IMMUNOLOGICAL PHYSIOPATHOLOGY OF CUTANEOUS ADVERSE DRUG-REACTIONS

Different mechanisms are responsible for cutaneous adverse drug reacti ons (ADR) and some of them are thought to be immunoallergological. The antigens involved in cutaneous ADR can be the active drug itself or t he excipients also contained in commercialized drugs. The epitopes rec ognized can be on the native drug or on metabolites. In ADR due to bet alactam antibiotics, the sensitization can involve one or more antigen ic determinants (major or minor) and could be stereoisomer-specific fo r a given epitope. Some drug-induced urticarias and angioedemas are tr iggered by immediate IgE-specific reactions. Sensitizing antigens, in the HLA molecules of antigen presenting cells, could be recognized by T cells. In ADR, dermal lymphocytes are mostly CD4(+). CD8(+) cells ca n be seen in the epidermis. Immunological mechanisms involved in eryth ema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis a nd bullous reactions are similar to those involved in graft-versus-hos t disease, with delayed T cell-mediated immune reactions mediated by d rug specific CD8(+) cells. Keratinocyte lysis could be induced by seve ral mechanisms: epidermal CD8(+) T cell cytotoxicity, release of TNF a lpha and/or a direct effect of the drug itself. Maculopapular rashes a re probably induced by a delayed T-cell mediated immune reaction, but whether CD4(+) or CD8(+) T cells are involved is still debated. Locali zed abnormal responses of keratinocytes to gamma IFN or TNF alpha and long-lasting epidermal CD8(+) T-cells could be involved in the onset o f fixed drug eruptions. Lichenoid drug eruptions could be related to t he activation of cytotoxic CD8(+) T cells.