34.

Chapter 27 Polymyositis and Dermatomyositis

Manual of Rheumatology and Outpatient Orthopedic Disorders


Chapter 27 Polymyositis and Dermatomyositis

J. Robert Polk and Lawrence J. Kagen

Disease classification
Pathogenesis
Clinical presentation
Laboratory studies
Differential diagnosis
Treatment
Prognosis

Polymyositis (PM) is an inflammatory disease of striated skeletal muscle. In some patients , a characteristic skin rash is present, thus the term dermatomyositis. Dermatomyositis (DM) was described by Unverricht in 1887. PM occurs at any age, but most cases occur between the fourth and sixth decades of life, with a mild female preponderance. A childhood form of DM has been recognized. Estimates of the prevalence of PM range from 0.2 to 0.6 cases per 100,000 population. DM may be associated with malignancy.

I. Disease classification. Various classification systems have been proposed. It should be remembered that not all patients who are weak have PM. The following is a useful classification system:

  1. Dermatomyositis
    1. Childhood.
    2. Adulthood.
  2. Polymyositis.
  3. Myositis associated with other connective tissue and inflammatory disorders (e.g., systemic lupus erythematosus, rheumatoid arthritis, scleroderma, sarcoidosis).
  4. Myositis associated with malignancy.
  5. Inclusion body myositis.
  6. Myositis secondary to infectious agents .
  7. Drug- and toxin-induced myositis.

II. Pathogenesis

  1. The etiology of PM is unknown. Current thoughts relate to possible aberrations in the immune system that give rise to an increased susceptibility to infectious agents, and to modifications of cellular immunity that lead to the development of mononuclear cells capable of injuring muscle. Complement may play a role in tissue injury in DM. Evidence of infection has been sought. At present, the best candidates are viruses and Toxoplasma gondii.

    Certain viruses, such as those of the influenza virus and coxsackievirus groups, may produce myopathy, and serologic evidence of recent viral infection has been found in some patients. Serologic evidence of recent Toxoplasma infection has also been demonstrated in some groups of patients with PM. This organism can produce myopathy in humans and experimental animals.

  2. The histologic appearance of muscle among these seven groups by ordinary light microscopy is quite similar. The principal feature is an inflammatory cellular infiltrate in muscle, with an associated degeneration and necrosis of muscle fibers. Regeneration of fibers and a perivascular inflammatory infiltrate may be seen. A later finding is interstitial fibrosis. Calcinosis may be seen, especially in the childhood form. Not all the changes of degeneration, inflammatory infiltrate, regeneration, necrosis, and fiber size variation need be present. In 10% to 20% of muscle biopsies, the findings may be normal. The vasculopathy of childhood myositis may be seen in small arteries of muscle, skin, and the gastrointestinal tract . Inclusion body myositis is characterized by the presence of eosinophilic inclusions in the sarcoplasm, nucleus, or both. Rimmed vacuoles filled with basophilic granules are seen on frozen sections. The inclusions appear as masses of filamentous material by electron microscopy.

    The infiltrates in PM and inclusion body myositis contain mainly CD8+ T lymphocytes and macrophages. B cells are more common in biopsy specimens of muscle tissue in DM.

  3. The skin findings are marked by an infiltrate of CD4+ T lymphocytes.

III. Clinical presentation

  1. General diagnostic considerations. Pearson has defined several criteria for classifying patients with PM. The diagnosis of PM is definite when four criteria are present, probable with three, and possible with two. DM must include the characteristic rash, and the diagnosis is definite with three or four criteria present, probable with two, and possible with one. The criteria are as follows :
    1. Symmetric proximal muscle weakness with or without dysphagia or respiratory muscle involvement.
    2. Elevation of serum enzymes: creatine kinase (CK), aldolase, lactic dehydrogenase, and serum aspartate aminotransferase.
    3. Typical electromyographic triad
      1. Small-amplitude, polyphasic motor unit potentials.
      2. Pseudomyotonic high-frequency pattern.
      3. Spontaneous fibrillation and positive sharp waves (sawtooth pattern) in resting muscle.
    4. Typical histology in muscle specimens, as described in section II.B.
    5. Characteristic skin rash of dermatomyositis, consisting of a lilac discoloration of the upper eyelids with periorbital edema (heliotrope rash) and an erythematous or atrophic scaling, patchy, or linear rash involving the extensor surfaces of the joints, face, neck, back, and chest in a V-shaped pattern.

      Erythematous scaling (Gottron's) papules occur over the metacarpophalangeal and proximal interphalangeal joints.

  2. Diagnostic characteristics of polymyositis types
    1. Childhood myositis
      1. Childhood DM-PM appears most commonly between ages 7 and 10 years . It occurs slightly more often in girls than in boys. Most patients have the characteristic rash of DM at presentation. About 90% present with proximal muscle weakness. Raynaud's phenomenon is said to be less common in childhood DM-PM, but up to 18% of patients may have it.
      2. Distinctive features of the myopathy are atrophy, contractures, and tissue calcifications. Calcifications usually appear after the disease has been present for a year or more.
      3. Visceral involvement is probably more frequent in the childhood than in the adult form. Abnormal pulmonary function, esophageal motility , and gastrointestinal absorption have been reported . Some patients may present with an acute myositis with accompanying fever , malaise, and abdominal pain. Gastrointestinal ulcerations caused by a diffuse necrotizing arteritis (which may also be seen in skin and muscle) may occur and lead to hemorrhage.
    2. Dermatomyositis in adults. Rash is the primary presenting feature of DM and is present initially in about 95% of patients. Only 50% to 60% of patients have proximal muscle weakness at presentation. Follow-up of patients with a rash is therefore essential, as it is a rare patient who will not eventually manifest proximal weakness. Arthralgia, Raynaud's phenomenon, and dysphagia are seen in 10% to 25% of DM patients. As in PM, interstitial pneumonitis, cardiomyopathy, and heart block have been reported but are rare manifestations .
    3. Polymyositis in adults. Proximal muscle weakness is the presenting feature in 90% to 95% of patients with PM. Myalgia is common. Arthralgia, Raynaud's phenomenon, and dysphagia are seen in 10% to 15%. Patients usually have an insidious onset of proximal weakness and their condition may remain undiagnosed for several months because their complaints are vague. They may note gradually increasing difficulty in climbing steps or getting out of a chair . They may complain of not being able to comb their hair or reach above their heads. Eventually, patients may become bedridden and be unable to raise their head from a pillow.
    4. Myositis associated with other connective tissue diseases. Overlap syndromes as defined here consist of PM or DM that fulfills the previously mentioned criteria and another connective tissue disease that fulfills a separate set of diagnostic criteria. These patients present more commonly than other PM patients with Raynaud's phenomenon, sclerodactyly, arthralgia, and myalgia (about 50%). Proximal muscle weakness is seen in 40% at presentation, and the characteristic rash of DM in 20%. The presenting features reflect the underlying connective tissue disease; systemic sclerosis, systemic lupus erythematosus, and rheumatoid arthritis are the diseases most commonly associated with PM features. Sicca syndrome and necrotizing vasculitis are also associated with PM-DM.
    5. Inflammatory myositis associated with malignancy. Controversy exists concerning the true association of PM and DM with malignancy. Most reports indicate that DM has a higher association with malignancy than does PM. Between 10% and 20% of patients with PM-DM may have an underlying malignancy. It is said that the possibility of malignancy in an elderly patient with PM-DM is four times greater than in an age-matched control. Dysphagia occurs in 15% of patients. In PM-DM of malignancy, myositis precedes malignancy by an average of 1 to 2 years in 70% of patients and follows it in 30%. In some of the patients, neuropathy may also be associated.
    6. Inclusion body myositis is typically a disorder of older men. Progress of disease is often insidious, with only borderline elevation of enzymes. Neuropathic features may be noted, and response to therapy is poor.
    7. Infectious agents. History and serologic findings often provide clues to the diagnosis. The following categories should be considered :
      1. Viral infection (e.g., influenza virus, coxsackievirus, human immunodeficiency virus).
      2. Toxoplasmosis.
      3. Bacterial pyomyositis.
      4. Lyme myositis.
    8. Drug- and toxin-induced myositis. Penicillamine employed to treat rheumatoid arthritis may be the cause of a syndrome indistinguishable from naturally occurring PM. In addition, myositis-like states have been noted in patients treated with propylthiouracil and azathioprine. Other agents (e.g., lovastatin and other statins, gemfibrozil) may rarely cause painful myopathy and rhabdomyolysis. Zidovudine [formerly called azidothymidine (AZT)] also has produced myopathy and myositis.

      Certain toxins (i.e., alcohol, cocaine) may also produce severe acute or chronic myopathy.

IV. Laboratory studies

  1. White blood cell count and hemoglobin level are generally normal.
  2. Erythrocyte sedimentation rate may be elevated or normal.
  3. Creatine kinase, aldolase, serum aspartate aminotransferase, and lactic dehydrogenase are elevated, with decreasing sensitivity as listed.
  4. Serum myoglobin is elevated.
  5. Urine may contain myoglobin but is otherwise usually normal.
  6. Antinuclear antibodies may be present.
  7. Total hemolytic complement is normal, except in childhood DM, where it may be low.
  8. Anti-tRNA synthetase may be present, especially in association with pulmonary disease.
  9. Electromyographic triad
    1. Short-duration, small-amplitude, and polyphasic potentials appear on voluntary contraction.
    2. Spontaneous high-frequency potentials (pseudomyotonic discharges) can be triggered by movement of the electrode.
    3. Spontaneous fibrillation and positive sharp waves (sawtooth pattern) are identical to the denervation pattern.
  10. Muscle biopsy reveals inflammatory cellular infiltration of muscle with degeneration, necrosis, and regeneration of muscle fibers.
  11. An age-appropriate evaluation for malignancy is appropriate in PM and DM patients over the age of 50.

V. Differential diagnosis

  1. Hypothyroid myopathy. Features such as weight gain, constipation, hoarseness, anemia, and a slow relaxation of deep tendon reflexes suggest this disorder. Serum CK and cholesterol may be elevated.
  2. Myasthenia gravis. Ocular symptoms and swallowing difficulties are prominent. Patients complain of increasing weakness with use of muscles and restoration of strength after rest. Muscle enzymes are normal, the result of the edrophonium test is positive, and the electromyogram has a characteristic pattern (see Chapter 10).
  3. Muscular dystrophies. A positive family history gives a clue to these disorders, and the average age at onset is younger than in PM. Electromyographic findings and muscle enzyme levels may be similar to those of PM; however, muscle biopsy usually serves to make the distinction, especially in children (see Chapter 10).
  4. Polymyalgia rheumatica. Levels of serum muscle enzymes are normal, the erythrocyte sedimentation rate is elevated, and malaise and proximal myalgia are prominent complaints (see Chapter 26).
  5. Fibromyalgia. Pain in muscles is a prominent complaint and multiple tender points are present, but weakness cannot be demonstrated clinically and muscle enzyme levels are normal (see Chapter 49).
  6. Alcohol abuse may be associated with acute rhabdomyolysis or chronic wasting myopathy.
  7. Trichinosis. The periorbital swelling and erythema may mimic those of DM. Distinguishing features include a history of ingesting undercooked pork, nausea, vomiting, abdominal pain, and eosinophilia.
  8. Electrolyte disturbances (especially of calcium, magnesium, phosphorus, and potassium) may be associated with myopathic symptoms and should be looked for, especially in patients on parenteral fluid replacement therapy.
  9. Metabolic disorders of carbohydrate and lipid metabolism (e.g., McArdle disease, carnitine palmityltransferase deficiency) may be associated with exertional myalgia and myoglobinuria.

VI. Treatment

  1. Supportive therapy. Patients may be hospitalized for diagnostic tests and initiation of rehabilitation . Range of motion and passive exercises should be performed to prevent contractures, especially in childhood myositis. However, active exercises are not tolerated well early in the course of severe disease.
  2. Corticosteroids. Once a firm diagnosis has been established, prednisone in a dosage of approximately 40 to 60 mg daily is begun. Clinical experience suggests that alternate-day steroid therapy is not as effective as initial therapy but may be used as the dosage is tapered. IV bolus steroids may also be used.

    Controversy exists concerning the best indicators of clinical response. Some experts believe that improvement in serum enzymes is the best indicator of response. The CK level will usually decrease to half its original value by 1 month but may not normalize for an average of 3 months. Because muscle strength often improves as CK levels return to normal, steroids may be tapered in small decrements with both muscle strength and serum enzyme levels used as guides. If relapse occurs, then a 60- to 80-mg daily dose of prednisone should be resumed immediately and tapering deferred until serum enzyme values approach normal. The goal is a daily dose of 5 to 15 mg of prednisone. This low dose of corticosteroid should be continued for 6 to 12 months to allow an adequate period of observation while some antiinflammatory effect is maintained . Discontinuation of steroids should then be attempted by slowly decreasing the dosage. A few patients may never be able to discontinue steroids because disease activity remains constant. If no clinical improvement occurs after 3 months of daily high doses of prednisone, cytotoxic drugs may be used.

  3. Cytotoxic drugs. See Appendix E for detailed drug information, including toxicity. The two most frequently used are methotrexate and azathioprine.
    1. Methotrexate is given PO at weekly intervals in doses from 7.5 to 30.0 mg. IV methotrexate in similar schedules has also been employed. Prednisone is also continued. As strength improves, prednisone may be slowly tapered and methotrexate continued. A response to methotrexate should be seen in about 12 weeks. Methotrexate may be tapered when clinical and laboratory parameters have improved. Hepatic fibrosis may develop with daily methotrexate therapy but is very rare in patients receiving the drug on a weekly schedule.
    2. Azathioprine (150 mg PO daily) may be used along with prednisone. Response may be noted after 1 to 3 months. Care should be taken to monitor frequently for side effects and to check blood counts regularly.
  4. Other therapies. A number of other agents have been used for patients who have not done well on the regimens described above. Among these agents have been cyclosporine and cyclophosphamide. Excellent results have recently been noted in certain patients given IV gamma globulin. Gamma globulin may be used early in therapy for selected patients.

VII. Prognosis. About 75% of patients respond to steroid therapy with improved muscle strength. About 90% of patients survive for long periods. The worst prognostic indicator is the presence of malignancy. Patients with myositis and malignancy have a poor 10-year survival. These data were collected retrospectively; some neoplasms may have been missed in this series because autopsies were not performed in all deceased patients. Patients with myositis of malignancy do not respond to steroid therapy as well as do other patients with PM. The leading cause of death, excluding malignancy, is sepsis. Patients treated early in the course of myositis seem to respond better than do those treated late in their illness . Myositis may occasionally improve during treatment of the underlying malignancy.

Bibliography

Kagen LJ. Management. In: Klippel JH, Dieppe PA, eds. Inflammatory muscle disease in rheumatology. London: Mosby, 1994:14.1.

Medsger TA, Oddis CV. Clinical features. In: Klippel JH, Dieppe PA, eds. Inflammatory muscle disease in rheumatology. London: Mosby, 1994:12.1.

Miller FW. Inflammatory myopathies: polymyositis, dermatomyositis, and related conditions. In: Koopman WJ, ed. Arthritis and allied conditions. Baltimore: Williams & Wilkins, 1997:1407.

Plotz PH, Miller FW. Etiology and pathogenesis. In: Klippel JH, Dieppe PA, eds. Inflammatory muscle disease in rheumatology. London: Mosby, 1994:13.1.

Spiera RF, Kagen L. Collagen vascular disease: polymyositis, dermatomyositis and inclusion body myositis. In: van de Putte DE, et al., eds. Therapy of systemic rheumatic disorders. New York: Marcel Dekker, 1998:547.

Wortman RL. Inflammatory disease of muscle and other myopathies. In: Kelley W, et al., eds. Textbook of rheumatology. Philadelphia: WB Saunders, 1997:1177.

Books@Ovid
Copyright 2000 by Lippincott Williams & Wilkins
Stephen A. Paget, M.D., Allan Gibofsky, M.D., J.D. and John F. Beary, III, M.D.
Manual of Rheumatology and Outpatient Orthopedic Disorders

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Manual of Rheumatology and Outpatient Orthopedic Disorders (LB Spiral Manuals)
Manual of Rheumatology and Outpatient Orthopedic Disorders (LB Spiral Manuals)
ISBN: N/A
EAN: N/A
Year: 2000
Pages: 315

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