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Rheumatology - Inflammatory Myopathies - Fast Facts | NEJM Resident 360

Inflammatory, or immune-mediated, myopathies (IMM) 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 IMM 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 subtype and is outlined in the following table:

Symptoms Associated with Subtypes of Inflammatory Myopathy

	Dermatomyositis	Polymyositis	Necrotising Autoimmune Myositis	Inclusion Body Myositis
Muscle Group Affected
Proximal	✔	✔	✔	✔
Distal				✔
Facial				✔
Neck/pharynx
(dysphagia)	✔	✔	✔	✔
Symmetry of weakness	Symmetrical	Symmetrical	Symmetrical	Asymmetrical
Associated Features
Antisynthetase syndrome, consisting of:

• myositis
• interstitial lung disease
• Raynaud phenomenon
• arthritis
• mechanic’s hand rash
• anti-RNA and anti-Jo1 antibodies | ✔ | ✔ | ✔ | | | Gottron papules | ✔ | | | | | Heliotrope rash | ✔ | | | | | Photodistributed rash:
• shawl sign, involving the back
• V sign, over the neck and upper chest | ✔ | | | | | Interstitial lung disease | ✔ | ✔ | | |

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 HMG-CoA 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

  • 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: An important differential diagnosis in some patients who take statins is statin-associated autoimmune myopathy. 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-methyl-glutaryl–coenzyme A reductase (HMGCR) and necrotizing myopathy that requires immunosuppression.

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. No specific guidelines exist for malignancy workup, and routine whole-body CT (informally, “pan scans”) or even positron emission tomography are not specifically recommended. However, many clinicians perform pan scanning, especially for adult patients with dermatomyositis (rather than another myopathy) or those with certain autoantibodies (including anti–transcriptional intermediary factor 1γ, antinuclear matrix protein-2). Age-appropriate cancer-screening guidelines should be followed, and any additional workup should be performed if clinically indicated. 

Treatment

Treatment for DM, PM, and NAM generally involves immunosuppression: Glucocorticoids are first-line treatment. Currently, there is no reliably effective therapy for IBM. The following table details the treatment algorithm for DM, PM, and NAM.

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

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