Disseminated histoplasmosis associated with acquired hemophagocytic lymphohistiocytosis

Key Clinical Message

Hemophagocytic lymphohistiocytosis (HLH) is a potentially life-threatening clinical syndrome caused by uncontrolled activation of lymphocytes and histiocytes resulting in high levels of cytokines. Acquired HLH occurs in autoimmune, inflammatory, infectious, and immunosuppressive disorders. Prompt identification and treatment of an underlying triggering cause improves clinical outcome.

Introduction

A 64-year-old female patient with scleroderma, monoclonal gammopathy of undetermined significance, chronic thrush, and kidney failure was admitted to ICU with confusion, high grade fevers and 20 lbs weight loss. Her laboratory workup showed WBC 5.4 × 10⁹/L (normal 3.5–10.5 × 10⁹/L) hemoglobin 78 g/L (normal 115–155 g/L), platelets 46 × 10⁹/L (normal 130–380 × 10⁹/L), fibrinogen 0.9 g/L (normal 1.9–4.5 g/L), lactate dehydrogenase 2613 U/L (normal 100–205 U/L), and ferritin 47,049 μg/L (normal 11–307 μg/L). There was no evidence of hepatosplenomegaly on physical examination.

The bone marrow revealed loose collections of histiocytes showing prominent hemophagocytosis (Fig.1A and B). Grocott–Gomori's methenamine silver stain performed on the marrow biopsy (Fig.1C) showed a few ovoid, 3–5 μm, narrow-based budding yeast cells, suggestive of histoplasmosis, with the yeast forms seen in black color against a green background. The Periodic acid-Schiff (PAS) stain (Fig.1D) showed the budding yeast as bright pink forms. Ziehl-Neelsen staining for acid fast bacilli was negative.

Figure 1.

Histoplasma capsulatum identified in bone marrow. (A) H&E stain of biopsy, (B) Wright-Giemsa stain of the aspirate, (C) Grocott-Gomori staining Histoplasma capsulatum, and (D) PAS staining Histoplasma capsulatum.

The hematopathologist reviewing these slides communicated the results to the microbiology department. Serology showed Histoplasma complement fixation nonreactive and Histoplasma H and M band immunodiffusion reactive compatible with serological evidence of recent or chronic infection. Bone marrow aspirate was collected in BACTEC™ Myco/F Lytic culture medium and after 3 weeks confirmed the presence of Histoplasma capsulatum.

The patient improved dramatically after initiation of antifungal therapy based on initial bone marrow microscopy findings, highlighting the importance of identifying yeast forms with bone marrow biopsy microscopic examination and the importance of interlaboratory communication to optimize patient care.

Conflict of Interest

None declared.