Idiopathic Inflammatory Myopathies and Associated Lung Disease

Idiopathic inflammatory myopathies constitute a group of rare systemic autoimmune disorders characterised principally by chronic inflammation of skeletal muscle, manifesting as muscle weakness and tissue damage. Key subtypes include polymyositis, dermatomyositis and inclusion body myositis, as well as clinically overlapping entities such as immune-mediated necrotising myopathy and antisynthetase syndrome. In many patients, immune-mediated muscle injury co-exists with extramuscular features; among these, interstitial lung disease is a major cause of morbidity and mortality. Pulmonary involvement ranges from subclinical ground-glass changes to rapidly progressive interstitial fibrosis, often correlating with specific autoantibody profiles. Clinical presentation may include dyspnoea, cough and impaired gas exchange, detected by high-resolution computed tomography and pulmonary function testing. Pathogenesis involves proinflammatory cytokines, complement activation and autoantibodies directed against tRNA synthetases or nucleic acid sensing proteins, which collectively drive both muscle and lung injury. Current management prioritises early recognition and combination immunosuppression, typically beginning with high-dose corticosteroids and addition of agents such as methotrexate, azathioprine or mycophenolate. Emerging strategies are targeting cytokines, complement pathways and oxidative stress to arrest both myositis and lung fibrosis. Multidisciplinary care is critical for optimising functional outcomes and mitigating treatment-related toxicity. Advances in serological subsetting and biomarker-driven therapy offer the prospect of personalised approaches, while global registry data continue to refine prognostic models.

Research from Nature Portfolio

Recent studies have advanced understanding of the interplay between immune mediators and metabolic dysregulation in both muscle and lung tissue. Experimental models have demonstrated that interferon γ drives mitochondrial dysfunction in muscle fibres, creating an oxidative-stress loop that perpetuates inflammation. Interruption of this loop with reactive oxygen species buffering compounds preserved mitochondrial ultrastructure and reduced inflammatory cell infiltrates. Such findings illuminate a mechanistic link between cytokine signalling and tissue injury, suggesting mitochondria-targeted or antioxidant therapies may alleviate both myositis and associated interstitial lung involvement.

Idiopathic Inflammatory Myopathies and Associated Lung Disease publication trend

The graph below shows the total number of articles in idiopathic inflammatory myopathies and associated lung disease across all publications each year (not limited to Nature Index journals).

Technical terms

Idiopathic inflammatory myopathies (IIMs): A group of autoimmune diseases causing chronic inflammation of skeletal muscle.

Antisynthetase syndrome: An IIM subset defined by autoantibodies against aminoacyl-tRNA synthetases, often with lung involvement.

Interstitial lung disease (ILD): A spectrum of lung disorders marked by inflammation and fibrosis of the lung interstitium.

Myositis-specific autoantibodies (MSA): Autoantibodies directed against muscle-related antigens, used to define clinical subgroups.

Interferon γ (IFNγ): A proinflammatory cytokine implicated in immune-mediated tissue damage.

Reactive oxygen species (ROS): Chemically reactive molecules causing oxidative stress and cellular injury.

References

1. IFNγ causes mitochondrial dysfunction and oxidative stress in myositis. Nature Communications (2024).
2. Common and Distinct Clinical Features in Adult Patients with Anti-Aminoacyl-tRNA Synthetase Antibodies: Heterogeneity within the Syndrome. PLOS ONE (2013).
3. Prognostic Factors for Myositis-Associated Interstitial Lung Disease. PLOS ONE (2014).
4. Dermatomyositis With Anti-MDA5 Antibodies: Bioclinical Features, Pathogenesis and Emerging Therapies. Frontiers in Immunology (2021).
5. The EuroMyositis registry: an international collaborative tool to facilitate myositis research. Annals of the Rheumatic Diseases (2017).