eMedicine Specialties > Rheumatology > Systemic Rheumatic Disease

Mixed Connective-Tissue Disease: Differential Diagnoses & Workup

Author: Robert W Hoffman, DO, FACP, FACR, Chief, Division of Rheumatology and Immunology, Professor, Departments of Medicine and Microbiology & Immunology, University of Miami
Coauthor(s): Eric L Greidinger, MD, Associate Professor, Department of Medicine, Division of Rheumatology and Immunology, University of Miami Miller School of Medicine, Miami Veterans Affairs Medical Center
Contributor Information and Disclosures

Updated: Aug 7, 2008

Differential Diagnoses

Dermatomyositis
Rheumatoid Arthritis
Polymyositis
Scleroderma
Pulmonary Hypertension, Primary
Sepsis, Bacterial
Raynaud Phenomenon
Systemic Lupus Erythematosus

Other Problems to Be Considered

Pleuritis
Respiratory distress syndrome
Stroke

Workup

Laboratory Studies

  • CBC count
  • Urinalysis
  • Routine blood chemistry
  • Muscle enzymes if myositis is suspected clinically
  • Antinuclear antibodies
    • High-titer speckled pattern fluorescent antinuclear antibody (FANA) is typical of mixed connective-tissue disease (MCTD).
    • FANA is not specific to MCTD.
  • High titers of anti–U1-RNP antibodies
    • Anti-RNP antibodies are required for diagnosis of MCTD.
    • The presence of anti–U1-70 kd is characteristic of MCTD.
  • Other immune studies
    • Antiphospholipid antibodies (including anticardiolipin antibodies and lupus anticoagulant) may be associated with pulmonary hypertension. In MCTD, however, the presence of these antibodies has not been associated with clotting events.
    • Rheumatoid factor is frequently detected.
    • Other lupus-specific antibodies (eg, anti–double-stranded DNA antibodies) are absent.
    • Scleroderma-specific antibodies, including anticentromere, anti–Scl-70 (topoisomerase), and anti–PM-1 (Pm-Scl), are absent.
    • C3 and C4 complement levels are more likely to be depleted in lupus than in MCTD
  • Amylase and lipase - To assess for pancreatitis if clinically indicated

Imaging Studies

  • Chest radiography - To assess for infiltrates, effusion, or cardiomegaly
  • Echocardiography - Used to evaluate for effusion, chest pain, pulmonary hypertension, or valvular disease (An exercise echocardiography may increase the sensitivity to identify pulmonary hypertension.)
  • 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

Other Tests

  • Pulmonary function testing - To screen for declining diffusing capacity of lung for carbon monoxide (DLCO), possibly indicating pulmonary hypertension
  • ECG and/or cardiac enzymes - To assess for myocardial ischemia and myocarditis
  • Cerebral spinal fluid (CFS) analysis - To monitor for infection, stroke, or neuropsychiatric manifestations
  • Six-minute walk - To assess for cardiopulmonary insufficiency, possibly indicating pulmonary hypertension

Procedures

  • Right-sided heart catheterization is the criterion standard for diagnosis of pulmonary hypertension.

Staging

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

More on Mixed Connective-Tissue Disease

Overview: Mixed Connective-Tissue Disease
Differential Diagnoses & Workup: Mixed Connective-Tissue Disease
Treatment & Medication: Mixed Connective-Tissue Disease
Follow-up: Mixed Connective-Tissue Disease
References
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References

  1. Sharp GC, Irvin WS, Tan EM, et al. Mixed connective tissue disease--an apparently distinct rheumatic disease syndrome associated with a specific antibody to an extractable nuclear antigen (ENA). Am J Med. Feb 1972;52(2):148-59. [Medline].

  2. Hoffman RW, Rettenmaier LJ, Takeda Y, et al. Human autoantibodies against the 70-kd polypeptide of U1 small nuclear RNP are associated with HLA-DR4 among connective tissue disease patients. Arthritis Rheum. May 1990;33(5):666-73. [Medline].

  3. Burdt MA, Hoffman RW, Deutscher SL, et al. Long-term outcome in mixed connective tissue disease: longitudinal clinical and serologic findings. Arthritis Rheum. May 1999;42(5):899-909. [Medline].

  4. Jais X, Launay D, Yaici A, et al. Immunosuppressive therapy in lupus- and mixed connective tissue disease-associated pulmonary arterial hypertension: a retrospective analysis of twenty-three cases. Arthritis Rheum. Feb 2008;58(2):521-31. [Medline].

  5. Alarcon-Segovia D, Villareal M. Classification and diagnostic criteria for mixed connective tissue disease. In: Kasukawa R, Sharp GC, eds. Mixed Connective Tissue Disease and Anti-Nuclear Antibodies. Amsterdam: Excerpta Medica; 1987:33-40.

  6. Greidinger EL, Zang Y, Jaimes K, et al. A murine model of mixed connective tissue disease induced with U1 small nuclear RNP autoantigen. Arthritis Rheum. Feb 2006;54(2):661-9. [Medline].

  7. Hoffman RW. Undifferentiated and mixed connective tissue disease. In: Wallace D, Hahn B, eds. Dubois Systemic Lupus Erythematosus. Lippincott, P: In press.

  8. Hoffman RW. Mixed connective tissue disease, overlap syndromes and Sjogren's syndrome. In: Lahita RG, ed. Systemic Lupus Erythematosus. 4th ed. San Diego, Calif: Academic Press; 2004.

  9. Hoffman RW. T cells in the pathogenesis of systemic lupus erythematosus. Clin Immunol. Oct 2004;113(1):4-13. [Medline].

  10. Hoffman RW, Cassidy JT, Takeda Y, et al. U1-70-kd autoantibody-positive mixed connective tissue disease in children. A longitudinal clinical and serologic analysis. Arthritis Rheum. Nov 1993;36(11):1599-602. [Medline].

  11. Hoffman RW, Greidinger EL. Mixed connective tissue disease. Curr Opin Rheumatol. Sep 2000;12(5):386-90. [Medline].

  12. Maldonado ME, Perez M, Pignac-Kobinger J, et al. Clinical and immunologic manifestations of mixed connective tissue disease in a Miami population compared to a Midwestern US Caucasian population. J Rheumatol. Mar 2008;35(3):429-37. [Medline].

  13. Perkins K, Hoffman RW, Bezruczko N. A Rasch analysis for classification of systemic lupus erythematosus and mixed connective tissue disease. J Appl Meas. 2008;9(2):136-50. [Medline].

  14. Smolen JS, Steiner G. Mixed connective tissue disease: to be or not to be?. Arthritis Rheum. May 1998;41(5):768-77. [Medline].

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Further Reading

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Keywords

mixed connective-tissue disease, MCTD, arthritis, arthralgia, esophageal reflux, secondary pulmonary hypertension, Raynaud phenomenon, systemic lupus erythematosus, SLE, scleroderma, myositis, anti–U1-ribonucleoprotein, anti–U1-RNP, acrosclerosis, esophageal dysmotility, myositis, rheumatic disease, antibodies against U1-70 kd, small nuclear ribonucleoprotein, snRNP

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Contributor Information and Disclosures

Author

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

Coauthor(s)

Eric L Greidinger, MD, Associate Professor, Department of Medicine, Division of Rheumatology and Immunology, University of Miami 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 and American College of Rheumatology
Disclosure: Nothing to disclose.

Medical Editor

Bryan L Martin, DO, Chief, Allergy Immunology Department, Walter Reed Army Medical Center; Associate Professor of Medicine and Pediatrics, Uniformed Services University of the Health Sciences; United States Army Consultant in Allergy Immunology and Immunizations
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, and American Osteopathic Association
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: Nothing to disclose.

Managing Editor

Elliot Goldberg, MD, Dean of the Western Pennsylvania Clinical Campus, Professor, Department of Medicine, Temple University School of Medicine
Elliot Goldberg, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians, and American College of Rheumatology
Disclosure: Nothing to disclose.

CME Editor

Alex J Mechaber, MD, FACP, Assistant Dean for Medical Curriculum, Associate Professor of Medicine, Division of General Internal Medicine, University of Miami Miller School of Medicine
Alex J Mechaber, MD, FACP is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians-American Society of Internal Medicine, and Society of General Internal Medicine
Disclosure: Nothing to disclose.

Chief Editor

Herbert S Diamond, MD, Professor of Medicine, Temple University School of Medicine; 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, and Phi Beta Kappa
Disclosure: medifocus Honoraria Review panel membership; health dialogs Honoraria Consulting; Merck, Amgen, Biogen, Zimmer, Wyeth, Johnson&Johnson, Stryker, Medtronic, Zimmer.Abbott,  Ownership interest Other; West Penn Allegheny Health System Consulting fee Consulting; Alpharma Honoraria Consulting; Proctor&Gamble Grant/research funds Independent contractor

 
 
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