Distinguishing Hemophagocytic Lymphohistiocytosis, Immune Reconstitution Inflammatory Syndrome, and HIV-Associated Immune Thrombocytopenic Purpura: A Challenging Case of Thrombocytopenia in AIDS.

Thrombocytopenia is a frequent hematologic complication in advanced HIV/AIDS, presenting significant diagnostic challenges due to overlapping etiologies. Hemophagocytic lymphohistiocytosis (HLH), immune reconstitution inflammatory syndrome (IRIS), and HIV-associated immune thrombocytopenic purpura (HIV-ITP) can all manifest with overlapping clinical features, which, despite their differing frequencies, may complicate diagnosis and management. We present a case of a 33-year-old male patient with advanced HIV/AIDS, metastatic Kaposi sarcoma, and inconsistent antiretroviral therapy (ART) adherence, who developed progressive thrombocytopenia, anemia, and pancytopenia. Initial workup, including an elevated HScore, suggested a possible HLH diagnosis; however, further immunologic testing did not meet HLH criteria. In the absence of definitive findings, HIV-ITP was identified as the most likely etiology. This case highlights the importance of a systematic, exclusion-based diagnostic approach in evaluating thrombocytopenia in immunocompromised patients, particularly when multiple concurrent conditions obscure the clinical picture.