Case 1: Persistent fever in a toddler

Abstract

A previously well 20-month-old girl, with a two-week history of persistent fever and neutropenia, was transferred from a secondary care hospital for investigation to rule out a possible diagnosis of leukemia. There was no history of infectious contacts or viral prodrome. The patient previously visited the family physician and emergency room on days 3, 7 and 12 of the fever, and was diagnosed with acute otitis media. She was treated with clarithromycin until day 7, when she was switched to amoxicillin due to continued fever. The medical history revealed a fully immunized, healthy child of Asian descent who, at nine months of age, developed a maculopapular rash following seven days of treatment with amoxicillin and ibuprofen for acute otitis media. A physical examination revealed an irritable child with a fever of 40°C, a new-onset generalized erythematous maculopapular rash and a palpable spleen, but no lymphadenopathy. The remainder of the examination was unremarkable. Specifically, there were no findings of nonpurulent conjunctivitis, oral-mucosal changes, cervical lymphadenopathy, palmar or plantar changes, cardiac murmur or arthritis. The initial workup revealed pancytopenia (absolute neutrophil count 0.2×109/L, hemoglobin 70 g/L, platelets 119×109/L), hypoalbuminemia, an elevated erythrocyte sedimentation rate (ESR), an elevated C-reactive protein (CRP) level, a positive Epstein-Barr virus (EBV) polymerase chain reaction (12,100 copies detected) and splenomegaly on abdominal ultrasound. Bone marrow biopsy and hemoglobin electrophoresis findings were normal. Other negative test results for infections included urine, blood and stool cultures, and serology for cytomegalovirus, varicella, hepatitis A, B and C, and HIV I and II. Because of a possible penicillin allergy, she was empirically treated with vancomycin and meropenem, which were discontinued following negative blood and urine cultures. She was also transfused with packed red blood cells and albumin because of low hemoglobin and albumin levels. The patient improved clinically and was discharged on day 21 of fever onset. She was febrile but clinically stable. The diagnosis was believed to be EBV infection and a subsequent hypersensitivity vasculitis reaction to penicillin. The toddler initially improved, then worsened with new-onset jaundice, irritability and hepatomegaly. She returned five days later with the following laboratory findings: pancytopenia (absolute neutrophil count 0.4×109/L, hemoglobin 76 g/L, platelets 24×109/L), hypertriglyceridemia (12.4 mmol/L), hypofibrinogenemia (1.56 g/L), hyperferritinemia (1230 μg/L), hyperbilirubinemia (68.7 μmol/L), transaminitis (alanine aminotransferase 313 U/L, aspartate aminotransferase 1507 U/L), coagulopathy (international normalized ratio 1.2, partial thromboplastin time 67 s) and a lactate dehydrogenase level of 5364 U/L. Her CRP level increased from 42 mg/L to 56 mg/L but her ESR decreased from 62 mm/h to 16 mm/h. A diagnosis was made based on the clinical findings and laboratory test results.