Subclinical oral involvement in patients with endemic pemphigus foliaceus

Abstract

BackgroundWe have described a variant of endemic pemphigus foliaceus (EPF) in El Bagre area known as pemphigus Abreu-Manu. Our previous study suggested that Colombian EPF seemed to react with various plakin family proteins, such as desmoplakins, envoplakin, periplakin BP230, MYZAP, ARVCF, p0071 as well as desmoglein 1.ObjectivesTo explore whether patients affected by a new variant of endemic pemphigus foliaceus (El Bagre-EPF) demonstrated oral involvement.Materials and MethodsA case-control study was done by searching for oral changes in 45 patients affected by El Bagre-EPF, as well as 45 epidemiologically matched controls from the endemic area matched by demographics, oral hygiene habits, comorbidities, smoking habits, place of residence, age, sex, and work activity. Oral biopsies were taken and evaluated via hematoxylin and eosin staining, direct immunofluorescence, indirect immunofluorescence, confocal microscopy, and immunohistochemistry.ResultsRadicular pieces and loss of teeth were seen in in 43 of the 45 El Bagre-EPF patients and 20 of the 45 controls (P < 0.001) (confidence interval [CI] 98%). Hematoxylin and eosin staining showed 23 of 45 El Bagre-EPF patients had corneal/subcorneal blistering and lymphohistiocytic infiltrates under the basement membrane zone and around the salivary glands, the periodontal ligament, and the neurovascular bundles in all cell junction structures in the oral cavity; these findings were not seen in the controls (P < 0.001) (CI 98%). The direct immunofluorescence, indirect immunofluorescence, confocal microscopy, and microarray staining displayed autoantibodies to the salivary glands, including their serous acini and the excretory duct cell junctions, the periodontal ligament, the neurovascular bundles and their cell junctions, striated muscle and their cell junctions, neuroreceptors, and connective tissue cell junctions. The autoantibodies were polyclonal. IgA autoantibodies were found in neuroreceptors in the glands and were positive in 41 of 45 patients and 3 of 45 controls.ConclusionsPatients affected by El Bagre-EPF have some oral anomalies and an immune response, primarily to cell junctions. The intrinsic oral mucosal immune system, including IgA and secretory IgA, play an important role in this autoimmunity. Our data contradict the hypothesis that pemphigus foliaceus does not affect the oral mucosa due to the desmoglein 1-desmoglein 3 compensation.

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“…The majority of these patients were not included in our initial description of EPF [1][2][3][4][5][6][7][8][9]. Only four of the patients originally studied were still alive at the time of this study.…”

“…Only four of the patients originally studied were still alive at the time of this study. Each year, there is a prevalence of around 4-6 new patients, but also 3-4 deaths/year, creating a steady prevalence of the disease endemicity [1][2][3][4][5][6][7][8][9].…”

“…We included only patients who fulfilled the complete diagnostic criteria for El Bagre-EPF: including: clinical and epidemiological features as previously described [1][2][3][4][5][6][7][8][9], residence in the endemic area [1][2][3][4][5][6][7][8][9], serum displaying intercellular staining between keratinocytes by direct immunofluorescence (DIF) and to the basement membrane zone (BMZ) of the skin by either DIF or by indirect immunofluorescence (IIF), using fluorescein isothiocyanate (FITC) conjugated monoclonal antibodies to IgG and/ or to IgG4, as described previously [1][2][3][4][5][6][7][8][9]. The patients also must have serum reactivity against desmoglein 1 (Dsg1) and plakin molecules using immunoblotting (IB) [7,8].…”

“…The patients also must have serum reactivity against desmoglein 1 (Dsg1) and plakin molecules using immunoblotting (IB) [7,8]. The patient's serum should also immunoprecipitated a Concanavalin A affinity-purified 45 kDa fragment of Dsg1 [1][2][3][4][5][6][7][8][9]. The final diagnostic criteria are that the patients must show positive for autoantibodies to pemphigus foliaceus antigens by ELISA [9].…”

“…The main laboratory findings found in El Bagre-EPF patients include autoantibodies to multiple cell junctions in the skin, and in one third of the patients against cells junctions in multiple organs [1][2][3][4][5][6][7][8]. A subclinical oral involvement [9], and in about one third of the patients, we discovered autoantibodies that appeared to be directed against the optic nerve envelope and its cell junctions [10], to cutaneous nerves and receptors [11], to the cell junctions of the cardiovascular system including its conductive system [12][13][14], and to cell junctions within the kidney [15]. In this study, we investigated nail abnormalities in patients affected by El Bagre-EPF as reported in the old Portuguese literature in patients affected by FS.…”