Overview.
Steroid myopathy is muscle atrophy and muscle weakness caused by corticosteroids, also known as corticosteroid polymyopathy. The disease can be divided into acute and chronic types. Chronic steroid myopathy is more common than acute, has an insidious onset, and is characterized by weakness of the pelvic girdle muscles, which progresses to include the scapular girdle muscles and proximal extremity muscle groups. Subjective symptoms of muscle weakness tend to be heavier than objective muscle strength tests. Myalgia is common and disappears after steroid tapering, indicating that myalgia is one of the symptoms of steroid myopathy. Steroids are widely used clinically and the disease is not uncommon.
Etiology
Steroid myopathy is a class of muscle lesions caused by the widespread use of corticosteroids, similar to Cushing’s syndrome with associated muscle changes. The exact pathogenesis is unknown. It is likely that the protein metabolism is affected, resulting in an imbalance between the synthesis and catabolism of muscle contractile components (e.g., myocardin, contractile proteins), leading to clinical muscle weakness and atrophy. Steroids can block protein synthesis by inhibiting RNA synthesis and reducing the efficiency of protein translation. Steroids also promote the breakdown of muscle contractile proteins through the ubiquitin protease system and alkaline myofibrillar protease. The direct consequence of reduced protein synthesis and hypercatabolism in myocytes is structural changes in myogenic fibers and decreased function. The occurrence of steroid myopathy is not definitely related to the dosage of steroids and the duration of treatment. A sudden increase in dosage during long-term treatment may lead to the occurrence of steroid myopathy, and it is also believed that the higher the dosage and the longer the duration of treatment, the more prone to the occurrence of steroid myopathy. In addition, fluorinated steroid preparations may be more likely to cause steroid myopathy.
The pathology of acute steroid myopathy is characterized by massive myofiber necrosis, regeneration, and phagocytosis, or there may be extensive myofibrillar atrophy, with involvement of both types of fibers. The main pathological changes of chronic steroid myopathy are selective type II muscle fiber atrophy, muscle necrosis and regeneration are not obvious, so some scholars suggest that the use of “steroid myasthenia gravis” is more accurate than “steroid myopathy” for this kind of patients. Ultrastructural observation shows a mild increase in glycogen and lipids under the muscle membrane and between myofibers, and mitochondrial degeneration.
Symptoms
1. Chronic steroid myopathy
Muscle lesions caused by long-term use of corticosteroids. Patients often have a history of high-dose corticosteroid use for months or years, and there is no significant correlation between the drug dose and the degree of muscle weakness. Fluoride-containing hormones are more susceptible to the disease than other hormones, and virtually all corticosteroids can cause the disease; the pathogenesis is unknown. In corticosteroid-treated animals, significant decreases in amino acid intake and protein synthesis levels have been found.
(1) Weakness of the proximal limb and limb-girdle muscles, symmetrically distributed. It first invaded the proximal part of the lower limb, gradually progressed, spread to the scapular girdle muscles, and finally to the distal muscle groups of the limb.
(2) Serum CK and aldolase were normal, EMG was normal or showed slight myogenic damage without spontaneous potentials. Myocardial biopsy reveals slight changes in muscle fiber size, which may be accompanied by type II fiber atrophy, with little muscle fiber necrosis and inflammatory cell infiltration. Electron microscopy reveals mitochondrial aggregates and glycogen lipid deposits with mild muscle fiber disuse atrophy. The above lesions are consistent with the characteristic changes of Cushing’s disease.
2. Acute steroid myopathy
Critical illness myopathy or acute tetraplegic myopathy caused by corticosteroids. Patients often due to severe intractable asthma or a variety of systemic diseases receiving high-dose corticosteroid therapy, also seen in sepsis and other critically ill patients, sometimes with neuromuscular blocking drugs, muscarinic drugs such as Pancuronium can induce this disease, but also due to the use of aminoglycoside antibiotics caused by the systemic disease improves in the emergence of severe muscle weakness. Muscle in the loss of innervation after the intake of large amounts of corticosteroids, selective myocardin deficiency can occur, is a characteristic manifestation of this type of disease, myocardin recovery is dependent on nerve regeneration rather than discontinuation of steroids, but patients with multiple sclerosis with high doses of corticosteroids, did not find corticosteroids myopathy and so on.
(1) The onset of the disease is rapid, extensive involvement of the limb muscle groups and respiratory muscles, severe generalized muscle weakness and dyspnea, tendon reflexes are normal or weakened, or even disappeared. It does not involve the sensory nervous system, and the patients get better in a few weeks after stopping the drug, and the muscle weakness can last for 1 year in a few patients.
(2) Early in the course of the disease, serum CK increases, severe muscle necrosis can be accompanied by a significant increase in CK levels, myoglobinuria and renal failure, etc. EMG can find myopathic features, common myofibrillar tremor. Myocardial biopsy shows different degrees of muscle fiber necrosis and vacuolar degeneration, mainly involving type II fibers, with obvious loss of thick myofilament myoglobin.
Examination
1. Serum myosin
Chronic steroid myopathy is mostly normal; serum CK is often increased in the early stage of acute steroid myopathy, and severe muscle necrosis can be accompanied by a significant increase in CK level.
2.urinary creatine
The excretion of urinary creatine increases significantly and appears in the early stage of the disease, which is a sensitive indicator for the diagnosis of this disease.
3. Electromyography
The examination is not specific, but it can detect the characteristics of myopathy, and muscle fiber tremor is common. Chronic steroid myopathy EMG is normal or shows slight myogenic damage without spontaneous potentials, which can be neurogenic, myogenic or mixed, and the acute type can be accompanied by a lot of spontaneous activity.
4. Muscle biopsy
The chronic form reveals slight changes in muscle fiber size, which may be accompanied by type II fiber atrophy, with little myofiber necrosis and inflammatory cell infiltration. Electron microscopy reveals mitochondrial aggregates and deposition of glycogen and lipids, accompanied by mild myofibrillar disuse atrophy, which are consistent with the characteristic changes of Cushing’s disease.
The acute form shows varying degrees of myofiber necrosis and vacuolar degeneration, predominantly involving type II fibers, often with marked loss of thick myofilament myoclastin.
Diagnosis
Acute steroid myopathy can be diagnosed according to the history and clinical manifestations; chronic steroid myopathy is insidious in onset and easy to miss the diagnosis, and the clinical diagnosis is mainly based on the following points:
1. Muscle weakness with severe Cushing’s syndrome and increased 24-hour uric acid excretion after steroid treatment.
2. Exacerbation of muscle weakness when applying steroid therapy for polymyositis, with stable serum CK level, increased 24-hour urinary creatine or muscle weakness after steroid dosage.
3. Muscle biopsy shows selective type II muscle fiber atrophy with increased lipids in type I fibers.
4. The diagnosis can be confirmed in patients suspected of having steroid myopathy when the muscle weakness resolves after discontinuing steroids.
Differential diagnosis
1. It should be differentiated from muscle weakness and myasthenia due to brain and spinal cord lesions, especially when a large amount of corticosteroids is applied after the crisis of brain diseases.
2. It should be differentiated from other types of skeletal muscle diseases.
Treatment
Chronic steroid myopathy can be recovered within weeks or months after stopping the drug, and the symptoms of myasthenia gravis can be relieved after switching to non-fluorinated agents in those who use fluorinated agents. The use of alternate-day dosing, reduction of steroid dosage, and regular physical activity such as bicycling and weight lifting are beneficial to the treatment and prevention of the disease. Patients with acute steroid myopathy improve within a few weeks after discontinuation of the drug, and in a few patients the weakness may persist for up to 1 year.
Prognosis
The majority of patients improve a few weeks after stopping the drug, and muscle strength gradually recovers and improves, while in a few patients, muscle weakness may last for more than 1 year.
Prevention
The male anabolic hormone nandrolone phenylpropionate partially counteracts the proteolytic effects of steroids and may be used to prevent the development of steroid myopathies.