Chest
Special FeaturesInterstitial Lung Disease Associated With the Idiopathic Inflammatory Myopathies: What Progress Has Been Made in the Past 35 Years?
Section snippets
Interstitial Lung Disease
ILD encompasses a diverse group of pulmonary disorders also known as diffuse parenchymal lung diseases.5 These diseases are typically classified together because of unifying clinical, physiologic, pathologic, and roentgenographic manifestations.6 Since its description in 1956 by Golden and Bronk7 and an initial effort at classification by Liebow and Carrington in 1969,8 a precise classification system for ILD has continued to evolve as new clinical, histopathologic, and radiographic information
Idiopathic Inflammatory Myopathies
The IIMs, initially defined by Bohan and Peter (Table 1) in 1975,9, 10 encompass a group of disorders in which muscle is targeted in an inflammatory, autoimmune attack that generally leads to muscle weakness. For the purposes of this review, we will not consider the myopathies associated with bacterial, viral, and parasitic diseases; the more uncommon inflammatory myopathies, such as granulomatous myositis or eosinophilic myositis; or inclusion body myositis, as these entities are rarely
The Intersection of ILD and IIM: MA-ILD
It is estimated that among patients diagnosed with PM/DM, 35% to 40% will be afflicted with ILD during the course of their illness, although there is variation in prevalence estimates in the literature and few large-scale cohort studies are available (Table 2).11, 12, 13, 14, 15, 16, 17, 18, 19 Little is known about how MA-ILD affects specific populations, including women, minorities, and people of various ages. Overall, ILD is a major contributor to morbidity and mortality, and once pulmonary
Pathogenesis
There is a great deal yet to be learned regarding the pathogenesis of ILD in the context of myositis. The leading hypothesis is that MA-ILD begins as a cellular inflammatory process that fails to appropriately terminate and progresses to a fibroproliferative condition22 often unresponsive to traditional immunosuppressive therapies. This hypothesis is supported by the longitudinal analysis of several biopsy-proven cases.4, 23 However, the variable progression of MA-ILD over time lends support to
Signs and Symptoms
The majority of patients with MA-ILD will have symptoms common to all interstitial lung diseases, including cough, dyspnea on exertion, decreased exercise tolerance, and fatigue. Clubbing of the digits may be seen, although it is often not apparent early in the disease. Importantly, this is a syndrome with extreme variability in its main features: patients may present with myositis or dermatologic manifestations or lung disease in any combination simultaneously or sequentially. Although the
Diagnosis
Based on the existing literature and our large single-center experience, we present a diagnostic algorithm for ILD. This algorithm can be considered for all patients with PM, DM, and ADM upon presentation (Fig 2).
Serum Biomarkers
The serum muscle enzyme creatine kinase has been examined as a biomarker of IIM disease activity, but its role in MA-ILD has not been studied to date. Other general markers of inflammation, such as the erythrocyte sedimentation rate83 and lactate dehydrogenase,83 have been shown to be elevated in MA-ILD in a single case study. More promising is the mucin-like glycoprotein KL-6, whose elevation in MA-ILD has been demonstrated in several small, prospective studies in Europe and Japan.84, 85, 86
Current Therapeutic Approaches
Despite the common use of steroids and various steroid-sparing agents, no prospectively tested therapeutic regimen for MA-ILD exists at this time. Since the recognition of MA-ILD, corticosteroids, either in oral or IV form, have been regarded as the mainstay of therapy. A number of immune modulating agents have been tested in small studies. The options for therapy are presented below, but it should be noted that the majority of the studies were neither placebo-controlled nor prospective.
In
Conclusion
Since the original reviews describing myositis-associated interstitial lung disease in the mid-1970s, much has changed in the way we view and approach this condition. As case series and cohort studies grow in number, multiple disciplines are contributing to advances in the science of this disease. With this growing body of literature, we are poised to make larger advances in the coming years. Although its effect on morbidity and mortality of those affected, as well as its cost to the health
Acknowledgments
Financial/nonfinancial disclosures: The authors have reported to CHEST that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.
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Funding/Support: This work was supported by funding from the Lisa Sandler Spaeth Fund to S. K. D.
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