Diagnostic Testing
Testing Component
Many patients are given a different diagnosis initially, including lupus erythematous and undifferentiated connective tissue disease. It is of paramount importance to determine the organ (i.e. skin, muscle, lung, heart) involvement at the onset of disease.
Diagnostic objectives include:
- Identify the muscle and cutaneous signs and symptoms of Dermatomyositis (DM)
- Exclude other causes of muscle weakness (e.g., inherited, infectious or endocrine myopathy)
- Determine if other organ systems are involved (respiratory, cardiac, gastrointestinal, joint)
- Evaluate possible underlying malignancy
Initial Workup
Initial evaluation for DM starts with a thorough history and physician examination.
- Physical examination can identify cutaneous features of DM and may include a total body skin examination and muscle strength testing of extremities and neck flexors.
- A detailed history to evaluate muscular disease with pointed questions and strength testing of muscle groups should be performed.…
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Testing Component
Many patients are given a different diagnosis initially, including lupus erythematous and undifferentiated connective tissue disease. It is of paramount importance to determine the organ (i.e. skin, muscle, lung, heart) involvement at the onset of disease.
Diagnostic objectives include:
- Identify the muscle and cutaneous signs and symptoms of Dermatomyositis (DM)
- Exclude other causes of muscle weakness (e.g., inherited, infectious or endocrine myopathy)
- Determine if other organ systems are involved (respiratory, cardiac, gastrointestinal, joint)
- Evaluate possible underlying malignancy
Initial Workup
Initial evaluation for DM starts with a thorough history and physician examination.
- Physical examination can identify cutaneous features of DM and may include a total body skin examination and muscle strength testing of extremities and neck flexors.
- A detailed history to evaluate muscular disease with pointed questions and strength testing of muscle groups should be performed. Questions should include those about difficulty combing hair, getting out of a seated position, difficulty swallowing, and change in voice.
Key Diagnostic Tests
Key diagnostic tests for the diagnosis of DM include:
- Muscle enzymes including creatine kinase and aldolase
- Myositis-specific antibodies (MSA) (antisynthase antibodies, anti-signal recognition particle, anti-Mi-2, antii-MDA5, anti-TIF-1 gamma, and NXP2)
- Myositis associated autoantibodies (MAA) l (Anti-U1 ribonucleoprotein, anti-Ku, anti-PM-Scl)
- Skin biopsy if classic rash is not evident
- Electromyography to evaluate for myopathic findings
- Muscle MRI – T2 SITR to evaluate for muscle edema
- Muscle biopsy
Lesional Cutaneous Punch Biopsy
A common diagnostic procedure is a lesional cutaneous punch biopsy (skin biopsy). Skin biopsy may be helpful if findings from physical examinations are subtle or atypical.
Characteristic histologic findings in DM skin biopsies include vacuolar interface dermatitis with keratinocyte dyskeratosis, increased reticular dermal mucin, superficial dermal vascular dilatation, and variably dense perivascular lymphohistiocytic inflammation. The absence of vacuolar changes or increased dermal mucin in skin biopsies does not exclude a DM diagnosis. Correlation between histology and clinical findings is critical for an accurate diagnosis. Skin biopsy findings may be affected by treatment with glucocorticoids and/or immunomodulatory medications at time of biopsy.
Muscle Biopsy
Muscle biopsy can confirm the diagnosis of DM and to exclude other causes of muscle weakness. It should be obtained on weak muscles as identified by physical exam or ideally guided by Electromyography (EMG) findings or muscle Magnetic resonance imaging (MRI). Approximately 6% of DM patients have no or subtle skin involvement and may benefit from muscle biopsy. Muscle biopsy is invasive and is being used less due to the discovery of the predictive value of autoantibodies, serologic muscle inflammation markers, pathognomonic cutaneous manifestations, and cutaneous histologic features.
Muscle biopsy findings consistent with DM include:
- Perivascular and perimysial inflammatory infiltrate that consists of B cells, CD4+ T helper cells, macrophages, and plasmacytoid dendritic cells.
- Atrophy of muscle fibers (perifascicular atrophy), especially around fascicles, with degenerating and regenerating muscle fibers.
- Microangiopathy caused by Injury to intramuscular blood vessels on capillaries
- Complement deposition on endomysial capillaries
- Decreased capillary density
Muscle Enzymatic Markers
Muscle enzymatic markers are released into the serum when skeletal muscle is damaged, such as creatine phosphokinase (CK), aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), and aldolase.
- CK is the most sensitive and specific for skeletal muscle damage and can be elevated up to 50X the upper normal limit in 70–80% of CDM patients.
- Levels of aldolase tend to show a relatively higher increase compared to serum creatine kinase in patients with muscle involvement, likely due to the higher expression of aldolase in the fascia.
- Transaminase elevation levels are tightly correlated with CK levels during muscle injury, typically with AST > ALT. As CK and transaminase levels can be elevated in hepatic disorders and CK levels can be elevated in myocardial injury, evaluation of elevated gamma-glutamyl transferase (GGT) levels can help differentiate hepatic versus skeletal muscle CK origin.
- Evaluating elevated troponin I and/or pro-BNP levels may help determine cardiac origin.
If clinical features and/or serologic data concerning myositis remain ambiguous and there is a suspicion of DM, electromyography (EMG) may be considered. EMG may provide information supporting diagnosis in ~70-90% of cases of DM.
T2-weighted muscle magnetic resonance imaging (MRI) can identify areas of muscle edema in patients with normal or only mildly elevated muscle enzymes. It can also detect the presence of the fasciitis. T1-weighted MRI images can be used to detect fatty replacement or chronic damage in myositis.
Patients should be evaluated for lung disease at baseline and screened regularly for pulmonary symptoms linked to Interstitial lung disease (ILD) via lung function tests. At baseline, evaluation with pulmonary function tests with a diffusion capacity for carbon monoxide is needed. If findings are abnormal on pulmonary function tests, a high-resolution chest computed tomography scan should be performed. At each clinic visit, symptoms should be thoroughly reviewed, including cough, shortness of breath, dyspnea on exertion. Pulmonary function tests should be repeated every 3–12 months, depending on the initial findings and the risk of ILD in the patient.
Patients should undergo age-appropriate cancer screening exams such as pelvic exams, breast exams, testicular exams, and rectal exams to screen for malignancy.
Once a DM diagnosis is made, patients should be monitored for development of visceral organ involvement and malignancy, which contribute to the patient’s morbidity and mortality.
References
- Aggarwal, R., Schessl, J., Charles-Schoeman, C. et al. Safety and tolerability of intravenous immunoglobulin in patients with active dermatomyositis: results from the randomised, placebo-controlled ProDERM study. Arthritis Res Ther 26, 27 (2024).
- ArgenX Press Release. Argenx Advances Clinical Development of Efgartigimod SC in Idiopathic Inflammatory Myopathies. November 20, 2024. https://argenx.com/content/dam/argenx-corp/newsroom/press-release-pdfs/PressRelease_argenx_ALKIVIA_Ph2_20241120.pdf.coredownload.inline.pdf
