A variety of muscle diseases affect the adult and elder population.
These conditions are:
- Idiopathic inflammatory myopathies, or myositis, which include: dermtomyositis, polymyositis, necrotizing myopathy, and inclusion body myositis (IBM).
- Adult onset congenital myopathies and dystrophies including facioscapulohumeral (FSH) dystrophy, mitochondrial myopathy, McArdle disease and familial myopathies
- Toxic and endocrine myopathies, including statin-induced and hypothyroidism myopathies.
- Polymyalgia rheumatica, which is not in itself an inflammatory muscle disease, but may mimic myositis.
- Causes include immunological, paraneoplastic, genetic, and toxic-metabolic.
- Sarcopenia is associated with inactivity, chronic illnesses, malnutrition, and metabolic effects of aging.
- Myosteatosis occurs as a consequence of the metabolic effects of aging, sedentarism, and malnutrition.
Epidemiology including risk factors and primary prevention
- Incidence of sarcopenia is estimated between 10-29% in aging individuals, but this information is unreliable since there is no available universal definition for sarcopenia.
- Inflammatory myopathies have an estimated yearly incidence of 7.8 per million/year, with the adult peak between ages 45 and 55. Females are more likely to be affected.
- IBM has a yearly incidence of 2 to 5 per million adults with a peak at ages 50 to 70, with male predominance. IBM is considered the most prevalent idiopathic inflammatory myopathy in the geriatric population, although cancer related dermatomyositis is more common.
- Statin-induced myopathy affects fewer than 5% and rhabdomyolysis occurs in less than 0.1% of patients, but risk increases with concomitant fibrate use.
- Polymyalgia rheumatica has an incidence of 20 per 100,000 person/years, most common in people with Northern European ancestry. Mean age of diagnosis is 70 years old and 75% of patients are female.
- Idiopathic inflammatory myopathies most likely occur due to a combination of genetic and environmental factors. Environmental factors include: infections (hepatitis B in polymyositis), malignancy (Dermatomyositis), and certain chemicals (D-penicillamine in polymyositis).
- Statins, except pravastatin are metabolized via the cytochrome P-450 system, making it a potential for drug interactions. The lipophilic cerivastatin, lovastatin and simvastatin are more myotoxic. The mechanism of the myopathy is not clear but may be related to reduction in CoQ10 synthesis, which impairs muscle energy production.
- In polymyalgia rheumatica, the cause is unknown but genetic and environmental factors play a role in disease severity and susceptibility to treatment. In Caucasians with the disease, it is linked to the HLA DR4 allele.
- Sarcopenia occur most likely due to multiple mechanisms which include: environmental, disease triggers, inflammation, mitochondrial pathology, alterations in the neuromuscular junctions, reduced satellite cell numbers, and hormonal changes.
- Myosteatosis may be due to increased fatty acid transport, uptake and storage and reduced fatty acid oxidation. Macrophage infiltration may also lead to adipocyte hypertrophy due to inhibition of adipocyte differentiation. Impaired mitochondrial function associated with aging may also direct fatty acids toward storage. Another possible mechanism is activation of quiescent muscle satellite cells into adipocytes.
Disease progression including natural history, disease phases or stages, disease trajectory (clinical features and presentation over time)
- Inflammatory myopathies present with worsening proximal muscle weakness and pain over several weeks to months. Steroid-induced myopathy exhibits proximal muscle weakness and may develop as early as during the first week of patients receiving high dose corticosteroids.
- Polymyalgia rheumatica may present with new onset shoulder pain, morning stiffness for more than 45 minutes, with symptoms lasting at least several days to weeks. Disease is usually self-limiting, but untreated patients may develop impairments due to myalgias and muscle stiffness. Up to 21% of patients with polymyalgia rheumatica may suffer from giant cell arteritis.
- Myosteatosis may occur within days of immobilization. It is reported that muscle fatty infiltration may increase up to 20% within 30 days of immobilization in young and healthy individuals.
- Muscular dystrophies and congenital myopathies are characterized by slowly progressive weakness and function loss.
- Inclusion body myositis develops over the years in an insidious manner, with weakness and atrophy of the proximal lower extremity muscles and distal arm. Dysphagia may occur as disease progresses.
- Sarcopenia develops over the decades and presents clinically as a loss of muscle bulk and power. Given that muscle is a metabolically active tissue, its loss has profound consequences in terms of overall health.
- Patients with polymyalgia rheumatica or other rheumatologic diseases who require chronic corticosteroid therapy should be monitored for medication side effects.
Specific secondary or associated conditions and complications
Development of dermatomyositis is usually associated with malignancy, with a cancer rate of 9-32%. Malignancies most commonly implicated in the development of dermatomyositis are ovarian, breast, stomach, colon, lung, melanoma, and non-Hodgkin lymphoma. Patients should undergo cancer screening after the diagnosis of dermatomyositis.
Myosteatosis is associated with an increased risk of developing insulin resistance and type-2 diabetes mellitus, arterial hypertension, and hyperlipidemia.
2. ESSENTIALS OF ASSESSMENT
History is varied in these disorders and can help to narrow the differential diagnosis.
- Sarcopenia and myosteatosis are associated to chronic diseases in the aging population such as rheumatic diseases, lung disease, chronic kidney and liver disease, and congestive heart failure.
- A history of cancer may be present in patients with dermatomyositis.
- Family history may portend risk of a congenital disorder.
- Medication use may be associated to toxic myopathies.
- Rapid onset of shoulder pain and stiffness is a hallmark of polymyalgia rheumatica, although neck and pelvic muscle pain is common. Although not included in the new diagnostic criteria, constitutional signs such as low-grade fever, anorexia, fatigue and weight loss can be seen are fairly common.
Physical examination may reveal muscle atrophy, swelling, weakness, and tenderness.
- Inclusion body myositis involves most commonly the long finger flexors, ankle dorsiflexors and quadriceps. In facioscapulohumeral muscular dystrophy, muscles involved are located in the facial, scapular, and proximal upper extremity muscles.
- Focal muscle tenderness characteristically seen with myositis.
- Joint pathology as well as skin involvement is associated with rheumatological disorders.
- Skin involvement such as scaly erythematous lesions in the finger joints (Gottron’s papules), upper eyelid violaceus eruptions (heliotrope rash) is characteristic of dermatomyositis.
- Patients with sarcopenia have decreased muscle bulk and strength.
- Mobility limitations will vary according to the muscles involved. Impaired loading response is observed in patients with knee extensor weakness such as those with inclusion body myositis. Muscular dystrophies, toxic, metabolic and autoimmune myopathies mostly express proximal weakness for which sit-to stand maneuver and stair climbing will be impaired.
- Self care limitations caused by proximal upper extremity weakness in FSH dystrophies and proximal myopathies include difficulty with grooming (due to inability to do activities above the shoulder level) or upper extremity dressing (due to impaired shoulder reach). Fine motor dexterity loss can be seen in inclusion body myositis due to distal muscle involvement.
- In the case of sarcopenia, decreased muscle endurance and strength translates into a higher risk for falls, disability, and decreased quality of life.
- In myosteatosis, the presence of intermuscular fat impairs muscle function, with fat deposits compressing the motor unit, and subsequent loss of muscle strength.
- Cognitive and behavior dysfunction is rare although assessment of affect is important considering the impact of pain and loss of function.
- Serum creatinine phosphokinase (CPK) may be elevated in several myopathies and values are not specific for any muscle disease.
- Rheumatological screen should include rheumatoid factor, anti-nuclear antibody, C-reactive protein, and erythrocyte sedimentation rate.
- Genetic testing is indicated in the presence of family history or high clinical suspicion.
- Evaluation of sarcopenia should include thyroid functions, vitamin D level, growth hormone and, in men, serum testosterone.
- Erythrocyte sedimentation rate may be elevated in inflammatory myopathies.
The use of ultrasound is being investigated for muscle disease. Although accessible, ultrasound is unable to distinguish between intramyocellular and extramyocellular fat in patients with muscle fatty infiltration. Despite its limitations, ultrasound enables assessment of muscle cross sectional area, muscle thickness, pennation angle, muscle length, and echogenicity.
Magnetic resonance imaging has the benefit of distinguishing several muscle groups, but is unable to accurately quantify muscle fat content. Magnetic resonance spectroscopy is a useful tool to measure intramyocellular lipids. Both imaging modalities are costly and not easily accessible in many centers.
Supplemental assessment tools
- EMG is helpful in identifying myopathy because it can both evaluate motor units and identify muscle necrosis and inflammation during spontaneous activity evaluation.
- Abnormal spontaneous activity is greatest in proximal muscles in polymyositis/dermatomyositis, with the thoracic paraspinal muscles targeted because of the unlikelihood of degenerative spine disease.
- Nerve conduction studies will most likely reveal no nerve dysfunction in pure muscle disease.
- EMG is typically normal in polymyalgia rheumatica and sarcopenia.
- Muscle biopsy is useful in distinguishing inflammatory muscle disease, dystrophies, vasculitis, and mitochondrial disorders. Statin-induced myopathies show nonspecific changes consistent with mitochondrial respiratory chain dysfunction (ragged red fibers, increased lipid, cytochrome-oxidase negative fibers).
- Temporal artery biopsy should be done in a patient with polymyalgia rheumatic and headache, vision loss, and tenderness along the temporal artery.
3. REHABILITATION MANAGEMENT AND TREATMENTS
At different disease stages
- No effective medication treatment strategy has been discovered for IBS.
- Polymyositis and dermatomyositis are treated with prednisone as the first line treatment; initial doses continued for 2-4 weeks. Steroid sparing strategies include methotrexate, azathioprine, mycophenolate mofetil, and IVIG for refractory myositis. Hydroxychloroquine is used for the skin manifestations of dermatomyositis. If steroid sparing agents are used concomitantly, Prednisone at a dose of 0.5mg/kg may aid in achieving remission induction.
- Minimizing statin dosage impacts the risk of myopathy. Factors for myopathies that influence dosing include liver and renal disease, other medications, hypothyroidism, heavy alcohol use, and regular heavy exercise.
- For polymyalgia rheumatica, prednisone at 10-20 mg daily will provide dramatic relief, typically in the first week of therapy. Lack of response should trigger further evaluation. The primary steroid sparing medication is methotrexate. Nonsteroidal anti-inflammatory medications may help sustain remission.
- Nonresistive exercise in inflammatory myopathies has shown efficacy in improving strength, aerobic capacity, endurance and function while decreasing fatigue during the acute and subacute phases of these diseases.
- Statins should be stopped before events that increase the risk of muscle injury (eg, vigorous physical exercise, surgery).
- Resistance training 3 times weekly in sarcopenia is effective in improving strength, muscle mass, and associated mobility deficits. In patients with sarcopenia secondary to androgen deprived prostate cancer patients, a 12-week resistance training intervention effectively improved sarcopenia, body fat percentage, strength and quality of life.
- Creatine phosphate supplementation provides further benefit for sarcopenia. Experts recommend a higher daily protein intake of 1.1g/kg (body weight) per day, if no renal insufficiency or other contraindications are presentlthough still controversial, recently reviewed data shows enhancements in both skeletal muscle mass and function with leucine supplementation. As part of a multi- modal intervention, increasing dietary protein intakes may support not only muscle mass maintenance but also bone health when calcium and vitamin D intakes are adequate.
- Testosterone replacement in men with sarcopenia shows a definite improvement in muscle mass and strength. The reported side effect regarding an elevated risk for prostate cancer in combination with other potential side effects such as allergic reactions, fluid retention, gynecomastia, polycythemia, sleep apnea, loss of appetite, nausea, depression, or mood changes limits its usefulness in the treatment of sarcopenia and authors saw also no clear indication for androgen therapy use in the older persons to counter sarcopenia
- Growth hormone replacement increases muscle mass but not strength in sarcopenia. Nonetheless, possible side effects, including fluid retention, joint swelling, joint pain, gynecomastia, orthostatic hypotension, increased risk of diabetes, and carpal tunnel syndrome may put into question it’s relative benefit vs. risk ratio.
- Resistive training and aerobic exercise have good efficacy in improving strength and function in patients with chronic inflammatory myopathies.
Pre-terminal or end of life care
A recent study determined an association between sarcopenia, quality of life and depression in patients with newly diagnosed incurable cancer. Future efforts addressing sarcopenia at the time of diagnosis may improve outcome and quality of life.
4. CUTTING EDGE/EMERGING AND UNIQUE CONCEPTS AND PRACTICE
Cutting edge concepts and practice
Idiopathic Inflammatory Myopathy Classification Criteria:
The EULAR/ACR criteria have been developed and validated with a robust methodology, an improvement over previous criteria sets, in order to facilitate identification of patients with undifferentiated arthritis who are at high risk of developing persistent/erosive disease. The new IIM classification criteria are a valuable addition to the myositis disease activity core measures endorsed by IMACS and the recently published ACR/EULAR adult PM/DM and juvenile DM response criteria
5. GAPS IN THE EVIDENCE-BASED KNOWLEDGE
Gaps in the evidence-based knowledge
- There is a lack of studies on multidisciplinary rehabilitation and its impact on function in geriatric muscle disease. This deficiency is especially important in disorders without specific treatment, such as dystrophies, mitochondrial myopathies, congenital myopathies, and inclusion body myositis.
- There is a lack of studies on severe disability in inflammatory myopathies, risks for severe disability, and the role of multidisciplinary treatment in its care.
- The extent to which life-long activity patterns and training could prevent age-related declines in strength capacities has not been prospectively examined in sarcopenia.
- Future research should focus on determining the optimal timing and modality of efforts to assess and treat sarcopenia while working to improve the QOL and mood outcomes of patients with advanced cancer.
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Original Version of the Topic
Anthony Chiodo, MD. Adult and Geriatric Muscle Disease. 12/27/2012.
Edwardo Ramos, MD
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Javier Gonzalez-Buonomo, MD
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Ana Ortiz-Santiago, MD
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