Laboratory Studies

Laboratory studies used in the workup for mixed connective-tissue disorder (MCTD) are as follows:

Complete blood cell count (CBC)
Urinalysis
Routine blood chemistry
Indicators of acute phase response (erythrocyte sedimentation rate [ESR] or C-reactive protein [CRP])
Muscle enzymes if myositis is suspected clinically
Antinuclear antibodies
Anti–U1-ribonucleoprotein (RNP) antibodies
Amylase and lipase - To assess for pancreatitis if clinically indicated
Serologic indicators of pulmonary hypertension (such as brain natriuretic peptide [BNP]) if clinically indicated

Antibody study results

High-titer speckled pattern fluorescent antinuclear antibody (FANA) is typical of MCTD. However, the presence of FANA is not specific to MCTD.

Anti-RNP antibodies are required for diagnosis of MCTD. Titers are typically high. The presence of anti–U1-70 kd is characteristic of MCTD but not specific.

MCTD can enter sustained remission later in the clinical course. Anti-RNP autoantibodies typically become undetectable in patients in remission.

Other immune studies

Further results are as follows:

Antiphospholipid antibodies (including anticardiolipin antibodies and lupus anticoagulant) may be associated with pulmonary hypertension
Rheumatoid factor is frequently detected
Other lupus-specific antibodies (eg, anti–double-stranded DNA antibodies) are typically absent
Scleroderma-specific antibodies, including anticentromere, anti–Scl-70 (topoisomerase), and anti–PM-1 (Pm-Scl), are typically absent
C3 and C4 complement levels are more likely to be depleted in lupus than in MCTD

Imaging Studies

Imaging studies used in the workup of patients with MCTD include the following:

Chest radiography - To assess for infiltrates, effusion, or cardiomegaly (see the image below)
Echocardiography - In patients with effusion or chest pain, used to evaluate for pulmonary hypertension or valvular disease (exercise echocardiography may have increased sensitivity for identifying pulmonary hypertension)^[35]
Ultrasonography/CT scanning - Used to evaluate abdominal pain (indicated for evidence of serositis, pancreatitis, or visceral perforation related to vasculitis)
MRI - Used to assess neuropsychiatric signs or symptoms

Chest radiograph in a patient with pulmonary hypertension reveals enlarged pulmonary arteries.

View Media Gallery

Other Tests

The following tests may be part of the workup for MCTD:

Pulmonary function testing is used to screen for declining diffusing capacity of lung for carbon monoxide (DLCO), possibly indicating pulmonary hypertension, ^[36] or to assess lung volumes and forced vital capacity to screen for suspicion/progression of interstitial lung disease.
Electrocardiogram and/or cardiac enzymes is helpful to assess for myocardial ischemia and myocarditis.
Infection, stroke, or neuropsychiatric manifestations may be monitored with cerebrospinal fluid (CFS) analysis.
The six-minute walk can be helpful to assess for cardiopulmonary insufficiency, possibly indicating pulmonary hypertension. ^[37]
Right-sided heart catheterization is the criterion standard for confirming the diagnosis of pulmonary hypertension

Treatment & Management

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Media Gallery

Raynaud phenomenon is a common feature of mixed connective tissue disease.
Chest radiograph in a patient with pulmonary hypertension reveals enlarged pulmonary arteries.

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Author

Eric L Greidinger, MD Associate Professor, Department of Medicine, Division of Rheumatology and Immunology, University of Miami, Leonard M Miller School of Medicine, Miami Veterans Affairs Medical Center

Eric L Greidinger, MD is a member of the following medical societies: American College of Physicians, American College of Rheumatology

Disclosure: Received research grant from: Corbus Pharmaceuticals; Eli Lilly & Company; Horizon Pharmaceuticals; INFLARX GBMH, Mitsubishi Pharmaceuticals, Reatta Pharmaceuticals, Swedish Orphan Biovitrum AB.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Elliot Goldberg, MD Dean of the Western Pennsylvania Clinical Campus, Professor, Department of Medicine, Lewis Katz School of Medicine at Temple University

Elliot Goldberg, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians, American College of Rheumatology

Disclosure: Nothing to disclose.

Chief Editor

Herbert S Diamond, MD Visiting Professor of Medicine, Division of Rheumatology, State University of New York Downstate Medical Center; Chairman Emeritus, Department of Internal Medicine, Western Pennsylvania Hospital

Herbert S Diamond, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians, American College of Rheumatology, American Medical Association, Phi Beta Kappa

Disclosure: Nothing to disclose.

Additional Contributors

Bryan L Martin, DO Associate Dean for Graduate Medical Education, Designated Institutional Official, Associate Medical Director, Director, Allergy Immunology Program, Professor of Medicine and Pediatrics, Ohio State University College of Medicine

Bryan L Martin, DO is a member of the following medical societies: American Academy of Allergy Asthma and Immunology, American College of Allergy, Asthma and Immunology, American College of Osteopathic Internists, American College of Physicians, American Medical Association, American Osteopathic Association

Disclosure: Nothing to disclose.

Acknowledgements

Robert W Hoffman, DO, FACP, FACR Chief, Division of Rheumatology and Immunology, Professor, Departments of Medicine and Microbiology & Immunology, University of Miami, Leonard M Miller School of Medicine

Robert W Hoffman, DO, FACP, FACR is a member of the following medical societies: American Association for the Advancement of Science, American Association of Immunologists, American College of Physicians, American College of Rheumatology, and Clinical Immunology Society

Disclosure: Nothing to disclose.