Visceral Leishmaniasis-Associated Hemophagocytic Lymphohistiocytosis in a Patient With Crohn's Disease in Therapy With Anti-TNFα: A Challenging Diagnostic Case Report.

BACKGROUND: Hemophagocytic lymphohistiocytosis (HLH) is a rare yet life-threatening hyperinflammatory syndrome, increasingly reported in patients with inflammatory bowel disease (IBD) receiving biologic therapy. While Epstein-Barr virus and cytomegalovirus represent the most frequent infectious triggers, visceral leishmaniasis (VL) is extremely uncommon and may be easily ignored outside endemic areas.

CASE PRESENTATION: We report the case of a 31-year-old man with Crohn's disease treated with escalated anti-TNFα therapy who presented with persistent fever, pancytopenia, hyperferritinemia, hypertriglyceridemia, and progressive systemic inflammation. Both infectious and oncologic workups were initially inconclusive. PET/CT showed splenomegaly, diffuse splenic, and bone marrow hypermetabolism, raising suspicion for a lymphoproliferative disorder; however, bone marrow aspirate revealed systemic inflammation and hemophagocytosis, suggesting HLH and detected intracellular amastigotes consistent with Leishmania spp., subsequently confirmed by serology. Liposomal amphotericin B prompted rapid clinical and biochemical improvement, with complete resolution of HLH. Anti-TNFα was discontinued and replaced with anti-IL-12/23 therapy to maintain IBD control while minimizing infectious risk.

CONCLUSION: In patients receiving anti-TNF therapy who present with persistent fever, cytopenias, hyperferritinemia, and unexplained systemic inflammation, HLH should be promptly investigated. Early bone marrow examination may facilitate diagnosis by revealing both hemophagocytosis and Leishmania amastigotes, enabling timely treatment. Following resolution of infection, transition to a biologic with a different mechanism of action, such as anti-IL-12/23 therapy, may represent a reasonable strategy for long-term IBD management.