Tests
1st tests to order
CBC
Test
Leukopenia, thrombocytopenia, and anemia of chronic disease seen in 50% to 75% of patients with mixed connective tissue disease (MCTD).
Not specific for MCTD; may be seen in other autoimmune conditions, including systemic lupus erythematosus, as well as in nonrheumatic diseases.
Result
variable; may show anemia, leukopenia
erythrocyte sedimentation rate
Test
Nonspecific marker; may be elevated due to an acute-phase response from any cause.
Result
elevated (nonspecific)
CRP
Test
Nonspecific marker; may be elevated due to an acute-phase response from any cause.
Result
elevated (nonspecific)
serum BUN and creatinine
Test
Renal insufficiency is a relatively uncommon manifestation of mixed connective tissue disease, but glomerulonephritis may occur, leading to renal dysfunction.
Rarely seen in other overlap syndromes.
Result
normal or elevated
rheumatoid factor
Test
If present, may indicate more classic rheumatoid arthritis.
Result
may be positive
antinuclear antibodies
Test
Appropriate initial test when the clinical evaluation reveals symptoms or signs suggesting underlying rheumatic disease.
Antinuclear antibody titers are seen in almost all patients with mixed connective tissue disease but are also present in other conditions such as systemic lupus erythematosus and scleroderma, and so are not diagnostic for an overlap syndrome.
Result
positive
anti-cyclic citrullinated peptide (anti-CCP) antibody
Test
May assist in the diagnosis of early rheumatoid arthritis, although can be elevated in overlap syndromes.
Result
may be positive
urinalysis
Test
Renal involvement in 25% of patients with mixed connective tissue disease (MCTD); rarely in other overlap syndromes.
In MCTD, focal proliferative glomerulonephritis is the most common cause. Rarely, membranous glomerulonephritis with nephrotic syndrome occurs.
Renal biopsy is indicated in patients with significant abnormalities on urinalysis and in some cases of declining renal function.
Result
variable; may show proteinuria, hematuria, occasional RBC casts
anti-U1 ribonucleoprotein
Test
Essential for the diagnosis of mixed connective tissue disease (MCTD). Anti-U1 ribonucleoprotein is typically present at positive or high titer positive levels in patients with classic MCTD, but may be borderline or negative in patients with undifferentiated connective tissue disease.
Result
may be positive
anti-Jo-1
Test
Anti-Jo-1 antibody is negative in patients with mixed connective tissue disease. When present, it is highly specific for antisynthetase syndrome. However, not all patients with myositis and lung involvement are positive for anti-Jo-1.
Result
may be positive
Tests to consider
creatine kinase
Test
Indicates underlying myositis as part of overlap syndrome.
Result
variable; may be elevated
anti-double-stranded DNA
Test
If positive, should suggest an alternative diagnosis of systemic lupus erythematosus rather than mixed connective tissue disease (MCTD). A subset of patients with MCTD may be positive for anti-double-stranded DNA.
Result
usually negative
Smith antigen
Test
If positive, should suggest alternative diagnosis of systemic lupus erythematosus rather than mixed connective tissue disease.
Result
negative
anti-SS-A and anti-SS-B
Test
If positive, should suggest an alternative diagnosis of primary Sjogren syndrome rather than mixed connective tissue disease (MCTD).
A subset of patients with MCTD may be positive for anti-SS-A and anti-SS-B and have secondary Sjogren syndrome.
Result
variable; usually negative
additional antibody tests (anti-Scl 70, anticentromere antibodies, anti-RNA polymerase III, anti-PM/Scl antibodies)
Test
May assist in the diagnosis of systemic sclerosis or polymyositis/scleroderma overlap syndrome but may also be positive in patients with overlap syndromes.
Result
may be positive
pulmonary function tests (spirometry, lung volumes and diffusion capacity measurement)
Test
Important to evaluate for restrictive lung disease and for pulmonary hypertension.
Should be done at onset followed by annual monitoring. If symptoms are progressing, should be done more frequently.
High-resolution CT scan of the chest should be done for declining lung volumes or functional status.
Referral to a pulmonologist and/or rheumatologist should be made if results are abnormal.
Result
interstitial lung disease: decrease in forced vital capacity (FVC) and diffusing capacity of the lung for carbon monoxide (DLCO) plus an overall restrictive pattern; pulmonary hypertension: disproportionate drop in DLCO compared with FVC
CXR
Test
Important to evaluate interstitial lung disease.
Should be done at onset if pulmonary function tests (PFTs) are abnormal and repeated if PFTs show a change.
High-resolution CT of the lungs is more sensitive than CXR for diagnosis of early interstitial lung disease and should therefore be performed if PFTs are abnormal or deteriorate.
Result
normal; evidence of interstitial lung disease demonstrated by bibasilar interstitial infiltrates; possibly cardiomegaly or signs of right-heart failure
high-resolution CT scan of chest
Test
Should be considered in those with abnormal pulmonary function tests indicative of restrictive lung disease.
May also be performed if lung volume or functional status declines.
This is a more sensitive test for the diagnosis of early interstitial lung disease than CXR, although CXR is often done initially.
Result
normal or evidence of interstitial lung disease demonstrated by ground-glass opacities (possible alveolitis), thickened interstitium (interstitial fibrosis); also traction bronchiectasis and honeycombing
echocardiogram
Test
Should be done at onset and yearly.
If symptoms are progressing, should be done more frequently.
Echo can estimate right ventricular systolic pressure (RVSP) based on tricuspid/pulmonic regurgitation jet.
Pleural effusions are generally small without hemodynamic compromise, but are a marker for poor prognosis.
Referral for right-heart catheterization and full evaluation should be done if RVSP is raised, as echo findings may not indicate true pulmonary artery pressures.
Result
pulmonary hypertension: rise in RVSP; pericardial effusion, right or left ventricular diastolic dysfunction may be present
right-heart catheterization
Test
The definitive diagnostic for pulmonary hemodynamic measurement and required to confirm presence of pulmonary hypertension, to establish specific diagnosis and determine severity of pulmonary hypertension.
Result
normal or mean pulmonary arterial pressure >25 mmHg at rest or >30 mmHg with exercise, with pulmonary capillary wedge pressure <15 mmHg and pulmonary vascular resistance >3 Wood units
barium swallow
Test
Can be helpful to look for features consistent with scleroderma, including dysmotility and reflux.
Should also be done if symptoms of heartburn worsen or do not improve with appropriate therapy.
Result
diminished esophageal peristalsis and gastroparesis; diminished muscle tone in lower esophagus, with reflux of barium; strictures
upper gastrointestinal endoscopy ± biopsy
Test
Indicated with new onset of dysphagia, to evaluate for stricture.
Needs to be performed with care due to possibility of esophageal stricture.
Result
esophageal inflammation, ulceration, strictures, Barrett metaplasia, adenocarcinoma may be present
plain x-ray of affected joint(s)
Test
Considered in patients with symptoms of arthralgia or arthritis.
Result
normal or may show inflammation, nonerosive arthritis; bony erosions
electromyography
Test
Indicated if weakness is present in the setting of elevated muscle enzymes and if diagnosis of inflammatory myositis is in question.
Identification of inflammatory myositis is important, as it requires treatment with immunosuppression.
Result
inflammatory myositis: abnormal with inflammatory features
nerve conduction studies
Test
Indicated if weakness is present in the setting of elevated muscle enzymes and if diagnosis of inflammatory myositis is in question.
Result
myopathic pattern
muscle biopsy
Test
Considered if inflammatory myositis is suspected.
Result
inflammatory myositis: abnormal with inflammatory features
lung biopsy
Test
Considered if interstitial lung disease is suspected.
Result
interstitial inflammation and fibrosis
renal biopsy
Test
Considered if immune-mediated glomerular disease is suspected.
Result
immune deposits, mesangial hypercellularity; focal, segmental, or global glomerulonephritis
Emerging tests
anti-Ku antibodies
Test
If positive, may suggest polymyositis/scleroderma (PM/Scl) overlap syndrome.
Result
variable; usually negative in mixed connective tissue disease
other antisynthetase antibodies (PL7, PL12, OJ, EJ, KS, Ha and others)
Test
May be present in antisynthetase syndromes, but are less common than anti-Jo1.
Result
variable; usually negative in mixed connective tissue disease, but highly specific for antisynthetase syndrome
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