Diagnosis and management of haemophagocytic lymphohistiocytosis in adults: A narrative review and practical approach

Haemophagocytic lymphohistiocytosis (HLH) is a rare, life-threatening hyperinflammatory state characterised by inappropriate survival of immune cells, cytokine storm, profound cytopenias, and rapidly progressive multi-organ failure. In adults with secondary HLH, the most common triggers include haematological malignancy, autoimmune/autoinflammatory conditions, and infections. In Asian contexts, both malignancy-induced (with higher rates of NK/T-cell lymphoma than B-cell lymphoma) and Epstein-Barr virus-induced HLH are particularly common. Additionally, there is a distinct “Asian” variant of intravascular B-cell lymphoma with no cutaneous manifestations that tends to manifest with HLH and may require random skin biopsies to diagnose. Diagnosis can be supported by the HLH-2004 diagnostic and therapeutic guidelines for haemophagocytic lymphohistiocytosis or the H-score in adult HLH, and subsequent management involves high-dose corticosteroids with targeted immunomodulatory treatments or chemotherapy directed at the underlying condition. In this narrative review article, the authors provide a comprehensive overview of HLH epidemiology, diagnosis, and management strategies with a practical approach for frontline clinicians practising in Asian contexts.