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How is inflammatory myopathy diagnosed? These "traps" to avoid!

 Last Update: 2023-01-01
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Choosing the right diagnostic tool in different situations can help to accurately determine
the disease.

The 2022 American College of Rheumatology (ACR) Annual Meeting was held
November 10-14, 2022 in Philadelphia, Pennsylvania, USA.
ACR Annual Meeting is the world's largest and most prestigious rheumatology academic conference, attended by more than 16,000 delegates from more than 100 countries around the world every year, and is an important platform
for relevant scholars to obtain the latest and most cutting-edge rheumatology research and clinical application information.

Inflammatory myopathy is a rare autoimmune disease that mainly affects muscles but can also affect other organs/tissues
.
Due to its ever-changing clinical features, how to accurately diagnose inflammatory myopathy is also a difficult clinical problem
.

Professor David Fiorentino from the Department of Dermatology at Stanford University School of Medicine and Jemima from Johns Hopkins University Professor Albayda introduced the role of auxiliary examinations in the diagnosis of inflammatory myopathy, and combined with the latest advances in the field, introduced the contribution
of serological testing, imaging, electromyography and histopathology to the diagnosis of myositis.

Advantages and disadvantages
of myositis antibodies, Professor David Fiorentino introduced the advantages and problems
of myositis antibodies in clinical applications.

When the body's immune tolerance is impaired, myositis antibodies can respond to the pathogenesis and have important potential
to provide biological information.
At the same time, myositis antibodies are highly stable, persistent, and convenient for testing
.
At present, more and more people are recognizing the clinical use
of myositis antibodies.
Myositis antibodies are gaining traction
in the diagnosis and classification of diseases, risk stratification of life-threatening diseases, and as bioactive markers.

Currently, there are many antigens and antibodies identified in different types of inflammatory myopathy that may be helpful in diagnosis, including: myositis-associated antibodies (PM-Scl, Ro52/Ro60, Ku, U1-RNP), dermatomyositis (TIF-γ, Mi2, MDA5, NXP2, SAE1/2), anti-tRNA synthetase antibodies (Jo-1, PL-7, PL-12, EJ, OJ, KS, Ha/Tyr, Zo, YRS, SC, JS, etc.
), immune-mediated necrotizing myopathy (HMGCR, SRP), and inclusion body myositis (NT5C1A), etc
.

Commonly used myositis antibody tests include immunoprecipitation, ELISA, beads, and western blotting
.
In the United States, several laboratories have conducted commercial testing of myositis antibodies (Table 1).

Table 1 Commonly used commercial laboratories
in the United States, however, there are some problems that need to be noted
in the actual application process.
Euroline blots, for example, are at risk of false positives, such as OJ itself that cannot be detected
by any western blotting.
Euroline blot has low sensitivity for detecting TIF-1γ, some TIF1-γ have conformational epitopes, and Euroline blot has significantly lower sensitivity (40%-60%) compared to IP, and Trinity and D-Tek blot kits also have such problems
.

The antigen of Mi-2 is two highly homologous polypeptides (α and β), and studies in large cohorts in the United States have compared Euroline with IP, with a sensitivity of about 65%-70% and a specificity > of 98% for Mi-2α positivity, a sensitivity of about 15%-20% and a specificity of > 85% for Mi-2α positivity alone, and a sensitivity of about 5% and specificity < 20%
for Mi-2β alone 。 Therefore, it is necessary to use LINE blot results reasonably, and confirmatory testing
should be performed when there is 1 positive > myositis antibody, a low signal is positive, or the test result does not meet the clinical situation.

The International Myositis Assessment and Clinical Research Group (IMACS) established the Scientific Group "Myositis Autoantibodies" composed of > 100 experts, which aims to address the unmet needs of myositis autoantibody detection, conduct a systematic literature review of the reliability of myositis autoantibody detection, promote interdisciplinary understanding of the clinical utility of myositis autoantibody detection, and provide a forum
for information exchange and collaborative research in the field of myositis serology.

With the deepening of various studies, the significance of myositis antibody detection for clinical reference will become more and more important
.
The reliability of myositis antibody tests may vary widely due to the characteristics of autoantigens, but many commercial tests still lack proper validation
.

In addition, there is much room
for improvement in effective communication between the orderer and the testing laboratory.
Although mixed, the interpretation of antibody test results is still highly controversial, so proper physician education can help avoid many of the myths
mentioned above.

Which is better for diagnosing inflammatory myopathy?

Professor Jemima Albayda presented the role of
electromyography and imaging in diagnosing inflammatory myopathy.

1
EMG

Electromyography includes NCS-function of sensory and motor nerve fibers, EMG-at rest, and potential analysis
at muscle activation.
Electromyography has the following characteristics: it can expand the scope of physical examination, locate peripherally weak muscles, exclude simulated disease, examine characteristic features to narrow the scope of differentiation, and determine the site
of biopsy.

Resting electromyography presents with spontaneous activity with fibrillation and positive sharp waves, complex repetitive discharges, and myotonic discharges
.
When activated voluntarily, the EMG appears as motor unit potential waves (MUAP), including morphology and recruitment patterns
.
Electromyographic findings in idiopathic inflammatory myopathy (IIM) include:

1) MUAPs have a short duration and low amplitude;

2) asynchronised signal (heterogeneous appearance) of the affected fiber;

3) Early or rapid fundraising mode;

4) Weakened recruitment pattern – severe end-stage myopathy with extensive muscle fiber loss
.

The limitations of electromyography are reflected in the following four aspects:
1.
IIM has typical findings on electromyography, but is not sufficient in itself to make a diagnosis
.

2.
The interpretation of the test results is subjective and will depend on the experience of
the reader.

3.
Muscle localization may become more difficult as muscles atrophy and fatigue – and with less experience
.

4.
EMG results reflect only a small number of active motor units near the needle
.

In addition, electromyography can increase muscle enzymes and damage muscles, and the accuracy of the test decreases
with steroid use.
2

Imaging
examination In muscle imaging, MRI is the gold standard test, and muscle ultrasound is also a commonly used imaging test
.
Imaging is a noninvasive assessment of the muscle and can confirm muscle involvement
.
Imaging can show disease activity and damage, and fully represent the overall shape of
the muscle.
Imaging tests can also evaluate other related structures, such as fascia and skin, and help determine the site
of the biopsy.

In muscle imaging, it is important to note that not all edema on MRI is inflammation
.
"Edema"-like signals may result from a variety of causes, including: inflammation, myonecrosis, muscle exertion, infection, subacute neurolactic changes, ischaemia, injury, and invasive tumors
.

Different types of myositis have their own MRI patterns [¹^]: dermatomyositis:
subcutaneous edema and calcifications can be seen, Sporadic distribution of edema within the muscle, asymmetric fascial edema
.

Immune-mediated necrotizing myopathy: earlier and more severe lesions than other IIMs, early fat replacement
.

Antisynthetase syndrome/overlap: frequent myofascial edema, muscle edema pattern similar to DM.

Sporadic inclusion body myositis (IBM): recurrent lower extremity asymmetry and distal leg involvement, and changes on MRI are specific to this condition
.

In the case of IBM, its MRI features include ^[²^]: Main criteria:

Fatty fibers at the distal quadriceps (VI and VM) infiltrate and atrophy, appearing "melted"
T1-weighted anomalies of the distal-proximal gradient of the quadriceps
The anterior > posterior compartment of the thigh is affected

Supporting Criteria:

Medial gastrocnemius muscle involvement
The pelvic muscles are less affected than the thigh muscles

IBM's MRI has two difficulties
.
Edema on MRI first only slightly increases signal intensity, and is more difficult to detect
on ultrasonography.
In addition, if edema and fat replacement are present at the same time in mode B, it is impossible to distinguish
between the two.

Imaging remains a number of limitations, starting with the fact that diagnosis alone is not sufficient
.
Although MRI is currently the most advanced test, its use is less widespread and has the best
effect on edema.

Ultrasonography is highly accessible but requires an experienced operator and is best suited to assess for chronic changes
.
Both tests can be used to assist in locating the target of the
biopsy.
MRI is characterized by simultaneous display of inflammation and damage
.
Ultrasound can examine
multiple ranges of muscles in real time as needed.

3
Muscle biopsy Muscle biopsy
is the gold standard for establishing IIM diagnosis and can be grouped
in IIM subtypes.
Monocytes infiltration and myofiber necrosis are common histopathological features
.

Typical biopsy findings for different types of myositis^[³^]:

Dermatomyositis: perivascular inflammation, perivascular atrophy, MHC class I molecules, MAC deposition
of vascular walls.
Antisynthetase syndrome/overlap: perivascular and perimucosal necrosis, MHC class I and II molecules, visually visible complement
.
Immune-mediated necrotizing myopathy: a large number of necrotic fibers are invaded or surrounded by macrophages; Lymphocyte infiltration is sparse, MHC class I upregulates mainly in necrotic fibers, and complement is on
capillaries and/or fascia.
Polymyositis: primary inflammation in the body mainly composed of CD8+ T cells, MHC class I upregulated
.
IBM: inflammatory changes in polymyositis; degenerative changes in the body (marginal vacuoles, congestive inclusion bodies, and polyprotein aggregation); Mitochondrial changes (COX-negative fiber increase).

Muscle biopsy also has its limitations
.
False-negative rates are typically 10% to 20%, mainly due to differences in the site of sampling, the possibility of missing key features if a biopsy of a severely asthenic muscle, and sometimes nonspecific changes
.
Inflammatory infiltrates can also occur in
other muscle disorders.
In addition, even for some key features, differences in the interpretation of results and in scoring individual biopsy abnormalities are often disappointing
.

Summary

The diagnosis of IIM focuses on common consideration
of clinical presentation, antibody testing, and other ancillary tests.
In clinical practice, it is necessary to choose the appropriate examination method
according to the specific situation.

As a non-invasive assessment, imaging can provide sensitive information
about the severity of the disease.

Electromyography is useful to rule out other neuromuscular mimics and comorbid conditions
.
Both imaging and electromyography confirm muscle involvement, exclude mimic disease, and localize
optimal biopsy.
Muscle biopsy is usually diagnostic and only biopsy can diagnose subgroups of IIM, but is not necessary
in the setting of typical clinical presentations.

References:

[1] Albayda J, Demonceau G, Carlier PG.
Muscle imaging in myositis: MRI, US, and PET.
Best Pract Res Clin Rheumatol.
2022; 36(2):101765.

[2] Tasca G, Monforte M, De Fino C, Kley RA, Ricci E, Mirabella M.
Magnetic resonance imaging pattern recognition in sporadic inclusion-body myositis.
Muscle Nerve.
2015 Dec; 52(6):956-62.

[3] Dalakas MC.
Inflammatory myopathies: update on diagnosis, pathogenesis and therapies, and COVID-19-related implications.
Acta Myol.
2020 Dec 1; 39(4):289-301.

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