Drug-induced multisystem syndromes: An overlooked challenge in pharmacovigilance

BackgroundDrug-Induced Multisystem Syndromes (DIMS) represent a clinically significant yet under-recognized group of delayed immune-mediated adverse drug reactions characterized by heterogeneous clinical presentations, diagnostic uncertainty, and substantial morbidity. Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) and Drug-Induced Hypersensitivity Syndrome (DIHS) are prototypical conditions within this spectrum.MethodsThis narrative review synthesizes current evidence on the immunopathogenesis, pharmacogenomic susceptibility, clinical manifestations, diagnostic challenges, and pharmacovigilance strategies associated with delayed multisystem drug hypersensitivity reactions. The DIMS framework is proposed as a mechanistic, hypothesis-driven construct intended to enhance pharmacovigilance signal recognition rather than replace existing diagnostic classifications.ResultsDIMS typically develop weeks after drug exposure and involve multisystem inflammatory injury affecting organs such as the liver, kidney, lungs, and heart. T-cell-mediated immune activation, cytokine amplification, and viral reactivation are central pathogenic mechanisms. Mortality varies by syndrome subtype, ranging from approximately 5-10% in DRESS/DIHS to 25-35% in Toxic Epidermal Necrolysis (TEN). Pharmacogenomic factors, including HLA alleles and cytochrome P450 polymorphisms, contribute to susceptibility.ConclusionThe DIMS framework may support improved early recognition, pharmacovigilance signal detection, and prevention strategies. Integration of pharmacogenomics and artificial intelligence-based analytics may facilitate risk stratification and safer, personalized therapeutic decision-making.