Aims: Epidermal necrolysis (EN) is a rare and severe condition characterized by a diffuse skin and mucosal detachment, mainly induced by drugs. Literature is scarce regarding the rate of recurrences and drug re-exposure. The aim was to assess the rate of subsequent EN recurrences such as re-exposure of high notoriety drugs in patients with EN. Methods: We used the French Health system database and included all EN patients. The primary outcome was the rate of EN recurrence. Secondary outcomes were high notoriety drugs re-exposure or cross exposure, i.e., exposure to a drug of the same family, after the acute phase of EN, when initially suspected. Results: A total of 1,203/1,440 patients (83.5%) survived the acute phase, with 27 patients (2.2% (CI95%: 1.5-3.2)) meeting the recurrence criteria. In patients with allopurinol as suspected drug, 10/77 (13.0%) were cross exposed to febuxostat, without recurrence. Similarly, in patients with carbamazepine/oxcarbazepine as suspected drug, 2/26 (7.6%) were cross exposed to lamotrigine, without recurrence. Conversely, 12/38 (31.5%) and 16/37 (43.2%) patients were respectively re-exposed to pantoprazole and esomeprazole when suspected, and 12/42 (28.6%) were re-exposed to amoxicillin. Only one recurrence was noted in a pantoprazole re-exposed patient. Conclusions: Among EN patients, the rate of recurrence seems low, contrasting with several re-exposures among beta lactam antibiotics and proton pump inhibitors, when 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.

Background: Since the 2002 SCAR study, erythema multiforme(EM), a post-infectious disease, has been distinguished from Stevens-Johnson syndrome (SJS), drug-induced. Nevertheless, EM cases are still reported in the French pharmacovigilance database (FPDB). Objectives: To describe EM reported in the FPDB and to compare the characteristics of the reports. Methods: This retrospective observational study selected all EM cases reported in the FPDB over two periods: period 1 (P1, 2008-2009) and period 2 (P2, 2018-2019). Inclusion criteria were 1) a diagnosis of clinically typical EM and/or one validated by a dermatologist; 2) a reported date of onset of the reaction; and 3) a precise chronology of drug exposure. Cases were classified confirmed EM (typical acral target lesions and/or validation by a dermatologist) and possible EM (not-otherwise-specified target lesions, isolated mucosal involvement, doubtful with SJS). We concluded possible drug-induced EM when EM was confirmed, with onset ranging from 5 to 28 days without an alternative cause. Results: Among 182 selected reports, 140(77%) were analyzed. Of these, 67(48%) presented a more likely alternative diagnosis than EM. Of the 73 reports of EM cases finally included (P1, n=41; P2, n=32), 36(49%) had a probable non-drug cause and 28(38%) were associated with only drugs with an onset time ≤4 days and/or ≥ 29 days. Possible drug-induced EM was retained in 9 cases (6% of evaluable reports). Conclusions: This study suggests that possible drug-induced EM is rare. Many reports describe “polymorphic” rashes inappropriately concluded as EM or post-infectious EM with unsuitable drug accountability subject to protopathic bias.