Hemophagocytic Lymphohistiocytosis in HIV/AIDS: Who Fired the First Shot, the Virus or Its Companions?

Hemophagocytic lymphohistiocytosis (HLH) is a rare, life-threatening hyperinflammatory syndrome caused by uncontrolled activation of T-lymphocytes and macrophages. It is classified as either familial (genetic) or acquired. Among acquired forms, infections are a common trigger, with human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS) and associated opportunistic infections frequently considered in the differential diagnosis. We report the case of a 20-year-old Hispanic male who presented with nausea and vomiting and was found to have bi-cytopenia, high ferritin level, mild splenomegaly, decreased natural killer (NK) cells, and bone marrow findings consistent with HLH. He was also diagnosed with HIV/AIDS, which was considered the underlying trigger for HLH, and was initiated on dexamethasone per HLH-2004 protocol. The patient was started on intravenous amphotericin B for disseminated histoplasmosis, along with trimethoprim-sulfamethoxazole (TMP-SMX) for Pneumocystis jirovecii pneumonia prophylaxis. Due to worsening mental status, increased amphotericin B and TMP-SMX dose for presumed central nervous system (CNS) histoplasmosis and toxoplasmosis, respectively. Brain magnetic resonance imaging (MRI) revealed multiple ring-enhancing lesions, and cerebrospinal fluid (CSF) was positive for Toxoplasma gondii. Amphotericin B was subsequently de-escalated, while TMP-SMX was continued at therapeutic dosing. The patient was co-managed in a multidisciplinary approach involving infectious disease, hematology, and neurology specialists. We conclude that early diagnosis of HLH is critical to prevent disease progression and improve patient outcomes. Identifying and treating the underlying trigger remains the cornerstone of effective management. The use of timely diagnostic tools and a multidisciplinary approach is essential to avoid delays in recognizing HLH and initiating appropriate therapy.