Approach Considerations
Treatment of polymyositis (PM) is empirical because of the rarity of the disease and the paucity of randomized, controlled trials. Established options include corticosteroids and immunosuppressants; limited data support the use of other agents.
Corticosteroids
Prednisone is the first-line treatment of choice for polymyositis. Typically, the dose is 1 mg/kg/day, either as a single dose or in divided doses. This high dose is usually continued for 4-8 weeks, until the creatine kinase (CK) level returns to reference ranges. Taper prednisone by 5-10 mg on a monthly basis until the lowest dose that controls the disease is reached.
Monitor response to therapy based on improvement in muscle strength and muscle endurance and decrease in CK levels. Closely monitor patients with polymyositis for disease activity and adverse effects of corticosteroids, such as weight gain, hypertension, diabetes mellitus, osteopenia, and steroid myopathy.
Corticosteroid myopathy can occur during the course of treatment and must be distinguished from reactivation of muscle disease. The CK level is usually within reference ranges in patients with steroid myopathy. No improvement is observed with raised doses of steroids; rather, the condition worsens if the dose is increased.
Immunosuppressants
Immunosuppressive agents are indicated in patients who do not improve with steroids within a reasonable period (ie, 4 wk) or in whom adverse effects from corticosteroids develop. Patients with poor prognostic indicators, such as dysphagia or dysphonia, are likely to require immunosuppressive agents. Under these circumstances, methotrexate is the second-line agent. Azathioprine, cyclophosphamide, and cyclosporine have been used with varying success as second-line agents for polymyositis. Patients with inclusion body myositis usually respond poorly to corticosteroids and immunosuppressive agents.
Obtain the following baseline tests before initiating immunosuppressive therapy:
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Complete blood cell count (CBC)
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Liver function tests
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Muscle enzymes
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Pulmonary function studies
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Chest x-ray
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Tuberculosis testing
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Hepatitis B and C serology
Other agents
Intravenous immunoglobulin (IVIG) has been used for the short-term treatment of steroid-resistant cases of polymyositis. [32, 33]
The role of newer agents, such as tumor necrosis factor (TNF) inhibitors, remains unclear. Case reports describe successful use of the TNF inhibitor infliximab in refractory cases, but small clinical trials have yielded mixed results, with clinical flares occurring in some patients. [34, 35, 36, 37, 38] In a randomized controlled trial with crossover, 4 of 12 patients with refractory dermatomyositis and polymyositis responded to infliximab at a dose of 5 or 7.5 mg/kg; infliximab was well tolerated. [39]
A small trial of the TNF inhibitor etanercept provided encouraging results. [40]
The anti-CD20 monoclonal antibody rituximab may be an approach to therapy for refractory cases. The benefit of rituximab was demonstrated in the Rituximab in Myositis (RIM) study, the largest randomized trial ever completed in myositis. RIM included 200 patients with polymyositis, dermatomyositis, or juvenile dermatomyositis not controlled by corticosteroids and other immunosuppressive agents. [41]
The study had a placebo phase design in which half the patients received two rituximab infusions at baseline, whereas the other half received rituximab 8 weeks later. At a median of approximately 20 weeks, 83% of study subjects receiving rituximab met the International Myositis Assessment and Clinical Studies Group preliminary definition of improvement. Whether rituximab was received early or late made no significant difference in the time to achieve the definition of improvement. [41]
The calcineurin inhibitor tacrolimus appears to be effective, safe, and well tolerated in patients with polymyositis that is refractory to other treatments. [42] In a systematic review, CK levels patients decreased in all patients treated with tacrolimus, the average glucocorticoid dosage was reduced from 33.8 to 11.5 mg/day, and the majority of patients showed improvement in muscle strength and physical function status. However, randomized, controlled trials of tacrolimus in poymyositis have yet to be conducted. [43]
Mycophenolate mofetil has been reported in case reports to be effective. [44]
ACTH gel has shown some promise in case series with improvement in muscle as well as skin disease. Further randomized trials are required. [45]
Diet and Activity
Patients with polymyositis may benefit from a high-protein diet. Monitor patients to avoid excessive weight gain due to corticosteroid use.
Encourage patients with polymyositis to start a supervised exercise program early in the disease course. [46] During the acute stage of polymyositis, patients may benefit from heat therapy, passive range-of-motion exercises, and splints to avoid contractures.
Once acute inflammation is under control, the rehabilitation program should include active range-of-motion exercises and isometric contractions of the muscle groups. With improvement in muscle strength, patients should perform isotonic exercises with light resistance. Encourage patients to do 15-30 minute sessions of aerobic exercise when the disease is inactive.
Consultations
A neurologist or rheumatologist is the primary consultant. Consultation may also be required with the following specialists:
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Pulmonary specialists
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Cardiologists
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Physical therapists
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Speech therapists (for swallowing evaluation)
Extramuscular Manifestations of Polymyositis
Treatment of extramuscular manifestations of polymyositis includes the following:
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Constitutional symptoms, such as fever and fatigue - Usually respond to corticosteroids
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Articular symptoms - Usually resolve with treatment of the myositis; some patients develop a rheumatoid-like arthropathy, which may require immunosuppressive treatment such as methotrexate
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Interstitial lung disease - These patients may benefit from high-dose steroids and immunosuppressive treatment, especially cyclophosphamide. In a study of 30 patients and a historical comparison group of 21 patients, Shimojima et al reported improved outcomes when corticosteroids were combined with cyclosporine, administered orally or by continuous intravenous (IV) infusion for more severe cases; IV cyclophosphamide pulse therapy was added for exacerbations. [47] In a study of 14 patients with dermatomyositis and acute interstitial pneumonia treated with infliximab, Chen et al reported satisfactory relief in the 10 patients given early treatment but treatment failure and death in those treated late. [48] Results of a study by Takada et al in 26 patients suggest that initial treatment with tacrolimus and corticosteroids may improve short-term mortality of patients with interstitial pneumonia. [49]
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Cardiac abnormalities - May respond to corticosteroids; symptomatic arrhythmias require antiarrhythmic therapy, and symptomatic heart block is treated with placement of a pacemaker
Dysphagia secondary to cricopharyngeal involvement in polymyositis/dermatomyositis is a rare manifestation and usually reflects poor prognosis. Dysphagia responds either slowly or poorly to immunosuppressive therapies or high-dose corticosteroids. A large case series indicated that treatment with IVIG can be effective in patients with steroid-resistant esophageal manifestations of polymyositis/dermatomyositis. [50]
Dysphagia may be severe enough to require enteral feeding through a gastrostomy tube or parenteral nutrition.
Inpatient and Outpatient Care
Inpatient care
Patients with polymyositis should be closely monitored in the hospital while they are taking high-dose corticosteroids. Ideally, testing for tuberculosis should be performed before initiation of corticosteroid treatment.
Serial creatine kinase (CK) levels should be monitored to assess improvement. Severe pulmonary or cardiac involvement may require management in an intensive care setting. In patients treated with immunosuppressive agents, regularly monitor CBC, liver function test and renal function. Patients with polymyositis usually need aggressive inpatient physical therapy.
Outpatient care
Patients with polymyositis should be seen every 2-3 weeks initially; if they are stable, they should be seen at monthly intervals thereafter.
Frequently check laboratory tests, including CK, and document muscle strength evaluation results. Check the patient's weight at each visit. Routine age-appropriate cancer screening is recommended. Arrange outpatient physical therapy.
Deterrence and Prevention
The following precautions can aid against the following complications associated with polymyositis or its treatment:
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Raynaud phenomenon - Patients with polymyositis should avoid cold exposure if Raynaud phenomenon is a significant problem
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Esophageal involvement - Patients with esophageal involvement can elevate the head of the bed and avoid eating before bedtime to minimize reflux and risk of aspiration; histamine-2 receptor antagonists, proton pump inhibitors, and/or prokinetic agents may be useful in patients with esophageal reflux and dysmotility.
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Osteoporosis - Check a baseline bone density scan. Prescribe calcium with vitamin D supplementation and oral bisphosphonates for osteoporosis prophylaxis or other agents for osteoporosis treatment.
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Polymyositis. MRI of thighs showing increased signal in the quadriceps muscles bilaterally consistent with inflammatory myositis.
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Polymyositis. Histopathology slide shows endomysial mononuclear inflammatory infiltrate and muscle fiber necrosis.
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Polymyositis. Close view of muscle biopsy, showing chronic inflammatory infiltrate consisting of T lymphocytes, especially CD8+ T lymphocytes.
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Polymyositis. Hematoxylin and eosin frozen section shows polymyositis. Endomysial chronic inflammation is present among intact myofibers, which are remarkable only for increased variability of fiber size. Image courtesy of Roberta J. Seidman, MD.
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Polymyositis. Hematoxylin and eosin paraffin section shows polymyositis. Patient had dense endomysial inflammation that contains an abundance of plasma cells, which can be observed in patients with chronic polymyositis. Two necrotic myofibers, characterized by dense eosinophilic staining, are observed. Focal fatty infiltration of the muscle is present in the lower left quadrant of the photomicrograph. Image courtesy of Roberta J. Seidman, MD.
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Polymyositis. Hematoxylin and eosin paraffin section shows polymyositis. Photomicrograph illustrates attack on a nonnecrotic myofiber by autoaggressive T lymphocytes. On the left, the central myofiber is intact. On the right, it is obliterated by a segmental inflammatory attack. If immunohistochemistry were performed, expected findings would include an admixture of CD8 T lymphocytes and macrophages in the inflammatory process. Image courtesy of Roberta J. Seidman, MD.
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Polymyositis. Hematoxylin and eosin paraffin shows dermatomyositis. In dermatomyositis, inflammation is characteristically perivascular and perimysial. Vessel oriented approximately vertically in the center has a mild perivascular chronic inflammatory infiltrate. The endothelium is plump. The wall is not necrotic. A few lymphocytes in the wall of the vessel are probably in transit from the lumen to the external aspect of the vessel. Some observers may interpret this finding as vasculitis, but it is certainly neither necrotizing vasculitis nor arteritis. Image courtesy of Roberta J. Seidman, MD.
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Polymyositis. Hematoxylin and eosin paraffin section shows polymyositis. Longitudinal section shows a dense, chronic, endomysial inflammatory infiltrate. Image courtesy of Roberta J. Seidman, MD.
