|Ahead of print publication
Exercise training in myositis recovery: Practical issues and challenges
Kristofer Magnus Andreasson
Department of Medicine, Karolinska Institutet, Karolinska University Hospital; Medical Unit Occupational and Physical Therapy, Karolinska University Hospital, Gaevlegatan, Stockholm, Sweden
|Date of Submission||01-Jul-2022|
|Date of Acceptance||01-Aug-2022|
|Date of Web Publication||20-Sep-2022|
Kristofer Magnus Andreasson,
Karolinska University Hospital, Gaevlegatan 55, Occupational & Physical Therapy, NB00:02, 17164, Solna, Stockholm
Source of Support: None, Conflict of Interest: None
Idiopathic inflammatory myopathies (IIMs), or myositis, are a heterogeneous group of autoimmune disorders characterized by chronic inflammation of the muscle with a variety in clinical manifestations. Muscle impairment, myalgia, fatigue, and extramuscular involvement are common, such as lung and cardiac involvement. Exercise is an important part of the treatment in IIM; however, knowledge on how to individually adjust and optimize exercise considering specific aspects of the disease and extramuscular involvement is scarce. In many studies, patients with extramuscular involvement are excluded which makes the safety and efficacy of exercise for these patients unclear. This study aims to review the practical issues and challenges of exercise regarding different aspects of the disease and extramuscular involvement, as well as to give a clinical perspective on how to initiate and progress exercise for these patients.
Keywords: Idiopathic inflammatory myopathies, physical therapy, rehabilitation, review, treatment
| Introduction|| |
Idiopathic inflammatory myopathies (IIMs), or myositis, are a heterogeneous group of autoimmune disorders characterized by chronic inflammation of the muscle with a variety of clinical manifestations. Muscle impairment in various degrees is common with muscle weakness and primarily reduced muscle endurance. Myalgia and fatigue are also frequent symptoms., The extramuscular symptoms, such as skin rash, interstitial lung disease (ILD), heart involvement, and arthritis, are common and emphasize the systemic nature of these disorders. In some patients, the extramuscular symptoms are dominant and muscle weakness is absent or near absent in the clinical picture, which makes the diagnosis challenging. Due to the heterogeneity and rarity, medical treatment is challenging. The first-line treatment is oral glucocorticoids; pulse glucocorticoid treatment can be given in acute onset or in case of severe muscle or vital organ involvement. To limit the duration of high-dose glucocorticoid treatment, immunosuppressants are used, usually methotrexate or azathioprine.
Exercise is an important part of the treatment for patients with IIM., A systematic review based on only randomized controlled trials (RCTs) published in 2020 reported limited evidence (++) to support the efficacy of a combination of moderate-to-high intensity aerobic and resistance exercise to reduce inflammation and improve aerobic capacity, muscle strength and quality of life in patients with low disease activity. There is insufficient evidence (+) supporting that low-to-moderate-intensity aerobic and resistance exercise is safe and can improve aerobic capacity and muscle endurance in patients with recent onset, active IIM. Other studies have been published with similar results, also stating that for patients with recent onset or refractory active IIM, exercise seems to be safe and effective; however, evidence is limited yet.,,,,
This study aims to review exercise in relation to extramuscular involvement and the rarity and heterogeneity of IIM, as well as give a clinical perspective on how to prescribe exercise for these patients.
| Overall Issue of Exercise Prescription|| |
Rarity, heterogeneity and possible severe vital organ involvement of the IIMs constitute a challenge when prescribing a specific exercise program. Since patients with severe vital-organ involvement have been excluded from exercise studies, exercise treatment for these patients is mainly based on research in other diseases or clinical experience. A holistic view including all aspects of disease and disease impact is important. Baseline screening is of importance for the presence of extramuscular involvement such as lungs, heart, skeletal (joints, bone density), and gastrointestinal (dysphagia). It is also important with regular follow-ups to assess changes in physical capacity where the Functional Index 2 and/or 3 are validated and disease specific.,
| Newly Diagnosed Patients|| |
Less is known about the safety and efficacy of exercise in newly diagnosed patients. One study reported the safety of an easy-moderate intensity home exercise program employed about 4 weeks after diagnosis. The exercise program was performed 5 days a week combined with 20-min walks. There were no signs of increased inflammation after 12 weeks of exercise. However, the exercise group did not improve significantly compared to those on medical treatment alone, likely due to the low intensity of the exercise. Since then, one additional study have been conducted on patients with established but active disease. Although small and open design it still shows thesame - exercise is safe and does not increase creatine kinase (CK) levels.
| Extramuscular Manifestations|| |
ILD is present to some degree in about 64% of patients. Although rare, rapidly progressive ILD is a major cause of mortality early in the disease. Milder forms of ILD are more common with a less severe prognosis, it can also be asymptomatic. Common symptoms of ILD are dyspnea, cough, and reduced exercise tolerance, and can precede muscular symptoms. Total lung capacity and diffusing capacity will likely be reduced. Respiratory muscle weakness and pulmonary arterial hypertension (PAH) can be present in IIM, often developed over time. It is important to evaluate the lung involvement with lung function testing (spirometry) to be able to adapt the exercise intervention and apply an adequate level of supervision during exercise.,
As patients with symptomatic ILD were excluded from most exercise studies, it is unclear how to take ILD into consideration when prescribing an exercise program for an IIM patient. On one hand, the pathophysiology of ILD can induce exercise intolerance and abnormal exertion dyspnea. On the other hand, patients with ILD (idiopathic, COVID-and SARS-related) tolerate exercise with positive effects on forced vital capacity, walking distance in the 6-min walking test and in health-related quality of life. However, a lower exercise response might be expected in IIM-ILD (as reported in connective-tissue disease-related ILD), that aerobic exercise is insufficient, and aquatic and strength training could improve response. Very little is known about the safety and effects of exercise in patients with PAH. Although uncommon in IIM, when present exercise needs to be adapted. One very recent study showed that a continuous aerobic exercise with an intensity of 5–6 out of 10 (Borg CR10-scale) and a sustained SpO2% was safe. Further, low-intensity strength training and inspiratory muscle training were performed and safe as well. It is however important to measure the pressure by heart catheterization before initiating exercise.
Myocarditis, inflammatory infiltration in the cardiac conduction system and replacement fibrosis, and subclinical electrocardiogram abnormalities can all be part of the cardiac involvement in IIM. Patients with IIM also have a higher risk of developing cardiovascular disease. Around 10%–15% of the patients have clinically relevant cardiac involvement and around 70% have sub-clinical cardiac involvement. These changes can lead to arrhythmias, heart failure, and ventricular dysfunction, the two latter might lead to dyspnea, as can myocarditis. To identify subclinical cardiac inflammation or irreparable changes early cardiac magnetic resonance imaging might be necessary.,, To be able to correctly adapt, supervise and safely conduct the exercise, a thorough pre-exercise examination of the cardiovascular system is relevant and important.
Exercise is widely used in cardiac rehabilitation and there is growing evidence supporting the efficacy of high-intensity interval training for patients with heart failure; however, only in the absence of other risk factors such as uncontrolled or untreated acute myo- or pericarditis, symptomatic heart failure or arrhythmias, unstable coronary artery disease which are absolute contraindications for such intensive exercise. However, stabilized with medical treatment, exercise is possible, however in a clinical setting with experienced staff using adequate monitoring, cardiac high-risk patients can safely manage the high-intensity exercise. For safety reasons, aerobic exercise can be reduced to moderate intensity.
Arthritis is present in 20%–50% of patients with IIM, especially in patients with the antisynthetase syndrome (ASyS) who more often present with erosive arthritis. Generally, arthritis is nonerosive and symmetric involving the small joints of the hand although not exclusively. Often the arthritis is nonerosive, nor the main symptom, but it can still be mistaken for rheumatoid arthritis (RA). Sometimes there is an IIM-RA overlap where arthritis more often is erosive., Both intensive aerobic exercise and resistance training is safe in patients with well-controlled RA., Based on this, we hypothesize that exercise is also safe in patients with IIM and arthritis if the exercise is adapted to pain levels with lower weights/higher repetitions. Pain might increase during the start of an exercise program, even though the pain is in the joints, it can be regarded as nonnegative exercise-related pain. However, sustained increased pain for more than 24 h indicates the need to reduce the intensity.
There is also a risk of osteopenia or osteoporosis. A reduced bone mineral density has been reported among IIM patients as early as 6 months from diagnosis, although more present with longer disease duration. Medical treatment is used to combat or minimize the loss of bone minerals with the use of glucocorticoids. In addition, exercise can increase bone mineral density. To minimize the risk of fractures, exercise should be done with the higher number of repetitions and lower weights, and without jumps and spinal flexion (e.g., sit-ups). Exercise adaptations are especially important with high doses of oral glucocorticoids and for women after menopause. With a high corticosteroid dose start with a low–moderate exercise intensity, then increasing exercise intensity along with a tapered glucocorticoid dose, [Figure 1].
|Figure 1: The relation between glucocorticoid dose and exercise intensity|
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Pain and fatigue
Pain and fatigue were by patients, health-care providers and caregivers considered the most important symptoms to assess in clinical trials and clinical practice. Patients with IIM seem to suffer from pain and fatigue to a further extent than normative populations,,, although prevalence, type of pain, localization, intensity, and progression over time are unclear. The cause of fatigue in IIM is also not quite clear and is probably multi-factorial as in other rheumatic inflammatory conditions, such as RA. Central fatigue due to inflammation itself, medication, pain, and poor sleep are a few factors that can contribute to central fatigue. Peripheral fatigue, functional or structural impairment of the muscle, could be due to multiple causes such as myofiber alterations, interstitial connective disarrangement, or altered muscle vascularization. These changes can be both structural and metabolic. Fatigue might emerge as a possible surrogate measure for disease activity as self-reported symptomatic flares are fatigue-based.
Exercise has been described to both worsen and mitigate pain in IIM. A systematic review by Misse et al. found that exercise might have a positive effect on pain and perceived fatigue. However, more research is needed to fully understand the characteristics and behavior of both pain and fatigue in IIM, and the effect of exercise. Until then, exercise, both aerobic and strength, should be used to try to combat pain and fatigue based on evidence indicating that exercise can reduce pain and fatigue in other inflammatory diseases such as systemic lupus erythematosus, RA, and psoriatic arthritis.,,,, In the presence of pain, the patient should start with low weight/intensity and a higher number of repetitions with frequent follow-up to not intensify the pain. As the exercise continues without intensification of the pain, the weight/intensity can increase, and the number of repetitions decreases.
Exercise prescription in relation to the disease and extramuscular manifestations
An inter-professional team approach is essential to optimize treatment for patients with IIM. As additional precautions, baseline measuring of the heart rate, blood pressure, and peripheral oxygen saturation can be done regularly, as well as asking the patient to rate the exertion and breathlessness or dizziness, chest pain, or general discomfort. To avoid muscle fatigue during exercise, change which muscle is targeted after each set in a circuit training fashion.
Exercise goal – the optimal amount of exercise
It is unclear what level of physical activity that is optimal for patients with IIM, however, in [Table 1] the best available recommendations are presented for patients with established, low-active IIM (inclusion body myositis [IBM] excluded). People with inflammatory systemic rheumatic conditions have a higher risk of developing cardiovascular disease. A high aerobic capacity is strongly associated with the absence of cardiovascular disease, thus aerobic exercise should be an important part of the exercise treatment.
|Table 1: Recommendations of exercise dose to improve muscle function and aerobic capacity for general population and for people with idiopathic inflammatory myopathy according to frequency, intensity, type, and time|
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To reach health-enhancing levels of physical activity, support from health care is needed for most patients with IIM, such as a physical therapist for assessments and specific advice on exercise and physical activity. Long-term follow-up is important for compliance. Examples of aerobic exercise are walking (or Nordic walking), swimming, aquatic training, stationary biking, jogging/running, or aerobics class. Strength training can be done at home, outdoors, or at a gym, with or without external loads. Daily activities can also be the exercise for patients with low fitness. There are a few considerations before, during, and after exercise [Table 2].
|Table 2: Extramuscular involvement, related auto-antibodies, manifestations, and symptoms with exercise considerations|
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What results can be expected?
Dysphagia, shorter time from symptom onset to treatment start and more intensive initial glucocorticoid treatment are associated with a higher rate of clinical improvement after 1 year of medical treatment. Since exercise is an important part of the treatment, it is likely that a shorter time to exercise start and higher initial exercise intensity than previously studied might be beneficial to avoid deterioration and irreversible damage as can be expected with a prolonged time from symptom onset to treatment. Further, clinical experience suggests that the degree of muscle atrophy or fat replacement in muscle and fibrosis in the lungs can influence the exercise response. In addition, medication tolerance and flares can also affect exercise response. It is not possible to in detail predict recovery by exercise, thus a longitudinal follow-up is essential to evaluate the outcome and adapt exercise according to possible improvement or worsening in disease.
Even without significant improvement in physical capacity, it is still important to continue with an exercise and physical capacity. Physical inactivity leads to a more rapid decrease in muscle function. Regular exercise will if not improve function, help to maintain, slow down the deterioration, and reduce the risk of cardiovascular disease, type 2 diabetes, and cancer. In case of reaching a plateau in exercise response, a visit with a physical therapist with experience of IIM is important. The exercise intensity, duration, or frequency might need adaption. Further, creatine supplementation can boost exercise response. Exercise in combination with daily creatine supplementation is more effective to improve muscle function than exercise and placebo in established PM and DM. It is important to screen for kidney health and that the patient already is exercising regularly on an adequate level at least twice a week.
Inclusion body myositis
IBM differs from the other forms of IIM mentioned in this article. IBM is autoimmune, with degenerative components. Mechanisms leading to impaired muscle functions are unclear but protein aggregation, muscle fiber, and mitochondrial dysfunction are suggested,,, although not the only mechanisms suggested. Distal muscle weakness is common to a further extent compared to other IIMs, often asymmetric as well. IBM has a slow progression over time and is usually unresponsive to medical treatment. There is in general no extra-skeletal muscular involvement in IBM, other than esophageal muscle weakness, leading to dysphagia. There are only a few studies evaluating the safety and efficacy of exercise in IBM, however, all support safety with unchanged levels of CK and inflammatory infiltrates in muscle tissue. However, evidence on efficacy to improve muscle function is less unified. One RCT indicates that blood-flow restricted submaximal resistance training can sustain quadriceps muscle strength compared to a nonexercising control group worsening almost 10% during the 12-week study period without signs of increased inflammation in muscle., A small, open study showed improvement in muscle strength even in the most affected muscle groups in IBM by a 16-week, twice-a-day home exercise program. Patients with IBM do not respond to exercise as well as patients with other IIM subtypes, and a sustained muscle function should be considered as a positive effect versus a decline that is part of the natural disease course. Careful goal setting and motivational conversations are two important parts of the exercise prescription and follow-up. Further, supervised exercise is of high importance later in the disease course when poor balance and muscle strength might hinder exercise in a regular gym. Aquatic training can be a safe and effective exercise mode.
Limitations with available research
Today, IIMs are classified by autoantibody status associated with various clinical profiles. Most exercise research has been done before the classification systems only including patients diagnosed according to Bohan and Peter criteria., Most likely, patients classified today as ASyS or immune-mediated necrotizing myopathy have participated in exercise studies but as polymyositis (PM) or dermatomyositis (DM) patients. This causes some difficulties as to how and if exercise research can be applied to all IIM patients or if it should be adjusted with regard to autoantibody, or to clinical or serological data.
The rarity of IIM makes larger studies difficult with a result that most exercise studies are small clinical studies and not RCTs with statistical power. However, all publications point in the same direction regarding exercise – it is safe and effective in combating the disease, disease-related manifestations as well as secondary co-morbidities.,, However, it is still unclear how to prescribe the optimal exercise program, and if the exercise must differ for newly diagnosed, active disease and inactive diseases. As we are moving from only PM/DM/IBM to a spectrum of IIMs with different disease severity and manifestations, it is likely that individualized exercise programs are needed. By combining evidence on exercise in IIM and other similar diseases (ILD, heart failure, myocarditis, and arthritis) and basic exercise physiology, we can prescribe exercise that would most likely be safe and effective to each individual patient.
| Summary|| |
Exercise is a safe and effective adjuvant therapy in established IIM with low extramuscular involvement to increase muscle strength, function and endurance, aerobic capacity and reduce inflammation and disease activity. It is still unclear how to optimize exercise for patients with recent onset disease or patients with much extramuscular involvement. However, exercise is safe even for patients with recent onset or active disease or extramuscular involvement – if it is supervised and individualized. As patients with severe vital-organ involvement are usually excluded from exercise studies, it should be prioritized to include patients with severe lung and heart involvement in future studies.
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Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2]