Index of Suspicion (2000)

A 15-year-old girl has had 10 days of fever (37.7°C to 37.8°C[100°F to 101°F]), aching joints, and difficulty walking. The moderately severe pain in her shoulders, wrists, and hips is bilateral, nonmigratory, and intermittent. Mild cervical spine and elbow pain and mild rhinorrhea also are present. She denies having sore throat, cough, abdominal pain, diarrhea, vaginal discharge, morning stiffness, tick bites, or rashes; has taken only acetaminophen and sporadic doses of ibuprofen; is not sexually active; and has not traveled. Her family history includes no collagen vascular diseases.On physical examination, her temperature is 102°F (38.9°C), pulse is 88 beats/min, respiratory rate is 20 breaths/min, and blood pressure is 114/66 mm Hg. She is a stoic, pleasant girl, who appears quiet but anxious. Her shoulders, wrists, and hip joints are exquisitely painful with passive motion, which elicits pleas to stop. Her range of motion is restricted to about two thirds of full passive flexion. Flexion of her elbows causes slight pain. None of the painful joints is red or swollen, and all other joints are normal. Her skin is clear, and findings on the rest of a complete examination are normal.A Westergren erythrocyte sedimentation rate (ESR) is 20 mm/hr;C-reactive protein (CRP) is elevated at 6.2 mg/L; leukocyte count is 12.8 × 109/L (12,800/cu mm) with 82% neutrophils;platelet count is 310 × 109/L (310 ×103/cu mm); hemoglobin is 135 g/L (13.5 g/dL);infectious mononucleosis spot test is negative; and creatine kinase level is 2 IU/L. Electrocardiographic findings are normal, with a PR interval of 0.16 mm and no ST changes. Antigen detection test by enzyme-linked immunosorbent assay for group A Streptococcus yields a negative result, and the urine is free of erythrocytes, leukocytes, protein, and glucose. A single laboratory test and her clinical response to therapy reveal the diagnosis.A 16-year-old African boy who moved to the United States from Nigeria 6 months ago is admitted for complaints of worsening fatigue. There is no history of surgery, and he is taking no medication.On physical examination, the patient appears pale and thin but is in no distress. His weight and height are both below the 5th percentile. His temperature is 36.6°C (97.9°F), pulse is 93 beats/min,respiratory rate is 22 breaths/min, and blood pressure is 120/65 mm Hg. The lid conjunctival membranes are pale. Cardiac examination reveals normal findings. His lungs are clear on auscultation.Laboratory results include hemoglobin, 45 g/L (4.5 g/dL);hematocrit, 0.156 (15.6%); white blood cell count, 3.0 ×109/L (3,000/cu mm) with 40% segmented cells, 45%lymphocytes, 2% eosinophils, and 13% monocytes; platelet count,110 × 109/L (110 × 103/cu mm); red blood cell distribution width, 17.2%; mean corpuscular volume, 51 fL; and reticulocyte count, 27 × 10−3 (2.7%). Blood smear reveals hypochromic, microcytic red blood cells, poikilocytosis, and target cells. Direct antiglobulin test and “sickle prep” yield negative results. Hemoglobin electrophoresis and glucose-6-phosphate dehydrogenase assay findings are normal. Further laboratory evaluation reveals the reason for his fatigue.A 14-year-old boy consults you because his hair is falling out. He noticed an increased amount of hair in his brush 2 weeks ago, and the quantity has increased since then. He has noticed hair thinning over the past week. He denies rashes, pruritus, burning, or pain in his scalp or recent skin changes. His past medical history is significant for attention deficit-hyperactivity disorder and a fractured right wrist 9 years ago; his only medication is methylphenidate. There is male pattern baldness in an uncle who began to lose his hair at age 30. The boy was arrested 3 months ago for auto theft and armed robbery and has been in a facility for violent youthful offenders since then. Prior to his incarceration, he smoked cigarettes and has tried marijuana and alcohol. He suffers from insomnia and occasional preprandial gastritis that is relieved by eating.On physical examination, he appears to be a quiet, somewhat nervous young man who has difficulty maintaining eye contact. All vital signs are within normal limits. His skin is intact, with no rashes or dryness. His scalp shows diffusely thinning hair without any patchy distribution. Anterior and posterior hairlines are normal. With gentle traction, some hair can be removed diffusely, but not in clumps. Findings on the remainder of the examination, including eyebrows,eyelashes, and axillary and pubic hair, are normal.The differential diagnosis for this girl who had polyarticular arthralgias included collagen vascular diseases, such as rheumatoid arthritis and systemic lupus erythematosus; acute rheumatic fever;arthritides associated with a host of viral and bacterial infections;postvaccine arthritis; inflammatory bowel disease; Lyme disease; and hematopoietic malignancy. Because of her extreme discomfort, therapy with naproxen 550 mg twice daily was initiated. She was instructed to phone the office the next day for the results of a throat culture and to return to the office if she developed rash or worsening symptomatology.Within 24 hours of starting naproxen, the arthralgias and fever had subsided totally. The girl’s throat culture yielded a heavy growth of nongroup A beta-hemolytic Streptococcus on selective blood agar after incubation overnight in a candle jar. She was treated with oral penicillin(500 mg twice daily) for 10 days. On further questioning, she remembered having had a mild sore throat for 2 days about 1 month prior to the onset of the arthralgias. Physical findings on follow-up heart and joint evaluation were normal. However, the palmar aspect of her hands, fingers, toes, and feet showed a nonerythematous exfoliation. The following tests gave negative results: rheumatoid factor (<10 IU/mL), antinuclear antibody (<1:40), Borrelia burgdorferi immunoglobulin G (IgG) and IgM titers (<1:16), and parvovirus B 19 IgG titer (0.08). Acute and convalescent titers for antistreptolysin and antiDNA-ase B were negative. Physical findings 1 month after completion of therapy had returned to normal.Poststreptococcal reactive arthritis caused by a strain of nongroup A Streptococcus was the etiology of this adolescent girl’s illness, although her physical examination did not reveal all the features of frank arthritis. Poststreptococcal reactive arthritis has been described as a nonmigratory polyarthritis that often affects both small and large joints and lasts for weeks. Some patients,such as this girl, show a rapid, dramatic, and complete resolution of symptoms in response to nonsteroidal anti-inflammatory medication, even before treatment with penicillin. Had this adolescent been given therapeutic doses of ibuprofen, her response should have been similar to that with naproxen. Other patients, however, will not respond as well and can experience symptoms for months.Groups C and G Streptococcus have been reported to cause reactive arthritis, and this patient’s throat culture was positive for nongroup A Streptococcus. In addition, she subsequently developed the characteristic dermatologic peeling of post-scarlet fever infection after antibiotic therapy had been initiated. Serologic testing for Streptococcus and for antibodies associated with other arthritides gave negative results, although serologic testing results are not uniformly reliable in diagnosing many of these illnesses. This case points out the importance of performing a throat culture in patients whose rapid test for streptococcal antigen is negative and also the value of looking for nongroup A Streptococcus. It is of interest that this girl’s C-reactive protein level was elevated, but her ESR was not, a reflection of the ESR nearly always lagging behind the C-reactive protein in acute inflammatory processes and a reminder that it can be helpful to perform both studies.Group A poststreptococcal (GAS) arthritis first was reported in 1982 by Goldsmith and Long.(1) In their series of 12 children 3 to 11 years of age, the arthritis was symmetric;primarily involved the knees, ankles, wrists, or fingers; and persisted for a mean of 20 days. Fever was present in all children for 3 to 42 days, and all had serologic evidence of a preceding streptococcal infection along with an elevated ESR, negative antinuclear antibodies, and negative rheumatoid factors. None of the children developed other signs of acute rheumatic fever or carditis. De Cunto et al in 1988 reported 12 patients who had poststreptococcal reactive arthritis.(2) Interestingly, only four of nine patients were positive by throat culture for group A beta-hemolytic Streptococcus, but all had serologic evidence of a preceding streptococcal infection. One child developed carditis 18 months after the initial episode.Both group C and group G streptococcal infections can cause disease similar to that associated with group A strains, including pharyngitis, dermatologic infections, pyogenic arthritis, and glomerulonephritis. However, groups C and G strains have not been documented to cause acute rheumatic fever (ARF). Infections with nongroup A strains also can produce serologic virulence factors of streptococcal infection (hyaluronidase and ASO).Clearly, the clinician who is caring for a child who develops arthritis in conjunction with beta-hemolytic streptococcal infection must keep ARF in mind. If studies indicate that the streptococcal organism is not in group A, the concern about ARF is alleviated. If the organism is group A Streptococcus, differentiation between reactive arthritis and ARF is crucial. It is helpful to know that unlike ARF,reactive arthritis affects small joints as well as large ones. Patients who have been diagnosed as having reactive arthritis following GAS infection typically do not develop carditis later, but a few have,which raises the question of whether patients who have had GAS reactive arthritis should receive the same antibiotic prophylaxis that is given to patients who have ARF.A complete list of the infections that are associated with arthritis is long, and the mechanism of the arthritis can be direct infection or an immunologically mediated reaction. Some organisms are associated with both mechanisms. (It is helpful to realize that the arthritides discussed here tend to affect more than one joint. In contrast, septic arthritis usually affects a single joint, except for gonococcal arthritis, which always is a possibility in adolescents.)Among the viruses associated with arthritis are parvovirus B 19,rubella (natural and vaccine strains), cytomegalovirus, Epstein-Barr virus, herpes zoster, and varicella, all of which can be isolated from infected joints. Arthritis associated with mumps virus, human immunodeficiency virus, and hepatitis B virus infections is presumed to be reactive because the virus has not been isolated from joints. Among bacterial infections, there is a well-known association of reactive arthritis with enteric infections, specifically Yersinia enterocolitica, Salmonella enteritidis, S typhimurium, and Campylobacter jejuni. Other organisms associated with reactive arthritis include Chlamydia trachomatis, C psittaci, C pneumoniae, Neisseria gonorrhoeae, Mycoplasma pneumoniae,and Streptococcus viridans. It is important to realize that some of these organisms can cause arthritis both by direct infection and by a reactive mechanism.Arthritis has been associated with some vaccines, specifically diphtheria and tetanus toxoids and vaccines against hepatitis B,rubella, and Lyme disease. (Stan Block, MD, Kentucky Pediatric Research, Bardstown, KY)The patient’s serum iron level was 3.2 mcmol/L (18 mcg/dL) and ferritin level was 1.1 mcg/L (1.1 ng/mL). Iron deficiency usually is caused either by dietary deficiency or blood loss. This boy’s dietary history revealed adequate sources of iron. Stool examination and urinalysis tested negative for blood. Because the patient had migrated from Nigeria and had severe iron deficiency anemia, a stool specimen was sent for ova and parasite examination; it revealed hookworm eggs. The hookworm infestation had caused the profound anemia, which was responsible for his fatigue.Hookworm infection is one of the leading causes of iron deficiency anemia in developing countries. The two most common species are Ancylostoma duodenale and Necator americanus,whose eggs are morphologically indistinguishable. The only way to differentiate the species is to examine the worms in their larval stage.The life cycle of the hookworm begins with the hatching of the ova into larvae in moist soil. The infective larvae enter the body through the skin (usually a bare foot) and migrate to the lungs via the lymphatics and venules. From the lungs, they are coughed up and then swallowed. The larvae latch on to the wall of the small intestine,where they mature into adult worms, feed, and mate. Each female organism produces as many as 30,000 ova per day. The estimated amount of blood loss is 0.2 mL per worm. The number of worms, or the worm burden, in an infected person can reach 1,000.Clinical manifestations of hookworm infestation include pruritus eor “ground itch” at the site of entry. Other manifestations are related to the anemia and hypoalbuminemia caused by the chronic presence of the worms in the small intestine. Learning disabilities,growth impairment, and developmental delay are other complications.The diagnosis is made by identifying the characteristic ova in feces under light microscopy. The peripheral blood smear may demonstrate eosinophilia.The usual treatment for hookworm infestation is mebendazole 100 mg orally twice a day for 3 days. For children who have severe anemia, such as this patient, iron therapy should be started prior to antihelminthic medication. A repeat stool examination after 2 weeks of therapy also is recommendedAfter treatment, this patient had a negative stool examination for ova and parasites. His hematocrit was 0.37 (37%) (he had been transfused with packed red blood cells before the underlying diagnosis had been made), white blood cell count was 4.1 × 109/L(4,100/cu mm), and platelet count was 272 × 109/L(272 × 103/cu mm). The leukopenia and thrombocytopenia at the time of infection may have been due to an intercurrent infection;hookworm infestation is not associated with bone marrow suppressionIt should be noted that primary hookworm infection does not confer long-lasting immunity; children in endemic regions of the world are susceptible to reinfection. Approximately 25% of the world’s population is infected with hookworm, and most infected individuals are asymptomatic. (Noha Ali-Ahmad, MD, Malathi Bathija, MD, Walid Abuhammour, MD, Children’s Hospital of Michigan, Detroit, MI)Low-powered microscopic examination of a few plucked hairs confirmed the diagnosis of telogen effluvium. Telogen effluvium was described in 1961 as acute and diffuse hair loss that occurs 2 to 4 months after experiencing any number of physiologic stresses. It is seen most often following febrile illnesses, emotional stress, and rapid weight loss. Telogen effluvium may be encountered by pediatricians in both patients and mothers of newborns. New mothers may mistake their diffuse hair loss as resulting from breastfeeding rather than the body’s response to the stress of childbirth. Other stressors include seizures, thyroid disorders, surgery and general anesthesia,and the use of medications such as oral contraceptives, valproic acid,propranolol, heparin, or coumadin.Telogen effluvium occurs when there is an abrupt, diffuse cessation of the anagen or active growth phase of the hair. Normally,the growth of each individual hair follicle is cyclical. The anagen phase lasts for several years and is followed by a transitional, or catagen phase, which lasts for days to weeks. Next the follicle enters the resting, or telogen phase, which lasts for 2 to 3 months. Following the telogen phase, the hair follicle resumes its active growth, and the old hair shaft is shed. Normally, 85% to 90% of hair is in the anagen phase. Because of the cyclical nature of the phases,approximately 100 to 200 hairs are shed each day. In telogen effluvium, the anagen phase is halted for a significant number of hairs in response to the initiating stress. When the hair follicles resume the anagen phase 2 to 3 months later, the old hair shafts are shed in greater-than-normal numbers. The number of hairs affected must comprise 25% to 50% of scalp hair for the loss to be apparent clinically. The pattern of hair loss is diffuse, and there are no underlying scalp abnormalities.If the diagnosis is unclear, microscopic examination of a few plucked hairs will demonstrate an increased number of telogen hairs. Anagen hairs have a long sheath covering the root; telogen hairs have no sheath and show a club-shaped root. The patient can be reassured that the hair loss actually indicates the resolution of the problem and that complete hair growth can be expected within 6 months.It has been estimated that 90% to 95% of cases of alopecia in children and adolescents result from one of the following causes:telogen effluvium, tinea capitis, alopecia areata, or hair trauma. Each of these disorders can be differentiated by history, physical examination, microscopic examination of the hair follicle, and a potassium hydroxide (KOH) preparation of plucked hairTinea capitis is a common fungal scalp infection that causes approximately 50% of cases of hair loss in children. Most cases prior to the 1970s were caused by This species on the hair which under a the primary of tinea capitis has which does not produce the characteristic The pattern of hair loss seen in tinea capitis is and the scalp shows and There may be in the affected which hair examination and a fungal culture of several hairs may be in the onset of alopecia may be with small of baldness developing and or dramatic, with rapid, loss. The affected demonstrate complete hair and the scalp appears and at the of the can be plucked the hair loss may affect the scalp diffusely, the diagnosis more The most severe of alopecia are alopecia which to complete loss of hair on the and alopecia which to complete hair loss over the Approximately 25% of patients who have these show such as and the disorder has been associated with disorders such as and inflammatory bowel disease. but the response with or systemic The response to treatment also is common causes of hair loss are and alopecia occurs when is on hair usually and occurs along the alopecia is seen in who on their and the hair of the posterior of their to the to out hair. The usually the scalp also may the or pubic hair. The pattern of hair loss is and the loss is The of alopecia will show hairs of and of hairs may be present. The scalp also may show of was that he was developing male pattern baldness and he was reassured that this was not the alopecia is the most common cause of hair loss it is in onset is more and occurs in a or distribution. The patient was seen for follow-up 2 months and had diffuse hair growth in a normal distribution. MD,