Lin Li, Peng Xin, Chen Lina, Dong Liqun, Zhong Lin
Department of Pediatric Pulmonary and Immunology, West China Second University Hospital, Sichuan University, No. 20, Section 3, South Renmin Road, Chengdu, 610041, Sichuan, China.
Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, Chengdu, 610041, Sichuan, China.
Pediatr Rheumatol Online J. 2025 Mar 31;23(1):35. doi: 10.1186/s12969-025-01086-3.
Childhood-onset eosinophilic granulomatosis with polyangiitis (cEGPA) is a rare type of systemic autoimmune disorder. Variants in the NFKB2 gene can manifest as common variable immunodeficiency or combined immunodeficiency, often accompanied by autoimmunity and ectodermal dysplasia. Here, we report a case of a Chinese patient who carries NFKB2 variants that coexist with cEGPA, a novel combination which, to our knowledge, has not been previously published.
We reported a 9-year and 10-month-old girl who presented with cough, wheezing, dyspnea, hypereosinophilia, and vasculitis. Notably, she had significant bilateral pulmonary interstitial lesions. We performed metagenomic next-generation sequencing (mNGS), bronchoscopy and immunological analysis. She was considered to have refractory cEGPA after six months of corticosteroid and immunosuppressive treatment. Tapering off corticosteroids posed a challenge, and multiple immunosuppressive agents were ineffective. Our patient suffered from recurrent fever, wheezing, dyspnea and perianal abscess, along with life-threatening infections, including pneumocystis jirovecii pneumonia (PJP) and severe coronavirus disease 2019 (COVID-19) pneumonia during the pandemic. Her cytokines and inflammatory markers showed a profound collapse. She developed significant hypoxemia, which necessitated mechanical ventilation. Primary immunodeficiency gene panel testing revealed a novel de novo variant in NFKB2 (c.2578 + 2 dup) that was classified as pathogenic. Despite treatment with antibacterial, antiviral, and antifungal agents, biologics, and plasma exchange, she ultimately succumbed to respiratory failure.
This case report establishes a novel link between NFKB2 variants and EGPA, particularly in the context of the COVID-19 pandemic. This study expands the spectrum of NFKB2 variants and vividly illustrates the complex interrelationships among autoimmunity, infection, and immunodeficiency.
儿童期起病的嗜酸性肉芽肿性多血管炎（cEGPA）是一种罕见的系统性自身免疫性疾病。NFKB2基因变异可表现为常见可变免疫缺陷或联合免疫缺陷，常伴有自身免疫和外胚层发育异常。在此，我们报告一例携带NFKB2变异且与cEGPA共存的中国患者，据我们所知，这种新的组合此前尚未见报道。
我们报告了一名9岁10个月大的女孩，她出现咳嗽、喘息、呼吸困难、嗜酸性粒细胞增多和血管炎。值得注意的是，她有明显的双侧肺间质病变。我们进行了宏基因组下一代测序（mNGS）、支气管镜检查和免疫学分析。在接受皮质类固醇和免疫抑制治疗6个月后，她被认为患有难治性cEGPA。逐渐减少皮质类固醇剂量面临挑战，多种免疫抑制剂均无效。我们的患者反复发热、喘息、呼吸困难和肛周脓肿，在疫情期间还出现危及生命的感染，包括耶氏肺孢子菌肺炎（PJP）和严重的2019冠状病毒病（COVID-19）肺炎。她的细胞因子和炎症标志物显示严重下降。她出现明显低氧血症，需要机械通气。原发性免疫缺陷基因检测显示NFKB2基因有一个新的新发变异（c.2578 + 2 dup），被分类为致病性变异。尽管接受了抗菌、抗病毒、抗真菌药物、生物制剂和血浆置换治疗，但她最终死于呼吸衰竭。
本病例报告在NFKB2变异与EGPA之间建立了新的联系，特别是在COVID-19大流行的背景下。本研究扩展了NFKB2变异的谱图，并生动地说明了自身免疫、感染和免疫缺陷之间复杂的相互关系。
