Author(s): Glendaliz Bosques, MD, Mani P. Singh, MD
Originally published: July 25, 2012 Last updated: July 22, 2020
Jump to:

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 the skin, heart, gastrointestinal tract, and lungs. Systemic symptoms may manifest in the forms of fever, arthralgias, Raynaud’s phenomenon, cardiac arrhythmias, or interstitial lung disease (ILD). 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. A number of autoantibodies are associated with these syndromes, some 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.2 

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. However, only the human retroviruses, human immunodeficiency virus (HIV) and human T cell lymphotropic virus type I (HTLV-I), the simian retroviruses, and coxsackievirus B have been etiologically connected with the disease.1 Genetic risk factors may contribute to these immune responses as well. Interactions between the HLA-DRB1*03 loci and anti-Jo-1 antibodies in polymyositis are being researched.3

Epidemiology including risk factors and primary prevention

PM is more common in women than men (2:1 ratio) and rarely affects the pediatric population. Among children affected with inflammatory myopathies, juvenile polymyositis (JPM) accounts for 4 % of these patients, with juvenile dermatomyositis (JDM) accounting for the majority. In patients within the pediatric population, the median age of onset is typically 11 years old, while the median age at diagnosis is closer to 12.1 years.4 Incidence can vary from 0.5-8.4 cases per 1 million people, with a higher incidence among Black Americans (black-to-white incidence of 5:1) and lower incidence among Hispanic children.4,5 PM usually affects the adult population in the age range of 40-60 years of age.5 Compared to adults, children with PM are less likely to suffer from ILD, have a lower mortality rate (0.7% in the first year of diagnosis vs. 9% in the first year of diagnosis for adults), and have a weaker association with pediatric malignancy.4

Genetic factors may play a role, as suggested by rare familial occurrences and associations with certain human leukocyte antigen (HLA) genes, such as DRB1*0301 alleles, HLA-B*08, and DQA1*0501.2,6 Other loci that may be implicated include genes coding for the pro-inflammatory markers involved in the pathophysiology of PM, including TNF-alpha, interleukin-1 (IL-1), PTPN22, and the immunoglobin heavy chains. PM can be associated with other autoimmune conditions including systemic lupus erythematosus, Sjogren’s syndrome, rheumatoid arthritis, scleroderma, and mixed connective tissue disease. Recent studies suggest there may be protective alleles as well, such as DQA1*0201, DQA1*0101, and DQA1*0202. These alleles are less frequently seen in patients with PM and are hypothesized to eliminate self-reactive T cells in the thymus.6

Patho-anatomy/physiology

The inflammatory infiltrates seen in PM are located in the endomysium and include CD4 and CD8 T cells, dendritic cells (DC), and macrophages. In healthy individuals, the sarcolemma of normal muscle fibers do not express the major histocompatibility complex (MHC) class I molecules. In PM, aberrant expression of MHC class I is thought to be caused by inappropriate activation of T cells and the production of cytokines. It is thought that CD8 T cells bind with the MHC class I molecules in the presence of autoantigens, releasing granules, including the cytolytic protein perforin, and inducing myofiber necrosis.3

Hypoxia may cause weakness in PM by reducing phosphocreatine and adenosine triphosphate (ATP) levels in muscle, inducing production of IL-21, tumor growth factor-b (TGF-b), and HMGB1, which induces muscle fatigue by irreversibly decreasing calcium (Ca) release. An autoimmune response to nuclear and cytoplasmic autoantigens is detected in about 60-80% of patients with polymyositis.1,5 Vascular changes are associated with PM as well. Inflammation may lead to microscopic areas of ischemia that can be visualized by examination of digital nailfold capillaries.4

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

Onset is typically gradually progressive, with symmetric proximal involvement greater than distal limb weakness and 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. In children, the prognosis for the juvenile inflammatory myopathies is relatively good. Twenty five percent of patients will have a monocyclic course with recovery and discontinuation of medications within two years. Another twenty five percent will have a polyphasic course with periods of remission and recurrence. However, the remaining fifty percent may have a chronic course with continued therapy for more than two years. Prognostic studies though include both PM and DM. Additional studies are needed with a focus solely on JPM prognostication.4

In adults, five-year survival rates have been estimated at more than 80%. Mortality is most often related to associated malignancy or pulmonary complications. 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 In pediatric patients, the risk for occult cancer is much lower. However, in patients with positive antisynthetase antibodies or positive anti-small ubiquitin-like modifier-1 (SUMO-1) activating enzyme (anti-SAE), dysphagia screening and pulmonary screening remain crucial given the high risk of dysphagia and interstitial lung disease.7

Specific secondary or associated conditions and complications

Pulmonary involvement can result in ILD in 5-30% of patients; half of these patients show anti-Jo-1 antibodies. 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.5 Oropharyngeal and/or esophageal weakness can result in dysphagia, dysphonia, nasal regurgitation, and aspiration pneumonia. Cardiac features are rare and, if present, portend a bad prognosis. They include rhythm abnormalities, heart failure, myocarditis, and pericarditis.8 Patients are also at elevated risks of thrombotic events, such as venous thromboembolism, pulmonary embolism, and deep vein thrombosis. One component of this association may be due to vessel wall damage caused by systemic inflammation, as well as the upregulation of procoagulants and the downregulation of anticoagulants.9 Antisynthetase 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. Among patients with myositis-specific antibodies, these patients have the highest mortality rate, likely related to the frequency of interstitial lung disease.6 PM with anti-signal recognition particle (SRP) autoantibodies is associated with acute-onset necrotizing myopathy with severe weakness and high serum creatine kinase (CK).10

ESSENTIALS OF ASSESSMENT

History

Patients complain of insidious onset, gradually progressive but 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. Other common signs or symptoms include proximal muscle weakness, frequent falls, arthralgias or arthritis, abdominal pain, dysphonia, dysphagia (in approximately one third of patients), wheezing, shortness of breath, and constipation.11 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.12

Children may have difficulties rising from the floor or low chairs. They may have difficulty squatting while playing, decreased sports performance, difficulty brushing hair, or new difficulties climbing stairs. Diagnosis is usually delayed, because, unlike in dermatomyositis, no associated rash occurs before the onset of muscle disease.4

PM is a diagnosis of exclusion but should be considered in patients with subacute proximal myopathy lacking an associated rash, family history of neuromuscular disease, involvement of facial muscles, or exposure to myotoxic drugs (such as statins, zidovudine, penicillamine).3 Myositis itself can be caused by multiple agents and should be carefully excluded when considering PM as a diagnosis. Infectious agents, such as influenza virus (A and B), coxsackie virus, HIV, hepatitis B, Staphylococcus, Streptococccus, Clostridum, Toxoplasmosis and others can result in myositis.3,4,13

Physical examination

Nothing is characteristic about the muscle weakness in PM, 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 muscles 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 generally preserved but may be absent in severely weakened or atrophied muscles. Sensory examination is normal as well as ocular muscle movements. 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 found at lung bases (Velcro lungs) which suggests interstitial lung disease.5 Additional features that may be present are described below.

  • Musculoskeletal: muscle atrophy, joint contractures
  • Respiratory: decreased breath sounds (following aspiration), crackles (interstitial lung disease)
  • Cardiovascular: arrhythmias, friction rub or muffled heart sounds (pericarditis, myocarditis)
  • Vascular: Raynaud’s phenomenon, digital fissuring without ulcerations, periungual capillary changes12

Functional assessment

When evaluating a child for JPM, the following measures of strength and physical function have been validated: Childhood Myositis Assessment Scale (CMAS), the Childhood Health Assessment Questionnaire (CHAQ), and Manual Muscle Testing. Clinical outcomes can be monitored using Functional Independence Measure scores. Patient-reported Quality of Life Scale can be used to monitor patient satisfaction during both acute inpatient stay and after discharge to home or subacute rehabilitation.4

Laboratory studies

Serum 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. Erythrocyte sedimentation rate (ESR) may also be elevated. Other enzymes, including aldolase, myoglobin, lactate dehydrogenase, aspartate aminotransferase (AST), and alanine aminotransferase (ALT), may be elevated.2 If there is concern for concomitant hepatic disease, gamma-glutamyl transferase (GGT), alkaline phosphatase, and bilirubin studies may also be ordered. GGT is specific to the liver and can help uncover hepatic inflammation as an etiology for elevated liver enzyme levels. Urine studies may show proteinuria, myoglobinuria, or signs indicative of proliferative glomerulonephritis.14

Antinuclear antibody (ANA) may be positive in up to 70% of patients with JPM.15 A number of other antigens/autoantibodies can be present, including (positive rate in PM): Jo-1 (33%), Mi-2 (15-35%), PM-Scl (8-12%), U1nRNP (4-17%), and SRP (4-5%).16 Anti-Jo-1, Mi-2, and SRP belong to a group known as aminoacyl tRNA synthetase (ARS) autoantibodies. As mentioned, the presence of ARS antibodies is associated with antisynthetase syndrome. Anti-Mi-2 may be more associated with DM whereas anti-SRP is more specific for PM.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.5,17

Imaging

Magnetic resonance imaging (MRI) is being increasingly used as it can detect muscle necrosis, degeneration, edema, and inflammation. Abnormalities are characterized by increased signal intensity on short-tau inversion recovery (STIR) images. 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, as laboratory markers are often unreliable once treatment has begun. MRI is extremely sensitive in identifying resolving areas of muscle edema, thus showing areas of active involvement. MRI also has a role in providing prognostic information and evaluating treatment response but is limited by availability and cost.9

Ultrasound, specifically Doppler sonography, contrast-enhanced ultrasound, and sonoelastography, is gaining an increasing role in differentiating between normal and pathologic muscle.1 Although MRI remains the most sensitive, ultrasound has many advantages in that it is cheap, noninvasive, and can be performed serially in multiple clinical settings. Studies have shown that muscle echogenicity in ultrasound correlated with disease duration and muscle atrophy while Doppler studies better reflected disease activity. Technical developments in ultrasound, such as power Doppler sonography or contrast-enhanced ultrasound have not been studied as well in the context of PM but are enhancing the diagnostic capabilities of ultrasound.18

In addition to these studies, a chest X-ray should be included, as well as a high-resolution computed tomography (CT) scan of the chest, if there is concern for interstitial lung disease. An echocardiogram should be done if there is concern of myocarditis or pericarditis.

Supplemental assessment tools

In addition to imaging and serologic studies, electrodiagnostic testing can be done. Furthermore, muscle biopsy (and skin biopsy in DM) is commonly done for confirmation.

Needle electromyographic (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.19 Motor unit action potentials (MUAP) can be used to assess PM patients. Decreased MUAP duration is a sensitive measure of PM. Some studies have shown that MUAP amplitude reduction may be correlated with disease duration (correlation found in biceps brachii data).20 In addition, location of EMG study is important. Although PM is typically thought to be a disease of proximal muscles, EMG studies of distal muscles of the lower limbs were found to uncover significant pathology, thus underscoring the importance of selecting multiple muscles in these patients. 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.19

Muscle biopsies can be a useful tool in the diagnosis of PM. The most electrophysiologically involved muscles are often good target muscles for biopsy on the contralateral limb. Biopsies are most useful when they are properly chosen, such as in muscles without advanced end-stage disease but still showing moderate symptoms. Depending on the clinical picture, biochemical assay tests run on the muscle biopsy specimen include testing for metabolic disorders and dystrophin. Analysis of muscle biopsies in PM patients will show perivascular inflammation, CD8+ T cell invasion, and non-necrotic muscle fibers expressing MHC class I antigen. Finding MHC-CD8 complexes can both help confirm the diagnosis and rule out nonimmune inflammation (seen in some muscular dystrophies).3

Muscle biopsy should be interpreted with caution given the patchy nature of the muscular disease.4 Some muscular dystrophies may show a moderate amount of inflammation on muscle biopsy as well. Immunostaining and/or genetic testing plays an important role in distinguishing between PM, dysferlinopathy, and other limb-girdle muscular dystrophies, particularly as corticosteroid treatment can worsen inflammation in the latter. Furthermore, muscle biopsies do not always correlate with muscle power or CK levels and may not be enough to differentiate between different types of idiopathic inflammatory myopathies by themselves.21 In order to circumvent this pitfall, combining muscle biopsies with MRI scans of biopsy sites has been shown to decrease false negative rates and increase the sensitivity of these tools in diagnosing polymyositis.22

Modified barium swallow studies and pulmonary function tests may be warranted based on clinical presentation.

No official classification system currently exists, as disagreement continues.23 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 five 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 of all 1-4 criteria suggested definite PM, three of 1-4 criteria indicated probable PM, and if two 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.24,25

A recent interdisciplinary effort developed classification criteria for the IIMs to guide future research on therapies. A set of criteria elements and methods to apply these elements were developed by the International Myositis Classification Criteria Project (IMCCP). These criteria are pending approval by the American College of Rheumatology (ACR) and the European League Against Rheumatism (EULAR). However, there is controversy since histological characterizations are not part of the classification criteria, potentially leading to lower sensitivity. Additionally, the 2017 EULAR criteria only consider the presence of anti-Jo-1 antibodies as part of their clinical criteria.23

Clinical Elements:

  1. Clinical Criteria
    • Inclusion Criteria:
      1. Onset typically postpuberty with exception of children with DM or nonspecific myositis
      2. Subacute or insidious onset
      3. Symmetrical weakness, proximal > distal, neck flexor > neck extensor
      4. Rash typical of dermatomyositis (not applied to PM)
    • Exclusion Criteria:
      1. Clinical features of IBM, including asymmetrical weakness
      2. Ocular weakness, neck extensor > neck flexor weakness
      3. Recent exposure to myotoxic drugs, endocrinopathy, family history of muscular dystrophy
  2. Elevated Serum CK
  3. Other Laboratory Criteria
    • Electromyography
      1. Inclusion Criteria: fibrillation potentials, positive sharp waves or complex repetitive discharged, short duration/small amplitude/polyphasic MUAPs
      2. Exclusion Criteria: long-duration/large-amplitude MUAPs, discharges suggestive of myotonic dystrophy, decreased recruitment pattern of MUAPs
    • MRI: diffuse or patchy increased signal within muscle tissue on STIR images
    • Myositis specific antibodies detected in serum
  4. Muscle Biopsy Criteria
    • Endomysial inflammatory cell infiltrate surround and invading non-necrotic muscle fibers
    • Endomysial CD1+ T cells surrounding but not invading muscle fibers OR ubiquitous MHC-1 expression
    • Perifascicular atrophy
    • MAC depositions on small blood vessels, reduced capillary density
    • Perivascular and perimysial inflammatory cell infiltrate
    • Scattered endomysial CD8+ T cell infiltrate
    • Many necrotic muscle fibers as predominant histologic findings
    • Rimmed vacuoles or findings that would suggest IBM
    • MAC deposition on sarcolemma of non-necrotic fibers or other indications of muscular dystrophies
Table 1. Clinical Elements of Juvenile Polymyositis

Scoring of the Classification to Define Polymyositis Using Above Clinical Elements:

  • Definitive Polymyositis:
    • All clinical criteria with exception of rash
    • Elevated serum CK
    • Muscle biopsy criteria include a and exclude c, d, h, i
  • Probable Myositis:
    • All clinical criteria with exception of rash
    • Elevated serum CK
    • Other laboratory criteria (1 of 3 possible criteria)

Early predictions of outcomes

Poor prognostic indicators include delay in diagnosis and/or initiation of treatment, older age, female sex, lower income, Black and non-Black minorities, presence of anti-Jo-1 antibodies, presence of anti-SRP antibodies, presence of anti-tRNA synthetase antibodies, presence of anti-MDA5 antibodies, dysphagia, dysphonia, associated malignancy and cardiac and pulmonary involvement.4,5 Studies show that in JDM, the presence of calcinosis and negative anti-nuclear antibodies are associated with increased morbidity and poorer outcomes.26 However, there is a lack of data analyzing such predictors of outcomes in JPM. 

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 (ADLs) 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.27

The main barrier for an optimal drug therapy for IIMs is 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.27

The current standard of care is high-dose corticosteroids, starting with prednisone at 1 mg/ kg/day (up to 100mg daily) with eventual taper to a minimal dose anywhere from four weeks to several months after initiation. Patients with severe disease, such as ILD, dysphagia, or profound weakness, are typically started on 1 g/day intravenous methylprednisolone for three to five days before switching to 1 mg/kg/day of oral prednisone for several months.28,29

Many patients symptomatically improve after starting corticosteroids, but recovery of strength gradually occurs over the next two to three 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 three to six months of prednisone, or if the patient relapses while tapering, a second-line immunosuppressive agent should be added.1

Common second-line choices include azathioprine (AZA), methotrexate (MTX), rituximab, and intravenous immunoglobulins (IVIG). Among these, MTX in combination with prednisone has the most data for clinical efficacy.6,30 Alternatively, IVIG can be used (2 g per kilogram in divided doses over a period of two to five consecutive days).3 IVIG has been found to be effective in patients with dysphagia and patients resistant to improvement with oral prednisone.  Less frequently used medications include mycophenolate mofetil, tacrolimus, cyclosporine, and cyclophosphamide.1 These medications (mycophenolate mofetil, cyclophosphamide) are often reserved for patients with rapidly progressive disease, patients with respiratory muscle failure or dysphagia, and in patients with extramuscular involvement.Adrenocorticotropic hormone (ACTH) gel and injections have also been used to improve muscle strength and decrease involvement of skin in certain IIMs.31,32

Recently, the Childhood Arthritis and Rheumatology Research Alliance (CARRA) formed consensus protocols in order to treat pediatric patients with IIM. Briefly, one favored protocol recommended treatment with steroids at 2 mg/kg/day in combination with MTX at 1 mg/kg in order to minimize side effects of steroids while still controlling disease activity. Other strategies suggested initiating treatment with intravenous pulse methylprednisolone for three consecutive days (with or without IVIG) prior to transitioning to an oral regimen. Regarding steroid tapering, the CARRA report recommends the goal should be to discontinue steroids ten to twelve months after the initial diagnosis of PM.6

New biologics are being tested for the treatment of JPM and IIM, but there is limited data. These biologics include abatacept, infliximab, tocilizumab, anakinra, alemtuzumab, sifalimumab, basiliximab, and tofacitinib. Other non-pharmacologic treatments being explored include plasma exchange and leukapheresis. Currently, their use in clinical practice is not recommended. 33  

Disease Assessment and Treatment Response

There are multiple tools available to assess the degree of disease activity and responses to treatment.

  • Disease Assessment and Overall Disease Activity
    • Physician Global Disease Activity
    • Likert Scale: 0 indicating no disease activity, 4 indicating severe disease activity
  • Muscle Testing
    • Manual Muscle Test (MMT): scores proximal, distal, and axial muscles
      • United Kingdom Medical Research Council System Scale (0-5): 0 indicates lowest strength, 5 indicates highest
  • Physical and Occupational Function
    • Stanford Health Assessment Questionnaire: self-assessment of activities of daily living (ADLs)
    • Myositis Activities Profile: ADLs in movement, personal care, hygiene, and other activities specific to IIM
    • Functional Index-2: measures repetitions in seven muscles to assess for muscle impairment in PM33

Rehabilitation Challenges

In general, the evidence is limited for specific exercise prescriptions in individuals with PM, particularly in the pediatric population.34 While strength and aerobic exercise training programs do not appear to cause harm there is limited evidence to support that they offer benefit.35,36 However, there is emerging evidence supporting the safety and efficacy of exercise training programs in patients with IIMs.37 Much of this evidence was obtained in the adult population. Recent research supports the role of exercise in preserving muscle strength, increasing aerobic fitness, functional performance and capacity, and lung function.38 Undergoing a standardized rehabilitation program may improve quality of life, pain levels, and result in lower levels on the Health Assessment Questionnaire Disability Index (HAQ-DI) compared to controls.39 General consensus supports that this population should begin early in the course of treatment with rehabilitation protocols.37

Rehabilitation varies depending on the severity of weakness. In severe weakness, treatment involves bed rest, passive range of motion (PROM) 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 is encouraged. Bowel, bladder, hydration, swallowing, respiratory, and cardiac systems need to be monitored. Some patients with severe disease may require splinting and bracing for further maintenance of PROM and to decrease the risk for significant disabling contractures.40,41 In adults, studies illustrate the safety and efficacy of aquatic therapies in patients with PM.42 Similar studies are needed in JPM.

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 participate in active pre-disease lifestyles 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, therapists, and family/caregivers regarding exercise regimens at the different stages of the disease, 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 PM who are not responsive to traditional immunosuppressive and/or corticosteroid therapy.

The International Myositis Assessment and Clinical Studies Group (IMACS), along with the Pediatric Rheumatology International Trials Organization (PRINTO) have begun developing a core set of disease activity measures (including measures such as Childhood Myositis Assessment Scale (CMAS) and CHAQ). The goal is for these disease activity measures to be used in future clinical trials. Thus far, this group has defined inactive disease as fulfilling 3 of the 4 following criteria:

  1. Manual Muscle Test (MMT-8) of at least 78 (0-80 scale)
  2. Physician Global Assessment of Muscle Disease Activity (PhyGloVAS) of 0.2 or less
  3. CMAS of at least 48
  4. CPK of 150 or less43

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 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 responds to corticosteroids. If it does not, steroid resistive PM, IBM and adult onset inherited myopathies should be considered.11

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. A recent large, randomized, double-blind, placebo-phase trial in patients with refractory PM found that 83% of patients showed improvement after treatment with Rituximab.14 Abatacept, 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 treatments for refractive DM and PM.1

Additional therapeutic trials are currently underway, such as trials evaluating if glucocorticoids and MTX may be better than glucocorticoids alone.14

IMCCP developed a web calculator to assist clinicians in categorizing myositis. As more patient data is added, more accurate information will be provided. http://www.imm.ki.se/biostatistics/calculators/imm23

Magnetic Resonance Elastography is being trialed as an imaging method to quantify the mechanical elasticity of muscles in patients affected by PM. A small study showed that in patients with active myositis, there may be reduced stiffness of the vastus medialis in the relaxed state compared to healthy controls. Data is scarce and this technique has not yet been translated to clinical practice.33

Recent studies show that disease activity may be correlated with peripheral blood levels of a type-1 interferon signature. Other studies have shown a correlation with IL-6 biomarkers and disease activity. More studies are needed to validate the use of these proinflammatory cytokines as sensitive biomarkers of disease activity.33 The Childhood Myositis Assessment Scale (CMAS) has been developed as a tool to evaluate muscle function and assess the severity of muscle involvement in children. The scoring system showed to have excellent inter- and intra- rater reliability to assess function, strength, and endurance with the goal to be used as a clinical tool and measure of outcomes in clinical trials.44

GAPS IN THE EVIDENCE-BASED KNOWLEDGE

Gaps in the evidence-based knowledge

Knowledge gaps include inciting agents, mechanism of action, and the fact that there is inadequate evidence for specific exercise prescriptions in neuromuscular disease.33 Large studies evaluating the role of exercise (including aquatic therapy) during rehabilitation for IIM have not been performed in the pediatric population. Similarly, there are no large randomized controlled trials comparing different treatment modalities in pediatric patients with PM. Data is limited on the efficacy and long-term toxicity of immunosuppressants in IIM in the pediatric population.44 As long-term studies are obtained, they should be used to fill in gaps of knowledge regarding predictors of outcome and epidemiology for JPM. There is data exploring the relationships between race, income, health disparities, and outcomes in patients with JDM but no such data exists for JPM.26,46

REFERENCES

  1. Findlay AR1, Goyal NA, Mozaffar T. An overview of polymyositis and dermatomyositis. Muscle Nerve. 2015 May;51(5):638-56. doi: 10.1002/mus.24566.
  2. Dalakas MC1, Hohlfeld R. Polymyositis and dermatomyositis. 2003 Sep 20;362(9388):971-82.
  3. Dalakas MC. Inflammatory Muscle Diseases. N Engl J Med. 2015;372:1734-1747.
  4. Huber AM. Juvenile Idiopathic Inflammatory Myopathies. Pediatr Clin N Am. 2018;65:739-756.
  5. Pappu R, Seetharaman M. Polymyositis [Medscape Web site]. Available at: http://emedicine.medscape.com/article/335925-overview#showall. Accessed November 6,2015.
  6. Pagnini I, Vitale A, Selmi C, et al. Idiopathic Inflammatory Myopathies: an Update on Classification and Treatment with Special Focus on Juvenile Forms. Clinic Rev Allerg Immunol. 2017;52:34-44.
  7. Satoh M, Tanaka S, Ceribelli A, et al. A Comprehensive Overview on Myositis-Specific Antibodies: New and Old Biomarkers in Idiopathic Inflammatory Myopathy. Clin Rev Allergy Immunol. 2017;52(1):1-19.
  8. 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.
  9. Lee YH, Song GG. Idiopathic inflammatory myopathy and the risk of venous thromboembolism: a meta-analysis. Rheumatol Int. 2017;37:1165-1173.
  10. O’Rourke KS. Sarcopenia and myopathies in the elderly. In: Nakasato Y, Yung RL, eds. Geriatric Rheumatology: A Comprehensive Approach. 1st ed. New York, NY: Springer; 2011:264-267.
  11. Amato AA, Russell JA. Inflammatory myopathies. In: Amato AA, Russell JA, eds. Neuromuscular Disorders. 1st ed. New York, NY: McGraw Hill Medical; 2008:681-719.
  12. Mamyrova G, Katz JD, Jones RV, et al. Clinical and Laboratory Features Distinguishing Juvenile Polymyositis and Muscular Dystrophy. Arthritis Care & Research. 2013;62(12):1969-1975.
  13.  (2009) Polymyositis. In: Dermatomyositis. Springer, Berlin, Heidelberg. Dermatomyositis. 2015:151-156.
  14. Davies R, Choy E. Idiopathic Inflammatory myopathy. Medicine. 2014;42(3):174-179.
  15. Pachman LM. Inflammatory myopathy in children. Rheum Dis Clin North Am. 1994;20(4):919-942.
  16. von Muhlen CA, Nakamura RM. Clinical and laboratory evaluation of systemic rheumatic diseases. In: McPherson RA, Pincus MR, eds. McPherson: Henry’s Clinical Diagnosis and Management by Laboratory Methods. 22nd ed. Philadelphia, PA: Elsevier; 2011:983.
  17. Haas RH, Dyck RF, Dubowitz V, Pepys MB. C-reactive protein in childhood dermatomyositis. Annals of the Rheumatic Diseases. 1982;41(5):483.
  18. Adler R, Garofalo G. Ultrasound in the evaluation of the inflammatory myopathies. Current Rheumatology Reports. 2009;11(4):302-308.
  19. Preston DC, Shapiro BE. Electromyography and Neuromuscular Disorders: Clinical-Electrophysiologic Correlations. 2nd ed. Philadelphia, PA: Elsevier; 2005:575-589.
  20. Yang F, Jing F, Chen Z, et al. Electrophysiological and Clinical Examination of Polymyositis: A Retrospective Analysis. The American Journal of the Medical Sciences. 2014;348(2):162-166.
  21. Suparaporn W, Songkiet S, Kantawut A, et al. The Correlation of Muscle Biopsy Scores with the Clinical Variables in Idiopathic Inflammatory Myopathies. The Open Rhematology Journal. 2016;10:141-149.
  22. Vlekkert J, Maas M, Joogendijk JE, et al. Combinding MRI and Muscle Biopsy Improves Diagnostic Accuracy in Subacute-Onset Idiopathic Inflammatory Myopathy. Muscle & Nerve. 2015;51(2):253-258.
  23. Lundberg IE, Miller FW, Tjarnlund A, Bottai M. Diagnosis and Classification of Idiopathic Inflammatory Myopathies. J Intern Med. 2016;280:39-51.
  24. Di Martino SJ, Kagen LJ. Newer therapeutic approaches: inflammatory muscle disorders. Rheum Dis Clin North Am. 2006;32:121-128.
  25. Targoff IN. Idiopathic Inflammatory Myopathy: Autoantibody Update. Current Rheumatology Reports. 2002;4:434-441.
  26. Phillippi K, Hoeltzel M, Robinson AB, Kim S. Race, Income and Disease Outcomes in Juvenile Dermatomyositis. J Pediatr. 2017;184:38-44.
  27. Dalakas M. Immunotherapy of myositis: issues, concerns and future prospects. Nat Rev Rheum 2010;6:129–137.
  28. Dalakas M. Immunotherapy of inflammatory myopathies: practical approach and future prospects. Curr Treat Options Neurol 2011;13: 311–323.
  29. Distad B, Amato A, Weiss M. Inflammatory myopathies. Curr Treat Options Neurol 2011;13:119–130.
  30. Moghadam-Kia S, Oddis CV, Aggarwal R. Modern Therapies for Idiopathic Inflammatory Myopathies (IIMs): Role of Biologics. Clinic Rev Allerg Immunol. 2017;52:81-87.
  31. Mimori T, Nakashima R, Hosono Y. Interstitial lung disease in myositis: clinical subsets, biomarkers, and treatment. Curr Rheumatol Rep 2012;14:264–274.
  32. Barsotti S, Lundberg IE. Current Treatment for Myositis. Curr Treat Options in Rheum. 2018;4:299-325.
  33. Emste FC, Reed AM. Idiopathic Inflammatory Myopathies: Current Trends in Pathogenesis, Clinical Features, and Up-to-Date Treatment Recommendations. Mayo Clin Proc. 2013;88(1):83-105.
  34. 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.
  35. 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.
  36. 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.
  37. Alexanderson H, Lundberg IE. Muscle Strength and Exercise in Patients with Inflammatory Myopathies. The Inflammatory Myopathies. 2009.
  38. Habers GEA, Takken T. Safety and efficacy of exercise training in patients with an idiopathic inflammatory myopathy – a systematic review. Rheumatology. 2011;50:211302124.
  39. Tiffreau V, Rannou F, Kopciuch F, et al. Postrehabilitation Functional Improvements in Patients With Inflammatory Myopathies: The Results of a Randomized Controlled Trial. Archives of Physical Medicine and Rehabilitation. 2017;98;227-234.
  40. Habers GEA, Bos GJFJ, Van Royen-Kerkhof A, et al. Muscles in motion: a randomized controlled trial on the feasibility, safety and efficacy of an exercise training programme in children and adolescents with juvenile dermatomyositis. Rheumatology. 2016;55(7):1251-1262.
  41. Klepper SE. Exercise in pediatric rheumatic diseases. Curr Opin Rheumatol. 2008;20(5):619-624.
  42. Alexanderson H, Dastmalchi M, Esbjornsson-Liljedahl ME, et al. Benefits of Intensive Resistance Training in Patients with Chronic Polymyositis or Dermatomyositis. Arthritis & Rheumatism. 2007;57(5):768-777.
  43. Ernste FC, Reed AM. Recent advances in juvenile idiopathic inflammatory myopathies. Curr Opin Rheumatol. 2014;26:67-678.
  44. Lovell DJ, Lindsley CB, Rennebohm RM, et al. Development of validated disease activity and damage indices for the juvenile idiopathic inflammatory myopathies. Arthritis & Rheumatism. 1999;42(10):2213-2219.
  45. Gordon PA, Winer JB, Hoogendijk JE, Choy EHS. Immunosuppressant and immunomodulatory treatment for dermatomyositis and polymyositis. Cochrane Database of Systematic Reviews 2012, Issue 8. Art. No.: CD003643.
  46. Hashkes PJ, Wright BM, Lauer MS, et al. Mortality Outcomes in Pediatric Rheumatology in the US. Arthritis & Rheumatism. 2010;62(2):599-608.
  47. Dalakas MC. Polymyositis, dermatomyositis and inclusion-body  myositis. N Engl J Med 1991; 325: 1487–98.
  48. Dalakas MC. How to diagnose and treat the inflammatory myopathies. Semin Neurol 1994; 92: 365–69.
  49. 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.
  50. Hočevar A, Rotar Z, Krosel M, et al. Performance of the 2017 European League Against Rheumatism/American College of Rheumatology classification criteria for adult and juvenile idiopathic inflammatory myopathies in clinical practice. Annals of the Rheumatic Diseases 2018;77:e90.

Original Version of the Topic:

Keith M. D’Souza, MD VA. Polymyositis. Publication Date: 7/25/2012

Previous Revision(s) of the Topic

Edwardo Ramos, MD. Brenda Castillo, MD. Rafael Arias, MD . Polymyositis. Publication Date: 8/17/2016

Author Disclosure

Glendaliz Bosques, MD
Nothing to Disclose

Mani P. Singh, MD
Nothing to Disclose