Sandbox: q fever

# DD
The table below summarizes the findings that differentiate watery causes of chronic diarrhea

# History and symptoms
- Q fever can present with a wide variety of symptoms related to multiple organs involved. Q fever can be classified into acute and chronic based on the onset of symptoms:
- Incubation period is usually 2 to 3 weeks.

## Acute Q fever:

### Flu like symptoms:
The most common manifestation is flu-like symptoms with abrupt onset of:
- High-grade fevers: Fever is usually accompanied by chills and night sweats.
- Headaches:  retrobulbar and associated with photophobia.
- Arthralgias.

### Pneumonia:
Usually mild and accidentally discovered on X rays
- If accompanied by a cough, cough is dry and nonproductive.
- Dyspnea
- Pleuritic chest pain
- Rarely progresses to ARDS which can be life threatening.

### Hepatitis:
- Abdominal right upper quadrant pain
- Jaundice
- GI symptoms as nausea, Malaise, vomiting, diarrhea and bloating.

### Rare acute Q fever symptoms:
- Pericarditis and myocarditis:
- Myocarditis is rare but carries a bad prognosis.
- Chest pain
- Dyspnea
- Palpitation

### Neurologic findings:
- Q fever can present with meningioencephalitis.
- Headache
- Confusion
- Seizures

### Dermatologic findings:
- Maculopapular rash
- Diffuse punctate rash
- Erythema nodosum

### Q fever during pregnancy:
- Most C. brutenii infection during pregnancy pass asymptomatic but in rare cases, it can be complicated with:
- Intrauterine growth retardation (IUGR)
- Intrauterine fetal death (IUFD).
Infection during the first trimester and placental infection are associated with increased risk of fetal compromise.

## Chronic Q fever:
Chronic Q fever, characterized by infection that persists for more than 6 months is uncommon but is a much more serious disease. Patients who have had acute Q fever may develop the chronic form as soon as 1 year or as long as 20 years after initial infection.

### Endocarditis:
Endocarditis is the main manifestation of Q fever.
- Characterized by being culture negative endocarditis.
- Patients who are predisposed to endocarditis include patients with valvular lesions, prosthetic valves, and immunocompromised patients.
- Presents with:
Low-grade fevers
Palpitations
Dyspnea
Embolic manifestations
- Low-grade fevers
- Palpitations
- Dyspnea
- Embolic manifestations

### Skeletal manifestations:
- Bone and joint infections are common manifestations of chronic Q fever.
- Presents with:
Low-grade fever
Bone and joint pain as in chronic osteomyelitis
- Low-grade fever
- Bone and joint pain as in chronic osteomyelitis

### Vascular lesions:
- Usually in previously affected vessel (e.g. aneurysm)

### Cardiopulmonary affection:
- Chronic pleural or pericardial effusion and Interstitial pulmonary fibrosis present with dyspnea and fatigue.

### Hepatic manifestations:
- Liver fibrosis or cirrhosis present with symptoms of chronic hepatic decompensation (e.g jaundice, abdominal pain, fatigue, etc)

### Chronic fatigue syndrome:
- Presents in up to 10% of chronic Q fever patients.

# Physical examination:

## Vital signs:
- Fever: High-grade fevers that are usually accompanied by chills and night sweats.
- Tachycardia
- Tachypnea

## General:
- Patient looks ill

## Skin:
- Maculopapular or punctate rash
- Erythema nodosum
- Spider nevi if hepatic decompensation is present

## HEENT:
- Jaundice
- Congested neck veins if endocarditis or myocarditis is complicated by heart failure

## Lungs:
- Minimal auscultatory findings in most of the cases
- Crackles especially in the lower lung fields
- Decreased breath sounds if pleural effusion is present

## Abdomen:
- Hepatomegaly
- Ascites if chronic hepatitis ensues

## Heart:
- S3 due to hyperdynamic circulation
- New onset murmur if endocarditis is present
- Pericardial rub and distant heart sounds if pericarditis and pericardial effusion is present

## Neurological examination:
- Neck rigidity and positive brudsiniski and kuring signs
- Signs of increased intracranial pressure (vomiting, convulsions, papilledema, etc)

## Extremities:
- Tenderness on palpation of the affected joints and bones
- Lower limb edema in presence of heart failure

# Physical examination:

## Vital signs:
- Fever: High-grade fevers that are usually accompanied by chills and night sweats.
- Tachycardia
- Tachypnea

## General:
- Patient looks ill

## Skin:
- Maculopapular or punctate rash
- Erythema nodosum
- Spider nevi if hepatic decompensation is present

## HEENT:
- Jaundice
- Congested neck veins if endocarditis or myocarditis is complicated by heart failure

## Lungs:
- Minimal auscultatory findings in most of the cases
- Crackles especially in the lower lung fields
- Decreased breath sounds if pleural effusion is present

## Abdomen:
- Hepatomegaly
- Ascites if chronic hepatitis ensues

## Heart:
- S3 due to hyperdynamic circulation
- New onset murmur if endocarditis is present
- Pericardial rub and distant heart sounds if pericarditis and pericardial effusion are present.

## Neurological examination:
- Neck rigidity and positive brudsiniski and kuring signs.
- Signs of increased intracranial pressure (vomiting, convulsions, papilledema, etc)

## Extremities:
- Tenderness on palpation of the affected joints and bones.
- Lower limb edema in presence of heart failure.
Q fever can present with a wide variety of symptoms related to multiple organs involved. Q fever can be classified into acute and chronic based on the onset of symptoms:
Acute Q fever:
Flu like symptoms:
High-grade fevers: Fever is usually accompanied by chills and night sweats.
Headaches:  retrobulbar and associated with photophobia. 
Arthralgias.
Pneumonia:
Usually mild and accidentally discovered on X rays
If accompanied by a cough, cough is dry and nonproductive.
Dyspnea
Pleuritic chest pain
Rarely progresses to ARDS which can be life threatening.
Hepatitis:
Abdominal right upper quadrant pain
Jaundice
GI symptoms as nausea, vomiting, diarrhea and bloating.
Rare acute Q fever symptoms:
Pericarditis and myocarditis:
Myocarditis is rare but carries a bad prognosis.
Chest pain
Dyspnea
Palpitation
Neurologic findings:
Q fever can present with meningoencephalitis.
Headache
Confusion
Seizures
Dermatologic findings:
Maculopapular rash
Diffuse punctate rash
Erythema nodosum
Q fever during pregnancy:
Most C. brutenii infection during pregnancy pass asymptomatic but in rare cases, it can be complicated with:
Intrauterine growth retardation (IUGR)
Intrauterine fetal death (IUFD).
Infection during the first trimester and placental infection are associated with increased risk of fetal compromise.
Chronic Q fever:
Endocarditis:
Endocarditis is the main manifestation of Q fever.
Characterized by being culture negative endocarditis.
Patients who are predisposed to endocarditis include patients with valvular lesions, prosthetic valves, and immunocompromised patients.
Presents with:
- Low-grade fevers
Palpitations
Dyspnea
Embolic manifestations
- Low-grade fevers
- Palpitations
- Dyspnea
- Embolic manifestations
Skeletal manifestations:
Bone and joint infections are common manifestations of chronic Q fever.
Presents with:
- Low-grade fever
Bone and joint pain as in chronic osteomyelitis
- Low-grade fever
- Bone and joint pain as in chronic osteomyelitis
Vascular lesions:
Usually in previously affected vessel (e.g. aneurysm)
Cardiopulmonary affection: 
Chronic pleural or pericardial effusion and Interstitial pulmonary fibrosis present with dyspnea and fatigue.
Hepatic manifestations:
Liver fibrosis or cirrhosis present with symptoms of chronic hepatic decompensation (e.g jaundice, abdominal pain, fatigue, etc)
Chronic fatigue syndrome:
Presents in up to 10% of chronic Q fever patients.
Physical examination:
Vital signs:
Fever: High-grade fevers that are usually accompanied by chills and night sweats.
Tachycardia
Tachypnea
General:
Patient looks ill
Skin: 
Maculopapular or punctate rash
Erythema nodosum
Spider nevi if hepatic decompensation is present
HEENT:
Jaundice
Congested neck veins if endocarditis or myocarditis is complicated by heart failure
Lungs:
Minimal auscultatory findings in most of the cases
Crackles especially in the lower lung fields
Decreased breath sounds if pleural effusion is present
Abdomen:
Hepatomegaly
Ascites if chronic hepatitis ensues
Heart: 
S3 due to hyperdynamic circulation
New onset murmur if endocarditis is present
Pericardial rub and distant heart sound if pericarditis and pericardial effusion are present.
Neurological examination:
Neck rigidity and positive brudsiniski and kuring signs.
Signs of increased intracranial pressure (vomiting, convulsions, papilledema, etc)
Extremities:
Tenderness on palpation of the affected joints and bones.
Lower limb edema in presence of heart failure.
Pathogenesis:
Transmission:
The organism is transmitted through:
Aerosoloes: Inhalation of contaminated aerosols is the main mode of transmission.
Ingestion of raw dairy products
Vertical (mother to fetus) transmission has been reported
Parenteral
Through tick bites
Pathogenesis:
C. Brutenii has the ability to exist in 2 forms:
Small cell form: 
Often described as the spore form of C. Brutenii
Resists the external environmental factors as heat, pressure, and disinfectants for long periods
Large cell form:
The active form of the organism
Large cell form persists in the macrophages inside acidic vacuoles.
Small and large cell forms are antigenically different and this plays a role in the virulence of the organism.
The genome of C. Brutenii has been analyzed in 1995. Multiple genes encoding for Na/ ion proton exchanger have been discovered and this explains the ability of the organism to survive in low PH.
The infection has 2 phases that correlate with changes in the lipopolysaccharide of C. Brutenii.
Phase I: characterized by smooth lipopolysaccharide capsule. Despite being less efficient in the invasion of host cells, antibodies against phase 1 is always isolated from acute Q fever patients.
Phase II: characterized by rough lipopolysaccharide capsule and antibodies against phase II have been isolated from chronic Q fever patients.
Q fever as a biological weapon:
C. Brutenii is an extremely virulent organism.
According to WHO estimates, an amount of 50 kg of  C. Brutenii if spread in an area of 2 square kilometers is capable of:
- Infecting 500,000 humans
- Killing 150 individuals
- Causing acute illness in 125,000 individuals
- Causing chronic illness in 9,000 individuals
Microscopic pathology:
- C. Brutenii is a gram negative polymorphic intracellular organism.
- It was previously classified as a rickettsia, but now is considered a proteobacterium.
Lab tests:
Serologic testing for Q fever:
Indirect immunofluorescence (IIF) is the method of choice for antibody detection and is preferred over ELISA and complement fixation.
Antibodies start to be detected after 7-14 days of infection with most patients testing positive by the third week.
Anti phase II antibodies are tested first. If positive, anti phase I antibodies are tested.
After acute infection, serologic follow up for serum anti phase I IgG antibodies. The test is done twice every 3 months for 2 years. If positive, Transesophageal echo should be done to rule out endocarditis.
All serologic test results should be used in the context of clinical data because false positive test results are seen in many other diseases (eg leptospirosis).
Polymerase chain reaction (PCR):
PCR can be used to detect C. brutenii DNA in cultures and clinical samples.
PCR is positive in the first week of infection, thus it can be used to diagnose Q fever in patients who are serologically negative in the early stages of the disease.
Quantitative PCR also can be used in patients whom anti phase IgG antibodies are persistently positive to detect chronic Q fever.
Cultures:
C. brutenii doesnt grow on ordinary blood cultures but can be cultivated on special media as embryonated eggs or cell culture. 
C. brutenii is extremely infectious and samples should be handled with caution.
Liver function tests: 
2-3 fold increase in AST and ALT is seen in most of the patients.
X ray chest:
In acute Q fever, X ray may show signs of atypical pneumonia (hazy non localized airspace opacities) and in some cases, it shows all the signs of typical pneumonia (lobar consolidation and occasional pleural effusions)
In chronic Q fever, interstitial fibrosis can be seen.
CT chest:
Similar to chest x ray, the CT can show scattered consolidation and opacities or lobar consolidation in one specific lobe.
According to the onset of symptoms, Q fever can be classified into:
Acute Q fever:
Characterized by a very rapid onset of flu like symptoms, pneumonia, and hepatitis.
Resolution of infection in less than 6 months
Chronic Q fever:
Characterized by the persistence of infection (clinically or serologically) for more than six months.
Chronic Q fever almost always means endocarditis.
Differential:
Q fever must be differentiated from other diseases that cause atypical pneumonia such as mycoplasma pneumonia and legionella pneumonia.Q fever also must be differentiated from diseases that cause gram negative endocarditis such as HACEK endocarditis.
Q fever pneumonia:
Q fever is characterized by abrupt onset of fever, myalgia, headache and other constitutional symptoms . Cough is the most prominent respiratory symptom and it is usually dry - Cough is associated with dyspnea and pleuritic chest pain.
LAB: antibody detection using Indirect immunofluorescence (IIF) is the preferred method for diagnosis - PCR can be used if IIF is negative or very early once disease is suspected -    C. brutenii doesnt grow on ordinary blood cultures but can be cultivated on special media as embryonated eggs or cell culture - 2-3 fold increase in AST and ALT is seen in most of the patients.
Mycoplasma pneumonia: 
CP: Can be asymptomatic - Headache, nausea and malaise usually precede the onset of symptoms - Cough which is intractable and nonproductive
LAB: 
Postitve coombs test
Leukocytosis
Thrombocytosis
Legionella pneumonia:
CP: Cough that is slightly productive - constitutional symptoms such as chills, myalgia, arthralgia - Gastrointestinal symptoms such as diarrhea, nausea and vomiting.
LAB: labs are non specific - renal and hepatic dysfunction - thrombocytopenia and leucocytosis - Hyponatraemia .
Chlamydia pneumonia:
CP: No specific clinical features for chlamydia pneumonia - Symptoms appear gradually - Chlamydia infection is usually associated with upper respiratory tract symptoms (pharyngitis, sinusitis, etc) - Might be associated with extrapulmonary manifestaions as meningitis and guillain barre syndrome.
LAB: usually associated with normal WBC count - diagnosed with the presence of antichlamydial antibody (through complement fixation or direct immunofluoroscence) or direct antigen detection -
There is a delay between the entry of the organism into the host cell and the fusion with lysosomes. This delay is thought to be due to the transform from the small cell variant into the large cell variant.
The acidic environment inside the lysosome has a little effect on the large cell form of the organism.
Virulence factors
Lipopolysaccharide capsule is one of the most important virulence factors of the organism.
The different phases of infection is associated with changes in the polysaccharide capsule.
Lipopolysaccharide phase I (smooth polysaccharide) is associated with protection against the host immune response).
Lipopolysaccharide phase 2 (rough) is isolated from avirulent non infectious host cells and is not associated with protection of the virus from the host cell.
Both humoral and cell mediated immunity are involved in the immune response against C.brutenii. However, cell mediated immunity is more important in the defense against the organism and people with deficient cell mediated immunity is more susceptible develop chronic infection.

# DD

# Differentiating Syphilis from other Diseases
Syphilis is named as a "great imitator" because symptomatology and physical exam findings of syphilis in different stages mimicks large variety of other diseases.
-  Silverberg MS, Satsangi J, Ahmad T, Arnott ID, Bernstein CN, Brant SR;  et al. (2005). "Toward an integrated clinical, molecular and serological classification of inflammatory bowel disease: report of a Working Party of the 2005 Montreal World Congress of Gastroenterology". Can J Gastroenterol. 19 Suppl A: 5A36A. PMID 16151544.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link) .mw-parser-output cite.citation{font-style:inherit}.mw-parser-output q{quotes:"\"""\"""'""'"}.mw-parser-output code.cs1-code{color:inherit;background:inherit;border:inherit;padding:inherit}.mw-parser-output .cs1-lock-free a{background:url("")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-limited a,.mw-parser-output .cs1-lock-registration a{background:url("")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-subscription a{background:url("")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration{color:#555}.mw-parser-output .cs1-subscription span,.mw-parser-output .cs1-registration span{border-bottom:1px dotted;cursor:help}.mw-parser-output .cs1-hidden-error{display:none;font-size:100%}.mw-parser-output .cs1-visible-error{display:none;font-size:100%}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration,.mw-parser-output .cs1-format{font-size:95%}.mw-parser-output .cs1-kern-left,.mw-parser-output .cs1-kern-wl-left{padding-left:0.2em}.mw-parser-output .cs1-kern-right,.mw-parser-output .cs1-kern-wl-right{padding-right:0.2em}
-  Sauter GH, Moussavian AC, Meyer G, Steitz HO, Parhofer KG, Jungst D (2002). "Bowel habits and bile acid malabsorption in the months after cholecystectomy". Am J Gastroenterol. 97 (7): 17325. doi:10.1111/j.1572-0241.2002.05779.x. PMID 12135027.CS1 maint: Multiple names: authors list (link)
-  Maiuri L, Raia V, Potter J, Swallow D, Ho MW, Fiocca R;  et al. (1991). "Mosaic pattern of lactase expression by villous enterocytes in human adult-type hypolactasia". Gastroenterology. 100 (2): 35969. PMID 1702075.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
-  RUBIN CE, BRANDBORG LL, PHELPS PC, TAYLOR HC (1960). "Studies of celiac disease. I. The apparent identical and specific nature of the duodenal and proximal jejunal lesion in celiac disease and idiopathic sprue". Gastroenterology. 38: 2849. PMID 14439871.CS1 maint: Multiple names: authors list (link)
-  Carlson JA, Dabiri G, Cribier B, Sell S (2011). "The immunopathobiology of syphilis: the manifestations and course of syphilis are determined by the level of delayed-type hypersensitivity". Am J Dermatopathol. 33 (5): 43360. doi:10.1097/DAD.0b013e3181e8b587. PMC 3690623. PMID 21694502.CS1 maint: Multiple names: authors list (link)
-  Jump up to: 6.0 6.1 6.2 Fatahzadeh M, Schwartz RA (2007). "Human herpes simplex virus infections: epidemiology, pathogenesis, symptomatology, diagnosis, and management". J. Am. Acad. Dermatol. 57 (5): 73763, quiz 7646. doi:10.1016/j.jaad.2007.06.027. PMID 17939933.
-  Jump up to: 7.0 7.1 O'Farrell N (2002). "Donovanosis". Sexually Transmitted Infections. 78 (6): 4527. PMC 1758360. PMID 12473810.
-  Jump up to: 8.0 8.1 Coovadia YM, Kharsany A, Hoosen A (1985). "The microbial aetiology of genital ulcers in black men in Durban, South Africa". Genitourin Med. 61 (4): 2669. PMC 1011828. PMID 2991120.
-  Jump up to: 9.0 9.1 Mabey D, Peeling RW (2002). "Lymphogranuloma venereum". Sexually Transmitted Infections. 78 (2): 902. PMC 1744436. PMID 12081191.
-  Jump up to: 10.0 10.1 Workowski, KA.; Berman, S.; Workowski, KA.; Bauer, H.; Bachman, L.; Burstein, G.; Eckert, L.; Geisler, WM.; Ghanem, K. (2010). "Sexually transmitted diseases treatment guidelines, 2010". MMWR Recomm Rep. 59 (RR-12): 1110. PMID 21160459. Unknown parameter |month= ignored (help)
-  Jump up to: 11.0 11.1 F. G. Bruins, F. J. A. van Deudekom & H. J. C. de Vries (2015). "Syphilitic condylomata lata mimicking anogenital warts". BMJ (Clinical research ed.). 350: h1259. PMID 25784708.
-  Jump up to: 12.0 12.1 12.2 12.3 Berger JR, Dean D (2014). "Neurosyphilis". Handb Clin Neurol. 121: 146172. doi:10.1016/B978-0-7020-4088-7.00098-5. PMID 24365430.
-  Jump up to: 13.0 13.1 Hotson JR (1981). "Modern neurosyphilis: a partially treated chronic meningitis". West J Med. 135 (3): 191200. PMC 1273113. PMID 7340118.
-  Jump up to: 14.0 14.1 Lukehart SA, Hook EW, Baker-Zander SA, Collier AC, Critchlow CW, Handsfield HH (1988). "Invasion of the central nervous system by Treponema pallidum: implications for diagnosis and treatment". Ann Intern Med. 109 (11): 85562. PMID 3056164.CS1 maint: Multiple names: authors list (link)
-  Jump up to: 15.0 15.1 Simon RP (1985). "Neurosyphilis". Arch Neurol. 42 (6): 60613. PMID 3890813.
-  Suresh E (2006). "Diagnostic approach to patients with suspected vasculitis". Postgrad Med J. 82 (970): 4838. doi:10.1136/pgmj.2005.042648. PMC 2585712. PMID 16891436.
-  Jump up to: 17.0 17.1 Sapira JD (1981 Apr). ""Quincke, de Musset, Duroziez, and Hill: some aortic regurgitations"". South Med J. 74 (4): 45967. Check date values in: |date= (help)
-  Jump up to: 18.0 18.1 Pugh PJ, Grech ED (2002). "Images in clinical medicine. Syphilitic aortitis". N Engl J Med. 346 (9): 676. doi:10.1056/NEJMicm010343. PMID 11870245.
-  Jump up to: 19.0 19.1 19.2 J. Deschenes, C. D. Seamone & M. G. Baines (1992). "Acquired ocular syphilis: diagnosis and treatment". Annals of ophthalmology. 24 (4): 134138. PMID 1590633. Unknown parameter |month= ignored (help)
-  Jump up to: 20.0 20.1 Young MF, Sanowski RA, Manne RA (1992). "Syphilitic hepatitis". Journal of Clinical Gastroenterology. 15 (2): 1746. PMID 1401840.
-  Jump up to: 21.0 21.1 T. F. Jr Schlaegel & S. F. Kao (1982). "A review (1970-1980) of 28 presumptive cases of syphilitic uveitis". American journal of ophthalmology. 93 (4): 412414. PMID 7072806. Unknown parameter |month= ignored (help)
-  Baron, Samuel (1996). Medical microbiology. Galveston, Tex: University of Texas Medical Branch at Galveston. ISBN 0-9631172-1-1.
-  Mandell, Gerald (2010). Mandell, Douglas, and Bennett's principles and practice of infectious diseases. Philadelphia, PA: Churchill Livingstone/Elsevier. ISBN 978-0-443-06839-3.
-  Baron, Samuel (1996). Medical microbiology. Galveston, Tex: University of Texas Medical Branch at Galveston. ISBN 0-9631172-1-1.
-  Mandell, Gerald (2010). Mandell, Douglas, and Bennett's principles and practice of infectious diseases. Philadelphia, PA: Churchill Livingstone/Elsevier. ISBN 978-0-443-06839-3.
-  Kang, Jin Han. "Febrile Illness with Skin Rashes." Infection & chemotherapy 47.3 (2015): 155-166.
-  Scolding N (2001). "The differential diagnosis of multiple sclerosis". Journal of Neurology, Neurosurgery, and Psychiatry. 71 Suppl 2: ii915. PMC 1765571. PMID 11701778.
-  Friedrich F, Geusau A, Greisenegger S, Ossege M, Aigner M (2009). "Manifest psychosis in neurosyphilis". General Hospital Psychiatry. 31 (4): 37981. doi:10.1016/j.genhosppsych.2008.09.010. PMID 19555800.
-  K. Doi, T. Kasaba & Y. Kosaka (1989). "". Masui. The Japanese journal of anesthesiology. 38 (11): 14271437. PMID 2585712. Unknown parameter |month= ignored (help)