State-of-the-art review of human autoimmune blistering diseases (AIBD).

Abstract

Autoimmune blistering diseases (AIBDs) are a heterogenous group of skin conditions, broadly classified into two categories depending on the location of blister formation: intraepidermal blistering in the pemphigus group and subepidermal blistering in the pemphigoid group. Although AIBDs occur in both humans and animals, the arsenal of data for human AIBDs far exceeds those of their animal counterpart. Therefore, the main purpose of this review is to highlight existing knowledge, and recent advances in the diagnosis and management of AIBDs in humans - to serve as a road map for veterinary dermatologists. AREAS COVERED: Recent findings include complement-independent pathways in the pathogenesis of bullous pemphigoid, as well as the role of desmoglein and desmocollin autoantibodies in inducing acantholysis. Systemic glucocorticoids are the mainstay of treatment for AIBDs in humans, yet their long-term use is associated with severe adverse effects and complications, thereby limiting their use. Therefore, researchers have been exploring new and safer alternative therapeutic options for human AIBDs such as anti-CD20 monoclonal antibodies (Rituximab), Bruton's tyrosine kinase inhibitors (BTKi) and neonatal Fc receptor (FcRn) blockers. EXPERT OPINION: Randomised controlled trial (RCT) level evidence show that Rituximab and short-course GC regimes are more effective and safer than traditional GC treatment for human AIBDs. FcRn blockers such as SYNT001 have shown positive results in preliminary phase 2 clinical trials for treatment of human pemphigus; further trials are required. Rilzabrutinib (PRN1008), an orally administered BTKi, has recently completed phase 2 trials in pemphigus and is in a phase 3 RCT in humans.