Dermatologic Manifestations of Mixed Connective Tissue Disease Workup

Updated: Apr 06, 2021
  • Author: Robert A Schwartz, MD, MPH; Chief Editor: William D James, MD  more...
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Laboratory Studies

Abnormal laboratory results are dependent on the spectrum of connective tissue disease symptoms, which can be similar to those recognized in systemic lupus erythematosus, systemic sclerosis (SSc), dermatomyositis, and polymyositis. For example, antiphospholipid antibodies were documented in 13.3% of patients with mixed connective-tissue disease (MCTD) in one survey. [35]

The complete blood cell count may reveal the following:

  • Anemia

  • Thrombocytopenia (unusual in adults but may be marked in children)

  • Decreased white blood cell count

Urine analysis may be helpful in detecting the following:

  • Proteinuria

  • Hematuria

An assessment of kidney function may show the following results:

  • Elevated creatinine level

  • Elevated urea level

Muscle enzyme tests may demonstrate the following:

  • Elevated aldolase level

  • Elevated creatine kinase (CK) level: CK is an enzyme in muscle cells that may be released into blood stream upon damage of myocytes. CK consists of 3 isoenzymes designated MM, MB, and BB. Adult skeletal muscle contains mainly CK-MM, cardiac muscle CK-MB, and smooth muscle CK-BB.

Tests for myocarditis may reveal elevated cardiac isoform troponin-I (cTnI) levels, which has the highest specificity for cardiac muscle and is the most reliable serum marker for detection of myocardial damage in patients with inflammatory muscle disease.

The erythrocyte sedimentation rate may be increased.

Hypergammaglobulinemia may be present.


Imaging Studies

Radiologic, manometric, videoendoscopic, and scintigraphic examination may reveal abnormal esophageal motility. Technetium Tc 99m-pyrophosphate scintigraphy permits detection of left ventricular global and regional wall abnormalities. Gadolinium diethylenetriaminepentaacetic–enhanced MRI is used to distinguish active myocardial inflammation from myocardial damage in humans with myocarditis with viral infections, sarcoidosis, or ischemic myocardial damage.

Chest x-ray films may show pleural thickening, fibrosis, and pericarditis.

Echocardiography can reveal pericarditis.

Angiography shows obstruction of the small blood vessels in some cases. [36]


Other Tests

Electromyography findings can reveal muscle destruction.

ECG is the basic method to detect arrhythmias, conduction defects, and ST-T changes.

Immunologic findings may be helpful in diagnosing mixed connective-tissue disease (MCTD).

Screening for connective-tissue disease–associated antibodies can be accomplished using an automated immunoassay. [37] An immunoassay that detects antibodies to a mixture of 17 antigens is an alternative to indirect immunofluorescence; combining them is best.

The presence of a high titer of immunoglobulin G antibodies against U1-ribonucleoprotein (RNP) as the only autoantibodies strongly supports a diagnosis of MCTD. These antibodies are directed against small ribonucleoproteins, which are referred to as extractable nuclear antigens. [38] The fluorescent antinuclear antibody test typically reveals a speckled pattern of staining on HEp-2 substrate. More sophisticated analysis identifies the target protein as the 68- to 70-kd U1-RNP complex. Recent studies revealed that antibodies directed to an apoptotic-specific epitope on 70K are more specifically associated with MCTD than other anti-70K antibodies. [39] Other antibodies such as dsDNA, anti-Ro/SS-A, and anti-La/SS-B occur incidentally. [40]

See the image below.

Indirect immunofluorescence testing shows the typi Indirect immunofluorescence testing shows the typical speckled pattern for ribonucleoprotein antibodies on a HEp-2 substrate.

Direct immunofluorescence: Performed on lesional skin of patients with MCTD, this may reveal epidermal nuclear immunoglobulin G staining. This staining is thought to be related to the high titers of U1-RNP antibodies in the patient's sera. In some cases, the lupus band test might be positive, with linear deposits of immunoglobulins, fibrin, and/or complement components present at the basement membrane. Immunoglobulin M is usually the main compound.

See the image below.

Direct immunofluorescence testing shows epidermal Direct immunofluorescence testing shows epidermal nuclear immunoglobulin G staining.

Pulmonary function testing may reveal ventilator disorders of the restrictive type, such as diminished vital capacity, normal residual volume, and total lung capacity. Respiratory function tests are usually consistent with radiographic findings (see Imaging Studies).


Histologic Findings

The histologic findings in mixed connective-tissue disease (MCTD) are not conclusive.