Suspect myopathy? Take this approach to the work-up

Basic labs for investigating suspected metabolic myopathy include serum electrolytes, glucose, LFTs, CK (which may or may not be elevated), lactate, ammonia, and UA for myoglobinuria. More advanced labs, such as serum total carnitine and acylcarnitine as well as urinary levels of dicarboxylic acids and acylglycines, may be needed if a metabolic disorder is strongly suspected.⁷ Muscle biopsy, EMG, and genetic testing can also prove helpful in diagnosis. Definitive diagnosis and treatment of metabolic myopathy usually requires a multidisciplinary team of providers, including subspecialty referral.

Toxic myopathy

The symptoms of drug-induced toxic myopathy are usually more insidious and lab abnormalities are usually more subtle than for other forms
 of myopathy. Toxic myopathy refers to muscle damage caused by an exogenous chemical agent, most often a drug. The mechanism of toxicity is not always clear and may result from the activation of inflammatory responses similar to autoimmune myopathy.²² Toxic myopathies may result from several commonly used medications; cholesterol-lowering medications are a common culprit.^13-15,23-25 Drug-induced myopathies vary in frequency and severity. For instance, in patients taking statins, the rate of myalgias is 6%, while the incidence of rhabdomyolysis is estimated to be 4 per 100,000, and is found most often in patients taking concomitant fibrates.²³

Drug-induced toxic myopathy differs from previously discussed myopathies in that symptoms are usually more insidious, findings on exam are more often mixed muscular and neurologic, and lab abnormalities are usually more subtle.^11,12 Symptoms of myopathy typically occur weeks or months after initiating a drug and usually improve or resolve within weeks after discontinuing the offending agent. Knowing the patient’s medication list and which medications cause certain patterns of myopathy symptoms can help guide the differential diagnosis (TABLE 4^11-15,22-25).

Cholesterol-lowering medications such as statins are a common cause of toxic myopathy. Risk factors for most medication-related myopathies are polypharmacy, renal or liver disease, and age over 50 years^13-15,23-25 The physical exam for patients with drug- or toxin-related myopathy will most often reveal relatively minor abnormalities such as muscle tenderness and mild weakness, except for the most severe or advanced cases. Most patients will not have physical signs that suggest an underlying illness. CK levels and LFTs should be obtained. Basic chemistry and UA may also be helpful in patients with risk factors for renal disease.

CASE › Ms. C has been taking a statin for more than 10 years, and the dose was recently increased. You are aware that statin-related muscle injury can develop even after years of use, and suspect the statin may be causing her myopathy. You order a CK test, which is mildly elevated. You recommend discontinuing the statin. After 8 weeks off her statin, Ms. C’s Symptoms do not improve. Given her lack of systemic complaints, myositic myopathy from an infectious or rheumatologic cause seems unlikely. You begin to consider an intrinsic cause of myopathy, and order the following tests: a CMP, UA, thyroid-stimulating hormone, repeat CK, and vitamin D level. This testing reveals a vitamin D deficiency at 17 ng/ml (normal range: 30-74 ng/ml). You recommend vitamin D, 50,000 IU per week for 8 weeks. At follow-up, Ms. C's vitamin D level is 40. She says she feels better and her muscle complaints have resolved.

CORRESPONDENCE
Brent W. Smith, MD, Travis Air Force Base Family Medicine Residency, 101 Bodin Circle, Travis Air Force Base, CA 94535; smithb@smithnet.us