Polymyositis

Author(s): Edwardo Ramos, MD, Brenda Castillo, MD, Rafael Arias, MD

Originally published:07/25/2012

Last updated:08/17/2016

1. DISEASE/DISORDER:

Definition

Polymyositis (PM) is an idiopathic inflammatory myopathy (IIM) causing predominantly symmetric proximal muscle weakness and chronic inflammation of skeletal muscle. Other organs are often involved, including skin, heart, gastrointestinal tract, and lungs. PM is grouped with other inflammatory myopathies such as dermatomyositis (DM), inclusion body myositis (IBM), nonspecific myositis and immune-mediated necrotizing myopathy (IMNM). IIM subtypes have been identified based on differences in clinical and histopathologic findings and a number of autoantibodies have now been associated with these syndromes, and some are associated with specific phenotypes and prognostic connotations.1 Polymyositis mimics many other myopathies and remains a diagnosis of exclusion. It should be viewed as a syndrome of diverse causes that occurs separately or in association with systemic autoimmune disorders or viral infections in patients who do not have any of the exclusion criterias.

Etiology

Polymyositis is an immune-mediated syndrome secondary to defective cellular immunity. It may be due to diverse causes that occur alone or in association with viral infections, malignancies, or connective-tissue disorders. Evidence points toward a T-cell–mediated cytotoxic process directed against unidentified muscle antigens. Supporting this conclusion are CD8 T-cells, which, along with macrophages, initially surround healthy non-necrotic muscle fibers and eventually invade and destroy them.

The factors triggering a T-cell–mediated process in polymyositis are unclear. Viruses have been implicated; so far, however, only the human retroviruses, human immunodeficiency virus (HIV) and human T-cell lymphotrophic virus type I (HTLV-I), the simian retroviruses, and coxsackievirus B have been etiologically connected with the disease.1

Epidemiology including risk factors and primary prevention

PM is more common in women than men (2:1 ratio) and rarely affects the pediatric population. PM usually affects the adult population in the age range of 40-60 years of age.3 Incidence can vary from 0.5-8.4 cases per 1 million people, with higher incidence among African Americans (black-to-white incidence of 5:1) and lower incidence among individuals of Japanese origin.3 Genetic factors may have a role, as suggested by rare familial occurrences and association with certain HLA genes, such as DRB1*0301 alleles.2 PM can be associated with other autoimmune conditions including systemic lupus erythematosus, Sjogren’s syndrome, rheumatoid arthritis, scleroderma, and mixed connective tissue disease.

Patho-anatomy/physiology

The inflammatory infiltrates seen in PM are located in the endomysium and include CD4 and CD8 T-cells, DCs, and macrophages. It is thought that CD8 T-cells bind with the major histocompatibility complex (MHC) class I molecules in the presence of autoantigens, releasing granules including the cytolytic protein perforin, inducing myofiber necrosis. Hypoxia may cause weakness in PM by reducing phosphocreatine and adenosine triphosphate (ATP) levels in muscle, inducing production of Interleukin (IL) 21, tumor growth factor-b (TGF-b), and HMGB1, which induces muscle fatigue by irreversibly decreasing Ca release. An autoimmune response to nuclear and cytoplasmic autoantigens is detected in about 60-80% of patients with polymyositis.1,3

Disease progression including natural history, disease phases or stages, disease trajectory (clinical features and presentation over time)

Onset typically involves gradually progressive, symmetric proximal greater than distal limb weakness with nonspecific symptoms including morning stiffness, fatigue, fever, and weight loss over a period of 3-6 months. This may progress to involve the cardiac, gastrointestinal, and pulmonary systems. Five-year survival rates have been estimated at more than 80%. Mortality is most often related to associated malignancy or pulmonary complications; however, elderly patients with cardiac involvement or dysphagia also have a higher mortality rate. Although the disease outcome has substantially improved, at least a third of patients are left with mild to severe disability.2

Specific secondary or associated conditions and complications

Pulmonary involvement can result from interstitial lung disease (ILD) in 5-30% of patients; half of these patients show anti-Jo-1 antibodies.3 Other pulmonary manifestations include exertional dyspnea secondary to weakness of chest wall muscles and diaphragmatic muscles, interstitial pneumonitis, bronchiolitis obliterans organizing pneumonia, and pulmonary capillaritis.3 Oropharyngeal and/or esophageal weakness can result in dysphagia, dysphonia, nasal regurgitation, and aspiration pneumonia. Cardiac features are rare and, if present, portends a bad prognosis. They include rhythm abnormalities, heart failure, myocarditis, and pericarditis.4Antisynthetase syndrome refers to PM with antisynthetase autoantibodies. Clinical features include fever, arthralgias, arthritis (usually symmetrical and involves the knees, wrists, and hands), ILD, mechanic’s hands (roughened and cracked skin of tips and lateral aspects of fingers), and Raynaud’s phenomena. PM with anti-signal recognition particle (SRP) autoantibodies is associated with acute-onset necrotizing myopathy with severe weakness and high serum creatine kinase (CK).5

2. ESSENTIALS OF ASSESSMENT

History

Patients complain of insidious onset, gradually progressive painless weakness (myalgias occur in fewer than 30% of patients), fatigue, fever, weight loss, and morning stiffness over a period of 3-6 months or longer. Diagnosis is usually delayed, because, unlike in dermatomyositis, no associated rash occurs before the onset of muscle disease. Other presenting complaints may include dysphonia, dysphagia in approximately one third of patients,6 wheezing, shortness of breath, polyarthralgia, and constipation. Family history, prescription and/or illicit drug use, risk factors for HIV infection, and features of connective tissue diseases are important in excluding other causes of myopathy.

Physical examination

Nothing is characteristic about the muscle weakness in polymyositis, but patients tend to show symmetric proximal greater than distal muscle weakness, including neck flexor weakness. It is not painful, although a minority of patients report aches or cramps. On occasion, the muscle may be sore to palpation and may have a nodular and grainy feel. Muscle atrophy is usually not seen except in chronic situations, where disuse atrophy may play a role. Muscle stretch reflexes are preserved, but may be absent in severely weakened or atrophied muscles. Sensory examination is normal as well as ocular muscles. Facial muscles remain normal except in rare advanced cases.  In advanced cases and rarely in acute cases, respiratory muscles are affected with evident dry inspiratory crackles are found at lung bases (velcro lungs) which suggests an interstitial lung disease.3

Functional assessment

Clinical outcomes can be monitored using Functional Independence Measure scores. Patient-reported Quality Of Life Scale can be used to monitor patient satisfaction both during acute inpatient stay and after discharge to home or subacute rehabilitation.

Laboratory studies

Serum creatine kinase (CK) levels in patients with active PM will be elevated 5-50 times the upper limit of normal. Serum CK levels do not correlate well with disease activity when comparing different patients, but they can reflect changes in disease activity within an individual patient. Other muscle enzymes, including aldolase, myoglobin, lactate dehydrogenase, aspartate amino- transferase (AST), and alanine aminotransferase (ALT), may also be elevated. 2 A number of antigens/autoantibodies can be present, these include (positive rate in PM): Jo-1 (33%), Mi-2 (15-35%), PM-Scl (8-12%), U1nRNP (4-17%), and SRP (4-5%).7 Complete blood count (CBC) may show leukocytosis (present in more than 50% of patients) or thrombocytosis. Positive rheumatoid factor , erythrocyte sedimentation rate or C-reactive protein level may be elevated in up to 50% of patients with polymyositis.3

Imaging

Magnetic resonance imaging (MRI) is being used increasingly as it can detect muscle necrosis, degeneration, and inflammation, and It is characterized by increased signal intensity on short-tau inversion recovery (STIR). T1-weighted images are useful for detecting atrophy and chronic muscle damage,  whereas T2-weighted images are useful for detecting active muscle inflammation, and their relaxation times have been correlated with disease activity.  MRI is also being used to identify muscle sites for biopsy and to monitor treatment response. Ultrasound, specifically Doppler sonography, contrast- enhanced ultrasound, and sonoelastography, may also be used to differentiate between normal and pathologic muscle.1

Supplemental assessment tools

Electrodiagnostic testing (EMG) and muscle biopsy (and skin biopsy in DM) are routinely done. Needle EMG findings of membrane instability are: increased insertional activity and spontaneous activity with  fibrillation potentials, positive sharp waves, and occasionally pseudomyotonic or complex repetitive discharges; polyphasic motor unit action potentials of low amplitude and short duration, and early recruitment.8 Paraspinal muscles show the most prominent features on EMG examination and should be included routinely.1 Needle EMG is usually done only on one side of the body to avoid needle artifact on subsequent muscle biopsy, which should be done on the contralateral side.8 The most involved muscles electrophysiologically are often good target muscles for biopsy on the contralateral limb. Depending on the clinical picture, biochemical assay tests run on the muscle biopsy specimen include testing for metabolic disorders and dystrophin. Bedside or barium swallow studies and pulmonary function tests can be done based on clinical presentation.

No official classification system currently exists, as disagreement continues. In 1975, Bohan and Peter proposed their system to establish clear guidelines for diagnosis and classification of PM and DM.  The original 1975 Bohan and Peter classification evaluated 5 criteria: 1) proximal symmetric muscle weakness, 2) muscle biopsy abnormalities, 3) elevated skeletal muscle enzyme levels, 4) abnormal EMG findings, and 5) typical skin rash of dermatomyositis. Presence all 1-4 criteria suggested definite PM, 3 of 1-4 criteria indicated probable PM, and if 2 of 1-4 criteria were met possible PM was suggested.1 Modifications to the original classification scheme were proposed in 1995 and 1997, with newer classification criteria using autoantibodies and histopathologic differentiating features.9

Early predictions of outcomes

Poor prognostic indicators include delay in diagnosis and/or initiation of treatment, older age, female sex, African American race, presence of anti-Jo-1 and anti-SRP antibodies, dysphagia, dysphonia, associated malignancy and cardiac and pulmonary involvement.3

3. REHABILITATION MANAGEMENT AND TREATMENTS

Available or current treatment guidelines

The goals of therapy are to improve the ability to carry out activities of daily living by increasing muscle strength and to ameliorate extramuscular manifestations.2 The mainstay of therapy is immunosuppression, physical therapy, monitoring for adverse events from medication, and prevention of complications.10

Main barrier for an optimal drug therapy for IIMs is impaired by the lack of consensus on classification, relevant clinical trials, reporting, and standardized outcome measures that correlate with changes in patient disability and quality of life.10

The current standard of care is high-dose corticosteroids, starting with prednisone at 1 mg/ kg/day with eventual taper to a minimal dose anywhere from 4 weeks to several months after initiation.11,12 Patients with severe disease, such as ILD, dysphagia, or profound weakness, are typically started on 1 g/day intravenous methylprednisolone for 3-5 days before switching to 1 mg/kg/day of oral prednisone for several months. 11,12

Many patients feel better immediately after starting corticosteroids, but strength improves over 2-3 months. In the case of “steroid-responsive” patients, the goal is to reduce the dose to the smallest, most effective amount. If there is no improvement after 3-6 months of prednisone, or if the patient relapses while tapering, a second-line immunosuppressive agent should be added.1

Common second-line choices include AZA, methotrexate, and immunoglobulins. Less frequently used mycophenolate mofetil, tacrolimus, rituximab, cyclosporine, and cyclophosphamide.1 These medications should also be started immediately in patients with rapidly progressive disease, patients with respiratorymuscle failure or dysphagia, and in patients with extramuscular involvement.13

Rehabilitation Challenges

In general, specific exercise prescriptions for individuals with neuromuscular disease do not exist because the evidence base is limited.18 High quality data supporting the role of exercise during rehabilitation is limited. While strength and aerobic exercise training programs do not appear to cause harm19 there is limited evidence to support that they offer benefit.20 General consensus supports that this population should begin early in the course of treatment with rehabilitation protocols.

Rehabilitation varies depending on the severity of weakness. In severe weakness, treatment involves bed rest, passive range of motion exercises at bedside, splinting to avoid contractures, pressure relieving heel protectors, special mattresses, bed turns every 2-4 hours, and ergonomic positioning of head and neck.

As the patient recovers, isometric exercise should be started, with gradual progression to more vigorous isotonic exercises and then resistive exercises. Sitting out of bed, with frequent rest breaks, and spacing out therapies. Bowel, bladder, hydration, swallowing, respiratory, and cardiac systems need to be monitored.

At later stages when residual weakness is mild, emphasis must be placed on gradually ramping up physical activities, allowing for adequate breaks and avoiding exercising to the point of exhaustion or fatigue.  This in order to encourage patients to participated in active pre-disease lifestyle as tolerated.

Coordination of care

Team approach is important both in outpatient and inpatient settings. Coordination of therapies, other specialty involvement (rheumatology, pulmonology, cardiology, and nephrology), and educating staff or therapists and family/caregivers regarding exercise regimens at the different stages of the disease and care for organ systems, as previously discussed, is crucial.

Patient & family education

The patient and family must be educated about disease pathology, long-term prognosis, and activity limitations. Patients and family members will often require time and emotional help dealing with realistic expectations about outcomes, especially when poor prognostic indicators are present.

Emerging/unique Interventions

The National Institute of Neurological Disorders and Stroke (NINDS) and other institutes of the National Institutes of Health (NIH) conduct research trying to explore patterns of gene expression among the inflammatory myopathies, the role of viral infection as a precursor to the disorders, and the safety and efficacy of various treatment regimens. Studies are being performed to determine the efficacy, safety and tolerability of novel immunomodulators in patients with polymyositis who are not responsive to traditional immunosuppressive and/or corticosteroid therapy.

Translation into practice: practice “pearls”/performance improvement in practice (PIPs)/changes in clinical practice behaviors and skills

PM and other inflammatory myopathies should be considered in adult patients with weakness without prominent sensory complaints and elevated CK. It should be distinguished from other conditions in the differential diagnosis by the lack of skin rash (DM), weakness in hip flexors more than quadriceps (IBM), and lack of family history (adult onset inherited myopathies). PM generally respond to corticosteroids. If it does not, steroid resistive PM, IBM and adult onset inherited myopathies should be considered.6

4. CUTTING EDGE/EMERGING AND UNIQUE CONCEPTS AND PRACTICE

Rituximab is a monoclonal antibody directed against CD20, a surface marker of B cells.1.  It has been used as a third-line agent for treating patients with IIM with increasing evidence of its benefit. Abatacept is a soluble fusion protein that inhibits binding of co-stimulatory protein CD28 on T-cells, and Sifalimumab a human anti–IFN-a monoclonal antibody are being studied as treatment for refractive DM and PM.1

5. GAPS IN THE EVIDENCE-BASED KNOWLEDGE

Gaps in the evidence-based knowledge

Knowledge gaps include inciting agent(s), mechanism of action, and the fact that inadequate evidence for specific exercise prescriptions in neuromuscular disease.18 Large studies of the role of exercise during rehabilitation for inflammatory myopathy have not been performed.

REFERENCES

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  3. Pappu R, Seetharaman M. Polymyositis [Medscape Web site]. Available at: http://emedicine.medscape.com/article/335925-overview#showall. Accessed November 6,2015.
  4. Villa-Forte A, Mandell BF. Rheumatic diseases of the cardiovascular system. In: Bonow RO, Mann DL, Zipes DP, Libby P, eds. Braunwald’s Heart Disease–A Textbook of Cardiovascular Medicine. 9th ed. Philadelphia, PA: Elsevier; 2012:1888.
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  8. Preston DC, Shapiro BE. Electromyography and Neuromuscular Disorders: Clinical-Electrophysiologic Correlations. 2nd ed. Philadelphia, PA: Elsevier; 2005:575-589.
  9. Di Martino SJ, Kagen LJ. Newer therapeutic approaches: inflammatory muscle disorders. Rheum Dis Clin North Am. 2006;32:121-128.
  10. Dalakas M. Immunotherapy of myositis: issues, concerns and future prospects. Nat Rev Rheum 2010;6:129–137.
  11. Dalakas M. Immunotherapy of inflammatory myopathies: practical approach and future prospects. Curr Treat Options Neurol 2011;13: 311–323.
  12. Distad B, Amato A, Weiss M. Inflammatory myopathies. Curr Treat Options Neurol 2011;13:119–130.
  13. Mimori T, Nakashima R, Hosono Y. Interstitial lung disease in myositis: clinical subsets, biomarkers, and treatment. Curr Rheumatol Rep 2012;14:264–274.
  14. Dalakas MC. Polymyositis, dermatomyositis and inclusion-body  myositis. N Engl J Med 1991; 325: 1487–98.
  15. Dalakas MC. How to diagnose and treat the inflammatory myopathies. Semin Neurol 1994; 92: 365–69.
  16. Dalakas MC1, Hohlfeld R. Polymyositis and dermatomyositis. Lancet. 2003 Sep 20;362(9388):971-82.
  17. Dalakas MC. Polymyositis, dermatomyositis and inclusion body myositis. In: Braunwald E, Fauci AS, Kasper DL, Hauser SL, Longo DL, Jameson JL, eds. Harrison’s principles of internal medicine, 15th edn. New York: McGraw-Hill, 2001: 2524–29.
  18. Abresch RT1, Carter GT, Han JJ, McDonald CM. Exercise in neuromuscular diseases. Phys Med Rehabil Clin N Am. 2012 Aug;23(3):653-73. doi: 10.1016/j.pmr.2012.06.001.
  19. Hicks JE1, Miller F, Plotz P, Chen TH, Gerber L. Isometric exercise increases strength and does not produce sustained creatinine phosphokinase increases in a patient with polymyositis.  J Rheumatol. 1993 Aug;20(8):1399-401.
  20. Voet NB1, van der Kooi EL, Riphagen II, Lindeman E, van Engelen BG, Geurts AC. Strength training and aerobic exercise training for muscle disease. Cochrane Database Syst Rev. 2013 Jul 9;7:CD003907. doi: 10.1002/14651858.CD003907.pub4.

Original Version of the Topic:

Keith M. D’Souza, MD VA. Polymyositis. Publication Date: 2012/07/25

Author Disclosure

Edwardo Ramos, MD
Nothing to Disclose

Brenda Castillo, MD
Nothing to Disclose

Rafael Arias, MD
Nothing to Disclose

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