Findings Highlight Need for Systematic, Unbiased Approach to Identifying Drug Culprit for SJS/TEN

In the absence of an available laboratory test that can identify the drug responsible for Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN), new study findings published in JAMA Dermatology bring to light the need for a systematic and unbiased approach to identifying the cause of the rare, serious skin reaction.

The retrospective study of patient hospital data showed that current approaches to identifying a culprit drug often overidentify drugs unlikely to be responsible for SJS/TEN while potentially missing the actual culprit. In fact, the researchers found that out of 104 drugs added to allergy lists, over 40 of the drugs were mislabeled as allergens and 9 drugs were missed.

“Prompt identification and discontinuation of a culprit drug is critical to improving patient outcomes and preventing recurrence. 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 6 medications at the time of their reaction,” explained the researchers.

“Consequently, many patients may be labeled as allergic to multiple agents. While failure to identify a culprit drug could have severe consequences, overlabeling (labeling a patient as allergic to drug(s) they can safely tolerate) is not insignificant. The patient may receive a less efficacious, more toxic, and/or more expensive agent than necessary, and in some cases may be left without treatment for their underlying disease.”

The researchers scrutinized nearly 2 decades worth of data—2000 through 2018—from Brigham and Women’s Hospital and Massachusetts General Hospital, identifying 48 patients who had confirmed cases of SJS/TEN overlap or TEN. Consistent with previous data, patients were taking a mean of 6.5 drugs in the 3 months before the onset of their reaction. Approximately 30% of the 48 patients were taking more than 10 drugs while only 5 were taking just 1.

All 48 patients had at least 1 drug that was labeled as an allergy. A single drug was considered the culprit among 17 patients, although just 7 of these cases were reported with certainty by the physician. Multiple antibiotics were labeled as allergens in approximately one-third of cases, while 4 cases listed multiple antiepileptics as culprits. Notably, certain cases labeled entire drug classes, in addition to a specific drug, as allergens.

“Given that each case is triggered by only 1 drug (possibly 0 if infection induced), 48 cases should yield 48 culprit drugs. More than double were labeled as allergies. Therefore, we investigated the approach physicians take to identify culprit drugs,” the authors wrote. “Physicians appeared to use primarily 2 factors: drug notoriety and timing of exposure compared with SJS/TEN onset. Identifying high-risk medications seemed heuristic, with 1 or more drugs in question noted in the record as a common culprit without reference to published or vetted data regarding risk. Regarding timing, drug charts when present in medical records were incomplete, as they focused predominantly on high-notoriety drugs.”

The group noted complexities in defining index day throughout the cases, which complicated the timing of drug exposure approach. Records often used the data of rash onset as the index day, although there were cases in which this was either not explicitly stated or it was not clear if or how prodromal symptoms were taken into account.

Reference

Li D, Velasquez G, Romar G, Schunkert E, Foreman R, Divito S. Assessment of need for improved identification of a culprit drug in Stevens-Johnson syndrome/toxic epidermal necrolysis. JAMA Dermatol. Published online June 21, 2023. doi:10.1001/jamadermatol.2023.1693