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Sulfonamide allergy in HIV-uninfected patients

Anthony Montanaro, MD, FAAAAI
Section Editor
N Franklin Adkinson, Jr, MD
Deputy Editor
Anna M Feldweg, MD


Sulfonamide-containing antibiotics are the second most frequent cause of allergic drug reactions, after the beta-lactams (penicillins and cephalosporins). In one large study, the incidence of reactions to trimethoprim-sulfamethoxazole (TMP-SMX) was 34 per 1000 patients exposed, compared with 51 per 1000 for amoxicillin [1]. However, the adverse reactions caused by sulfonamides differ significantly from those attributed to beta-lactams, and the evaluation and management of sulfonamide reactions are distinct. The pathophysiology of allergic (or hypersensitivity) reactions to sulfonamides is complex and poorly understood.

This topic review describes the most prevalent types of reactions to sulfonamides, the evaluation of patients with reported allergy, and cross-reactivity issues. Management options for patients with past reactions who require similar medications again are also presented. Most of the available literature concerns allergic reactions to antimicrobial sulfonamides, particularly TMP-SMX. However, reactions to nonantimicrobial sulfonamides (eg, diuretics, sulfonylureas, and others) and sulfones (eg, dapsone) will be briefly addressed as well.

This review does not address the treatment of acute drug reactions. These are presented elsewhere, according to specific type of reaction. (See "Stevens-Johnson syndrome and toxic epidermal necrolysis: Pathogenesis, clinical manifestations, and diagnosis" and "Drug eruptions" and "Anaphylaxis: Emergency treatment" and "Drug fever".)


The imprecise term "sulfa drugs" is most often applied to sulfonamide antimicrobials, although it is variably used for other medications as well. This term has contributed to ongoing confusion about relevant cross-reactivity among sulfonamide drugs. It is preferable to avoid "sulfa allergy" and instead document the specific medication that caused the adverse reaction and the symptoms that were involved.

Types of sulfonamides — Sulfonamide medications are drugs that contain a sulfonamide moiety (SO2NH2) [2]. There are two distinct groups of sulfonamides that differ in chemical structure as well as clinical use:

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Literature review current through: Oct 2017. | This topic last updated: Sep 23, 2016.
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