The four main types of inflammatory muscle disease — dermatomyositis, polymyositis, necrotizing autoimmune myositis, and inclusion-body myositis — are summarized in a new review article. Pathogenesis, differential diagnosis, and treatment approaches are discussed.
The inflammatory myopathies constitute a heterogeneous group of disorders that are best classified, on the basis of distinct clinicopathologic features, as four subtypes: dermatomyositis, polymyositis, necrotizing autoimmune myositis, and inclusion-body myositis.
- What are the general clinical features of the inflammatory myopathies?
Patients with inflammatory myopathies have increasing difficulty with tasks requiring the use of proximal muscles, such as getting up from a chair, climbing steps, or lifting objects. In all disease subtypes, neck-extensor and pharyngeal muscles can be involved, which results in difficulty holding up the head (head drop) or in dysphagia. In advanced and rare acute cases, the respiratory muscles can be affected. Extramuscular manifestations may occur in all inflammatory myopathies, although they occur in inclusion-body myositis only in rare cases.
- Are there any clues to facilitate the early clinical diagnosis of inclusion-body myositis?
Inclusion-body myositis is the most common and disabling inflammatory myopathy among persons 50 years of age or older. Although inclusion-body myositis is commonly suspected when a patient with presumed polymyositis does not respond to therapy, features that can lead to an early clinical diagnosis include the observation of early involvement of distal muscles, especially foot extensors and finger flexors; evident atrophy of the forearms and quadriceps muscles; a history of frequent falls due to quadriceps muscle weakness causing buckling of the knees; and the presence of mild facial-muscle weakness.
Morning Report Questions
Q: What are some of the features of polymyositis and necrotizing autoimmune myositis?
A: Polymyositis is rare and often misdiagnosed. It remains a diagnosis of exclusion and is best defined as a subacute proximal myopathy in adults who do not have rash, a family history of neuromuscular disease, exposure to myotoxic drugs (e.g., statins, penicillamine, and zidovudine), involvement of facial and extraocular muscles, endocrinopathy, or the clinical phenotype of inclusion-body myositis. Necrotizing autoimmune myositis is a distinct clinicopathologic entity that occurs more frequently than polymyositis, accounting for up to 19% of all inflammatory myopathies. It can occur at any age but is seen primarily in adults; it starts either acutely, reaching its peak over a period of days or weeks, or subacutely, progressing steadily and causing severe weakness and very high creatine kinase levels. Necrotizing autoimmune myositis occurs alone or after viral infections, in association with cancer, or in patients taking statins, in whom the myopathy continues to worsen after statin withdrawal. Most patients with necrotizing autoimmune myositis have antibodies against signal recognition particle (SRP) or against 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR).
Q: How are the inflammatory myopathies diagnosed and treated?
A: The diagnosis of the exact subtype of inflammatory myopathy is based on the combination of clinical history, tempo of disease progression, pattern of muscle involvement, muscle enzyme levels, electromyographic findings, muscle-biopsy analysis, and for some conditions, the presence of certain autoantibodies. Oral prednisone administered once daily after breakfast at a dose of 1 mg per kilogram of body weight, up to 100 mg per day, is the first-line drug for the treatment of dermatomyositis, polymyositis, and necrotizing autoimmune myositis; this choice of drug is based on experience but not on controlled trials. In patients whose condition responds to glucocorticoids, azathioprine, mycophenolate mofetil, methotrexate, or cyclosporine is empirically used for glucocorticoid sparing. When glucocorticoids fail to induce remission or in rapidly progressive cases, intravenous immune globulin therapy is appropriate. With respect to inclusion-body myositis, glucocorticoids, methotrexate, cyclosporine, azathioprine, and mycophenolate are ineffective, and although some patients initially have mild improvements when treated with one of these agents, no long-term benefit is achieved.
Intravenous immune globulin has been found to be ineffective in controlled trials but may transiently help some patients, especially those with dysphagia.