Download

Download Full Text (512 KB)

Description

Hemophagocytic lymphohistiocytosis (HLH) is a rare, life-threatening disorder characterized by hyperinflammation resulting from uncontrolled activation of macrophages and lymphocytes. HLH can lead to endothelial injury, multiorgan failure, and death. HLH may be caused by genetic mutations or in the setting of infection, malignancy, autoimmune disorders, or immunosuppressive therapies 1, 2. Diagnosis is based on the presence of at least 5 of 8 criteria: fever, splenomegaly, bicytopenia, hypertriglyceridemia and/or hypofibrinogenemia, hemophagocytosis, low NK cell activity, hyperferritinemia, and elevated IL-2 levels 3. Histoplasmosis-associated HLH is exceedingly rare, with roughly 60 cases reported worldwide, and poses a unique management challenge 4, 5. This case report aims to increase awareness of this presentation and highlight the diagnostic and therapeutic complexities involved.

A 58-year-old male with a past medical history of ankylosing spondylitis on Infliximab and Methotrexate presented to the hospital with shortness of breath, jaundice, and right upper quadrant (RUQ) pain. Vitals were significant for tachycardia and hypoxia at 86% on room air. Physical exam was pertinent for scleral icterus, jaundice, bilateral crackles, RUQ tenderness, and splenomegaly. Initial labs were significant for lactic acidosis, elevated liver enzymes, hyperbilirubinemia, low fibrinogen, elevated D-dimer, and significantly elevated ferritin. CT thorax showed bilateral ground-glass opacities, CT Abdomen/Pelvis revealed hepatomegaly, and MRCP was significant for splenomegaly without evidence of biliary obstruction. Microbiology results showed positive histoplasmosis antigen and negative blood cultures. Subsequent labs showed elevated IL-2 and hypertriglyceridemia. Bronchoalveolar lavage positive for fungal elements with budding yeast and bone marrow biopsy positive for HLH.

Histoplasmosis-associated HLH is a rare complication in immunosuppressed adults and can present with nonspecific findings that mimic severe infection or drug toxicity. This case highlights the need for a high index of suspicion for HLH in patients with systemic inflammation, cytopenias, and organ dysfunction while on biologic or antimetabolite therapy. It also adds to the limited literature describing the therapeutic challenge of balancing immunosuppression with active fungal infection, emphasizing the importance of early multidisciplinary evaluation.

Publication Date

5-8-2026

Disciplines

Internal Medicine

Comments

2026 Research Day Corewell Health West, Grand Rapids, MI, May 8, 2026. Abstract 2038

Histoplasmosis-Induced Hemophagocytic Lymphohistiocytosis in an Adult Patient on Immunosuppressive Therapy

Share

COinS