Clinical features, diagnosis, and treatment of primary Sjögren's disease with interstitial lung disease: A narrative review

原发性干燥综合征合并间质性肺疾病的临床特征、诊断和治疗:叙述性综述

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Abstract

Interstitial lung disease (ILD) is a severe and frequent extraglandular manifestation of primary Sjögren's disease (pSjD), conferring significant morbidity and mortality. This narrative review synthesizes current evidence on the epidemiology, pathogenesis, clinical phenotypes, diagnosis, and management of pSjD-ILD, with a focus on phenotype-stratified care and evidence limitations. Key risk factors include anti-Ro52 antibody seropositivity, advanced age, and male sex. Diagnosis relies on a multidisciplinary approach integrating clinical assessment, serology, high-resolution computed tomography (predominantly fibrotic nonspecific interstitial pneumonia pattern), and pulmonary function tests. Pathogenesis involves a complex interplay of autoantibody-mediated damage, immune cell dysregulation, and dysbalanced pro-fibrotic signaling. We emphasize a phenotype-stratified treatment strategy: immunosuppression forms the cornerstone for inflammatory-predominant disease, while antifibrotic agents are pivotal for progressive fibrotic phenotypes. Critical limitations of current evidence include the extrapolation of most therapeutic data from other connective tissue disease-associated ILDs (CTD-ILDs) and a lack of pSjD-ILD-specific randomized controlled trials (RCTs). Emerging therapies, including rituximab and nintedanib, show promise but require further validation in pSjD-ILD cohorts. This review provides a pragmatic clinical framework to guide diagnosis, risk stratification, and individualized management, while highlighting critical unmet needs for future research, such as validated prognostic scores and pSjD-ILD-specific clinical trials.

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