Laboratory Evaluation of Inflammatory Myopathies

Myositis may be idiopathic or caused by conditions such as microbial infections, drugs, or injury leading to inflammation and damage in the muscles.

Idiopathic inflammatory myopathies (IIM) are a rare and heterogeneous group of autoimmune diseases characterized by acute, subacute, or chronic muscle weakness. IIM may broadly be categorized into dermatomyositis (DM), polymyositis (PM), inclusion body myositis (IBM), necrotizing autoimmune myopathy (NAM), and overlap syndromes.

Frequency

Myositis is listed as a "rare disease" by the Office of Rare Diseases (ORD) of the National Institutes of Health (NIH). This means that myositis, or a subtype of myositis, affects less than 200,000 people in the US population. The incidence of idiopathic inflammatory myopathy is approximately 2 to 8 cases per million people each year. For unknown reasons, polymyositis and dermatomyositis are about twice as common in women as in men, while sporadic inclusion body myositis is more common in men.

Disease Presentation

The symptoms of myositis can include muscle weakness, muscle pain and muscle tenderness. Muscle weakness may not be observed in the early stages of disease as in some patients with DM. In general patients with myositis may present with one or more of these symptoms at disease onset:

  • Difficulty standing up from a seated position
  • Difficulty lifting the arms
  • Fatigue after standing or walking a long time
  • Trouble swallowing or breathing
  • Muscle pain that does not subside within a few weeks
  • A red or purple colored rash on the eyelids, elbows, knees and knuckles

Autoantibody Evaluation for Myositis

Autoantibodies have been recognized to have a role in distinguishing between subtypes of myositis, and clinic-serological classifications have been proposed. In addition, specific antibodies may have some relevance in stratifying patients based on risk for certain organ involvement, predict cancer or response to treatment. In these regard, if present, autoantibodies may be useful in long-term management of patient with myositis.

A comprehensive autoantibody panel for IMM as well as the main clinical subsets including connective tissue disease associated with ILD is offered by ARUP Laboratories:
ARUP Consult: Inflammatory Myopathies

AntibodyFrequency %Clinical Associations
Jo-115-20

Antisynthetase syndrome
• Polymyositis
• Interstitial lung disease (89%)
• Arthritis (94%)
• Raynaud's (67%)
• Fevers (87%)
• Mechanic's hand (71%)
PL-7<5
PL-12<5
EJ<5
OJ<5
KS<5
Ha<1
Zo<1
SRP Necrotizing myopathy
HMGCR6Necrotizing myopathy
Mi-210-30Classic DM, low cancer risk, good response to steroid treatment. Favorable prognosis
P155/14013-30Aggressive skin lesions in DM and JDM. Cancer in adults >50 years
NXP-2~25Young-onset, severe cutaneous lesions, including calcinosis, and muscle contractures. Associated with cancers (>50 years onset)
MDA520-30Amyopathic DM (CADM). Rapidly progressive ILD with poor prognosis
SAE~8Amyopathic DM at presentation, severe skin disease, dysphagia and systemic features. Favorable prognosis
PM/Scl10-15Polymyositis-SSc overlap
Ku20-30Polymyositis-SSc overlap
SS-A/Ro≥35ILD in IIM

Test Panels

The presence of specific autoantibodies is a hallmark in the diagnosis of certain clinical subsets of IIM. Most of these autoantibodies target intracellular proteins, including nuclear and cytoplasmic antigens. Based on their specificity, can be grouped into myositis-specific (MSA) and myositis-associated autoantibodies (MAA). Testing for MSA and MAA is a useful aid for the diagnosis, subset classification, and management of IMM.


Test Number Test Name Antibodies Tested Ordering Recommendation
2013961 Myositis Extended Panel Mi-2, PL-7, PL12, P155/140, EJ, Ku, OJ, PM/Scl, SRP, U2RNP, U1RNP, Ro52, Ro60, Jo-1, U3 Fib, SAE1, NXP2, MDA5, TIF1-gamma May be useful for differential evaluation of polymyositis, dermatomyositis, necrotizing autoimmune myopathy, or overlap syndromes associated with connective tissue disease.
2013992 Polymyositis and Dermatomyositis Panel PL-7, PL12, EJ, OJ, SRP, Jo-1, Mi-2, P155/140, SAE1, MDA5, NXP2, TIF1-gamma May be useful for the evaluation of patients with progressive proximal muscle weakness and/or cutaneous manifestations suggestive of dermatomyositis and/or associated connective tissue disease.
2013990 Polymyositis Panel PL-7, PL12, EJ, OJ, SRP, Jo-1 May be useful for evaluation of patients with progressive proximal muscle weakness and antisynthetase syndrome.
2013991 Dermatomyositis Panel Mi-2, P155/140, SAE1, MDA5, NXP2, TIF1-gamma May be useful for evaluation of patients with characteristic cutaneous manifestations of dermatomyositis with or without muscle weakness.
2013993 Interstitial Lung Disease Panel Ro52, Ro60, Jo-1, PL-7, PL12, EJ, Ku, SRP, OJ, PM/Scl-100, MDA5, CCP, Scl-70, RA, ANA, NXP-2 May be useful for evaluation of interstitial lung disease in the context of connective tissue disease.

Frequently Asked Questions

What is the significance of autoantibody testing in myositis?

Myositis-specific (MSA) or -associated autoantibodies (MAA) are closely linked to characteristic clinical manifestations and may facilitate diagnosis, prognosis, and treatment choice.

In general, MSA are mutually exclusive and closely associated with distinct disease subsets differing in clinical involvement and prognosis. Based on their unique associations with specific clinical subsets, they are thought to be useful biomarkers to help in the diagnosis of myositis. MAA are not specific to myositis, may occur with or without with MSA, and are mostly found in myositis overlap syndromes, primarily polymyositis-systemic sclerosis (PM/SSc). MAA can also be found in patients with non-myositis or myositis overlap syndromes.

How is testing for myositis performed?

Testing for some myositis antibodies is performed by immunoprecipitation of radiolabeled proteins, which is time-consuming and requires interpretation expertise. The technique allows for the simultaneous detection of classic and identification of novel autoantibodies.

More information on the methods used for detecting the different myositis antibodies can be found here.

How accurate are the different autoantibody tests for myositis?

Myositis is a heterogeneous disease and the prevalence of specific autoantibodies will vary by method of their detection, clinical subset as well as population demographic.

Prevalence of myositis antibodies in different clinical subsets can be reviewed here.

Diagnostic performance of myositis autoantibodies is dependent on the method of their detection. More on this can be reviewed using this link.

Method comparison studies for PL-7, PL-12, EJ, OJ, and SRP antibodies detected by immunoprecipitation at ORMF and ARUP Laboratories showed excellent performance.

Do corticosteroids or medications affect the performance characteristics of myositis antibodies?

Some autoantibodies may be affected my immunosuppressive treatment. For example, early and/or aggressive immunosuppressant therapies are associated with decline in SRP and HMGCR antibody levels.

Read more FAQs about rare diseases here.

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