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Interstitial lung disease (ILD) is a major complication of the idiopathic interstitial myopathies and is associated with increased mortality.
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Antisynthetase syndrome is a unique subset of patients with myositis with anti-aminoacyl-tRNA antibodies, ILD, mechanic’s hands, fever, and arthritis.
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Anti-melanoma differentiation factor 5 antibodies are associated with rapidly progressive ILD and overall poor prognosis.
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Corticosteroids are first-line therapy for myositis-associated ILD, but addition of
Interstitial Lung Disease in Polymyositis and Dermatomyositis
Section snippets
Key points
Idiopathic inflammatory myopathies
The idiopathic inflammatory myopathies (IIMs) are a diverse group of connective tissue diseases characterized by varying degrees of muscle inflammation and systemic involvement. In adults they include polymyositis (PM), dermatomyositis (DM), and inclusion body myositis (IBM). Criteria for the diagnosis of the IIMs was first proposed by Bohan and Peter1, 2 and included 5 clinical criteria: symmetric proximal muscle weakness, muscle biopsy with evidence of necrosis, serum elevation of the
Antisynthetase syndrome
Antibodies directed against aminoacyl-tRNA synthetase enzymes (ARS antibodies) have collectively come to define a distinct subtype of myositis known as the antisynthetase syndrome (AS). First described in a case series of patients with myositis and ILD,17 AS is now classified by the presence of anti-ARS antibodies and a group of clinical manifestations including myositis, ILD, polyarthritis, Raynaud phenomenon, fever, and mechanic’s hands (see Fig. 1).18 The autoantigen for ARS antibodies are
Anti-melanoma differentiation factor 5
Apart from anti-ARS antibodies, anti-MDA5 antibodies have also been shown to be highly associated with ILD in patients with myositis. These antibodies were originally discovered against a 140-kDa polypeptide in patients with CADM, and thus previously termed anti-CADM-140.33 The autoantigen was later determined to be an RNA-helicase encoded by the MDA5 gene, which plays an important role in the innate immune response to intracellular viral infection.34 Although originally identified in patients
Myositis-associated antibodies
Antibodies to anti-SSA/Ro, specifically the 52-kDA protein complex (anti-Ro52), are the most frequently detected MAA, occurring in 31% to 46% of all patients with PM/DM.6, 8, 14 Anti-Ro52 has been shown to be highly associated with anti-ARS antibodies, especially anti-Jo-1.8, 14, 32, 43, 44 Several studies have demonstrated that anti-Ro52–positive patients with PM/DM have higher rates of ILD, even after correcting for anti-Jo-1 positivity.6, 8, 43 In patients with anti-synthetase syndrome,
Other myositis-specific antibodies
Most other MSAs have not been shown to be associated with increased risk of ILD. Antibodies to signal recognition particle (anti-SRP) are associated with severe necrotizing myopathy with high rates of profound muscle weakness and dysphagia; however, rates of ILD are similar to that of myositis controls.49 Anti-Mi2 antibody is specific to DM and is associated with classic DM skin findings and low rates of ILD.8, 43 Patients with antibodies to transcriptional intermediate factor 1-gamma, TIF1-γ
Pathology
Surgical lung biopsy is not routinely performed in patients with MA-ILD, as it is not necessary to confirm the diagnosis and has limited utility for changing management decisions. Many studies report only a limited sample of biopsy data, and the results are highly variable. Nonspecific interstitial pneumonia (NSIP) appears to be the most common pattern identified in MA-ILD patients.30, 50, 51 Organizing pneumonia (OP) and usual interstitial pneumonia are also frequently reported.19, 25, 50, 51,
Pulmonary function tests
Pulmonary function testing of patients with PM/DM is important both for the diagnosis of ILD and for monitoring disease progression over time. The interpretation of PFTs in patients with myositis has unique challenges, as diaphragmatic weakness can result in changes in FVC and DLCO and intrapatient testing can vary significantly as muscle strength improves with treatment.18 For this reason, concurrent HRCT is needed for the definitive diagnosis of ILD. PFTs in patients with MA-ILD typically
Radiographic manifestations
HRCT is a useful tool in the diagnosis and management of ILD. The computed tomography (CT) findings of patients with PM/DM-associated ILD can be highly variable depending on the severity and acuity of the pulmonary process (Fig. 2). In patients with anti-ARS antibody ILD, the most frequent findings are ground glass opacities (GGOs) and reticulations, although consolidations are also common.55 In fact, patients with PM/DM-associated ILD are much more likely to present with consolidations than
Treatment
There is no standard treatment regimen for the management of MA-ILD and practices vary considerably. Most of the data to support the use of various immunosuppressive agents are based on retrospective reviews and case series, and there are few prospective or randomized controlled trials. Corticosteroids are the mainstay of therapy for myositis-associated ILD, although this is generally based on historical precedent.59 Patients with severe exacerbations or RP-ILD are typically treated with pulse
Clinical course and prognosis
Despite these advances in therapy, the development of ILD is associated with increased mortality in patients with myositis.10, 11 For this reason, it is important to determine which patients with myositis are at risk for developing ILD over the course of their disease. As stated previously, anti-MDA5 antibodies, anti-Jo-1 antibodies, and anti-Ro52 antibodies are all associated with increased risk of ILD in patients with myositis.6, 15 Other studies have found that older age, presence of
Summary
The IIMs, including PM and DM, are autoimmune CTDs with variable degrees of muscle inflammation and systemic involvement. ILD is a common complication of the IIMs and is associated with increased mortality. Many patients with PM/DM have MSA/MAAs that result in distinct clinical phenotypes. Among these MSAs, anti-ARS antibodies and anti-MDA5 antibodies have high rates of ILD. Corticosteroids are the mainstay of treatment, although the addition of other immunosuppressive therapy is typically
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Disclosure Statement: The authors have no financial interests to disclose.