Evaluating hemophagocytic lymphohistiocytosis criteria in patients with drug-induced hypersensitivity syndrome

Background: Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening syndrome of uncontrolled immune activation causing fever, cytopenias, hepatosplenomegaly, and organ dysfunction.Diagnosis is made using the HLH-2004 or -2009 criteria.Drug-induced hypersensitivity syndrome (DIHS) is a severe T-cell mediated drug reaction with overlapping features, including fever, rash, hematologic abnormalities, and organ involvement.Objective: To evaluate how frequently DIHS patients meet established HLH diagnostic criteria.Methods: A systematic review was conducted of studies describing individual DIHS cases with HLHrelevant clinical and laboratory data.Extracted information included demographics, HLH criteria, and fulfillment of HLH-2004 and HLH-2009 diagnostic guidelines.Results: Seventy-three DIHS patients were included.Twenty met HLH-2004 criteria, and 41 met HLH-2009 criteria.Fever, hepatitis, and hyperferritinemia were the most frequently reported features, present in 96%, 96%, and 89% of cases, respectively.Among those not meeting full HLH-2004 criteria, 18 met two, 14 met three, and 16 met four criteria.Limitations: Inclusion was limited to published cases with HLH-related data, introducing potential selection bias. Conclusion:Many DIHS patients met partial or full HLH criteria, suggesting that existing HLH frameworks may lack specificity for distinguishing HLH from mimics like DIHS.Refinement of HLH criteria is needed for improved diagnostic accuracy.( JAAD Reviews 2025;5:103-6.