AUTHOR AND EDITOR INFORMATION

Section 1 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• References

INTRODUCTION

Section 2 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• References

Background

Steroid myopathy is usually an insidious disease process, which causes weakness mainly to the proximal muscles of the upper and lower limbs and neck flexors. Cushing originally described it in 1932. 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. Excess exogenous corticosteroid production can result from steroid treatment for asthma, chronic obstructive pulmonary disease, and inflammatory processes, such as polymyositis, connective tissue disorders, and rheumatoid arthritis.

Pathophysiology

Steroid myopathy may be more frequent with the use of fluorinated steroids, such as dexamethasone or triamcinolone, than with nonfluorinated ones, such as prednisone or hydrocortisone. The exact mechanism of the muscle pathology is unclear but 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.

Frequency

United States

The exact incidence of steroid myopathy is unknown, with each person having different sensitivities to the particular medication used.

Mortality/Morbidity

The weakness seen with steroid myopathy typically resolves after the corticosteroid dose is reduced or discontinued, although it can take weeks to months for recovery. Case studies have reported lack of full recovery and difficulty weaning patients off mechanical ventilation. Osteoporosis, which can be due to the corticosteroid or decreased mobility and respiratory impairment, is a comorbidity that can be seen with steroid myopathy. Other comorbidities, which could occur in any condition causing weakness and immobility, include joint contractures, pressure ulcers, and deep vein thrombi. Mortality has not been described. Although some case studies reported some patient mortalities, there was no indication that steroid myopathy was the cause.

Sex

Women appear to be twice as likely as men to develop muscle weakness for a given dose of steroid, although the reason is unclear.

CLINICAL

Section 3 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• References

History

• Chronic (classic) steroid myopathy
• • This form is the classic presentation of steroid myopathy.
  • This condition can develop after prolonged administration of prednisone at a dose of 40-60 mg/d. Although there is no clear length of time, onset of weakness has been found to occur within weeks to years following initiation of corticosteroid administration.
  • Several studies suggest that severely asthmatic patients under oral steroids show a greater risk for steroid-induced myopathy. One study found no significant difference in the prevalence of myopathy in oral steroid users and inhaled steroids users.¹
  • Fluorinated steroids seem to produce weakness and myopathy more frequently than nonfluorinated ones.
  • Insidious onset of proximal muscle weakness of the upper and lower limbs is a prominent clinical feature.
  • Progressive proximal muscle weakness of the upper and lower limbs is reported.
  • Patients typically complain of progressive inability to rise from chairs, climb stairs, and perform overhead activities.
  • Patients note little difficulty with strength in the hands initially.
  • The facial and sphincter muscles usually are spared.
  • Myalgias can become a prominent feature with time.
  • Contrary to previous beliefs, several studies have shown involvement of the respiratory muscles (eg, the diaphragm); thus, pulmonary symptoms may be present.
• Acute steroid myopathy
• • This form is encountered less frequently than the chronic type.
  • Acute generalized weakness, including weakness of the respiratory muscles, typically occurs 5-7 days after onset of treatment with high-dose corticosteroids. Some case reports describe the development of muscle weakness after the administration of a single dose of corticosteroid.
  • One study indicates a possible correlation between the occurrence of acute steroid myopathy and the total dose of steroid administered; acute atrophy was encountered with total doses greater than 5.4 g of hydrocortisone in 6 days, whereas no signs of myopathy were noted with total doses less than 4 g.
  • Previous systemic corticosteroid use does not appear to contribute to development of myopathy.

Physical

• Chronic (classic) steroid myopathy
• • Proximal muscle weakness is more pronounced than distal muscle weakness; however, severe relative weakness of the anterior tibialis muscle can be found.
  • Pelvic girdle muscles usually are affected more severely and earlier than pectoral girdle muscles.
  • Muscle bulk typically is normal, but muscle atrophy can occur.
  • Muscle stretch reflexes typically are normal.
  • Sensory examination should be normal.
• Acute steroid myopathy
• • Generalized muscle weakness, not limited to a more proximal distribution, is noted.
  • Muscle stretch reflexes typically are normal.
  • Sensory examination should be normal.

DIFFERENTIALS

Section 4 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• References

Other Problems to be Considered

Myopathies

Inflammatory myopathies (eg, polymyositis/dermatomyositis)
Muscular dystrophies
Drug/toxin–induced myopathies

Neuropathies

Diabetic amyotrophy
Motor neuron disease
Critical illness neuropathy

Neuromuscular junction disease

Myasthenia gravis
Eaton-Lambert syndrome

WORKUP

Section 5 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• References

Lab Studies

• Chronic (classic) steroid myopathy
• • Serum levels of creatinine kinase typically are within the reference range.
  • Creatinine excretion in the urine increases dramatically and can precede the clinical appearance of myopathy by several days.
  • Myoglobinuria and rhabdomyolysis are absent.
• Acute steroid myopathy: In most cases, high levels of serum creatine kinase are found, as well as associated myoglobinuria.

Other Tests

• Muscle biopsy in chronic (classic) steroid myopathy
• • Muscle biopsy shows preferential atrophy of type II fibers, particularly the fast-twitch glycolytic fibers (type IIB).
  • Some atrophy of other type II fibers and, to a small degree, type I muscle fibers can occur.
  • Increased variation in diameter of muscle fibers occurs.
  • Lack of evidence of muscle fiber inflammation is reported.
  • A distinct lack of necrosis or regeneration of muscle is present.
  • Less active muscles appear to be affected preferentially.
• Muscle biopsy in acute steroid myopathy: Muscle biopsy shows focal and diffuse necrosis of all fiber types, without predilection for type II fibers.
• Electromyography (EMG) and nerve conduction studies (NCSs) in chronic (classic) steroid myopathy
• • Motor and sensory NCS results typically are normal.
  • Repetitive stimulation studies do not reveal significant decrement or increment.
  • EMG studies reveal normal insertional activity with little abnormal spontaneous activity (positive sharp waves and fibrillation potentials).
  • EMG may reveal mild decrease in motor unit action potential amplitude during maximal recruitment.
  • In moderate-to-severe cases, studies may show an early recruitment pattern.
• EMG and NCS in acute steroid myopathy: Some case reports have indicated abnormal EMG findings, including abnormal spontaneous activity (positive sharp waves and fibrillation potentials), small polyphasic motor units, and early recruitment, as well as findings suggestive of associated neuropathy following high-dose corticosteroid treatment.

Histologic Findings

Muscle biopsy typically shows preferential atrophy of type II fibers, particularly the fast-twitch glycolytic fibers (type IIB), with some atrophy of other fiber types. A distinct lack of necrosis or regeneration of muscle is present. Some studies, however, have reported focal and diffuse necrosis of all fiber types, without predilection for type II fibers.

TREATMENT

Section 6 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• References

Rehabilitation Program

Physical Therapy

Some literature suggests that aerobic exercises and resistance training may help prevent or reduce severity of weakness. 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 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.

Occupational Therapy

Occupational therapy may focus on maximizing independence for performance of activities of daily living. Training may include the use of assistive devices to enhance the patient's ability to perform self-care tasks, such as a balanced forearm orthosis to allow positioning of the upper arm to allow for more independent feeding. Other adaptive equipment may include a raised toilet seat and similar equipment that allow easier standing from sitting and/or a motorized lift for ascending stairs.

Consultations

Any adjustments of the patient's corticosteroid medications should be coordinated with the physician who has been prescribing those medications for the patient. Given reports of respiratory muscle weakness causing respiratory impairments, consider consultation with a pulmonologist. Consultation with a neurologist can be considered for assisting with diagnosis and for excluding other potential causes of weakness. Consultation with a physiatrist can also be included for assistance with diagnosis and management of a therapy program.

Other Treatment

• In cases of myopathy due to long-term corticosteroid use, decreasing the corticosteroid dose below a threshold of 30 mg/d may result in resolution of muscle weakness. In cases due to a short course of high-dose corticosteroid use, partial or complete recovery has been reported following discontinuation of steroid administration.
• Preliminary studies [on rats] suggest that creatine plays a part in the prophylaxis of steroid-induced myopathy. Further studies are needed to explore this possible treatment/prevention option.²

MEDICATION

Section 7 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• References

Various medications, including potassium supplements, phenytoin, vitamin E, and anabolic steroids, have been tried as potential treatments for steroid myopathy. None have been shown clearly to demonstrate prevention or reversal of the muscle weakness induced by steroid myopathy. The main treatment recommendations are to decrease the dose of steroid to below a threshold level or to discontinue use of the corticosteroid. Alternate-day dosing could also be considered. Another recommendation is to change the steroid used to one that is not fluorinated.

FOLLOW-UP

Section 8 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• References

Deterrence/Prevention:

• Consider judicious use of steroids.

Complications:

• Although prior studies have reported full motor recovery, some patients may be left with some residual weakness of varying degrees.

Prognosis:

• In chronic (classic) steroid myopathy, recovery of weakness may take weeks to months following discontinuation or dose reduction of corticosteroid.
• In acute steroid myopathy, recovery may be prolonged (>6 mo).

Patient Education:

• Inform patients of the potential of development of myopathy when starting high-dose or long-term corticosteroid therapy.

MISCELLANEOUS

Section 9 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• References

Medical/Legal Pitfalls

• The main potential pitfall in diagnosing steroid myopathy is in patients with polymyositis/dermatomyositis, which typically is treated with corticosteroids. The main symptom of polymyositis/dermatomyositis is proximal upper and lower extremity weakness. When these patients, while treated on corticosteroids, develop increasing weakness, it can be difficult to determine whether the weakness is secondary to the polymyositis or to steroid myopathy.
• Laboratory studies can aid in differentiating between the two. Creatine kinase typically is elevated significantly in polymyositis/dermatomyositis. In steroid myopathy, it typically has been described that, although there is elevated urinary creatinine excretion, the serum creatine kinase is not elevated significantly. However, some studies have reported elevations of creatine kinase in some cases of the previously described acute form of steroid myopathy.
• On electrodiagnostic study, polymyositis typically demonstrates normal NCS results, as also is found typically with steroid myopathy. However, on EMG study, polymyositis demonstrates abnormal spontaneous activity and increased polyphasic waveforms with short durations. The classic form of steroid myopathy has been described as not demonstrating significant abnormal EMG findings. Again, some studies have described an acute form of steroid myopathy that can demonstrate abnormal spontaneous activity, small polyphasic waveforms, and early recruitment pattern.
• Initial recommendation is to decrease or discontinue the use of the corticosteroid. If the weakness improves, then steroid myopathy is the most likely diagnosis. If the weakness persists or worsens, then the most likely diagnosis is worsening of the polymyositis.

ACKNOWLEDGMENTS

Section 10 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• References

Debra Ibrahim, 4th year medical student, New York College of Osteopathic Medicine, Class of 2008, assisted with the 2007 revision of this manuscript.

REFERENCES

Section 11 of 11

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• References

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2. Menezes LG, Sobreira C, Neder L, et al. Creatine supplementation attenuates corticosteroid-induced muscle wasting and impairment of exercise performance in rats. J Appl Physiol. Feb 2007;102(2):698-703. [Medline]. [Full Text].
3. Afifi AK, Bergman RA, Harvey JC. Steroid myopathy. Clinical, histologic and cytologic observations. Johns Hopkins Med J. Oct 1968;123(4):158-73. [Medline].
4. Askari A, Vignos PJ Jr, Moskowitz RW. Steroid myopathy in connective tissue disease. Am J Med. Oct 1976;61(4):485-92. [Medline].
5. Baschetti R. Fludrocortisone and chronic fatigue syndrome. N Z Med J. Aug 8 2003;116(1179):U549. [Medline].
6. Batchelor TT, Taylor LP, Thaler HT, et al. Steroid myopathy in cancer patients. Neurology. May 1997;48(5):1234-8. [Medline].
7. Dekhuijzen PN, Decramer M. Steroid-induced myopathy and its significance to respiratory disease: a known disease rediscovered. Eur Respir J. Sep 1992;5(8):997-1003. [Medline].
8. Dumitru D. Myopathies. In: Electrodiagnostic Medicine. San Antonio, Tex: University of Texas;1995:1031-129.
9. Hanson P, Dive A, Brucher JM, et al. Acute corticosteroid myopathy in intensive care patients. Muscle Nerve. Nov 1997;20(11):1371-80. [Medline].
10. Hollister JR. The untoward effects of steroid treatment on the musculoskeletal system and what to do about them. J Asthma. 1992;29(6):363-8. [Medline].
11. Kumar S. Steroid-induced myopathy following a single oral dose of prednisolone. Neurol India. Dec 2003;51(4):554-6.
12. Lacomis D, Smith TW, Chad DA. Acute myopathy and neuropathy in status asthmaticus: case report and literature review. Muscle Nerve. Jan 1993;16(1):84-90. [Medline].

Article Last Updated: May 15, 2008