A 2.5-Year-Old Girl With Fever and Pancytopenia
A 2.5-year-old girl with no significant medical history presented to the emergency department with febrile seizures and a six-day history of fever above 102°F treated hitherto with amoxicillin and clavulanic acid without any improvement. No weight loss or unusual fatigue were reported.
She had been tracking along her growth curves and meeting her developmental milestones appropriately. She was born full-term with no significant complications. There was no significant family medical history. Her only recent medications included acetaminophen and ibuprofen.
Physical examination revealed prominent lymphadenopathy involving cervical and supraclavicular lymph nodes. Diagnostic workup included abdominal ultrasound and computed tomography imaging, which revealed multiple enlarged abdominal lymph nodes and hepatosplenomegaly. Blood tests showed bilineage cytopenia (white blood cell count, 1.77 × 109/L; absolute lymphocytes, 0.86 × 109/L; absolute neutrophils, 0.73 × 109/L; hemoglobin, 10.1 g/dL; and platelets, 70 × 109/L), which progressed to pancytopenia in the days following admission. Blood, urine, stool, and cerebrospinal fluid cultures were negative. A viral serological panel detected the presence of Epstein-Barr virus (EBV) anti-VCA IgM antibodies (1.87 signal-to-cutoff). Due to the atypical presentation of EBV infection with pancytopenia, an oncologic workup was initiated to rule out malignancy. A bone marrow biopsy was performed, which showed a normocellular marrow with no evidence of a neoplastic process. However, numerous hemophagocytic histiocytes could be observed in the bone marrow smear (Figure 1).
Figure 1. Microphotographs of the patient’s bone marrow smear. Courtesy of Dr. Alicja Siwicka.
Additional blood tests showed hyperferritinemia (2,858 mg/dL), high lactate dehydrogenase (LDH; 1278 U/L), and aspartate transaminase (AST) and alanine aminotransferase (ALT) levels above the normal range. The activity of lysosomal β-glucosidase was normal. Immunoglobulin levels were tested, and the IgA level was decreased. Rheumatoid factor and HIV ELISA were negative. Peripheral blood immunophenotyping and functional natural killer (NK) cytotoxicity tests were performed (Table 1) and demonstrated a significant decrease in the frequency of both CD4+ and CD8+ T cells as well as NK cells. NK cell activity and perforin expression were within the normal range, though perforin expression in CD8+ T cells was decreased.
Table 1. Immunophenotype and natural killer (NK) cell test results performed on patient’s peripheral blood mononuclear cells (PBMCs).
|NK cell activity||9.3% (norm >3%)|
● in CD8 T cells
● in NK cells
NK cells (CD16+ CD56+)
● CD4+ HLA-DR+
● CD8+ HLADR+
B lymphocytes CD19+
Degranulation test (NK cells stimulated with K562 cells)
● baseline CD107a+
● CD107a+ after 3h stimulation