Autoimmune blistering diseases provoked during the treatment of chronic inflammatory disease with biologic agents: a systematic review

Background To investigate the clinical course of autoimmune blistering diseases (AIBDs) following treatment with biologic agents (BAs) for chronic inflammatory diseases. Methods A comprehensive review of available, published literature was performed using PubMed and CINAHL search engines. Diagnostic criteria of AIBD included positive direct immunofluorescence studies and/or positive serology with clinically suggestive features. Results A total of 22 cases of AIBDs provoked by the use of BAs were found. The most commonly implicated agents were tumor necrosis factor-alpha inhibitors (n = 14). The mean age of onset of AIBD was 59.4 years (median 61.5 years, range 31-82). Average time to onset of AIBD following initiation of the suspected BA was 33.7 +/- 43.8 weeks (range 3 days to 152 weeks). Psoriasis was the most common associated condition for which the BA was prescribed (n = 11), followed by rheumatoid arthritis (n = 6) and ulcerative colitis (n = 5). Of the 21 cases reporting AIBD outcome, 17 reported remission or complete resolution upon stopping treatment with the involved BA. Four cases reported continued bullae formation without worsening of disease following cessation of the BA or systemic corticosteroids used to treat the AIBD. Five cases rechallenged the patient with the involved BA and four of the five reported recurrence, often with quicker onset and more severe symptoms. Conclusions BAs may be suspected in patients developing AIBD while being treated for chronic inflammatory diseases. A majority of cases resolve upon cessation of the offending agent.