Incidence and Survival of Hemophagocytic Lymphohistiocytosis Over Two Decades: A Population-Based Study

Adult hemophagocytic lymphohistiocytosis (HLH) is a rare, life-threatening syndrome triggered by various conditions. A nationwide study of the incidence and outcomes of HLH in Denmark over 23 years (2000-2023) was performed. Adults (≥ 18 years) with HLH and triggering diseases were identified in the Danish National Patient Registry and/or the Danish Pathology Registry. A total of 325 cases were identified. The incidence increased from 0.82 per 1 million person-years (1 M-PY) (95% CI 0.61-1.04) in 2000-2011 to 4.05 per 1 M-PY (95% CI 3.56-4.53) in 2012-2023. Hematologic malignancies were the triggering diagnosis in 46% of cases, mostly lymphomas (32%). There was no clear improvement in overall survival over time. However, survival differed markedly between subgroups, with the lowest 1-year overall survival of 31% for hematologic malignancy-associated HLH, compared with 75% for idiopathic HLH. In conclusion, HLH remains a rare syndrome with a dismal prognosis, especially when associated with hematologic malignancy.