Abstract
Introduction: Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening hyperinflammatory syndrome driven by dysregulated activation of cytotoxic T lymphocytes and macrophages. While infections and malignancies represent the most frequently identified triggers, HLH precipitated by arthropod envenomation is exceptionally rare, with prior reports confined predominantly to paediatric populations. Case description: A 65-year-old male with multiple comorbidities developed progressive fever, cytopenias, extreme hyperferritinaemia (>8,000 ng/ml), and multiorgan dysfunction following a suspected spider bite to the inner left thigh. Evaluation revealed markedly elevated soluble interleukin-2 receptor (sCD25 >4,000 pg/ml) and CXCL9 (35,623 pg/ml; 55-fold above the upper limit of normal), along with reduced natural killer (NK) cell counts. Bone marrow biopsy confirmed haemophagocytosis. The patient fulfilled 6 of 8 HLH-2004 diagnostic criteria, with an HScore of approximately 197, corresponding to a >90-95% probability of HLH. Treatment with high-dose corticosteroids, ruxolitinib, and anakinra resulted in rapid suppression of inflammatory markers. The course was complicated by acute kidney injury requiring temporary haemodialysis. By early 2026, the patient achieved normalization of all laboratory parameters and returned to near-baseline functional status. Conclusion: This case illustrates an exceptionally rare adult presentation of envenomation-associated secondary HLH. Clinicians should consider HLH in patients with persistent fever, cytopenias, and extreme hyperferritinaemia following arthropod exposure. Early immunomodulatory therapy, including cytokine-directed agents such as ruxolitinib and anakinra, may avert irreversible organ damage in the absence of cytotoxic etoposide-based therapy.