Marianne Lerch1, Werner J Pichler. 1. Division of Allergology, Clinic for Rheumatology and Clinical Immunology/Allergology, University of Bern, Inselspital, Bern, Switzerland.
Abstract
PURPOSE OF REVIEW: Drug-induced exanthems are the most common manifestations of drug hypersensitivity and are observed in as much as 2-3% of hospitalized patients. Here we summarize new concepts of the immune mechanisms underlying various forms of drug-induced exanthems. RECENT FINDINGS: Alpha-betaTCR+, CD4 and CD8+ T cells are involved in different drug hypersensitivity reactions. Their function determines the clinical picture. In maculopapular, bullous and pustular exanthems cytotoxic T cells are involved, while a high IL-5 and eotaxin production by tissue cells is frequently found in maculopapular and occasionally in bullous and in pustular exanthems. High IL-8 (CXCL-8) and granulocyte-macrophage colony stimulating factor production by T cells is a hallmark of pustular drug exanthems. In the most severe and potentially life-threatening forms of exanthems (Stevens-Johnson syndrome/toxic epidermal necrolysis) cytotoxic CD8+ T cells with natural killer cell markers can be found in the blister fluid. SUMMARY: These findings are the basis for a new subclassification of delayed, type IV hypersensitivity reactions into type IVa (T helper type 1 cells, e.g. tuberculin reaction and contact dermatitis), IVb (T helper type 2 cells, maculopapular exanthem with eosinophilia), IVc (cytotoxic T cells, contact dermatitis, maculopapular and bullous exanthem), and IVd reactions (CXCL-8/granulocyte-macrophage colony stimulating factor-producing T cells and neutrophil attraction, pustular exanthems), by which, in most reactions, various mechanisms occur together but one reaction dominates the clinical picture.
PURPOSE OF REVIEW: Drug-induced exanthems are the most common manifestations of drug hypersensitivity and are observed in as much as 2-3% of hospitalized patients. Here we summarize new concepts of the immune mechanisms underlying various forms of drug-induced exanthems. RECENT FINDINGS: Alpha-betaTCR+, CD4 and CD8+ T cells are involved in different drug hypersensitivity reactions. Their function determines the clinical picture. In maculopapular, bullous and pustular exanthems cytotoxic T cells are involved, while a high IL-5 and eotaxin production by tissue cells is frequently found in maculopapular and occasionally in bullous and in pustular exanthems. High IL-8 (CXCL-8) and granulocyte-macrophage colony stimulating factor production by T cells is a hallmark of pustular drug exanthems. In the most severe and potentially life-threatening forms of exanthems (Stevens-Johnson syndrome/toxic epidermal necrolysis) cytotoxic CD8+ T cells with natural killer cell markers can be found in the blister fluid. SUMMARY: These findings are the basis for a new subclassification of delayed, type IV hypersensitivity reactions into type IVa (T helper type 1 cells, e.g. tuberculin reaction and contact dermatitis), IVb (T helper type 2 cells, maculopapular exanthem with eosinophilia), IVc (cytotoxic T cells, contact dermatitis, maculopapular and bullous exanthem), and IVd reactions (CXCL-8/granulocyte-macrophage colony stimulating factor-producing T cells and neutrophil attraction, pustular exanthems), by which, in most reactions, various mechanisms occur together but one reaction dominates the clinical picture.
Authors: Mark McCormack; Ana Alfirevic; Stephane Bourgeois; John J Farrell; Dalia Kasperavičiūtė; Mary Carrington; Graeme J Sills; Tony Marson; Xiaoming Jia; Paul I W de Bakker; Krishna Chinthapalli; Mariam Molokhia; Michael R Johnson; Gerard D O'Connor; Elijah Chaila; Saud Alhusaini; Kevin V Shianna; Rodney A Radtke; Erin L Heinzen; Nicole Walley; Massimo Pandolfo; Werner Pichler; B Kevin Park; Chantal Depondt; Sanjay M Sisodiya; David B Goldstein; Panos Deloukas; Norman Delanty; Gianpiero L Cavalleri; Munir Pirmohamed Journal: N Engl J Med Date: 2011-03-24 Impact factor: 91.245