Inflammatory Myopathies

Idiopathic inflammatory, or immune-mediated, myopathies (IIM) are a group of systemic diseases characterized by autoimmunity, inflammation, muscle involvement, and often systemic features. The hallmark of inflammatory myositis is painless muscle weakness, though myalgia can be experienced. Fibromyalgia is covered in the Ambulatory Care rotation guide.

The four subtypes of inflammatory myopathies are:

• dermatomyositis (DM)

• polymyositis (PM)

• necrotizing autoimmune myositis (NAM)

• inclusion body myositis (IBM)

Diagnosis

Immune-mediated myopathies should be considered as a differential diagnosis in all cases of elevated serum creatine kinase, in patients reporting weakness or myalgia, and in patients with suggestive skin findings. In addition, myopathy (inflammatory or otherwise) should be considered in patients with abnormal liver function tests, particularly when the aspartate aminotransferase is greater than the alanine aminotransferase. Differentiating the types of IIM requires correlation of clinical and MRI findings with the autoantibody profile (if detected), and histologic and immunohistochemical features of the affected muscle tissue.

Distribution of affected muscles and associated features differs for each IIM subtype as outlined in the following table:

Workup:

• History and physical examination:

  • statin exposure

  • concomitant autoimmune diseases or inflammatory arthritis

  • distribution and involvement of muscle weakness

  • cutaneous manifestations for DM and antisynthetase syndrome

  • pulmonary manifestations

  • features suggestive of malignancy

• Serology and biochemistry:

  • creatine kinase, alanine and aspartate aminotransferases, lactate dehydrogenase (all are typically elevated with muscle inflammation); aldolase measurement is not routinely needed

  • antinuclear antibodies, anti-Ro and anti-La antibodies, myositis-specific antibodies (including anti-hydroxymethylglutaryl-coenzyme A [HMG-CoA] reductase antibodies)

• MRI is the best imaging modality for inflammatory myopathy and should include:

  • bilateral limbs to assess for distribution of muscle inflammation and aid target for biopsy

  • a fat-suppressed MRI sequence to assess for muscle inflammation

  • Note: In the right clinical context, muscle edema may indicate active disease, but the specificity of this finding for myositis may be limited; muscle atrophy and fatty replacement suggest muscle damage without disease activity.

• Tissue biopsy is the gold-standard diagnostic test, performed where active disease is identified; however, as the lower limbs are frequently affected, “blind” biopsies of the vastus lateralis muscle can be performed.

  • Tissue should be analyzed for histologic, immunohistochemical, and electron microscopic features that aid in differentiating various muscle diseases (i.e., IMM vs. muscular degeneration vs. mitochondrial disorders).

• Additional investigations may be performed to assess for extramuscular involvement if indicated (e.g., interstitial lung disease, cardiac involvement, malignancy).

The following chart summarizes the diagnostic approach for each of the four subtypes of inflammatory myopathies:

(Source: Inflammatory Muscle Diseases. N Engl J Med 2015.)

Differential diagnosis: Proximal muscle weakness, with or without elevation in muscle enzymes, can be seen in a variety of conditions in addition to IIMs, including glucocorticoid myopathy, thyroid myopathy, and metabolic myopathies. Myalgia without proximal muscle weakness is not typical of IIMs and is more likely to occur in the setting of polymyalgia rheumatica, fibromyalgia, and noninflammatory musculoskeletal conditions.

An important diagnostic consideration in patients who take statins is the distinction between statin-associated necrotizing autoimmune myopathy and statin-associated myalgias. Some patients taking statins may develop myalgias, cramps, and occasionally elevated levels of creatinine kinase (CK) that resolve with statin discontinuation. A minority of patients exposed to statins develop antibodies against 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) and necrotizing myopathy that requires immunosuppression. The autoimmune myopathy associated with the anti-HMGCR antibodies can occasionally develop in patients with no prior exposure to statins, as well.

Inflammatory myopathy can also be seen in other autoimmune conditions, such as sarcoidosis, polyarteritis nodosa, systemic lupus erythematosus, mixed connective tissue disease, and overlap syndromes.

Evaluation for malignancy: Patients with DM, and to a lesser extent PM, have a higher risk for malignancy than the general population. Practice patterns with respect to malignancy screening in patients with DM or PM vary among providers and between patients, depending on individual risk factors. All age-appropriate cancer-screening guidelines should be followed. In patients with especially high risk of malignancy (particularly those with constitutional symptoms, older age, and high-risk autoantibodies such as anti-transcriptional intermediary factor 1 gamma and antinuclear matrix protein 2), additional testing such as transvaginal ultrasound, whole-body CT scan, or PET scan may be considered.

Treatment

Treatment for DM, PM, and NAM generally involves immunosuppression: Glucocorticoids are first-line treatment, and most patients require the addition of other immunosuppressive agents. Physical therapy is an essential element of the therapeutic approach in these conditions. Unlike the other forms of IIM, there is no evidence that immunosuppressive treatments alter the course of IBM. However, physical therapy is effective at slowing the progression of muscle weakness in IBM. The following table details an approach to treatment for DM, PM, and NAM.

(Source: Inflammatory Muscle Diseases. N Engl J Med 2015.)