Hemophagocytic Lymphohistiocytosis in Adults: A Retrospective Case Series and Review

Introduction Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening hyperinflammatory syndrome triggered by infections, malignancies, and autoimmune diseases, often mimicking severe sepsis and delaying diagnosis. We present a case series of three patients with HLH from distinct etiologies to highlight diagnostic challenges, management, and outcomes, along with a review of HLH. Case Series Case 1 involved pregnancy-related HLH with delayed diagnosis and death prior to HLH-directed therapy. Case 2 involved autoimmune-associated HLH in patient with previous HLH secondary to Legionella infection, treated with the HLH-94 protocol with survival. Case 3 involved lymphoma-associated HLH with parvovirus B19, resulting in death despite treatment. Discussion Persistent fever despite antimicrobial therapy and elevated CXCL9 levels were observed in all cases, with higher levels associated with worse outcomes. Median time to HLH consideration was 10 days. Conclusion HLH remains diagnostically challenging with limited tools. Early recognition and multidisciplinary management are essential to improve outcomes.