Sparanese Sydney, Brager Rae, Fahmy David, Garkaby Jenny
Department of Medicine, University of British Columbia, Vancouver, Canada.
Department of Pediatrics, Division of Immunology, Allergy, and Dermatology, Hamilton Health Sciences, McMaster University, Hamilton, Canada.
Endocrinol Diabetes Metab Case Rep. 2025 Jul 24;2025(3). doi: 10.1530/EDM-25-0054. Print 2025 Jul 1.
This case report describes a 54-year-old woman with multiple endocrine autoimmune pathologies and recurrent mucocutaneous Candida spp. infections that were inappropriately attributed to her glycemic control. Following an allergic reaction over four decades later, the patient was referred to clinical immunology. The combination of persistent Candida infections, autoimmune endocrinopathies, and a positive family history prompted investigation for an inborn error of immunity (IEI). Genetic testing revealed a novel, missense mutation in STAT1. Functional analysis confirmed enhanced STAT1 protein phosphorylation, confirming a gain-of-function phenotype that explained her infectious and autoimmune manifestations. She was started on the JAK inhibitor, ruxolitinib, with clinical improvement. This case underscores the shared molecular mechanisms between IEIs and autoimmune endocrinopathies and highlights the importance of early recognition of IEI in patients with unusual or treatment-refractory infections alongside autoimmune disease. Endocrinologists and primary care providers may be the first to encounter such patients and should consider referral for immunologic and genetic evaluation. Early diagnosis can reduce long-term morbidity and open the door to targeted therapies that address the root cause of immune dysregulation.
Persistent mucocutaneous candidiasis in patients with autoimmune endocrinopathies warrants evaluation for underlying IEI: while candidiasis is common in individuals with diabetes, recurrent or treatment-refractory infections - particularly in the presence of additional autoimmune conditions - should prompt consideration of IEI, including STAT1 gain-of-function mutations. Autoimmunity and immunodeficiency represent overlapping spectra of immune dysregulation: genetic syndromes such as STAT1 GOF may manifest with both autoimmune endocrinopathies and increased susceptibility to fungal infections, underscoring the importance of a unifying diagnostic approach to seemingly disparate clinical features. Early referral to clinical immunology and genetic testing can enable timely diagnosis and targeted therapy: early recognition of IEI allows for disease-modifying treatment, such as JAK inhibition, which may alleviate infectious susceptibility and autoimmune manifestations, ultimately reducing morbidity and improving the quality of life. A thorough family history can provide critical diagnostic clues in cases of immune dysregulation: subtle patterns of autoimmunity or recurrent infections in family members - particularly in non-consanguineous pedigrees - may indicate heritable immunologic disorders and should inform the clinical threshold for pursuing genetic evaluation.
本病例报告描述了一名54岁女性，患有多种内分泌自身免疫性疾病，反复发生黏膜皮肤念珠菌属感染，这些感染曾被不恰当地归因于她的血糖控制。四十多年后，在一次过敏反应后，该患者被转诊至临床免疫学。持续的念珠菌感染、自身免疫性内分泌病以及阳性家族史促使对先天性免疫缺陷（IEI）进行调查。基因检测发现STAT1存在一种新的错义突变。功能分析证实STAT1蛋白磷酸化增强，证实了功能获得性表型，这解释了她的感染和自身免疫表现。她开始使用JAK抑制剂鲁索替尼治疗，临床症状有所改善。本病例强调了IEI与自身免疫性内分泌病之间的共同分子机制，并突出了在患有不寻常或治疗难治性感染以及自身免疫性疾病的患者中早期识别IEI的重要性。内分泌学家和初级保健提供者可能是首批接诊此类患者的人，应考虑转诊进行免疫学和基因评估。早期诊断可以降低长期发病率，并为针对免疫失调根本原因的靶向治疗打开大门。
自身免疫性内分泌病患者持续的黏膜皮肤念珠菌病需要评估潜在的IEI：虽然念珠菌病在糖尿病患者中很常见，但反复或治疗难治性感染——尤其是在存在其他自身免疫性疾病的情况下——应促使考虑IEI，包括STAT1功能获得性突变。自身免疫和免疫缺陷代表免疫失调的重叠谱系：诸如STAT1功能获得等遗传综合征可能表现为自身免疫性内分泌病和对真菌感染易感性增加，强调了对看似不同的临床特征采用统一诊断方法的重要性。早期转诊至临床免疫学和基因检测能够实现及时诊断和靶向治疗：早期识别IEI可进行疾病改善治疗，如JAK抑制，这可能减轻感染易感性和自身免疫表现，最终降低发病率并提高生活质量。详尽的家族史可为免疫失调病例提供关键的诊断线索：家庭成员中自身免疫或反复感染的细微模式——尤其是在非近亲家系中——可能表明遗传性免疫疾病，应告知进行基因评估的临床阈值。
