Acquired non-inflammatory myopathy

Cause

Acquired non-inflammatory myopathy can arise from metabolic abnormalities, drugs, nutritional deficiency, trauma, or upstream abnormalities that reduce function. Two of the most common causes are hyperthyroidism and excessive steroid use, while many drugs used to treat rheumatism are known inducing agents. Most cases are linked to drugs or dietary abnormalities. Drugs can damage muscle fibers at the molecular level, altering organelle function such as that of mitochondria, and using multiple such drugs together increases risk.

Statins, prescribed for dyslipidemia, are associated with muscle toxicity that includes cramping, weakness, aching, or tenderness, often in the quadriceps, pectoral, biceps, low back, or abdominal region. Symptoms worsen with exercise and often persist after stopping statin therapy. Statins induce myopathy by inhibiting protein synthesis within muscle, and damage is often found in the mitochondria. Corticosteroids cause proximal muscle weakness, neck flexor weakness, and in extreme cases respiratory muscle weakness, along with muscle atrophy and local or diffuse cell death.

Colchicine, especially in patients with compromised renal function, produces proximal muscle weakness, distal sensory loss, and areflexia, with biopsy showing vacuolar myopathy without significant cell death or inflammation.

Diagnosis

Patient history is key in diagnosing acquired non-inflammatory myopathy, used to analyze symptom onset, family history, medication or drug use, and any trauma from illness or infection. Basic exams test for proximal and distal muscle strength and signs of neurogenic symptoms such as impaired sensation, deep tendon reflexes, and atrophy. Advanced diagnostic tools include measurement of serum muscle enzymes (creatine kinase, aldolase, aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase), electromyography (EMG), magnetic resonance imaging (MRI), and muscle biopsy.

Abnormal enzyme levels indicate both inflammatory myopathy and ANIM. EMG helps locate affected muscle groups and determines myopathy distribution by measuring spontaneous electrical activity at rest, polyphasic shorter amplitude motor unit action potentials during stimulation, and inability to differentiate large from small motor plate stimulation. MRI may show edema in inflammatory patients but in ANIM typically shows nothing or some atrophy. If a metabolite defect is suspected, additional tests assess enzyme function at rest and during exercise, enzyme intermediates, and molecular genetic testing for predisposition.

Treatment

Treatment for acquired non-inflammatory myopathy focuses on resolving the underlying condition, pain management, and muscle rehabilitation. Drug-induced ANIM can be reversed or improved by tapering off the offending drugs and finding alternatives. Hyperthyroidism-induced ANIM is treated with anti-thyroid drugs, surgery, and avoiding high-iodine foods like kelp, leading to complete recovery.

Vitamin D deficiency-related ANIM resolves with vitamin supplements and increased sunlight exposure. Pain is managed through massage and nonsteroidal anti-inflammatory drugs (NSAIDs). Exercise, physical therapy, and occupational therapy help rehabilitate affected muscles and resist atrophy, while walkers, canes, and braces may assist mobility.

Research direction

A diagnostic test for statin-associated auto-immune necrotizing myopathy is expected soon to help differentiate myopathy types during diagnosis. Abnormal spontaneous electrical activity in resting muscles indicates an irritable myopathy and may reflect an active necrotising myopathic process or unstable muscle membrane potential, but this finding has poor sensitivity and specificity for predicting inflammatory myopathy on biopsy; further research may improve differential diagnosis.

Muscle biopsy remains critical unless genetic testing secures the diagnosis, and molecular genetic testing is available for many common metabolic myopathies and muscular dystrophies, though costly and best used for confirmation rather than screening. Improved testing methods may reduce costs and increase access. Increased study of muscle pathophysiology helps differentiate inflammatory from non-inflammatory myopathies and guide treatment. Better classification schemes and continued research into pathophysiology will improve clinicians' ability to administer appropriate therapy.

The mechanism of myopathy in low vitamin D is not fully understood; decreased 250HD availability leads to mishandling of cellular calcium transport to the sarcoplasmic reticulum and mitochondria, associated with reduced actomyosin content of myofibrils.

Did You Know?

• The forearm ischemic exercise test screens for disorders of glycogen metabolism and AMPD deficiency by measuring lactate and ammonia levels.
• Patients with glycogen storage disease show a normal increase in ammonia but no change in lactate during ischemic exercise.