Figure 1.

Scheme illustrating the proposed mechanisms of sulphamethoxazole hypersensitivity reactions. Pathway 1 involves sequential oxidation to the reactive nitroso metabolite that can bind irreversibly to thiol groups of either circulating or cell surface proteins. Antigen presenting cells process and present the antigenic peptide fragment to T-cells. T-cells proliferate and in the presence of the appropriate co-stimulatory signals may cause hypersensitivity. Pathway 2, proposed by Pichler et al. (Mauri-Hellweg et al., 1995; Schnyder et al., 1997; Zanni et al., 1998; von Greyerz et al., 1999), suggests that sulphamethoxazole stimulates T-cell proliferation, in the absence of drug metabolism and antigen processing, via a direct, reversible interaction between the parent drug and an antigenic peptide embedded within the MHC binding groove of antigen presenting cells.