Polymyositis and Dermatomyositis
Polymyositis and dermatomyositis are uncommon systemic rheumatic disorders characterized by inflammatory and degenerative changes in the muscles (polymyositis) or in the skin and muscles (dermatomyositis). The most specific skin signs are Gottron papules over the knuckles and a periorbital heliotropic rash. Manifestations include symmetric weakness, some tenderness, and later atrophy, principally of the proximal limb girdle muscles. Complications can include visceral involvement and cancer. Diagnosis is by clinical findings and abnormalities on muscle tests, which may include muscle enzymes, MRI, electromyography, and muscle biopsy. Treatment is with corticosteroids, usually combined with immunosuppressants or IV immune globulin.
The female:male ratio is 2:1. These disorders may appear at any age but occur most commonly from age 40 to 60 or, in children, from age 5 to 15.
The cause seems to be an autoimmune reaction to muscle tissue in genetically susceptible people. Familial clustering occurs, and HLA subtypes -DR3, -DR52, and -DR6 seem to be the genetic predisposition. Possible inciting events include viral myositis and underlying cancer. Picornavirus-like structures have been found in muscle cells, but their significance is not known, and viruses can trigger similar disorders in animals. 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.
Pathologic changes in both disorders 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.
Myositis has been divided into several subtypes:
Primary idiopathic polymyositis can occur at any age and does not involve the skin.
Primary idiopathic dermatomyositis is similar to primary idiopathic polymyositis but also involves the skin.
Polymyositis or dermatomyositis associated with cancer can occur at any age but is most common among older adults; the cancer can develop up to 2 yr before or after the myositis.
Childhood dermatomyositis can be associated with systemic vasculitis.
Polymyositis or dermatomyositis can occur with an associated disorder such as progressive systemic sclerosis, mixed connective tissue disease, RA, SLE, or sarcoidosis.
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), has a longer duration, responds poorly to therapy, and has a different histologic appearance.
Onset of polymyositis may be acute (particularly in children) or insidious (particularly in adults). Polyarthralgias, Raynaud phenomenon, dysphagia, pulmonary symptoms, and constitutional complaints (notably fever, fatigue, and weight loss) may also occur.
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. Patients may become wheelchair-bound or 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 escape involvement. Limb contractures may eventually develop.
Joint manifestations include polyarthralgia or polyarthritis, often with swelling, effusions, and other characteristics of nondeforming arthritis, which occur in about 30% of patients. However, joint manifestations tend to be mild. 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 polymyositis than in some other rheumatic disorders (eg, SLE, systemic sclerosis). Occasionally, and especially in patients with antisynthetase antibodies, interstitial pneumonitis (manifested by dyspnea and cough) is the most prominent manifestation. Cardiac arrhythmias, especially including conduction disturbances or ventricular dysfunction, can occur. GI symptoms, more common among children, are due to an associated vasculitis and may include hematemesis, melena, and ischemic bowel perforation.
Skin changes, which occur in dermatomyositis, tend to be dusky and erythematous. 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. The primary skin lesions frequently fade completely but may be followed by secondary changes (eg, brownish pigmentation, atrophy, scarring, vitiligo). Rash on the scalp may appear psoriaform and be intensely pruritic. Subcutaneous calcification may occur, particularly in children.
Polymyositis should be suspected in patients with proximal muscle weakness with or without muscle tenderness. Dermatomyositis should be suspected in patients with a heliotropic rash or Gottron papules, even without myositis, and in patients with symptoms of polymyositis and any skin findings compatible with dermatomyositis. Polymyositis and dermatomyositis share certain clinical findings with systemic sclerosis or, less frequently, with SLE or vasculitis. Establishing the diagnosis requires as many as possible of the following 5 criteria:
Muscle biopsy excludes some similar conditions such as inclusion body myositis and postviral rhabdomyolysis. Biopsy findings can be variable, but chronic inflammation and muscle degeneration and regeneration are typical. A definite diagnosis made by muscle biopsy is recommended before treatment of polymyositis to exclude other muscle disorders. 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:
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. Detailed testing of ANA, when present, is important in identifying other overlap syndromes, most often those with another autoimmune disorder. About 30% of patients have myositis-specific autoantibodies: antibodies to aminoacyl-tRNA synthetases (anti-synthetase antibodies), including anti–Jo-1; antibodies to signal recognition particle (SRP—anti-SRP antibodies); and antibodies to Mi-2, a nuclear helicase. 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 phenomenon.
Periodic measurement of CK is helpful in monitoring treatment. However, in patients with widespread muscle atrophy, levels are occasionally normal despite chronic, active myositis. Muscle biopsy, MRI, or high CK levels can often differentiate a relapse of polymyositis from corticosteroid-induced myopathy. Aldolase is a less specific marker for muscle injury than CK.
Cancer screening is recommended by some authorities for patients ≥ 40 yr who have dermatomyositis or for patients ≥ 60 yr who have polymyositis because these patients often have unsuspected cancers. Screening should include a physical examination that includes breast, pelvis, and rectum (with occult blood testing); CBC; biochemical profile; mammogram; carcinoembryonic antigen; urinalysis; chest x-ray; and any other tests appropriate based on patient’s age. Additional investigation should be based on history and physical examination findings. Some authorities recommend CT of the chest, abdomen, and pelvis. Younger patients without symptoms of cancer need not undergo screening.
Long remissions (even apparent recovery) occur in up to 50% of treated patients within 5 yr, more often in children. Relapse, however, may still occur at any time. Overall 5-yr 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. Polymyositis tends to be more severe and resistant to treatment in patients with cardiac or pulmonary involvement. Death in children may be a result of bowel vasculitis. Cancer, if present, generally determines the overall prognosis.
Physical activities should be modestly curtailed until the inflammation subsides. Corticosteroids are the drugs of choice initially. For acute disease, adults receive prednisone ≥ 40 to 60 mg po once/day. Serial measurements of CK provide the best early guide of therapeutic effectiveness, falling toward or reaching normal in most patients in 6 to 12 wk, followed by improved muscle strength. Once enzyme levels have returned to normal, prednisone can be gradually reduced. If muscle enzyme levels rise, the dose is increased. Patients who seem to recover can have treatment gradually withdrawn with close monitoring, but most adults require chronic maintenance with prednisone (up to 10 to 15 mg/day). Children require initial doses of prednisone of 30 to 60 mg/m2 once/day. In children, it may be possible to stop prednisone after ≥ 1 yr of remission.
Occasionally, patients treated chronically with high-dose corticosteroids become increasingly weak because of a superimposed corticosteroid myopathy.
If a patient does not to respond to corticosteroids, depends on a high to moderate dose of corticosteroids, or develops a corticosteroid myopathy or another complication that necessitates stopping or decreasing prednisone, immunosuppressants (eg, methotrexate, azathioprine, mycophenolate mofetil, rituximab, cyclosporine, IV immune globulin) should be tried. Some clinicians combine prednisone with an immunosuppressant at the time treatment is initiated. Some patients have received only methotrexate (generally in higher doses than used for RA) for ≥ 5 yr. IV immune globulin can be effective in some patients refractory to drug treatment, but the prohibitive cost has discouraged comparative trials.
Myositis associated with cancer or inclusion body myositis usually 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, should be added if combination immunosuppressive therapy is used.
Muscle weakness indicates advanced myositis.
Heliotropic rash and Gottron papules are relatively specific for dermatomyositis.
To establish the diagnosis, look for characteristic muscle weakness and rash, elevated CK level, and muscle changes on electromyography or MRI.
If necessary, do a muscle biopsy to confirm the diagnosis.
Screen patients ≥ 40 yr with dermatomyositis and patients ≥ 60 yr with polymyositis for cancer.
Treat most patients with corticosteroids and sometimes other immunosuppressants.