Myopathy

Myopathy, a disorder of muscle, should be suspected in patients with weakness without numbness. The diagnosis is supported by elevated creatine kinase (CK) levels, although a normal CK does not exclude myopathy. Electromyography (EMG) can be a useful diagnostic tool, with the limitation that mild myopathies may appear normal, and chronic myopathies may appear neuropathic on EMG. The temporal course of symptom onset (acute/subacute vs. chronic) is important to focus the diagnostic evaluation. When present, a family history of myopathy may directly suggest the likely diagnosis.

Acute or Subacute Myopathy

A.

Typical skin findings in dermatomyositis (DM) include erythema of sun exposed areas (e.g., face and chest), purple discoloration around the eyes (“heliotrope” rash), papules on the fingers (Gottron papules), and dry, cracked skin on the lateral surface of the fingers (“mechanic’s hands”). Calcium deposits in the skin (“calcinosis cutis”) are rare in adults but commonly seen in children. The combination of weakness and any of the above suggests DM. Skin or muscle biopsy can be diagnostic. Skin biopsy typically demonstrates perivascular lymphocytes and vacuoles in the basal keratinocyte layer, and muscle biopsy demonstrates perivascular inflammation, perifascicular atrophy, and membrane attack complex deposition on capillaries. DM is frequently associated with malignancy; cancer screening should be performed at diagnosis and over the subsequent 2 years.
B.

Sporadic inclusion body myositis is an acquired myopathy typically seen in older adults with a fairly distinct pattern of long finger flexor and/or quadriceps weakness. Patients may report difficulty climbing stairs or opening jars. Dysphagia is common. Characteristic changes on biopsy include rimmed vacuoles, inclusions, and the presence of inflammatory cells. NT5c1A antibodies are seen in 60%–70% of patients.
C.

Chronic exposure to high-dose corticosteroids can cause insidiously progressive proximal weakness in addition to systemic Cushingoid features. The serum CK and EMG are usually normal. Characteristic changes on biopsy include atrophy of type 2 muscle fibers.
D.

Critically ill patients with systemic inflammatory response syndrome or hyperglycemia are at increased risk of developing an acute myopathy, which often manifests as proximal weakness and difficulty weaning from the ventilator. The serum CK may be elevated but is often normal. Nerve conduction studies may demonstrate prolonged distal compound muscle action potential duration or the muscle may be electrically inexcitable. There is frequently coexistent critical illness neuropathy.
E.

Consider toxic myopathies in patients presenting with acute/subacute weakness, elevated CK, and exposure to a potential offending agent. Statins are a common offender and may cause either a toxic or immune-mediated necrotizing myopathy (IMNM; see section H). Immune-mediated myopathies may also be seen with check-point inhibitor antineoplastic agents.
F.

Inherited myopathies occasionally present more acutely and can mimic an acquired myopathy.
G.

Sporadic late-onset nemaline myopathy is a rare acquired myopathy presenting with rapid onset of proximal muscle weakness with normal or mildly elevated CK. The diagnosis is confirmed by the presence of nemaline bodies on muscle biopsy. Patients frequently also have a monoclonal gammopathy. Cardiac involvement is common.
H.

Necrotizing myopathies are defined by necrotic muscle fibers with scant inflammation and may be immune mediated or due to toxic exposures. Signal recognition particle (SRP) and anti–HMG-CoA are the antibodies most commonly associated with IMNMs. IMNMs are often refractory to treatment and may require more aggressive immunomodulatory therapy. Like dermatomyositis, necrotizing myopathies are frequently associated with malignancy; cancer screening should be performed at diagnosis and over the subsequent 2 years.
I.

Polymyositis is uncommon, and necrotizing myopathy, inclusion body myositis, and inherited myopathy are frequently misdiagnosed as polymyositis. Polymyositis is defined by characteristic changes on biopsy, including endomysial inflammation composed of CD8 T cells and macrophages invading nonnecrotic fibers. Polymyositis can be associated with malignancy but less frequently than dermatomyositis or necrotizing myopathy; cancer screening should be performed at diagnosis and over the subsequent 2 years.
J.

In patients with a presumed inflammatory myopathy that is unresponsive to treatment, reconsider the diagnosis. Inherited myopathies mimicking an acquired myopathy will not respond to treatment.