Pediatric Mixed Connective Tissue Disease Workup

Updated: Jul 23, 2021
  • Author: Marisa S Klein-Gitelman, MD, MPH; Chief Editor: Lawrence K Jung, MD  more...
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Laboratory Studies

The initial laboratory evaluation of mixed connective tissue disease (MCTD) should include the following:

  • Complete blood cell (CBC) count with platelets and reticulocyte count: Leukopenia, thrombocytopenia, and hemolytic anemia are common findings. If the patient has a combination of these findings, carefully consider the possibility of leukemia.

  • Complete chemistry panel to evaluate electrolytes, liver, and kidney function

    • Unsuspected autoimmune hepatitis may be found based on elevated liver function test (LFT) results.

    • Patients with nephritis may have elevated creatinine and abnormal electrolyte levels.

    • Patients with nephrosis may have low albumin and high cholesterol levels.

  • Urine analysis

    • Patients with mixed connective tissue disease and nephritis may have protein, red blood cells (RBCs), white blood cells (WBCs), or casts on evaluation of urine.

    • Patients with nephrotic syndrome have high urinary protein levels.

  • Muscle enzymes: Myositis may be found by measurement of creatine kinase, aldolase, aspartate aminotransferase, alanine aminotransferase, and lactic dehydrogenase levels.

  • Acute phase reactants: Measure acute phase reactants with erythrocyte sedimentation rate or C-reactive protein.

Diagnostic laboratory studies include the following:

  • Antinuclear antibody: This test result is usually positive in high titers. [15]

  • Anti–double-stranded DNA: This test result is usually negative but is occasionally positive in individuals with mixed connective tissue disease.

  • Autoantibody panel, including antibodies against ribonucleoprotein (RNP), Smith, Ro(SSA), La(SSB), Scl-70, phospholipids, cardiolipin and histone, total hemolytic complement, C3, C4, quantitative immunoglobulins, and thyroid studies

    • Other than anti-RNP and anti-Sm, these laboratory test findings may be positive or negative depending on the characteristics of the individual patient's disease.

    • By definition, anti-RNP should be positive, and anti-Sm should be negative. Anti-Sm and anti-RNP antibodies can be measured by double diffusion, counterimmunoelectrophoresis, passive hemagglutination, and enzyme immunoassay. The double diffusion assay uses crude antigens, and positivity is based on the identity of precipitation lines for test standard and test sera. This test is specific but not sensitive.

    • Purified Sm proteins are available for testing; however, RNP antigen has not been separated from Sm and is detected as a complex.

    • Counterimmunoelectrophoresis and passive hemagglutination improve the ability to distinguish anti-Sm from anti-RNP by modifying the antigen extract.

    • The antigen for anti-Sm antibodies is treated with RNase, removing RNP from the preparation.

    • A decrease in titer of approximately 5 tubes (or more) dilution from before and after RNase digestion is characteristic of mixed connective tissue disease sera.

    • The antigens in the enzyme immunoassay are prepared by immunoaffinity chromatography using human autoantibodies and murine monoclonal antibodies to separate Sm from the RNP/Sm antigen complex and are sensitive to detecting anti-RNP antibodies.

  • Thyroid studies (thyroid stimulating hormone [TSH], free T4, thyroid autoantibody screen). In one study of 1517 adult patients with rheumatic diseases, 21% of the patients with mixed connective tissue disease had Hashimoto thyroiditis, and 2.5% had Graves disease, with prevalence rates 556- and 76-fold higher than the general population, respectively.


Imaging Studies

Initial imaging studies should include the following:

  • Chest radiography should be performed.

  • Barium swallow should be performed to evaluate esophageal motility.

  • Echocardiography should be performed to evaluate myocardial and valvular function and to obtain an estimate of pulmonary artery pressure. Obtain baseline echocardiogram to look for evidence of myocarditis, valvulitis, and pulmonary hypertension. Of particular importance, monitor for pulmonary hypertension over time. Early diagnosis may lead to better response to treatments with corticosteroids. Currently, the use of sildenafil is under investigation to determine therapeutic benefit.

In addition to chest radiography, pulmonary function tests, and clinical symptoms, high-resolution CT scan of the lung may be necessary to determine if pulmonary fibrosis exists. The presence of interstitial lung disease is often missed. [16] Screening for this problem is important as it is more readily treated early in the disease course.

Other imaging studies should be guided by clinical manifestations and may include the following:

  • Brain MRI

  • Renal ultrasonography, nuclear medicine evaluation of renal function, or both

  • Plain films to evaluate arthritis

Inhaled aerosol clearance times of Tc 99m–labeled diethylene-triamine penta-acetate (Tc 99m–DTPA) should be obtained to evaluate pulmonary interstitial fibrosis and improvement after treatment.


Other Tests

Obtain baseline pulmonary function tests, including diffusing capacity of lung for carbon monoxide.

Nailfold capillaroscopy can be helpful because it is associated with mixed connective tissue disease, particularly in patients who have more scleroderma features. [17, 18, 19]

Echocardiography should be considered because patients may have unexpected pulmonary artery hypertension, which should be monitored and treated.



Perform tissue biopsy as indicated to evaluate disease severity.

In particular, kidney biopsy should be considered when hypocomplementemia is present, even if initial urine evaluations are negative, because some studies suggest that patients with mixed connective tissue disease can have nonclinical nephritis.

Histologic findings

No specific histologic findings aid in the diagnosis of mixed connective tissue disease as a separate autoimmune disease. For example, nephritis in mixed connective tissue disease is usually indistinguishable from lupus nephritis.


Mixed connective tissue disease is not staged.