Unmasking Hemophagocytic Lymphohistiocytosis After Minimal Tumor Necrosis Factor-Alpha (TNF-α) Blockade: An Interplay of Contributing Elements

Presented is a case of hemophagocytic lymphohistiocytosis (HLH) in a 25-year-old African American female patient with Behçet disease and seronegative rheumatoid arthritis who developed fever, nausea, vomiting, and diarrhea 14 days after her first adalimumab dose. The diagnosis was established based on clinical and laboratory parameters meeting five of eight HLH-2004 criteria. The temporal relationship between drug initiation and symptom onset, along with prior improvement in arthritis symptoms, favored drug-induced HLH over macrophage activation syndrome. The patient was successfully treated with high-dose dexamethasone monotherapy per the HLH-2004 protocol, with etoposide deferred given the suspected drug-induced etiology and normal NK activity, achieving clinical improvement within 48 to 72 hours. This case demonstrates that HLH can occur after minimal tumor necrosis factor-alpha inhibitor exposure, likely through idiosyncratic mechanisms potentiated by multiple autoimmune conditions.