When Myositis Hits the Lungs: What Every Rheumatologist Should Know About ILD Save

When idiopathic inflammatory myopathies (IIM) affect the lungs, the consequences can be serious. Interstitial lung disease (ILD) is not only common in IIM, but also one of the leading causes of death, contributing to up to 80% of mortality in this patient group (1). For rheumatologists, two subsets stand out: anti-synthetase syndrome (ASyS) and anti-MDA-5 positive dermatomyositis (MDA5-DM). These patients present with distinct clinical clues, very different disease trajectories, and unique treatment challenges. Recognizing ILD early and acting decisively can make the difference between stabilizing a chronic course and facing a rapidly progressive, often fatal decline (1,2).

Diagnosis: Clinical Suspicion and Key Tools

ILD may be the first or even sole manifestation of ASyS, preceding muscle or joint involvement. Clinical suspicion should be heightened in patients with unexplained dyspnea, persistent dry cough, or systemic signs such as mechanic’s hands, Raynaud’s phenomenon, or unexplained fever (3). In MDA5-DM, amyopathic or minimally symptomatic muscle disease accompanied by skin ulcerations or palmar papules should prompt immediate pulmonary evaluation(4).

Serological testing is central to diagnosis. Anti-Jo-1 and other anti-synthetase antibodies (PL-7, PL-12, OJ, EJ, KS, Zo, YRS, etc.) strongly support ASyS-ILD, while anti-MDA5 antibodies identify patients at high risk for rapidly progressive ILD (RP-ILD)(5). Coexistent anti-Ro52 antibodies have been associated with more severe ILD in both conditions (6).

High-resolution computed tomography (HRCT) remains the diagnostic gold standard. In ASyS, nonspecific interstitial pneumonia (NSIP) and organizing pneumonia (OP) are most frequent(3), whereas in MDA5-DM, OP often predominates and may evolve into diffuse alveolar damage, leading to a fulminant course (7). Pulmonary function tests (PFTs), particularly forced vital capacity (FVC) and diffusing capacity for carbon monoxide (DLCO), provide essential baseline assessment and are critical for longitudinal monitoring(1). DLCO is often the earliest parameter to decline, and serial testing every 2-3 months facilitates early detection of progression. Among functional measures, a reduction in FVC is a well-validated predictor of mortality in ILD (8–10).

Disease Course and Prognosis

Prognosis diverges between these entities (2). ASyS-ILD often follows a chronic, sometimes indolent, but usually progressive course. Ten-year survival approaches 75%, yet many patients require lifelong immunosuppression (11,12). Prognosis varies by antibody profile: anti-Jo-1 is associated with more favorable outcomes, whereas non-Jo-1 (especially anti-PL7, PL12) are associated with diagnostic delay due to lack of reliable antibody testing and often predict more severe, lung-dominant disease (13).

MDA5-DM, by contrast, frequently develops RP-ILD, with reported six-month mortality rates ranging from 33% to 66% (4). Adverse prognostic indicators include advanced age, reduced baseline pulmonary function, and elevated inflammatory markers such as C-reactive protein or serum ferritin (14)

Therapeutics: Tailored and Aggressive When Needed:

Corticosteroids remain the backbone of therapy. However, steroid-sparing agents are essential to achieve disease control and reduce toxicity (1,15).

In ASyS-ILD, first-line treatment commonly combines corticosteroids with either mycophenolate mofetil or azathioprine. Calcineurin inhibitors such as tacrolimus or cyclosporine, as well as rituximab, are frequently employed in cases of inadequate response or refractory disease (3). In MDA5-DM ILD, by contrast, early and intensive immunosuppression is crucial. Patients with RP-ILD are often treated with upfront triple therapy, consisting of high-dose corticosteroids, calcineurin inhibitor, and either cyclophosphamide or rituximab (4). Emerging data also suggest a role for Janus kinase inhibitors, particularly tofacitinib, in the management of RP-ILD (16).

For patients with progressive fibrosing ILD, antifibrotic therapy (e.g., nintedanib) may be added to slow functional decline (17). Supportive measures, including infection prophylaxis and pulmonary rehabilitation, remain integral. In cases of refractory or end-stage disease, timely referral to transplant-capable centers is vital, as lung transplantation can be lifesaving (1,18).

Conclusion

Effective management of ILD in ASyS and MDA5-DM requires vigilance, systematic evaluation, and timely intervention. Antibody testing, HRCT, and serial pulmonary function monitoring form the backbone of diagnosis and risk stratification. Prognosis differs substantially between the two conditions, with ASyS-ILD typically chronic progressive but manageable, and MDA5-DM ILD often rapidly fatal without aggressive treatment. 
 

A multidisciplinary approach between rheumatology and pulmonology can optimize diagnosis and treatment decisions. The landscape continues to evolve with emerging targeted therapies, refined prognostic biomarkers, and improved understanding of IIM-ILD pathophysiology. Maintaining a low threshold for suspicion and intervening early with tailored immunosuppression remain the most effective strategies to improve patient outcomes.

References:

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