Delayed skin drug hypersensitivity syndrome

Many of the reactions to sulfonamides involve the skin and mucous membranes. The more severe reactions that occur include potentially lethal toxidermias and a delayed hypersensi-tivity-type syndrome characterized by fever, skin rash, and multi-organ toxicity, hnmediate type I reactions are the most well-defined sulfonamide-induced hypersensitivity reactions with the best defined allergenic drug structmes. Sulfonamides with one methyl substituent on a five- or six-membered aromatic heterocyclic ring on the carbon p to the sulfon-amido substituent are the structmes most complanentary to anti-sulfamethoxazole IgE antibody combining sites. 

Type IVc. T cells themselves can also act as effector cells. They migrate to the tissue and can kill tissue cells such as hepatocytes or keratinocytes in a perforin/ granzymeB- and FasL-dependent manner (Schnyder et al. 1998 Nassif et al. 2002, 2004 Kuechler et al. 2004). Such reactions occur in most drug-induced delayed hypersensitivity reactions, mostly together with other type IV reactions (monocyte, eosinophil, or neutrophil recruitment and activation). Cytotoxic T cells thus play an important role in maculopapular or bullous skin diseases as well as in conditions characterized by neutrophilic inflammation (acute generalized exanthematous pustulosis, AGEP), and in contact dermatitis. Type IVc reactions appear to be dominant in bullous skin reactions such as Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), where activated CD8-t T cells kill keratinocytes (Schnyder et al. 1998 Nassif et al. 2002, 2004). They may also be the dominant cell type in hepatitis or interstitial nephritis. 

The chemically similar teicoplanin, not approved in the USA, is not inferior to vancomycin with regard to efficiency of treating grampositive infections. It shows a lower rate of adverse reactions, particularly nephrotoxicity and, as already discussed, is used as a substitute for vancomycin in red man syndrome. When hypersensitivity reactions do occur with teicoplanin they are generally of the delayed type, but there are a few documented cases of apparent IgE antibody-mediated reactions implicated, for example, by an immediate wheal and flare skin reaction to the drug or by teicoplanin-induced histamine release from a patient s basophils. Despite the chemical and pharmacological... 

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