Practice Essentials
Steroid myopathy is usually an insidious disease process that causes weakness mainly to the proximal muscles of the upper and lower limbs and to the neck flexors. Cushing originally described it in 1932, and Muller and Kugelberg first studied it systemically in 1959. An excess of either endogenous or exogenous corticosteroids is believed to cause the condition. Excess endogenous corticosteroid production can arise from adrenal tumors. An excess of exogenous corticosteroid can result from steroid treatment for asthma, chronic obstructive pulmonary disease, and inflammatory processes, such as polymyositis, connective tissue disorders, and rheumatoid arthritis. [1, 2, 3, 4] Some literature suggests that aerobic exercises and resistance training may help to prevent weakness or reduce its severity in steroid myopathy.
Signs and symptoms of corticosteroid-induced myopathy
Chronic (classic) steroid myopathy physical findings are as follows:
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Proximal muscle weakness is more pronounced than is distal muscle weakness; however, severe relative weakness of the anterior tibialis muscle can be found
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Pelvic girdle muscles usually are affected more severely and earlier than are pectoral girdle muscles
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Muscle bulk typically is normal, but muscle atrophy can occur
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Muscle stretch reflexes typically are normal
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Sensory examination should be normal
Acute steroid myopathy physical findings are as follows:
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Generalized muscle weakness, not limited to a more proximal distribution, is noted
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Involvement of bulbar and respiratory muscles can occur [5]
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Muscle stretch reflexes typically are normal
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Sensory examination should be normal
Workup in corticosteroid-induced myopathy
In acute steroid myopathy, most patients have high levels of serum creatine kinase, as well as associated myoglobinuria.
Although circulating muscle proteins such as creatine kinase and myoglobin are increased in acute steroid myopathy, glucocorticoid down-regulation of protein synthesis may lead to decreased levels of these proteins in chronic steroid myopathy.
In chronic steroid myopathy, muscle biopsy shows preferential atrophy of type II fibers, particularly the fast-twitch glycolytic fibers (type IIB). [6, 7] Some atrophy of other type II fibers and, to a small degree, type I muscle fibers can occur. Increased variation in the diameter of muscle fibers occurs.
In acute steroid myopathy, muscle biopsy shows focal and diffuse necrosis of all fiber types, without predilection for type II fibers.
Ultrasonography can be used in steroid myopathy to visualize details such as muscle echogenicity, muscle size, and the presence or absence of muscle movement. The thickness and overall appearance of the intermuscular/intramuscular fascia can also be assessed using ultrasonography. Myopathic disorders often display ultrasonographic abnormalities, which can vary between different types of myopathies. [8]
Management of corticosteroid-induced myopathy
Some literature suggests that aerobic exercises and resistance training may help to prevent weakness or reduce its severity. Although there are no definitive recommendations regarding therapy for steroid myopathy, it would seem reasonable to direct therapy to address the weakness and resulting impaired mobility. Range-of-motion exercises (either passive, active-assisted, or active, depending on the degree of weakness) and stretching exercises should be performed to prevent joint contractures. As a general rule, resistance exercises should be limited to muscles with greater than antigravity strength. Bed mobility, balance activities, transfer training, and gait training should be included to address decreased mobility. However, high-intensity exercise should be avoided because, according to some preliminary animal research models, it may be harmful. [9]
Occupational therapy may focus on maximizing the patient's ability to independently perform activities of daily living.
There is a risk of chronic and irreversible changes with acute steroid myopathy. Therefore, the corticosteroid dose should generally be reduced or discontinued completely when possible. [5]
In cases of myopathy caused by long-term corticosteroid use, decreasing the corticosteroid dose to below a 30 mg/d threshold may result in resolution of muscle weakness. In patients in whom myopathy has resulted from a short course of high-dose corticosteroid use, partial or complete recovery has been reported following the discontinuation of steroid administration. [10]
Pathophysiology
Steroid myopathy may be more frequent with the use of fluorinated steroids, such as dexamethasone [11] or triamcinolone, than with nonfluorinated ones, such as prednisone or hydrocortisone. [12, 13] Although the exact mechanism of the muscle pathology is unclear, it may be related to decreased protein synthesis, increased protein degradation, alterations in carbohydrate metabolism, mitochondrial alterations, electrolyte disturbances, and/or decreased sarcolemmal excitability. Sedentary lifestyle may increase the risk of muscle weakness in a patient taking corticosteroids, since corticosteroids seem to affect less active muscles preferentially. Two distinct types of steroid myopathy exist, acute and chronic. The chronic (or classic) form occurs after prolonged use of corticosteroids and has a more insidious course. The acute form is less common, is associated with rhabdomyolysis, and occurs abruptly while the patient is receiving high-dose corticosteroids.
One study used skeletal muscle biopsy of the vastus lateralis and real-time polymerase chain reaction (PCR) assay to investigate the effects of dexamethasone on skeletal muscle. Twenty-four subjects were studied before and after the administration of dexamethasone 4 mg by mouth daily for 4 days. Following dexamethasone, all subjects (12 female and 12 male) demonstrated similar decreases in serum testosterone and transcription factor 4 (TCF4), an androgen-responsive transcription factor. Additionally, a significant decrease in skeletal muscle androgen receptor mRNA levels occurred following dexamethasone administration. Furthermore, plasma insulinlike growth factor-1 (IGF-1), produced by the liver, increased significantly following dexamethasone administration, whereas skeletal muscle IGF-1 mRNA levels decreased. Further studies are needed to investigate the significance of these findings. [14]
In a study performed by Levin et al, 60% of participants who used inhaled corticosteroids daily for a year or greater reported muscle weakness and 20% of that group showed objective signs of weakness. These researchers measured inhaled steroid–induced myopathy using a peripheral motor deficits scale, stepper test, ankle/wrist index, neuropathy disability score, and statistical analysis. Peripheral motor deficits scale was formulated to determine early stages of myopathy with physician's rating of the participant's weakness while (1) walking up and down stairs and (2) with difficulty in buttoning/unbuttoning, sewing, or picking up coins. Muscle atrophy measurements were made using an ankle/wrist index, in which the smallest circumference of the dominant leg above the ankle and that of the forearm above the wrist were compared. Neuropathy disability score was determined by evaluation of sensory functions and reflexes. [15]
A study by Minetto et al found that short-term glucocorticoid administration in healthy subjects produced the sorts of changes in muscle fibers that arise prior to the clinical appearance of myopathy in patients treated with glucocorticoids. In the study, in which dexamethasone was administered to five healthy males for 7 days, type 1 and type 2A muscle fibers demonstrated a reduction in cross-sectional area, myosin, and specific force. [16]
Similarly, a study by Nawata et al suggested that steroid therapy is associated with a reduction in muscle volume. The study, which included seven patients with myositis and eight controls, used computed tomography (CT) scanning to observe steroidal effects on a cross section of skeletal muscle at the caudal end of the third lumbar vertebra. The investigators found that in both groups, following treatment with high doses of steroids, the cross-sectional area of skeletal muscle was reduced, while the low muscle-attenuation rate was increased. Nonetheless, the patients with myositis experienced an increase in muscle strength, apparently due to factors other than muscle volume change. [17]
Epidemiology
Frequency
United States
The exact incidence of steroid myopathy is unknown; sensitivity to particular medications varies among patients.
Mortality/Morbidity
The weakness seen with steroid myopathy typically resolves after the corticosteroid dose is reduced or discontinued, although recovery can take weeks or months. Case studies have reported a lack of full recovery, as well as difficulty weaning patients off of mechanical ventilation. Osteoporosis, which can occur as a comorbidity with steroid myopathy, can result from the corticosteroid or from decreased mobility and respiratory impairment. [6] Other comorbidities include joint contractures, pressure ulcers, and deep vein thrombi, although these can occur in any condition causing weakness and immobility. Mortality has not been described. Some case studies have reported patient mortalities, but they provided no indication that steroid myopathy was the cause.
Sex
For a given dose of steroid, women appear to be twice as likely as men to develop muscle weakness, although the reason is unclear.
