Drug Patch Testing in Stevens-Johnson Syndrome Reveals Antiepileptic Culprits

Patch testing that identifies causative medications in Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) shows antiepileptic drugs to have the highest positivity rate, according to study findings published in Annals of Allergy, Asthma & Immunology.

Investigators evaluated outcomes following patch testing in SJS/TEN to evaluate safety during testing and to quantify the positivity rate of common drug classes.

They conducted a systematic review of the PubMed database from inception to December 2021 without language restriction for original reports describing 1 or more patients undergoing patch testing for SJS/TEN. Studies that reported on patch testing performed for overlap syndromes of SJS/TEN with drug reaction with eosinophilia and systemic symptoms, acute generalized exanthematous pustulosis, or erythema multiforme were excluded, as were manuscripts lacking full text or those that could not be translated to English.

Among the 58 articles that met inclusion criteria, 41 studies were performed in Europe, 13 in Asia, 3 in Africa, and 1 in Canada. Of the included studies, 29 were case series, 25 were case reports, and 4 were prospective trials of patch testing performed in the setting of delayed cutaneous adverse drug reactions.

Overall, 82 patients (median age 41 years, range 3-90) underwent patch testing for SJS/TEN, accounting for 104 positive reactions to 49 unique medications (overall positivity rate 21.9% [104/475 patch test results]). The investigators determined that 48.1% of positive reactions were caused by antiepileptic drugs. Antibiotics were responsible for 28.8% of positive reactions, and nonsteroidal anti-inflammatory drugs (NSAIDs) were responsible for 6.7% of positive reactions. Among the 45 patients with available data, median time to onset of SJS/TEN was 7 days (IQR 12 days; range 1-49) after starting the presumed causative medication.

Investigators noted that the positivity rates of antiepileptic drugs, antibiotics, and NSAIDs were 33.1%, 13.1%, and 21.9%, respectively. These rates were adjusted to 54.3%, 77.8%, and 54.5%, respectively, when accounting for suspected causality.

Among the 36 patients with documentation of the duration between SJS/TEN resolution and patch testing, the median latency time was 3 months (range 0.5-120). The investigators noted that 14 patients reacted to multiple medications, and there were 36/49 medications with only 1 positive test.

Systemic reactions requiring conservative treatment occurred in 3 patients during patch testing; 2 of these patients were HIV-positive with active tuberculosis.

Limitations of this study include its design, the inclusion of case reports and case series, publication bias, lack of uniform data, and the small number of tests performed.

“When patch tests are performed using drugs suspected to be causative of SJS/TEN, the positivity rates are encouragingly high, supporting the clinical usefulness of this test,” the investigators concluded. Drug categories with the most positive patch test results include antiepileptic drugs and antibiotics. Patch testing appears to be safe in most patients, but the investigators urge caution when testing in the setting of HIV and active tuberculosis. They wrote “Patch testing can be readily performed with the proper training and can provide highly useful information to patients and physicians.” Ex vivo tests could potentially evaluate triggers for SJS/TEN with improved safety considerations; however, such tests are nonstandardized, not widely available, and possibly cost-prohibitive.

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.