Autoimmune myositis is characterized by inflammatory and degenerative changes in the muscles (polymyositis, necrotizing immune-mediated myopathy) 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 creatine kinase test, 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.
Autoimmune myositis is more common in females than males by a 2:1 ratio. The incidence is 3 to 4 times higher in Black people 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 of Autoimmune Myositis
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 of Autoimmune Myositis
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, polymyositis is characterized by direct T cell–mediated muscle injury, and necrotizing immune-mediated myopathies are characterized by macrophage-predominant infiltrates and myophagocytosis.
Classification of Autoimmune Myositis
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, which can be 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 most often include signal recognition particle (SRP) antibody–related myositis and statin-induced myositis, usually have an aggressive presentation, very elevated creatine kinase (CK) levels, and do not involve extramuscular organs (1).
Inclusion body myositis causes proximal leg muscle weakness, but frequently involves distal muscles (eg, hand and foot muscles) often with muscle wasting. It develops at an older age, has a slower progression, and does not generally respond to 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).
Classification reference
1. Lundberg IE, Fujimoto M, Vencovsky J, et al. Idiopathic inflammatory myopathies. Nat Rev Dis Primers 7(1):86, 2021. doi:10.1038/s41572-021-00321-x
Symptoms and Signs of Autoimmune Myositis
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 rarely develop.
Joint manifestations include polyarthralgia or polyarthritis with swelling 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, lateral thighs, elbows and knees, medial malleoli, and dorsal aspects of the proximal interphalangeal and metacarpophalangeal joints (Gottron papules—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.
This photo shows violaceous rash around the eyes and in the nasolabial folds and chin in a patient with dermatomyositis.
© Springer Science+Business Media
Gottron papules are scaly, erythematous to violaceous papules on extensor surfaces of proximal interphalangeal and metacarpophalangeal joints.
© Springer Science+Business Media
This photo shows Gottron papules (on metacarpophalangeal joints), subcutaneous calcifications (on metacarpophalangeal, proximal interphalangeal, and distal interphalangeal joints), and periungual erythema and thickening.
© Springer Science+Business Media
This image shows dusky, erythematous skin changes resulting from dermatomyositis.
Image courtesy of Karen McKoy, MD.
This photo shows hyperkeratosis and fissuring of the fingers in a patient with antisynthetase syndrome.
© Springer Science+Business Media
This photo shows violaceous rash around the eyes and in the nasolabial folds and chin in a patient with dermatomyositis.
© Springer Science+Business Media
Gottron papules are scaly, erythematous to violaceous papules on extensor surfaces of proximal interphalangeal and metacarpophalangeal joints.
© Springer Science+Business Media
This photo shows Gottron papules (on metacarpophalangeal joints), subcutaneous calcifications (on metacarpophalangeal, proximal interphalangeal, and distal interphalangeal joints), and periungual erythema and thickening.
© Springer Science+Business Media
This image shows dusky, erythematous skin changes resulting from dermatomyositis.
Image courtesy of Karen McKoy, MD.
This photo shows hyperkeratosis and fissuring of the fingers in a patient with antisynthetase syndrome.
© Springer Science+Business Media
Diagnosis of Autoimmune Myositis
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 creatine kinase [CK] is not elevated, aminotransferases or aldolase, which are far 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.
Autoantibodies in Autoimmune Myositis
Autoantibodies | Clinical Features |
|---|---|
Antisynthetase syndrome* | |
Anti-Jo-1 | Myositis† Interstitial lung disease |
Anti-PL-7 | Interstitial lung disease† Myositis |
Anti-PL-12 | 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 the more prominent one. 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. doi:10.1016/B978-0-444-63432-0.00025-6 | |
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 for Autoimmune Myositis
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 of Autoimmune Myositis
Corticosteroids
IV immune globulin
Physical activities should be modestly curtailed until the inflammation subsides.
Serial measurements of creatine 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 occasionally be positive in patients with myositis and normal CK levels. As enzyme levels fall toward or reach normal in many patients in 6 to 12 weeks, followed later by improved muscle strength, the corticosteroid dose can be gradually decreased. If muscle enzyme levels rise again, the corticosteroid dose is usually increased while awaiting the full effect of other medications.
2 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. If combination immunosuppressive therapy is used, patients should be given prophylaxis for opportunistic infections, such as Pneumocystis jirovecii (see prevention of Pneumocystis jirovecii pneumonia), and vaccines against common infections (eg, streptococcal pneumonia, influenza, COVID-19).
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 creatine 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.
