Immunosuppressive therapy–induced secondary hemophagocytic lymphohistiocytosis in psoriatic arthritis: diagnostic and therapeutic challenges

Hemophagocytic lymphohistiocytosis (HLH) is a rare, life-threatening syndrome characterized by excessive immune activation, often triggered by infections, malignancies, or autoimmune disorders. We report a case of 54-year-old obese woman with hypothyroidism and psoriatic arthritis (PsA), managed with methotrexate and sulfasalazine, who presented with persistent fever, acute kidney injury, and transaminitis. Initially diagnosed as sulfasalazine hypersensitivity. However, her condition deteriorated, developing severe pancytopenia, hypotensive episodes, hepatomegaly with hepatic injury (evidenced by hyperbilirubinemia, transaminitis, hypofibrinogenemia, and coagulopathy), elevated D-dimer, hypertriglyceridemia, and hyperferritinemia, ultimately fulfilling the diagnostic criteria for HLH. Genetic testing was performed to exclude primary (inherited) HLH. Despite diagnostic challenges due to overlapping features with sepsis or multiple organ dysfunction syndrome, pending genetic results did not delay the initiation of urgent HLH treatment. The patient received pulsed corticosteroids (methylprednisolone followed by high-dose dexamethasone), intravenous immunoglobulin, granulocyte-colony stimulating factor, prophylactic antimicrobials, and blood transfusions. Following treatment, her symptoms resolved completely, achieving full clinical and biochemical remission. To our knowledge, this is the first reported case of HLH in an adult with PsA on combined methotrexate and sulfasalazine therapy. This case underscores the critical need for early recognition of HLH in patients with unexplained fever, cytopenias, and transaminitis, and the importance of prompt corticosteroid-based therapy to improve outcomes.