Fragoulis George E, Nikiphorou Elena, Larsen Jörg, Korsten Peter, Conway Richard
First Department of Propaedeutic Internal Medicine, National and Kapodistrian University of Athens, Laiko General Hospital, Athens, Greece.
Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, United Kingdom.
Front Med (Lausanne). 2019 Oct 23;6:238. doi: 10.3389/fmed.2019.00238. eCollection 2019.
Rheumatoid arthritis (RA) is a type of inflammatory arthritis that affects ~1% of the general population. Although arthritis is the cardinal symptom, many extra-articular manifestations can occur. Lung involvement and particularly interstitial lung disease (ILD) is among the most common. Although ILD can occur as part of the natural history of RA (RA-ILD), pulmonary fibrosis has been also linked with methotrexate (MTX); a condition also known as MTX-pneumonitis (M-pneu). This review aims to discuss epidemiological, diagnostic, imaging and histopathological features, risk factors, and treatment options in RA-ILD and M-pneu. M-pneu, usually has an acute/subacute course characterized by cough, dyspnea and fever. Several risk factors, including genetic and environmental factors have been suggested, but none have been validated. The diagnosis is based on clinical and radiologic findings which are mostly consistent with non-specific interstitial pneumonia (NSIP), more so than bronchiolitis obliterans organizing pneumonia (BOOP). Histological findings include interstitial infiltrates by lymphocytes, histiocytes, and eosinophils with or without non-caseating granulomas. Treatment requires immediate cessation of MTX and commencement of glucocorticoids. RA-ILD shares the same symptomatology with M-pneu. However, it usually has a more chronic course. RA-ILD occurs in about 3-5% of RA patients, although this percentage is significantly increased when radiologic criteria are used. Usual interstitial pneumonia (UIP) and NSIP are the most common radiologic patterns. Several risk factors have been identified for RA-ILD including smoking, male gender, and positivity for anti-citrullinated peptide antibodies and rheumatoid factor. Diagnosis is based on clinical and radiologic findings while pulmonary function tests may demonstrate a restrictive pattern. Although no clear guidelines exist for RA-ILD treatment, glucocorticoids and conventional disease modifying antirheumatic drugs (DMARDs) like MTX or leflunomide, as well as treatment with biologic DMARDs can be effective. There is limited evidence that rituximab, abatacept, and tocilizumab are better options compared to TNF-inhibitors.
类风湿关节炎（RA）是一种炎症性关节炎，影响约1%的普通人群。虽然关节炎是主要症状，但也会出现许多关节外表现。肺部受累，尤其是间质性肺疾病（ILD）是最常见的表现之一。虽然ILD可作为RA自然病程的一部分出现（RA-ILD），但肺纤维化也与甲氨蝶呤（MTX）有关；这种情况也称为MTX肺炎（M-肺炎）。本综述旨在讨论RA-ILD和M-肺炎的流行病学、诊断、影像学和组织病理学特征、危险因素及治疗选择。M-肺炎通常呈急性/亚急性病程，以咳嗽、呼吸困难和发热为特征。已经提出了几种危险因素，包括遗传和环境因素，但均未得到证实。诊断基于临床和放射学表现，这些表现大多与非特异性间质性肺炎（NSIP）一致，比闭塞性细支气管炎伴机化性肺炎（BOOP）更为常见。组织学表现包括淋巴细胞、组织细胞和嗜酸性粒细胞的间质浸润，可有或无非干酪样肉芽肿。治疗需要立即停用MTX并开始使用糖皮质激素。RA-ILD与M-肺炎有相同的症状。然而，它通常病程更慢性。RA-ILD发生在约3-5%的RA患者中，不过当使用放射学标准时，这一比例会显著增加。普通间质性肺炎（UIP）和NSIP是最常见的放射学类型。已确定RA-ILD的几种危险因素，包括吸烟、男性、抗瓜氨酸化肽抗体和类风湿因子阳性。诊断基于临床和放射学表现，而肺功能测试可能显示限制性模式。虽然对于RA-ILD的治疗尚无明确指南，但糖皮质激素和传统的改善病情抗风湿药物（DMARDs）如MTX或来氟米特，以及生物DMARDs治疗可能有效。有有限的证据表明，与肿瘤坏死因子抑制剂相比，利妥昔单抗、阿巴西普和托珠单抗是更好的选择。
