What makes mucosal and anergic diffuse cutaneous leishmaniases so clinically and immunopathogically different? A review in Brazil.

American cutaneous leishmaniasis (ACL) is a parasitic protozoan disease caused by different Leishmania species widely distributed throughout Latin America. 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.