Finding culprit drug challenging in Stevens-Johnson syndrome/toxic epidermal necrolysis

Key takeaways:

• Of 48 Stevens-Johnson syndrome/toxic epidermal necrolysis cases, physicians identified a singular culprit drug for 17.
• Physicians identified 104 drugs as allergens for 48 patients.

Physicians must change their approaches to finding culprit drugs when treating Stevens-Johnson syndrome/toxic epidermal necrolysis, according to a study.

Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) is a severe mucocutaneous desquamative disease that is almost always triggered by certain medications, Dayan J. Li, MD, PhD, of the department of dermatology at the Brigham and Women’s Hospital, and colleagues wrote.

Identifying the culprit drug for a patient diagnosed with this condition is a vital step in treatment; however, identifying the culprit drug is quite challenging, according to the researchers.

“Identification is difficult because there is no laboratory test or other criterion standard (in the absence of rechallenge) to identify a culprit drug, and patients take on average six medications at the time of their reaction,” Li and colleagues wrote. “Consequently, many patients may be labeled as allergic to multiple agents.”

Not only do the current practices for finding the culprit drug seem to fail, but they also tend to over-label patients as being allergic to drugs they, in fact, can tolerate. This combination of consequences can severely limit patients’ improvement, according to the researchers.

In this retrospective study, Li and colleagues investigated the outcomes of current methods for culprit drug identification and evaluated whether improvements should be made.

Of the 48 patients, 26 of whom had SJS/TEN and 22 of whom had TEN, the culprit drug was identified in a minority of cases, whereas drug allergies were over-labeled in most.

“Given that each case is triggered by only one drug, 48 cases should yield 48 culprit drugs,” the researchers wrote. However, instead of 48 drug allergies, a total of 104 drugs were labeled as allergies across all cases, with some being entire drug classes.

Only 17 cases listed a singular drug as the culprit, with physicians reporting confidence in seven cases. Multiple antibiotics were labeled as allergies in 18 cases and multiple antiepileptics were labeled as allergies in four cases.

The authors found that physicians focused on the timing of drug exposure relative to SJS/TEN onset when deciding a culprit. Even more so, physicians relied on heuristic identification of high-risk drugs and did not consider the eight medications previously reported as culprit drugs in literature.

The Algorithm for Drug Causality for Epidermal Necrolysis, a tool for assessment of drug causality in this indication, was discordant with the lists labeled by physicians in 28 cases. The algorithm also labeled an additional nine drugs missed by physicians and cleared 43 drugs that were physician-labeled as allergens.

There were also 20 cases where one of multiple drugs added to the allergy list presented human leukocyte antigen allele or another gene variation associated with SJS/TEN.

The authors say it was clear that “physicians erred on the side of caution as to not risk re-exposure to a potential culprit drug.” As a result, they emphasize that a laboratory test is needed to identify culprit drugs and recommend that physicians utilize one of the aforementioned systematic unbiased approaches moving forward.