Beyond Cutaneous Injury: Immunopathogenesis, Early Recognition, and Therapeutic Challenges in DRESS and Stevens–Johnson Syndrome/Toxic Epidermal Necrolysis

Severe cutaneous adverse drug reactions represent a major clinical challenge due to their complex immunological mechanisms, heterogeneous manifestations, and potential to cause life-threatening systemic complications. This narrative review examines the immunopathogenesis, early recognition, diagnostic assessment, and therapeutic management of drug reaction with eosinophilia and systemic symptoms (DRESS) and Stevens–Johnson syndrome/toxic epidermal necrolysis (SJS/TEN). Twenty scientific publications, including clinical investigations, systematic reviews, and international consensus recommendations, were analyzed through a qualitative synthesis incorporating contributions from Latin America. The findings revealed distinct patterns of immune-mediated injury, characterized by systemic inflammation, T-cell activation, and potential herpesvirus reactivation in DRESS, compared with cytotoxic keratinocyte destruction mediated by granulysin and other inflammatory pathways in SJS/TEN. Clinical evidence emphasized the relevance of early drug withdrawal, multidisciplinary assessment, and standardized instruments, including RegiSCAR, ALDEN, and SCORTEN. Therapeutic investigations identified potentially favorable outcomes associated with selected immunomodulatory interventions, including systemic corticosteroids, cyclosporine, and tumor necrosis factor-alpha inhibitors; however, methodological heterogeneity and limited randomized evidence restrict definitive conclusions regarding comparative effectiveness. Latin American contributions highlighted the importance of regional clinical guidelines and improved access to specialized care. Overall, integrating immunological knowledge with structured clinical assessment and evidence-based management may contribute to earlier recognition and more individualized care. Further multicenter investigations are required to clarify therapeutic effectiveness, identify reliable biomarkers, and improve long-term outcomes.