Gastrointestinal disseminated histoplasmosis in HIV-infected patients: A descriptive and comparative study

Abstract

Disseminated histoplasmosis is one the main AIDS-defining opportunistic infections in HIV-infected patients, notably in Latin America. The non-specific and proteiform clinical presentation leads to diagnostic delays that may lead to fatal outcomes. This retrospective multicentric study aimed to describe the frequency and manifestations of gastrointestinal histoplasmosis in French Guiana, and to compare patients with disseminated histoplasmosis with or without gastrointestinal involvement. Between January 1, 1981 and October 1, 2014 co-infections with HIV and histoplasmosis were enrolled. Inclusion criteria were: age >18 years, confirmed HIV infection; first proven episode of histoplasmosis. Among 349 cases of disseminated histoplasmosis, 245 (70%) had a gastrointestinal presentation. Half of patients with gastrointestinal signs had abdominal pain or diarrhea, mostly watery. Half of patients with abdominal pain had diarrhea (63/124) and half of those with diarrhea (63/123) had abdominal pain. A significant proportion of patients also had hepatomegaly and, to a lesser degree, splenomegaly. After adjusting for potential confounding, the presence of lymphadenopathies >2cm (AOR = 0.2, IC95 = 0.04–0.7, P = 0.01), Haitian origin (AOR = 0.04, IC95 = 0.004–0.4, P = 0.006) were associated with a lower prevalence of gastrointestinal signs and positive gastrointestinal presence of H. capsulatum. Persons with a gastrointestinal H. capsulatum were more likely to have a decreased prothrombin time, lower ferritin, lower liver enzymes, and lower concentrations of LDH than those without gastrointestinal signs and symptoms. They also had a shorter interval between symptoms onset and diagnosis. Patients with a positive gastrointestinal identification of H. capsulatum were less likely to die at 1 month than those without a gastrointestinal presentation (respectively, 4.6% vs 18.5%, P = 0.01). Subacute or chronic gastrointestinal presentations are very frequent during disseminated histoplasmosis, they seem less severe, and should lead to suspect the diagnosis in endemic areas. There were populational or geographic differences in the frequency of gastrointestinal manifestations that could not be explained.

Histoplasmosis Diagnosed in Europe and Israel: A Case Report and Systematic Review of the Literature from 2005 to 2020

“…A diagnosis of histoplasmosis was the AIDS-revealing condition in 52% of our PLWH and was associated with severe immunodepression as confirmed by the very low median CD4+ cell count and the observation of concomitant opportunistic infections in nearly 30% of the patients. Although gastrointestinal involvement was less frequent than in highly endemic areas such as French Guiana [155,156], it is worth noting that 5.3% of the patients had localised intestinal histoplasmosis, and that the fungus was visualised and/or cultured in 10.5% of the cases. Skin lesions were described in 32% of PLWH, 21.4% of the patients with OIC, and 4.9% of the immunocompetent patients; furthermore, primary cutaneous histoplasmosis was observed in an HIV-positive patient and an immunocompetent laboratory technician [39,106].…”

Coinfecção entre HIV e Histoplasma capsulatum

“…Isso pode representar apenas associações aleatórias, mas pode-se discutir diferenças na microbiota, patógenos gastrointestinais endêmicos ou práticas culturais de alimentação que de alguma forma modulam o risco de localizações gastrointestinais. Focos inflamatórios podem atrair monócitos / macrófagos infectados que, portanto, trazem o fungo para o tubo digestivo rico em estruturas imunológicas (Nacher et al, 2021b).…”

“…Os autores (Nacher et al, 2021b) histoplasmose adrenal e a insuficiência adrenal primária são manifestações características de pacientes com histoplasmose e HIV, nesta pesquisa foi observado que apenas 0,85% apresentaram insuficiência adrenal e que a imunossupressão das glândulas supra-renais não representam um nicho particular para a proliferação do Histoplasma.…”

“…O diagnóstico diferencial da histoplasmose é fundamental, já que a forma disseminada apresenta sintomas inespecíficos que somados a um histórico de exposição incerto, pode criar desafios diagnósticos (Cáceres et al, 2018;Basso et al, 2021) Existem testes para detecção do fungo com base em métodos de cultura, métodos sorológicos, histopatológicos, microscopia, métodos de detecção de antígeno e métodos moleculares (Hatakeyama et al, 2019;Kuate et al, 2021). Cultura de amostras de sangue, espécimes respiratórios, tecido da pele, mucosa oral, medula óssea, linfonodos, fígado e, muito frequentemente, o sistema gastrointestinal, são examinados e cultivados a fim de identificar H. capsulatum (Caceres et al, 2016;Nacher et al, 2021b).…”

“…Globalmente, existem 37 milhões de pessoas com HIV e nos últimos anos, tem sido relatado um aumento da histoplasmose disseminada, principalmente associada a pacientes com AIDS nas Américas (Damasceno et al, 2019;UNAIDS, 2021). Entre os pacientes com HIV, histoplasmose disseminada tem sido a infecção definidora de AIDS mais frequente e a primeira causa de morte, a mortalidade se aproxima de 50%, especialmente naqueles com manifestações graves (Samayoa et al, 2017;Nacher et al, 2021b).…”