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Autoimmune Myositis

By

Alana M. Nevares

, MD, The University of Vermont Medical Center

Last full review/revision Feb 2020| Content last modified Feb 2020
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Autoimmune myositis is characterized by inflammatory and degenerative changes in the muscles (polymyositis) or in the skin and muscles (dermatomyositis). Manifestations include symmetric weakness, occasionally tenderness, and fibrous replacement of muscle, sometimes with atrophy, principally of the proximal limb girdle muscles. Diagnosis is by clinical findings and abnormalities on muscle tests, which may include muscle enzymes (aldolase and creatine phosphokinase), MRI, electromyography, and muscle biopsy. Several types of myositis have pulmonary and cardiac manifestations. Treatment is with corticosteroids combined with immunosuppressants and/or IV immune globulin.

The female:male ratio is 2:1. The incidence is 3 to 4 times higher in black than in white people. These disorders may appear at any age but occur most commonly from age 40 to 60 or, in children, from age 5 to 15.

Etiology

The cause of autoimmune myositis seems to be an autoimmune reaction to muscle tissue in genetically susceptible people. Familial clustering occurs, and human leukocyte antigen (HLA) subtypes are associated with myositis. For example, the alleles of the 8.1 ancestral haplotype (HLA-DRB1*03-DQA1*05-DQB1*02) increase risk of polymyositis, dermatomyositis, and interstitial lung disease. Possible inciting events include viral myositis and underlying cancer. The association of cancer with dermatomyositis (less so with polymyositis) suggests that a tumor may incite myositis as the result of an autoimmune reaction against a common antigen in muscle and tumor.

Pathophysiology

Pathologic changes include cellular damage and atrophy, with variable degrees of inflammation. Muscles in the hands, feet, and face are affected less than other skeletal muscles. Involvement of muscles in the pharynx and upper esophagus and occasionally the heart can impair the functions of those organs. Inflammation may occur in joints and lungs, especially in patients with antisynthetase antibodies.

Dermatomyositis is characterized by immune complex deposition in the vessels and is considered a complement-mediated vasculopathy. In contrast, the main pathophysiologic abnormality in polymyositis is direct T cell–mediated muscle injury.

Classification

Autoimmune myositis can be classified into 4 groups, mainly based on histopathology and clinical presentation:

  • Polymyositis

  • Dermatomyositis

  • Necrotizing immune-mediated myopathies

  • Inclusion body myositis

Dermatomyositis can be distinguished from polymyositis by the characteristic skin findings of dermatomyositis (see Symptoms and Signs). Muscle histopathology also differs. Dermatomyositis and polymyositis can manifest as pure muscle diseases or as part of antisynthetase syndrome when associated with arthritis (usually nonerosive), fever, interstitial lung disease, hyperkeratosis of the radial aspect of the digits (mechanic's hands), and Raynaud syndrome.

Necrotizing immune-mediated myopathies include signal recognition particle (SRP) antibody–related myositis and statin-induced myositis, usually have an aggressive presentation, have very elevated creatine kinase (CK) levels, and do not involve extramuscular organs.

Inclusion body myositis is a separate disorder that has clinical manifestations similar to chronic idiopathic polymyositis; however, it develops at an older age, frequently involves distal muscles (eg, hand and foot muscles) often with muscle wasting, has a slower progression, and does not respond to therapy (immunosuppressive therapy).

Autoimmune myositis can also overlap with other autoimmune rheumatic disorders—eg, systemic lupus erythematosus, systemic sclerosis, mixed connective tissue disease. These patients have symptoms and signs of the overlap disorders in addition to myositis (manifest as either dermatomyositis or polymyositis).

Symptoms and Signs

Onset of autoimmune myositis may be acute (particularly in children) or insidious (particularly in adults). Polyarthralgias, Raynaud syndrome, dysphagia, pulmonary symptoms (eg, cough, dyspnea), and constitutional complaints (notably fever, fatigue, and weight loss) may also occur. Severe disease is characterized by dysphagia, dysphonia, and/or diaphragmatic weakness.

Muscle weakness may progress over weeks to months. However, it takes destruction of 50% of muscle fibers to cause symptomatic weakness (ie, muscle weakness indicates advanced myositis). Patients may have difficulty raising their arms above their shoulders, climbing steps, or rising from a sitting position. Sometimes muscle tenderness and atrophy develop. Patients may require the use of a wheelchair or become bedridden because of weakness of pelvic and shoulder girdle muscles. The flexors of the neck may be severely affected, causing an inability to raise the head from the pillow. Involvement of pharyngeal and upper esophageal muscles may impair swallowing and predispose to aspiration. Muscles of the hands, feet, and face are not involved except in inclusion body myositis, in which distal involvement, especially of the hands, is characteristic. Limb contractures may eventually develop.

Joint manifestations include polyarthralgia or polyarthritis, often with swelling, effusions, and other characteristics of nondeforming arthritis. They occur more often in a subset with Jo-1 or other antisynthetase antibodies.

Visceral involvement (except that of the pharynx and upper esophagus) is less common in autoimmune myositis than in some other rheumatic disorders (eg, systemic lupus erythematosus, systemic sclerosis). Occasionally, and especially in patients with antisynthetase antibodies, interstitial lung disease (manifested by dyspnea and cough) is the most prominent manifestation. Cardiac involvement, especially conduction disturbances and ventricular dysfunction, can occur. Gastrointestinal symptoms, more common among children, are due to an associated vasculitis and may include abdominal pain, hematemesis, melena, and ischemic bowel perforation.

Skin changes, which occur in dermatomyositis, tend to be dusky and erythematous. Photosensitivity and skin ulceration are visible. Periorbital edema with a purplish appearance (heliotrope rash) is relatively specific for dermatomyositis. Elsewhere, the rash may be slightly elevated and smooth or scaly; it may appear on the forehead, V of the neck and shoulders, chest and back, forearms and lower legs, elbows and knees, medial malleoli, and radiodorsal aspects of the proximal interphalangeal and metacarpophalangeal joints (Gottron papules—also a relatively specific finding). The base and sides of the fingernails may be hyperemic or thickened. Desquamating dermatitis with splitting of the skin may evolve over the radial aspects of the fingers. Subcutaneous and muscle calcification may occur, particularly in children. The primary skin lesions frequently fade completely but may be followed by secondary changes (eg, brownish pigmentation, atrophy, persistent neovascularization, scarring). Rash on the scalp may appear psoriaform and be intensely pruritic. Characteristic skin changes can occur in the absence of muscle disease, in which case the disease is called amyopathic dermatomyositis.

Skin Changes in Dermatomyositis

Diagnosis

  • Clinical criteria

  • Muscle biopsy (definitive)

Autoimmune myositis should be suspected in patients with proximal muscle weakness with or without muscle tenderness. Dermatomyositis should be suspected in patients with symptoms of myositis and skin findings compatible with dermatomyositis. Establishing the diagnosis of autoimmune myositis requires as many as possible of the following 5 criteria:

  • Proximal muscle weakness

  • Characteristic rash

  • Elevated serum muscle enzymes (if CK is not elevated, aminotransferases or aldolase [which are less specific than CK])

  • Characteristic electromyographic or MRI muscle abnormalities

  • Muscle biopsy changes (the definitive test)

Biopsy findings can vary, but chronic inflammation with muscle degeneration and some regeneration is typical. Polymyositis and dermatomyositis can often be distinguished by muscle biopsy. A definite diagnosis made by muscle biopsy is recommended before treatment of polymyositis to exclude other muscle disorders, such as those due to missing or defective enzymes, necrotizing myositis, and postviral rhabdomyolysis. Muscle biopsy is not usually necessary when skin findings are characteristic for dermatomyositis. There is no pathognomic skin finding for dermatomyositis on biopsy, but the absence of direct immunofluorescence helps distinguish the rash from the rash in patients with systemic lupus erythematosus.

To increase the sensitivity of the biopsy results, the biopsy sample should be obtained from a muscle that has one or more of the following characteristics:

  • Weakness on clinical examination

  • Muscle edema identified on MRI

  • Contralateral pair of a muscle shown to be abnormal on electromyography

Laboratory studies can increase or decrease suspicion for the disorder, assess its severity, identify overlaps, and help detect complications. Autoantibodies should be tested. Antinuclear antibodies (ANA) are positive in up to 80% of patients with dermatomyositis and polymyositis. If the ANA test is positive, further testing for specific types of antibodies is important in increasing the suspicion for an overlap syndrome.

Clinical course and manifestations are associated with particular antibodies as described in table Autoantibodies in Autoimmune Myositis. The relationship between these autoantibodies and disease pathogenesis remains unclear, although antibody to Jo-1 is a significant marker for fibrosing alveolitis, pulmonary fibrosis, arthritis, and Raynaud syndrome. There are no antibodies specific for polymyositis.

Table
icon

Autoantibodies in Autoimmune Myositis

Autoantibodies

Clinical Features

Antisynthetase syndrome*

Anti-Jo-1

Myositis†

Interstitial lung disease

Anti-PL-7

Interstitial lung disease†

Myositis

Anti-PL12

Interstitial lung disease†

Myositis

Anti-EJ

Interstitial lung disease

Myositis

Anti-OJ

Interstitial lung disease

Myositis

Anti-KS

Interstitial lung disease†

Myositis

Anti-ZO

Interstitial lung disease

Myositis

Anti-HA

Interstitial lung disease

Myositis

Dermatomyositis

Anti-Mi-2

Severe skin disease

Responds well to treatment

Anti-MDA5

Cardiopulmonary syndrome

Amyopathic dermatomyositis, palmar papules

Anti-TIF1g

Increased cancer risk

Anti-NXP-2

Subcutaneous calcinosis

Increased cancer risk

Necrotizing immune-mediated myopathy

Anti-SRP

Severe, difficult to treat

Anti-HMGCR

Immune-mediated statin-associated myopathy (can rarely be present without previous exposure to prescription statins)

Inclusion body myositis

Cytosolic 5'-nucleotidase 1A

Inclusion body myositis

* All of these autoantibodies can be present in patients with complete or incomplete forms of antisynthetase syndrome. Antisynthetase syndrome features include fever, nonerosive arthritis, interstitial lung disease, hyperkeratosis of the radial aspect of the digits (mechanic's hands), and Raynaud syndrome. The rash of dermatomyositis may or may not be present. Patients with antisynthetase syndrome antibodies and muscle disease may have findings of dermatomyositis or polymyositis.

† This feature is more prominent than the other ones.

Modified from Mammen A: Autoimmune Muscle Disease. In Handbook of Clinical Neurology, edited by SJ Pittock and A Vincent. Elsevier BV, 2016, pp. 467–484.

Evidence for increased risk of cancer is relatively strong in dermatomyositis and less strong for polymyositis. Therefore, cancer screening should be considered for patients ≥ 40 years who have dermatomyositis or for patients 60 years who have polymyositis because these patients often have unsuspected cancers. Screening should include at least a physical examination that includes the breasts, pelvis, and rectum (with occult blood testing); complete blood count (CBC); biochemical profile; mammogram; urinalysis; chest x-ray; and any other tests appropriate based on the patient’s age. Additional investigation should be based on history and physical examination findings. Some authorities recommend CT of the chest, abdomen, and pelvis as well as colonoscopy, particularly in patients who have dermatomyositis. Younger patients without symptoms of cancer need not undergo screening.

Prognosis

Long remissions (even apparent recovery) occur in up to 50% of treated patients within 5 years, more often in children. Relapse, however, may still occur at any time. Overall 5-year survival rate is 75% and is higher in children. Death in adults is preceded by severe and progressive muscle weakness, dysphagia, undernutrition, aspiration pneumonia, or respiratory failure with superimposed pulmonary infection. Death in children with dermatomyositis may be a result of bowel vasculitis. Dermatomyositis and polymyositis have been linked to an increased cancer risk. Cancer, if present, generally determines the overall prognosis.

Treatment

  • Corticosteroids

  • Immunosuppressants (eg, methotrexate, azathioprine, mycophenolate mofetil, rituximab, tacrolimus)

  • IV immune globulin

Physical activities should be modestly curtailed until the inflammation subsides.

Corticosteroids are the drugs of choice initially. For acute disease, adults receive oral prednisone 1 mg/kg (usually about 40 to 60 mg) once a day. For severe disease with dysphagia or respiratory muscle weakness, treatment usually starts with pulse corticosteroid therapy (eg, methylprednisolone 0.5 to 1 g IV once a day for 3 to 5 days).

Serial measurements of creatinine kinase (CK) provide the best early guide of therapeutic effectiveness. However, in patients with widespread muscle atrophy, levels are occasionally normal despite chronic, active myositis. MRI findings of muscle edema or high CK levels generally differentiate a relapse of myositis from corticosteroid-induced myopathy. Aldolase is an alternative, being less specific for muscle injury than CK, but can be positive in patients with myositis and normal CK levels. Enzyme levels fall toward or reach normal in most patients in 6 to 12 weeks, followed by improved muscle strength. Once enzyme levels have returned to normal, prednisone can be gradually reduced. CK normalization usually precedes return of muscle strength. If muscle enzyme levels rise, the dose is increased.

The overall goal is to minimize corticosteroid exposure, which is why a second drug (typically methotrexate, tacrolimus, or azathioprine as first-line noncorticosteroid drugs) is started at the same time as corticosteroids or shortly after so that prednisone can be tapered to a maximum dose of 5 mg a day, ideally within about 6 months. IV immune globulin is a good option for patients who do not respond rapidly to therapy, develop infectious complications with high-dose corticosteroids and other immunosuppressants, or who are undergoing chemotherapy. Some experts may use a combination of all 3 therapies in severe cases or when corticosteroid toxicity is present. Children require initial doses of prednisone of 30 to 60 mg/m2 once a day.

Occasionally, patients treated chronically with high-dose corticosteroids become increasingly weak after the initial response because of a superimposed, painless corticosteroid myopathy. In these patients, CK remains normal even though the patients are weaker.

Myositis associated with cancer is more refractory to corticosteroids. Cancer-associated myositis may remit if the tumor is removed.

People with an autoimmune disorder are at higher risk of atherosclerosis and should be closely monitored. Patients on long-term corticosteroid therapy should receive osteoporosis prophylaxis. Prophylaxis for opportunistic infections, such as Pneumocystis jirovecii (see prevention of Pneumocystis jirovecii pneumonia), should be added if combination immunosuppressive therapy is used.

Key Points

  • Muscle weakness caused by myositis is most often proximal.

  • Heliotropic rash and Gottron papules are specific for dermatomyositis.

  • To establish the diagnosis, look for characteristic rash, muscle weakness, elevated creatinine kinase level, and muscle changes on electromyography or MRI.

  • Unless patients have the characteristic skin findings, do a muscle biopsy to confirm the diagnosis.

  • Consider screening patients ≥ 40 years with dermatomyositis and patients ≥ 60 years with polymyositis for cancer.

  • Treat patients with corticosteroids and other immunosuppressants.

Drugs Mentioned In This Article

Drug Name Select Trade
MEDROL
Gammagard S/D
CELLCEPT
OTREXUP
IMURAN
PROGRAF
RAYOS
RITUXAN
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