Approach
Assessment of patients with suspected idiopathic inflammatory myopathy (IIM) begins with detailed history taking and physical examination followed by a careful selection of investigations.
History
The patient history should include questions which assess the presence of symptoms suggesting:[2]
Proximal weakness (difficulties in performing activities such as combing hair, reaching out for overhead objects, getting up from chair, and climbing stairs)
Distal weakness (difficulties in writing, knitting, and sewing)
Truncal weakness (difficulties in turning in bed and sitting up)
Neck weakness (difficulty in lifting head up)
Frequent falls
Patients with all IIM-subtypes except sporadic inclusion body myositis experience symptoms of symmetrical proximal weakness at disease onset before developing global weakness at later stages of disease.[2] In contrast, patients with inclusion body myositis develop distal weakness early. In addition, patients with inclusion body myositis often report frequent falls as a result of early quadriceps involvement.[72] Myalgia may occur in patients with immune-mediated necrotising myopathy.[73]
In addition to determining the pattern of weakness, the following information should also be obtained:[2]
Acuity of weakness
Chronic (usually more than 1 year) in inclusion body myositis
Acute to subacute onset in other IIM-subtypes
Presence of triggers (e.g., drugs, toxins, infections)
Other causes such as metabolic and endocrine
Subsequent history taking should focus on determining presence of extramuscular involvement. These should include:[2][74]
Presence of dysphagia and dysphonia. Assess for aspiration pneumonia resulting from dysphagia
Skin involvement with typical dermatomyositis rash
Some patients with IIM (e.g., anti-synthetase syndrome and anti-MDA5 disease) only present with typical dermatomyositis rash but do not experience any symptoms of weakness or raised serum creatine kinase.
Mechanics hands and other rashes on hands are often misdiagnosed as contact dermatitis.
Interstitial lung disease symptoms; for example, dry cough, breathlessness, and reduced effort tolerance
Cardiac involvement; for example, chest pain, palpitations, reduced effort tolerance, heart failure symptoms
Peripheral joint pain, swelling and early morning stiffness suggesting joint involvement
Raynaud’s phenomenon
Constitutional symptoms such as fever and weight loss
Presence of other connective tissue disease symptoms
Screening for malignancy. Questions should include unintentional weight loss, family history of cancer, smoking, unexplained fever, and night sweats
Other relevant history such as personal medical history and family history should also be obtained.
Physical examination
Each IIM-subtype has a unique pattern of muscle and extramuscular involvement. Physical examination of patients suspected of having IIM should therefore cover the following areas:
Manual muscle strength testing
Skin involvement
Targeted systemic examination
Manual muscle strength testing
The following should be assessed when performing muscle strength testing :
Symmetry of muscle involvement
Muscle group(s) involved (e.g., proximal vs. distal)
The degree of strength in each muscle group
The degree of muscle strength can be determined using either the Medical Research Council or Kendall scale.[75][76]
The strength of the following muscle groups should be tested:[77]
Deltoid
Biceps
Wrist extensors
Quadriceps
Ankle dorsiflexors
Neck flexors
Gluteus medius
Gluteus maximus
While the pathognomonic feature of IIM is symmetrical proximal weakness, there are exceptions to this rule.
Inclusion body myositis. The pattern of muscle weakness may be asymmetrical, with early quadriceps weakness.[77] Finger/wrist flexors, and knee extensors are more predominantly affected.[78] Mild facial weakness sparing extra-ocular muscles may occur in up to 60% of patients.[27] This is seen to a lesser extent in other IIM-subtypes. Later in the disease, all muscle groups can eventually become affected.
Clinically amyopathic dermatomyositis. Some IIM patients (e.g., anti-synthetase syndrome and anti-MDA5 disease) only present with typical dermatomyositis rash but do not experience any symptoms of weakness, exhibit any weakness on muscle strength testing or raised serum creatine kinase.[2]
Presence of extra-ocular muscle weakness is unlikely in IIM and should probe evaluation for other causes.
Skin involvement
The characteristic skin lesions seen in patients with IIM are:[4][72][77][79]
Periorbital violaceous erythema often associated with oedema (heliotrope rash)
Erythematous to violaceous papules (Gottron papules) and macules (Gottron sign) overlying extensor surfaces of joints
Periungual nail fold erythema with cuticular punctate haemorrhage
Erythema over lower anterior neck and upper chest (V sign)
Erythema over posterior shoulders, neck, and upper back (shawl sign)
Poikiloderma - concurrence of hyperpigmentation, hypopigmentation, telangiectasia, and superficial atrophy
Ulcerations over joints and palmar papules (especially in anti-MDA5 dermatomyositis)
Non-pruritic, hyperkeratotic eruptions on the lateral surfaces of digits (mechanic’s hands) which is a hallmark feature in anti-synthetase syndrome patients
Calcinosis in juvenile dermatomyositis patients, particularly in association with positive anti-NXP2 and anti-TIF1gamma
Targeted systemic examination
Patients should be assessed for the presence of dysphagia caused by muscle weakness in the pharyngeal muscles or in the upper portion of the oesophagus.[4]
The presence of arthritis is common in patients with IIM, particularly in those with anti-synthetase syndrome. Targeted systemic examination usually finds symmetrical involvement of the small joints of the hands, which can be mistaken for rheumatoid arthritis.[4]
Cardiac and respiratory system examinations should be performed to assess for the presence of interstitial lung disease, cardiac involvement, and signs of cardio-respiratory failure. Patients with anti-MDA5 antibody positive dermatomyositis with rapidly progressive interstitial lung disease can develop into adult respiratory distress syndrome and respiratory failure which carry a poor prognosis.[4][79]
The presence of abnormalities suggestive of malignancy should be assessed with focused examinations that include abdominal/pelvic, breast and lymph node (cervical/axillary/inguinal), and posterior nasal space for nasopharyngeal carcinoma.[74][80]
Initial investigations
Investigations for IIM consist of laboratory, serological, biological tests, imaging studies, and muscle biopsy.[72][77]
Laboratory tests
Muscle-derived enzymes:[1][4][77]
Serum creatine kinase is the most sensitive diagnostic and monitoring marker, although its levels can be normal in some patients with IIM. Creatine kinase can rise up to 50 times the upper normal limit in polymyositis, dermatomyositis, overlap myositis, and anti-synthetase syndrome. In patients with immune-mediated necrotising myopathy creatine kinase levels can be markedly elevated at up to 100 times the upper normal limit, but creatine kinase levels tend to be normal or mildly raised at no more than 10 times the upper normal limit in patients with inclusion body myositis. It is important to note that serum creatine kinase can also be raised in patients with rhabdomyolysis, infections, toxin-related myopathy, metabolic diseases, neurogenic myopathy, and congenital myopathy which therefore have to be carefully excluded.
Lactate dehydrogenase, aldolase, myoglobin, and aspartate aminotransferase and alanine aminotransferase may also be elevated, but they are less specific for muscle injury. Rarely, serum aldolase levels are selectively increased without creatine kinase level elevation.
Erythrocyte sedimentation rate may be elevated with concurrent arthritis, serositis, or infection, but it is less commonly elevated in patients with only myositis.
Serological tests for autoantibodies
Myositis-specific antibodies (MSA)/myositis-associated antibodies (MAA):
MSAs/MAAs are found in up to 70% of patients with IIM.[4][6]
Immunoprecipitation is the gold-standard for MSA/MAA testing, but it is too time consuming to be considered suitable for routine testing. Other available tests (e.g., enzyme-linked immunosorbent assay, addressable laser bead immunoassay, and immunoblotting techniques) do not detect the full repertoire of MSAs, show variable results in terms of performance, and lack a standardised approach.[4][6]
The majority of MSAs will yield a positive anti-nuclear antibody test but the staining pattern on indirect immunofluorescence is not distinctive enough to confirm the antibody specificity. Certain MSAs (especially those associated with anti-synthetase syndrome) can yield a negative or only weakly positive ANA test.[6]
Anti-mitochondrial autoantibodies (AMA) may be found in a small percentage of adults with dermatomyositis, polymyositis, and inclusion body myositis. In these AMA positive patients, Raynaud’s phenomenon, dysphagia, cardiomyopathy, and more severe IIM disease were reported. However, AMA has not been formally recognised as an MSA or MAA at present.[6]
Autoantibodies associated with other connective tissue diseases such as systemic lupus erythematosus and systemic sclerosis, relevant associated autoantibodies can also be performed depending on the clinical context in patients with IMM with clinical features of other connective tissue disease.[6] See Systemic lupus erythematosus and Systemic sclerosis.
Biomarkers for IIM
Several biomarkers associated with disease severity assessment and prognostication for specific IIM-subtypes (particularly anti-MDA5 dermatomyositis) have been suggested. These include ferritin, neutrophil-to-lymphocyte ratio, peripheral lymphocyte count, IL-6, and Krebs von den Lungen 6 (KL6).[79]
Potential imaging studies for patients with IIM include electromyography, magnetic resonance imaging, and muscle ultrasound.[77]
Electromyography (EMG)
EMG is performed to confirm the myopathic pattern of the disorder and for the exclusion of a primary neurogenic disorder.
Typical EMG recordings include:
Myopathic motor unit potentials characterised by early recruitment
Short duration and low amplitude polyphasic motor units on voluntary activation
Increased spontaneous activity at rest
These abnormalities are not specific for IIM; they may be seen in a variety of myopathies and only in the acute phase of the disease.[77]
Magnetic resonance imaging (MRI)
MRI, usually of the thighs, is performed to assess extent of muscle inflammation, presence of muscle atrophy, and muscle fatty replacement. If there is any doubt about the most appropriate site for muscle biopsy, an MRI may help to determine the best site, either at the initial stage or for any subsequent biopsies.[72][81] Muscle inflammation is indicated when high signal uptake is observed on T2 fat suppression and short-tau inversion recovery (STIR) images representing muscle oedema, or T1 images show fatty infiltration as high signal uptake, indicative of chronic injury.[2]
Muscle ultrasound
Muscle ultrasound is an easily available imaging technique to assess patients with IIM. It has high sensitivity for the detection of biopsy proven IIM, with high positive and negative predictive values when performed by an experienced practitioner. Result may include the following:[2]
Acute IIM - mild 'see through' echogenicity with normal or increased muscle bulk, likely indicative of oedema.
Chronic IIM - the muscle appears more atrophied (increased echogenicity with reduced bulk)
Dermatomyositis - fascial thickness, indicative of fasciitis, is increased
Inclusion body myositis - higher echogenicity is seen in the flexor digitorum profundus compared to flexor carpi ulnaris, known as the ‘FDP-FCU echogenicity contrast'
Muscle biopsy
Muscle biopsy can be used to confirm muscle inflammation, identify the subtype of IIM, and exclude other potential causes of myopathy.[72][77]
Investigations for extramuscular manifestations
Extramuscular manifestations for patients with IIM may involve the lungs, heart, and increased risk of malignancy.[58] If extramuscular manifestations are suspected, investigations may include the following depending on presentation of symptoms:[2][58][74][82]
Lungs - interstitial lung disease:
High-resolution computed tomography (HRCT) of lungs
Pulmonary function test
Diffusion capacity
Heart - cardiac involvement:
Troponins
Electrocardiography
Echocardiography
Cardiac MRI
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