title: The immunological and clinical spectrum of delayed drug-induced exanthems.
abstract: OBJECTIVE
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.affiliation: Division of Allergology, Clinic for Rheumatology and Clinical Immunology/Allergology, University of Bern, Inselspital, Bern, Switzerland.
authors.forename: Marianne
authors.initials: M
authors.lastname: Lerch
authors.forename: Werner J
authors.initials: WJ
authors.lastname: Pichler
mesh_terms: D003875:Drug Eruptions / Q000235:genetics / Q000276:immunology* / Q000503:physiopathology; D005076:Exanthema / Q000235:genetics / Q000276:immunology* / Q000503:physiopathology; D006801:Humans; D013997:Time Factors