Drug‐induced linear immunoglobulin A bullous dermatosis: A French retrospective pharmacovigilance study of 69 cases

Abstract

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 Among them, enoxaparin, minocycline and vibramycin were previously unpublished. For all patients, the suspect drug was withdrawn; 15 did not receive any treatment.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

Skin lesions and vancomycin use in a hemodialysis patient

“…Its incidence is estimated to be 0.23 to 2.3 cases per million persons per year . LABD is either idiopathic or drug‐induced . While many drugs may be responsible, the most likely is vancomycin, because it induces antibodies directed against epidermal basement membrane proteins including collagen VII or proteolytic fragments of collagen XVII (1).…”

“…While many drugs may be responsible, the most likely is vancomycin, because it induces antibodies directed against epidermal basement membrane proteins including collagen VII or proteolytic fragments of collagen XVII (1). The typical lesions are pruriginous blisters, with a mucosal involvement in up to 42% in drug‐induced LABD vs. 60% in idiopathic LABD . The diagnosis is based on direct immunofluorescence of the skin biopsy, showing linear IgA on the dermo‐epidermal junction sometimes associated with C3 and/or IgG …”

“…Our patient was treated using dermocorticoids, which is the most commonly used treatment. Some patients have been successfully treated with dapsone or oral steroids in line with the treatment of the idiopathic form …”

“…LABD is either idiopathic or druginduced. 4 While many drugs may be responsible, the most likely is vancomycin, because it induces antibodies directed against epidermal basement membrane proteins including collagen VII or proteolytic fragments of collagen XVII (1). The typical lesions are pruriginous blisters, with a mucosal involvement in up to 42% in druginduced LABD vs. 60% in idiopathic LABD.…”

“…4,5 The diagnosis is based on direct immunofluorescence of the skin biopsy, showing linear IgA on the dermo-epidermal junction sometimes associated with C3 and/or IgG. 4 A recent study reviewed 69 LABD cases over 33 years. 4 Vancomycin was involved in 56.5% of these and males were slightly more represented (male:female ratio of 1.3:1).…”