Journal of General Internal Medicine

, Volume 32, Issue 9, pp 1060–1062 | Cite as

Fever, Splenomegaly, and Pancytopenia: Histoplasma-Associated Hemophagocytic Lymphohistiocytosis

Clinical Practice: Clinical Images


infectious diseases hematology clinical images 


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



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Conflict of Interest

The authors declare that they do not have a conflict of interest.


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© Society of General Internal Medicine 2017

Authors and Affiliations

  1. 1.Department of Internal MedicineUniversity of Texas Southwestern Medical CentreDallasUSA
  2. 2.Rutgers New Jersey Medical SchoolNewarkUSA
  3. 3.Departments of PathologyUniversity of Texas Southwestern Medical CentreDallasUSA

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