Mucous membrane pemphigoids (MMPs) and bullous pemphigoid (BP) are autoimmune bullous diseases that share physiopathological features: both can result from autoantibodies directed against BP180 or BP230 antigens. An association has been reported between BP and intake of gliptins, which are dipeptidyl peptidase-IV inhibitors used to treat type 2 diabetes mellitus. Clinical and immunological differences have been reported between gliptin-induced BPs and classical BPs: mucosal involvement, non-inflammatory lesions, and target BP180 epitopes other than the NC16A domain. Those findings accorded gliptins extrinsic accountability in triggering MMP onset. Therefore, we examined gliptin intrinsic accountability in a cohort of 313 MMP patients. To do so, we (1) identified MMP patients with gliptin-treated (challenge) diabetes; (2) selected those whose interval between starting gliptin and MMP onset was suggestive or compatible with gliptin-induced MMP; (3) compared the follow-ups of patients who did not stop (no dechallenge), stopped (dechallenge) or repeated gliptin intake (rechallenge); (4) compared the clinical and immunological characteristics of suggestive-or-compatible-challenge patients to 121 never-gliptin-treated MMP patients serving as controls; and (5) individually scored gliptin accountability as the trigger of each patient’s MMP using the World Health Organization-Uppsala Monitoring Center, Naranjo- and Begaud-scoring systems. 17 out of 24 gliptin-treated diabetic MMP patients had suggestive (≤12 weeks) or compatible challenges. Complete remission at 1 year of follow-up was more frequent in the 11 dechallenged patients. One rechallenged patient’s MMP relapsed. These 17 gliptin-treated diabetic MMP patients differed significantly from the MMP controls by more cutaneous, less buccal, and less severe involvements and no direct immunofluorescence IgA labeling of the basement membrane zone. Multiple autoantibody-target antigens/epitopes (BP180–NC16A, BP180 mid- and C-terminal parts, integrin α6β4) could be detected, but not laminin 332. Last, among the 24 gliptin-treated diabetic MMP patients, five had high (I4–I3), 12 had low (I2-I1) and 7 had I0 Begaud intrinsic accountability scores. These results strongly suggest that gliptins are probably responsible for some MMPs. Consequently, gliptins should immediately be discontinued for patients with a positive accountability score. Moreover, pharmacovigilance centers should be notified of these events.

Cyclosporine has shown promising results for mortality in patients with Stevens-Johnson syndrome/toxic epidermal necrolysis. However, available studies included only a small number of patients and did not include a validated and homogenous control group. We present the results from a retrospective monocentric study including 174 patients with Stevens-Johnson syndrome/toxic epidermal necrolysis during 2005-2016. Among them, 95 received cyclosporine (3 mg/kg/day) plus supportive care, and 79 received supportive care only. Both a traditional exposed/unexposed method and a propensity score-matching method were used to compare the progression of skin detachment between day 0 and day 5, the proportion of patients with cutaneous re-epithelialization starting on day 5 or mucosal re-epithelialization on day 10, the duration of progression, and the number of deaths between the two groups. None of these outcomes significantly favored cyclosporine, either by the exposed/unexposed method or the propensity score method. Acute renal failure affected more patients receiving cyclosporine (P = 0.05). Overall, the results of this epidemiological study did not show a beneficial effect of cyclosporine in patients with Stevens-Johnson syndrome/toxic epidermal necrolysis. They are discordant with those previously published. The large number of patients and the use of a propensity score method provide valuable insights. The main limitation of the study is the lack of randomization.

Background Cross‐reactivity among beta‐lactam antibiotics (BL) is essentially reported in immediate hypersensitivity. Objectives To evaluate cross‐reactivity beyond BLs in patients with non‐immediate cutaneous adverse drug reaction (non‐immediate CADR) managed in a dermatology reference centre of toxic bullous and severe CADRs. Patients/Materials/Methods We conducted a retrospective single‐centre study in consecutive patients consulting between 2010 and 2018 with an active BL‐suspected non‐immediate CADR and explored by cutaneous tests [patch tests (PT) and intradermal tests (P‐IDR)] for at least three penicillin's subclasses and amino‐ and non‐amino‐cephalosporins (at least one aminocephalosporin). Cross‐reactivity among subclasses was investigated for patients with positive tests. Results We included 56 patients, among whom 46 amoxicillin‐suspected were and seven cephalosporin‐suspected. Twenty‐nine had severe CADR, and 27 had non‐immediate maculopapular exanthema (MPE). Twenty‐two had positive tests (18 for AS and four for CS). Among the 18 positive amoxicillin‐suspected, 10 (55.6%) showed cross‐reactivity with one or more other BL: 9 (50%) with another penicillin and 3 (16.5%) with a non‐aminocephalosporin. No amoxicillin‐ or cephalosporin‐suspected patient showed cross‐reactivity with aztreonam or carbapenems. P‐IDR showed cross‐reactivity only once. Conclusion After a suspected BL‐induced non‐immediate CADR, a large allergologic exploration is needed to confirm the diagnosis and evaluate cross‐reactivity. In our population including cases of severe CADRs and MPE with late delay of onset, cross‐reactivity was frequent and PT was sufficient to this purpose. The frequent cross‐reactivity among penicillins encourages stopping this whole family and to test cephalosporins, aztreonam and carbapenems for which cross‐allergies are rarer.

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