A 6-Year-Old Child with Fever of Unknown Origin, Anemia, and Abdominal Pain

The patient is a previously healthy 6-year-old Caucasian girl with a 1-month history of fever, anemia, diminished appetite, and a 3-pound weight loss. She had received courses of trimethaprim-sulfamethoxazole and amoxicillin for suspected sinusitis and lower urinary tract infections. Despite this treatment, fever up to 104°F persisted, occurring primarily in the evenings. Although there were no identifiable preceding human sick contacts, her dog had died from canine parvovirus infection 1 month before the onset of her symptoms. The patient presented as a pale child in the 50th and 75th percentiles for weight and height, respectively. She was normotensive, with a hyperdynamic tachycardia during febrile periods. Her physical examination was notable for mild nail clubbing, along with mild, diffuse abdominal tenderness with no palpable mass or hepatosplenomegaly. Her stools were positive for occult blood before she received any aspirin or nonsteroidal anti-inflammatory drug therapy. The ophthalmologic examination was normal. Laboratory findings indicated profound systemic inflammation, anemia, elevated D-dimers, sterile pyuria, and twice the normal levels of transaminases (Table I; available at www.jpeds.com). The initial peripheral blood examination revealed a normochromic, normocytic anemia with reticulocytopenia, moderate neutrophilia, atypical lymphocytes, occasional Dohle bodies without significant toxicity, and Rouleaux formation suggestive of an inflammatory process. Evaluation of a bone marrow specimen revealed hypocellularity (60%), with the erythroid series shifted to the left with many pronormoblasts, some of them giant, suggesting early recovery from marrow suppression. In addition, large normoblasts exhibited intranuclear inclusions suggestive of a viral process. Serum antinuclear antibody and antineutrophil cytoplasmic antibody tests were negative. Cultures of the patient’s blood, urine, and stool were negative. Blood polymerase chain reaction (PCR) studies for adenovirus and enterovirus, in addition to serologies to Epstein-Barr virus, toxoplasma, cytomegalovirus, parvovirus B19, bartonella, leptospirosis, and Coxiella burnetii, failed to identify an infectious etiology for this prolonged illness. Because of the patient’s anemia, reticulocytopenia, and parvovirus exposure, parvovirus remained an etiologic consideration. Initially, the patient received aspirin and 2 doses of intravenous immune globulin for presumed atypical Kawasaki disease, but a later echocardiogram was normal. After this treatment, her fever resolved for 36 hours, but then returned. Two months into the patient’s illness, her anemia worsened, necessitating multiple packed red blood cell transfusions. She also began experiencing daily intermittent headaches coinciding with worsening periumbilical abdominal pain, a painful buccal ulceration, and pelvic and low back pain. Her fevers became more hectic, with nighttime diaphoresis but without rigor. Nonsteroidal medication was discontinued because of her increasing abdominal pain, nausea, and vomiting (with an episode of coffee-ground emesis). Her urinalysis demonstrated microscopic hematuria.