Human leukocyte antigen-associated severe cutaneous adverse drug reactions: from bedside to bench and beyond

Despite their being uncommon, severe cutaneous adverse drug reactions (SCARs) result in a very great burden of disease. These reactions not only carry with them a high mortality (10%–50%) and high morbidity (60%) with severe ocular complications, alopecia, oral and dental complications and development of autoimmune diseases, but also create a substantial economic burden for patients' families and society. SCARs are, therefore, an important medical problem needing a solution in many countries, especially in Asia. The clinical spectrum of SCARs comprises Stevens-Johnson syndrome, toxic epidermal necrolysis, DRESS (drug rash with eosinophilia and systemic symptoms) (also known as drug hypersensitivity syndrome or drug-induced hypersensitivity syndrome) and acute generalised exanthematous pustulosis. Recent crucial advances in determining genetic susceptibility and understanding how T cells recognise certain medications or their metabolites via the major histocompatibility complex and the effects of cofactors, have led to the implementation of cost-effective screening programs enabling prevention in a number of countries, and to further understanding of the patho-mechanisms involved in SCARs and their significance. In this review, we document comprehensively the journey of SCARs from bedside to bench and outline future perspectives in SCARs research.