Barbosa Layala Stefane de Paula, Ely Marina Miranda, Salomé Túlio Máximo, de Almeida de Souza Gleyce Hellen, Santos Daniel Assis, Bastos Rafael Wesley, Rossato Luana
Faculdade de Ciências da Saúde (FCS), Rodovia Dourados/Itahum, Federal University of Grande Dourados (UFGD), Dourados, Mato Grosso do Sul, Brazil.
Departamento de Microbiologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
Mycoses. 2025 Mar;68(3):e70040. doi: 10.1111/myc.70040.
TNF-α inhibitors, including infliximab, adalimumab and etanercept, are used to treat various inflammatory diseases, such as arthritis, psoriasis and ankylosing spondylitis. However, these treatments may predispose patients to fungal infections, including histoplasmosis, candidiasis and aspergillosis. In this study, we systematically reviewed case reports to critically examine the correlations between anti-TNF-α therapies and the occurrence of invasive and superficial fungal infections. Infliximab was the most commonly used TNF-α inhibitor (50.65%). The highest number of fungal infections during anti-TNF34 α therapy was reported in the USA (84.25%). The conditions treated primarily included rheumatoid arthritis. A total of 517 invasive fungal infections were identified, including histoplasmosis, invasive candidiasis and aspergillosis, with histoplasmosis being the most common. Most studies were conducted in higher-income countries, highlighting the critical lack of research on the use of immunobiologicals in relation to fungal diseases in African countries, which requires further attention. Logistic regression analysis revealed significant associations between adalimumab use and increased risks of candidiasis, coccidioidomycosis, onychomycosis and pityriasis versicolor. For etanercept, significant associations were found with aspergillosis, coccidioidomycosis, cryptococcosis, dermatophytosis, invasive candidiasis, pityriasis versicolor and onychomycosis. Infliximab use was significantly associated with coccidioidomycosis, onychomycosis, aspergillosis, cryptococcosis, histoplasmosis and invasive candidiasis. The data presented in this study clearly demonstrate an association between the use of TNF-α inhibitors and an increased risk of fungal infections. It is imperative that healthcare professionals maintain a high level of vigilance when managing patients on these medications. Regular monitoring and proactive management strategies are essential to mitigate risks and ensure patient safety.
肿瘤坏死因子-α（TNF-α）抑制剂，包括英夫利昔单抗、阿达木单抗和依那西普，用于治疗各种炎症性疾病，如关节炎、银屑病和强直性脊柱炎。然而，这些治疗可能使患者易患真菌感染，包括组织胞浆菌病、念珠菌病和曲霉病。在本研究中，我们系统回顾了病例报告，以严格审查抗TNF-α治疗与侵袭性和浅表真菌感染发生之间的相关性。英夫利昔单抗是最常用的TNF-α抑制剂（50.65%）。美国报告的抗TNF-α治疗期间真菌感染数量最多（84.25%）。主要治疗的疾病包括类风湿性关节炎。共确定了517例侵袭性真菌感染，包括组织胞浆菌病、侵袭性念珠菌病和曲霉病，其中组织胞浆菌病最为常见。大多数研究在高收入国家进行，这凸显了非洲国家在免疫生物制剂与真菌疾病相关使用方面严重缺乏研究，这需要进一步关注。逻辑回归分析显示，使用阿达木单抗与念珠菌病、球孢子菌病、甲癣和花斑癣风险增加之间存在显著关联。对于依那西普，发现与曲霉病、球孢子菌病、隐球菌病、皮肤癣菌病、侵袭性念珠菌病、花斑癣和甲癣存在显著关联。使用英夫利昔单抗与球孢子菌病、甲癣、曲霉病、隐球菌病、组织胞浆菌病和侵袭性念珠菌病显著相关。本研究提供的数据清楚地表明，使用TNF-α抑制剂与真菌感染风险增加之间存在关联。医疗保健专业人员在管理使用这些药物的患者时必须保持高度警惕。定期监测和积极的管理策略对于降低风险和确保患者安全至关重要。
