A scoring system was reasonably good at predicting hypersensitivity reactions.

Allergies to sulfonamide antibiotics (e.g. sulfamethoxazole-trimethoprim [TMP-SMX]) are notorious for causing drug hypersensitivity reactions; as many as 8% of hospitalised patients report sulfa-related adverse events. Patients can have immediate or delayed reactions, ranging from mild exanthems to life-threatening Stevens-Johnson syndrome/toxic epidermal necrolysis. Researchers adapted PEN-FAST, a scoring tool originally created for penicillin allergy (NEJM JW Gen Med Apr 15 2020 and JAMA Intern Med 2020; 180: 745-752), to risk stratify 320 US and Australian patients with previous TMP-SMX reactions.

PEN-FAST (SULF-FAST) criteria are as follows:

• allergy event occurred five or less years ago (two points)
• allergy event was anaphylaxis/angioedema or severe cutaneous adverse reaction (SCAR; two points)
• treatment was required for allergy event (one point).

Most patients had oral challenges, but a small number of patients with histories of severe reactions had patch tests. A SULF-FAST score of lower than three had a less than 5% risk for a hypersensitivity reaction, whereas a score of three or more was associated with a greater than 20% risk for a reaction.

Comment: Although this tool requires further validation, it gives us some direction for choosing patients in whom sulfamethoxazole-trimethoprim oral challenges are safe, namely patients with mild cutaneous reactions or more-severe (but remote) non-SCAR reactions. Clinicians should always be very wary of previous Stevens-Johnson syndrome/toxic epidermal necrolysis, serum sickness, haemolytic anaemia or aseptic meningitis. And remember, with the exception of sulfasalazine, sulfamethoxazole-trimethoprim does not cross react with nonantibiotic sulfonamides such as furosemide, thiazides and celecoxib (NEJM JW Gen Med Dec 1 2003 and  N Engl J Med 2003; 349: 1628-1635).

David J. Amrol, MD, Associate Professor of Clinical Internal Medicine, Director of the Division of Allergy and Immunology, University of South Carolina School of Medicine, Columbia, USA.

Waldron JL, et al. Development and  validation of a sulfa antibiotic allergy clinical decision rule. JAMA Netw Open 2023; 6: e2316776.

This summary is taken from the following Journal Watch titles: General Medicine, Ambulatory Medicine, Hospital Medicine.