Delayed drug reactions toxic epidermal necrolysis

Mechanisms of non-immediate reactions are unclear but may be immunological and non-immunological. Delayed reactions of the IgE type are known (131). Aminopenicillins seem to be an important cause of non-immediate reactions (132-134). The morbilliform rash that begins 1-10 days after amoxicillin can be caused by a delayed cell-mediated immune reaction (135) as can fixed drug eruptions (136,137), toxic epidermal necrolysis (138-140), bullous erythroderma (141), and contact eczema (142). Investigation of these disorders should include delayed readings of skin tests (135). In patients with chronic urticaria, penicillin allergy was demonstrated by cutaneous tests. 

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. 

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