Defining interstitial lung disease related to idiopathic inflammatory myopathies: a systematic review protocol of the Myositis Clinical Trial Consortium (MCTC).

Abstract

Background: Idiopathic inflammatory myopathies (IIM) are systemic autoimmune diseases that include dermatomyositis, polymyositis, antisynthetase syndrome, and immune-mediated necrotizing myopathy in both adult and juvenile populations. Interstitial lung disease (ILD) is a common and serious complication of IIM, with a highly variable clinical course ranging from indolent disease to rapidly progressive respiratory failure, often influenced by underlying myositis-specific autoantibody profiles. Despite the substantial morbidity and mortality associated with IIM-ILD in both adults and children, high-quality evidence to guide clinical management remains limited. A major barrier to progress in this field is the lack of standardized disease nomenclature and uniform diagnostic or classification criteria, which hampers cohort development, limits comparability across studies, and restricts generalizability of findings. To address this gap, we will conduct a systematic review to inform a consensus-based disease definition for adult and juvenile IIM-ILD, with detailed methodology outlined in this protocol. This review will not evaluate prognosis, treatment, or clinical outcomes, but instead focus exclusively on how IIM-ILD is defined and operationalized across studies.

Methods: Following PRISMA 2020 statement and Cochrane methodology, we will search PubMed, EMBASE, Scopus, Cochrane Systematic Reviews, and Cochrane Central from inception to June 30, 2025, using a ''Peer Review of Electronic Search Strategies (PRESS)''-validated strategy. Eligible studies will include randomized controlled trials (RCTs), cohort and case-control studies, systematic reviews, meta-analyses, guidelines, and consensus statements explicitly reporting IIM-ILD definitions in human participants of all ages. Study selection will be performed in Covidence using predefined criteria. Data extraction will capture case definitions, classification criteria, diagnostic methods, ILD patterns, autoantibody profiles, and study characteristics. Quantitative synthesis will summarize the frequency and components of definitions where possible; otherwise, a structured narrative synthesis will be performed.

Discussion: Our systematic review protocol is the first comprehensive attempt at synthesizing the highly heterogenous disease nomenclature currently employed in adult and juvenile IIM-ILD literature. Findings will map areas of agreement and inconsistency in existing definitions, forming an evidence base for subsequent consensus processes, such as Delphi, to establish standardized nomenclature. Harmonized definitions are expected to improve research reproducibility, facilitate multicentric collaboration, and improve patient stratification in clinical practice and trials.

Systematic review registration: PROSPERO ID: 1129967.