INTRODUCTION — Dermatomyositis (DM) and polymyositis (PM) are classified as idiopathic inflammatory myopathies [1-3]. Both disorders, as defined clinically, have prevalence rates estimated at approximately one per 100,000 in the general population. There is a female to male predominance of about 2:1. The peak incidence in adults occurs between the ages of 40 and 50, but individuals of any age may be affected [4,5].

The prevalence of the many clinical and serologic features of DM and PM varies widely among affected individuals, depending upon the patient's immunogenetic profile and presumably a host of potential environmental triggers [6,7].

The clinical manifestations and diagnosis of DM and PM in adults will be reviewed here. Treatment approaches to these diseases and of the related disorders that occur in children (known as juvenile DM and PM) are discussed separately. (See "Initial treatment of dermatomyositis and polymyositis in adults" and "Treatment of recurrent and resistant dermatomyositis and polymyositis in adults" and "Pathogenesis and clinical manifestations of juvenile dermatomyositis and polymyositis".)

DIFFERENCES BETWEEN DM AND PM — Although DM and PM share the clinical feature of muscle weakness, there are both clinical and pathogenetic differences between these disorders:

• DM is associated with a variety of characteristic skin manifestations, including Gottron's sign, the shawl sign, the heliotrope rash, and a generalized erythroderma. (See 'Skin findings' below.)

• DM is more likely to be associated with cancer. (See "Malignancy in dermatomyositis and polymyositis".)

• DM is characterized by immune complex deposition in the vessels and is considered to be in part a complement-mediated vasculopathy. In contrast, PM appears to reflect direct T cell-mediated muscle injury. (See 'Immunopathogenesis' below.)

CLASSIFICATION CRITERIA — Several sets of classification criteria have been developed for DM and PM.

Bohan and Peter criteria — The original Bohan and Peter criteria, formulated in 1975, included the following features [3]:

• Symmetric proximal muscle weakness
• Typical rash of DM, which was the only distinguishing feature between DM and PM
• Elevated serum muscle enzymes
• Myopathic changes on electromyography
• Characteristic muscle biopsy abnormalities and the absence of histopathologic signs of other myopathies

These criteria were formulated before testing for myositis-specific autoantibodies was available. In addition, inclusion body myositis, which shares clinical features with DM and PM, was not recognized until the 1980s. (See 'Autoantibodies' below and 'Differential diagnosis' below.)

As a result, patients who were classified as DM or PM according to these criteria may have some other disorder. This was illustrated in a retrospective review of 160 patients with "myositis" who were seen between 1977 and 1998 [8]. When the patients were reevaluated one year after presentation, 59 (35 percent) were classified more precisely as DM and only 4 (2 percent) were categorized as PM (compared to nine with this diagnosis at presentation, with the other five having inclusion body myositis) [8]. At least 65 patients (40 percent) were recognized to have a connective tissue disorder that was often not identifiable at the time of the initial myositis diagnosis.

The main reason so few patients were classified as PM in this study was that the investigators required a strict histologic definition of PM, rather than myositis specific autoantibodies or inclusion body myositis.

Similar findings were noted in another report [9]. In this review of 100 patients with idiopathic inflammatory myopathy, 45 percent were classified as PM by the Bohan and Peter criteria, compared to only 14 percent with a modified classification.

In summary, when compared to the Bohan and Peter criteria, under more recent classification systems and definitions, the percentage of inflammatory myopathy cases classified as pure adult PM has declined, while the percentage of cases classified as "overlap" myositis (ie, related to a connective tissue disorder) has increased substantially [9].

Alternative classification schemes — Two alternative classification schemes have emerged since 2004 [9,10]. The two new systems address significantly different populations. In addition, one relies heavily on histologic criteria while the other relies heavily on clinical features.

One approach, based upon a longitudinal study of 100 French-Canadian patients, classified patients according to a "clinicoserologic" approach that relied upon extensive testing for autoantibodies. Excluding inclusion body myositis, four categories of inflammatory myopathy were recognized:

• Pure PM
• Pure DM
• Overlap myositis, which was defined as myositis plus any associated clinical overlap feature other than rash and/or any overlap autoantibody. (See 'Autoantibodies' below.)

• Cancer-associated myositis, which was defined as myositis with clinical paraneoplastic features and without an overlap autoantibody or anti-Mi-2 antibodies. (See 'Myositis-specific autoantibodies' below.)

The second scheme, proposed by an international workshop of myositis experts focused on criteria for the inclusion of patients in clinical trials, excluded myositis associated with either a connective tissue disease or malignancy but included the following categories [10]:

• Inclusion body myositis
• Definite PM
• Probable PM
• Definite DM
• Probable DM
• Amyopathic DM, also called dermatomyositis sine myositis
• Possible dermatomyositis sine dermatitis
• Nonspecific myositis
• Immune-mediated necrotizing myopathy

These categories were based upon clinical, histopathologic, and laboratory findings, including autoantibody determinations.

Both newer approaches to the classification of inflammatory myopathies allow greater accuracy in predicting the course of the disease and response to treatment than do the Bohan and Peter criteria. Future studies of DM and PM are likely to employ one of these newer classification systems [10,11].

IMMUNOPATHOGENESIS — Although the histologic features of both DM and PM include muscle fiber necrosis, degeneration and regeneration, and an inflammatory cell infiltrate, certain characteristic findings in these two different diseases reflect their distinct pathophysiologic pathways:

• DM is considered to be a humorally–mediated disorder in which the cellular infiltrate, located principally in perifascicular regions, is often focused around blood vessels (picture 1) [12-14]. The terminal complement C5b–9 membrane attack complex is detectable in vessel walls before the appearance of inflammatory cell infiltration in DM but not in PM (picture 2) [12].

Although DM is clearly associated with a vasculopathy in which complement is involved, it is not known if the vasculopathy is mediated purely by complement or if the deposition of complement proteins and other immune complexes associated with this diagnosis is secondary to other pathophysiologic events [15,16].

The inflammatory infiltrate is composed of B cells and plasmacytoid dendritic cells that are CD4+. Other typical features include perifascicular atrophy and fibrosis. Abnormal muscle fibers are usually grouped in one portion of the fascicle, suggestive of microinfarction mediated by blood vessel dysfunction [12].

• In PM, the cellular infiltrate is predominantly within the fascicle with inflammatory cells invading individual muscle fibers (picture 3) [14]. In contrast to DM, abnormal muscle fibers are scattered throughout the fascicle, not limited to one portion. There are no signs of vasculopathy or immune complex deposition. There is, however, evidence of cell–mediated immune mechanisms with increased numbers of cytotoxic CD8+ T cells, which appear to recognize an antigen on the muscle fiber surface [13], and enhanced expression of major histocompatibility complex (MHC) antigens by the muscle fibers [17].

Proinflammatory cytokines may contribute to muscle weakness in the absence of overt histologic inflammatory changes. Both interleukin (IL)-1 and tumor necrosis factor (TNF)-alpha are increased in muscle tissue of patients with DM and PM. Both of these cytokines, as well as upregulation of MHC class I molecules on myocytes, may lead to disturbed muscle function [18].

CLINICAL MANIFESTATIONS — DM and PM are both multisystem disorders with a wide variety of potential clinical findings.

Muscle weakness — Muscle weakness is the most common presenting feature of DM and PM. The onset is usually insidious, with gradual worsening over a period of several months before medical attention is sought. However, an acute onset has been described.

The distribution of weakness is typically symmetric and proximal. Distal muscle weakness, if present, tends to be mild and usually does not cause significant functional impairment. Rare patients present with focal myositis that usually but not always progresses to the typical generalized form over time [19]. (See "Approach to the patient with muscle weakness".)

Myalgias and muscle tenderness occur in 25 to 50 percent of cases. These symptoms tend to be mild, unlike the more prominent muscle pain that occurs in polymyalgia rheumatica, fibromyalgia, and viral or bacterial myositis.

Muscle atrophy is generally not seen in early cases, even in patients with marked weakness, but may occur in severe, long-standing disease.

Skin findings — Several distinct rashes, generally present at the time of clinical presentation, occur in DM but not PM:

• Gottron's sign — Gottron's sign is an erythematous, often scaly eruption that occurs in a symmetric fashion over the metacarpophalangeal and interphalangeal joints (picture 4A-C). Similar lesions can be seen over the extensor aspects of the elbows and knees, mimicking psoriasis.
• Heliotrope rash — The heliotrope rash is a violaceous eruption on the upper eyelids, often accompanied by eyelid swelling (picture 5A-C).
• Shawl sign and V sign — The shawl sign is a diffuse, flat erythematous lesion occurring over the chest and shoulders or in a V–shaped distribution over the anterior neck and chest (picture 6). This finding, which corresponds generally to the site covered by a shawl, may be exacerbated by exposure to ultraviolet light.
• Erythroderma — Erythroderma refers to erythema that resembles the shawl sign but is seen in a variety of other cutaneous areas, including the malar region (picture 7A-B) and the forehead (picture 8A-B). Erythroderma is often associated with extensive areas of skin redness.
• Periungual abnormalities — The capillary nailbeds in DM may be erythematous and show vascular changes similar to those observed in other connective tissue disorders (eg, scleroderma and systemic lupus erythematosus). Abnormal capillary nailbed loops may be evident, with alternating areas of dilatation and dropout (picture 9A-B) and periungual erythema (picture 10).
• Mechanic's hands — Patients with either DM or PM may have "mechanic's hands," a roughening and cracking of the skin of the tips and lateral aspects of the fingers, resulting in irregular, dirty-appearing lines that resemble those of a manual laborer (picture 11) [20]. These lesions are classically associated with the anti-synthetase syndrome, but have also been reported with other autoantibodies. (See 'Anti-synthetase syndrome' below.)

• Psoriasiform changes in scalp — Changes in the scalp resembling psoriasis probably occur in a high percentage of patients with dermatomyositis (picture 12). Dermatomyositis of the scalp is often misdiagnosed as psoriasis.
• Flagellate erythema — Flagellate erythema comprises linear, violaceous streaks on the trunk [21] (picture 13). Because of their truncal location in DM, these lesions are sometimes termed "centripetal" flagellate erythema. Recurrent scratching of the skin is believed to play an important role in the etiology of these lesions.
• Calcinosis cutis — The deposition of calcium within the skin, a finding known as calcinosis cutis, occurs commonly in juvenile DM, but is unusual in adult DM.

A number of other, more unusual skin manifestations of DM include ichthyosis, panniculitis, lichen planus, porcelain white atrophic scars, vesicle and bullae formation, follicular hyperkeratosis, malakoplakia, and papular mucinosis [22].

Lung disease — Interstitial lung disease (ILD) is an important complication in approximately 10 percent of cases of DM and PM. In addition, respiratory failure may result from diaphragmatic and chest wall muscle weakness.

The occurrence of ILD may be associated with rapidly progressive pulmonary failure and death. ILD in the inflammatory myopathies often occurs in the context of anti-synthetase antibodies and the anti-synthetase syndrome. (See "Pulmonary disease in dermatomyositis and polymyositis" and 'Myositis-specific autoantibodies' below and 'Anti-synthetase syndrome' below.)

Malignancy — An increased rate of malignancy has been described, with a greater risk in patients with DM. The spectrum of malignancies parallels the distribution in the general population with a few possible exceptions. This issue is discussed separately. (See "Malignancy in dermatomyositis and polymyositis".)

Esophageal disease — Weakness of the striated muscle of the upper one-third of the esophagus (and/or the oropharyngeal muscles) may lead to dysphagia, nasal regurgitation, and/or aspiration [23]. Esophageal involvement is more common in elderly patients and may underlie the increased incidence of bacterial pneumonia [24].

Cardiac disease — Cardiac involvement with histologic evidence of myocarditis is well described in DM and PM [25]. However, myocardial involvement severe enough to cause heart failure is unusual.

Patients with myositis may have an elevated serum CK-MB fraction due either to increased expression of CK B chain from inflamed skeletal muscle [26], or to involvement of the myocardium by the myositis. However, the most common reason for increased CK-MB levels is that the fraction of MB is increased in regenerating muscle. Myocardial infarction may be suspected in these patients. (See "Troponins and creatine kinase as biomarkers of cardiac injury" and "Clinical manifestations and diagnosis of myocarditis in adults", section on 'Cardiac enzymes'.)

Cardiac troponin I, a more specific and sensitive marker of cardiac damage than CK-MB, can be used to assess the cause of elevated serum CK-MB levels in patients with myositis. Normal plasma troponin I concentrations provide some reassurance against cardiac involvement, but the clinical utility of this assay in DM and PM requires further evaluation [27]. (See "Troponins and creatine kinase as biomarkers of cardiac injury".)

Other — Patients with severe disease may present with a variety of other manifestations, including fever, weight loss, Raynaud phenomenon, and a nonerosive inflammatory polyarthritis.

Anti-synthetase syndrome — Up to 30 percent of patients with DM or PM have a constellation of clinical findings termed "the anti-synthetase syndrome." These findings include the relatively acute disease onset, constitutional symptoms (eg, fever), Raynaud's phenomenon, mechanic's hands, arthritis, and ILD. Affected patients have anti-synthetase antibodies that are highly specific for DM and PM. (See 'Myositis-specific autoantibodies' below, [28,29].

With regard to the anti-synthetase syndrome, several points should be noted:

• Not all patients with anti-synthetase antibodies or even those classified as having the anti-synthetase syndrome have all manifestations of this syndrome.
• This group of clinical findings or this general clinical picture is not specific for anti-synthetase antibodies. Patients with other types of autoantibodies, eg, anti-PM-Scl, anti-U1RNP, can also present with these types of features.
• Finally, some patients with anti-synthetase antibodies have relatively little myositis but more prominent other features of this disease spectrum, such as ILD.

Amyopathic DM — Amyopathic dermatomyositis and dermatomyositis sine myositis are terms used to describe patients with the typical rash and dermatopathology of DM who do not have clinical evidence of myopathy. Most of these patients eventually develop clinical, histologic, or radiologic evidence of myositis; however, muscle involvement may not be seen as long as six years after disease onset [30-32]. Sometimes the term "clinically-amyopathic DM" is used if subclinical or asymptomatic muscle disease has not been excluded with the utmost rigor.

Antibodies to an uncharacterized protein (called CADM-140) may be seen and may be specific for amyopathic DM. In one report, these antibodies were present in eight Japanese patients with amyopathic DM, four of whom also had rapidly progressive interstitial lung disease [33]. Further study in other populations will be needed to assess the diagnostic utility of this test.

Overlap syndromes — DM and PM may overlap with features of other connective tissue diseases, particularly scleroderma, systemic lupus erythematosus, mixed connective tissue disease and, less often, rheumatoid arthritis and Sjögren's syndrome. The myopathy associated with the other connective tissue diseases varies from clinically insignificant (with minimal muscle enzyme elevations and minimal inflammatory changes on muscle biopsy) to typically severe PM or DM in which myopathy dominates the clinical picture [4,5,34].

DIAGNOSIS — The diagnosis of DM or PM is suggested by the above clinical findings. The medical history can help eliminate use of prescription and illicit drugs as a cause of muscle damage (eg, colchicine, statins, hydroxychloroquine, alcohol, cocaine). In addition, risk factors for HIV infection and features of connective tissue diseases should also be sought.

Both measurement of serum muscle enzyme levels and testing for the presence of specific autoantibodies play important roles in the assessment of patients with suspected DM and PM.

Muscle enzymes — Creatine kinase (CK), lactate dehydrogenase (LD), aldolase, aspartate aminotransferase (AST), and alanine aminotransferase (ALT) are the muscle enzymes routinely measured in the evaluation of myopathy. Blood should not be drawn soon after the performance of electromyography (EMG), because the trauma associated with needle insertion into the muscle can lead to elevated serum muscle enzyme levels. (See "Muscle enzymes in the evaluation of neuromuscular diseases".)

At some point in the course of the disease, almost all patients with DM and PM have an elevation in at least one muscle enzyme; most have elevations in all enzymes. In a review of 153 patients with DM or PM, CK was normal in 5 percent, aldolase in 4 percent, LD in 9 percent and the aminotransferases in 15 to 17 percent [4]. However, these data may underestimate the frequency of normal CK concentrations, because the Bohan and Peter criteria employed in that study include muscles enzyme elevation as a criterion for the disease. In addition, the study was performed before autoantibodies and magnetic resonance (MR) imaging studies were available to facilitate diagnoses.

In severe cases, the serum CK concentration may be elevated 50-fold. Although a correlation between the severity of the weakness and the height of elevation in serum muscle enzymes may be seen [5], the degree of muscle dysfunction may be much greater than the enzyme levels would suggest. An important concept in the treatment of DM and PM is that therapy should be guided primarily by patients' strength, not the concentration of their muscle enzymes. (See "Initial treatment of dermatomyositis and polymyositis in adults".)

The occurrence of muscle weakness with relatively normal enzyme levels is more likely to occur in DM than PM. Persistently low serum muscle enzyme levels in the setting of obvious muscle weakness may also occur in patients with advanced disease and significant loss of muscle mass.

Autoantibodies — Antinuclear antibodies (ANA) detected by standard immunofluorescence methods are present in up to 80 percent of patients with DM or PM [35,36]. Detailed autoantibody testing designed to identify the specific autoantibody responsible for the ANA pattern is much more useful. Specific autoantibody testing in the setting of inflammatory myopathies is useful in two contexts:

• Diagnosis of connective tissue disorders associated with myositis.
• Detection of myositis-specific autoantibodies, which may offer valuable information regarding prognosis and potential future patterns of organ involvement.

Autoantibodies and connective tissue disorders — The detection of anti-Ro, anti-La, anti-Sm, or anti-ribonucleoprotein (RNP) antibodies strongly suggests a diagnosis of myositis associated or overlapping with another connective tissue disease [35]. As an example, anti-RNP antibodies are associated with the overlap of myositis with features of either scleroderma or systemic lupus erythematosus, a clinical entity termed mixed connective tissue disease [37]. (See "Definition and diagnosis of mixed connective tissue disease".)

The precise diagnosis of an underlying connective tissue disease is critical to patient management because of the prognostic and treatment implications of specific diagnoses. (See "Antibodies to DNA, Sm, and RNP" and "Clinical significance of anti-Ro/SSA and anti-La/SSB antibodies".)

Myositis-specific autoantibodies — Several categories of autoantibodies directed against cytoplasmic RNA synthetases, other cytoplasmic proteins, ribonucleoproteins, and certain nuclear antigens are called myositis-specific autoantibodies [28,38-40]. These autoantibodies occur in approximately 30 percent of patients with DM and PM.

It appears increasingly likely that myositis-specific autoantibodies play specific roles in the pathophysiology of DM and PM. Although the exact role of myositis-specific autoantibodies remains unknown, it appears increasingly likely that they reflect important processes in the pathophysiology of DM and PM. In addition, a fuller understanding of myositis-specific autoantibodies is likely to reveal essential information regarding diagnosis and prognosis.

There are three major categories of myositis-specific autoantibodies: antibodies to aminoacyl-tRNA synthetases (anti-synthetase antibodies), including anti-Jo-1; antibodies to signal recognition particle (anti-SRP antibodies); and antibodies to Mi-2, a nuclear helicase.

• Anti-Jo-1 — Anti–Jo–1 antibodies are the most common myositis-specific autoantibody. Anti-Jo-1 antibodies directed against the anti–histidyl–tRNA synthetase, one of a group of enzymes that catalyze the attachment of specific amino acids to their cognate tRNAs during the process of protein synthesis. Anti-Jo-1 antibodies are strongly associated with ILD, Raynaud's phenomenon, arthritis, and mechanic's hands (picture 11) [38,39]. One study suggested correlations between anti-Jo-1-antibody levels and disease activity in patients with inflammatory myopathy, but data in the overall literature are conflicting on this point [41].

Other anti-synthetase antibodies include antibodies to the OJ, EJ, PL-7, PL-12, KS, and Zo antigens [29,42]. Patients who possess these other anti-synthetase antibodies manifest clinical features similar to those with anti-Jo-1-antibodies.

• Anti-SRP antibodies — The signal recognition particle (SRP) is involved in the translocation of newly synthesized proteins into the endoplasmic reticulum. Anti-SRP antibodies occur almost exclusively in PM. Anti-SRP antibodies are associated with severe myopathy and aggressive disease that is difficult to control, even with high-dose glucocorticoids and adjunct immunosuppressive agents. (See "Initial treatment of dermatomyositis and polymyositis in adults".)

• Anti-Mi-2 antibodies — Anti-Mi-2 antibodies are directed against a helicase involved in transcriptional activation [43]. Among patients with DM, anti-Mi-2 antibodies are present in about 7 percent of Caucasians and 30 percent of those from Central America [6]. They are associated with the relatively acute onset of classic DM with erythroderma and the shawl sign [37,38].

A number of other myositis-specific autoantibodies have been described in different populations of patients with myositis:

• Antibodies directed against hPMS-1, a DNA mismatch repair enzyme, is a myositis-specific autoantibody reported to occur in 7.5 percent of patients with myositis [44].
• Both anti-Ku and anti-PM-Scl antibodies have been identified in patients with overlapping features of myositis and scleroderma [45]. Because many of these patients do not have myositis, they are sometimes termed "myositis-associated autoantibodies" rather than myositis-specific autoantibodies.
• Antibodies to a 140 kD polypeptide (anti-CADM-140) may be a serologic feature of amyopathic DM. (See 'Amyopathic DM' above.)

• Antibodies to a 155-kD protein were found in sera of 51 of 244 DM patients (21 percent), but in only 1 of 108 patients with other connective tissue diseases and no normal controls [46]. Caucasian patients with this autoantibody had a unique HLA risk factor, DQA1*0301, and an increased frequency of the V sign rash. Patients with this autoantibody were clinically distinct from those with autoantibodies to aminoacyl-transfer RNA synthetases.
• An MSA reactive with 155 and 140 kD nuclear proteins, now known as the anti-155/140 antibody, has been described [47]. This autoantibody appears to be distinct from the anti-CADM-140 and the 155-kD antibodies described above. The anti-155/140 antibody was detected in seven of 52 (13 percent) Japanese patients with DM but in none of the disease controls with PM, SLE, SSc, or idiopathic interstitial pneumonia tested. Clinical associations of the anti-155/140 antibody included flagellate erythema and internal malignancy, in addition to the conventional cutaneous DM findings of Gottron's papules and heliotrope rash.

Myositis-specific autoantibodies and histopathology — Studies that have correlated the presence of myositis-specific autoantibodies with histopathologic features suggest that such autoantibodies are associated with a humorally-mediated immune-complex microangiopathy typical of DM [48-50]. However, anti-synthetase antibodies occur in both DM and PM.

There also appears to be some histopathological variation according to the specific type of myositis-specific autoantibody [45,50]. As examples:

• The histopathologic pattern of anti-Jo-1 antibody-positive patients appears to differ from that of anti-SRP antibody-positive patients.
• The histopathologic pattern of patients with the clinical phenotype of DM and either anti-synthetase or anti-SRP antibodies differs from that of patients with DM who do not have these autoantibodies. For example, anti-Jo-1 antibody-positive patients have the perifascicular atrophy typical of DM but not the characteristic capillary pathology. In contrast, anti-SRP patients have the capillary pathology but not the perifascicular atrophy.
• Anti-Jo-1 patients are reported to have perimysial connective tissue fragmentation, a finding not observed in DM patients without such autoantibodies but one that is observed in fasciitis.
• Patients with anti-SRP antibodies are reported to have less intramuscular inflammation than do other patients with DM or PM.

Gene expression profiling — Gene expression profiling of tissue from patients with DM and controls demonstrates increased expression of various genes that share a responsiveness to induction by interferon-alpha and interferon-beta [16,49].

Immunohistochemical staining confirmed an increase in the presence one gene production, human myxovirus resistance protein, in muscle fibers and microvasculature [16]. In addition, plasmacytoid dendritic cells, were abundant in involved muscle and accounted for 30 to 90 percent of all CD4 positive cells.

ELECTROMYOGRAPHY AND TISSUE BIOPSIES — In addition to laboratory testing for muscle enzymes and autoantibodies, electromyography (EMG) and tissue biopsies of skin and/or muscle are important facets of the evaluation of patients with possible DM or PM.

Electromyography — The EMG shows evidence of increased membrane irritability in the form of a classic triad:

• Increased insertional activity and spontaneous fibrillations
• Abnormal myopathic low amplitude, short–duration polyphasic motor potentials
• Complex repetitive discharges

In addition, an early finding in myopathy is that of early recruitment; ie, an increased number of motor units firing rapidly in order to produce a low level of contraction. The findings of abnormal spontaneous activity such as insertional activity, fibrillation potentials, and complex repetitive discharges can be seen in a wide range of myogenic processes, but are much more frequently seen in inflammatory myopathies.

A normal EMG is unusual in a patient with otherwise typical DM or PM, occurring in one study in 16 of 153 patients (11 percent) [4].

EMG abnormalities may support the diagnosis of DM or PM but are not diagnostic. Similar findings occur in various infectious, toxic, or metabolic myopathies. However, the EMG is of value in distinguishing weakness of myopathic origin from neuropathic disorders, such as amyotrophic lateral sclerosis, peripheral polyneuropathy, or myasthenia gravis.

The EMG is also useful in directing the site of muscle biopsy. (See "Clinical neurophysiology".) Because muscle involvement may not be generalized, the electromyographer should sample multiple sites before concluding that there are no myopathic changes. Highly localized disease, although atypical, sometimes occurs in DM and PM.

Skin biopsy in DM — Histopathologic confirmation of the diagnosis of DM should be achieved whenever possible. Biopsy of a variety of DM skin findings, including Gottron's sign, the shawl sign, and erythroderma can provide confirmation of the diagnosis in the proper clinical setting. (See 'Skin findings' above.)

Thus, skin biopsy may seal the diagnosis and avoid the need for muscle biopsy in a patient with weakness in a pattern typical of inflammatory myopathy (symmetric; proximal greater than distal), elevation of serum muscle enzymes, and cutaneous findings characteristic of DM.

On light microscopy, DM skin lesions usually demonstrate mild atrophy of the epidermis with vacuolar changes in the basal keratinocyte layer. A perivascular lymphoid infiltrate often prevails in the dermis [31].

Assessment by light and immunofluorescence microscopy are essential to make the histologic diagnosis of DM. Immunofluorescence reveals an interface dermatitis (deposition of complement proteins and immunoglobulin at the dermal-epidermal junction) that is generally not distinguishable on light microscopy from systemic lupus erythematosus (picture 14). (However, in DM, immunoglobulin deposition as opposed to complement is less common than in lupus). Deposits of the membrane attack complex are found along the dermal-epidermal junction and within the walls of dermal blood vessels (picture 2) [51].

Muscle biopsy — For the majority of myositis cases, the definitive test for establishing the diagnosis of inflammatory myopathy and excluding the many other causes of muscle weakness is muscle biopsy. The biopsy should be obtained from a muscle that is weak on clinical examination. The usual muscle targets for biopsy are the quadriceps or the deltoid. Biopsying the muscle contralateral to one demonstrated to be abnormal by EMG increases the likelihood of a diagnostic biopsy.

Muscles with severe weakness, marked atrophy, or recent EMG testing should be avoided. In addition, biopsy of the calf muscles is discouraged because of the frequency of artifactual findings in biopsies from that region.

If physical examination and EMG fail to identify an appropriate muscle for biopsy, magnetic resonance (MR) imaging may be useful. MR may reveal areas of increased T2 signal in muscles that can then be selected for biopsy. Targeted study of the most accessible muscles (eg, deltoid, biceps, quadriceps) by MR is one approach, but whole-body imaging is another option (picture 15) [52]. (See 'MR imaging' below.)

An open biopsy is preferred to a closed needle biopsy because larger specimens can be obtained and muscle fiber orientation is better preserved. Muscle biopsy via a small incision using local anesthesia and a sharp-jawed surgical instrument (conchotome) may also yield a diagnostically adequate specimen with a low complication rate.

The efficacy of this technique was evaluated in a report in which 149 muscle biopsies were obtained from 122 patients [53]. Only four biopsies (2.7 percent) failed to provide an adequate sample for histologic analysis. Eighty-three percent of patients who met clinical criteria for definite or probable DM or PM had biopsies that revealed myositis.

Proper processing of the muscle biopsy is essential. Once obtained, the muscle tissue should be preserved appropriately for later testing. Some tissue should be fixed for routine light and electron microscopy, and some tissue should be frozen in isopentane cooled in liquid nitrogen for biochemical assays. Important biochemical assays include:

• Testing for glycogen storage disorders and defects in lipid metabolism
• Testing for mutant proteins (Western blotting for dystrophin)
• Genetic testing
• Immunohistologic studies, eg

• - Dystrophin for Duchenne/Becker dystrophy
• - Merosin for congenital muscular dystrophy
• - Sarcoglycan for limb-girdle muscular dystrophy

The experience of the laboratory in processing muscle biopsy specimens correlates highly with the usefulness of diagnostic information obtained from the procedure. The team performing and processing the biopsy should be provided with detailed clinical information.

The clinician requesting the biopsy should communicate directly with the surgeon and pathologist prior to the procedure. A set of detailed instructions for handling of muscle biopsy specimens is available at the following site: (www.medicine.uiowa.edu/Path_Handbook/Appendix/AnatomicPath/ex_muscle_biopsy.html).

MR IMAGING — MR imaging has emerged as an important technique in the clinical evaluation of patients with DM and PM [54]. MR imaging can demonstrate areas of muscle inflammation, edema with active myositis, fibrosis, and calcification. Unlike muscle biopsy, MR imaging can assess large areas of muscle, thereby avoiding problems with sampling error (picture 15). Because MR imaging is noninvasive, it has the additional advantage of permitting serial assessments, which may be useful in defining the response to therapy.

Some centers now utilize MRI as a routine part of the evaluation of patients with inflammatory myopathy. However, these studies do not replace EMG and muscle biopsy in making the diagnosis.

Another MR modality, MR spectroscopy, provides a view of muscle metabolism by comparing the ratio of muscle phosphorus contained in phosphocreatine to the level of inorganic phosphorus. This ratio is decreased in abnormal muscle in which the generation of high energy compounds such as phosphocreatine is reduced. (See "Energy metabolism in muscle".)

MR spectroscopy is very sensitive and has been used to detect muscle abnormalities in amyopathic DM in which muscle strength and muscle enzymes are normal [55]. (See 'Amyopathic DM' above.)

The precise utilities of MR spectroscopy in the evaluation and longitudinal follow-up of patients with inflammatory myopathies require further study.

DIFFERENTIAL DIAGNOSIS — DM and PM must be distinguished from other conditions that cause muscle weakness, with or without muscle enzyme elevation. The differential diagnosis of DM and PM includes other inflammatory myopathies, motor neuron disease, myasthenia gravis, and the muscular dystrophies. In addition, a variety of inherited, metabolic, drug–induced, endocrine, and infectious myopathies must also be considered (table 1) [56]. (See "Approach to the patient with muscle weakness".)

None of these disorders is associated with the skin lesions that are characteristic of DM. (See 'Skin findings' above.)

Inclusion body myositis — Inclusion body myositis (IBM) is the most common inflammatory myopathy to be misdiagnosed as PM and, in cases of "refractory PM," the correct diagnosis often proves to be IBM. Distinction between these two disorders is critical because their prognoses differ significantly. (See "Clinical manifestations and diagnosis of inclusion body myositis".)

In contrast to PM, IBM generally has a more insidious onset and more prominent distal muscle weakness (table 2). Muscle atrophy and weakness of the wrist and finger flexors in the upper extremities and of the quadriceps and anterior tibial muscles in the legs are characteristic [11,57]. Furthermore, in many patients with IBM, the muscle involvement is asymmetric, particularly in the beginning.

On average, serum muscle enzyme levels are lower in IBM than in PM, although substantial elevations may occur. The presence of typical inclusion bodies on muscle biopsy is diagnostic of this disorder, but a single biopsy lacks the characteristic histopathologic features in 20 to 30 percent of patients [57].

MR imaging findings may help to distinguish PM from IBM. Whereas MR changes suggestive of inflammation are noted along fascial planes in PM, such changes are observed throughout the muscle in IBM [58]. Fatty infiltration and muscle atrophy are more prominent in IBM than PM, perhaps owing to the longer preclinical phase and the relative refractoriness to treatment exhibited by IBM.

Hypothyroidism — The myopathy associated with hypothyroidism can mimic the presentation of inflammatory myopathy, causing a subacute onset of proximal muscle weakness and elevated muscle enzymes. (See "Hypothyroid myopathy".)

Drug-induced myopathy — A number of drugs can produce a myopathy that can mimic the inflammatory myopathies. These include corticosteroids, statins, antimalarials, antipsychotic drugs, colchicine, penicillamine, alcohol, cocaine, and certain antiretroviral drugs. (See "Drug-induced myopathies" and "Muscle injury associated with lipid lowering drugs" and "Muscle disease in HIV-infected patients", section on 'NRTI myopathy'.)

HIV infection — Weakness in an HIV–infected patient presents a diagnostic challenge. In addition to causing weakness through chronic disease and cachexia, HIV infection may be associated with an inflammatory myopathy that is identical to PM. The myopathy can be either a presenting manifestation of HIV infection or occur in the later stages of infection. A myopathy may also be induced by certain antiretroviral drugs. (See "Muscle disease in HIV-infected patients", section on 'HIV myopathy'.)

Amyotrophic lateral sclerosis — Amyotrophic lateral sclerosis (ALS, also called motor neuron disease) has a number of clinical features that differ from DM and PM:

• ALS may present with distal rather than with proximal weakness, and onset is not usually symmetric.
• Long-tract signs are typically present in ALS, since there is dysfunction of both upper and lower motor neurons.
• ALS is not associated with myopathic changes on EMG because the central problem is neuronal death.
• Serum muscle enzyme levels are usually normal in ALS, although elevations of CK to the range of approximately 1000 may be observed.

(See "Clinical features of amyotrophic lateral sclerosis" and "Diagnosis of amyotrophic lateral sclerosis".)

Myasthenia gravis — Myasthenia gravis is a disorder of the neuromuscular junction, caused by antibodies to the acetylcholinesterase receptor. Although the classic physical examination finding in myasthenia gravis is muscle fatiguability (the development of muscle weakness as exercise proceeds), the disease can occasionally cause diffuse weakness without prominent fatiguability symptoms.

Myasthenia gravis is distinguished from myositis by the frequent presence of facial muscle weakness, normal muscle enzymes, characteristic EMG changes, and the presence of anti–acetylcholine receptor antibodies. (See "Clinical manifestations of myasthenia gravis".)

In contrast to myasthenia gravis, DM and PM rarely involve the oculobulbar muscles. A condition related to myasthenia gravis known as the Lambert-Eaton syndrome, can mimic DM and PM more closely, because the oculobulbar muscles are usually spared. (See "Clinical features and diagnosis of Lambert-Eaton myasthenic syndrome".)

Muscular dystrophy and myotonic dystrophy — The muscular dystrophies are an inherited group of progressive myopathic disorders resulting from defects in a number of genes required for normal muscle function. Patients with muscular dystrophy occasionally have a prominent endomysial inflammatory cell infiltrate.

This may cause diagnostic confusion, particularly in dystrophic disorders such as limb-girdle and facioscapulohumeral muscular dystrophies. However, the inflammatory cell infiltrate in muscular dystrophy is typically limited to areas adjacent to necrotic muscle fibers, in contrast to the tendency of PM to involve nonnecrotic muscle fibers. (See "Limb-girdle muscular dystrophy" and "Facioscapulohumeral, oculopharyngeal, distal, and congenital muscular dystrophies".)

Proximal myotonic myopathy (PROMM), also known as myotonic dystrophy type 2, must also be considered in the differential diagnosis. (See "Myotonic dystrophy: Etiology, clinical features, and diagnosis".)

Inherited metabolic myopathies — Inherited metabolic myopathies include such disorders of carbohydrate and lipid metabolism as carnitine deficiency and myoadenylate deaminase deficiency. These diseases are characterized by intermittent episodes of acute muscle pain and tenderness, usually induced by exertion. The episodes are often accompanied by myoglobinuria with red or brown urine. Occasional patients develop chronic weakness after years of repeated acute episodes [59]. (See "Approach to the metabolic myopathies" and "Causes of metabolic myopathies".)

Other — A variety of other myopathies may be mimics of PM.

• Acute viral or bacterial infections (pyomyositis), immobilization, and trauma can be characterized by acute, fulminant presentations that are often complicated by rhabdomyolysis. However, rhabdomyolysis has been described in case reports in the inflammatory myopathies [60,61]. (See "Rhabdomyolysis", section on 'Inflammatory myopathies' and "Pyomyositis".)

• Muscle weakness occurring in multiple family members is not always due to inherited metabolic defects or dystrophies, but may result from the development of idiopathic myositis in several members of the same family. The clinical features of familial idiopathic inflammatory myopathy are similar to those of sporadic disease, although the frequency of myositis-specific autoantibodies is lower with the familial disorder [62].
• Muscle disease that is clinically and histopathologically similar to PM has been well documented in patients with chronic graft-versus-host (GVH) disease [63]. The estimated frequency is 0.6 percent. The onset of myositis is typically more than one year after transplantation [64]. (See "Clinical manifestations and diagnosis of chronic graft-versus-host disease".)

• Rare patients present with focal myositis that usually but not always progresses to the typical generalized form over time [19].
• Amyloid myopathy, which can occur in immunoglobulin-related or familial amyloidosis [65]. (See "Musculoskeletal manifestations of amyloidosis".)

• Sarcoid myopathy (see "Sarcoid: Muscle, bone, and vascular disease manifestations", section on 'Myopathy')

• Parasitic infections, eg, trichinellosis. (See "Trichinellosis".)

INFORMATION FOR PATIENTS — Educational materials on this topic are available for patients. We encourage you to print or e-mail this topic review, or to refer patients to our public web site, www.uptodate.com/patients, which includes this and other topics. (See "Patient information: Myositis".)

SUMMARY AND RECOMMENDATIONS — DM and PM are two forms of inflammatory myopathy. Overlap myositis is the occurrence of myositis in association with another connective tissue disease; eg, scleroderma, systemic lupus erythematosus, rheumatoid arthritis, or Sjögren's syndrome.

Immunopathogenesis — Histologic features of DM and PM include muscle fiber necrosis, degeneration and regeneration, and inflammatory cell infiltration.

• In DM, the cellular infiltrate is predominantly perifasicular and often perivascular. B lymphocytes and an increased number of plasmacytoid dendritic cells are also typical of DM (picture 1).
• In PM, the cellular infiltrate is found predominantly within the fascicle, where there are increased numbers of cytotoxic CD8+ T cells (picture 3).

Clinical manifestations — The major clinical manifestations of these inflammatory myopathies are muscle weakness and, in DM, rash.

• Muscle weakness is typically symmetric and predominantly proximal. Muscle atrophy may be present in severe, long-standing disease. Oropharyngeal and upper esophageal muscle involvement may lead to dysphagia, nasal regurgitation, or aspiration. Respiratory failure may result from weakness of the diaphragm and chest wall muscles. (See 'Muscle weakness' above.)

• Rash is a feature of DM. The most common skin findings are (see 'Skin findings' above:

• - Gottron's sign, which is characterized by symmetric, roughened, erythematous skin changes over the extensor surfaces of the metacarpophalangeal and interphalangeal joints of the fingers, elbows, and/or knees (picture 4A-B).
• - Heliotrope rash, which is a violaceous eruption on the upper eyelids, sometimes accompanied by edema (picture 5A).
• - Shawl sign, which is a diffuse flat erythema in a shawl-like distribution over the chest and shoulder or in a V-shaped pattern over the anterior neck and chest (picture 6).
• - Erythroderma, a generalized redness that occurs at a variety of other skin sites, including the malar region and forehead (picture 7A-B).
• - Periungual abnormalities in which the capillary nailbeds are erythematous and show vascular changes similar to those observed in other connective tissue disorders. Abnormal capillary nailbed loops may be evident, with alternating areas of dilatation and dropout (picture 9A-B)
• - Mechanic's hands, which are characterized by painful roughening and cracking of the skin and lateral aspects of the fingers (picture 11).

• Interstitial lung disease may occur with DM and PM and also with overlap myositis. (See 'Lung disease' above.)

• Although CK-MB elevation is not unusual, symptomatic cardiac muscle involvement is uncommon. (See 'Cardiac disease' above.)

Laboratory evaluation — The diagnosis of an inflammatory myopathy is made on the basis of a combination of the clinical, laboratory, electromyography, and/or biopsy findings, and exclusion of other disorders with similar features (table 1).

Serum muscle enzyme concentrations and autoantibody tests are useful in making the diagnosis, following disease activity, and defining disease phenotypes.

• Elevations in serum creatine kinase, lactate dehydrogenase, aldolase, and aminotransferases occur in most patients. (See 'Muscle enzymes' above.)

• Autoantibodies are found in a majority of patients. Antinuclear antibodies in high titer suggest the presence of another connective tissue disease. (See 'Autoantibodies' above.)

• Among the myositis-specific antibodies, anti-histidyl-tRNA synthase antibodies (eg, the anti-Jo-1 antibody) has been associated with interstitial lung disease, Raynaud phenomenon, arthritis, and mechanic's hands, a syndrome known as the anti-synthetase syndrome. (See 'Anti-synthetase syndrome' above.)

Additional myositis-specific autoantibodies include other anti-synthetase antibodies, anti-signal recognition particle antibodies, and anti-Mi-2 antibodies. (See 'Myositis-specific autoantibodies' above.)

Electromyography — Electromyography (EMG) shows evidence of muscle irritability. EMG findings are helpful in confirming the presence of a myopathic process and in indicating which muscle groups are most involved. This information can be valuable in selecting a site for muscle biopsy. However, EMG findings are not specific for either DM or PM and the EMG is normal in about 11 percent of patients. (See 'Electromyography' above.)

Tissue biopsies — Skin and/or muscle biopsies may establish the diagnosis in DM. Muscle biopsy is the definitive test for PM, in which skin lesions are not seen.

• Skin biopsy may be sufficient to confirm the diagnosis of DM in a patient with weakness in a pattern typical of inflammatory myopathy (symmetric; proximal > distal), elevation of serum muscle enzymes, and classic cutaneous findings. A diagnostic skin biopsy in the appropriate clinical setting obviates the need for muscle biopsy. (See 'Skin biopsy in DM' above.)

• Even in clinical scenarios highly consistent with PM, muscle biopsy is essential to establishing the correct diagnosis and excluding other disorders. Open muscle biopsy is preferred to needle biopsy as the former provides larger specimens. The clinician ordering the muscle biopsy should confer with the surgeon and pathologist before the procedure. (See 'Muscle biopsy' above.)

Magnetic resonance imaging — Magnetic resonance (MR) imaging may be useful if physical examination and EMG fail to identify a suitable target for muscle biopsy. MR may also be useful in the longitudinal follow-up of patients, as an adjunct test to assess treatment responses and to diagnose disease flares. (See 'MR imaging' above.)