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BackgroundThe clinical and pathological aspects of fixed drug eruption (FDE) have been described based on a few case series. ObjectivesTo compare bullous FDE (BFDE) and non-bullous FDE (NBFDE) and to determine whether BFDE can be histologically distinguished from other dermatoses presenting with an apoptotic pan-epidermolysis. Materials &MethodsIn this retrospective monocentre study (2005-2016), FDE was classified as BFDE or NBFDE and localized (one anatomical site) or generalized (≥ two sites; GBFDE). Clinical data were extracted from charts, and images were reviewed. Skin biopsies were analysed and compared to the clinical presentation. Three dermatopathologists, blinded to the final clinical diagnosis, evaluated a subset of BFDE cases ( n = 8) and 25 biopsies of other bullous diseases known to have an epidermal necrolysis (EN)-like pattern. In total, 73 patients were included in the study. ResultsPatients with BFDE ( n = 58; GBFDE n = 48) were significantly older ( p < 0.001). All patients with GBFDE were hospitalized; 25 had a complication (infectious; n = 19), and eight died (median age: 80). Histology revealed spongiotic (6.7%), interface dermatitis (48.3%) and EN-like (66.3%) patterns. The EN-like pattern was more frequent in BFDE than NBFDE (74% vs 27%; p = 0.008). Melanophages (100% vs 66%; p = 0.02) and massive dermal melanosis (40% vs 4%; p = 0.0005) were more prominent in NBFDE than BFDE. BFDE could not be reliably distinguished from other bullous diseases with EN-like patterns. ConclusionBFDE belongs to the spectrum of skin conditions with an EN pattern, for which the concept of acute syndrome of apoptotic pan-epidermolysis (ASAP) was previously introduced. Clinical-pathological correlation is mandatory for a diagnosis of BFDE.