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ObjectiveTo define the characteristics and the outcome of myelitis associated with immune checkpoint inhibitors (ICIs).MethodsWe performed a retrospective research in the databases of the French Pharmacovigilance Agency and the OncoNeuroTox network for patients who developed myelitis following treatment with ICIs (2011–2020). A systematic review of the literature was performed to identify similar cases.ResultsWe identified 7 patients who developed myelitis after treatment with ICIs (anti-PD1 [n = 6], anti-PD1 + anti-CTLA4 [n = 1]). Neurologic symptoms included paraparesis (100%), sphincter dysfunction (86%), tactile/thermic sensory disturbances (71%), and proprioceptive ataxia (43%). At the peak of symptom severity, all patients were nonambulatory. MRI typically showed longitudinally extensive lesions, with patchy contrast enhancement. CSF invariably showed inflammatory findings. Five patients (71%) had clinical and/or paraclinical evidence of concomitant cerebral, meningeal, caudal roots, and/or peripheral nerve involvement. Despite the prompt discontinuation of ICIs and administration of high-dose glucocorticoids (n = 7), most patients needed second-line immune therapies (n = 5) because of poor recovery or early relapses. At last follow-up, only 3 patients had regained an ambulatory status (43%). Literature review identified 13 previously reported cases, showing similar clinical and paraclinical features. All patients discontinued ICIs and received high-dose glucocorticoids, with the addition of other immune therapies in 8. Clinical improvement was reported for 10 patients.ConclusionMyelitis is a rare but severe complication of ICIs that shows limited response to glucocorticoids. Considering the poor functional outcome associated with longitudinally extensive myelitis, strong and protracted immune therapy combinations are probably needed upfront to improve patient outcome and prevent early relapses.

AIMSLinear immunoglobin A (IgA) bullous dermatosis is a rare autoimmune dermatosis considered spontaneous or drug-induced (DILAD). We assessed all DILAD cases, determined the imputability score of drugs and highlighted suspected drugs. METHODSData for patients with DILAD were collected retrospectively from the French Pharmacovigilance network (from 1985 to 2017) and from physicians involved in the Bullous Diseases French Study Group and the French Investigators for Skin Adverse Reactions to Drugs. Drug causality was systematically determined by the French imputability method. RESULTSOf the 69 patients, 42% had mucous membrane involvement, 20% lesions mimicking toxic epidermal necrolysis (TEN), 21% eosinophil infiltrates and 10% keratinocytes necrosis. Direct immunofluorescence, in 80%, showed isolated linear IgA deposits. Vancomycin (VCM) was suspected in 39 cases (57%), 11 had TEN-like lesions, as compared with three without VCM suspected. Among the 33 patients with a single suspected drug, 85% had an intrinsic imputability score of I4. Among them, enoxaparin, minocycline and vibramycin were previously unpublished. For all patients, the suspect drug was withdrawn; 15 did not receive any treatment. First-line therapy for 31 patients was topical steroids. Among the 60 patients with British Journal of Clinical Pharmacology Br J Clin Pharmacol (2019) 85 570-579 570 available follow-up, 52 achieved remission, 10 without treatment. Four patients experienced relapse, four died and five had positive accidental rechallenges. CONCLUSIONSThere is no major clinical difference between DILAD and idiopathic linear IgA bullous dermatosis, but the former features a higher prevalence of patients mimicking TEN. VCM, suspected in more than half of the cases, might be responsible for more severe clinical presentations. We report three new putative drugs. WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT• Linear IgA bullous dermatosis (LABD) is a rare autoimmune dermatosis that may be spontaneous or drug induced.• Vancomycin (VCM) is the most frequent putative drug.• Drug-induced LABD (DILAD) may be more severe than idiopathic LABD, mimicking toxic epidermal necrolysis with Nikolsky sign and large erosions WHAT THIS STUDY ADDS• In this large series of DILAD, we systematically assessed the imputability of suspect drugs. Most of them are antibiotics with VCM as the most frequent. Eighty percent of suspect drugs had a high causality score. Three drugs had never been reported to induce DILAD before (enoxaparin, minocyclin, vibramycin). • Twenty percent of cases (especially those induced by VCM) mimicked toxic epidermal necrolysis. Data collectionFor each case, data collected from pharmacovigilance or medical files included epidemiological and clinical characteristics Drug-induced linear immunoglobulin A bullous dermatosis Br J Clin Pharmacol (2019) 85 570-579 571 Drug-induced linear immunoglobulin A bullous dermatosis Br J Clin Pharmacol (2019) 85 570-579 579

vaccination, young age and previous reports 3,4 are arguments that support our cases' link between HZ and vaccination. COVID-19 vaccine-associated HZ was not reported in published vaccine studies, 9,10 and case reports may help to define this possible side effect.

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