University of Trieste, Piazzale Europa 1, Trieste, 34127, Italy.
Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
Ital J Pediatr. 2023 Sep 4;49(1):111. doi: 10.1186/s13052-023-01509-5.
Ataxia-telangiectasia (A-T) is a rare autosomal recessive DNA repair disorder, characterized by progressive cerebellar degeneration, telangiectasia, immunodeficiency, recurrent sinopulmonary infections, radiation sensitivity, premature aging and predisposition to cancer. Although the association with autoimmune and chronic inflammatory conditions such as vitiligo, thrombocytopenia and arthritis has occasionally been reported, an onset with articular involvement at presentation is rare.
We herein report the case of a 7-year-old Caucasian girl who was admitted to the Rheumatology Department with a history of febrile chough and polyarthritis which led initially to the suspicion of an autoinflammatory disease. She had overt polyarthritis with knees deformities and presented with severe pneumonia. A chest Computed Tomography (CT) scan showed bilateral bronchiectasis, parenchymal consolidation and interstitial lung disease; rheumatoid factor and type I interferon signature resulted negative, therefore excluding COatomer Protein subunit Alpha (COPA) syndrome. A diagnosis of sarcoidosis had been suspected based on histological evidence of granulomatous liver inflammation, but ruled out after detecting normal angiotensin converting enzyme and chitotriosidase blood levels. Based on her past medical history characterized by at least six episodes of pneumonia in the previous 4 years, immunological phenotyping was performed. This showed complete IgA and IgE deficiency with defective antigen-specific antibodies to Pneumococcal, Tetanus toxin and Hemophilus Influenzae B vaccines. Additionally, low numbers of B cells and recent thymic emigrants (RTE) were found (CD4Ra 1.4%), along with a low CD4+/CD8 + T cells ratio (< 1). Finally, based on gait disturbances (wobbly wide-based walking), serum alfa-fetoprotein was dosed, which resulted increased at 276 ng/ml (normal value < 7 ng/ml). A diagnosis of Ataxia-Telangiectasia was made, strengthened by the presence of bulbar telangiectasia, and then confirmed by Whole Exome Sequencing (WES).
Although rare, A-T should always be ruled out in case of pulmonary bronchiectasis and gait disturbances even in the absence of bulbar or skin telangiectasia. Autoimmune and granulomatous disorders must to be considered as differential diagnosis.
共济失调毛细血管扩张症（A-T）是一种罕见的常染色体隐性 DNA 修复障碍，其特征为进行性小脑退行性变、毛细血管扩张、免疫缺陷、反复鼻窦肺感染、辐射敏感性、早衰和易患癌症。尽管偶尔有报道称其与自身免疫性和慢性炎症性疾病有关，如白癜风、血小板减少症和关节炎，但初诊时就出现关节受累的情况较为罕见。
我们在此报告一例 7 岁白人女孩的病例，她因发热性咳嗽和多发性关节炎入住风湿科，最初怀疑为自身炎症性疾病。她有多发性关节炎，膝关节畸形，并伴有严重肺炎。胸部 CT 扫描显示双侧支气管扩张、肺实质实变和间质性肺病；类风湿因子和 I 型干扰素特征呈阴性，因此排除 COP 亚基 α（COPA）综合征。基于组织学证据显示肝脏有肉芽肿性炎症，曾怀疑为结节病，但在检测到正常的血管紧张素转换酶和壳三糖苷酶血水平后排除。根据她过去的病史，过去 4 年中至少有 6 次肺炎发作，进行了免疫表型分析。结果显示完全 IgA 和 IgE 缺乏，对肺炎球菌、破伤风毒素和流感嗜血杆菌 B 疫苗的抗原特异性抗体也有缺陷。此外，还发现 B 细胞和近期胸腺迁出细胞（RTE）数量减少（CD4Ra 1.4%），同时 CD4+/CD8+T 细胞比值较低（<1）。最后，由于步态不稳（摇晃的宽基底行走），测定了血清甲胎蛋白，结果为 276ng/ml（正常值<7ng/ml）。诊断为共济失调毛细血管扩张症，存在球部毛细血管扩张症支持这一诊断，随后通过全外显子组测序（WES）得到证实。
即使没有球部或皮肤毛细血管扩张症，也应始终排除肺部支气管扩张和步态不稳的情况下的 A-T。必须考虑到自身免疫和肉芽肿性疾病作为鉴别诊断。
