Disseminated Talaromyces marneffei infection presenting as multiple intestinal perforations and diffuse hepatic granulomatous inflammation in an infant with STAT3 mutation: a case report

Abstract

Background: Talaromyces marneffei is a highly pathogenic fungus that can cause life-threatening fatal systemic mycosis. Disseminated Talaromycosis marneffei affects multiple organs, including the lungs, skin, and reticuloendothelial system. However, T. marneffei infection has rarely been reported in human immunodeficiency virus (HIV)-negative infants with multiple intestinal perforations and diffuse hepatic granulomatous inflammation. Case presentation: We present the case of an HIV-negative 37-month-old boy who has had recurrent pneumonia since infancy and was infected with disseminated Talaromycosis. Contrast-enhanced computed tomography of the whole abdomen showed hepatomegaly and intestinal wall thickening in the ascending colon and cecum with mesenteric lymphadenopathy. Colonoscopy showed a cobblestone pattern with erosion, ulcer, polypoid lesions, and lumen deformation ranging from the colon to the cecum. T. marneffei was isolated from the mucous membrane of the colon, liver, and bone marrow. After antifungal treatment and surgery, his clinical symptoms significantly improved. Whole-exome sequencing using the peripheral blood of the patient and his parents' revealed a heterozygous missense mutation in exon 17 of the STAT3 gene (c.1673G>A, p.G558D). Conclusions: In T. marneffei infection-endemic areas, endoscopic examination, culture, or histopathology from the intestine tissue should be performed in disseminated Talaromycosis patients with gastrointestinal symptoms. Timely and systemic antifungal therapy could improve the prognosis. Immunodeficiency typically should be considered in HIV-negative infants with opportunistic infections.

Case Report: Disseminated Talaromyces marneffei Infection in a Patient With Chronic Mucocutaneous Candidiasis and a Novel STAT1 Gain-of-Function Mutation

“…However, there have been few reports of T. marneffei infection in patients with primary immunodeficiency. Pan et al reported that a child with primary immunodeficiency carrying a STAT3 mutation suffered from T. marneffei invasion of the intestinal system, which was characterized by multiple intestinal perforations, erosion, ulcers and polypoid lesions, among other symptoms of intestinal invasion (19).…”

Successful Management of Mixed Mycosis in HIV-Negative Patients With Different Immune Status: A Case Series Report

“…In China, most patients with cryptococcosis do not have an immunocompromised status (Ye et al, 2012;Cheng et al, 2021). Talaromycosis marneffei infection, an endemic fungal disease in Asian populations, also occurs in HIV-negative immunocompetent populations (Lee et al, 2019;Pan et al, 2020). Although some patients have been confirmed to have nonclassical immunodeficiency, such as hyper-IgE syndrome and anti-IFN-g autoantibody-associated immunodeficiency syndrome, most patients do not have clear immunodeficiency or hypofunction (Lee et al, 2019;Pan et al, 2020).…”

“…Talaromycosis marneffei infection, an endemic fungal disease in Asian populations, also occurs in HIV-negative immunocompetent populations (Lee et al, 2019;Pan et al, 2020). Although some patients have been confirmed to have nonclassical immunodeficiency, such as hyper-IgE syndrome and anti-IFN-g autoantibody-associated immunodeficiency syndrome, most patients do not have clear immunodeficiency or hypofunction (Lee et al, 2019;Pan et al, 2020). Due to the lack of specificity in the clinical manifestations of pulmonary mycosis in immunocompetent hosts, mycosis is often not the first consideration during clinical diagnosis and treatment.…”

Talaromyces marneffei activates the AIM2-caspase-1/-4-GSDMD axis to induce pyroptosis in hepatocytes

“…Previous studies and clinical observations have shown that T.marneffei infection may cause liver damage. While the liver can show different pathological alterations depending on immune status after T.marneffei infection, aspectrum of pathological damage to the liver has been observed in cases of hepatic talaromycosis in some clinicopathological studies [ 15 , 16 ]. However, the specific pathological mechanism is not clear.…”