A Case Report of SAVI Mimicking Early-Onset ANCA Vasculitis.
A Case Report of SAVI Mimicking Early-Onset ANCA Vasculitis.
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模仿早发性 ANCA 血管炎的 SAVI 病例报告。
DOI：
10.1007/s10875-021-01072-w
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发表时间：
2021
影响因子：
9.1
通讯作者：
Khojah,Amer
中科院分区：
文献类型：
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作者：
Ochfeld,Elisa;Curran,MeganL;Chiarella,SergioE;Ardalan,Kaveh;Khojah,Amer
婴儿期发作的STING相关血管病变（SAVI）是一种1型干扰素病，其典型特征是早期发作的全身性炎症伴皮肤血管炎和间质性肺病（ILD）。SAVI是由STING 1中的显性功能获得性突变引起的。虽然皮肤血管病变是一种常见的特征，但并非所有SAVI患者都表现出这种表型，并且缺乏皮肤血管炎不应排除对这种疾病的评估。ILD似乎是SAVI最突出的临床发现。在一项大型全球SAVI患者队列中，21/21例患者患有ILD，而18/21例患者患有皮肤血管病变[1]。人们也越来越认识到慢性干扰素信号传导可导致自身免疫性疾病。这是一例西班牙裔女性，表现为发育不良、反复发热、间歇性咳嗽伴口周发绀。症状开始于6个月大，并归因于反复的病毒和细菌感染。在14个月大时首次出现在我们的中心，她因发热和低氧血症（氧饱和度70%）住院，自6个月大以来有咳嗽史。胸部X线（CXR）显示肺间质纹理突出，诊断为肺炎。计算机断层扫描（CT）证实了CXR检查结果，并排除了解剖异常。她失去了随访2年，然后在3岁时再次出现呼吸状态恶化，活动和睡眠时咳嗽发作增加。当时进行的CT扫描显示间质增厚恶化。除了免疫球蛋白G（IgG）水平升高外，免疫检查（包括定量免疫球蛋白、CH 50、淋巴细胞亚群和疫苗应答滴度（肺炎球菌和破伤风））无异常。表面活性物质功能障碍突变的基因检测为阴性。胸腔镜肺活检显示间质纤维化，PAS阳性颗粒肺泡蛋白沉积症，II型细胞增生和淋巴滤泡。6岁时，她因心包积液入院。咨询了血液流变学，以评价频繁发热和持续升高的炎症标志物，担心心包炎是自身炎症。当时她的ANA（> 1：2560均匀模式，参考值< 80）、IL-6（378.88 pg/mL，参考值0.31-5.00 pg/mL）和IgG（2020 mg/dL，参考值423-1090 mg/dL）升高。她有核周ANCA模式，髓过氧化物酶抗体阳性（91.2 EIA/U，参考< 20 EIA/U）。抗dsDNA、Smith和Scl 70均为阴性。患者接受类固醇和羟氯喹治疗，需氧量有所改善。
STING-associated vasculopathy with onset in infancy (SAVI) is a type 1 interferonopathy that is typically characterized by early onset systemic inflammation with cutaneous vasculitis and interstitial lung disease (ILD). SAVI is caused by dominant gain-of-function mutations in STING1. While skin vasculopathy is a common feature, not all SAVI patients display this phenotype, and lack of cutaneous vasculitis should not preclude evaluation for this disorder. ILD appears to be the most prominent clinical finding of SAVI. In a large worldwide cohort of SAVI patients, 21/21 patients had ILD, compared to 18/21 patients with skin vasculopathy [1]. It is also increasingly recognized that chronic interferon signaling can lead to autoimmune disease. This is the case of a Hispanic female who presented with failure to thrive, recurrent fevers, and intermittent cough with perioral cyanosis. Symptoms began at age 6 months and were attributed to recurrent viral and bacterial infections. On initial presentation to our center at 14 months old, she was hospitalized with fever and hypoxemia (O2 saturations 70%), with history of cough since age 6 months. Chest X-ray (CXR) showed prominent interstitial lung markings and she was diagnosed with pneumonia. Computed tomography (CT) scan confirmed CXR findings and ruled out anatomical anomaly.She was lost to follow-up for 2 years, then re-presented at age 3 with worsening respiratory status, with increasing coughing fits during activity and sleep. A CT scan performed at that time demonstrated worsening interstitial thickening. Immune workup, including quantitative immunoglobulins, CH50, lymphocyte subsets, and vaccine response titers (pneumococcal and tetanus), was unremarkable, except for elevated immunoglobulin G (IgG) levels. Genetic testing for surfactant dysfunction mutations was negative. Thoracoscopic lung biopsy revealed interstitial fibrosis, PAS-positive granular alveolar proteinosis, type II cell hyperplasia, and lymphoid follicles. At age 6, she was admitted for a pericardial effusion. Rheumatology was consulted for evaluation of frequent fevers and persistently elevated inflammatory markers, with concern that the pericarditis was autoinflammatory. She had an elevated ANA (> 1: 2560 homogeneous pattern, reference< 80), IL-6 (378.88 pg/mL, reference 0.31–5.00 pg/mL), and IgG (2020 mg/dL, reference 423–1090 mg/dL) at that time. She had a perinuclear ANCA pattern with positive myeloperoxidase antibodies (91.2 EIA/U, reference< 20 EIA/U). Anti dsDNA, Smith, and Scl70 were negative. She was treated with steroids and hydroxychloroquine with some improvement in oxygen requirement.