Polymyositis

Updated: Dec 21, 2022
  • Author: Mythili Seetharaman, MD; Chief Editor: Herbert S Diamond, MD  more...
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Overview

Practice Essentials

Polymyositis is an idiopathic inflammatory myopathy characterized by the following [1] :

  • Symmetrical, proximal muscle weakness
  • Elevated skeletal muscle enzyme levels
  • Characteristic electromyography (EMG) and muscle biopsy findings (see the image below)
Polymyositis. Histopathology slide shows endomysia Polymyositis. Histopathology slide shows endomysial mononuclear inflammatory infiltrate and muscle fiber necrosis.

Polymyositis is one of several idiopathic inflammatory myopathies. [2] Clinically similar to polymyositis, dermatomyositis is an idiopathic inflammatory myopathy associated with characteristic dermatologic manifestations. [3, 4] Inclusion body myositis is a slowly progressive, idiopathic, inflammatory myopathy with characteristic pathologic findings that is generally found in older men. Bohan and Peter classified the idiopathic inflammatory myopathies as follows [5] :

  • I - Primary idiopathic polymyositis
  • II - Primary idiopathic dermatomyositis
  • III - Polymyositis or dermatomyositis associated with malignancy [6]
  • IV - Childhood polymyositis or dermatomyositis
  • >V - Polymyositis or dermatomyositis associated with another connective-tissue disease
  • VII - Miscellaneous (eg, eosinophilic myositis, myositis ossificans, focal myositis, giant cell myositis)

Necrotizing autoimmune myopathy (NAM) is a recently recognized form of idiopathic inflammatory myopathy that is identified by finding macrophage-predominant myocyte destruction, with few to no lymphocytes, on muscle biopsy. NAM has been associated with malignancy and statin use. [7]

See Etiology, Presentation, and Workup.

Polymyositis and dermatomyositis have many shared clinical features. Both present as symmetrical muscle weakness that develops over weeks to months. Initial treatment with corticosteroids usually produces a response; however, nonresponders require further treatment. Moreover, both conditions may be associated with malignancies. [6] Despite these similarities, muscle biopsy findings and characteristic skin findings of dermatomyositis reveal each as a distinct clinical entity.

Although classified as an inflammatory myopathy, inclusion body myositis shows minimal evidence of inflammation. This is the most common inflammatory myopathy in patients older than age 50 years. It more commonly presents as asymmetrical, distal weakness and also has distinct biopsy findings. Studies so far have yielded less favorable results than treatment for polymyositis and dermatomyositis. (See Treatment and Medication.)

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Pathophysiology

The pathogenesis of polymyositis points toward a T-cell–mediated cytotoxic process directed against unidentified muscle antigens. Supporting this conclusion is the involvement of CD8 T cells, which, along with macrophages, initially surround healthy nonnecrotic muscle fibers and eventually invade and destroy them. [8]  (See the image below.)

Polymyositis. Close view of muscle biopsy, showing Polymyositis. Close view of muscle biopsy, showing chronic inflammatory infiltrate consisting of T lymphocytes, especially CD8+ T lymphocytes.

The factors triggering a T-cell–mediated process in polymyositis are unclear. Viruses have been implicated; so far, however, the only viruses that have been etiologically connected with the disease are the human retroviruses human immunodeficiency virus (HIV) and human T-cell lymphotrophic virus type I (HTLV-I), the simian retroviruses, and coxsackievirus B. Those viruses may directly invade the muscle tissue, damaging the vascular endothelium and releasing cytokines, which then induce abnormal expression of the major histocompatibility complex (MHC) and render the muscle susceptible to destruction.

An autoimmune response to nuclear and cytoplasmic autoantigens is detected in about 60-80% of patients with polymyositis and dermatomyositis. Some serum autoantibodies are shared with other autoimmune diseases (ie, myositis-associated antibodies [MAAs]), and some are unique to myositis (ie, myositis-specific antibodies [MSAs]). MSAs are found in approximately 40% of patients with polymyositis or dermatomyositis, whereas MAAs are found in 20-50% of these patients.

Myositis-specific antibodies

The identified MSA targets include the following 3 distinct groups of proteins:

  • Aminoacyl–transfer ribonucleic acid (tRNA) synthetases (anti–Jo-1)
  • Nuclear Mi-2 protein
  • Components of the signal-recognition particle (SRP)

Most of the anti-tRNA synthetase antibodies are directed toward functional and highly conserved domains of the enzyme. As many as 6 of 20 aminoacyl-tRNA synthetases have been described, but anti-histidyl-tRNA synthetase (Jo-1) is most common (20-30%). Autoantibodies directed toward the other synthetases specific for alanine (anti-PL12), glycine (anti-EJ), isoleucine (anti-OJ), threonine (anti-PL7), and asparagine (anti-KS) have been reported in only about 1% of patients.

Anti–Jo-1 autoantibodies were originally described as precipitating autoantibodies in sera of patients with polymyositis. Subsequently, the anti-Jo-1 antibodies were recognized to be specific for patients with polymyositis. The target for the anti-Jo-1 antibodies was the aminoacyl-tRNA synthetases, a family of distinct cellular enzymes.

The Jo-1 antigen is histidyl-tRNA synthetase. This enzyme is partially responsible for attaching tRNA to its cognate ribosomal RNA (rRNA). The Jo-1 antigen migrates as a 53-kd protein on sodium dodecyl sulfate–polyacrylamide gel electrophoresis (SDS-PAGE).

The presence of autoantibodies against the Jo-1 antigen has been reported in 15-30% of polymyositis patients by immunodiffusion. Anti–Jo-1 antibodies are almost completely specific for myositis and are more common in polymyositis than in dermatomyositis; they are rare in children. The presence of anti–Jo-1 antibodies defines a distinct group of polymyositis patients with interstitial lung disease, arthritis, and fevers. The anti–Jo-1 response appears to be self-antigen driven, having a broad spectrotype over time and undergoing isotype switching. Anti–Jo-1 antibodies also inhibit the function of histidyl-tRNA synthetase in humans more than they do in other species.

Anti–Mi-2 antibodies recognize a major protein of a nuclear complex formed by at least 7 proteins that is involved in the transcription process. Autoantibodies recognizing Mi-2 are considered specific serologic markers of dermatomyositis. They are detected in about 10% of patients with myositis and are associated with relatively acute onset, a good prognosis, and a good response to therapy.

Anti-SRP antibodies are directed toward an RNA-protein complex that consists of 6 proteins and a 300-nucleotide RNA molecule (7SL RNA) and present in 5% of myositis patients [9] . Patients with anti-SRP antibodies have acute polymyositis with cardiac involvement, a poor prognosis, and a poor response to therapy.

Myositis-associated antibodies

The MAA are found in the sera of 20-50% of patients and are commonly encountered in other connective tissue diseases. The most important antigenic targets of the MAA are the following:

  • PM/Scl nucleolar antigen
  • Nuclear Ku antigen
  • Small nuclear ribonucleoproteins (snRNP)
  • Cytoplasmic ribonucleoproteins (RoRNP)

Anti-PM/Scl autoantibodies are generally found in patients affected by polymyositis overlapping with scleroderma. Anti-Ku antibodies are found in patients with myositis overlapping with other connective tissue diseases.

Antibodies directed against snRNP are frequently found in patients with myositis and in patients with connective tissue–disease overlap syndrome, whereas antibodies toward Ro/SSA 60 kD, Ro/SSA 52 kD, and La/SSB protein components of the RoRNP complex are almost exclusively found in patients with Sjögren syndrome and systemic lupus erythematosus (SLE).

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Etiology

Polymyositis is an immune-mediated syndrome secondary to defective cellular immunity that is most commonly associated with other systemic autoimmune diseases. It may be due to diverse causes that occur alone or in association with viral infections, malignancies, or connective-tissue disorders.

Risk factors

An increased association of myositis has been found with human leukocyte antigen (HLA) haplotypes A1, B8, and DR3, which also increase the risk for autoimmune diseases. Environmental triggers, especially infectious agents, have been suggested as etiologic agents. These include the following:

  • Coxsackievirus B1
  • HIV
  • HTLV-1
  • Hepatitis B virus
  • Influenza
  • Echovirus
  • Adenovirus

Many drugs are known to cause myopathy. Most of those drugs, such as hydroxychloroquine and colchicine, cause a toxic or metabolic myopathy. However, several drugs may rarely induce an immune-mediated myopathy or myositis; in these cases, muscle biopsy shows chronic inflammatory changes consistent with polymyositis. Drugs such as D-penicillamine, hydralazine, procainamide, phenytoin, and angiotensin-converting enzyme (ACE) inhibitors have been associated with this type of inflammatory myopathy. Statins can cause severe muscle inflammation and rhabdomyolysis.

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Epidemiology

Frequency

Idiopathic inflammatory myopathies are relatively rare diseases, with an incidence in the United States that ranges from 0.5-8.4 cases per million population. Polymyositis is more common in the United States within the Black population, with the estimated Black-to-White incidences for polymyositis and dermatomyositis being 5:1 and 3:1, respectively. Internationally, polymyositis is less common among the Japanese. 

Sex- and age-related demographics

Polymyositis and dermatomyositis are more common in women than in men (2:1 ratio), while inclusion body myositis is twice as common in men.

Polymyositis usually affects adults older than 20 years, especially those aged 45-60 years. Polymyositis rarely affects children. The age of onset of polymyositis with another collagen vascular disease is related to the associated condition.

Although dermatomyositis is primarily a disease of adults, it can be seen in children, usually those aged 5-14 years. Eighty percent of patients with inclusion body myositis are older than 50 years at onset.

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Prognosis

In most patients, polymyositis responds well to treatment, although residual weakness occurs in approximately 30% of patients. Osteoporosis, a common complication of long-term corticosteroid therapy, may cause significant morbidity. A study from Taiwan determined that the risk of osteoporosis was 2.99 times higher in patients with polymyositis, and that the risk was independent of corticosteroid and immunosuppressant treatment. [10]

Poor prognostic factors include the following:

  • Advanced age
  • Female sex
  • African-American race
  • Interstitial lung disease
  • Presence of anti-Jo-1 (lung disease) and anti-SRP antibodies (severe muscle disease, cardiac involvement)
  • Associated malignancy
  • Delayed or inadequate treatment
  • Dysphagia, dysphonia
  • Cardiac and pulmonary involvement

Watanabe et al reported that negative assays for myositis-specific autoantibodies and the absence of severe muscle weakness requiring assistance at diagnosis are independent predictive factors for sustained remission in adult patients with polymyositis/dermatomyositis. [11]

Complications

Complications of polymyositis may include the following:

  • Interstitial lung disease (ILD)
  • Aspiration pneumonia
  • Heart block
  • Arrhythmias
  • Congestive heart failure
  • Pericarditis
  • Dysphagia
  • Malabsorption
  • Pneumonia
  • Infection [12]
  • Myocardial infarction [13]
  • Carcinoma - Especially in the breast and lung [14]
  • Steroid myopathy or other complications of steroid therapy

Carruthers et al reported that patients with polymyositis are at increased risk for venous thromboembolism (VTE), with hazard ratios of 7.0 for VTE, 6.16 for deep venous thrombosis, and 7.23 for pulmonary embolism. Overall, the highest calculated incidence rate ratios were observed in the first year after diagnosis of polymyositis. [15]

A meta-analysis estimated that worldwide, the prevalence of ILD in patients with polymyositis and dermatomyositis is 41%, with the highest prevalence among Asians (50%). ILD was more frequently associated with anti-Jo-1 and anti-melanoma differentiation–associated gene 5 antibodies than other myositis-specific autoantibodies. [16]

The incidence of lung, bladder, and non-Hodgkin lymphoma may be increased in patients with polymyositis, especially in the first year after diagnosis. Nicoletis et al reported that a high pretreatment neutrophil-to-lymphocyte ratio (≥5.5) is associated with an increased risk of cancer in patients with polymyositis/dermatomyositis. These authors concluded that in patients age 60 years and older, a high neutrophil-to-lymphocyte ratio should prompt investigation for cancer, both at diagnosis of polymyositis and during follow-up. [17]

Polymyositis shares pathologic characteristics and immunologic features with amyotrophic lateral sclerosis (ALS), and a nationwide cohort study from Taiwan found that a diagnosis of polymyositis increased the likelihood of a subsequent diagnosis of ALS (P < 0.001). The association was independent of sex, age, and concomitant autoimmune diseases. [18]

Five-year survival rates in polymyositis have been estimated at more than 80%. Mortality is most often related to associated malignancy or pulmonary complications; however, elderly patients with cardiac involvement or dysphagia also have a higher mortality rate. [19]

 

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Patient Education

Patients with polymyositis should be educated early about the disease, its complications, and treatment options and should be provided with realistic expectations about outcomes. Most patients show significant improvement with treatment. Stress the need for close follow-up care, continued physical therapy, and long-term therapy with monitoring of several parameters including medication toxicity and screening for malignancy. 

For patient education information, see Polymyositis. In addition, patients may visit The Myositis Association Web site.

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