016 Three North American cases of cutaneous Pemphigus vulgaris with no history of mucosal disease

Abstract

Pemphigus is a group of autoimmune blistering diseases including Pemphigus vulgaris (PV) and Pemphigus foliaceus (PF). Explanation of lesion morphology has been elegantly proffered by the Desmoglein Compensation Hypothesis (DCH) based on the epidermal distribution of desmoglein (Dsg) proteins and autoantibody profiles. In this theory, PF is characterized by subcorneal lesions in the presence of only anti-Dsg1 antibodies, while PV lesions are suprabasilar and associated with anti-Dsg3 in mucosal PV, or anti-Dsg1 and -Dsg3 in mucocutaneous PV. However, logical inconsistencies in the DHC have emerged and exceptions have been published in multiple small-scale studies. One of these inconsistencies described by our group and others is that some PV patients present with solely cutaneous disease (cPV) without concomitant mucosal lesions, in violation of the tenets of the DHC. To date, cPV patients reported in the literature have been classified as such based on their lesion status at time of presentation. We report here three cases of clinically and histologically confirmed cPV without any history of mucosal lesions (cPVwohm). Of these patients, two do not carry the most common PV associated HLA alleles, DRB1*04:02 or DQB1*05:03. The same two patients also tested negative for the primary PV associated autoantibodies, anti-Dsg 3 and anti-Dsg 1, while in active disease status. We confirm the first documented individual cases of cPVwohm in North America, supporting the existence of PV patients that develop cutaneous disease without a history of mucosal lesions, further challenging the fidelity of the DCH. Two of the 3 patients reported did not type for the common PV-associated HLA genes or display anti-Dsg autoantibodies while in active disease, suggesting some cPV patients may develop Pemphigus via genetic and immune mechanisms that differ from typical mucosal or mucocutaneous PV.