eMedicine Specialties > Rheumatology > Systemic Rheumatic Disease

Polymyositis

Ramesh Pappu, MD, Adjuct Associate Professor of Medicine, Drexel University College of Medicine
Mythili Seetharaman, MD, Clinical Assistant Professor, Thomas Jefferson University Hospital, Consulting Staff, Einstein Arthritis Center, Albert Einstein Medical Center, St Christopher's Hospital for Children

Updated: Nov 6, 2009

Introduction

Background

Polymyositis (PM) is an idiopathic inflammatory myopathy that causes symmetric proximal muscle weakness, elevated skeletal muscle enzyme levels, and characteristic electromyography (EMG) and muscle biopsy findings. Clinically similar to polymyositis, dermatomyositis (DM) is an idiopathic inflammatory myopathy associated with characteristic dermatologic manifestations. Inclusion body myositis (IBM) is a slowly progressive idiopathic inflammatory myopathy with characteristic pathological findings generally found in older males. Bohan and Peter classify the idiopathic inflammatory myopathies as follows:¹

• I - Primary idiopathic polymyositis
• II - Primary idiopathic dermatomyositis
• III - Polymyositis or dermatomyositis associated with malignancy
• IV - Childhood polymyositis or dermatomyositis
• V - Polymyositis or dermatomyositis associated with another connective-tissue disease
• VI - Inclusion body myositis
• VII - Miscellaneous (eg, eosinophilic myositis, myositis ossificans, focal myositis, giant cell myositis)

Pathophysiology

Although the agent that initially causes polymyositis remains unknown, possibilities include virus-mediated muscle injury or microvascular insult leading to release of muscle autoantigens. These autoantigens are then presented to T lymphocytes by macrophages in the muscle. Activated T lymphocytes proliferate and release cytokines such as interferon gamma (IFN-gamma) and interleukin 2 (IL-2). IFN-gamma promotes further macrophage activation and release of mediators of inflammation such as IL-1 and tumor necrosis factor-alpha (TNF-alpha).

Additionally, these cytokines induce aberrant expression of major histocompatibility complex (MHC) class I and II molecules and adhesion molecules on muscle cells. Muscle fibers are destroyed when CD8⁺ T lymphocytes (cytotoxic) encounter antigens in conjunction with MHC class I molecules on muscle cells. Macrophages further the process of destruction both directly and by secreting cytokines.

Frequency

United States

Idiopathic inflammatory myopathies are relatively rare diseases, with an incidence that ranges from 0.5-8.4 cases per million population.

International

Polymyositis is less common among Japanese persons.

Mortality/Morbidity

Most patients with polymyositis respond favorably to immunosuppressive therapy but may require lifelong treatment. Five-year survival rates have been estimated at more than 80%. Causes of death include severe muscle weakness, pulmonary involvement, cardiac involvement, associated malignancy, and complications of immunosuppressive therapy, especially infection.

Race

In the United States, polymyositis is more common among blacks.

Sex

Polymyositis is more common in women than in men (2:1 ratio); inclusion body myositis is twice as common in men.

Age

Polymyositis usually affects adults older than 20 years, especially those aged 45-60 years. Polymyositis rarely affects children, unlike dermatomyositis.

• The age of onset of polymyositis with another collagen vascular disease is related to the associated condition.
• Eighty percent of patients with inclusion body myositis are older than 50 years at onset.

Clinical

History

Symptoms of polymyositis (PM) gradually develop over a period of 3-6 months. Diagnosis is usually delayed because, unlike in dermatomyositis, no associated rash occurs before the onset of muscle disease.

• Muscular manifestations
  • Patients with polymyositis usually present with symmetric proximal muscle weakness in the upper and lower extremities.
  • Weakness of neck flexors also occurs.
  • Initially, distal muscle weakness is rare but may occur late in the disease course.
  • Patients with polymyositis may report muscle pain and tenderness that may be confused with polymyalgia rheumatica.
  • Dysphagia secondary to oropharyngeal and esophageal involvement occurs in about one third of patients with polymyositis and is a poor prognostic sign. Dysphonia is also a poor prognostic sign but is much less common.
  • Ocular muscles are never involved in generalized polymyositis. However, isolated orbital myositis, an inflammatory disorder involving the extraocular muscles, is well described.
  • Facial and bulbar muscle weakness is extremely rare in individuals with polymyositis.
• Constitutional manifestations (Polymyositis is a systemic disease.)
  • Morning stiffness
  • Fatigue
  • Anorexia
  • Fever (associated with anti-synthetase antibodies such as anti-Jo-1)
  • Weight loss
• Pulmonary manifestations
  • Pharyngeal and esophageal weakness may lead to aspiration pneumonia.
  • Patients with polymyositis may experience exertional dyspnea secondary to weakness of chest wall muscles and diaphragmatic muscles.
  • Patients receiving immunosuppressants are at an increased risk of infections.
  • Interstitial lung disease occurs in 5-30% of patients with idiopathic inflammatory myopathy (associated with anti-synthetase antibodies, especially anti-Jo-1). Patients may be asymptomatic or present with exertional dyspnea, cough, and fever.²
  • Interstitial pneumonitis, bronchiolitis obliterans organizing pneumonia, and pulmonary capillaritis have all been described in conjunction with polymyositis.
• Cardiac manifestations
  • Cardiac involvement is unusual and, if present, portends a bad prognosis.
  • Rhythm disturbances, conduction defects, congestive heart failure, pericarditis, pulmonary hypertension, and myocarditis can occur.
• Joint involvement
  • Patients can present with arthralgias or arthritis.
  • Arthritis is usually symmetric and involves the knees, wrists, and hands (associated with antisynthetase antibodies).
  • A severe deforming arthropathy without erosions has been reported; erosive changes are very rare.
• Overlap syndromes
  • Polymyositis has been associated with other connective-tissue diseases such as systemic lupus erythematosus, rheumatoid arthritis, mixed connective-tissue disease, Sjögren syndrome, and scleroderma.
  • About 25% of patients with scleroderma have myositis; this phenomenon has been associated with anti-PM-Scl (anti-PM-1) antibody.
  • In Japan, anti-Ku antibody has been described with this condition.
• Gastrointestinal manifestations
  • Dysphagia
  • Odynophagia
  • Nasal regurgitation
  • Reflux esophagitis
  • Abdominal bloating
  • Constipation
• Renal manifestations: Intrinsic renal disease is rare in patients with polymyositis. Occasionally, severe rhabdomyolysis with myoglobinuria can result in acute tubular necrosis.
• Skin manifestations
  • Rash is absent in patients with polymyositis, unlike with dermatomyositis.
  • "Mechanic's hands" (associated with antisynthetase antibodies), ie, hyperkeratotic eruptions over the finger pads and lateral aspects of the fingers, have been reported.
  • Raynaud phenomenon has been described in patients with antisynthetase antibodies.
  • Rarely, periorbital edema may occur (best described in dermatomyositis).
  • Calcinosis occurs in approximately 5% of patients with polymyositis (in association with sclerodermalike illness).
  • Telangiectasias are uncommon.
• Inclusion body myositis: This condition is a slowly progressive idiopathic inflammatory myopathy that mostly affects men older than 50 years. Muscle involvement includes predominantly proximal muscles but may also include distal muscles (50%), and involvement may be asymmetric. Dysphagia is found in most patients (60%).

Physical

Physical examination findings of gout generally include symmetric proximal muscle weakness.

• Deep tendon reflexes are usually preserved, and sensory examination findings are normal.
• Muscle tenderness may be present.
• Dysphonia with nasal speech may be noted.
• Lung examination findings may include evidence of interstitial lung disease such as dry inspiratory crackles in the lung bases ("Velcro").
• Inclusion body myositis manifests as severe proximal muscle weakness with atrophy, often with distal muscle weakness. The weakness may be asymmetric. Deep tendon reflexes may be impaired or absent if weakness is severe.

Causes

The causes of polymyositis are still poorly understood, although the condition is believed to be an immune-mediated process triggered by environmental agents in genetically predisposed individuals. Recognition of other autoimmune diseases with polymyositis and the presence of circulating autoantibodies strongly favor an autoimmune etiology. An increased association of myositis has been found with HLA haplotypes A1, B8, and DR3, which also increases the risk for autoimmune diseases. Environmental triggers, especially infectious agents, have been suggested as etiologic agents, as follows:

• Infectious agents
  • Coxsackievirus B1
  • HIV
  • Human T-cell lymphotropic virus type 1 (HTLV-1)
  • Hepatitis B
  • Influenza
  • Echovirus
  • Adenovirus
• Noninfectious agents
  • Many drugs are known to cause myopathy. Most drugs, such as hydroxychloroquine and colchicine, cause a toxic or metabolic myopathy.
  • Several drugs, however, rarely induce an immune-mediated myopathy or myositis. Muscle biopsy shows chronic inflammatory changes consistent with polymyositis. Drugs such as D-penicillamine, hydralazine, procainamide, phenytoin, and angiotensin-converting enzyme (ACE) inhibitors have been associated with this type of inflammatory myopathy.
  • Statins occasionally cause severe muscle inflammation and rhabdomyolysis.

Differential Diagnoses

Other Problems to Be Considered

• Other idiopathic inflammatory myopathies
  • Inclusion body myositis
  • Eosinophilic myositis
  • Myositis ossificans
  • Focal myositis
  • Giant cell myositis
• Amyotrophic lateral sclerosis
• Diabetic polyradiculopathy
• Drug-induced myopathy
  • Alcohol
  • Antimalarials
  • Clofibrate
  • Colchicine
  • Ketoconazole and other azole antifungal agents
  • Statin/3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors
  • D-penicillamine
  • Vincristine
  • Zidovudine (AZT)
• Metabolic myopathy
• Muscular dystrophy
• Myasthenia gravis
• Overlap connective-tissue diseases

Workup

Laboratory Studies

• Serum creatine kinase (CK) levels are usually elevated in persons with polymyositis, ranging from 5-50 times the reference range. Serum CK levels, along with careful physical examination, may be used to monitor myositis activity. However, serum CK levels may be within reference ranges despite increased disease activity (eg, in cases of chronic and late-stage polymyositis [PM]). CK levels are usually minimally elevated or within the reference range in patients with inclusion body myositis. CK levels are within the reference range in patients with corticosteroid-induced myopathy.
• Other muscle enzymes may be elevated.
  • Lactic dehydrogenase
  • Aspartate aminotransferase
  • Alanine aminotransferase
  • Aldolase
• Nonspecific markers of inflammation include the following:
  • CBC count may show leukocytosis or thrombocytosis.
  • The erythrocyte sedimentation rate or C-reactive protein level is elevated in 50% of patients with polymyositis.
• Antinuclear antibody assay findings are positive in one third of patients with polymyositis and in only 15% of patients with inclusion body myositis.
• Myositis-specific antibodies are associated with polymyositis.
  • Antisynthetase antibodies, such as anti-Jo-1 antibodies, are associated with certain clinical features. Antisynthetase syndrome may manifest as idiopathic inflammatory myopathy, interstitial lung disease, arthritis, Raynaud phenomenon, fever, and/or mechanic's hands.
  • Approximately 4% of patients with polymyositis have antibodies to signal recognition particles (SRPs), which are associated with acute onset of severe weakness, increased incidence of cardiac involvement, and higher mortality rates.
• Perform age-appropriate evaluation for malignancy.

Imaging Studies

• Muscle-imaging techniques such as MRI and ultrasonography may be useful to document and localize the extent of muscle involvement (see Image 1).
  
  

  

  MRI of thighs showing increased signal in the quadriceps muscles bilaterally consistent with inflammatory myositis.

  
  
• Chest radiography and high-resolution CT scanning of the chest are helpful for evaluation of interstitial lung disease.
• Barium swallow studies are helpful for evaluation of dysphagia or dysphonia.

Other Tests

• EMG findings are abnormal in almost all patients (90%) with polymyositis. Various abnormalities consistent with polymyositis may be found, depending on the stage of disease. In patients with inclusion body myositis, both myopathic and neuropathic changes may be present.
  • Evidence of membrane irritability, increased insertional activity, fibrillation potentials, positive sharp waves at rest
  • Myopathic changes of motor unit action potential, decreased amplitude and duration, increased polyphasic potentials, bizarre high-frequency repetitive discharges
  • Chronic changes, evidence of denervation-reinnervation
• Pulmonary function tests and diffusion capacity for evaluation of interstitial lung disease may be appropriate.

Procedures

• Muscle biopsy is crucial in helping diagnose polymyositis and in excluding other rare muscle diseases. MRI can be used to guide the site of biopsy. Avoid biopsy of sites recently studied by EMG by using the contralateral side.

Histologic Findings

Muscle biopsy shows muscle fibers in varying stages of inflammation, necrosis, and regeneration (see Images 2-3). Findings include focal endomysial infiltration by mononuclear cells (consisting of mostly CD8⁺ T lymphocytes and macrophages), capillary obliteration, endothelial cell damage, and increased amounts of connective tissue. Later in the course of polymyositis, muscle-cell degeneration, fibrosis, and regeneration may be observed. Inclusion body myositis is histologically similar to polymyositis with the additional presence of intracytoplasmic inclusion bodies observed on electron microscopy. Dermatomyositis shows inflammatory changes, predominantly in the perimysial and perivascular regions with CD4⁺ T and B lymphocytes. Corticosteroid-induced myopathy causes no inflammatory changes. Type II fiber atrophy is the characteristic feature.

Histopathology of polymyositis showing endomysial mononuclear inflammatory infiltrate and muscle fiber necrosis.

Close view of muscle biopsy, showing chronic inflammatory infiltrate consisting of T lymphocytes, especially CD8+ T lymphocytes.

Treatment

Medical Care

Treatment of polymyositis (PM) is empirical because of the rarity of the disease and the paucity of randomized controlled trials.

• Prednisone is the first-line treatment of choice for polymyositis.
  • Typically, the dose is 1 mg/kg/d, either as a single or divided dose. This high dose is usually continued for 4-8 weeks, until the 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, osteopenia, and steroid myopathy.
  • Corticosteroid myopathy can occur during the course of treatment and must be distinguished from reactivation of muscle disease. CK level is usually within reference ranges in patients with steroid myopathy. No improvement is observed with raised doses of steroids, and the condition worsens if the dose is increased.
• Immunosuppressive agents are indicated in patients who do not improve with steroids within a reasonable period (ie, 4 wk) or if 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. Patients with inclusion body myositis usually respond poorly to corticosteroids and immunosuppressive agents.
  • Obtain baseline liver function tests and pulmonary functions before initiating therapy.
  • Azathioprine, cyclophosphamide, chlorambucil, and cyclosporine have been used with varying success as second-line agents for polymyositis.
• Intravenous immunoglobulin (IVIG) has been used for the short-term treatment of steroid-resistant cases of polymyositis.^3,4
• The role of newer agents, such as TNF inhibitors, remains unclear. However, the use of TNF inhibitors in refractory cases has demonstrated some success.⁵
• Recently, an open-label study of patients with dermatomyositis treated with rituximab (anti-CD20 monoclonal antibody) provided encouraging results.⁶ This may be a new approach to therapy for refractory cases.
• A study is currently under way to evaluate the safety of interferon alfa-2a in adult patients with dermatomyositis or polymyositis.
• A study to evaluate the effectiveness of an anti-C5 (complement) in the treatment of dermatomyositis was recently completed at the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS).
• Extramuscular manifestations of polymyositis are treated as follows:
  • Constitutional symptoms of polymyositis, such as fever and fatigue, usually respond to corticosteroids.
  • Articular symptoms of polymyositis usually resolve with treatment of the myositis. Some patients develop a rheumatoidlike arthropathy, which may require immunosuppressive treatment such as methotrexate.
  • Patients with severe interstitial lung disease may benefit from high-dose steroids and immunosuppressive treatment, especially cyclophosphamide.
  • Cardiac abnormalities may respond to corticosteroids. Symptomatic arrhythmias require antiarrhythmic therapy, and symptomatic heart block is treated with placement of a pacemaker.
  • Dysphagia responds either slowly or poorly to immunosuppressive therapies and may be severe enough to require enteral feeding through a gastrostomy tube or parenteral nutrition.

Consultations

• Rheumatologists
• Neurologists
• Pulmonary specialists
• Cardiologists
• Physical therapists
• Speech therapists (for swallow evaluation)

Diet

• Patients with polymyositis may benefit from a high-protein diet. Histamine 2 receptor antagonists, proton pump inhibitors, and/or prokinetic agents may be useful in patients with esophageal reflux and dysmotility.
• Monitor patients to avoid excessive weight gain due to corticosteroid use.
• Prescribe calcium with vitamin D supplementation and oral bisphosphonates for osteoporosis prophylaxis.

Activity

• Encourage patients with polymyositis to start a supervised exercise program early in the disease course.⁷
• 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 minutes of aerobic exercise when the disease is inactive.

Medication

The goals of pharmacotherapy are to reduce morbidity and to prevent complications.

Corticosteroids

These agents inhibit the inflammatory process via multiple mechanisms, including inhibiting proinflammatory cytokine production, monocyte/macrophage function, and angiogenesis.

Prednisone (Sterapred)

Anti-inflammatory and immunosuppressive agent used in the treatment of autoimmune disorders; may decrease inflammation by reversing increased capillary permeability and suppressing neutrophilic activity. Also stabilizes lysosomal membrane and suppresses lymphocytes, reducing cytokine and antibody production.

Dosing

Adult

1 mg/kg/d PO for 4-8 wk until CK findings return to normal limits; initially administered in divided doses; taper gradually to maintain control of disease activity

Pediatric

0.5-2 mg/kg/d PO for 4-8 wk until CK findings return to normal limits; initially administered in divided doses; taper gradually to maintain control of disease activity

Interactions

Coadministration with estrogens may decrease clearance; concurrent use with digoxin may cause digitalis toxicity secondary to hypokalemia; phenobarbital, phenytoin, and rifampin may increase metabolism of corticosteroids (consider increasing maintenance dose); monitor for hypokalemia with coadministration of diuretics

Contraindications

No absolute contraindication; severe bacterial, viral, or fungal infections; active peptic ulcer disease; diabetes mellitus

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Abrupt discontinuation of corticosteroids may cause adrenal crisis; hyperglycemia, edema, osteonecrosis, myopathy, peptic ulcer disease, hypokalemia, osteoporosis, euphoria, psychosis, growth suppression, and infections may occur with corticosteroid use

Immunosuppressants

These agents may be of benefit in patients whose conditions have not responded to steroids or in patients unable to tolerate prednisone.

Methotrexate (Rheumatrex, Folex PFS)

Unknown mechanism of action in treatment of chronic inflammatory diseases; may affect immune function, including inhibition of production of proinflammatory cytokines. Ameliorates symptoms of inflammation (eg, pain, swelling, stiffness). Adjust dose gradually to attain satisfactory response.

Dosing

Adult

7.5 mg/wk PO/SC given as single dose; increase weekly dose by 2.5-5 mg, depending on clinical response and toxicity; not to exceed a dose of 25 mg/wk; may also be administered IV

Pediatric

0.25 mg/kg/wk PO/SC given as a single dose; increase weekly dose to a maximum of 0.6 mg/kg/wk, depending on clinical response and toxicity

Interactions

Oral aminoglycosides may decrease absorption and blood levels of concurrent oral MTX; charcoal lowers levels; administration with etretinate may increase hepatotoxicity; administration of NSAIDs (eg, indomethacin, phenylbutazone) can increase plasma levels; may decrease phenytoin serum levels; probenecid, salicylates, procarbazine, and sulfonamides, including TMP-SMZ, may increase effects and toxicity; may increase plasma levels of thiopurines

Contraindications

Documented hypersensitivity; alcoholism; hepatic insufficiency; documented immunodeficiency syndromes; preexisting blood dyscrasias (eg, bone marrow hypoplasia, leukopenia, thrombocytopenia, significant anemia); renal insufficiency

Precautions

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Monitor CBC counts monthly and liver and renal function q1-3mo during therapy (monitor more frequently during initial dosing, dose adjustments, or risk of elevated levels [dehydration]; has toxic effects on hematologic, renal, GI, pulmonary, and neurologic systems; discontinue with significant drop in blood counts; aspirin, NSAIDs, or low-dose steroids may be administered concomitantly; (possibility of increased toxicity with NSAIDs, including salicylates, has not been tested); folic acid 1 mg/d decreases the incidence of mucositis and other adverse GI effects

Azathioprine (Imuran)

Purine analog that inhibits synthesis of DNA, RNA, and proteins. May decrease proliferation of immune cells, which results in lower immunological activity.

Dosing

Adult

Starting dose of 1 mg/kg/d PO for 4-8 wk; increase by 0.5 mg/kg qmo, depending on clinical and hematologic response and toxicity up to 2.5-3 mg/kg/d

Pediatric

Starting dose of 0.5-1 mg/kg/d PO for 4-8 wk; increase by 0.5 mg/kg qmo, depending on clinical and hematologic response and toxicity up to 2.5-3 mg/kg/d

Interactions

Toxicity increases with allopurinol; concurrent use with ACE inhibitors may induce severe leukopenia; may increase levels of MTX metabolites; decreases the effects of anticoagulants, neuromuscular blockers, and cyclosporine

Contraindications

Documented hypersensitivity; low levels of serum TPMT; active infection; severe cytopenias

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Nausea and vomiting, leukopenia, thrombocytopenia, anemia, infection, abnormal LFTs may occur, rarely, pancreatitis

Immune globulin, intravenous (Sandoglobulin, Gamimune, Gammagard)

Neutralizes circulating myelin antibodies through anti-idiotypic antibodies; down-regulates proinflammatory cytokines, including IFN-gamma; blocks Fc receptors on macrophages; suppresses helper T and B lymphocytes and augments suppressor T lymphocytes. Exact mechanism of action in treatment of polymyositis is unknown.

Dosing

Adult

1-2 g/kg IV over 2 d, given qmo for 6 mo

Pediatric

Administer as in adults

Interactions

Increases toxicity of live virus vaccine (MMR); do not administer within 3 mo of vaccine

Contraindications

Documented hypersensitivity; IgA deficiency; anti-IgE/IgG antibodies

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Check serum IgA before IVIG (use an IgA-depleted product, eg, Gammagard S/D); infusions may increase serum viscosity and thromboembolic events; infusions may increase risk of migraine attacks, aseptic meningitis (10%), urticaria, pruritus, or petechiae (2-5 d postinfusion to 30 d); increases risk of renal tubular necrosis in elderly patients and in patients with diabetes, volume depletion, and preexisting kidney disease; lab result changes associated with infusions include elevated antiviral or antibacterial antibody titers for 1 mo, 6-fold increase in ESR for 2-3 wk, and apparent hyponatremia

Chlorambucil (Leukeran)

Alkylates and cross-links strands of DNA, inhibiting DNA replication and RNA transcription.

Dosing

Adult

0.1-0.2 mg/kg/d PO; average maintenance dose is 2-4 mg/d

Pediatric

Administer as in adults

Interactions

None reported

Contraindications

Documented hypersensitivity; active infection; depressed bone marrow function

Precautions

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Caution with history of seizure disorder or with bone marrow suppression; increased risk of hematologic malignancy

Cyclophosphamide (Cytoxan, Neosar)

Chemically related to nitrogen mustards. As an alkylating agent, the mechanism of action of the active metabolites may involve cross-linking of DNA, which may interfere with growth of normal cells such as lymphocytes and neoplastic cells.

Dosing

Adult

1-3 mg/kg/d PO; may be given as pulse therapy at 500-1000 mg/m²/mo IV

Pediatric

Administer as in adults

Interactions

May potentiate doxorubicin-induced cardiotoxicity; may reduce digoxin serum levels and antimicrobial effects of quinolones; chloramphenicol may increase half-life while decreasing metabolite concentrations; coadministration with high doses of phenobarbital may increase rate of metabolism and leukopenic activity; inhibits cholinesterase activity for up to 10 d after an intravenous dose, which can potentiate the effect of succinylcholine chloride

Contraindications

Documented hypersensitivity; active infection; severely depressed bone marrow function

Precautions

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Regularly examine hematologic profile (particularly neutrophils and platelets) to monitor for hematopoietic suppression; regularly examine urine for RBCs, which may precede hemorrhagic cystitis, especially when taking PO; obtain serial CBC counts and LFTs during course of treatment; monitor for leukopenia and elevated liver enzymes; increased risk of bladder cancer and hematologic malignancy; can cause sterility

Cyclosporine (Sandimmune, Neoral)

Cyclic polypeptide that suppresses cell-mediated immune reactions such as delayed hypersensitivity and, to a lesser extent, humoral immunity, allograft rejection, experimental allergic encephalomyelitis, and graft vs host disease for a variety of organs. Selectively inhibits transcription of IL-2, predominately in helper lymphocytes.

Dosing

Adult

3-5 mg/kg/d PO divided bid

Pediatric

Administer as in adults

Interactions

Carbamazepine, phenytoin, isoniazid, rifampin, and phenobarbital may decrease cyclosporine levels; macrolide antibiotics, triazole antifungal agents, calcium channel blockers, grapefruit juice, aminoglycosides, acyclovir, amphotericin B; may increase cyclosporine toxicity; acute renal failure, rhabdomyolysis, myositis, and myalgias increase when taken concurrently with lovastatin

Contraindications

Documented hypersensitivity; uncontrolled hypertension or malignancies; do not administer concomitantly with PUVA or UV-B radiation in psoriasis because of possibly increased risk of cancer

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Evaluate renal and liver functions often by measuring BUN, serum creatinine, serum bilirubin, and liver enzymes; may increase risk of infection and lymphoma; use IV only for patients who cannot take PO; raises serum uric acid level and increases risk of gout

Tumor necrosis factor inhibitors

These agents may be used in refractory cases of polymyositis that have failed to respond to conventional therapy with steroids.

Etanercept (Enbrel)

Binds specifically to TNF and blocks its interaction with cell surface TNF receptors, rendering TNF biologically inactive.

Dosing

Adult

25 mg SC twice a week

Pediatric

0.4 mg/kg SC twice a week; not to exceed 25 mg/dose

Interactions

None reported

Contraindications

Documented hypersensitivity; sepsis

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Caution in impaired renal function and asthma; discontinue administration if a serious infection develops; adverse effects may include injection site pain, localized erythema, rash, URTI symptomatology, GI upset, nausea, vomiting, rhinitis, and cough; congestive heart failure may worsen based on recent evidence; affects host defenses against malignancy and infections, although impact on infection and malignancy is not fully understood; may lead to formation of autoantibodies; local injection site reactions have been noted in about 37% of patients

Infliximab (Remicade)

Binds to soluble and transmembranous forms of TNF-alpha, rendering TNF biologically inactive.

Dosing

Adult

3 mg/kg IV as an induction regimen at 0, 2, and 6 wk; repeat q2mo thereafter

Pediatric

Administer as in adults

Interactions

None reported

Contraindications

Documented hypersensitivity; sepsis, NHYA class III/IV heart failure

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Anti-TNF therapies, such as infliximab, may adversely affect normal immune responses and allow development of superinfections (TNF-alpha modulates cellular immune responses); may increase risk of reactivation of tuberculosis in patients with particular granulomatous infections; caution in patients with recent neurological events such as demyelination of central nervous system or seizures, infections, and lymphoproliferative disorders; autoantibody production with lupuslike syndromes and injection-related infusion reactions reported

Follow-up

Further Inpatient Care

• Patients with polymyositis should be closely monitored in the hospital while they are taking high-dose corticosteroids.
• Monitor serial CK levels to assess improvement.
• Severe pulmonary or cardiac involvement may require management in an intensive care setting.
• Ideally, purified protein derivative should be placed prior to initiation of corticosteroid treatment.
• Regularly monitor CBC counts, liver function test findings, and renal function in patients treated with immunosuppressive agents.
• Patients with polymyositis usually need aggressive inpatient physical therapy.

Further Outpatient Care

• Patients with polymyositis should be seen every 2-3 weeks initially; if they are stable, see them at monthly intervals thereafter.
• Frequently check laboratory tests, including CK (as outlined in Lab Studies), and document muscle strength evaluation results.
• Check patients' weight during each visit.
• Routine age-appropriate cancer screening is recommended.
• Arrange outpatient physical therapy.

Deterrence/Prevention

• Patients with polymyositis should avoid cold exposure if Raynaud phenomenon is a significant problem.
• Patients with esophageal involvement can elevate the head of the bed and avoid eating before bedtime to minimize reflux and risk of aspiration.

Complications

• Pulmonary disease
  • Interstitial lung disease
  • Aspiration pneumonia
• Cardiac
  • Heart block
  • Arrhythmias
  • Congestive heart failure
  • Pericarditis
• Gastrointestinal
  • Dysphagia
  • Malabsorption
• Malignancy: Incidence of lung, bladder, and non-Hodgkin lymphoma may be increased in patients with polymyositis, especially in the first year after diagnosis.

Prognosis

• In most patients, polymyositis responds well to treatment, although residual weakness is common. Osteoporosis, a common complication of long-term corticosteroid therapy, may cause significant morbidity.
• Poor prognostic factors include the following:
  • Advanced age
  • Female sex
  • African American race
  • Interstitial lung disease
  • Presence of anti-Jo-1 (lung disease) and anti-SRP antibodies (severe muscle disease, cardiac involvement)
  • Associated malignancy
  • Delayed or inadequate treatment
  • Dysphagia, dysphonia
  • Cardiac and pulmonary involvement

Patient Education

• Patients with polymyositis should be educated early about the disease and should be provided with realistic expectations about outcomes. Most patients show significant improvement with treatment.
  • Stress the need for close follow-up care, continued physical therapy, and long-term therapy.
  • Warn patients regarding adverse events related to medications.
  • Patients may visit the Myositis Association of America Web site for more information.
• For excellent patient education resources, visit eMedicine's Muscle Disorders Center. Also, see eMedicine's patient education article Chronic Fatigue Syndrome.

Miscellaneous

Medicolegal Pitfalls

• Delay in diagnosis
• Misdiagnosis
• Failure to diagnose malignancy
• Failure to inform patient about potential drug toxicity

Multimedia

Media file 1: MRI of thighs showing increased signal in the quadriceps muscles bilaterally consistent with inflammatory myositis.

Media file 2: Histopathology of polymyositis showing endomysial mononuclear inflammatory infiltrate and muscle fiber necrosis.

Media file 3: Close view of muscle biopsy, showing chronic inflammatory infiltrate consisting of T lymphocytes, especially CD8+ T lymphocytes.

References

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Keywords

polymyositis, PM, primary idiopathic polymyositis, idiopathic inflammatory myopathy, dermatomyositis, DM, inclusion body myositis, IBM, virus-mediated muscle injury, microvascular insult, collagen vascular disease

Contributor Information and Disclosures

Author

Ramesh Pappu, MD, Adjuct Associate Professor of Medicine, Drexel University College of Medicine
Ramesh Pappu, MD is a member of the following medical societies: American Association of Physicians of Indian Origin, American College of Rheumatology, and American Medical Association
Disclosure: Nothing to disclose.

Coauthor(s)

Mythili Seetharaman, MD, Clinical Assistant Professor, Thomas Jefferson University Hospital, Consulting Staff, Einstein Arthritis Center, Albert Einstein Medical Center, St Christopher's Hospital for Children
Mythili Seetharaman, MD is a member of the following medical societies: American College of Rheumatology and American Medical Association
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Medical Editor

Kristine M Lohr, MD, MS, Program Director, Professor, Department of Internal Medicine, Division of Rheumatology and Women's Health, University of Kentucky School of Medicine
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Herbert S Diamond, MD, Professor of Medicine, Temple University School of Medicine; Chairman Emeritus, Department of Internal Medicine, Western Pennsylvania Hospital
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