Dermatologic Manifestations of Mixed Connective Tissue Disease 

  • Author: Robert A Schwartz, MD, MPH; Chief Editor: William D James, MD   more...
 
Updated: Apr 16, 2012
 

Background

Mixed connective-tissue disease (MCTD) is a disorder with features of systemic sclerosis (SSc), lupus erythematosus, and polymyositis. U1-ribonucleoprotein (RNP) antibodies are a specific marker of the disease. MCTD is considered a distinct syndrome and should not be confused with other connective-tissue disease overlap syndromes with features of various connective-tissue diseases.[1] The course of MCTD is chronic and usually milder than other connective-tissue diseases. Although MCTD is a distinct clinical entity, a subgroup of patients may evolve into having another connective-tissue disease.[2]

Next

Pathophysiology

A defining feature of mixed connective-tissue disease (MCTD) is the presence of antibodies against the U1-RNP complex, but other autoantibodies have also been described in MCTD. Some hypotheses implicate modified self-antigens and/or infectious agents in the pathogenesis of MCTD.

The U1 small nuclear ribonucleoprotein particle (snRNP) is a target of autoreactive B cells and T cells in MCTD.[3] Understanding the interactions between U1-snRNP and the immune system may prove beneficial.

The pathogenesis of MCTD is not completely known. As with other connective-tissue diseases, MCTD is considered an autoimmune disease to which individuals who express specific HLA antigens such as human leukocyte antigens (HLA) HLA-DR4 or HLA-DQB1 are genetically predisposed. The frequency of HLA-DR4 in patients with MCTD is estimated to be 52%. Its strong HLA association with MCTD was further shown in the significantly increased frequency of the combination of HLA-B15 with HLA-DR4. Thus, the genetic background in patients with MCTD seems to be different from that in patients with systemic lupus erythematosus (SLE) or systemic sclerosis. This observation could partly explain the clinical differences between these diseases. The specific nature of the HLA associations that occur in patients with MCTD may vary depending on the ethnicity of the population studied.

Previous
Next

Epidemiology

Frequency

International

Mixed connective-tissue disease (MCTD) is uncommon worldwide. The incidence of adult-onset mixed connective-tissue disease (MCTD) in Norway was found to be 2.1 per million per year.[4] It has a female predominance. Its incidence and prevalence is lower than for polymyositis, dermatomyositis, systemic sclerosis, and systemic lupus erythematosus.

Mortality/Morbidity

  • The prognosis for patients with mixed connective-tissue disease (MCTD) is generally better than that of patients with systemic lupus erythematosus, systemic sclerosis, and dermatomyositis.
  • About 4% of patients die, usually as a result of pulmonary hypertension, nephritis, myocarditis, or widespread vasculitis.
  • In one case series, solid tumors developed in approximately 10% of patients.

Sex

  • Women are affected by mixed connective-tissue disease (MCTD) more often than men.
  • The female-to-male ratio is 4:1.

Age

  • Mixed connective-tissue disease (MCTD) usually occurs in individuals aged 30-50 years.
  • MCTD also affects children, in whom the course is more severe because cardiac and renal involvement are more common.
  • MCTD-related thrombocytopenia, which is unusual in adults, may be marked in children.
Previous
Proceed to Clinical Presentation
 
 
Contributor Information and Disclosures
Author

Robert A Schwartz, MD, MPH  Professor and Head, Dermatology, Professor of Pathology, Pediatrics, Medicine, and Preventive Medicine and Community Health, University of Medicine and Dentistry of New Jersey-New Jersey Medical School

Robert A Schwartz, MD, MPH is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American College of Physicians, and Sigma Xi

Disclosure: Nothing to disclose.

Coauthor(s)

Anna Sysa-Jedrzejowska, MD, PhD  Head, Professor, Department of Dermatology and Venereology, Medical University of Lodz, Poland

Disclosure: Nothing to disclose.

Anna Wozniacka, MD, PhD  Adjunct Lecturer, Department of Dermatology, Medical University of Lodz, Poland

Anna Wozniacka, MD, PhD is a member of the following medical societies: European Academy of Dermatology and Venereology

Disclosure: Nothing to disclose.

Specialty Editor Board

Russell Hall, MD  J Lamar Callaway Professor And Chair, Department of Dermatology, Duke University Medical Center, Duke University School of Medicine

Russell Hall, MD is a member of the following medical societies: American Academy of Dermatology, American Dermatological Association, American Federation for Medical Research, American Society for Clinical Investigation, and Society for Investigative Dermatology

Disclosure: Genetech Grant/research funds Principle Investigator; Centecor Grant/research funds Principle Investigator; Vernallis Honoraria Consulting

Michael J Wells, MD  Associate Professor, Department of Dermatology, Texas Tech University Health Sciences Center, Paul L Foster School of Medicine

Michael J Wells, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Medical Association, and Texas Medical Association

Disclosure: Nothing to disclose.

Van Perry, MD  Assistant Professor, Department of Medicine, Division of Dermatology, University of Texas School of Medicine at San Antonio

Van Perry, MD is a member of the following medical societies: American Academy of Dermatology and American Society for Laser Medicine and Surgery

Disclosure: Nothing to disclose.

Glen H Crawford, MD  Assistant Clinical Professor, Department of Dermatology, University of Pennsylvania School of Medicine; Chief, Division of Dermatology, The Pennsylvania Hospital

Glen H Crawford, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Medical Association, Phi Beta Kappa, and Society of USAF Flight Surgeons

Disclosure: Nothing to disclose.

Chief Editor

William D James, MD  Paul R Gross Professor of Dermatology, Vice-Chairman, Residency Program Director, Department of Dermatology, University of Pennsylvania School of Medicine

William D James, MD is a member of the following medical societies: American Academy of Dermatology and Society for Investigative Dermatology

Disclosure: Elsevier Royalty Other

References

  1. Aringer M, Steiner G, Smolen JS. Does mixed connective tissue disease exist? Yes. Rheum Dis Clin North Am. Aug 2005;31(3):411-20, v. [Medline].

  2. Cappelli S, Bellando Randone S, Martinovic D, Tamas MM, Pasalic K, Allanore Y, et al. "To be or not to be," ten years after: evidence for mixed connective tissue disease as a distinct entity. Semin Arthritis Rheum. Feb 2012;41(4):589-98. [Medline].

  3. Kattah NH, Kattah MG, Utz PJ. The U1-snRNP complex: structural properties relating to autoimmune pathogenesis in rheumatic diseases. Immunol Rev. Jan 2010;233(1):126-45. [Medline].

  4. Gunnarsson R, Molberg O, Gilboe IM, Gran JT. The prevalence and incidence of mixed connective tissue disease: a national multicentre survey of Norwegian patients. Ann Rheum Dis. Mar 11 2011;[Medline].

  5. Grader-Beck T, Wigley FM. Raynaud's phenomenon in mixed connective tissue disease. Rheum Dis Clin North Am. Aug 2005;31(3):465-81, vi. [Medline].

  6. Hall S, Hanrahan P. Muscle involvement in mixed connective tissue disease. Rheum Dis Clin North Am. Aug 2005;31(3):509-17, vii. [Medline].

  7. Swart JF, Wulffraat NM. Diagnostic workup for mixed connective tissue disease in childhood. Isr Med Assoc J. Aug-Sep 2008;10(8-9):650-2. [Medline].

  8. Oh YB, Jun JB, Kim CK, et al. Mixed connective tissue disease associated with skin defects of livedoid vasculitis. Clin Rheumatol. 2000;19(5):381-4. [Medline].

  9. Yamamura K, Takahara M, Masunaga K, Sawabe T, Kitano M, Mashino T, et al. Subcutaneous calcification of the lower legs in a patient with mixed connective tissue disease. J Dermatol. Mar 21 2011;[Medline].

  10. Weber P, Ganser G, Frosch M, Roth J, Hülskamp G, Zimmer KP. Twenty-four hour intraesophageal pH monitoring in children and adolescents with scleroderma and mixed connective tissue disease. J Rheumatol. Nov 2000;27(11):2692-5. [Medline].

  11. Fagundes MN, Caleiro MT, Navarro-Rodriguez T, et al. Esophageal involvement and interstitial lung disease in mixed connective tissue disease. Respir Med. Jun 2009;103(6):854-60. [Medline].

  12. Aalokken TM, Lilleby V, Soyseth V, et al. Chest abnormalities in juvenile-onset mixed connective tissue disease: assessment with high-resolution computed tomography and pulmonary function tests. Acta Radiol. May 2009;50(4):430-6. [Medline].

  13. Colin G, Nunes H, Hatron PY, Cadranel J, Tillie I, Wallaert B. [Clinical study of interstitial lung disease in mixed connective tissue disease]. Rev Mal Respir. Mar 2010;27(3):238-46. [Medline].

  14. Nowicka-Sauer K, Czuszynska Z, Majkowicz M, Smolenska Z, Jarmoszewicz K, Olesinska M, et al. Neuropsychological assessment in mixed connective tissue disease: comparison with systemic lupus erythematosus. Lupus. Mar 20 2012;[Medline].

  15. Lundberg IE. Cardiac involvement in autoimmune myositis and mixed connective tissue disease. Lupus. 2005;14(9):708-12. [Medline].

  16. Gourley I, Bell AL, Biggart D. Kikuchi's disease as a presenting feature of mixed connective tissue disease. Clin Rheumatol. Jan 1995;14(1):104-7. [Medline].

  17. Peller JS, Gabor GT, Porter JM, Bennett RM. Angiographic findings in mixed connective tissue disease. Correlation with fingernail capillary photomicroscopy and digital photoplethysmography findings. Arthritis Rheum. Jul 1985;28(7):768-74. [Medline].

  18. Sharp GC, Irvin WS, Tan EM, Gould RG, Holman HR. 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].

  19. Hof D, Raats JM, Pruijn GJ. Apoptotic modifications affect the autoreactivity of the U1 snRNP autoantigen. Autoimmun Rev. Jul 2005;4(6):380-8. [Medline].

  20. Hasegawa EM, Caleiro MT, Fuller R, Carvalho JF. The frequency of anti-beta2-glycoprotein I antibodies is low and these antibodies are associated with pulmonary hypertension in mixed connective tissue disease. Lupus. Jun 2009;18(7):618-21. [Medline].

  21. Seguchi M, Soejima Y, Tateishi A, et al. Mixed connective tissue disease with multiple organ damage: successful treatment with plasmapheresis. Intern Med. Dec 2000;39(12):1119-22. [Medline].

  22. Ortega-Hernandez OD, Shoenfeld Y. Mixed connective tissue disease: An overview of clinical manifestations, diagnosis and treatment. Best Pract Res Clin Rheumatol. Feb 2012;26(1):61-72. [Medline].

 
Previous
Next
 
Sclerodermalike changes on the face.
Sausage-shaped fingers in a patient with Raynaud phenomenon.
Direct immunofluorescence testing shows epidermal nuclear immunoglobulin G staining.
Indirect immunofluorescence testing shows the typical speckled pattern for ribonucleoprotein antibodies on a HEp-2 substrate.
 
 
 
All material on this website is protected by copyright, Copyright © 1994-2012 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.

DISCLAIMER: The content of this Website is not influenced by sponsors. The site is designed primarily for use by qualified physicians and other medical professionals. The information contained herein should NOT be used as a substitute for the advice of an appropriately qualified and licensed physician or other health care provider. The information provided here is for educational and informational purposes only. In no way should it be considered as offering medical advice. Please check with a physician if you suspect you are ill.