The immunological and clinical spectrum of delayed drug-induced exanthems

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.

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.

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.