Recurrences and rechallenges of suspected drugs in patients with epidermal necrolysis

Epidermal necrolysis (EN) is a rare and severe condition characterized by diffuse skin and mucosal detachment and mainly induced by drugs. The literature is scarce regarding the rate of recurrences and culprit drug re-exposure.

To assess the rate of EN recurrences and to examine re-exposure to high-notoriety drugs in patients with EN.

We used the French health system database and included all patients with EN. Suspected drugs were assessed at the onset of EN. The primary outcome was the rate of EN recurrence. Secondary outcomes were re-exposure or cross-exposure to high-notoriety drugs (exposure to a drug of the same family) after the acute stage of EN.

In total, 1203 of 1440 patients (83.5%) survived the acute stage, with 27 patients (2.2%, 95% confidence interval 1.5-3.2) meeting the recurrence criteria. In patients with allopurinol as the suspected drug, 10 of 77 (13%) were cross-exposed to febuxostat, without recurrence. Similarly, in patients with carbamazepine or oxcarbazepine as the suspected drug, 2 of 26 (8%) were cross-exposed to lamotrigine, without recurrence. Conversely, 12 of 38 (32%) and 16 of 37 (43%) patients were respectively re-exposed to pantoprazole and esomeprazole when initially suspected, and 12 of 42 (29%) were re-exposed to amoxicillin. Only one recurrence was noted in a patient re-exposed to pantoprazole.

Among patients with EN, the rate of recurrence seems low, contrasting with several re-exposures to beta-lactam antibiotics and proton pump inhibitors when initially suspected. Although we cannot exclude that the suspected drugs were not the responsible ones for several patients, future studies should assess the possible existence of transient risk factors inducing EN.