associated with meals, consider mesenteric ischemia, PUD, biliary disease, pancreatitis, or bowel pathology.
A family history of abdominal pain may indicate familial Mediterranean fever or acute intermittent porphyria.
If peritoneal signs, shock, or impending shock is present, emergent exploratory laparotomy is necessary. A positive β-hCG in the setting of shock is a ruptured ectopic pregnancy until proven otherwise. Abdominal pain plus syncope or shock in an older patient is a ruptured abdominal aortic aneurysm (AAA) until proven otherwise.
If the patient is stable, a complete physical exam—including a rectal exam and, in women, a pelvic exam—is mandatory.
Obtain electrolytes, LFTs, amylase, lipase, urine or serum β-hCG, UA, and a CBC with differential.
Consider a CXR for suspected perforation or pulmonary pathology. AXR may be useful for obstruction, but CT is more sensitive and specific. CT is used to diagnose appendicitis, diverticulitis, abscess, renal stones, AAA, obstruction, and other pathology. Ultrasound is the best tool for diagnosing gallstones and gynecologic pathology. Bedside ultrasound (FAST and aortic views) can diagnose hemoperitoneum and AAA in unstable patients.
Hemodynamically unstable patients must have emergent surgical management.In stable patients, expectant management may include NPO status, NG tube placement, IV fluids, placement of a Foley catheter (to monitor urine output and fluid status), and vital sign monitoring with serial abdominal exams and serial labs.
Give broad-spectrum antibiotics to all patients with perforation or signs of sepsis. Antibiotics may also be indicated for patients with infectious processes such as cholecystitis, diverticulitis, and pyelonephritis.
Type and cross all unstable patients.The inciting event is obstruction of the appendiceal lumen with subsequent inflammation and infection. Rising intraluminal pressure leads to vascular compromise of the appendix, ischemia, necrosis, and possible perforation. Etiologies include hypertrophied lymphoid tissue (55–65%), fecalith (35%), foreign body, tumor (e.g., carcinoid tumor), and parasites. Incidence peaks in the early teens (most patients are between 10 and 30 years of age), and the male-to-female ratio is 2:1.
Presents with dull periumbilical pain lasting 1–12 hours that leads to sharp RLQ pain at McBurney’s point.
Also presents with nausea, vomiting, anorexia (“hamburger sign”), and low-grade fever.
Psoas, obturator, and Rovsing’s signs are insensitive tests that may be .
If the patient remembers the exact moment of pain onset, think perforation.
Pneumonia can present as right or left upper quadrant abdominal pain.
All female patients with an acute abdomen require a pelvic exam and a pregnancy test to rule out PID, ectopic pregnancy, and ovarian torsion.
McBurney’s point is located one-third of the distance from the anterior superior iliac spine to the umbilicus.
“Hamburger sign”: If a patient wants to eat, consider a diagnosis other than appendicitis. Anorexia is 80% specific for appendicitis.
Psoas sign: Passive extension of the hip leading to RLQ pain.
Obturator sign: Passive internal rotation of the fl exed hip leading to RLQ pain.
Rovsing’s sign: Deep palpation of the LLQ leading to RLQ pain.
In perforated appendix, partial pain relief is possible, but peritoneal signs (e.g., rebound, guarding, hypotension, ↑ WBC count, fever) will ultimately develop.
Children, the elderly, pregnant women, and those with retrocecal appendices may have atypical presentations that may result in misdiagnosis and ↑ mortality.
Diagnosed by clinical impression.Look for fever, mild leukocytosis (11,000–15,000 cells/μL) with left shift, and UA with a few RBCs and/or WBCs.
If the clinical diagnosis is unequivocal, no imaging studies are necessary. Otherwise, studies include the following:
KUB: Fecalith or loss of psoas shadow.Ultrasound: Enlarged, noncompressible appendix.CT scan with contrast (95–98% sensitive): Periappendiceal stranding or fluid; enlarged appendix.
The patient should be NPO and should receive IV hydration and antibiotics with anaerobic and gram-coverage.
Immediate open or laparoscopic appendectomy is the definitive treatment. If appendicitis is not found, complete exploration of the abdomen is performed.
Perforation: Administer antibiotics until the patient is afebrile with a normalized WBC count; the wound should be closed by delayed 1° closure.
Abscess: Treat with broad-spectrum antibiotics and percutaneous drainage; an elective appendectomy should be performed 6–8 weeks later.
The second leading cause of death in children. Serious burn patients should be treated in an ICU setting. Burns can be chemical, electrical, or thermal and are categorized by depth of tissue destruction:
First degree: Only the epidermis is involved. The area is painful and erythematous, but blisters are not present, and capillary refill is intact. Looks like a sunburn.
Second degree: The epidermis and partial thickness of the dermis are involved. The area is painful, and blisters are present.
Third degree: The epidermis, the full thickness of the dermis, and potentially deeper tissues are involved. The area is painless, white, and charred.
Patients may present with obvious skin wounds, but significant deep destruction may not be visible, especially with electrical burns.
Conduct a thorough airway and lung exam to assess for inhalation injury.
Always assume carbon monoxide poisoning in patients with inhalation injury.
Consider cyanide poisoning in closed-space fires with burning carpets and textiles.
Assess the ABCs. If airway compromise is impending, intubate.Be vigilant for shock, inhalation injury, and carbon monoxide poisoning. Obtain a CXR and a carboxyhemoglobin level.
Evaluate the percentage of body surface area (% BSA) involved.
Supportive measures; tetanus, stress ulcer prophylaxis, and IV narcotic analgesia.
For secondand third-degree burns, fluid repletion using the Parkland formula is critical; adjust repletion on the basis of additional insensible losses to maintain at least 1 cc/kg/hr of urine output.
Topical silver sulfadiazine and mafenide may be used prophylactically; however, there is no proven benefit associated with the use of PO/IV antibiotics or corticosteroids.
Shock and superinfection, with the latter most likely due to Pseudomonas or gramcocci.
Criteria for transfer to a burn center include the following:
Full-thickness burn > 5% of BSA.Partial-thickness burn > 10% BSA.Any fullor partial-thickness burn over critical areas (face, hands, feet, genitals, perineum, major joints).
Circumferential burns; chemical, electrical, or lightning injury; inhalation injury.Any special psychosocial or rehabilitative care needs.Use the “rule of 9’s” to estimate % BSA in adults:
Parkland formula: Fluids for the first 24 hours = 4 ×patient’s weight in kg × % BSA. Give 50% of fl uids over the first eight hours and the remaining 50% over the following 16 hours.
The 5 W’s of postoperative fever:Wind: Atelectasis,Occurs in 40% of all postoperative patients. Remember the mnemonic “Wind, Water, Wounds, Walking, and Wonder drugs.” ■↓ the risk of postoperative fever with incentive spirometry, preand postoperative antibiotics when indicated, short-term Foley catheter use, early ambulation, and DVT prophylaxis (e.g., anticoagulation, compression stockings).
Fevers before postoperative day 3 are unlikely to be infectious unless Clostridium or β-hemolytic streptococci are involved.
pneumonia Water: UTI Wounds: Wound infection, abscess Walking: DVT Wonder drugs: Drug ■A body temperature < 95° F (35° C) accompanied by mental status and neurologic deficits.
TABLE 2.17-2.  Types of ShockHypovolemic Trauma, blood loss, dehydration with inadequate f uid repletion, third spacing, burns. ↓↓↑Replete with isotonic solution (e.g., LR or NS) and blood in a 3:1 (f uid-to-blood) ratio. Cardiogenic CHF, arrhythmia, structural heart disease (severe mitral regurgitation, VSD), Ml (> 40% of left ventricular function). ↓↑↑Identify the cause and treat if possible. Give inotropic support with pressors such as dopamine (if hypotensive) or dobutamine (if not hypotensive). Obstructive Cardiac tamponade, tension pneumothorax, massive pulmonary embolism. ↓↑↑Treat the underlying cause: pericardiocentesis, decompression of pneumothorax, thrombolysis. Bacteremia, especially gram-organisms. ↑↓↓Administer broad-spectrum antibiotics. Measure central venous pressure (CVP) and give fuid until CVP = 8. Then give pressors (dopamine or norepinephrine). Obtain cultures prior to administration of antibiotics if possible. Bee stings, medication, food allergies. ↑↓↓Give diphenhydramine. If severe, administer 1:1000 epinephrine. a PCWP = pulmonary capillary wedge pressure. b PVR = peripheral vascular resistance.
Remove the patient from the cold or windy environment and remove wet clothing. In mild cases, rewarm the patient with blankets or warm water. In more severe cases, the patient may need a heating blanket, warmed oxygen, or warm IV fluids. In unstable patients, invasive rewarming may be necessary (e.g., NG or bladder lavage, pleural lavage, or cardiac bypass). If the patient has frostbite, thaw the affected areas with the same methods. Patients will need narcotic analgesia for thawing.
Monitor the ECG for arrhythmias such as bradycardia and slow atrial fibrillation. The stereotypic sign is the J wave (aka Osborn wave). Also monitor electrolytes and acid-base balance.
Do not stop resuscitation efforts until the patient has been warmed.
A body temperature > 104° F (40° C), possibly from heat stroke.
Cool the patient with cold water, wet blankets, and ice. Consider a benzodiazepine to prevent convulsions. Rule out causes of fever such as infection or drug reaction.
A hypoxemic poisoning syndrome seen in patients who have been exposed to automobile exhaust, smoke inhalation, barbecues, or old appliances in poorly ventilated locations.
Presents with hypoxemia, cherry-red skin (rare), confusion, and headaches. Coma or seizures occur in severe cases.
Chronic low-level exposure may cause fl ulike symptoms with generalized myalgias, nausea, and headaches. Ask about symptoms in others living in the same house.
Suspect smoke inhalation in the presence of singed nose hairs, facial burns, hoarseness, wheezing, or carbonaceous sputum.
Check an ABG and serum carboxyhemoglobin level (normal is < 5% in nonsmokers and < 10% in smokers).
Check an ECG in the elderly and in patients with a history of cardiac disease.
Treat with 100% O2 until asymptomatic and carboxyhemoglobin falls to normal levels.
Use hyperbaric O2 for pregnant patients, nonresponders, those with signs of CNS or cardiac ischemia, or those with severely ↑ carboxyhemoglobin to facilitate displacement of carbon monoxide from hemoglobin.
Patients with airway burns or smoke inhalation may require early intubation, since upper airway edema can rapidly lead to complete obstruction.
Table 2.17-3 outlines drug interactions and reactions that are commonly encountered in a clinical setting.
Table 2.17-4 summarizes antidotes and treatments for substances commonly encountered in overdoses and intoxications. If a patient is unresponsive, it is common to empirically treat with a dose of Narcan.
Malignant hyperthermia and neuroleptic malignant syndrome (NMS) should be ruled out in any suspected case of hyperthermia. Malignant hyperthermia would be seen after halothane exposure, and NMS after a neuroleptic. Both conditions are treated with dantrolene.
In carbon monoxide poisoning, the patient’s oxygen saturation is usually normal. This is because carboxyhemoglobin is read by the pulse oximeter as a normal saturated hemoglobin molecule.
T AB LE 2.1 7 -3. Drug Interactions and Reactions
Induction of P-450 enzymes Barbiturates, phenytoin, carbamazepine, rifampin, quinidine, griseofulvin. Inhibition of P-450 enzymes Cimetidine, ketoconazole, INH, grapefruit, erythromycin, sulfonamides. Metabolism by P-450 enzymes Benzodiazepines, amide anesthetics, metoprolol, propranolol, nifedipine, phenytoin, quinidine, theophylline, warfarin, barbiturates. ↑ risk of digoxin toxicity Quinidine, cimetidine, amiodarone, CCBs. Competition for albumin-binding sites Warfarin, ASA, phenytoin. Blood dyscrasias Ibuprofen, quinidine, methyldopa, chemotherapeutic agents. Hemolysis in G6PD-defcient patients Sulfonamides, isoniazid (INH), ASA, ibuprofen, nitrofurantoin, primaquine, pyrimethamine, chloramphenicol. Gynecomastia Spironolactone, Estrogens, Digitalis, Cimetidine, chronic Alcohol use, Ketoconazole: “Some Excellent Drugs Create Awesome Knockers.” Stevens-Johnson syndrome Ethosuximide, sulfonamides. Photosensitivity Tetracycline, amiodarone, sulfonamides. Drug-induced SLE Procainamide, hydralazine, INH, penicillamine, chlorpromazine, methyldopa, quinidine.
TABLE 2.17-4.  Specif c AntidotesAcetaminophen N-acetylcysteine. Acid/alkali ingestion Upper endoscopy to evaluate for stricture. Anticholinesterases, organophosphates Atropine, pralidoxime. Antimuscarinic/anticholinergic agents Physostigmine. Arsenic, mercury, gold Succimer, dimercaprol. β-blockers Glucagon. Barbiturates (phenobarbital) Urine alkalinization, dialysis, activated charcoal, supportive care. Benzodiazepines Flumazenil (can precipitate withdrawal).
TABLE 2.17-4.  Specifc Antidotes (continued)Black widow bite Calcium gluconate, methocarbamol. Carbon monoxide 100% O2, hyperbaric O2. Copper, arsenic, lead, gold Penicillamine. Cyanide Amyl nitrate, sodium nitrate, sodium thiosulfate. Digitalis Normalize K+ but avoid giving Ca++, Mg++, or lidocaine (for torsades), antidigitalis Fab. Heparin Protamine sulfate. INH Pyridoxine. Iron salts Deferoxamine. Lead Succimer, CaEDTA, dimercaprol. Methanol, ethylene glycol (antifreeze) EtOH, fomepizole, dialysis, calcium gluconate for ethylene glycol. Methemoglobin Methylene blue. Opioids Naloxone. Salicylates Urine alkalinization, dialysis, activated charcoal. TCAs Sodium bicarbonate for QRS prolongation; diazepam or lorazepam for seizures; cardiac monitor for arrhythmias. Theophylline Activated charcoal. Consider repeat doses. tPA, streptokinase Aminocaproic acid. Warfarin Vitamin K, FFP.
Table 2.17-5 outlines the major side effects of select drugs.
Management of Drug WithdrawalTable 2.17-6 summarizes common drug withdrawal symptoms and treatment.Table 2.17-7 summarizes the signs and symptoms of key vitamin deficiencies.
TABLE 2.17-5.  Drug Side EffectsACEIs Cough, rash, proteinuria, angioedema, taste changes, teratogenic effects. Amantadine Ataxia, livedo reticularis. Aminoglycosides Ototoxicity, nephrotoxicity (acute tubular necrosis). Amiodarone Acute: AV block, hypotension, bradycardia. Chronic: pulmonary f brosis, peripheral deposition leading to bluish discoloration, arrhythmias, hypo-/hyperthyroidism, corneal deposition. Amphotericin Fever/rigors, nephrotoxicity, bone marrow suppression, anemia. Antipsychotics Sedation, acute dystonic reaction, akathisia, parkinsonism, tardive dyskinesia, NMS. Azoles (e.g., fuconazole) Inhibition of P-450 enzymes. AZT Thrombocytopenia, megaloblastic anemia. β-blockers Asthma exacerbation, masking of hypoglycemia, impotence, bradycardia, AV block, CHF. Benzodiazepines Sedation, dependence, respiratory depression. Bile acid resins Gl upset, malabsorption of vitamins and medications. CCBs Peripheral edema, constipation, cardiac depression. Carbamazepine Induction of P-450 enzymes, agranulocytosis, aplastic anemia, liver toxicity. Chloramphenicol Gray baby syndrome, aplastic anemia. Cisplatin Nephrotoxicity, acoustic nerve damage. Clonidine Dry mouth; severe rebound headache and hypertension. Clozapine Agranulocytosis. Corticosteroids Mania, hyperglycemia (acute), immunosuppression, bone mineral loss, thinning of skin, easy bruising, myopathy, cataracts (chronic). Cyclophosphamide Myelosuppression, hemorrhagic cystitis. Digoxin Gl disturbance, yellow visual changes, arrhythmias (e.g., junctional tachycardia or SVT). Doxorubicin Cardiotoxicity (cardiomyopathy). Ethyl alcohol Renal dysfunction, CNS depression. Fluoroquinolones Cartilage damage in children; Achilles tendon rupture in adults. Furosemide Ototoxicity, hypokalemia, nephritis, gout. Gemf brozil Myositis, reversible ↑ in LFTs.
TABLE 2.17-5. Drug Side Effects (continued)Halothane Hepatotoxicity, malignant hyperthermia. HCTZ Hypokalemia, hyponatremia, hyperuricemia, hyperglycemia, hypercalcemia. HMG-CoA reductase inhibitors Myositis, reversible ↑ in LFTs. Hydralazine Drug-induced SLE. Hydroxychloroquine Retinopathy. INH Peripheral neuropathy (prevent with pyridoxine/vitamin B6), hepatotoxicity, inhibition of P-450 enzymes, seizures with overdose, hemolysis in G6PD def ciency. MAOIs Hypertensive tyramine reaction, serotonin syndrome (with meperidine). Methanol Blindness. Methotrexate Hepatic fbrosis, pneumonitis, anemia. Methyldopa Coombs’ test, drug-induced SLE. Metronidazole Disulfram reaction, vestibular dysfunction, metallic taste. Niacin Cutaneous f ushing. Nitroglycerin Hypotension, tachycardia, headache, tolerance. Penicillamine Drug-induced SLE. Penicillin/β-lactams Hypersensitivity reactions. Phenytoin Nystagmus, diplopia, ataxia, arrhythmia (in toxic doses), gingival hyperplasia, hirsutism, teratogenic effects. Prazosin First-dose hypotension. Procainamide Drug-induced SLE. Propylthiouracil Agranulocytosis, aplastic anemia. Quinidine Cinchonism (headache, tinnitus), thrombocytopenia, arrhythmias (e.g., torsades de pointes). Reserpine Depression. Rifampin Induction of P-450 enzymes; orange-red body secretions. Salicylates Fever; hyperventilation with respiratory alkalosis and metabolic acidosis; dehydration, diaphoresis, hemorrhagic gastritis. SSRIs Anxiety, sexual dysfunction, serotonin syndrome if taken with MAOIs.
TABLE 2.17-5. Drug Side Effects (continued)Succinylcholine Malignant hyperthermia, hyperkalemia. TCAs Sedation, coma, anticholinergic effects, seizures and arrhythmias. Tetracyclines Tooth discoloration, photosensitivity, Fanconi’s syndrome, Gl distress. Trimethoprim Megaloblastic anemia, leukopenia, granulocytopenia. Valproic acid Teratogenicity leads to neural tube defects; rare fatal hepatotoxicity. Vancomycin Nephrotoxicity, ototoxicity, “red man syndrome” (histamine release; not an allergy). Vinblastine Severe myelosuppression. Vincristine Peripheral neuropathy, paralytic ileus.
T AB LE 2.1 7 -6. Symptoms and Treatment of Drug Withdrawal
Alcohol Tremor (6–12 hours). Tachycardia, hypertension, agitation, seizures (within 48 hours). Hallucinations, DTs—severe autonomic instability leading to tachycardia, hypertension, delirium, and possibly death (within 2–7 days). Mortality is 15–20%. Benzodiazepines (can require massive doses); haloperidol for hallucinations; thiamine, folate, and multivitamin replacement (do not affect withdrawal, but most alcoholics are def cient). Barbiturates Anxiety, seizures, delirium, tremor; cardiac and respiratory depression. Benzodiazepines. Benzodiazepines Rebound anxiety, seizures, tremor, insomnia. Benzodiazepines. Monitor for DTs. Cocaine/ amphetamines Depression, hyperphagia, hypersomnolence. Supportive treatment. Avoid pure β-blockers (may lead to unopposed α activity, causing hypertension). Opioids Anxiety, insomnia, fulike symptoms, piloerection, fever, rhinorrhea, lacrimation, yawning, nausea, stomach cramps, diarrhea, mydriasis. Antiemetics, muscle relaxers, and NSAIDs for mild symptoms; clonidine, buprenorphine, or methadone for moderate to severe symptoms.
TABLE 2.17-7. Vitamin Functions and Def cienciesVitamin A Night blindness, dry skin. Vitamin B1 (thiamine) Beriberi (polyneuritis, dilated cardiomyopathy, high-output CHF, edema), Wernicke-Korsakoff syndrome. Vitamin B2 (ribofavin) Angular stomatitis, cheilosis, corneal vascularization. Vitamin B3 (niacin) Pellagra (diarrhea, dermatitis, dementia). Vitamin B5 (pantothenate) Dermatitis, enteritis, alopecia, adrenal insuff ciency. Vitamin B6 (pyridoxine) Convulsions, hyperirritability; required during administration of INH. Vitamin B12 (cobalamin) Macrocytic, megaloblastic anemia; neurologic symptoms (e.g., optic neuropathy, subacute combined degeneration, paresthesias); glossitis. Vitamin C Scurvy (e.g., swollen gums, bruising, anemia, poor wound healing). Vitamin D Rickets in children (bending bones), osteomalacia in adults (soft bones), hypocalcemic tetany. Vitamin E ↑ fragility of RBCs. Vitamin K Neonatal hemorrhage; ↑ PT and aPTT, normal BT. Biotin Dermatitis, enteritis. Can be caused by ingestion of raw eggs or antibiotic use. Folic acid The most common vitamin defciency in the United States. Sprue; macrocytic, megaloblastic anemia without neurologic symptoms. Magnesium Weakness, muscle cramps, exacerbation of hypocalcemic tetany, CNS hyperirritability leading to tremors, choreoathetoid movement. Selenium Keshan disease (cardiomyopathy).
Classic ECG finding in atrial flutter. Definition of unstable angina. Antihypertensive for a diabetic patient with proteinuria. Beck’s triad for cardiac tamponade. Drugs that slow AV node transmission. Hypercholesterolemia treatment that leads to fl ushing and pruritus. Murmur—hypertrophic obstructive cardiomyopathy (HOCM).
Murmur—aortic insufficiency.Murmur—aortic stenosis.Murmur—mitral regurgitation. Murmur—mitral stenosis. Treatment for atrial fibrillation and atrial flutter.
Treatment for ventricular fibrillation. Autoimmune complication occurring 2–4 weeks post-MI. IV drug use with JVD and holosystolic murmur at the left sternal border. Treatment? Diagnostic test for hypertrophic cardiomyopathy.
A fall in systolic BP of > 10 mmHg with inspiration. Classic ECG findings in pericarditis. Definition of hypertension. Eight surgically correctable causes of hypertension.
“Sawtooth” P waves. Angina is new, is worsening, or occurs at rest. ACEI. Hypotension, distant heart sounds, and JVD. β-blockers, digoxin, calcium channel blockers. Niacin.
Systolic ejection murmur heard along the lateral sternal border that ↑ with Valsalva maneuver and standing. Diastolic, decrescendo, high-pitched, blowing murmur that is best heard sitting up; ↑ with ↓ preload (handgrip maneuver).
Systolic crescendo/decrescendo murmur that radiates to the neck; ↑ with ↑ preload (Valsalva maneuver). Holosystolic murmur that radiates to the axillae or carotids.
Diastolic, midto late, low-pitched murmur. If unstable, cardiovert. If stable or chronic, rate control with calcium channel blockers or β-blockers.
Immediate cardioversion. Dressler’s syndrome: fever, pericarditis, ↑ ESR. Treat existing heart failure and replace the tricuspid valve.
Echocardiogram (showing thickened left ventricular wall and outfl ow obstruction).
Pulsus paradoxus (seen in cardiac tamponade).Low-voltage, diffuse ST-segment elevation.BP > 140/90 on three separate occasions two weeks apart.
Renal artery stenosis, coarctation of the aorta, pheochromocytoma, Conn’s syndrome, Cushing’s syndrome, unilateral renal parenchymal disease, hyperthyroidism, hyperparathyroidism.
Evaluation of a pulsatile abdominal mass and bruit. Indications for surgical repair of abdominal aortic aneurysm. Treatment for acute coronary syndrome.
What is metabolic syndrome?Appropriate diagnostic test?A 50-year-old man with angina can exercise to 85% of maximum predicted heart rate.
A 65-year-old woman with left bundle branch block and severe osteoarthritis has unstable angina. Target LDL in a patient with diabetes.
Signs of active ischemia during stress testing. ECG findings suggesting MI.
Coronary territories in MI.A young patient has angina at rest with ST-segment elevation. Cardiac enzymes are normal. Common symptoms associated with silent Mls. The diagnostic test for pulmonary embolism. An agent that reverses the effects of heparin.
The coagulation parameter affected by warfarin. A young patient with a family history of sudden death collapses and dies while exercising.
Endocarditis prophylaxis regimens.The 6 P’s of ischemia due to peripheral vascular disease.
Virchow’s triad. The most common cause of hypertension in young women. The most common cause of hypertension in young men.
Abdominal ultrasound and CT.> 5.5 cm, rapidly enlarging, symptomatic, or ruptured.Morphine, O2, sublingual nitroglycerin, ASA, IV β-blockers, heparin.Abdominal obesity, high triglycerides, low HDL, hypertension, insulin resistance, prothrombotic or proinfl ammatory states.
Exercise stress treadmill with ECG.Pharmacologic stress test (e.g., dobutamine echo).< 70. Angina, ST-segment changes on ECG, or ↓ BP. ST-segment elevation (depression means ischemia), flattened T waves, and Q waves.
Anterior wall (LAD/diagonal), inferior (PDA), posterior (left circumflex/oblique, RCA/marginal), septum (LAD/diagonal). Prinzmetal’s angina.
CHF, shock, and altered mental status. V/Q scan. Protamine. PT. Hypertrophic cardiomyopathy.
and gentamicin before and amoxicillin after. Pain, pallor, pulselessness, paralysis, paresthesia, poikilothermia.
Stasis, hypercoagulability, endothelial damage. OCPs. Excessive EtOH.“Stuck-on” appearance. Red plaques with silvery-white scales and sharp margins. The most common type of skin cancer; the lesion is a pearly-colored papule with a translucent surface and telangiectasias.
Honey-crusted lesions. A febrile patient with a history of diabetes presents with a red, swollen, painful lower extremity.
Nikolsky’s sign. Nikolsky’s sign.A 55-year-old obese patient presents with dirty, velvety patches on the back of the neck. Dermatomal distribution. Flat-topped papules. Iris-like target lesions. A lesion characteristically occurring in a linear pattern in areas where skin comes into contact with clothing or jewelry.
Presents with a herald patch, Christmas-tree pattern. A 16-year-old presents with an annular patch of alopecia with broken-off, stubby hairs.
Pinkish, scaling, flat lesions on the chest and back; KOH prep has a “spaghetti-and-meatballs” appearance. Four characteristics of a nevus suggestive of melanoma.
A premalignant lesion from sun exposure that can lead to squamous cell carcinoma. “Dewdrops on a rose petal.” “Cradle cap.” Associated with Propionibacterium acnes and changes in androgen levels.
Seborrheic keratosis. Psoriasis. Basal cell carcinoma.Impetigo. Cellulitis.Pemphigus vulgaris. Bullous pemphigoid. Acanthosis nigricans. Check fasting blood glucose to rule out diabetes. Varicella zoster. Lichen planus. Erythema multiforme. Contact dermatitis.
Pityriasis rosea. Alopecia areata (an autoimmune process).Pityriasis versicolor.Asymmetry, border irregularity, color variation, and large diameter.Actinic keratosis.Lesions of 1° varicella. Seborrheic dermatitis. Treat with antifungals. Acne vulgaris.
A painful, recurrent vesicular eruption of mucocutaneous surfaces.Inflammation and epithelial thinning of the anogenital area, predominantly in postmenopausal women.
Exophytic nodules on the skin with varying degrees of scaling or ulceration; the second most common type of skin cancer.
Herpes simplex.Lichen sclerosus.Squamous cell carcinoma.Bias introduced into a study when a clinician is aware of the patient’s treatment type.
Bias introduced when screening detects a disease earlier and thus lengthens the time from diagnosis to death.
If you want to know if geographical location affects infant mortality rate but most variation in infant mortality is predicted by socioeconomic status, then socioeconomic status is a _____.
The number of true positives divided by the number of patients with the disease is _____.
Sensitive tests have few false negatives and are used to rule _____ a disease.
PPD reactivity is used as a screening test because most people with TB (except those who are anergic) will have a
PPD. Highly sensitive or specific?Chronic diseases such as SLE—higher prevalence or incidence?Epidemics such as influenza—higher prevalence or incidence?Cross-sectional survey—incidence or prevalence?Cohort study—incidence or prevalence?Case-control study—incidence or prevalence?Describe a test that consistently gives identical results, but the results are wrong.
Difference between a cohort and a case-control study.Observational bias.Lead-time bias.Confounding variable.Highly sensitive for TB.Higher prevalence.Higher incidence.Prevalence. Incidence and prevalence. Neither. High reliability, low validity.Cohort studies can be used to calculate relative risk (RR), incidence, and/or odds ratio (OR). Case-control studies can be used to calculate an OR.
Attributable risk?Relative risk?Odds ratio?Number needed to treat?In which patients do you initiate colorectal cancer screening early?
The most common cancer in men and the most common cause of death from cancer in men. The percentage of cases within one SD of the mean? Two SDs? Three SDs?
Birth rate? Fertility rate?Mortality rate? Neonatal mortality rate?Postnatal mortality rate?Infant mortality rate?Fetal mortality rate?Perinatal mortality rate?Maternal mortality rate?The incidence rate (IR) of a disease in exposed – the IR of a disease in unexposed.
The IR of a disease in a population exposed to a particular factor ÷ the IR of those not exposed.
The likelihood of a disease among individuals exposed to a risk factor compared to those who have not been exposed.
1 ÷ (rate in untreated group – rate in treated group).
Patients with IBD; those with familial adenomatous polyposis (FAP)/hereditary nonpolyposis colorectal cancer (HNPCC); and those who have first-degree relatives with adenomatous polyps (< 60 years of age) or colorectal cancer.
Prostate cancer is the most common cancer in men, but lung cancer causes more deaths.
68%, 95.4%, 99.7%.Number of live births per 1000 population in one year.
Number of live births per 1000 females (15–44 years of age) in one year.
Number of deaths per 1000 population in one year.Number of deaths from birth to 28 days per 1000 live births in one year.
Number of deaths from 28 days to one year per 1000 live births in one year.
Number of deaths from birth to one year of age per 1000 live births (neonatal + postnatal mortality) in one year.
Number of deaths from 20 weeks’ gestation to birth per 1000 total births in one year.
Number of deaths from 20 weeks’ gestation to one month of life per 1000 total births in one year.
Number of deaths during pregnancy to 90 days postpartum per 100,000 live births in one year.
True or false: Once patients sign a statement giving consent, they must continue treatment.
A 15-year-old pregnant girl requires hospitalization for preeclampsia. Is parental consent required?
A doctor refers a patient for an MRI at a facility he/she owns.
Involuntary psychiatric hospitalization can be undertaken for which three reasons?
True or false: Withdrawing a nonbeneficial treatment is ethically similar to withholding a nonindicated one.
When can a physician refuse to continue treating a patient on the grounds of futility?
An eight-year-old child is in a serious accident. She requires emergent transfusion, but her parents are not present.
Conditions in which confidentiality must be overridden.Involuntary commitment or isolation for medical treatment may be undertaken for what reason?
A 10-year-old child presents in status epilepticus, but her parents refuse treatment on religious grounds.
A son asks that his mother not be told about her recently discovered cancer.
False. Patients may change their minds at any time. Exceptions to the requirement of informed consent include emergency situations and patients without decision-making capacity.
No. Parental consent is not necessary for the medical treatment of pregnant minors.
Conflict of interest.The patient is a danger to self, a danger to others, or gravely disabled (unable to provide for basic needs).
When there is no rationale for treatment, maximal intervention is failing, a given intervention has already failed, and treatment will not achieve the goals of care.
Treat immediately. Consent is implied in emergency situations.Real threat of harm to third parties; suicidal intentions; certain contagious diseases; elder and child abuse.
When treatment noncompliance represents a serious danger to public health (e.g., active TB).
Treat because the disease represents an immediate threat to the child’s life. Then seek a court order.
A physician can withhold information from the patient only in the rare case of therapeutic privilege or if the patient requests not to be told. A patient’s family cannot require the physician to withhold information from the patient.
Diagnostic modality used when ultrasound is equivocal for cholecystitis.Risk factors for cholelithiasis.Inspiratory arrest during palpation of the RUQ.The most common cause of SBO in patients with no history of abdominal surgery.
The most common cause of SBO in patients with a history of abdominal surgery.
Identify key organisms causing diarrhea:A 25-year-old Jewish man presents with pain and watery diarrhea after meals. Exam shows fistulas between the bowel and skin and nodular lesions on his tibias.
Inflammatory disease of the colon with ↑ risk of colon cancer.
Extraintestinal manifestations of IBD.Medical treatment for IBD.Difference between Mallory-Weiss and Boerhaave tears.Charcot’s triad.Reynolds’ pentad.Medical treatment for hepatic encephalopathy.HIDA scan.Fat, female, fertile, forty, fl atulent.Murphy’s sign, seen in acute cholecystitis.S. aureus E. coli O157:H7 Bacillus cereus Salmonella Vibrio, HAV Isospora, Cryptosporidium, Mycobacterium avium complex
Crohn’s disease.Ulcerative colitis (greater risk than Crohn’s).Uveitis, ankylosing spondylitis, pyoderma gangrenosum, erythema nodosum, 1° sclerosing cholangitis.
5-ASA agents and steroids during acute exacerbations.Mallory-Weiss—superficial tear in the esophageal mucosa; Boerhaave—full-thickness esophageal rupture.RUQ pain, jaundice, and fever/chills in the setting of ascending cholangitis.
Charcot’s triad plus shock and mental status changes, with suppurative ascending cholangitis.
↓ protein intake, lactulose, rifaximin.First step in the management of a patient with an acute GI bleed.
A four-year-old child presents with oliguria, petechiae, and jaundice following an illness with bloody diarrhea. Most likely diagnosis and cause?
Post-HBV exposure treatment.Classic causes of drug-induced hepatitis.A 40-year-old obese woman with elevated alkaline phosphatase, elevated bilirubin, pruritus, dark urine, and clay-colored stools.
Hernia with highest risk of incarceration—indirect, direct, or femoral?A 50-year-old man with a history of alcohol abuse presents with boring epigastric pain that radiates to the back and is relieved by sitting forward. Management?
Establish the ABCs.Hemolytic-uremic syndrome (HUS) due to E. coli O157: H7.HBV immunoglobulin.TB medications (INH, rifampin, pyrazinamide), acetaminophen, and tetracycline.Biliary tract obstruction.Femoral hernia.Confirm the diagnosis of acute pancreatitis with elevated amylase and lipase. Make the patient NPO and give IV fl uids, O2, analgesia, and “tincture of time.”
Four causes of microcytic anemia.An elderly man with hypochromic, microcytic anemia is asymptomatic. Diagnostic tests? Precipitants of hemolytic crisis in patients with G6PD deficiency.
The most common inherited cause of hypercoagulability. The most common inherited bleeding disorder. The most common inherited hemolytic anemia. Diagnostic test for hereditary spherocytosis. Pure RBC aplasia. Anemia associated with absent radii and thumbs, diffuse hyperpigmentation, café au lait spots, microcephaly, and pancytopenia. Medications and viruses that lead to aplastic anemia.
TICS—Thalassemia, Iron deficiency, anemia of Chronic disease, and Sideroblastic anemia.
Fecal occult blood test and sigmoidoscopy; suspect colorectal cancer.Sulfonamides, antimalarial drugs, fava beans.Factor V Leiden mutation. von Willebrand’s disease. Hereditary spherocytosis. Osmotic fragility test. Diamond-Blackfan anemia. Fanconi’s anemia.
Chloramphenicol, sulfonamides, radiation, HIV, chemotherapeutic agents, hepatitis, parvovirus B19, EBV.
How to distinguish polycythemia vera from 2° polycythemia.Thrombotic thrombocytopenic purpura (TTP) pentad?HUS triad? Treatment for TTP.Treatment for idiopathic thrombocytopenic purpura (ITP) in children.Which of the following are ↑ in DIC: fibrin split products, D-dimer, fibrinogen, platelets, and hematocrit.
An eight-year-old boy presents with hemarthrosis and ↑ PTT with normal PT and bleeding time. Diagnosis? Treatment?
A 14-year-old girl presents with prolonged bleeding after dental surgery and with menses, normal PT, normal or ↑ PTT, and ↑ bleeding time. Diagnosis? Treatment?
A 60-year-old African-American man presents with bone pain. Workup for multiple myeloma might reveal? Reed-Sternberg cells. A 10-year-old boy presents with fever, weight loss, and night sweats. Exam shows an anterior mediastinal mass.
Suspected diagnosis? Microcytic anemia with ↓ serum iron, ↓ total iron-binding capacity (TIBC), and normal or ↑ ferritin.
Microcytic anemia with ↓ serum iron, ↓ ferritin, and ↑ TIBC. An 80-year-old man presents with fatigue, lymphadenopathy, splenomegaly, and isolated lymphocytosis. Suspected diagnosis? The lymphoma equivalent of CLL. A late, life-threatening complication of chronic myelogenous leukemia (CML). Auer rods on blood smear. AML subtype associated with DIC.
Both have ↑ hematocrit and RBC mass, but polycythemia vera should have normal O2 saturation and low erythropoietin levels.
“FAT RN”: Fever, Anemia, Thrombocytopenia, Renal dysfunction, Neurologic abnormalities.Anemia, thrombocytopenia, and acute renal failure.Emergent large-volume plasmapheresis, corticosteroids, antiplatelet drugs.Usually resolves spontaneously; may require IVIG and/or corticosteroids.Fibrin split products and D-dimer are elevated; platelets, fibrinogen, and hematocrit are ↓.
A) or factor VIII or IX supplements.von Willebrand’s disease; treat with desmopressin, FFP, or cryoprecipitate.Monoclonal gammopathy, Bence Jones proteinuria, “punched-out” lesions on x-ray of the skull and long bones. Hodgkin’s lymphoma. Non-Hodgkin’s lymphoma.
Anemia of chronic disease.Iron deficiency anemia. Chronic lymphocytic leukemia (CLL).Small lymphocytic lymphoma. Blast crisis (fever, bone pain, splenomegaly, pancytopenia).
Acute myelogenous leukemia (AML). M3.Electrolyte changes in tumor lysis syndrome. Treatment for AML M3. A 50-year-old man presents with early satiety, splenomegaly, and bleeding. Cytogenetics show t(9,22). Diagnosis? Heinz bodies?
An autosomal-recessive disorder with a defect in the GPIIbIIIa platelet receptor and ↓ platelet aggregation.
Virus associated with aplastic anemia in patients with sickle cell anemia.
A 25-year-old African-American man with sickle cell anemia has sudden onset of bone pain. Management of pain crisis?
A significant cause of morbidity in thalassemia patients. Treatment?↓ Ca2+, ↑ K+, ↑ phosphate, ↑ uric acid. Retinoic acid. CML.
Intracellular inclusions seen in thalassemia, G6PD deficiency, and postsplenectomy.Glanzmann’s thrombasthenia.Parvovirus B19.O2, analgesia, hydration, and, if severe, transfusion.Iron overload; use deferoxamine.The three most common causes of fever of unknown origin (FUO).
Four signs and symptoms of streptococcal pharyngitis. A nonsuppurative complication of streptococcal infection that is not altered by treatment of 1° infection.
Asplenic patients are particularly susceptible to these organisms. The number of bacteria on a clean-catch specimen to diagnose a UTI.
Which healthy population is susceptible to UTIs?A patient from California or Arizona presents with fever, malaise, cough, and night sweats. Diagnosis? Treatment?
Nonpainful chancre.A “blueberry muffin” rash is characteristic of what congenital infection?
Infection, cancer, and autoimmune disease.Fever, pharyngeal erythema, tonsillar exudate, lack of cough. Postinfectious glomerulonephritis.
Encapsulated organisms—pneumococcus, meningococcus,Haemophilus infl uenzae, Klebsiella.105 bacteria/mL.Pregnant women. Treat this group aggressively because of potential complications.
Coccidioidomycosis. Amphotericin B.1° syphilis. Rubella.Meningitis in neonates. Causes? Treatment?Meningitis in infants. Causes? Treatment?What should always be done prior to LP?CSF findings:Low glucose, PMN predominanceNormal glucose, lymphocytic predominanceInitially presents with a pruritic papule with regional lymphadenopathy; evolves into a black eschar after 7–10 days. Treatment?
Findings in 3° syphilis.Characteristics of 2° Lyme disease.Cold agglutinins.A 24-year-old man presents with soft white plaques on his tongue and the back of his throat. Diagnosis? Workup? Treatment?
Begin Pneumocystis jiroveci (formerly P. carinii) pneumonia prophylaxis in an HIV-positive patient at what CD4 count? Mycobacterium avium–intracellulare (MAI) prophylaxis?
Risk factors for pyelonephritis.Neutropenic nadir postchemotherapy.Erythema migrans.Classic physical findings for endocarditis.Aplastic crisis in sickle cell disease.Ring-enhancing brain lesion on CT with seizures.Group B strep, E. coli, Listeria. Treat with gentamicin and ampicillin.
Pneumococcus, meningococcus, H. infl uenzae. Treat with cefotaxime and vancomycin.
Check for ↑ ICP; look for papilledema.Cutaneous anthrax. Treat with penicillin G or ciprofl oxacin.Tabes dorsalis, general paresis, gummas, Argyll Robertson pupil, aortitis, aortic root aneurysms.
Arthralgias, migratory polyarthropathies, Bell’s palsy, myocarditis.Candidal thrush. Workup should include an HIV test. Treat with nystatin oral suspension.
≤ 200 for P. jiroveci (with TMP-SMX); ≤ 50–100 for MAI (with clarithromycin/azithromycin).
Pregnancy, vesicoureteral reflux, anatomic anomalies, indwelling catheters, kidney stones. 7–10 days.
Lesion of 1° Lyme disease. Fever, heart murmur, Osler’s nodes, splinter hemorrhages, Janeway lesions, Roth’s spots.
Parvovirus B19. Taenia solium (cysticercosis).Name the organism:Pregnant women with petsAlcoholic with pneumoniaA 55-year-old man who is a smoker and a heavy drinker presents with a new cough and flulike symptoms. Gram stain shows no organisms; silver stain of sputum shows gram-negative rods. What is the diagnosis?
A middle-aged man presents with acute-onset monoarticular joint pain and bilateral Bell’s palsy. What is the likely diagnosis, and how did he get it? Treatment?
A patient develops endocarditis three weeks after receiving a prosthetic heart valve. What organism is suspected?
Legionella pneumonia.Lyme disease, Ixodes tick, doxycycline.S. aureus or S. epidermidis.Back pain that is exacerbated by standing and walking and relieved with sitting and hyperflexion of the hips.
Joints in the hand affected in rheumatoid arthritis.Joint pain and stiffness that worsen over the course of the day and are relieved by rest.
Genetic disorder associated with multiple fractures and commonly mistaken for child abuse.
Hip and back pain along with stiffness that improves with activity over the course of the day and worsens at rest. Diagnostic test?
Arthritis, conjunctivitis, and urethritis in young men. Associated organisms?A 55-year-old man has sudden, excruciating first MTP joint pain after a night of drinking red wine. Diagnosis, workup, and chronic treatment?
Spinal stenosis.MCP and PIP joints; DIP joints are spared.Osteogenesis imperfecta.Suspect ankylosing spondylitis. Check HLA-B27.Reactive (Reiter’s) arthritis. Associated with Campylobacter, Shigella, Salmonella, Chlamydia, and Ureaplasma.
Gout. Needle-shaped, negatively birefringent crystals are seen on joint fluid aspirate. Chronic treatment with allopurinol or probenecid.
Rhomboid-shaped, positively birefringent crystals on joint fl uid aspirate. An elderly woman presents with pain and stiffness of the shoulders and hips; she cannot lift her arms above her head. Labs show anemia and ↑ ESR.
An active 13-year-old boy has anterior knee pain. Diagnosis? Bone is fractured in a fall on an outstretched hand. Complication of scaphoid fracture. Signs suggesting radial nerve damage with humeral fracture. A young child presents with proximal muscle weakness, waddling gait, and pronounced calf muscles. A first-born female who was born in breech position is found to have asymmetric skin folds on her newborn exam. Diagnosis? Treatment? An 11-year-old obese African-American boy presents with sudden onset of limp. Diagnosis? Workup? The most common 1° malignant tumor of bone.
Polymyalgia rheumatica.Osgood-Schlatter disease. Distal radius (Colles’ fracture). Avascular necrosis. Wrist drop, loss of thumb abduction. Duchenne muscular dystrophy.
Developmental dysplasia of the hip. If severe, consider a Pavlik harness to maintain abduction.
Slipped capital femoral epiphysis. AP and frog-leg lateral view.Multiple myeloma.Unilateral, severe periorbital headache with tearing and conjunctival erythema. Prophylactic treatment for migraine.
The most common pituitary tumor. Treatment? A 55-year-old patient presents with acute “broken speech.” What type of aphasia? What lobe and vascular distribution?
The most common cause of SAH.A crescent-shaped hyperdensity on CT that does not cross the midline. A history significant for initial altered mental status with an intervening lucid interval. Diagnosis? Most likely source? Treatment? CSF findings with SAH.
Cluster headache.Antihypertensives, antidepressants, anticonvulsants. Prolactinoma. Dopamine agonists (e.g., bromocriptine). Broca’s aphasia. Frontal lobe, left MCA distribution.
Trauma; the second most common is berry aneurysm. Subdural hematoma—bridging veins torn.
Epidural hematoma. Middle meningeal artery. Neurosurgical evacuation.Elevated ICP, RBCs, xanthochromia.Albuminocytologic dissociation.Cold water is flushed into a patient’s ear, and the fast phase of the nystagmus is toward the opposite side. Normal or pathologic?
The most common 1° sources of metastases to the brain.
May be seen in children who are accused of inattention in class and confused with ADHD. The most frequent presentation of intracranial neoplasm. The most common cause of seizures in children (2–10 years).
The most common cause of seizures in young adults (18–35 years). First-line medication for status epilepticus. Confusion, confabulation, ophthalmoplegia, ataxia. What % lesion is an indication for carotid endarterectomy? The most common causes of dementia. Combined UMN and LMN disorder. Rigidity and stiffness with resting tremor and masked facies. The mainstay of Parkinson’s therapy. Treatment for Guillain-Barré syndrome. Rigidity and stiffness that progress to choreiform movements, accompanied by moodiness and altered behavior. A six-year-old girl presents with a port-wine stain in the V2 distribution as well as with mental retardation, seizures, and ipsilateral leptomeningeal angioma.
Café au lait spots on skin. Hyperphagia, hypersexuality, hyperorality, and hyperdocility. May be administered to a symptomatic patient to diagnose myasthenia gravis.
Guillain-Barré syndrome (↑ protein in CSF without a significant ↑ in cell count).
Lung, breast, skin (melanoma), kidney, GI tract. Absence seizures.Headache. Infection, febrile seizures, trauma, idiopathic.Trauma, alcohol withdrawal, brain tumor.IV benzodiazepine. Wernicke’s encephalopathy due to a deficiency of thiamine. Seventy percent if the stenosis is symptomatic. Alzheimer’s and multi-infarct. ALS. Parkinson’s disease. Levodopa/carbidopa. IVIG or plasmapheresis. Huntington’s disease.
Sturge-Weber syndrome. Treat symptomatically. Possible focal cerebral resection of the affected lobe.
Neurofibromatosis type 1. Klüver-Bucy syndrome (amygdala). Edrophonium.1° causes of third-trimester bleeding.Classic ultrasound and gross appearance of complete hydatidiform mole. Chromosomal pattern of a complete mole. Molar pregnancy containing fetal tissue. Symptoms of placental abruption. Symptoms of placenta previa. When should a vaginal exam be performed with suspected placenta previa? Antibiotics with teratogenic effects.
Shortest AP diameter of the pelvis.Medication given to accelerate fetal lung maturity. The most common cause of postpartum hemorrhage. Treatment for postpartum hemorrhage. Typical antibiotics for group B streptococcus (GBS) prophylaxis.
A patient fails to lactate after an emergency C-section with marked blood loss. Uterine bleeding at 18 weeks’ gestation; no products expelled; membranes ruptured; cervical os open. Uterine bleeding at 18 weeks’ gestation; no products expelled; cervical os closed.
Placental abruption and placenta previa.Snowstorm on ultrasound. “Cluster-of-grapes” appearance on gross examination. 46,XX. Partial mole. Continuous, painful vaginal bleeding. Self-limited, painless vaginal bleeding. Never.
Tetracycline, fl uoroquinolones, aminoglycosides, sulfonamides. Obstetric conjugate: between the sacral promontory and the midpoint of the symphysis pubis.
Betamethasone or dexamethasone × 48 hours. Uterine atony. Uterine massage; if that fails, give oxytocin. IV penicillin or ampicillin.
Sheehan’s syndrome (postpartum pituitary necrosis).Inevitable abortion.Threatened abortion.Cause of amenorrhea with normal prolactin, no response to estrogen-progesterone challenge, and a history of D&C. Therapy for polycystic ovarian syndrome.
Medication used to induce ovulation. Diagnostic step required in a postmenopausal woman who presents with vaginal bleeding.
Indications for medical treatment of ectopic pregnancy.Medical options for endometriosis. Laparoscopic findings in endometriosis. The most common location for an ectopic pregnancy. How to diagnose and follow a leiomyoma. Natural history of a leiomyoma. A patient has ↑ vaginal discharge and petechial patches in the upper vagina and cervix. Treatment for bacterial vaginosis. The most common cause of bloody nipple discharge. Contraceptive methods that protect against PID. Unopposed estrogen is contraindicated in which cancers? A patient presents with recent PID with RUQ pain. Breast malignancy presenting as itching, burning, and erosion of the nipple.
Annual screening for women with a strong family history of ovarian cancer. A 50-year-old woman leaks urine when laughing or coughing. Nonsurgical options?
A 30-year-old woman has unpredictable urine loss. Examination is normal. Medical options? Lab values suggestive of menopause. The most common cause of female infertility.
Asherman’s syndrome.Weight loss and OCPs. Clomiphene citrate. Endometrial biopsy.Stable, unruptured ectopic pregnancy of < 3.5 cm at < 6 weeks’ gestation. OCPs, danazol, GnRH agonists. “Chocolate cysts,” powder burns. Ampulla of the oviduct. Ultrasound. Regresses after menopause. Trichomonas vaginitis.
Oral or topical metronidazole. Intraductal papilloma. OCPs and barrier contraception. Endometrial or estrogen receptor– breast cancer. Consider Fitz-Hugh–Curtis syndrome. Paget’s disease.
CA-125 and transvaginal ultrasound.Kegel exercises, estrogen, pessaries for stress incontinence.Anticholinergics (oxybutynin) or β-adrenergics (metaproterenol) for urge incontinence.↑ serum FSH. Endometriosis.Nontender abdominal mass associated with elevated VMA and HVA.The most common type of tracheoesophageal fistula (TEF). Diagnosis?Not contraindications to vaccination.Tests to rule out shaken baby syndrome.A neonate has meconium ileus.Bilious emesis within hours after the first feeding.A two-month-old baby presents with nonbilious projectile emesis. What are the appropriate steps in management?
The most common 1° immunodeficiency.An infant has a high fever and onset of rash as fever breaks. What is he at risk for?
What is the immunodeficiency?A boy has chronic respiratory infections. Nitroblue tetrazolium test is .
A child has eczema, thrombocytopenia, and high levels of IgA.
A four-month-old boy has life-threatening Pseudomonas infection.Acute-phase treatment for Kawasaki disease.Treatment for mild and severe unconjugated hyperbilirubinemia.Sudden onset of mental status changes, emesis, and liver dysfunction after taking aspirin.
A child has loss of red light reflex. Diagnosis?Esophageal atresia with distal TEF (85%). Unable to pass NG tube. Mild illness and/or low-grade fever, current antibiotic therapy, and prematurity.
Ophthalmologic exam, CT, and MRI. CF or Hirschsprung’s disease. Duodenal atresia. Correct metabolic abnormalities. Then correct pyloric stenosis with pyloromyotomy. Selective IgA deficiency. Febrile seizures (roseola infantum).
High-dose aspirin for inflammation and fever; IVIG to prevent coronary artery aneurysms.
Phototherapy (mild) or exchange transfusion (severe).Reye’s syndrome.Suspect retinoblastoma.Vaccinations at a six-month well-child visit. Tanner stage 3 in a six-year-old girl. Infection of small airways with epidemics in winter and spring. Cause of neonatal RDS. A condition associated with red “currant-jelly” stools. A congenital heart disease that causes 2° hypertension. First-line treatment for otitis media. The most common pathogen causing croup. A homeless child is small for his age and has peeling skin and a swollen belly.
Defect in an X-linked syndrome with mental retardation, gout, self-mutilation, and choreoathetosis. A newborn girl has a continuous “machinery murmur.”
HBV, DTaP, Hib, IPV, PCV. Precocious puberty. RSV bronchiolitis.Surfactant deficiency. Intussusception. Coarctation of the aorta. Amoxicillin × 10 days. Parainfluenza virus type 1. Kwashiorkor (protein malnutrition).
Lesch-Nyhan syndrome (purine salvage problem with HGPRTase deficiency).Patent ductus arteriosus (PDA).First-line pharmacotherapy for depression.Antidepressants associated with hypertensive crisis.Galactorrhea, impotence, menstrual dysfunction, and ↓ libido.A 17-year-old girl has left arm paralysis after her boyfriend dies in a car crash. No medical cause is found.
Name the defense mechanism:A mother who is angry at her husband yells at her child.
A pedophile enters a monastery.A woman calmly describes a grisly murder.A hospitalized 10-year-old begins to wet his bed.Life-threatening muscle rigidity, fever, and rhabdomyolysis.Amenorrhea, bradycardia, and abnormal body image in a young female.
SSRIs. MAOIs. Patient on dopamine antagonist.Conversion disorder.Neuroleptic malignant syndrome. Anorexia.A 35-year-old man has recurrent episodes of palpitations, diaphoresis, and fear of going crazy.
The most serious side effect of clozapine.A 21-year-old man has three months of social withdrawal, worsening grades, flattened affect, and concrete thinking.
Key side effects of atypical antipsychotics.A young weight lifter receives IV haloperidol and complains that his eyes are deviated sideways. Diagnosis? Treatment?
Medication to avoid in patients with a history of alcohol withdrawal seizures.
A 13-year-old boy has a history of theft, vandalism, and violence toward family pets.
A five-month-old girl has ↓ head growth, truncal dyscoordination, and ↓ social interaction.
A patient hasn’t slept for days, lost $20,000 gambling, is agitated, and has pressured speech. Diagnosis? Treatment?
After a minor fender bender, a man wears a neck brace and requests permanent disability.
A nurse presents with severe hypoglycemia; blood analysis reveals no elevation in C-peptide.
A patient continues to use cocaine after being in jail, losing his job, and not paying child support.
A violent patient has vertical and horizontal nystagmus.A woman who was abused as a child frequently feels outside of or detached from her body.
A man has repeated, intense urges to rub his body against unsuspecting passengers on a bus.
A schizophrenic patient takes haloperidol for one year and develops uncontrollable tongue movements. Diagnosis? Treatment?
A man unexpectedly flies across the country, takes a new name, and has no memory of his prior life.
Panic disorder.Schizophreniform disorder (diagnosis of schizophrenia requires ≥ 6 months of symptoms). Weight gain, type 2 DM, QT prolongation. Acute dystonia (oculogyric crisis). Treat with benztropine or diphenhydramine.
Conduct disorder.Rett’s disorder.Acute mania. Start a mood stabilizer (e.g., lithium).Factitious disorder (Munchausen syndrome).Substance abuse.Phencyclidine hydrochloride (PCP) intoxication. Depersonalization disorder.Frotteurism (a paraphilia).Tardive dyskinesia. ↓ or discontinue haloperidol and consider another antipsychotic (e.g., risperidone, clozapine).
Dissociative fugue.Risk factors for DVT.Criteria for exudative effusion. Causes of exudative effusion.Causes of transudative effusion.may indicate? Dyspnea, lateral hilar lymphadenopathy on CXR, noncaseating granulomas, ↑ ACE, and hypercalcemia.
PFTs showing ↓ FEV1/FVC. PFTs showing ↑ FEV1/FVC. Honeycomb pattern on CXR. Diagnosis? Treatment?
Treatment for SVC syndrome. Treatment for mild, persistent asthma. Treatment for COPD exacerbation.
Treatment for chronic COPD.Acid-base disorder in pulmonary embolism.Non–small cell lung cancer (NSCLC) associated with hypercalcemia. Lung cancer associated with SIADH. Lung cancer highly related to cigarette exposure. A tall white male presents with acute shortness of breath.
Diagnosis? Treatment? Treatment of tension pneumothorax.Stasis, endothelial injury, and hypercoagulability (Virchow’s triad).Pleural/serum protein > 0.5; pleural/serum LDH > 0.6. Think of leaky capillaries. Malignancy, TB, bacterial or viral infection, pulmonary embolism with infarct, and pancreatitis.
Think of intact capillaries. CHF, liver or kidney disease, and protein-losing enteropathy. Fatigue and impending respiratory failure.
Obstructive pulmonary disease (e.g., asthma). Restrictive pulmonary disease. Diffuse interstitial pulmonary fibrosis. Supportive care.
Steroids may help. Radiation. Inhaled β-agonists and inhaled corticosteroids. O2, bronchodilators, antibiotics, corticosteroids with taper, smoking cessation. Smoking cessation, home O2, β-agonists, anticholinergics, systemic or inhaled corticosteroids, flu and pneumococcal vaccines. Hypoxia and hypocarbia (respiratory alkalosis). Squamous cell carcinoma.
Small cell lung cancer (SCLC). SCLC. Spontaneous pneumothorax. Spontaneous regression.
Supplemental O2 may be helpful. Immediate needle thoracostomy.Characteristics favoring carcinoma in an isolated pulmonary nodule.Hypoxemia and pulmonary edema with normal pulmonary capillary wedge pressure.
Sequelae of asbestos exposure.↑ risk of what infection with silicosis? Causes of hypoxemia.
Classic CXR findings for pulmonary edema.Age > 45–50 years; lesions new or larger in comparison to old films; absence of calcification or irregular calcification; size > 2 cm; irregular margins.
Pulmonary fibrosis, pleural plaques, bronchogenic carcinoma (mass in lung field), mesothelioma (pleural mass).
Mycobacterium tuberculosis.Right-to-left shunt, hypoventilation, low inspired O2 tension, diffusion defect, V/Q mismatch.
Cardiomegaly, prominent pulmonary vessels, Kerley B lines, “bat’s-wing” appearance of hilar shadows, and perivascular and peribronchial cuffing.
Renal tubular acidosis (RTA) associated with abnormal H+ secretion and nephrolithiasis.
RTA associated with abnormal HCO3 and rickets.RTA associated with aldosterone defect. “Doughy” skin Differential of hypervolemic hyponatremia. Chvostek’s and Trousseau’s signs. The most common causes of hypercalcemia. T-wave flattening and U waves. Peaked T waves and widened QRS. First-line treatment for moderate hypercalcemia. Type of ARF in a patient with FeNa < 1%. A 49-year-old man presents with acute-onset flank pain and hematuria. The most common type of nephrolithiasis. A 20-year-old man presents with a palpable flank mass and hematuria. Ultrasound shows bilateral enlarged kidneys with cysts. Associated brain anomaly?
Type I (distal) RTA.Type II (proximal) RTA. Type IV (distal) RTA. Hypernatremia. Cirrhosis, CHF, nephritic syndrome. Hypocalcemia. Malignancy and hyperparathyroidism. Hypokalemia. Hyperkalemia. IV hydration and loop diuretics (furosemide). Prerenal. Nephrolithiasis.
Calcium oxalate. Cerebral berry aneurysms (autosomal-dominant PCKD).Hematuria, hypertension, and oliguria.Proteinuria, hypoalbuminemia, hyperlipidemia, hyperlipiduria, and edema. The most common form of nephritic syndrome. The most common form of glomerulonephritis. Glomerulonephritis with deafness. Glomerulonephritis with hemoptysis. Presence of red cell casts in urine sediment. Eosinophils in urine sediment. Waxy casts in urine sediment and Maltese crosses (seen with lipiduria). Drowsiness, asterixis, nausea, and a pericardial friction rub. A 55-year-old man is diagnosed with prostate cancer.
Treatment options?Low urine specific gravity in the presence of high serum osmolality. Treatment of SIADH? Hematuria, flank pain, and palpable flank mass. Testicular cancer associated with β-hCG, AFP. The most common type of testicular cancer. The most common histology of bladder cancer. Complication of overly rapid correction of hyponatremia. Salicylate ingestion occurs in what type of acid-base disorder? Acid-base disturbance commonly seen in pregnant women. Three systemic diseases that lead to nephrotic syndrome. Elevated erythropoietin level, elevated hematocrit, and normal O2 saturation suggest? A 55-year-old male presents with irritative and obstructive urinary symptoms. Treatment options?
Nephritic syndrome. Nephrotic syndrome.Membranous glomerulonephritis. IgA nephropathy (Berger’s disease). Alport’s syndrome. Wegener’s granulomatosis and Goodpasture’s syndrome. Glomerulonephritis/nephritic syndrome. Allergic interstitial nephritis. Nephrotic syndrome.
Uremic syndrome seen in patients with renal failure.Wait, surgical resection, radiation and/or androgen suppression. Diabetes insipidus.Fluid restriction, demeclocycline. Renal cell carcinoma (RCC). Choriocarcinoma. Seminoma, a type of germ cell tumor. Transitional cell carcinoma. Central pontine myelinolysis. Anion gap acidosis and 1° respiratory alkalosis due to central respiratory stimulation. Respiratory alkalosis. DM, SLE, and amyloidosis. RCC or other erythropoietin-producing tumor; evaluate with
CT scan. Likely BPH. Options include no treatment, terazosin, finasteride, or surgical intervention (TURP).
Class of drugs that may cause syndrome of muscle rigidity, hyperthermia, autonomic instability, and extrapyramidal symptoms.
Side effects of corticosteroids.Treatment for DTs. Treatment for acetaminophen overdose. Treatment for opioid overdose. Treatment for benzodiazepine overdose. Treatment for neuroleptic malignant syndrome and malignant hyperthermia. Treatment for malignant hypertension. Treatment of atrial fibrillation. Treatment of supraventricular tachycardia.
Causes of drug-induced SLE.Macrocytic, megaloblastic anemia with neurologic symptoms. Macrocytic, megaloblastic anemia without neurologic symptoms.
A burn patient presents with cherry-red flushed skin and coma. SaO2 is normal, but carboxyhemoglobin is elevated. Treatment?
Blood in the urethral meatus or high-riding prostate. Test to rule out urethral injury. Radiographic evidence of aortic disruption or dissection.
Radiographic indications for surgery in patients with acute abdomen.Antipsychotics (neuroleptic malignant syndrome).Acute mania, immunosuppression, thin skin, osteoporosis, easy bruising, myopathies. Benzodiazepines. N-acetylcysteine. Naloxone. Flumazenil. Dantrolene.
Nitroprusside. Rate control, rhythm conversion, and anticoagulation. If stable, rate control with carotid massage or other vagal stimulation; if unsuccessful, consider adenosine.
INH, penicillamine, hydralazine, procainamide, chlorpromazine, methyldopa, quinidine. B12 deficiency.Folate deficiency.Treat CO poisoning with 100% O2 or with hyperbaric O2 if poisoning is severe or the patient is pregnant.
Bladder rupture or urethral injury.Retrograde cystourethrogram.Widened mediastinum (> 8 cm), loss of aortic knob, pleural cap, tracheal deviation to the right, depression of left main stem bronchus.
Free air under the diaphragm, extravasation of contrast, severe bowel distention, space-occupying lesion (CT), mesenteric occlusion (angiography).
The most common organism in burn-related infections. Method of calculating fluid repletion in burn patients. Acceptable urine output in a trauma patient. Acceptable urine output in a stable patient. Cannon “a” waves. Signs of neurogenic shock. Signs of ↑ ICP (Cushing’s triad).
CO, ↓ pulmonary capillary wedge pressure (PCWP), peripheral vascular resistance (PVR).
CO, ↑ PCWP, ↑ PVR.CO, ↓ PCWP, ↓ PVR. Treatment of septic shock. Treatment of cardiogenic shock. Treatment of hypovolemic shock. Treatment of anaphylactic shock. Supportive treatment for ARDS. Signs of air embolism.
Trauma series.Parkland formula. 50 cc/hr. 30 cc/hr. Third-degree heart block. Hypotension and bradycardia. Hypertension, bradycardia, and abnormal respirations. Hypovolemic shock.
Cardiogenic (or obstructive) shock. Septic or anaphylactic shock. Fluids and antibiotics. Identify cause; pressors (e.g., dopamine). Identify cause; fluid and blood repletion. Diphenhydramine or epinephrine 1:1000. Continuous positive airway pressure. A patient with chest trauma who was previously stable suddenly dies. AP chest, AP/lateral C-spine, AP pelvis.
This section is a database of recommended clinical science review books, sample examination books, and commercial review courses marketed to medical students studying for the USMLE Step 2 CK. For each book, we list the Title of the book, the First Author (or editor), the Current Publisher, the Copyright Year, the Edition, the Number of Pages, the ISBN Code, the Approximate List Price, the Format of the book, and the Number of Test Questions. Most entries also include Summary Comments that describe the style and utility of each book for studying. Finally, each book receives a Rating. The books are sorted into a comprehensive section as well as into sections corresponding to the six clinical disciplines (internal medicine, neurology, OB/GYN, pediatrics, psychiatry, and surgery). Within each section, books are arranged first by Rating, then by Author, and finally by Title.
For this seventh edition of First Aid for the USMLE Step 2 CK, the database of review books has been completely revised, with in-depth summary comments on more than 100 books and software. A letter rating scale with six different grades reflects the detailed student evaluations. Each book receives a rating as follows:
The Rating is meant to reflect the overall usefulness of the book in preparing for the USMLE Step 2 CK exam. This is based on a number of factors, including:
The cost of the bookThe readability of the textThe appropriateness and accuracy of the bookThe quality and number of sample questionsThe quality of written answers to sample questionsThe quality and appropriateness of the illustrations (e.g., graphs, diagrams, photographs)
The length of the text (longer is not necessarily better)
The quality and number of other books available in the same discipline
The importance of the discipline on the USMLE Step 2 CK exam
Please note that the rating does not reflect the quality of the book for purposes other than reviewing for the USMLE Step 2 CK exam. Many books with low ratings are well written and informative but are not ideal for boards preparation. We have also avoided listing or commenting on the wide variety of general textbooks available in the clinical sciences.
Evaluations are based on the cumulative results of formal and informal surveys of hundreds of medical students from medical schools across the country. The summary comments and overall ratings represent a consensus opinion, but there may have been a large range of opinions or limited student feedback on any particular book.
Please note that the data listed are subject to change because:
Publishers’ prices change frequently.Individual bookstores often charge an additional markup.New editions come out frequently, and the quality of updating varies.
The same book may be reissued through another publisher.We actively encourage medical students and faculty to submit their opinions and ratings of these clinical science review books so that we may update our database (see “How to Contribute,” p. xv). In addition, we ask that publishers and authors submit review copies of clinical science review books, including new editions and books not included in our database, for evaluation. We also solicit reviews of new books or suggestions for alternate modes of study that may be useful in preparing for the examination, such as flash cards, computer-based tutorials, commercial review courses, and Internet Web sites.
No material in this book, including the ratings, reflects the opinion or influence of the publisher. All errors and omissions will gladly be corrected if brought to the attention of the authors through the publisher.
Lippincott Williams & Wilkins, 2006, 3rd ed., 546 pages, ISBN 9781405105095
A concise book presented in outline format, packed with key information across the various fields of medicine. Pros: Very high yield. Makes nice use of tables and charts. Good for quick study and last-minute review. Useful on the wards as well, and fits in a pocket. Cons: Small print. Not tremendously detailed, but covers many topics. More in-depth books are required for further explanation. Summary: A good, comprehensive review, but lacks some detail.
Hanley & Belfus, 2004, 2nd ed., 350 pages, ISBN 9781560536109 Includes 750 vignette-style questions in 15 test blocks. Pros: Questions are case based and offer a good approximation of real boards questions. Questions cover high-yield topics, and explanations are terse but adequate. Many questions also include images and associated laboratory findings. Cons: Explanations may not be adequate for those who require an in-depth review of certain topics. Summary: Excellent vignette-type questions in mock exam format.
Hanley & Belfus, 2004, 2nd ed., 250 pages, ISBN 9781560536086
Typical Secrets-series format, with questions and answers organized by specialty. Pros: A concise review of many high-yield topics. Makes good use of clinical images, including patient photos, blood smears, and radiographs. Gives clinical pearls that help differentiate and diagnose common clinical presentations. Cons: Contains no clinical vignettes; simply lists questions that might be posed on the wards. Does not follow Step 2 CK format. Expensive. Content overlaps with that of other books by Brochert. Summary: An excellent book to page through during brief periods of “downtime.” Does not substitute for a formal review or practice tests. A portable book that stresses relevant topics in a quick, easy format.
$39.95 Review $35.95 Test/750 q $39.95 ReviewFirst Aid Cases for the USMLE Step 2 CK $41.95 Review
LE McGraw-Hill, 2006, 1st ed., 272 pages, ISBN 9780071464116 A review of high-yield clinical vignettes for the Step 2 CK exam. Pros: Cases provide detailed answers to high-yield topics and are arranged in an easy-to-follow format. Emphasizes the most likely diagnosis, the next step, and initial management answers. Cons: Some topics are either not covered or given only brief treatment. Summary: A good review with emphasis on vignette-style case presentations and boardsrelevant answers, but not sufficient as a stand-alone text for review.
B+Crush Step 2 BROCHERT Mosby, 2007, 3rd ed., 352 pages, ISBN 9781416029762 A comprehensive review of many high-yield topics, organized by spe-cialty. Pros: Places good emphasis on key points. The conversational style is easy to read. Makes good use of charts and diagrams. Covers surgical topics in more depth than similar books. Cons: Not compre-hensive. Contains no practice questions or vignettes. Not sufficiently detailed to be used alone for Step 2 CK preparation. Summary: A solid review of key points and frequently tested topics. Should probably be supplemented with other review material and practice tests. $39.95 Review B+Lange Q&A: USMLE Step 2 CHAN McGraw-Hill, 2008, 6th ed., 440 pages, ISBN 9780071494007 Review questions organized by specialty along with two comprehen-sive practice exams. Pros: Overall question content is good, with broad coverage of high-yield topics. Well illustrated. Cons: Vignettes are brief, with short explanations. Some questions are more detailed than actual Step 2 CK questions. Summary: Well suited to focused spe-cialty review by virtue of overall review questions on high-yield topics. A good buy for the number of questions. $44.95 Test/1000+ q B+Lange Practice Tests: USMLE Step 2 GOLDBERG McGraw-Hill, 2005, 3rd ed., 288 pages, ISBN 9780071446167 Comprehensive test questions. Pros: A great source of high-yield ques-tions covering all topics. Many questions include clinically relevant ra-diographs and photographs of pathology. Offers adequate explanations. Cons: Some questions are not vignette style and do not refl ect boards format. Summary: A good compilation of test questions that focus on high-yield material, but some questions still do not reflect boards style. A good source of supplemental questions. $44.95 Test/900 q
NMS Review for USMLE Step 2 CK $46.95 Test/900 q
Lippincott Williams & Wilkins, 2006, 3rd ed., 654 pages, ISBN 9780781765220 A comprehensive review book in question-and-answer format. Pros: Offers clear, concise, and broad coverage of high-yield topics, presented in a format similar to that of the actual Step 2 CK exam. Complete explanations. Cons: Questions are more detailed than needed for the boards. Lacks illustrations or images. Summary: A good source of Step 2 CK–style questions with appropriate format and content, but questions may be more detailed than those on the actual exam.
B+Underground Clinical Vignettes: Step 2 Bundle KIM Lippincott Williams & Wilkins; 2007, 4th ed., 256 pages, ISBN 9780781763639 A set containing clinical case scenarios of the various specialties, in-cluding OB/GYN, neurology, internal medicine, surgery, emergency medicine, psychiatry, and pediatrics, along with an extensive color at-las supplement. Pros: Well organized by focus points: pathogenesis, epidemiology, management, complications, and associated diseases. Small, portable texts. Cons: Not comprehensive; best used as a supple-ment for review. Summary: Organized and easy-to-read clinical vi-gnettes. Excellent as a supplement to studying, but not sufficient by it-self. More economical to purchase the nine-volume set than individual volumes. $159.95 Review B+Step-Up to USMLE Step 2 VAN KLEUNEN Lippincott Williams & Wilkins, 2007, 2nd ed., 352 pages, ISBN 9780781771566 A Step 2 CK test review typical of the Step-Up series format, organized by system. Pros: A concise boards review resource with many tables or-ganizing the information and quick facts isolated in the page margins. Cons: Not very detailed, but covers most boards exam topics and serves as a good source of study organization. Summary: A good, com-prehensive review for the Step 2 CK exam with many quick-study fea-tures. $39.95 Review
B Lange Outline Review: USMLE Step 2 GOLDBERG McGraw-Hill, 2006, 5th ed., 650 pages, ISBN 9780071451925 A comprehensive boards review book with chapters organized by clini-cal discipline. Pros: A comprehensive review source with extensive coverage of clinical topics and an organized, in-depth review of each. Cons: Covers some low-yield topics. Includes relatively few images, figures, or tables. Summary: A solid, single-source, comprehensive re-view for the Step 2 CK exam. $41.95 Review B−USMLE Step 2 Made Ridiculously Simple CARL MedMaster, 2006, 3rd ed., 356 pages, ISBN 9780940780729 A general review of topics for the Step 2 CK exam. Presented in out-line format with tables and brief discussions. Pros: A quick review. Useful in areas that might otherwise be overlooked—e.g., ophthalmol-ogy, dermatology, and ENT. Helpful for last-minute review. Cons: The tabular format does not provide substantive details but aids in the memorization of lists. Some have found it too simple. Summary: Highlights most high-yield topics, but should not be used alone for re-view. $29.95 Review
A compilation of online programs for Step 2 CK review, including a large test bank. Pros: Questions can be arranged by topic or randomly to simulate the real exam. Tests are timed to simulate boards conditions. Includes an extensive number of questions in vignette format. The content level of questions reflects the boards test. Explanations are thorough, and the text now reports the national average for each question. Allows students to identify strong and weak points. Cons: Very expensive. Online lectures can be difficult to watch for extensive periods of time. Summary: A good source of questions with thorough explanations, but the price may be prohibitive for many.
Step 2 CK Qmax A test bank with more than 2600 questions. Pros: Written by students who have done well on the Step 2 CK exam; then reviewed by faculty experts. Offers highly comprehensive explanations. Cons: A newer resource that is still evolving. Summary: A great question bank source. New, but feedback from students has been excellent thus far.
A test bank with more than 2000 questions. Similar to the Kaplan test bank. Pros: Features well-written questions with explanations. Cheaper than Kaplan. Questions tend to be more difficult than those on the actual exam, but many students find this an advantage during preparation. Cons: Some questions are overly picky. Summary: An excellent source of questions that is cheaper than Kaplan.
A comprehensive test bank with more than 3300 questions and explanations. Similar in style to the Kaplan question bank described above. Pros: Features a large number of questions. Mimics the CBT format. Cheaper than Kaplan. Access is often free through medical libraries. Cons: Questions can be more obscure than those appearing on the actual exam. Questions overlap with those of the PreTest series of review books. Summary: A fair source of questions that may be good for supplemental review, especially in preparation for clerkship shelf exams.
A−Step-Up to Medicine AGABEGI Lippincott Williams & Wilkins, 2008, 2nd ed., 560 pages, ISBN 9780781771535 A comprehensive review of commonly tested diseases and topics in in-ternal medicine, organized in an outline format. Includes a color atlas and an appendix on interpreting x-rays, ECGs, and physical exam find-ings. Pros: Very comprehensive, with informative tables and diagrams to help synthesize information. Includes occasional clinical vignettes that correlate with the topic being discussed. Quick facts to remember are included in the margins of each page. Cons: Very lengthy. Geared more toward clerkship preparation than Step 2 CK review. Summary: A good book that is packed with useful information for the wards, but may be too lengthy and detailed for the Step 2 CK exam. $42.95 Review A−High-Yield Internal Medicine NIRULA Lippincott Williams & Wilkins, 2006, 3rd ed., 128 pages, ISBN 9780781781695 A core review of internal medicine in outline format. Pros: Focuses on high-yield diseases and symptoms. A quick and easy read. Cons: Not comprehensive. Lacks many illustrations and has no index. Summary: A good, fast review presented in a format that allows for quick and re-petitive reading. Best used as a supplement, not as a primary study source. $26.95 Review
First Aid for the Medicine Clerkship $42.95 ReviewMcGraw-Hill, 2005, 2nd ed., 416 pages, ISBN 9780071448758 A high-yield review of symptoms and diseases. Pros: A comprehensive review that is well organized by symptom with good illustrations, scenarios, diagrams, algorithms, and mnemonics. Cons: May not be suited to readers who prefer information arranged in text form. May be too basic for certain topics. Summary: An excellent, concise review of medicine for those who prefer its format.
Underground Clinical Vignettes: Emergency Medicine $22.95 ReviewLippincott Williams & Wilkins, 2007, 4th ed., 256 pages, ISBN 9780781768344 A clinical vignette–based review of emergency medicine topics. Pros: Well organized by focus points: pathogenesis, epidemiology, management, complications, and associated diseases. Well illustrated, and includes high-yield “minicases” and links to the Underground Clinical Vignettes’ Clinical and Basic Science Color Atlases. Cons: Not comprehensive; best used as a supplement. Summary: An organized and easy-to-read supplement to studying.
Underground Clinical Vignettes: Internal Medicine, Vols. I and IILippincott Williams & Wilkins, 2007, 4th ed., 256 pages each, ISBN 9780781768351, 9780781768368
A clinical vignette–based review of common topics in internal medicine. Pros: Well organized by focus points: pathogenesis, epidemiology, management, complications, and associated diseases. Vignettes mirror the boards-style presentation of questions. Cons: Not comprehensive; best used as a supplement. Summary: An organized and easy-to-read supplement to studying.
Lippincott Williams & Wilkins, 2006, 2nd ed., 425 pages, ISBN 9781405104913
A compendium of vignette-type cases arranged by symptom, followed by related questions and answers. Pros: An excellent companion to the Blueprints series. Focuses on high-yield cases. Easy to read with nice illustrations and a good review of management. Cons: Not comprehensive; use as a supplement for review. Better suited to clerkship preparation than to the Step 2 CK exam. Summary: An organized and easy-to-read supplement. Adds clinical correlates to the Blueprints series. Best used with the Blueprints text.
Hanley & Belfus, 2004, 4th ed., 608 pages, ISBN 9781560533870 A question-and-answer text typical of the Secrets series. Pros: Covers a great deal of clinically relevant information. Concise answers are given with pearls, tips, and memory aids. Cons: Too lengthy and detailed for USMLE review. Summary: Not a focused review. May be more appropriate for wards use.
$22.95 Review each $29.95 Test/200 q $39.95 ReviewB Medicine Recall BERGIN Lippincott Williams & Wilkins, 2007, 3rd ed., 832 pages, ISBN 9780781794145 A review book presented in standard Recall-series question-and-answer format, organized by medical specialty. Pros: Addresses a broad range of high-yield clinical topics. Presented in a format that is good for self-quizzing. Appropriate level of detail. Cons: Contains no vignettes or images; requires significant time commitment. Style simulates ques-tions asked on rounds, not those on the Step 2 CK exam. Summary: Written in a style that may be more conducive to wards than to boards preparation. Best used as a supplement to other resources. $39.95 Review B In A Page Emergency Medicine CATERINO Blackwell Publishing, 2003, 1st ed., 344 pages, ISBN 9781405103572 A collection of short, one-page summaries of 250 medical emergencies discussed in terms of etiology, differential diagnosis, presentation, diag-nostic tests, treatment, and disposition. Pros: Concise and high yield. Covers a wide variety of emergencies seen in the ER. Cons: The text is crowded and somewhat confusing. Contains no images or diagrams. Summary: Good for use during the emergency medicine clerkship, but may not be appropriate for Step 2 CK review. $34.95 Review B Blueprints Clinical Cases in Family Medicine CHANG Lippincott Williams & Wilkins, 2006, 2nd ed., 437 pages, ISBN 9781405104951 A compendium of vignette-type cases arranged by symptom, followed by related questions and answers. Pros: An excellent companion to the Blueprints series. Focuses on high-yield cases. Easy to read with nice illustrations and a good review of management. Cons: Not compre-hensive; best used as a supplement for review. Summary: An organized and easy-to-read supplement. Adds clinical correlates to the Blueprints series. Best if used with the Blueprints text. $34.95 Test/200 q
B Internal Medicine Pearls HEFFNER Elsevier, 2001, 2nd ed., 249 pages, ISBN 9781560534044 One-page reviews of more than 200 diseases discussed by etiology, epi-demiology, signs/symptoms, differential diagnosis, diagnostic tests, treatment, and prognosis. Pros: A fast and concise review of high-yield information on common diseases. Cons: Text is crowded onto one page without any images or diagrams. Summary: Useful for quick study on the wards, but may not be comprehensive enough for the Step 2 CK exam. $41.95 Review B Blueprints Q & A Step 2 Medicine SHINAR Lippincott Williams & Wilkins, 2004, 2nd ed., 276 pages, ISBN 9781405103893 Two hundred vignette-style questions. Pros: A nice companion to the Blueprints series. Focuses on high-yield topics. Explanations are easy to follow. Cons: Not comprehensive; best used as a supplement for re-view. Expensive; includes few questions given the cost of the book. Summary: An organized and easy-to-read supplement. Adds clinical correlates to the Blueprints series. $19.95 Test/200 q B First Aid for the Emergency Medicine Clerkship STEAD McGraw-Hill, 2006, 2nd ed., 416 pages, ISBN 9780071448734 A high-yield review of symptoms and diseases. Pros: A comprehensive review; well organized by symptom with good illustrations, scenarios, diagrams, algorithms, and mnemonics. Cons: May not be suited to the reader who prefers information arranged in text form. Summary: An excellent review of emergency medicine and a nice presentation of high-yield topics for Step 2 CK preparation, but not sufficient for stand-alone review for the Step 2 CK exam. $42.95 Review B Blueprints in Medicine YOUNG Lippincott Williams & Wilkins, 2009, 5th ed., 448 pages, ISBN 9780781788700 A text review of internal medicine, organized by common diseases and common symptoms. Includes a question-and-answer section with ex-planations. Pros: A well-organized, concise review that makes for easy reading. Differential diagnoses for symptoms are helpful. Contains good charts and diagrams. Cons: Offers few illustrations. Contains some superfluous details, and some areas are too broad and simplistic to be useful for testing purposes. Summary: Poorly illustrated, but a good primary boards review for internal medicine. $38.95 Review/Test/100 q
PreTest Medicine $26.95 Test/500 qMcGraw-Hill, 2006, 11th ed., 356 pages, ISBN 9780071455534 A question-and-answer format organized by medical subspecialty. Pros: Organization by subspecialty helps readers pinpoint weak areas. Offers a substantial number of vignette-style questions with detailed explanations. Cons: Many questions are more detailed than needed for the boards and are geared more toward the shelf exam. Few illustrations. Summary: A solid source of challenging review questions.
A−Blueprints in Neurology DRISLANE Lippincott Williams & Wilkins, 2009, 3rd ed., 256 pages, ISBN 9780781796859 A review of neurology by disease and symptom with a brief exam. Pros: Reviews high-yield topics of a complex discipline while remaining easy to follow. Makes good use of tables, images, and diagrams. Questions in the exam are similar to those found on both the shelf exam and Step 2 CK. Cons: Lengthy. Summary: An excellent review of high-yield material for the wards and the Step 2 CK exam. $37.95 Review B+PreTest Neurology ANSCHEL McGraw-Hill, 2009, 7th ed., 352 pages, ISBN 9780071597920 A question-and-answer review of neurology. Pros: Offers thorough cov-erage of neurology topics with a good number of clinical vignettes. Places appropriate emphasis on common topics and thorough explana-tions of answers. Good practice for interpreting common head CTs/ MRIs that might be tested. Cons: Some questions may be more de-tailed than needed for the boards. Summary: A good source of test questions for rapid review of neurology, but may be too detailed for boards review. $26.95 Test/500 q
B+Underground Clinical Vignettes: Neurology KIM Lippincott Williams & Wilkins, 2007, 4th ed., 256 pages, ISBN 9780781768375 A clinical vignette–based review of high-yield topics in neurology. Pros: Well organized by focus points: pathogenesis, epidemiology, management, complications, and associated diseases. Well illustrated, and includes “minicases,” links to a color atlas supplement, and up-dated treatments. Cons: Not comprehensive; best used as a supple-ment for review. Summary: An organized and easy-to-read supplement to studying. Lengthy for a dedicated review of neurology. $22.95 Review B Neurology Recall MILLER Lippincott Williams & Wilkins, 2003, 2nd ed., 377 pages, ISBN 9780781745888 Brief question-and-answer format. Pros: Reviews many important facts, making it useful for self-quizzing. Cons: Not a comprehensive review. Lengthy and lacks illustrations. Concepts are not integrated. Sum-mary: Good for review of some high-yield concepts, but not a stand-alone resource for this topic. $36.95 Review
B Neurology Secrets ROLAK Elsevier, 2004, 4th ed., 480 pages, ISBN 9781560536215 A review book presented in Secrets-series question-and-answer format. Pros: A concise review of many high-yield topics. Makes good use of clinical images. Cons: Contains no clinical vignettes; instead, offers lists of questions that might be posed on the wards. Lacks a structured format, and leaves out important information. Relatively expensive and lengthy. Not a reference book. Summary: Overall, good content for self-quizzing and study, but does not substitute for a formal review or practice tests. More appropriate for clerkship than for boards review. $45.95 Review B Blueprints Clinical Cases in Neurology SHETH Lippincott Williams & Wilkins, 2006, 2nd ed., 390 pages, ISBN 9781405104944 Vignette-type cases organized by symptom, followed by related ques-tion and answers. Pros: An excellent companion to the Blueprints sub-specialty series. Focuses on high-yield cases. Easy to read, with nice il-lustrations and a good review of management. Cons: Not comprehensive; best used as a supplement. Offers few illustrations. Summary: Organized and easy to read. Adds clinical correlates to the Blueprints series. $29.95 Review
A−Blueprints in Obstetrics and Gynecology CALLAHAN Lippincott Williams & Wilkins, 2008, 5th ed., 368 pages, ISBN 9780781782494 A text review with tables and illustrations. Includes a short exam with explanations. Pros: Places strong emphasis on high-yield topics with concise text, clear diagrams, and many classic illustrations. Makes for easy reading. Appropriate for both clinical clerkship and Step 2 CK preparation. Cons: Some topics are overly detailed, while some are not detailed enough. Summary: Overall, a good choice for boards and wards preparation. $38.95 Review/Test/100 q A−Blueprints Clinical Cases in Obstetrics and Gynecology CAUGHEY Lippincott Williams & Wilkins, 2006, 2nd ed., 418 pages, ISBN 9781405104906 Vignette-type cases arranged by symptom, followed by related ques-tions and answers. Pros: An excellent companion to the Blueprints se-ries. Focuses on high-yield cases. Easy to read, with nice illustrations and a good review of management. Cons: Not comprehensive; best used as a supplement. Summary: An organized and easy-to-read sup-plement. Adds clinical correlates to the Blueprints series. $29.95 Test/200 q A−
Underground Clinical Vignettes: OB/GYN $22.95 ReviewLippincott Williams & Wilkins, 2007, 4th ed., 256 pages, ISBN 9780781768405
A clinical vignette–style review of frequently tested diseases in obstetrics and gynecology. Pros: Well organized by focus points: pathogenesis, epidemiology, management, complications, and associated diseases. Well illustrated. An easy read that stresses high-yield facts. Cons: Not comprehensive; best used as a supplement. Summary: Wellorganized and easy-to-read practice vignettes.
B+NMS Obstetrics and Gynecology PFEIFER Lippincott Williams & Wilkins, 2007, 6th ed., 496 pages, ISBN 9780781770712 A detailed outline of OB/GYN with few tables and diagrams. Pros: A comprehensive review for both wards and boards. The final exam is relatively good and offers complete explanations. Cons: The OB/GYN review is dense and lengthy. Many questions do not reflect the boards format. Lacks illustrations. Summary: A complete review with ques-tions and discussions. Better for clerkship studying than for boards re-view. $48.95 Review/Test/500 q B+High-Yield Obstetrics and Gynecology SAKALA Lippincott Williams & Wilkins, 2005, 2nd ed., 208 pages, ISBN 9780781796309 A review of high-yield topics in outline format. Clinical scenarios at the end of each chapter highlight key points. Pros: Easy to read, with a good discussion of high-yield topics. Cons: Lacks depth and contains no practice questions. Summary: A quick but superficial review. $26.95 Review B+B+
First Aid for the OB/GYN ClerkshipMcGraw-Hill, 2006, 2nd ed., 304 pages, ISBN 9780071448741 A high-yield review of symptoms and diseases. Pros: A comprehensive review with nice diagrams, images, charts, algorithms, and mnemonics. Cons: Lengthy review. Summary: An excellent review of OB/ GYN, but too lengthy for boards review.
Case Files: Obstetrics and GynecologyMcGraw-Hill, 2009, 3rd ed., 456 pages, ISBN 9780071605809A review of OB/GYN in case format with questions and answers following each vignette. Pros: Cases reflect high-yield topics and are arranged in an easy-to-follow format. Cons: Some topics are either not covered or given only brief treatment. Contains few diagrams and images. Lengthy and time-consuming for one topic. Explanations are terse. Summary: A good review of the subject in clinical vignette format, but may be too detailed for Step 2 CK review.
$42.95 Review $32.95 ReviewB+Blueprints Q & A Step 2 Obstetrics & Gynecology TRAN Lippincott Williams & Wilkins, 2004, 2nd ed., 168 pages, ISBN 9781405103909 One hundred vignette-style questions. Pros: A nice companion to the Blueprints series. Focuses on high-yield topics. Explanations are easy to follow. Cons: Not comprehensive; best used as a supplement for re-view. Sparse images. Some questions are esoteric and not boards-like. Summary: A well-organized and easy-to-read supplement. Adds clini-cal correlates to the Blueprints series. $19.95 Test/200 q B Obstetrics and Gynecology Secrets BADER Mosby, 2004, 3rd ed., 448 pages, ISBN 9780323034159 A review book presented in Secrets-series question-and-answer format, organized by topic within OB/GYN. Pros: Offers good coverage of many high-yield, clinically relevant topics. Cons: Too detailed to be useful for rapid review. Contains no vignettes and few illustrations or images. Summary: Good clinical content, but does not serve as a for-mal topic review. Better for use during clerkship than for Step 2 CK preparation. $31.95 Review B PreTest Obstetrics and Gynecology SCHNEIDER McGraw-Hill, 2009, 12th ed., 355 pages, ISBN 9780071599795 A question-and-answer review with detailed explanations for OB/GYN. Pros: Organization by subtopic may be useful for studying weak areas. Good content emphasis. Generally well illustrated. Cons: Some ques-tions are too difficult or detailed. Vignette-based questions are shorter and more simplistic than those on the Step 2 CK. Summary: A decent source of questions to supplement topic study, especially for addressing specific areas of weakness. $26.95 Test/500 q B−Obstetrics and Gynecology Recall BOURGEOIS Lippincott Williams & Wilkins, 2007, 3rd ed., 608 pages, ISBN 9780781770699 A review book presented in standard Recall-series question-and-answer style. Pros: The two-column format makes the text useful for self-quiz-zing. Reviews many high-yield concepts and facts. Cons: Questions emphasize individual facts but do not integrate concepts. Contains no vignettes or images. Coverage of some topics is spotty. Summary: Use-ful for review of selected concepts, but not a comprehensive source for Step 2 CK preparation. More appropriate for clerkship than for boards. $36.95 Review/Test/350 q
A−Platinum Vignettes: Pediatrics BROCHERT Hanley & Belfus, 2002, 1st ed., 104 pages, ISBN 9781560535331 A clinical vignette–based review of common topics in pediatrics. Pros: Well-written cases are similar to boards-type vignettes. Well illustrated. The discussion is organized by pathophysiology, diagnosis and treat-ment, and more high-yield facts. Cons: Expensive for the amount of material. Not comprehensive; best used as a supplement. Has not been updated since 2002. Summary: An organized and easy-to-read supplement to studying. $29.95 Review A−Underground Clinical Vignettes: Pediatrics KIM Lippincott Williams & Wilkins, 2007, 4th ed., 256 pages, ISBN 9780781768443 A clinical vignette review of frequently tested topics in pediatrics. Pros: Well organized by focus points: pathogenesis, epidemiology, manage-ment, complications, and associated diseases. Well illustrated, and the new edition includes “minicases” to broaden subject material and present more high-yield information. Cons: Not comprehensive; best used as a supplement to text review. Summary: Well organized and easy to read, but intended as a supplement for review. $22.95 Review A−
PreTest Pediatrics $26.95 Test/500 qMcGraw-Hill, 2006, 11th ed., 464 pages, ISBN 9780071455527 A question-and-answer review with detailed discussion. Pros: Organization by organ system is useful for pinpointing weaknesses. Gives strong, thorough explanations. Includes a fair number of vignette-style questions. Well illustrated. Cons: Some questions are too detailed or emphasize low-yield topics. Summary: A good source of questions and review for pediatrics. Solid content with good illustrations, although not entirely in Step 2 CK format.
B+Blueprints Q & A Step 2 Pediatrics FOTI Lippincott Williams & Wilkins, 2004, 2nd ed., 176 pages, ISBN 9781405103916 Vignette-style questions. Pros: A nice companion to the Blueprints se-ries. Focuses on high-yield topics. Explanations are easy to follow. Cons: Not comprehensive; best used as a supplement for review. Sparse images. Summary: An organized and easy-to-read supplement. Adds clinical correlates to the Blueprints series. $17.95 Test/100 q B+In A Page Pediatrics KAHAN Lippincott Williams & Wilkins, 2008, 2nd ed., 384 pages, ISBN 9780781770453 One-page reviews of 228 diseases/topics discussed by etiology, epide-miology, signs/symptoms, differential diagnosis, diagnostic tests, treat-ment, and prognosis. Pros: A fast and concise review of high-yield in-formation on common diseases. Cons: Each topic is crowded onto one page without any images or diagrams. Includes low-yield topics. Sum-mary: Useful for quick study on the wards, but too time intensive for Step 2 CK review. $34.95 Review B+Blueprints Clinical Cases in Pediatrics LONDHE Lippincott Williams & Wilkins, 2006, 2nd ed., 426 pages, ISBN 9781405104920 Vignette-type cases arranged by symptom followed by related questions and answers. Pros: An excellent companion to the Blueprints series. Focuses on high-yield cases. Easy to read with nice illustrations and a good review of management. Cons: Not comprehensive; best used as a supplement for review. Summary: An organized and easy-to-read supplement. Adds clinical correlates to the Blueprints series. $29.95 Test/200 q B+Blueprints in Pediatrics MARINO Lippincott Williams & Wilkins, 2008, 5th ed., 384 pages, ISBN 9780781782517 A text review of pediatrics with tables and diagrams. Includes a ques-tion-and-answer section with explanations. Pros: Appropriate focus on high-yield topics. Cons: A relatively dense text with few illustrations. Overly detailed. Summary: Good for a more comprehensive review. $38.95 Review/Test/100 q
B+Case Files: Pediatrics TOY McGraw-Hill, 2006, 2nd ed., 576 pages, ISBN 9780071463027 A review of pediatrics in case format with questions and answers fol-lowing each vignette. Pros: Cases reflect high-yield topics and are ar-ranged in an easy-to-follow format. Emphasizes the next step and the most likely diagnosis. Cons: Not suited for high-yield rapid review. Summary: An excellent review with emphasis on vignette-style case presentation and important boards-type answers, but may be too de-tailed for a stand-alone boards review book. Excellent for clerkship preparation. $29.95 Review B+A&L’s Review of Pediatrics VIESSMAN McGraw-Hill, 2004, 6th ed., 250 pages, ISBN 9780838503034 A question-and-answer review of pediatrics with detailed explanations. Pros: Questions focus on boards-relevant content. The last chapter in-cludes excellent vignette-based questions. Offers thorough, wellwritten explanations. Includes a nice primer on test-taking strategies. Cons: Non-vignette-based questions are shorter and more straightfor-ward than those on the Step 2 CK exam. Some questions may be too detailed for Step 2 CK preparation. Poorly illustrated. Summary: An excellent, concise review with appropriate content and good discus-sions, but the majority of questions do not reflect Step 2 CK style. $41.95 Test/1000+ q B−NMS Pediatrics DWORKIN Lippincott Williams & Wilkins, 2008, 5th ed., 480 pages, ISBN 9780781770750 A general review of pediatrics in outline format. Includes questions at the end of each chapter. Pros: A thorough, detailed review of pediat-rics. Boldfacing highlights key points. Case studies and a comprehen-sive exam at the end of the book (also provided on CD-ROM) are helpful. Includes a good discussion. Cons: A dense, lengthy text. Lacks good illustrations of any kind. Summary: A thorough review, but more appropriate for clerkships than for Step 2 CK review, in large part be-cause of its depth. $42.95 Review/Test/100+ q
Pediatrics Recall $36.95 ReviewLippincott Williams & Wilkins, 2007, 3rd ed., 508 pages, ISBN 9780781771184
A review book presented in a concise question-and-answer format typical of the Recall series. Pros: The two-column format makes self-quizzing easy. Emphasis is placed on diagnosis and management. Cons: Requires time commitment, and not all topics are covered thoroughly. Contains no vignettes. Summary: Useful material, but does not provide a systematic review or a substitute for practice tests. Better suited to clerkship review.
Pediatric Secrets $39.95 ReviewElsevier, 2005, 4th ed., 688 pages, ISBN 9781560536277A question-and-answer text typical of the Secrets series, organized by pediatric subspecialty. Pros: Includes a thorough discussion of a wide variety of clinical topics. Cons: Detailed content is geared toward the wards and requires significant time investment. Contains no images or illustrations. Summary: Too detailed for USMLE review; better suited to clerkship.
A Blueprints in Psychiatry MURPHY Lippincott Williams & Wilkins, 2007, 2nd ed., 304 pages, ISBN 9781405104968 A brief text review of psychiatry with DSM-IV criteria. Includes a brief question-and-answer section at the end of the book. Pros: A clear, con-cise review of psychiatry with helpful tables. Offers good coverage of high-yield topics, including pharmacology. A quick read. Cons: Too general in certain areas; requires some supplementation. Summary: A rapid review with appropriate coverage of high-yield topics. $29.95 Review/Test/74 q A−Blueprints Clinical Cases in Psychiatry HOBLYN Lippincott Williams & Wilkins, 2007, 2nd ed., 304 pages, ISBN 9781405104968 Vignette-type cases arranged by symptom, followed by related ques-tions and answers. Pros: An excellent companion to the Blueprints se-ries. Focuses on high-yield cases. Easy to read with nice illustrations and a good review of management. Cons: Not comprehensive; best used as a supplement for review. Summary: An organized and easy-to-read supplement. Adds clinical correlates to the Blueprints series. $29.95 Test/200 q
Underground Clinical Vignettes: Psychiatry $22.95 ReviewLippincott Williams & Wilkins, 2007, 4th ed., 256 pages, ISBN 9780781768467
A clinical vignette–based review of frequently tested topics in psychiatry. Pros: Well organized by focus points: pathogenesis, epidemiology, management, and associated diseases. Well illustrated, and includes “minicases” that present high-yield information. Cons: Not comprehensive; best used as a supplement. Summary: Offers organized and easy-to-read practice vignettes.
PreTest Psychiatry $26.95 Test/500 qMcGraw-Hill, 2006, 11th ed., 355 pages, ISBN 9780071455541 A question-and-answer review of topics in psychiatry. Pros: Questions are well written and organized. Most questions have appropriate content level. Offers good explanations. Cons: Includes too few vignette-type questions. Some questions are too detailed. Summary: A good source of questions and review for psychiatry and the Step 2 CK exam, although the format may not reflect the actual test.
Lippincott Williams & Wilkins, 2003, 2nd ed., 150 pages, ISBN 9780781742689 A brief outline-format review of psychiatry. Pros: A quick read, with clinical vignettes scattered throughout. Offers concise tables. Cons: Not sufficiently detailed for in-depth review. Summary: An excellent, quick review of psychiatry for use as an additional study source. Similar to High-Yield Behavioral Sciences by the same author.
A&L’s Review of PsychiatryMcGraw-Hill, 2003, 7th ed., 304 pages, ISBN 9780071402538 A general review of psychiatry with questions and answers. Pros: Includes 114 vignette-style questions appropriate for boards review. Appropriate content emphasis; thorough explanations. The new edition features updated treatment and management sections. Cons: Questions are shorter and more straightforward than those of the boards. Summary: A decent source of boards review for psychiatry, but does not reflect boards format.
Case Files: PsychiatryMcGraw-Hill, 2006, 2nd ed., 408 pages, ISBN 9780071462822A review of psychology in case format with questions and answers following each vignette. Pros: Cases reflect high-yield topics and are arranged in an easy-to-follow format. Emphasizes the next step, the most likely diagnosis, and the best initial treatment. Cons: Not suited to high-yield rapid review, and may be too detailed for Step 2 CK review. Summary: An excellent subject review that places emphasis on vignette-style case presentation and important boards-type answers. Great for the wards, and a good supplement for the boards.
$28.95 Review $34.95 Test/900+ q $29.95 ReviewREVIEW RESOURCESB Platinum Vignettes: Psychiatry BROCHERT Hanley & Belfus, 2002, 1st ed., 102 pages, ISBN 9781560535348 A clinical vignette review of common topics in psychiatry. Pros: Well-written cases are similar to boards-type vignettes. Well illustrated. Dis-cussion is organized by pathophysiology, diagnosis and treatment, and more high-yield facts. Cons: Not comprehensive; best used as a sup-plement. Summary: An organized and easy-to-read supplement to studying. Needs updating. $29.95 Review B Blueprints Q & A Step 2 Psychiatry MCLOONE Lippincott Williams & Wilkins, 2004, 2nd ed., 96 pages, ISBN 9781405103923 Vignette-style questions. Pros: A nice companion to the Blueprints se-ries. Focuses on high-yield topics. Explanations are easy to follow. Cons: Not comprehensive; best used as a supplement for review. Sparse images. Some questions are esoteric and not boards-like. Sum-mary: An organized and easy-to-read supplement. Adds clinical corre-lates to the Blueprints series. $17.95 Test/200 q B NMS Psychiatry SCULLY Lippincott Williams & Wilkins, 2007, 5th ed., 300 pages, ISBN 9780781765145 A general review of topics in outline format with questions at the end of each chapter and a comprehensive final exam. Pros: A well-written text with concise disease discussions. Includes an expanded pharma-cology section. Questions test appropriate content and have complete explanations, and the new edition offers more vignette-style questions. A good companion text for the clerkship. Cons: Does not contain enough vignette-style questions. Lengthy for purposes of boards review. Summary: A detailed review that requires time commitment. A good single choice for clerkship study, but may be too long for Step 2 CK re-view. $42.95 Review/Test/500 q
First Aid for the Psychiatry Clerkship $42.95 ReviewMcGraw-Hill, 2005, 2nd ed., 208 pages, ISBN 9780071448727 A high-yield review of symptoms and diseases. Pros: A comprehensive review that includes DSM-IV criteria with nice mnemonics and scenarios. Includes high-yield tear-out cards. Cons: May not appeal to readers who prefer information in text format. Summary: A good review of high-yield topics in psychiatry, but better suited to clerkship than to Step 2 CK study.
B−Psychiatry Recall FADEM Lippincott Williams & Wilkins, 2009, 3rd ed., 210 pages, ISBN 9780781776981 A review book presented in the quick question-and-answer format typi-cal of the Recall series. Pros: The two-column format is conducive to self-quizzing. Covers many high-yield facts and concepts necessary for the USMLE. Cons: Lacks vignettes, so does not substitute for practice tests. Summary: Requires time commitment. Some topics are glossed over. Best used as a supplement to other resources. $36.95 Review B−Psychiatry Made Ridiculously Simple GOOD MedMaster, 2005, 4th ed., 98 pages, ISBN 9780940780682 Part of the “Made Ridiculously Simple” series. Pros: A comprehensive, fast read with nice tables and entertaining illustrations to highlight key points. Cons: Some areas are not detailed enough, while others are too verbose. Not boards oriented. Summary: A good, fast review, but more helpful for clerkship than for the boards. $13.95 Review B−Psychiatric Secrets JACOBSON Hanley & Belfus, 2000, 2nd ed., 536 pages, ISBN 9781560534181 A review book presented in the question-and-discussion format typical of the Secrets series, organized by topic. Pros: Offers clear explanations of important concepts in psychiatry. Makes for good wards reading. Cons: Too detailed and lengthy for review purposes. Lacks vignettes. Summary: Requires significant time commitment; not for rapid, fo-cused review. Best suited to clerkship review. $39.95 Review B−BRS Psychiatry SHANER Lippincott Williams & Wilkins, 2000, 2nd ed., 419 pages, ISBN 9780683307665 A comprehensive review of psychiatry in outline format. Vignette-style questions follow each chapter. Pros: A thorough, systematic review of clinical psychiatry. Clear, concise definitions are provided. Cons: Great deal of information for single-topic review. The pharmacology section is out of date. Summary: Good material, but requires a large time investment; needs updating. $37.95 Review/400 q
A−Underground Clinical Vignettes: Surgery KIM Lippincott Williams & Wilkins, 2007, 4th ed., 256 pages, ISBN 9780781768474 A clinical vignette–based review of frequently tested surgical topics. Pros: Well organized by focus points: pathogenesis, epidemiology, management, complications, and associated diseases. Well illustrated and includes “minicases” that present high-yield information. Cons: Not comprehensive; best used as a supplement to review. Summary: Well-organized and easy-to-read practice vignettes. $22.95 Review A−Case Files: Surgery TOY McGraw-Hill, 2006, 2nd ed., 504 pages, ISBN 9780071463041 A review of surgery in case format with questions and answers follow-ing each vignette. Pros: Cases reflect high-yield topics and are ar-ranged in an easy-to-follow format. Emphasizes the next step and the most likely diagnosis. Cons: Not suited to high-yield rapid review, and may be too detailed for Step 2 CK preparation. Summary: An excel-lent review with emphasis on vignette-style case presentation and im-portant boards-type answers. Great for clerkship study, and a good sup-plement for boards study. $29.95 Review
B+Platinum Vignettes: Surgery and Trauma BROCHERT Hanley & Belfus, 2002, 1st ed., 102 pages, ISBN 9781560535355 A clinical vignette–based review of common topics in surgery and trauma medicine. Pros: Well-written cases are similar to boards-type vi-gnettes. Well illustrated. Discussion is organized by pathophysiology, diagnosis and treatment, and more high-yield facts. Cons: Expensive for the amount of material. Not comprehensive; best used as a supple-ment. Summary: An organized and easy-to-read supplement to study-ing. $29.95 Review B+PreTest Surgery KAO McGraw-Hill, 2009, 12th ed., 373 pages, ISBN 9780071598637 A review of topics in general surgery in question-and-answer format. Pros: Predominantly case based. Well organized by subspecialty. Cons: Many questions are too detailed or esoteric and do not refl ect boards style. Some explanations are overly detailed. Summary: A thorough re-view, but questions may be beyond the level needed for Step 2 CK preparation. $26.95 Test/500 q
B NMS Surgery JARRELL Lippincott Williams & Wilkins, 2007, 5th ed., 645 pages, ISBN 9780781759014 An outline review of general surgery and surgical subspecialties. Pros: Well organized and thorough. Vignette-style questions are included af-ter each chapter with good explanations. Cons: Dense, detailed text. Few tables or illustrations. Summary: A comprehensive surgery review, but very time consuming. More appropriate for clerkship than for boards review. $42.95 Review/Test/350 q B In A Page Surgery KAHAN Lippincott Williams & Wilkins, 2003, 1st ed., 288 pages, ISBN 9781405103657 One-page reviews of diseases/topics discussed by etiology, epidemiol-ogy, signs/symptoms, differential diagnosis, diagnostic tests, treatment, and prognosis. Pros: A fast and concise review of high-yield informa-tion on common diseases. Cons: Text is crowded onto one page with-out any images or diagrams. Includes low-yield topics. Summary: Use-ful for quick study on the wards, but too time intensive for Step 2 CK review. $34.95 Review
Blueprints in Surgery $38.95 Review/Test/100 qLippincott Williams & Wilkins, 2009, 5th ed., 320 pages, ISBN 9780781788687
A short text review of general surgery with tables and diagrams. A brief question-and-answer section is included. Pros: Well organized. Easy to read, with a strong focus on high-yield topics. Includes clear diagrams. Cons: Some sections are overly detailed (e.g., anatomy), while others are occasionally too simplistic. Too few illustrations. Summary: A good review of surgery, but not ideal for Step 2 CK preparation.
Blueprints Clinical Cases in Surgery $29.95 Test/200 qLippincott Williams & Wilkins, 2006, 2nd ed., 304 pages, ISBN 9781405104937
Vignette-type cases arranged by symptom followed by related questions and answers. Pros: A excellent companion to the Blueprints series. Focuses on high-yield cases. Easy to read with nice illustrations and a good review of management. Cons: Not comprehensive; best used as a supplement for review. Summary: An organized and easy-to-read supplement. Adds clinical correlates to the Blueprints series.
B High-Yield Surgery NIRULA Lippincott Williams & Wilkins, 2005, 2nd ed., 160 pages, ISBN 9780781776561 An outline review of most common general surgery topics. Pros: Con-cise; useful for quick topic review. Well organized. Cons: Information can be superficial. Some topics are omitted. Offers no practice ques-tions. Summary: A lean text for rapid review. $26.95 Review B A&L’s Review of Surgery WAPNICK McGraw-Hill, 2003, 4th ed., 320 pages, ISBN 9780071378147 A general review of surgery with questions and answers. Pros: Good clinical emphasis. Includes many vignette-style questions. Explana-tions are thorough. Cons: Some questions are too short, and the style does not reflect that of the Step 2 CK exam. Questions are highly vari-able in difficulty and are often far too detailed. Offers few illustrations. Summary: Good content for the exam, but much too detailed for clerkship and Step 2 CK review. $34.95 Test/1000+ q B−Surgical Recall BLACKBOURNE Lippincott Williams & Wilkins, 2008, 5th ed., 800 pages, ISBN 9780781770767 A review book presented in standard Recall-series question-and-answer format. Pros: Questions emphasize important, high-yield clinical con-cepts. Columns allow for self-testing. Fast review. Good preparation for “pimping” on rounds. Cons: Does not feature boards-type questions. Poorly organized. Coverage of some topics is spotty. Summary: A use-ful adjunct to a more organized topic review. Much more appropriate for clerkship than for boards review. $44.95 Review BAbernathy’s Surgical Secrets HARKEN Elsevier, 2008, 6th ed., 534 pages, ISBN 9780323057110 A review book presented in a question-and-answer format typical of the Secrets series. Pros: Discussions are up to date and thorough. Cons: Too detailed for the purposes of the Step 2 CK, yet not comprehen-sive. Summary: Not a well-organized review. Better suited to clerkship than to boards preparation. $47.95 Review−
Pocket Surgery $36.95 ReviewLippincott Williams & Wilkins, 2001, 1st ed., 160 pages, ISBN 9780781735797 A review of high-yield surgical material in outline format. Pros: A fast, easy read. Portable. Highlights high-yield information in “fact boxes.” Cons: Some material is not detailed enough. Offers no illustrations. Summary: Good for rapid review during clerkship. Does not contain enough detailed information to be used as a single study source for the boards.
First Aid for the International Medical Graduate $39.95 ReviewMcGraw-Hill, 2002, 2nd ed., 313 pages, ISBN 9780071385329A high-yield review for the IMG on how to pass the USMLE boards and adapt to medical culture in the United States. Pros: A comprehensive, well-organized review. Cons: Some readers may need to obtain additional information from other sources. Immigration and visa information is outdated. Summary: An excellent review of material for the IMG. Best used as a primer for boards review.
Commercial preparation courses can be helpful for some students, but such courses are typically expensive and require significant time commitment. They are usually effective in organizing study material for students who feel overwhelmed by the sheer volume of material involved in Step 2 CK preparation. Note that multiweek courses may be quite intense and may thus leave limited time for independent study. Also note that some commercial courses are designed for first-time test takers while others focus on students who are repeating the exam. In addition, some courses are geared toward IMGs who want to take all three Steps in a limited amount of time.
Student experience and satisfaction with review courses are highly variable. We suggest that you discuss options with recent graduates of the review courses you are considering. In addition, course content and structure can change rapidly. Some student opinions can be found in discussion groups on the World Wide Web. Listed below is contact information for some Step 2 CK commercial review courses.
440 Wrangler Drive, Suite 100 Coppell, TX 75019 (214) 632-5466 Fax: (214) 292.8568 info@falconreviews.com www.falconreviews.com 700 South Flower Street Los Angeles, CA 90017 (800) KAP-TEST (800-527-8378) www.kaptest.com
P.O. Box 22174 East Lansing, MI 48909-2174 (866) MedPass (866-633-7277) Fax: (517) 347-7005 contactus@northwesternmedicalreview.com http://northwesternmedicalreview.com 1909 Tyler Street, Suite 305 Hollywood, FL 33020 (877) 662-2005 Fax: (954) 926-3333 sales@pmre.com www.pmre.com
Youel’s Prep, Inc.P.O. Box 31479 Palm Beach Gardens, FL 33420 (800) 645-3985 Fax: (561) 622-4858 info@youelsprep.com www.youelsprep.com
A-a alveolar-arterial (oxygen gradient) AAA abdominal aortic aneurysm AAMC Association of American Medical
Colleges ABG arterial blood gas ABI ankle-brachial index ABVD Adriamycin (doxorubicin), bleomycin, vinblastine, dacarbazine AC abdominal circumference ACA anterior cerebral artery ACC American College of Cardiology ACE angiotensin-converting enzyme ACEI angiotensin-converting enzyme (protocol) ACTH adrenocorticotropic hormone AD Alzheimer’s disease ADA American Diabetes Association,
Americans with Disabilities Act ADH antidiuretic hormone ADHD attention-defcit hyperactivity disorder ADPKD autosomal-dominant polycystic disease 5-aminosalicylic acid acetylsalicylic acid atypical squamous cells atypical squamous cells suspicious of high-grade dysplasia atypical squamous cells of tachycardia abdominal x-ray British anti-Lewisite (dimercaprol), cytoplasmic antibody CBC complete blood count CBT cognitive-behavioral therapy, computer-based testing CCB calcium channel blocker CCS computer-based case simulation CD cluster of differentiation CEA carcinoembryonic antigen CF cystic f brosis CFU colony-forming unit CGD chronic granulomatous disease cGMP cyclic guanosine monophosphate CHF congestive heart failure CHOP cyclophosphamide (Cytoxan), hydroxydaunorubicin (Adriamycin), Oncovin (vincristine), prednisone
CI conf dence interval CIN candidate identif cation number, cervical intraepithelial neoplasia CJD Creutzfeldt-Jakob disease CK clinical knowledge, creatine kinase CKD chronic kidney disease CK-MB creatine kinase, MB fraction CLL chronic lymphocytic leukemia CML chronic myelogenous leukemia CMP comprehensive metabolic panel CMV cytomegalovirus CN cranial nerve CNS central nervous system CO carbon monoxide COGME Council on Graduate Medical disease continuous positive airway pressure cardiopulmonary resuscitation child protective services creatinine crown-rump length C-reactive protein clinical skills central sleep apnea combined system disease cerebrospinal f uid contraction stress test computed tomography carpal tunnel syndrome cerebrovascular accident central venous pressure chorionic villus sampling chest x-ray dilation and curettage dilation and evacuation developmental age diastolic blood pressure desmopressin acetate diethylstilbestrol dual-energy x-ray absorptiometry direct f uorescent antibody dehydroepiandrosterone dehydroepiandrosterone sulfate Department of Homeland Security diabetes insipidus disseminated intravascular coagulation distal interphalangeal (joint) diabetic ketoacidosis diffusion capacity of carbon monoxide diabetes mellitus disease-modifying antirheumatic drug Duchenne muscular dystrophy dimercaptosuccinic acid deoxyribonucleic acid do not intubate do not resuscitate durable power of attorney for health acid Diagnostic and Statistical Manual (of mental disorders) diphtheria, tetanus, acellular pertussis (vaccine) deep tendon ref exes
ENT ear, nose, and throatER emergency room, estrogen receptorFeNa fractional excretion of sodiumFiO2 fraction of inspired oxygenFSMB Federation of State Medical BoardsFTT failure to thriveHHV 5-HIAA Hib 5-f uorouracil fever of unknown origin forced vital capacity glucose-6-phosphate dehydrogenase gestational age gamma-aminobutyric acid global assessment of functioning group A streptococcus glioblastoma multiforme, glomerular basement membrane group B streptococcus, Guillain- stimulating factor gram-negative rod gonadotropin-releasing hormone gestational trophoblastic disease genitourinary graft-versus-host disease hematoxylin and eosin highly active antiretroviral therapy hepatitis A virus hemoglobin A1c hepatitis B core antibody hepatitis B core antigen hepatitis B surface antibody hepatitis B surface antigen hepatitis B virus human chorionic gonadotropin hairy cell leukemia hydrochlorothiazide hepatitis C virus Huntington’s disease, Hodgkin’s nonketotic (coma) hyperosmolar hyperglycemic state,
Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure juvenile rheumatoid arthritis jugular venous distention jugular venous pulse potassium hydroxide Kaposi’s sarcoma Kaposi’s sarcoma–related herpesvirus kidney, ureter, bladder left anterior descending (artery) left atrial enlargement left bundle branch block large bowel obstruction low back pain lateral collateral ligament lactate dehydrogenase low-density lipoprotein loop electrosurgical excision procedure lower esophageal sphincter liver function test lymphogranuloma venereum luteinizing hormone left lower quadrant lower motor neuron last menstrual period low-molecular-weight heparin lumbar puncture lactated Ringer’s, likelihood ratio low-grade squamous intraepithelial lesion latent tuberculosis infection left upper quadrant left ventricular hypertrophy membrane attack complex, concentration medial collateral ligament metacarpophalangeal (joint) mean corpuscular volume,
MgSO4 magnesium sulfate MGUS monoclonal gammopathy of undetermined signif cance MHPSA Mental Health Professional Shortage
Area MI myocardial infarction MIBG metaiodobenzylguanidine (scan) MMA methylmalonic acid MMF mycophenolate mofetil MMR measles, mumps, rubella (vaccine) MoM multiple of the median MOPP mechlorethamine, Oncovin (vincristine), procarbazine, prednisone MPTP 1-methyl-4-phenyl-1,2,3,6 cholangiopancreatography MRI magnetic resonance imaging MRSA methicillin-resistant S. aureus MS multiple sclerosis MSAFP maternal serum α-fetoprotein MSSA methicillin-susceptible S. aureus MTP metatarsophalangeal (joint) MUA manual uterine aspiration MUA/P Medically Underserved Area and
Population MuSK muscle-specif c kinase MVA motor vehicle accident NaHCO3 sodium bicarbonate NBME National Board of Medical disorder oral contraceptive pills overdose operating room open reduction and internal f xation obstructive sleep apnea over the counter partial pressure of carbon dioxide in cytoplasmic antibody partial pressure of oxygen in arterial blood pregnancy-associated plasma protein A period acid–Schiff posterior cerebral artery percutaneous coronary intervention polycystic kidney disease posterior cruciate ligament partial pressure of carbon dioxide polycystic ovarian syndrome phencyclidine hydrochloride polymerase chain reaction polycythemia vera, pneumococcal vaccine pulmonary capillary wedge pressure patent ductus arteriosus phosphodiesterase pulseless electrical activity positive end-expiratory pressure positron emission tomography pulmonary function test prostaglandin protease inhibitor posterior inferior cerebellar artery pelvic inf ammatory disease proximal interphalangeal (joint) polycystic kidney disease phenylketonuria point of maximal impulse promyelocytic leukemia polymorphonuclear (leukocyte) paroxysmal nocturnal dyspnea per os (by mouth) partial pressure of oxygen product of conception tuberculin) PPI proton pump inhibitor PPROM preterm premature rupture of vaccine, positive predictive value PR per rectum, progesterone receptor PRBC packed red blood cell PRN pro re nata (as needed) PROM premature rupture of membranes PSA prostate-specif c antigen PT prothrombin time PTCA percutaneous transluminal coronary angioplasty PTH parathyroid hormone PTHrP parathyroid hormone–related protein PTSD post-traumatic stress disorder PTT partial thromboplastin time PUD peptic ulcer disease PUVA psoralen plus ultraviolet A PVC premature ventricular contraction PVR peripheral vascular resistance PVS persistent vegetative state QD once a day RA rheumatoid arthritis RAIU radioactive iodine uptake RBBB right bundle branch block RBC red blood cell RDS respiratory distress syndrome RDW red cell distribution width REM rapid eye movement RF rheumatoid factor RLQ right lower quadrant ROM range of motion, rupture of
Information System Student and Exchange Visitor Program syndrome of inappropriate secretion
TMJ temporomandibular joint TMP-SMX trimethoprim-sulfamethoxazole TMS transcranial magnetic stimulation TNF tumor necrosis factor TNM tumor, node, metastasis (staging) TOEFL Test of English as a Foreign
Language tPA tissue plasminogen activator TPN total parenteral nutrition TPO thyroid peroxidase TPPA  T. pallidum particle agglutination purpura TURP transurethral resection of the prostate TV tidal volume UA urinalysis UMN upper motor neuron URI upper respiratory infection USDA United States Department of
Examination urinary tract infection ultraviolet Department of Veterans Affairs vital capacity voiding cystourethrography Venereal Disease Research
Laboratory vascular endothelial growth factor ventricular f brillation vulvar intraepithelial neoplasia very low density lipoprotein vanillylmandelic acid vaso-occlusive crisis vestibulo-ocular ref ex ventriculoperitoneal ventilation/perfusion (scan) vancomycin-resistant S. aureus ventricular septal defect ventricular tachycardia von Willebrand’s disease von Willebrand factor varicella-zoster virus white blood cell World Health Organization
Hemoglobin, plasmaMean corpuscular hemoglobin Platelet count Prothrombin time Reticulocyte count Sedimentation rate, erythrocyte (Westergren) Proteins, total 1–4 mg/dL 0.16–0.62 μmol/L 4500–11,0 00/mm3 4.5–11.0  109/L 54–62% 0.54–0.62 3–5% 0.03–0.05 1–3% 0.01–0.03 0–0.75% 0–0.0075 25–33% 0.25–0.33 3–7% 0.03–0.07 25.4–34.6 pg/cell 0.39–0.54 fmol/cell 150,000–400,000/mm3 150–400  109/L 11–15 seconds 11–15 seconds 0.5–1.5% of red cells 0.005–0.015 Male: 0–15 mm/h 0–15 mm/h Female: 0–20 mm/h 0–20 mm/h < 150 mg/24 h < 0.15 g/24 h