Marilia Brasil Xavier, Cláudia Maria de Castro Gomes, Rita Catarina Medeiros Sousa, Edna Aoba Yassui Ishikawa, Elza Baía de Brito, Silvia Ferreira Rodrigues Müller, Lucas dos Santos Fontes, João Augusto Gomes de Souza Monteiro de Brito, Larissa dos Santos Alcantara, Carlos Eduardo Pereira Corbett
HIV-associated Immune Reconstitution Inflammatory Syndrome (IRIS) may significantly alter the immunopathological presentation of American Tegumentary Leishmaniasis (ATL), occasionally causing paradoxical clinical exacerbations. We report the long-term follow-up of a 39-year-old female coinfected with HIV and disseminated mucocutaneous leishmaniasis caused by Leishmania (Viannia) sp., who experienced severe lesion exacerbation four months after initiating High-Activity Antiretroviral Therapy (HAART). Despite successful viral suppression and CD4+ T-cell recovery, she developed aggressive mucocutaneous plaques with nasal septum destruction. Immunohistochemical analysis of a skin biopsy revealed a profile distinct from HIV-negative ATL controls: classic pro-inflammatory markers (CD68, iNOS, IL-6, and IL-17) were markedly suppressed, while CD163, IL-10, TGF-β and IL-18 were elevated, signalling M2 macrophage activation and paradoxical Th2 polarisation. CD8+ T cells were the most preserved lymphocyte subset, which is consistent with their reported cytotoxic, tissue-damaging role in mucosal leishmaniasis caused by L. (Viannia) braziliensis. Standard pentavalent antimonial combined with sustained HAART led to complete resolution without recurrence over 16 years. This case illustrates how IRIS may be associated with atypical Th2-polarised pathology and CD8-mediated tissue injury in ATL, highlighting the need for awareness of this presentation in coinfected patients from endemic areas.