Sulfonamide-induced reactions in desensitized patients with AIDS-The role of covalent protein haptenation by sulfamethoxazole

Background: Adverse reactions to sulfonamides cause significant morbidity in patients with AIDS. We have demonstrated previously a ≅40 kd sulfamethoxazole (SMX)-substituted protein in the serum of some individuals treated with SMX. Objective: The purpose of this study was to examine patients with AIDS who had undergone SMX desensitization because of a prior history of SMX allergy for the presence of SMX-haptenated serum proteins and to determine whether these proteins, SMX-specific IgG antibodies, or both predict the development of subsequent clinical reactivity. Methods: Four patients with no history of allergy and in whom SMX prophylaxis was initiated and eight patients with AIDS who had undergone SMX desensitization because of prior allergy were evaluated. SMX-conjugated serum proteins were identified with an immunoblotting assay, and SMX-specific IgG antibodies were identified by ELISA inhibition. Results: One of the four patients receiving SMX prophylactic treatment demonstrated SMX-protein haptenation, none had detectable SMX-specific IgG antibodies, and none developed an SMX-associated reaction during the time in which they were followed. Of the eight patients who underwent SMX desensitization, six (75%) demonstrated SMX-protein haptenation, and three of these six (50%) subsequently developed SMX-induced cutaneous reactions. Only one of these six patients had detectable SMX-specific IgG antibodies. The two individuals who did not demonstrate SMX-protein haptenation have not developed a clinical reaction. Conclusion: These preliminary data suggest that SMX haptenation, but not SMX-specific antibodies, may be important in the development of clinical sensitivity in patients with AIDS who have undergone SMX desensitization.