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Mycoplasma pneumoniae infection has been documented in erythema multiforme (EM) and Stevens-Johnson syndrome–toxic epidermal necrosis (SJS-TEN). Clinical aspects of M pneumoniae–related EM have been poorly described in the literature.To highlight differences between M pneumoniae EM and non–M pneumoniae EM.This single-center, retrospective cohort study included all patients admitted to our dermatology department for EM during 2000-2015. We compared epidemiologic, clinical, and histologic data and follow-up for M pneumoniae EM and non–M pneumoniae EM cases.Thirty-three patients with M pneumoniae EM were compared with 100 patients with non–M pneumoniae EM. Disease onset in winter was more frequent with M pneumoniae EM (P = .003). Acrally distributed lesions (32% vs 88%, P < .0001) and typical targets (45% vs 74%, P = .01) were less common in M pneumoniae EM than non–M pneumoniae EM. Multiple (≥2) mucousal membrane involvement was more frequent in M pneumoniae EM than non–M pneumoniae EM (97% vs 60%; P < .0001), as were mucosal and respiratory tract sequelae (P < .05). The mean hospital stay was longer with M pneumoniae EM patients: 9.5 days versus 5.1 days (P = .0002). A TEN-like pattern was observed in all 14 (100%) M pneumoniae EM skin biopsies versus 10 of 27 (48%) non–M pneumoniae EM biopsies (P < .001).The retrospective design.M pneumoniae EM has a distinctive presentation compared with non–M pneumoniae EM, with more diffuse and atypical targets, more mucositis and respiratory tract sequelae. Histologic data show a TEN-like pattern in all M pneumoniae EM skin samples.