Interstitial lung disease in dermatomyositis and polymyositis: Clinical manifestations and diagnosis

INTRODUCTION — Dermatomyositis (DM) and polymyositis (PM) are classified as idiopathic inflammatory myopathies. Among patients with DM or PM, interstitial lung disease (ILD) is a major cause of morbidity and mortality. A general approach to the evaluation of ILD is provided separately. (See "Approach to the adult with interstitial lung disease: Clinical evaluation" and "Approach to the adult with interstitial lung disease: Diagnostic testing".)

In patients with DM or PM, ILD must be distinguished from other causes of pulmonary disease:

●Infection

●Drug-induced pneumonitis

●Pneumomediastinum

●Respiratory muscle weakness

The clinical manifestations and evaluation of ILD associated with DM and PM will be reviewed here. The treatment of respiratory diseases in DM and PM and the clinical manifestations and diagnosis of myositis are discussed separately. (See "Interstitial lung disease in dermatomyositis and polymyositis: Treatment" and "Juvenile dermatomyositis and other idiopathic inflammatory myopathies: Epidemiology, pathogenesis, and clinical manifestations" and "Clinical manifestations of dermatomyositis and polymyositis in adults".)

EPIDEMIOLOGY — The prevalence of interstitial lung disease (ILD) varies widely (from 20 to 80 percent) among case series of patients with polymyositis (PM) and dermatomyositis (DM) [1-4]. This variability is related to several factors, including the methods used to identify ILD (eg, lower rates if high-resolution computed tomography [HRCT] is not used), the proportions of the different subsets of myositis (eg, amyopathic DM, presence of antisynthetase antibodies, presence of melanoma differentiation-associated gene 5 [MDA-5] antibodies), and the presence of an underlying malignancy [1-3,5-12].

Certain subsets of DM and PM appear to be associated with different frequencies of ILD. As examples:

●In a retrospective study of 62 patients with inflammatory myopathies, ILD was diagnosed in approximately half of patients with PM or DM, and almost all of patients with clinically amyopathic dermatomyositis [12].

●In another retrospective series of 90 patients with DM or PM and serum anti-Jo-1 antibodies (an antisynthetase antibody), ILD was identified in 86 percent [13]. (See 'Laboratory testing' below.)

●ILD is less common in patients with inflammatory myositis associated with malignancy [11,14,15]. (See "Malignancy in dermatomyositis and polymyositis", section on 'Clinical risk factors'.)

One study evaluating over 1200 patients with inflammatory myopathies found an association between HLA alleles belonging to ancestral haplotype 8.1 (HLA B*08, HLA C*07, HLA DRB1*03) and the development of ILD [16]. Ancestral haplotype 8.1 is present in approximately 6 percent of the European population, but it can also be found in 1 percent of Black or Hispanic Americans. The ILD association is mediated primarily by the propensity for individuals with this haplotype to develop anti-Jo-1 antibodies [16,17].

HISTOPATHOLOGY — The histopathologic appearance of ILD in DM and PM reflects the patterns of lung pathology associated with the idiopathic interstitial pneumonias (table 1). (See "Idiopathic interstitial pneumonias: Classification and pathology".)

The histologic patterns of ILD that have been observed in biopsy and autopsy studies of patients with PM and DM include [15,18,19]:

●Nonspecific interstitial pneumonia (NSIP) (see "Causes, clinical manifestations, evaluation, and diagnosis of nonspecific interstitial pneumonia", section on 'Histopathology and interpretation')

●Usual interstitial pneumonia (UIP) (see "Idiopathic interstitial pneumonias: Classification and pathology", section on 'Usual interstitial pneumonia')

●Organizing pneumonia (OP), previously known as bronchiolitis obliterans with organizing pneumonia (BOOP) (see "Cryptogenic organizing pneumonia" and "Cryptogenic organizing pneumonia", section on 'Histopathologic diagnosis of organizing pneumonia')

●Diffuse alveolar damage (DAD), seen in patients with acute interstitial pneumonia (AIP) (see "Acute interstitial pneumonia (Hamman-Rich syndrome)" and "Acute interstitial pneumonia (Hamman-Rich syndrome)", section on 'Pathology')

These patterns are indistinguishable histopathologically from the idiopathic interstitial pneumonias and the forms of ILD that occur in other systemic rheumatic diseases such as systemic lupus erythematosus, rheumatoid arthritis, and systemic sclerosis. Details related to the specific histopathologic features of these subtypes of ILD are discussed separately. (See "Idiopathic interstitial pneumonias: Classification and pathology".)

Lung biopsy is typically not necessary for the diagnosis or management of ILD in PM/DM, thus data are limited on histopathologic patterns. NSIP is the most common histopathologic pattern of ILD in small series of patients with DM and PM [15,19-21]. The relative frequency of the different histopathologic patterns was evaluated in a series of 22 patients with DM or PM who underwent lung biopsy [15]. NSIP was by far the most common finding (18 patients), followed by DAD (two patients), UIP (one patient), and OP (one patient). In a separate series of patients with anti-aminoacyl-tRNA synthetase antibodies (anti-Jo-1) who underwent lung biopsy, four had NSIP and four had OP [21]. Additionally, NSIP and OP can be present concomitantly [22,23].

CLINICAL FEATURES — Patients with interstitial lung disease (ILD) typically complain of dyspnea and a nonproductive cough, although some patients are asymptomatic and ILD is suspected because of an abnormal lung exam or an abnormal chest radiograph [24,25]. Occasionally, dermatomyositis (DM) or polymyositis (PM)-related ILD presents with rapid onset and progression, particularly in patients with amyopathic dermatomyositis [26]. The respiratory manifestations of ILD in patients with DM or PM parallel those described for patients with the idiopathic interstitial pneumonias, although the muscle weakness associated with these myopathies may influence the degree of dyspnea and risk of aspiration. (See "Approach to the adult with interstitial lung disease: Clinical evaluation" and 'Respiratory muscle weakness' below.)

The temporal relationship between the onset of ILD and myositis is variable [27]. ILD can precede the diagnosis of overt myositis by months or years, appear simultaneously with myositis, or develop after the muscle disease, usually within the first few months from the onset of weakness. In some patients, ILD appears in the absence of any muscle symptoms (clinically amyopathic).

The lung examination may be clear on chest auscultation or reveal dry bibasilar crackles. In patients with ILD who have not yet been diagnosed with DM or PM, the presence of these disorders may be suspected in those who also have proximal muscle weakness, abnormal nailfold capillary microscopy, or unexplained rashes. However, patients may appear clinically amyopathic and rashes may be more difficult to discern in patients who are more darkly pigmented. The other signs and symptoms of PM and DM are described separately. (See "Clinical manifestations of dermatomyositis and polymyositis in adults", section on 'Clinical manifestations'.)

The following subtypes of PM and DM warrant particular attention:

●Antisynthetase syndrome – A subset of patients may present with a constellation of clinical features, including myositis, ILD, nonerosive arthritis, "mechanic's hands" (picture 1), “hiker’s feet,” fever, and Raynaud phenomenon, called the "antisynthetase syndrome" [2,5,27-29]. This syndrome is supported by the presence of two or more of the aforementioned clinical features as well as autoantibodies to an aminoacyl-transfer RNA synthetase [2,28,30-33]. (See 'Laboratory testing' below and "Overview of and approach to the idiopathic inflammatory myopathies", section on 'Myositis-specific autoantibodies'.)

●Amyopathic dermatomyositis – Clinically amyopathic dermatomyositis (CADM), which is characterized by the cutaneous findings of DM (eg, Gottron papules of the extensor aspects of the metacarpophalangeal (MCP) and interphalangeal (IP) joints, facial heliotrope rash, and periungual erythema) with no muscle involvement or only minimal weakness, affects 20 percent of patients with DM, but may be more common with specific autoantibodies like PL12 or melanoma differentiation-associated gene 5 (MDA-5) (picture 2 and picture 3 and picture 4 and picture 5) [26,34,35]. (See "Clinical manifestations of dermatomyositis and polymyositis in adults", section on 'Skin findings in dermatomyositis' and "Cutaneous dermatomyositis in adults: Overview and initial management".)

●Anti-MDA-5 antibodies – MDA-5 antibodies (previously referred to as anti-CADM-140 antibodies) can be associated with a rapidly progressive course of ILD and vasculopathy affecting the skin [36]. Anti-MDA-5 positivity has a similar frequency among patients with CADM and classic DM [35]. Cutaneous findings include digital and palmar papules and ulcerations (picture 6), alopecia, and oral ulcers. Anti-MDA-5 disease can be present in the absence of muscle enzyme abnormalities or other autoantibodies and portends a worse prognosis and a greater likelihood of rapidly progressive ILD [37-39]. (See "Clinical manifestations of dermatomyositis and polymyositis in adults", section on 'MDA5-associated dermatomyositis'.)

●Overlap syndromes – DM and PM may overlap with features of other systemic rheumatic diseases, including systemic sclerosis (SSc), systemic lupus erythematosus (SLE), mixed connective tissue disease, rheumatoid arthritis, and Sjögren’s syndrome. The myopathy associated with the other systemic rheumatic diseases can vary from clinically insignificant (with minimal muscle enzyme elevations and minimal inflammatory changes on muscle biopsy) to severe myopathy, in which DM or PM dominates the clinical picture [40]. Patients with anti-PM-Scl and anti-Ku antibodies may have features of both PM/DM and SSc, including sclerodactyly, Raynaud phenomenon, and interstitial lung disease [41]. (See "Clinical manifestations of dermatomyositis and polymyositis in adults".)

EVALUATION — The evaluation of potential dermatomyositis (DM) or polymyositis (PM) associated interstitial lung disease (ILD) usually begins when a patient with known DM or PM develops clinical or radiographic features of ILD or a patient with suspected ILD is found to have clinical features of DM or PM. The evaluation is designed to characterize the underlying rheumatic disease, to identify the type and severity of ILD, and to exclude other explanations for the patient's symptoms and signs (eg, infection, drug-induced lung toxicity, respiratory muscle weakness, myocardial dysfunction). The evaluation typically includes laboratory testing, high-resolution computed tomography (HRCT) , pulmonary function testing, and sometimes bronchoalveolar lavage. Rarely patients may need a lung biopsy. (See "Approach to the adult with interstitial lung disease: Diagnostic testing".)

Laboratory testing — When ILD is suspected, initial laboratory testing should include a complete blood count and differential, hepatic and renal function tests, ferritin [42], and, if pulmonary vascular congestion is suspected, a brain natriuretic peptide (BNP) or N-terminal-proBNP. (See "Approach to the adult with interstitial lung disease: Diagnostic testing", section on 'Laboratory tests'.)

The main role of additional laboratory testing is to establish the diagnosis of the underlying inflammatory myopathy. For patients who do not have a confirmed diagnosis of DM or PM, we usually obtain serum muscle enzymes (eg, creatine kinase and aldolase), an antinuclear antibody (ANA) test, and an anti-Jo-1 antibody (anti-histidyl-transfer [t] RNA synthetase). If the anti-Jo-1 antibody is negative, we obtain a panel of the other myositis-specific autoantibodies, such as those directed against other aminoacyl-tRNA synthetases (eg, anti-PL-7 [anti-threonyl-tRNA synthetase], anti-PL-12 [anti-alanyl-tRNA synthetase]) and MDA-5. Of note, a negative ANA with cytoplasmic staining should raise suspicion for the presence of anti-synthetase autoantibodies since aminoacyl-tRNA synthetase enzymes reside in the cell cytoplasm. (See "Measurement and clinical significance of antinuclear antibodies", section on 'Cytoplasmic fine speckled'.)

If the ANA test is positive and an overlap syndrome is suspected, we also test for other specific autoantibodies such as anti-dsDNA, anti-Sm, anti-Ro/SSA, anti-La/SSB, anti-U1 ribonucleoprotein (RNP), anti-topoisomerase (anti-Scl-70), anti-PM-Scl, and anti-Ku. The laboratory evaluation of patients with DM or PM is discussed separately. (See "Clinical manifestations of dermatomyositis and polymyositis in adults", section on 'Myositis-associated autoantibodies'.)

The presence of individual myositis antibodies may play a role in determining the likelihood of the various disease manifestations in a given patient, although this is still an area of investigation [43]. The presence of antisynthetase antibodies appears to be associated with a greater likelihood of ILD [4,13,15,44-46]. As an example, in a series of 90 patients with anti-Jo-1 antibodies, the incidence of ILD approached 90 percent [13]. In a separate series of 95 patients with antisynthetase syndrome, ILD was present in 68 percent of those with anti-Jo-1 antibodies and 90 percent of those with anti-PL-7 or anti-PL-12 antibodies [44]. (See "Clinical manifestations of dermatomyositis and polymyositis in adults", section on 'Myositis-associated autoantibodies'.)

Among patients with DM or clinically amyopathic dermatomyositis (CADM), the antimelanoma differentiation-associated gene 5 (MDA-5) antibody (also known as anti-CADM-140 antibodies) may portend a more aggressive form of ILD and a worse prognosis [47]. (See 'Clinical features' above.)

Other serum markers have been used to assess prognosis and guide disease management, but their clinical role is not established. These include HLA class II associations, serum biomarkers such as Kerbs von Lungren factor (KL-6), surfactant protein D (SP-D), ferritin, and serum chemokine levels (eg, CXCL9 and CXCL10) [13,42,48-50].

Imaging — A conventional chest radiograph is often obtained when a patient with DM or PM has a cough or dyspnea, crackles on lung exam, abnormal pulmonary function tests, or positive tests for anti-synthetase antibodies, but high-resolution computed tomography (HRCT) is preferred due to the greater sensitivity and ability to characterize the extent and pattern of interstitial changes [32]. We obtain a HRCT to screen for ILD in all patients with antisynthetase or melanoma differentiation-associated gene 5 (MDA-5) antibodies. In addition, we typically obtain a computed tomography (CT) scan of the abdomen and pelvis if there is clinical suspicion of lung malignancy.

The most common findings on chest radiography are diffuse reticular and nodular opacities, predominantly at the lung bases. Patients with fulminant disease may have patchy, "ground glass" opacities (image 1). Pleural effusions are not seen [27].

HRCT is performed in the supine and prone positions if it is unclear whether opacities in dependent areas are due to gravity-induced atelectasis. Radiographic patterns include patchy ground glass opacification, basilar consolidation, septal thickening, honeycombing, and irregular linear opacities (image 2 and image 3) [24,51]. (See 'Histopathology' above and "High resolution computed tomography of the lungs", section on 'Ground-glass opacification'.)

Sometimes the HRCT findings correlate with the underlying histopathology, and more than one pattern can be present. As examples:

●Ground glass opacification suggests cellular nonspecific interstitial pneumonia (NSIP)

●Predominantly reticular changes suggest fibrotic NSIP or usual interstitial pneumonia (UIP)

●Honeycombing suggests UIP

●Patchy consolidative opacities are suggestive of organizing pneumonia (OP, previously called bronchiolitis obliterans organizing pneumonia [BOOP]) or infection

HRCT has the advantage of being noninvasive and repeatable, permitting an assessment of response to therapy. In addition, sampling error is unlikely because the entire lung is imaged, whereas sampling error may be a problem with lung biopsy [52-55]. Several patterns have been described that can help distinguish connective tissue disease (CTD)-associated ILD from idiopathic pulmonary fibrosis (IPF) including anterior upper lobe honeycombing, exuberant basilar honeycombing, and the straight-edge sign (fairly sharp demarcation between fibrotic changes and normal lung orthogonal to the lateral chest wall) [56].

Pulmonary function tests — Pulmonary function tests (PFTs) are used to help distinguish the cause of dyspnea (eg, ILD versus respiratory muscle weakness) and to assess the severity of respiratory impairment [57]. (See "Overview of pulmonary function testing in adults" and "Diffusing capacity for carbon monoxide".)

In patients with ILD, PFTs typically demonstrate a restrictive pattern (low forced vital capacity [FVC] and low total lung capacity [TLC]) and a diminished diffusing capacity. Patients with early interstitial lung disease may have normal or near-normal PFTs, except for a mild decrease in oxygen saturation with six-minute walk testing.

In contrast, patients with respiratory muscle weakness without ILD may have a restrictive pattern but will typically have a normal diffusing capacity and clear lung fields on HRCT. (See 'Respiratory muscle weakness' below.)

Bronchoscopy — Bronchoscopy with bronchoalveolar lavage can help to exclude other causes of diffuse pulmonary parenchymal opacities such as infection and alveolar hemorrhage. This is particularly important in patients who present with a worsening of pulmonary function after treatment with immunosuppressive drugs or rapid deterioration in lung function. (See "Role of bronchoalveolar lavage in diagnosis of interstitial lung disease".)

DIAGNOSIS

Diagnosis of ILD in patients with DM or PM — In patients with known dermatomyositis (DM) or polymyositis (PM), the diagnosis of interstitial lung disease (ILD) is usually based on the combination of clinical presentation, laboratory tests, high-resolution computed tomography (HRCT) appearance, and pulmonary function test (PFT) results, as described above. (See 'Evaluation' above.)

While HRCT is the most important test for determining the presence and type of ILD, other studies (eg, laboratory and pulmonary function tests) help to identify other causes of ILD and characterize the degree to which ILD explains the patient's symptoms. As examples for patients with DM or PM:

●Increased peripheral blood eosinophils favor drug-induced pneumonitis

●A positive anti-Jo-1, or other antisynthetase antibody, increases the likelihood of ILD due to DM or PM

●PFTs showing proportionately more restriction than gas transfer abnormality suggest a greater contribution of respiratory muscle weakness than ILD to the person's dyspnea

●A disproportionately low DLCO relative to lung volume may suggest pulmonary hypertension

Determining the type of ILD — The types of ILD follow the histopathology of the various idiopathic interstitial pneumonias such as nonspecific interstitial pneumonia (most common), usual interstitial pneumonia (UIP), organizing pneumonia (OP), or acute interstitial pneumonia (AIP) (table 1). In general, the HRCT appearance is used to determine the type of ILD. Bronchoalveolar lavage (BAL) findings are not adequate to differentiate among the histopathologic types of ILD. A lung biopsy, while not indicated for determination of the type of ILD, may be warranted to rule out an alternative process such as a malignancy. (See 'Histopathology' above and 'Imaging' above and 'Bronchoscopy' above.)

Atypical or rapidly progressive ILD — When the clinical course or imaging studies are atypical (eg, associated with fever, rapidly progressive, flaring during immunosuppressive therapy), bronchoscopy with BAL is typically indicated to exclude infection or drug toxicity. Acute interstitial pneumonitis can be the presenting type of ILD in patients with DM or PM but requires exclusion of other causes of diffuse alveolar damage (DAD). (See "Approach to the adult with interstitial lung disease: Diagnostic testing", section on 'Role of bronchoalveolar lavage' and "Role of bronchoalveolar lavage in diagnosis of interstitial lung disease" and "Role of lung biopsy in the diagnosis of interstitial lung disease" and "Acute interstitial pneumonia (Hamman-Rich syndrome)".)

Diagnosis of DM or PM in patients with ILD — Occasionally, ILD may be the initial manifestation of DM or PM. In these patients, the diagnosis of underlying DM or PM is based on the presence of clinical findings such as cutaneous manifestations (eg, Gottron papules (picture 2 and picture 3), "mechanic's hands" (picture 1)) or “hiker’s feet”, symmetric proximal muscle weakness, nail bed capillary microscopic changes, and/or laboratory testing showing consistent serology. Muscle biopsy or thigh MRI may help to confirm the diagnosis. The diagnosis of PM or DM and the evaluation of ILD in general are discussed separately. (See 'Clinical features' above and 'Laboratory testing' above and "Approach to the adult with interstitial lung disease: Diagnostic testing".)

In patients with cutaneous findings suggestive of DM but without evidence of muscle weakness, the diagnosis of clinically amyopathic dermatomyositis should be considered as these patients have a high frequency of developing ILD. The diagnosis of amyopathic dermatomyositis is discussed separately.

DIFFERENTIAL DIAGNOSIS — Complications of dermatomyositis (DM) and polymyositis (PM) as well as the immunosuppressive therapy used to treat myositis or interstitial lung disease (ILD) may cause dyspnea and cough independent of or in addition to ILD. We present several conditions below that should be considered in the initial differential diagnosis of ILD as well as in patients who develop clinical worsening or do not respond to treatment.

Cardiac causes — Cardiac involvement due to DM or PM is rarely a cause of clinically apparent heart failure but should also be considered in the differential diagnosis of dyspnea. Similarly, pulmonary hypertension due to a primary vasculopathy or thromboembolic disease can present with significant dyspnea on exertion as well as a low diffusing capacity for carbon monoxide (DLCO). (See "Clinical manifestations of dermatomyositis and polymyositis in adults", section on 'Cardiac involvement' and "Clinical features and diagnosis of pulmonary hypertension of unclear etiology in adults".)

Infection — Lung infection is a common and potentially lethal complication of DM and PM. Several factors may contribute to this problem [5,28,58,59]:

●Respiratory muscle weakness can lead to a weak cough, atelectasis, and consequently, a predisposition to bacterial pneumonia. (See "Respiratory muscle weakness due to neuromuscular disease: Clinical manifestations and evaluation".)

●Oropharyngeal and esophageal dysfunction may increase the risk of aspiration pneumonia [60]. (See "Aspiration pneumonia in adults".)

●Lymphopenia affecting both T and B cells is a frequent finding in DM, even before the initiation of immunosuppressive treatment [61]. In one series, patients with lymphopenia had an increased frequency of pneumonia compared with those with normal cell counts.

●Therapy with high-dose glucocorticoids and other immunosuppressive agents increases the risk of opportunistic infections, including Pneumocystis jirovecii (previously called P. carinii), other fungi, and Nocardia [31,61-64].

Features that suggest infection include a rapid worsening of respiratory symptoms and new radiographic abnormalities, a productive cough, fever, and leukocytosis. Evaluation generally includes blood cultures, sputum smear, and culture for bacteria, fungi, and mycobacteria. Induced sputum can be obtained for P. jirovecii immunofluorescence. If initial studies are unrevealing, bronchoscopy with bronchoalveolar lavage (BAL) may be needed to identify the infecting organism. Often, empiric antibiotic therapy is initiated while waiting for the results of these studies. (See "Approach to the immunocompromised patient with fever and pulmonary infiltrates".)

Aspiration — Patients with swallowing difficulties due to DM or PM are at increased risk for recurrent aspiration and associated lung injury. Typically, recurrent aspiration leads to focal scarring, most commonly in the lower lobes. Centrilobular fibrosis, nodules, and the "tree-in-bud" pattern are HRCT features of recurrent aspiration. (See "High resolution computed tomography of the lungs", section on 'Centrilobular nodules'.)

Drug-induced pneumonitis — In patients with inflammatory myopathy, drug-induced ILD needs to be differentiated from ILD associated with the underlying myopathy. Methotrexate and tumor necrosis factor (TNF) inhibitors have been associated with the development of drug-induced pneumonitis. One of the key diagnostic steps is assessing the response to drug withdrawal.

●Methotrexate – Methotrexate-induced pneumonitis can occur at any dose and at any time during a patient's use of the medication, although most cases occur within the first year. Discontinuation of the drug usually leads to rapid improvement. Methotrexate pneumonitis is discussed in detail separately. (See "Methotrexate-induced lung injury" and "Drug-induced lung disease in rheumatoid arthritis".)

The following issues deserve emphasis in patients with DM and PM:

•The clinical manifestations are similar to those seen with ILD or infection. One exception is that basilar predominance of opacities on chest radiograph is unusual in methotrexate pneumonitis and is common in ILD associated with DM and PM. (See 'Clinical features' above and 'Imaging' above.)

•Lung biopsy does not distinguish between methotrexate pneumonitis and an ILD caused by the underlying myositis [62]. Infection, which is another major consideration in the differential diagnosis, can usually be excluded by bronchoalveolar lavage.

•Peripheral eosinophilia, when present, suggests methotrexate-induced pneumonitis rather than ILD due to the underlying myositis. However, this finding is nonspecific and its sensitivity is unknown, particularly in patients treated with glucocorticoids.

●TNF inhibitors – TNF inhibitors are sometimes used to manage arthritis associated with DM/PM and are potential causes of drug-associated pneumonitis [65]. (See "Tumor necrosis factor-alpha inhibitors: An overview of adverse effects", section on 'Pulmonary disease'.)

Alveolar hemorrhage — Rare cases of diffuse alveolar hemorrhage (DAH) complicating DM and PM have been reported [66-68]. Possibly, these patients developed DAH as a complication of acute interstitial pneumonitis (the clinical presentation of idiopathic diffuse alveolar damage). The diagnosis of DAH is discussed separately. (See "The diffuse alveolar hemorrhage syndromes".)

OTHER CAUSES OF DYSPNEA IN DM AND PM — Spontaneous pneumomediastinum, respiratory muscle weakness, pulmonary hypertension, and venous thromboembolism are complications of dermatomyositis (DM) and polymyositis (PM) that should be assessed in patients with DM or PM who present with dyspnea or chest discomfort.

Spontaneous pneumomediastinum — Spontaneous pneumomediastinum is a rare complication of inflammatory myositis and occurs more commonly in DM than PM (image 4) [69,70]. Virtually all patients with DM or PM who develop a pneumomediastinum have interstitial lung disease (ILD), and the pneumomediastinum is occasionally the presenting clinical manifestation of ILD. The management of spontaneous pneumomediastinum in DM and PM is discussed separately. (See "Interstitial lung disease in dermatomyositis and polymyositis: Treatment", section on 'Spontaneous pneumomediastinum'.)

Approximately one-half of patients with DM who develop a pneumomediastinum have amyopathic DM, and many have antibodies to MDA-5 [69,71]. (See "Clinical manifestations of dermatomyositis and polymyositis in adults", section on 'Interstitial lung disease'.)

It is thought that the main cause of pneumomediastinum in patients with DM and PM is architectural distortion of lung tissue due to ILD. Another possible explanation is that vasculopathic lesions within the respiratory tract may result in bronchial or alveolar wall injury and subsequent air leakage. This theory is based upon the association of pneumomediastinum with the cutaneous vasculopathic lesions that can be seen in DM and the finding of endobronchial areas of subepithelial necrosis [72].

●Clinical features – The typical presentation of pneumomediastinum is the acute onset of retrosternal chest pain with neck and face swelling due to subcutaneous emphysema, which may be detectable as crepitus with palpation over areas of swelling. Some patients also complain of dyspnea [73]. In addition, patients often have evidence of a flare of their underlying DM or PM with fever, worsening skin manifestations, Raynaud phenomenon, or weight loss.

●Imaging – A pneumomediastinum is often visible on a plain chest radiograph as a narrow streak of air along the descending aorta, left hilum, and left cardiac shadow. This streak may extend up into the neck. When mediastinal air outlines the superior surface of the diaphragm and separates it from the heart, the finding is known as the "continuous diaphragm sign." Subcutaneous air is often seen in the neck.

A high-resolution computed tomography (HRCT) scan is usually performed to delineate the extent and characteristics of the pneumomediastinum. (See 'Imaging' above.)

Respiratory muscle weakness — Respiratory muscle weakness can complicate both DM and PM and must be considered in the differential diagnosis for patients with worsening dyspnea without worsening radiographic opacities. Typical inflammatory myopathic changes have been documented in the diaphragm, intercostal muscles, and accessory muscles [5]. The severity of impairment ranges from asymptomatic to respiratory failure.

Estimates of prevalence have varied from 4 to 78 percent [5,6,74,75]. This variation is largely dependent on the method used to assess respiratory involvement (eg, symptom report, pulmonary function tests, or transdiaphragmatic pressures) as respiratory muscle weakness may be subclinical in patients whose activity level is reduced by skeletal muscle weakness. As an example, one study evaluated diaphragm strength in 12 patients with inflammatory myopathy [74]. Static inspiratory and expiratory pressures, as well as mouth and transdiaphragmatic pressure responses to bilateral phrenic nerve stimulation, were assessed. Diaphragm weakness was noted in 78 percent.

Respiratory muscle weakness is more likely to be seen in patients with more profound skeletal muscle weakness, so the characteristics of the population studied may also affect the reported prevalence.

●Clinical presentation – Symptomatic patients may complain of dyspnea, orthopnea, insomnia, daytime sleepiness, and impaired cognition. Symptoms and signs of bulbar muscle weakness (eg, difficulty swallowing, dysarthria, nasal speech) may also be present. (See "Respiratory muscle weakness due to neuromuscular disease: Clinical manifestations and evaluation", section on 'Clinical manifestations'.)

Hypercapnic respiratory failure caused by diaphragmatic muscle weakness has been reported in PM and DM, rarely as the presenting manifestation [8-10].

●Pulmonary function testing – Objective physiologic testing is necessary to confirm and monitor respiratory muscle weakness and usually includes measurement of forced vital capacity (FVC) sitting and supine, maximum voluntary ventilation (MVV), maximal inspiratory pressure (MIP), maximum expiratory pressure (MEP), and gas transfer. A decrease in FVC of >10 percent from sitting to supine suggests respiratory muscle weakness. The interpretation of these tests is discussed separately. (See "Respiratory muscle weakness due to neuromuscular disease: Clinical manifestations and evaluation", section on 'Diagnostic evaluation'.)

When respiratory muscle weakness is identified, the adequacy of oxygenation should be assessed when the patient is at rest, during exertion, and during sleep.

The arterial carbon dioxide tension (PaCO₂) should be assessed in the following situations [8]:

•Complaint of daytime sleepiness

•Maximal inspiratory and expiratory pressures are less than 30 percent of normal

•FVC is less than 55 percent of predicted

●Management – The treatment of respiratory muscle weakness in DM and PM follows the regimen used for skeletal myositis and is discussed separately. (See "Initial treatment of dermatomyositis and polymyositis in adults", section on 'Initial therapy'.)

Supportive care for patients with respiratory muscle weakness includes supplemental oxygen, noninvasive ventilation (NIV), nocturnal BPAP, and cough assistance. The decisions about when and where to initiate NIV and cough assistance measures are discussed separately. (See "Respiratory muscle weakness due to neuromuscular disease: Management" and "Noninvasive ventilation in adults with chronic respiratory failure from neuromuscular and chest wall diseases: Practical aspects of initiation" and "Noninvasive ventilation in adults with acute respiratory failure: Benefits and contraindications".)

Pulmonary hypertension — Pulmonary hypertension (group 3) can develop as a consequence of severe ILD in patients with DM or PM [76-79]. In a series of 203 consecutive patients with antisynthetase syndrome, pulmonary hypertension was suggested by transthoracic echocardiogram in 47 and confirmed in 16 of the 21 who underwent right heart catheterization [76]. ILD was present in all of the confirmed cases, although the severity of pulmonary hypertension was thought to suggest concomitant pulmonary vasculopathy in 13 patients and thromboembolic disease in one.

Thromboembolic disease — The risk of venous thromboembolism (VTE) is increased among patients with DM or PM [80,81]. The evaluation and diagnosis of VTE are discussed separately. (See "Clinical presentation, evaluation, and diagnosis of the nonpregnant adult with suspected acute pulmonary embolism".)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Dermatomyositis and polymyositis".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5^th to 6^th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10^th to 12^th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

●Beyond the Basics topics (see "Patient education: Polymyositis, dermatomyositis, and other forms of idiopathic inflammatory myopathy (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS

●ILD occurs in approximately 60 to 80 percent of patients with dermatomyositis (DM) or polymyositis (PM); it may be chronic and slowly progressive or acute and rapidly progressive. (See 'Epidemiology' above.)

●Several histologic patterns of ILD are associated with DM and PM: nonspecific interstitial pneumonia (NSIP), usual interstitial pneumonia (UIP), organizing pneumonia (OP, also known as bronchiolitis obliterans with organizing pneumonia [BOOP]), and acute interstitial pneumonia (AIP, also known as diffuse alveolar damage [DAD]). (See 'Histopathology' above.)

●Patients with DM or PM-associated ILD typically complain of dyspnea and a nonproductive cough, although some patients are asymptomatic, and ILD is suspected because of an abnormal lung exam or an abnormal chest radiograph. (See 'Clinical features' above.)

●Certain subtypes of PM and DM warrant particular attention as they are more likely to manifest ILD or to have more severe disease. These subtypes include patients with the antisynthetase syndrome (associated with "mechanics hands"), antimelanoma differentiation-associated gene 5 (MDA-5) antibodies, which are associated with distinct cutaneous findings (eg, palmar papules and ulcerating lesions (picture 6)), and the overlap syndromes associated with features of other systemic rheumatic diseases in addition to DM or PM. (See 'Clinical features' above.)

●Initial laboratory testing typically includes a complete blood count and differential, hepatic and renal function tests, and a brain natriuretic peptide (BNP) or N-terminal-proBNP. If the diagnosis of DM or PM has not been confirmed, we usually obtain serum muscle enzymes (eg, creatine kinase and aldolase), an antinuclear antibody test, and an anti-Jo-1 antibody. Additional testing (eg, other antisynthetase antibodies, anti-antimelanoma differentiation-associated gene 5 [MDA-5] antibodies, testing for an overlap syndrome) is based on the clinical examination and results of the initial tests. (See 'Clinical features' above and 'Laboratory testing' above.)

●High-resolution computed tomography (HRCT) is the preferred imaging test due to its greater sensitivity and ability to characterize the extent and pattern of interstitial changes. Radiographic patterns reflect the underlying pathology and include ground glass opacification, peripheral or basal consolidation, septal thickening, honeycombing, and irregular linear opacities, with patchy ground glass opacities and septal thickening being most common (image 2). (See 'Imaging' above.)

●The diagnosis of ILD in patients with known DM and PM can usually be established based on the clinical presentation, chest imaging studies (ie, HRCT), and pulmonary function tests. Lung biopsy is usually not necessary. However, when the clinical course or imaging studies are atypical (eg, associated with fever, rapidly progressive, developing during immunosuppressive therapy), bronchoscopy with bronchoalveolar lavage (BAL) is typically performed to exclude infection or drug toxicity. If the diagnosis remains in doubt, a lung biopsy may be indicated. (See 'Diagnosis of ILD in patients with DM or PM' above.)

●ILD may be the initial manifestation of DM or PM. In these patients, the diagnosis of underlying DM or PM is based on the presence of clinical findings such as cutaneous manifestations (eg, Gottron papules (picture 3), "mechanic's hands" (picture 1)), symmetric proximal muscle weakness, nail bed capillary microscopic changes, and/or laboratory testing. Muscle biopsy or thigh MRI may be needed to confirm the diagnosis. (See 'Diagnosis of DM or PM in patients with ILD' above.)

●The differential diagnosis of ILD in patients with DM or PM includes heart failure, infection, recurrent aspiration, drug-induced pneumonitis), pulmonary hypertension, and, rarely, alveolar hemorrhage. Any drug suspected of causing pneumonitis should be discontinued and the response to drug withdrawal assessed. (See 'Differential diagnosis' above.)

●Additional etiologies of deteriorating pulmonary status that should be assessed in patients with DM or PM include spontaneous pneumomediastinum, respiratory muscle weakness, pulmonary hypertension, and venous thromboembolism. (See 'Other causes of dyspnea in DM and PM' above.)

●Treatment of ILD in patients with DM or PM is discussed separately. (See "Interstitial lung disease in dermatomyositis and polymyositis: Treatment".)

ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Marc Miller, MD, who contributed to earlier versions of this topic review.