Characteristics of Talaromyces marneffei infection associated with inborn errors of immunity

Abstract Background: Talaromycosis is a systemic disease caused by Talaromyces marneffei. To capture the characteristics of talaromycosis patients with inborn errors of immunity (IEI) prompts us to develop a systematic review. Objective: To systematically review studies reporting cases of talaromycosis with IEI. We aimed to describe the susceptibility genotypes and clinical characteristics of talaromycosis in IEI patients and understand the underling mechanism of Talaromyces marneffei defence. Methods: A systematic literature review was performed by searching PubMed, Cochrane Central Register of Controlled Trials, Web of Science, EMBASE, and Scopus. Data from patients with genetic diagnosis of IEI with talaromycosis, IEI genotypes, immunology, and clinical characteristics were collected. Results: Fifty talaromycosis patients with IEI were included: XHIM (30.00%), STAT3-LOF (20.00%), STAT1-GOF (20.00%), IL2RG (6.00%), IFNGR1 (6.00%), IL12RB1 (4.00%), CARD9 (4.00%), COPA (4.00%), ADA (2.00%), RELB deficiency (2.00%), and NFKB2 (2.00%) were the underlying genetic mutations. mNGS was a rapid and effective diagnostic method. The onset of clinical manifestations included atypical presentations, generally with fever, cough, lymphadenopathy, abdominal discomfort, and pneumonia. Respiratory, skin, lymph node, digestive, and hematologic systems were commonly involved. Variable lung CT findings were commonly misdiagnosed as tuberculosis. Forty-seven patients received antifungal therapy, and 34 patients improved. Conclusions: The XHIM, STAT1-GOF, and STAT3-LOF genotypes exhibited the highest susceptibility to talaromycosis. Pathogen infection should be tested by mNGS in IEI patients with suspected talaromycosis, and antifungal therapy should be rapidly initiated. Immunological and genetic diagnoses are necessary for non-HIV patients with talaromycosis in children.