{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,2,21]],"date-time":"2025-02-21T19:20:36Z","timestamp":1740165636020,"version":"3.37.3"},"reference-count":58,"publisher":"Mattioli1885","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Dermatol Pract Concept"],"abstract":"<jats:p>Background: We have described a variant of endemic\u00a0pemphigus\u00a0foliaceus (EPF) in El Bagre area known as pemphigus Abreu-Manu. Our previous\u00a0study\u00a0suggested that\u00a0Colombian\u00a0EPF seemed to react with various plakin family proteins, such as desmoplakins, envoplakin, periplakin BP230, MYZAP, ARVCF, p0071 as well as desmoglein 1.\r\nObjectives: To explore whether patients affected by a new variant of endemic pemphigus foliaceus (El Bagre-EPF) demonstrated oral involvement.\r\n\u00a0\r\nMaterials and Methods: A 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.\r\n\u00a0\r\nResults: Radicular pieces and loss of teeth were seen in in 43 of the 45 El Bagre-EPF patients and 20 of the 45 controls (P &lt; 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 &lt; 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.\r\nConclusions: Patients 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.<\/jats:p>","DOI":"10.5826\/dpc.0804a02","type":"journal-article","created":{"date-parts":[[2019,4,16]],"date-time":"2019-04-16T23:07:02Z","timestamp":1555456022000},"page":"252-261","source":"Crossref","is-referenced-by-count":2,"title":["Subclinical oral involvement in patients with endemic pemphigus foliaceus"],"prefix":"10.5826","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7692-4133","authenticated-orcid":false,"given":"Ana Maria","family":"Abreu-Velez","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael S.","family":"Howard","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hector Jose","family":"Lambra\u00f1o Padilla","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sergio","family":"Tobon-Arroyave","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"27750","published-online":{"date-parts":[[2018,10,31]]},"reference":[{"key":"ref0","doi-asserted-by":"publisher","unstructured":"Abreu Velez AM, Hashimoto T, Bollag W, et al. 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The tryptic cleavage product of the mature form of the bovine desmoglein 1 ectodomain is one of the antigen moieties immunoprecipitated by all sera from symptomatic patients affected by a new variant of endemic pemphigus. Eur J Dermatol. 2003;13(4):359-366."},{"key":"ref4","doi-asserted-by":"publisher","unstructured":"Abr\u00e9u V\u00e9lez AM, Yepes MM, Pati\u00f1o PJ, Bollag WB, Montoya F Sr. A cost-effective, sensitive and specific enzyme linked immunosorbent assay useful for detecting a heterogeneous antibody population in sera from people suffering a new variant of endemic pemphigus. Arch Dermatol Res. 2004;295(10):434-441.","DOI":"10.1007\/s00403-003-0441-4"},{"key":"ref5","unstructured":"Lacaz Netto R, Macedo NL. Pemphigus foliaceus: a clinical histopathological study of the gingiva [in Portuguese]. Rev Odontol UNESP. 1983;12: 61-69."},{"key":"ref6","doi-asserted-by":"publisher","unstructured":"Sotto MN, Shimizu SH, Costa JM, et al. South American pemphigus foliaceus: electron microscopy and immunoelectron localization of bound immunoglobulin in the skin and oral mucosa. Br J Dermatol. 1980;102(5):521-527.","DOI":"10.1111\/j.1365-2133.1980.tb07649.x"},{"key":"ref7","unstructured":"Marcucci G, Cuc\u00e9 LC, Sotto MN, et al. Contribui\u00e7\u00e3o ao estudo da ultra-estrutura da mucosa bucal em doentes de p\u00eanfigo foli\u00e1ceo brasileiro. Rev Fac Odontol Univ S\u00e3o Paulo. 1982;205-225."},{"key":"ref8","doi-asserted-by":"crossref","unstructured":"Hietanen J, Salo OP, Kanerva L, et al. Ultrastructure of uninvolved oral mucosa in pemphigus patients. Acta Derm Venereol.\u00a01983;63(6):63491-63494.","DOI":"10.2340\/0001555563491494"},{"key":"ref9","doi-asserted-by":"publisher","unstructured":"Rivitti EA, Sanches JA, Miyauchi LM, et al. Pemphigus foliaceus autoantibodies bind both epidermis and squamous mucosal epithelium, but tissue injury is detected only in the epidermis. 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N Am J Med Sci. 2016;8(3):151\u2013155.","DOI":"10.4103\/1947-2714.179132"},{"key":"ref19","doi-asserted-by":"publisher","unstructured":"Abreu Velez AM, Howard MS, Hashimoto T. Palms with a polyclonal autoimmune response in patients affected by a new variant of endemic pemphigus foliaceus in Colombia, South America. Eur J Dermatol. 2010;20(1):74-81.","DOI":"10.5826\/dpc.0801a01"},{"key":"ref20","doi-asserted-by":"publisher","unstructured":"Abreu Velez AM, Howard MS, Hashimoto K, et al. Autoantibodies to sweat glands detected by different methods in serum and in tissue from patients affected by a new variant of endemic pemphigus foliaceus. Arch Dermatol Res. 2009;301(10):711-718.","DOI":"10.1007\/s00403-009-0972-4"},{"key":"ref21","doi-asserted-by":"publisher","unstructured":"Feller L, Altini M, Khammissa RA, et al. Oral mucosal immunity. Oral Surg Oral Med Oral Pathol Oral Radiol. 2013;116(5):576-583.","DOI":"10.1016\/j.oooo.2013.07.013"},{"key":"ref22","doi-asserted-by":"publisher","unstructured":"Tomasi TB Jr, Zigelbaum S. The selective occurrence of gamma-1a globulins in certain body fluids. J Clin Invest. 1963 Oct;42:1552\u20131560.","DOI":"10.1172\/jci104840"},{"key":"ref23","doi-asserted-by":"publisher","unstructured":"Chodirker WB Tomasi TB Jr. Gamma-globulins: quantitative relationships in human serum and nonvascular fluids. Science. 1963;142(3595):1080\u20131081.","DOI":"10.1126\/science.142.3595.1080"},{"key":"ref24","doi-asserted-by":"crossref","unstructured":"Tomasi TB Jr, Tan EM, Solomon A, Prendergast RA. Characteristics of an immune system common to certain external secretions. J Exp Med. 1965 Jan 1;121:101\u2013124.","DOI":"10.1084\/jem.121.1.101"},{"key":"ref25","doi-asserted-by":"crossref","unstructured":"26. Russel AL. A system of classification and scoring for prevalence surveys of periodontal disease. J Dent Res. 1956;35(3):350-359.","DOI":"10.1177\/00220345560350030401"},{"key":"ref26","doi-asserted-by":"publisher","unstructured":"Abreu-Velez AM, Howard MS, Yi H, Gao W, et al. Neural system antigens are recognized by autoantibodies from patients affected by a new variant of endemic pemphigus foliaceus in Colombia. J Clin Immunol. 2011;31(3):356-368.","DOI":"10.1007\/s10875-010-9495-1"},{"key":"ref27","doi-asserted-by":"publisher","unstructured":"Abreu Velez AM, Yi H, Warfvinge G, Howard MS. Autoantibodies to full body vascular cell junctions colocalize with MYZAP, ARVCF, desmoplakins I and II and p0071 in endemic pemphigus in Colombia, South America. Int J Dermatol. 2018;57(3):291-298.","DOI":"10.1111\/ijd.13827"},{"key":"ref28","doi-asserted-by":"publisher","unstructured":"Habre-Hallage P, Dricot L, Hermoye L, et al. Cortical activation resulting from the stimulation of periodontal mechanoreceptors measured by functional magnetic resonance imaging (fMRI). Clin Oral Investig. 2014;18(8):1949-1961.","DOI":"10.1007\/s00784-013-1174-1"},{"key":"ref29","doi-asserted-by":"publisher","unstructured":"1. Abreu Velez AM, Hashimoto T, Bollag W, et al. A unique form of endemic pemphigus in Northern Colombia. J Am Acad Dermatol. 2003;49(4):599-608. PubMed","DOI":"10.1067\/s0190-9622(03)00851-x"},{"key":"ref30","doi-asserted-by":"publisher","unstructured":"2. Abreu Velez AM, Beutner EH, Montoya F, Hashimoto T. Analyses of autoantigens in a new form of endemic pemphigus foliaceus in Colombia. J Am Acad Dermatol. 2003;49(4):609-614. PubMed","DOI":"10.1067\/s0190-9622(03)00852-1"},{"key":"ref31","doi-asserted-by":"publisher","unstructured":"3. Hisamatsu Y, Abreu Velez AM, Amagai M et al. Comparative study of autoantigen profile between Colombian and Brazilian types of endemic pemphigus foliaceus by various biochemical and molecular biological techniques. J Dermatol Sci. 2003;32(1):33-41. PubMed","DOI":"10.1016\/s0923-1811(03)00034-3"},{"key":"ref32","unstructured":"4. Abreu Velez AM, Javier Pati\u00f1o P, Montoya F, et al. The tryptic cleavage product of the mature form of the bovine desmoglein 1 ectodomain is one of the antigen moieties immunoprecipitated by all sera from symptomatic patients affected by a new variant of endemic pemphigus. Eur J Dermatol. 2003;13(4):359-366. PubMed"},{"key":"ref33","doi-asserted-by":"publisher","unstructured":"5. Abr\u00e9u V\u00e9lez AM, Yepes MM, Pati\u00f1o PJ, Bollag WB, Montoya F Sr. A cost-effective, sensitive and specific enzyme linked immunosorbent assay useful for detecting a heterogeneous antibody population in sera from people suffering a new variant of endemic pemphigus. Arch Dermatol Res. 2004;295(10):434-441. PubMed CrossRef","DOI":"10.1007\/s00403-003-0441-4"},{"key":"ref34","unstructured":"6. Lacaz Netto R, Macedo NL. Pemphigus foliaceus: a clinical histopathological study of the gingiva [in Portuguese]. Rev Odontol UNESP. 1983;12: 61-69."},{"key":"ref35","doi-asserted-by":"publisher","unstructured":"7. Sotto MN, Shimizu SH, Costa JM, et al. South American pemphigus foliaceus: electron microscopy and immunoelectron localization of bound immunoglobulin in the skin and oral mucosa. Br J Dermatol. 1980;102(5):521-527.","DOI":"10.1111\/j.1365-2133.1980.tb07649.x"},{"key":"ref36","doi-asserted-by":"publisher","unstructured":"8. Marcucci G, Cuc\u00e9 LC, Sotto MN, et al. Contribui\u00e7\u00e3o ao estudo da ultra-estrutura da mucosa bucal em doentes de p\u00eanfigo foli\u00e1ceo brasileiro. Rev Fac Odontol Univ S\u00e3o Paulo. 1982;205-225.","DOI":"10.11606\/issn.2318-8235.v50i0p344-363"},{"key":"ref37","doi-asserted-by":"crossref","unstructured":"9. Hietanen J, Salo OP, Kanerva L, et al. Ultrastructure of uninvolved oral mucosa in pemphigus patients. Acta Derm Venereol. 1983;63(6):63491-63494.","DOI":"10.2340\/0001555563491494"},{"key":"ref38","doi-asserted-by":"publisher","unstructured":"10. Rivitti EA, Sanches JA, Miyauchi LM, et al. Pemphigus foliaceus autoantibodies bind both epidermis and squamous mucosal epithelium, but tissue injury is detected only in the epidermis. J Am Acad Dermatol. 1994;31(6):31954-31958.","DOI":"10.1016\/s0190-9622(94)70263-2"},{"key":"ref39","doi-asserted-by":"publisher","unstructured":"11. Guedes AC, Rotta O, Leite HV, et al. Ultrastructural aspects of mucosas in endemic pemphigus foliaceus. Arch Dermatol. 2002;138(7):949-954.","DOI":"10.1001\/archderm.138.7.949"},{"key":"ref40","doi-asserted-by":"publisher","unstructured":"12. Abreu-Velez AM, Howard MS, Yi H, et al. Patients affected by a new variant of endemic pemphigus foliaceus have autoantibodies colocalizing with MYZAP, p0071, desmoplakins 1-2 and ARVCF, causing renal damage. Clin Exp Dermatol. 2018;43(6):692-702.","DOI":"10.1111\/ced.13566"},{"key":"ref41","doi-asserted-by":"publisher","unstructured":"13. Abreu-Velez AM, Valencia-Yepes CA, Upegui-Zapata YA, et al. Patients with a new variant of endemic pemphigus foliaceus have autoantibodies against arrector pili muscle, colocalizing with MYZAP, p0071, desmoplakins 1 and 2 and ARVCF. Clin Exp Dermatol. 2017;42(8):874-880.","DOI":"10.1111\/ced.13214"},{"key":"ref42","doi-asserted-by":"publisher","unstructured":"14. Abreu-Velez AM, Gao W, Howard MS. Patients affected by endemic pemphigus foliaceus in Colombia, South America exhibit autoantibodies to optic nerve sheath envelope cell junctions. Dermatol Pract Concept. 2018; 31;8(1):1-6.","DOI":"10.5826\/dpc.0801a01"},{"key":"ref43","doi-asserted-by":"publisher","unstructured":"15. Abreu Velez AM, Howard MS, Velazquez-Velez JE. Cardiac rhythm and pacemaking abnormalities in patients affected by endemic pemphigus in Colombia may be the result of deposition of autoantibodies, complement, fibrinogen, and other molecules. Heart Rhythm. 2018;15(5):725-731.","DOI":"10.1016\/j.hrthm.2017.12.023"},{"key":"ref44","doi-asserted-by":"publisher","unstructured":"16. Shirakata Y, Amagai M, Hanakawa Y, et al. Lack of mucosal involvement in pemphigus foliaceus may be due to low expression of desmoglein 1. J Invest Dermatol. 1998;110(1):76-78.","DOI":"10.1046\/j.1523-1747.1998.00085.x"},{"key":"ref45","doi-asserted-by":"publisher","unstructured":"17. Mahoney MG, Wang Z, Rothenberger K, Koch PJ, Amagai M, Stanley JR. Explanations for the clinical and microscopic localization of lesions in pemphigus foliaceus and vulgaris. J Clin Invest. 1999;103(4):461\u2013468.","DOI":"10.1172\/jci5252"},{"key":"ref46","doi-asserted-by":"publisher","unstructured":"18. Amagai M, Tsunoda K, Zillikens D, et al. The clinical phenotype of pemphigus is defined by the anti-desmoglein autoantibody profile. J Am Acad Dermatol. 1999;40(2 Pt 1):167-170.","DOI":"10.1016\/s0190-9622(99)70183-0"},{"key":"ref47","doi-asserted-by":"publisher","unstructured":"19. Abreu Velez AM, Upegui Zapata YA, Howard MS. Periodic acid-Schiff staining parallels the immunoreactivity seen by direct immunofluorescence in autoimmune skin diseases. N Am J Med Sci. 2016;8(3):151\u2013155.","DOI":"10.4103\/1947-2714.179132"},{"key":"ref48","doi-asserted-by":"crossref","unstructured":"20. Abreu Velez AM, Howard MS, Hashimoto T. Palms with a polyclonal autoimmune response in patients affected by a new variant of endemic pemphigus foliaceus in Colombia, South America. Eur J Dermatol. 2010;20(1):74-81.","DOI":"10.1684\/ejd.2010.0834"},{"key":"ref49","doi-asserted-by":"publisher","unstructured":"21. Abreu Velez AM, Howard MS, Hashimoto K, et al. Autoantibodies to sweat glands detected by different methods in serum and in tissue from patients affected by a new variant of endemic pemphigus foliaceus. Arch Dermatol Res. 2009;301(10):711-718.","DOI":"10.1007\/s00403-009-0972-4"},{"key":"ref50","doi-asserted-by":"publisher","unstructured":"22. Feller L, Altini M, Khammissa RA, et al. Oral mucosal immunity. Oral Surg Oral Med Oral Pathol Oral Radiol. 2013;116(5):576-583.","DOI":"10.1016\/j.oooo.2013.07.013"},{"key":"ref51","doi-asserted-by":"publisher","unstructured":"23. Tomasi TB Jr, Zigelbaum S. The selective occurrence of gamma-1a globulins in certain body fluids. J Clin Invest. 1963 Oct;42:1552\u20131560.","DOI":"10.1172\/jci104840"},{"key":"ref52","doi-asserted-by":"publisher","unstructured":"24. Chodirker WB Tomasi TB Jr. Gamma-globulins: quantitative relationships in human serum and nonvascular fluids. Science. 1963;142(3595):1080\u20131081.","DOI":"10.1126\/science.142.3595.1080"},{"key":"ref53","doi-asserted-by":"crossref","unstructured":"25. Tomasi TB Jr, Tan EM, Solomon A, Prendergast RA. Characteristics of an immune system common to certain external secretions. J Exp Med. 1965 Jan 1;121:101\u2013124.","DOI":"10.1084\/jem.121.1.101"},{"key":"ref54","doi-asserted-by":"crossref","unstructured":"26. Russel AL. A system of classification and scoring for prevalence surveys of periodontal disease. J Dent Res. 1956;35(3):350-359.","DOI":"10.1177\/00220345560350030401"},{"key":"ref55","doi-asserted-by":"publisher","unstructured":"27. Abreu-Velez AM, Howard MS, Yi H, Gao W, et al. Neural system antigens are recognized by autoantibodies from patients affected by a new variant of endemic pemphigus foliaceus in Colombia. J Clin Immunol. 2011;31(3):356-368.","DOI":"10.1007\/s10875-010-9495-1"},{"key":"ref56","doi-asserted-by":"publisher","unstructured":"28. Abreu Velez AM, Yi H, Warfvinge G, Howard MS. Autoantibodies to full body vascular cell junctions colocalize with MYZAP, ARVCF, desmoplakins I and II and p0071 in endemic pemphigus in Colombia, South America. Int J Dermatol. 2018;57(3):291-298.","DOI":"10.1111\/ijd.13827"},{"key":"ref57","doi-asserted-by":"publisher","unstructured":"29. Habre-Hallage P, Dricot L, Hermoye L, et al. Cortical activation resulting from the stimulation of periodontal mechanoreceptors measured by functional magnetic resonance imaging (fMRI). 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