Mechanistic perspectives on sulfonamide-induced cutaneous drug reactions.
OBJECTIVE
Idiosyncratic drug reactions continue to limit the therapeutic utility of sulfonamide drugs because of their associated morbidity and mortality. Cutaneous reactions are the predominant reasons for withdrawal of such drugs from use in patients. As a consequence of the recognized metabolic and immunologic capability of the skin, an understanding of the pathogenic role of this tissue in the development of sulfonamide-induced cutaneous drug reactions may provide insight into the mechanisms and risk factors for these and other adverse drug events.


RESULTS
In the present review we discuss currently available mechanistic information, including issues related to drug bioactivation and adduct formation, immunoresponsiveness, and immune dysregulation, for the development of sulfonamide-induced (delayed-type) cutaneous drug reactions. The potential application of findings from several related areas of research are also discussed within the context of the pathogenesis of these cutaneous reactions.


CONCLUSIONS
Despite progress, numerous unresolved issues support the testing of novel hypotheses, the search for additional risk factors, and the need for a global approach, including links between laboratory and clinical paradigms. These issues must be addressed if we are to gain an understanding of the mechanistic bases for these cutaneous drug reactions.
Molecular and Cellular Toxicology Section, Laboratory of Molecular Immunology, NHLBI/NIH, 9000 Rockville Pike, Building 10, Room 8N110, Bethesda, MD 20892-2760, USA. ReillyT@nhlbi.nih.gov
Timothy P
TP
Reilly
Cynthia
C
Ju
D000890:Anti-Infective Agents / Q000009:adverse effects* / Q000276:immunology; D003875:Drug Eruptions / Q000209:etiology*; D006801:Humans; D013449:Sulfonamides / Q000009:adverse effects* / Q000276:immunology
D000890:Anti-Infective Agents; D013449:Sulfonamides