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Glucocorticoid-induced myopathy

Glucocorticoid-induced myopathy
Literature review current through: Jan 2024.
This topic last updated: May 31, 2022.

INTRODUCTION — Myopathy has been recognized as a side effect of glucocorticoid therapy since its introduction as a therapeutic agent in the 1950s [1]. Myopathy can occur with systemic glucocorticoid therapy. Similar symptoms can occur in patients with Cushing's syndrome. (See "Epidemiology and clinical manifestations of Cushing syndrome".)

The major aspects of glucocorticoid-induced myopathy will be reviewed here. Other side effects associated with glucocorticoid therapy, both oral and inhaled, are discussed separately. (See "Major adverse effects of systemic glucocorticoids" and "Major side effects of inhaled glucocorticoids".)

PATHOGENESIS — Glucocorticoids exert both catabolic and antianabolic effects on skeletal muscle. Activation of the glucocorticoid receptor appears to be involved [2,3] since myopathy can be prevented by a glucocorticoid receptor antagonist [2].

Breakdown of myofibrillar proteins and dissociation of actin and myosin proteins are mediated through the activation of the ubiquitin-proteasome system, the lysosomal system (cathepsins), and the calcium-dependent system (calpains). In addition, glucocorticoids increase myocyte apoptosis.

Antianabolic effects include inhibition of amino acid transport into cells, inhibition of muscle insulin-like growth factor 1 (IGF-1) production, and downregulation of differentiation of satellite cells into muscle fibers resulting in inhibition of both muscle protein synthesis and myogenesis. IGF-1 appears to play a prominent role in maintaining muscle integrity by both increasing protein synthesis and inhibiting proteolysis and apoptosis [4].

RISK FACTORS

Glucocorticoid-related risk factors

Dose and duration of treatment – There is wide variation in the dose and duration of treatment prior to the onset of muscle weakness. Some patients become weak after a low dose of glucocorticoids for a few weeks, while others never develop myopathy despite receiving large doses of glucocorticoids for months or years. Despite this variability, there is a general dose relationship with systemic glucocorticoid therapy [5]:

Glucocorticoid myopathy is unusual in patients treated with less than 10 mg/day of prednisone or its equivalent.

The higher the dose of glucocorticoid, the greater the likelihood of developing myopathy and the more rapid the onset of weakness. Initiation of 40 to 70 mg/day of prednisone can result in steroid myopathy within 30 days [6].

The risk of developing glucocorticoid myopathy may be lower in patients receiving alternate-day dosing, particularly among patients being treated for Duchenne muscular dystrophy or myasthenia gravis [7,8]. However, alternate-day dosing may not be efficacious for the treatment of various rheumatologic diseases, and some data suggest such dosing may result in increased adrenal suppression [9].

Glucocorticoid preparation – The clinical features described below generally refer to systemic glucocorticoid therapy (see 'Clinical features' below). Inhaled glucocorticoids are rarely associated with muscle weakness. Patients who take high doses of inhaled glucocorticoids absorb 20 to 40 percent of the administered dose and can develop some systemic signs. However, only isolated case reports describe muscle weakness that resolves with cessation of glucocorticoid therapy [10]. Myopathy after epidural glucocorticoid injection has also been described [11]. (See "Major side effects of inhaled glucocorticoids".)

Experimental and some clinical observations suggest that the risk of myopathy is increased with fluorinated preparations, such as dexamethasone and triamcinolone, compared with nonfluorinated preparations, such as prednisone and prednisolone [12-15].

Patient-related risk factors — Patient-specific factors that appear to be associated with an increased risk of glucocorticoid-induced myopathy include older age, physical inactivity, presence of cancer, or the presence of conditions that affect respiratory muscles [16].

CLINICAL MANIFESTATIONS

Clinical features

Muscle weakness — Patients with glucocorticoid myopathy typically present with gradual onset of proximal muscle weakness, followed by atrophy of proximal muscle groups. Myalgias and muscle tenderness do not occur. Lower extremity weakness usually occurs before upper extremity weakness and is more severe. The myopathy may interfere with the activities of daily living, resulting in difficulties in getting up from a chair, climbing stairs, or performing overhead tasks.

There is wide variability in the time course of symptom onset (from a few weeks to many months after therapy has begun) that is determined, in part, by the glucocorticoid dose. In one report of patients with primary brain tumors treated with daily dexamethasone, two-thirds became symptomatic in the third to fourth months of therapy [13]. Inactivity sensitizes skeletal muscle to the catabolic effect of glucocorticoids [17].

Glucocorticoid myopathy in patients with a systemic malignancy may present somewhat differently, with involvement of the respiratory muscles. In 1 report of 15 adult cancer patients, 9 developed proximal muscle weakness [18]. Respiratory dysfunction developed in 10, including 2 of 6 without proximal muscle weakness.

Lower inspiratory muscle strength and endurance has also been reported in glucocorticoid-dependent asthma versus nonglucocorticoid-dependent asthma [19,20]. There have been no reported statistically significant differences in maximal expiratory pressures between these two groups.

Other symptoms — Other features of Cushing's syndrome such as moon facies, diabetes, mood alteration, skin fragility, and osteoporosis are often (but not always) present [5]. (See "Epidemiology and clinical manifestations of Cushing syndrome" and "Major adverse effects of systemic glucocorticoids".)

Laboratory findings and other tests — Muscle enzymes are normal [6]; electromyography (EMG) may be normal or can show a nonirritable myopathy; and muscle biopsy reveals nonspecific atrophy of type IIb fibers without signs of necrosis or inflammation [5,21].

DIAGNOSIS — There is no definitive diagnostic test for glucocorticoid myopathy. The diagnosis is based upon the history and timing of glucocorticoid exposure and upon the absence of other causes of myopathy. The diagnosis is generally established by demonstrating improved strength within three to four weeks after sufficient dose reduction, which is usually to doses of less than 10 mg/day of prednisone or its equivalent. The sufficient dose reduction will vary from patient to patient, as does the dose at which weakness appears. However, there is generally some improvement in muscle strength as glucocorticoid dose is reduced to below 10 mg/day even without complete discontinuation of the glucocorticoids.

DIFFERENTIAL DIAGNOSIS — Several disorders can mimic glucocorticoid-induced myopathy. While it is beyond the scope of this review to provide a comprehensive list of all possible alternative diagnoses, the differential diagnosis includes conditions that cause muscle weakness such as infectious and drug-induced myopathies, idiopathic inflammatory myopathies (eg, dermatomyositis, polymyositis, myositis as part of a rheumatic disease overlap syndrome, antisynthetase syndrome, immune-mediated necrotizing myopathy, and inclusion body myositis), sarcoid myopathy, amyloid myopathy, hypothyroid myopathy, muscular dystrophy, inherited metabolic myopathies, motor neuron disease, myasthenia gravis, and myositis caused by graft-versus-host disease. (See "Overview of and approach to the idiopathic inflammatory myopathies".)

One setting in which the diagnosis of possible glucocorticoid-induced myopathy may be particularly challenging is in patients treated with neuromuscular blocking agents. Patients requiring large doses of intravenous glucocorticoids and a neuromuscular blocking agent (often because of mechanical ventilation in status asthmaticus) may develop critical illness myopathy, which is characterized by severe diffuse proximal and distal weakness. Although the use of intravenous glucocorticoids in the intensive care unit setting has been thought to be the main risk factor for the development of critical illness myopathy, there remains some uncertainty as some patients may develop critical illness myopathy in the absence of exposure to intravenous glucocorticoids. (See "Neuromuscular weakness related to critical illness", section on 'Critical illness myopathy' and "Neuromuscular weakness related to critical illness", section on 'Epidemiology and risk factors'.)

MANAGEMENT — Minimizing the dose and duration of glucocorticoid exposure is the most important intervention. Muscle strength begins to improve within three to four weeks after sufficient dose reduction, and eventually resolves in virtually all patients if glucocorticoid therapy can be discontinued [5]. In patients treated with a fluorinated preparation, such as dexamethasone, substituting a nonfluorinated preparation, such as prednisone, can be tried if the patient cannot be weaned from glucocorticoid therapy [13]. The lowest effective dose should be used, and, if symptoms persist, alternative therapies should be considered.

There is some evidence that resistance exercises of involved muscles may limit the initial severity of weakness in glucocorticoid-treated patients or hasten recovery of muscle strength as glucocorticoids are tapered, although evidence for the effectiveness of therapeutic exercise from controlled trials is lacking [22-24]. Conversely, there is some evidence from animal studies that high-intensity exercise may slow recovery of muscle strength [25].

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Side effects of anti-inflammatory and anti-rheumatic drugs".)

SUMMARY AND RECOMMENDATIONS

Risk factors – Myopathy, a well-recognized side effect of glucocorticoid therapy, can occur with any of the glucocorticoid preparations but is more common with systemic glucocorticoids. The risk is increased in patients who are older, physically inactive, and in those with cancer. (See 'Risk factors' above.)

Dose and duration of treatment – Although there is wide variation in the dose and duration of treatment prior to the onset of muscle weakness, there is a general dose relationship with systemic glucocorticoid therapy. Initiation of 40 to 70 mg/day of prednisone can result in steroid myopathy within 30 days. By comparison, glucocorticoid myopathy is unusual in patients treated with less than 10 mg/day of prednisone or its equivalent. (See 'Glucocorticoid-related risk factors' above.)

Muscle weakness – Glucocorticoid-induced myopathy can occur with the initiation of systemic therapy as well as in chronic maintenance therapy when the dose is increased. Affected patients typically present with gradual onset of proximal muscle weakness, followed by atrophy of proximal muscle groups. Myalgias and muscle tenderness do not occur. Lower extremity weakness usually occurs before upper extremity weakness and is more severe. (See 'Muscle weakness' above.)

Other symptoms – Other features of Cushing's syndrome such as moon facies, diabetes, mood alteration, skin fragility, and osteoporosis are often (but not always) present. (See 'Other symptoms' above.)

Laboratory findings and other tests – Muscle enzymes are normal; electromyography (EMG) may be normal or can show a nonirritable myopathy; and muscle biopsy reveals nonspecific atrophy of type IIb fibers without signs of necrosis or inflammation. (See 'Laboratory findings and other tests' above.)

Diagnosis – There is no definitive diagnostic test for glucocorticoid myopathy. The diagnosis is based upon the history and timing of glucocorticoid exposure and upon the absence of other causes of myopathy. The diagnosis is generally established by demonstrating improved strength within three to four weeks after dose reduction. (See 'Diagnosis' above.)

Management – Minimizing the dose and duration of glucocorticoid exposure is the most important intervention. Muscle strength begins to improve within three to four weeks after sufficient dose reduction and eventually resolves in virtually all patients if glucocorticoid therapy can be discontinued. (See 'Management' above.)

ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Marc L Miller, MD, who contributed to an earlier version of this topic review.

  1. Bunim JJ, Ziff M, McEwen C. Evaluation of prolonged cortisone therapy in rheumatiod arthritis: a four-year study. Am J Med 1955; 18:27.
  2. Konagaya M, Bernard PA, Max SR. Blockade of glucocorticoid receptor binding and inhibition of dexamethasone-induced muscle atrophy in the rat by RU38486, a potent glucocorticoid antagonist. Endocrinology 1986; 119:375.
  3. Sun L, Trausch-Azar JS, Muglia LJ, Schwartz AL. Glucocorticoids differentially regulate degradation of MyoD and Id1 by N-terminal ubiquitination to promote muscle protein catabolism. Proc Natl Acad Sci U S A 2008; 105:3339.
  4. Schakman O, Gilson H, Thissen JP. Mechanisms of glucocorticoid-induced myopathy. J Endocrinol 2008; 197:1.
  5. Bowyer SL, LaMothe MP, Hollister JR. Steroid myopathy: incidence and detection in a population with asthma. J Allergy Clin Immunol 1985; 76:234.
  6. Askari A, Vignos PJ Jr, Moskowitz RW. Steroid myopathy in connective tissue disease. Am J Med 1976; 61:485.
  7. Jenkins RB. Treatment of myasthenia gravis with prednisone. Lancet 1972; 1:765.
  8. Drachman DB, Toyka KV, Myer E. Prednisone in Duchenne muscular dystrophy. Lancet 1974; 2:1409.
  9. Axelrod L. Glucocorticoid therapy. Medicine (Baltimore) 1976; 55:39.
  10. Herzog AG. Proximal myopathy associated with inhaled steroids. JAMA 1999; 281:37.
  11. Boonen S, Van Distel G, Westhovens R, Dequeker J. Steroid myopathy induced by epidural triamcinolone injection. Br J Rheumatol 1995; 34:385.
  12. Afifi AK, Bergman RA, Harvey JC. Steroid myopathy. Clinical, histologic and cytologic observations. Johns Hopkins Med J 1968; 123:158.
  13. Dropcho EJ, Soong SJ. Steroid-induced weakness in patients with primary brain tumors. Neurology 1991; 41:1235.
  14. Braunstein PW Jr, DeGirolami U. Experimental corticosteroid myopathy. Acta Neuropathol 1981; 55:167.
  15. Kelly FJ, McGrath JA, Goldspink DF, Cullen MJ. A morphological/biochemical study on the actions of corticosteroids on rat skeletal muscle. Muscle Nerve 1986; 9:1.
  16. Gupta A, Gupta Y. Glucocorticoid-induced myopathy: Pathophysiology, diagnosis, and treatment. Indian J Endocrinol Metab 2013; 17:913.
  17. Ferrando AA, Stuart CA, Sheffield-Moore M, Wolfe RR. Inactivity amplifies the catabolic response of skeletal muscle to cortisol. J Clin Endocrinol Metab 1999; 84:3515.
  18. Batchelor TT, Taylor LP, Thaler HT, et al. Steroid myopathy in cancer patients. Neurology 1997; 48:1234.
  19. Akkoca O, Mungan D, Karabiyikoglu G, Misirligil Z. Inhaled and systemic corticosteroid therapies: Do they contribute to inspiratory muscle weakness in asthma? Respiration 1999; 66:332.
  20. Wu K, Michalski A, Cortes D, et al. Glucocorticoid-induced myopathy in people with asthma: a systematic review. J Asthma 2022; 59:1396.
  21. Khaleeli AA, Edwards RH, Gohil K, et al. Corticosteroid myopathy: a clinical and pathological study. Clin Endocrinol (Oxf) 1983; 18:155.
  22. Barel M, Perez OA, Giozzet VA, et al. Exercise training prevents hyperinsulinemia, muscular glycogen loss and muscle atrophy induced by dexamethasone treatment. Eur J Appl Physiol 2010; 108:999.
  23. Nagashima M, Takahashi D, Mizushima T, Yamauchi K. Effects of exercise in patients with connective tissue disease receiving high-dose glucocorticoids: A pilot prospective cohort study. Eur J Appl Physiol 2021; 121:2253.
  24. Braith RW, Welsch MA, Mills RM Jr, et al. Resistance exercise prevents glucocorticoid-induced myopathy in heart transplant recipients. Med Sci Sports Exerc 1998; 30:483.
  25. Uchikawa K, Takahashi H, Hase K, et al. Strenuous exercise-induced alterations of muscle fiber cross-sectional area and fiber-type distribution in steroid myopathy rats. Am J Phys Med Rehabil 2008; 87:126.
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