From bench to bedside: evolving therapeutic targets in autoimmune blistering disease.

Autoimmune blistering diseases comprise a group of heterogenous conditions characterized by the loss of tolerance and subsequent development of autoantibodies targeting epidermal and subepidermal adhesion proteins. Blisters and erosions form on the skin and mucous membranes leading to significant morbidity and mortality. Traditional therapies rely on systemic immunosuppression. Advancements in our understanding of the pathophysiology of pemphigus and pemphigoid have led to the development of molecules which target specific pathways involved in induction and perpetuation of disease. In this review, we outline the novel therapeutic strategies including B-cell depletion, T-regulatory cell repletion, cell signalling inhibitors and small molecular inhibitors, inhibitory monoclonal antibodies, as well as complement inhibition. We additionally review their current level of clinical evidence. We lastly review therapeutics targets gleaned from the experimental epidermolysis bullosa acquisita mouse model. These emerging treatments offer an exciting progression from basic science discoveries that have the potential to transform the treatment paradigm in autoimmune blistering diseases.

Gastrointestinal symptoms, gastrointestinal bleeding and the role of diet in patients with autoimmune blistering disease: a survey of the International Pemphigus and Pemphigoid Foundation.

BACKGROUND: Autoimmune blistering diseases are a group of severe mucocutaneous conditions that typically require the use of prolonged corticosteroids and immunosuppression. Properly managing associated comorbidities is an integral part of these patients' care. The frequency of gastrointestinal symptoms, particularly gastrointestinal bleeding in these patients, is not known. Likewise, the effect of diet on disease is unknown. OBJECTIVE: To determine the incidence of gastrointestinal comorbidities and the role of diet in patients with autoimmune blistering disease. METHODS: We distributed an e-survey to patients with autoimmune blistering disease utilizing the International Pemphigus and Pemphigoid Foundation's listserv. The incidence of gastrointestinal symptoms and gastrointestinal bleeding were recorded, as were foods avoided and those noted to be beneficial in patients' disease. Historical incidences in the general population were used as controls. RESULTS: A total of 200 responses were collected. 30.3% of patients experienced gastroesophageal reflux following treatment of their autoimmune blistering disease, with 51.7% utilizing some form of gastrointestinal symptomatic treatment. The incidence of gastrointestinal bleeding following an autoimmune blistering diagnosis was 2.1%, which remained significant despite correction for non-steroidal anti-inflammatory use (NSAID), but not corticosteroid use. 65.2% of patients reported dietary limitations because of their autoimmune blistering disease. Significant intolerances after correction for multiple comparisons included alcohol, citrus and spicy foods. Greater than 10% of patients reported improvements in their disease with vegetables and dairy. CONCLUSIONS: Gastrointestinal comorbidities are common in patients with autoimmune blistering diseases, with gastrointestinal bleeding occurring in 2.1% of patients following a diagnosis of autoimmune blistering disease. While further work is needed to determine the relative risk of routine gastrointestinal prophylaxis in this population, gastrointestinal bleeding prophylaxis should be considered in patients receiving corticosteroids, particularly those taking NSAIDs. Dietary limitations are additionally frequent in this population. Patients should be cautious of alcohol, citrus and spicy foods.