Involvement of the Areae Compositae of the Heart in Endemic Pemphigus Foliaceus

Abstract

Background: A new variant of endemic pemphigus foliaceus in El Bagre (El Bagre-EPF), Colombia, South America, shares features with Senear-Usher syndrome and occurs in an endemic fashion. Patients affected by El Bagre-EPF have heterogeneous antigenic reactivity not only to the skin but to other organs, including the heart. Here we test for autoantibodies to the areae compositaeof the heart (structure consisting of typical desmosomal amalgamated fascia adherensmolecules)and evaluate any possible clinical correlation.
 Methods: A case-control study comparing 45 patients and 45 controls from the endemic area, matched by demographics including age, gender, weight, work activities, and comorbidities, was performed. Direct and indirect immunofluorescence, immunohistochemistry, confocal microscopic studies, and echocardiogram studies were completed.
 Results: The main clinical abnormally seen in the El Bagre-EPF patients was left ventricular hypertrophy in 15/45 patients, compared with no such findings in the control population (P < 0.1). Seventy percent of El Bagre-EPF patients and none of the controls displayed polyclonal autoreactivity using different immunoglobulins and complement to the areae compositae of the heart using different methods and antibodies (P < 0.1).
 Conclusions: Patients affected by El Bagre-EPF demonstrated autoantibodies to the areae compositae of the heart. This finding was associated with left ventricular hypertrophic cardiomyopathy.The areae compositaemay play a role incell junction tension and the El Bagre-EPF patients’ autoantibodies possibly disrupting these junctions and thereby contributing to the left ventricular hypertrophy.

Pemphigus‐associated cardiomyopathy: report of autoimmune myocarditis and review of literature

“…Although pemphigus has been associated with various autoimmune disorders as well as haematological, oropharyngeal, gastrointestinal, and lung neoplasias, 3 cardiac involvement in pemphigus has been rarely documented. [6][7][8][9][10][11][12][13][14][15] In the case of pemphigus, the most likely explanation is an antigenic mimicry between cardiomyocytes and the basement membrane zone. For example, collagen XVII, which is an antigen of bullous pemphigus, has been shown to be expressed in mouse heart.…”

“…Although pemphigus has been associated with various autoimmune disorders as well as haematological, oropharyngeal, gastrointestinal, and lung neoplasias, 3 cardiac involvement in pemphigus has been rarely documented. 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 …”

“…In a further report, Abreu‐Velez et al . 14 demonstrated that patients with the variant ‘El‐Bagre’ of endemic pemphigus foliaceus have polyclonal autoantibodies reactive against the areae compositae that are a special type of cardiac intercellular junctions with the role of stabilizing the intercellular junctions in the heart. Patients with reactive autoantibodies against the areae compositae also showed ventricular hypertrophy at echocardiography; therefore, the authors hypothesized that the rupture of these junctions, due to an autoimmune process, may be implicated in the development of myocardial hypertrophy as a compensatory mechanism.…”