结缔组织病（CTD）的肺部并发症常见，可累及间质、气道、胸膜和肺血管。间质性肺病（ILD）可见于所有CTD（CTD-ILD），并可能从限制性、非进行性肺部受累，发展为突发的致命性疾病。在此为临床医生提供框架文本，有助于CTD-ILD的评估和管理。
关键词：临床诊断和管理；胶原血管病；结缔组织病；间质性肺疾病
CTD-ILD的诊断方法
整合临床、血清学和高分辨率计算机断层扫描（HRCT）检查结果，结合ILD-MDM（ILD-多学科会议）探讨，是确诊CTD-ILD的关键[1，2]。
非特异性间质性肺炎（NSIP）是与CTD相关ILD最常见的放射学和组织学模式[3，4–6]。
尽管肺活检通常并不提供有意义的额外诊断或预后信息，但对于ILD-MDM讨论后主要诊断不明的病例应予以实施[6，7–9]。
CTD-ILD的管理方法
CTD-ILD治疗决策受CTD诊断和诊断后时长、ILD严重程度、疾病轨迹、CTD肺外临床表现和患者个体因素的影响。
以炎症成分为主的进展性CTD-ILD（根据临床和放射学评估确定），可通过适当的强化免疫抑制实现显著逆转[10，11]。
以纤维化成分为主的进展性和/或严重CTD-ILD，经强化免疫抑制治疗通常不会明显消退，尽管使用低剂量皮质类固醇、使用或不使用限制激素的免疫抑制剂可能起到稳定作用。
连续的肺功能检测（PFT）是监测CTD-ILD的基础，包括对治疗的反应[12，13–15]。
特殊的CTD-ILD
1.系统性硬化病（SSc）
严重和/或进展性SSc-ILD的危险因素包括HRCT影像ILD程度更重、PFT下降、Scl-70自身抗体阳性以及在SSc病程中早期ILD的进展[15，16-19]。
霉酚酸酯（MMF）已被证实能稳定SSc-ILD，通常视为按需首选疗法。硫唑嘌呤或环磷酰胺（通常为静脉注射，考虑到较低的毒性蓄积）可能是MMF的替代品[20–22]。
联合使用皮质类固醇是有争议的，如果使用的话，应尽量减少剂量（<10–15 mg/d），以降低包括SSc肾危象风险在内的副作用。
尼达尼布已被证明能减缓SSc-ILD的肺功能下降，尽管在澳大利亚或新西兰还未被证实有此适应症[23]。
2.类风湿性关节炎（RA）
在RA-ILD中，普通型间质性肺炎（UIP）较低的基线PFT和PFT下降其预后较差[24-27]。
管理RA-ILD的对照治疗试验数据缺乏。多种免疫抑制剂（包括环磷酰胺、硫唑嘌呤、MMF或利妥昔单抗）可有效改善RA-ILD恶化。
在RA-ILD进展期，应考虑停止使用缓解疾病的抗风湿药物（来氟米特和肿瘤坏死因子抑制剂），鉴于这些药物有可能导致ILD恶化。
3.特发性炎性肌病（IIM）
ILD是IIM死亡的主要因素，需要加快评估和治疗[28，29]。
初始大剂量皮质类固醇（口服或静脉注射）、静脉注射环磷酰胺或利妥昔单抗行强化免疫抑制，以控制进行性IIM-ILD。静脉注射用免疫球蛋白和血浆置换可能在急性期发挥作用[30-34]。
经初始高剂量治疗后，通常需要使用低剂量皮质类固醇和类固醇保护剂（包括MMF、硫唑嘌呤和钙调磷酸酶抑制剂）以维持免疫抑制，但无明显制剂优先证据[31，35-37]。
CTD-ILD周详管理中需考虑因素
在CTD中肺动脉压升高会对预后产生显著的负面影响，需要在有经验的肺动脉高压（PH）中心进行评估。
在结缔组织病相关肺动脉高压（CTD-PAH，WHO1组）中，肺血管扩张治疗有益，一旦确诊PAH，就应立即进行，最理想的情况是WHO功能II级[38–41]。
推荐根据ESC/ERS指南对联合疗法的CTD-PAH进行治疗升级[41]
。
汇总意见
CTD-ILD的准确诊断、严重程度分级和进展监测有时需临床、放射学、生理学和血清学数据的复杂整合，通常需要非呼吸专家的实质性介入。考虑到一些CTD-ILD的罕见性和缺乏具体治疗证据，治疗方法通常是从其他假定具有类似疾病机制的CTD-ILD推断而来的，这代表了在诸多CTD-ILD中未得到满足的主要临床需求，应作为未来研究重点。
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MCC号Xo921032694有效期2022-03-18，资料过期，视同作废。
孟爱宏 主任医师
· 医学博士/主任医师/教授/博士生导师
· 河北医科大学第二医院北院区呼吸与危重症医学科主任
高思洁 研究生
· 河北医科大学第二医院2020级硕士研究生
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