SELECTED ARTICLES FROM THE RECENT LITERATURE 2003

12/17/03

Sulfa antibiotics likely do not cross-react with non-antibiotic sulfonamides

Summary
There is still some question whether individuals with prior allergic reactions to sulfonamide antibiotics (S-ABx) can tolerate non-antibiotic agents containing the sulfonamide moiety ((N-A Bx) such as thiazides, furosemide, celecoxib and some oral anti-diabetic agents. Strom et al of the Univ. of Pennsylvania in Philadelphia, PA carried out a retrospective cohort study using the General Practice Research Database of the UK. They compared the risk of allergic reactions within 30 days after receipt of a N-ABx drug in 2 populations: 1) those with evidence of an allergic reaction during previous therapy with a S-ABx agent; 2) individuals without evidence of such a prior allergic reaction to S-ABx.

They found that 9.9% of 969 patients with reported previous reactions to S-ABx described an allergic reaction after they subsequently received a N-ABx agent. This compared with allergic reactions after N-ABx treatment in 1.6% of the 19,257 individuals without histories of allergic reactions to prior S-Abx treatment (Adjusted Odds Ratio (OR)=2.8). However, the antigenic specificity of this association was brought into question by an even greater tendency to exhibit allergic reactions to penicillin (chemically unrelated to the sulfonamides) in those with histories of adverse reactions to previous S-ABx treatment (OR=3.9). Furthermore, there was a lower incidence of allergic reactions to N-ABx in those with histories of previous allergic reactions to S-Abx than in those with histories of previous allergic reactions to penicillins. The authors concluded that the association of an allergic reaction to N-ABx with a history of previous reaction to S-ABx is due to a predisposition to allergic reactions in this population rather than a true allergic cross-reactivity between the S-ABx and the N-ABx.

Reference
N Eng J Med 2003;349:1628-35

Editor's Comments
This large epidemiologic study used a well-validated database that reflects the "real world" situation in primary care practice rather than the potentially selected patient populations evaluated in tertiary referral centers. The authors concluded that the moderately greater incidence of reported allergic reactions to N-ABx in those with histories of S-ABx allergy is not due to true allergic cross-reactivity between S-ABx and N-ABx. This impression is supported by what is known about true allergic reactions to S-ABx. As reviewed by Shapiro and Shear (Drug Safety 2001;24:239-47) S-ABx contain a substituted ring at the N1 position of the molecule, thought to be critical as the target for IgE-mediated allergic reactions. This N1 substituted ring molecular characteristic of S-ABx is not present in N-Bx sulfonamides such as thiazides, furosemide, sulfonylurea anti-diabetic drugs, and celecoxib, a COX-2 inhibitor.

However, if we accept the authors' conclusions, we are left with the question why individuals with previous allergic reactions to S-ABx would be more likely to exhibit "allergic" reactions to chemically unrelated agents. More investigation is warranted.
 

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