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Fifteen Leishmania species belonging to the subgenera Viannia, Leishmania and Mundinia are known to cause ACL. Seven of these species are found in Brazil, of which Leishmania (Viannia) braziliensis and Leishmania (Leishmania) amazonensis have the highest potential to cause mucosal (ML) and anergic diffuse cutaneous leishmaniasis (DCL), respectively, the most severe forms of ACL. The clinical and immunopathological differences between these two clinical forms are reviewed here, taking into account their different physiopathogenic mechanisms of dissemination from cutaneous lesions to mucosal tissues in the case of ML and to almost all body surfaces in the case of anergic DCL. We also discuss some immunopathogenic mechanisms of species-specific Leishmania antigens (from the subgenera Viannia and Leishmania) that are most likely associated with the clinical and immunopathological differences between ML and anergic DCL. Those discussions emphasize the pivotal importance of some surface antigens of L. (V.) braziliensis and L. (L.) amazonensis, such as lipophosphoglycan, phosphatidylserine and CD200 (an immunoregulatory molecule that inhibits macrophage activation), that have been shown to exert strong influences on the clinical and immunopathological differences between ML and anergic DCL.<\/jats:p>","DOI":"10.1093\/trstmh\/trz037","type":"journal-article","created":{"date-parts":[[2019,4,22]],"date-time":"2019-04-22T15:17:18Z","timestamp":1555946238000},"page":"505-516","source":"Crossref","is-referenced-by-count":49,"title":["What makes mucosal and anergic diffuse cutaneous leishmaniases so clinically and immunopathogically different? A review in Brazil"],"prefix":"10.1093","volume":"113","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0412-6060","authenticated-orcid":false,"given":"Fernando T","family":"Silveira","sequence":"first","affiliation":[{"name":"Leishmaniasis Laboratory Prof. Dr. Ralph Lainson, Parasitology Department, Evandro Chagas Institute , Rod. BR 316-KM 07, Levil\u00e2ndia, Ananindeua, Par\u00e1 State,","place":["Brazil"]},{"name":"Nucleus of Tropical Medicine, Federal University of Par\u00e1 , Bel\u00e9m, Par\u00e1 State,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2019,5,29]]},"reference":[{"key":"2026041420131691200_trz037C1","first-page":"1","volume-title":"The leishmaniases in biology and medicine","author":"Lainson","year":"1987"},{"key":"2026041420131691200_trz037C2","first-page":"313","volume-title":"Topley & Wilson\u2019s microbiology and microbial infections","author":"Lainson","year":"2010","edition":"10th ed."},{"key":"2026041420131691200_trz037C3","first-page":"1691","volume-title":"Tratado de Dermatolog\u00eda","author":"Silveira","year":"2018","edition":"3rd ed"},{"issue":"4","key":"2026041420131691200_trz037C4","first-page":"1","article-title":"An appraisal of the taxonomy and nomenclature of trypanosomatids presently classified as Leishmania and Endotrypanum","volume":"145","author":"Espinosa","year":"2016","journal-title":"Parasitology"},{"issue":"3","key":"2026041420131691200_trz037C5","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1590\/S0074-02762004000300001","article-title":"Clinical and immunopathological spectrum of American cutaneous leishmaniasis with special reference to the disease in the Amazonian Brazil","volume":"99","author":"Silveira","year":"2004","journal-title":"Mem Inst Oswaldo Cruz"},{"issue":"5","key":"2026041420131691200_trz037C6","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1590\/S0074-02762005000500013","article-title":"Further observations on clinical, histopathological and immunological features of borderline disseminated cutaneous leishmaniasis caused by Leishmania (Leishmania) amazonensis","volume":"100","author":"Silveira","year":"2005","journal-title":"Mem Inst Oswaldo Cruz"},{"issue":"8","key":"2026041420131691200_trz037C7","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1111\/j.1365-3024.2009.01116.x","article-title":"Immunopathogenic competences of Leishmania (V.) braziliensis and L. 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