CASE
A 26-year-old man with acquired immunodeficiency syndrome (AIDS) taking no medications presented with fever and anorexia. Examination showed a febrile cachectic man with splenomegaly. Laboratory analysis revealed pancytopenia (white cell count 2.1 × 103/μL, hemoglobin 8.1 gm/dL, platelet count 49 × 103/μL) and CD4 count 2/μL. Serum ferritin (8312 mcg/L) and fasting triglycerides (312 mg/dL) were elevated. Urinary Histoplasma antigen was positive. Bone marrow biopsy demonstrated histiocytes with intracellular yeast and ingested red blood cells (Figs. 1 and 2). The patient was diagnosed with disseminated histoplasmosis that manifested as hemophagocytic lymphohistiocytosis (HLH) and was treated with antiretroviral therapy, intravenous amphotericin B for 2 weeks, and oral itraconazole for 1 year.
Figure 1.
Several enlarged histiocytes containing numerous yeast forms which are surrounded by a clear zone, characteristic of Histoplasma (red arrows). One histiocyte (at the top) also contains an engulfed red blood cell (black arrow). Bone marrow, Wright-Giemsa stain, ×1000.
Figure 2.
GMS stain highlights numerous fungal organisms identified as capsulated yeast (red arrows). Bone marrow, Gomori methenamine silver (GMS) stain, ×50.
HLH is a hyperinflammatory disorder caused by uncontrolled proliferation of activated lymphocytes and macrophages secreting inflammatory cytokines.1 Although a primary genetic form exists, secondary HLH is often associated with immunodeficiency, malignancy, and infection, commonly in patients with AIDS with histoplasmosis.2 , 3 Current diagnostic criteria require fulfillment of five out of eight criteria: fever, splenomegaly, cytopenia, hyperferritinemia, hypertriglyceridemia/hypofibrinogenemia, pathological evidence of hemophagocytosis, low natural killer cell activity, and elevated levels of soluble CD25.1 , 2 Treatment of HLH involves treating the underlying cause; additional therapy with corticosteroids, intravenous immunoglobulin (IVIG), etoposide, or cyclosporine may be required.1
Acknowledgements
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Conflict of Interest
The authors declare that they do not have a conflict of interest.
REFERENCES
- 1.Schram AM, Berliner N. How I treat hemophagocytic lymphohistiocytosis in the adult patient. Blood. 2015;125(19):2908–2914. doi: 10.1182/blood-2015-01-551622. [DOI] [PubMed] [Google Scholar]
- 2.Huang AM. Hemophagocytic lymphohistiocytosis and disseminated histoplasmosis. Blood. 2014;123(16):2449. doi: 10.1182/blood-2014-01-550657. [DOI] [PubMed] [Google Scholar]
- 3.Townsend JL, Shanbhag S, Hancock J, Bowman K, Nijhawan AE. Histoplasmosis-induced hemophagocytic syndrome: a case series and review of the literature. Open Forum Infect Dis. 2015;2(2):ofv055. doi: 10.1093/ofid/ofv055. [DOI] [PMC free article] [PubMed] [Google Scholar]