Hemophagocytic lymphohistiocytosis associated with visceral leishmaniasis

A 15-year-old boy, who had recently emigrated from Sudan to the United States, presented with persistent high fevers of 2 months’ duration, and a reported diagnosis of malaria with intermittent therapy. On admission, he was pancytopenic and imaging studies showed hepatosplenomegaly. Investigations for malaria, Epstein-Barr virus (EBV), cytomegalovirus, HIV, Babesia, Ehrlichia, and dengue virus were negative. Additional investigations showed elevated ferritin, soluble interleukin-2 receptor (CD25) levels, and absent natural killer (NK)-cell activity, supportive of hemophagocytic lymphohistiocytosis (HLH). He was started on dexamethasone and transferred to our institution for management of HLH and possible bone marrow transplantation. Mutational analysis for familial HLH was not performed. Bone marrow biopsy showed a hypocellular marrow with trilineage hematopoiesis (panel A; hematoxylin and eosin [H&E], original magnification ×100) and macrophages with microorganisms (panel B; H&E, original magnification ×400). The aspirate showed prominent hemophagocytic macrophages (panel C; Wright Giemsa, original magnification ×1000) with intra- and extracellular amastigotes (panel D; Wright Giemsa, original magnification ×1000) consistent with visceral leishmaniasis. Amphotericin B (liposomal) therapy was initiated with resolution of fever, splenomegaly, ferritin levels, and recovery of blood counts within 72 hours.

Acquired HLH is typically associated with not only EBV infections, T-/NK-cell lymphomas, and autoimmune diseases but also malaria and leishmaniasis. In the absence of morphology and serology, the most reliable test of visceral leishmaniasis is bone marrow polymerase chain reaction. This case illustrates the importance of recognizing other infectious etiologies of HLH, especially in patients from areas of endemicity, and initiating appropriate therapy to prevent life-threatening complications.