Propranolol Off-Target: A New Therapeutic Option in Neutrophil-Dependent Dermatoses?

Epidermolysis bullosa acquisita (EBA) is a rare subepidermal blistering dermatosis characterized by autoantibodies targeting collagen VII (COL7), an essential component of the anchoring fibrils, located in the sublamina densa of the dermal‒epidermal junction. In EBA, tissue-bound autoantibodies cause the recruitment and subsequent activation of neutrophils, which eventually lead to subepidermal blistering through the release of proteases and ROS. Thus, targeting either pathogenic IgG autoantibodies or neutrophil recruitment or activation has shown efficacy in experimental murine EBA models and patients with EBA. In this issue, Stüssel et al. demonstrate that propranolol, a nonselective β-adrenoreceptor blocker, markedly inhibits the neutrophil release of ROS induced by complexes of COL7 and/or anti-COL7 IgG in vitro and ameliorates the formation of blisters and erosions in an antibody passive-transfer model of murine EBA. These findings warrant further investigations aimed at characterizing the therapeutic efficacy of propranolol in EBA and possibly beyond.