Skip to main content
SpringerLink
Log in

Mixed Connective Tissue Disease

  • Chapter
Autoimmune Diseases of the Skin

  • 1871 Accesses

Summary

Pulmonary hypertension in MCTD patients is the most critical factor affecting the prognosis of MCTD patients. Corticosteroids are occasionally effective during the early stage of the disease. Anticoagulants (warfarin potassium), antiplatelets (ticlopidine hydrochloride), and vasodilatators (prostaglandin or prostacyclin derivatives, calcium antagonists) are used for the progressive stage of pulmonary hypertension. Digitalis products and diuretics are used to treat heart failure in the advanced stage of pulmonary hypertension. A combination of cyclophosphamide and cyclosporin A was reported to be effective against the pulmonary hypertension in MCTD patients (Dahl et al., 1992). However, to date no promising therapeutic methods have been established for both primary and secondary type of the pulmonary hypertension. Inhalation of NO in addition to O2 is effective against pulmonary hypertension (Pepke-Zaba, 1991).

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 89.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 119.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Alarcon-Segovia D (1976) Symptomatic Sjoegren’s syndrome in mixed connective tissue disease. J Rheumatol 3:191–195

    PubMed  CAS  Google Scholar 

  • Alarcon-Segovia D, Villarreal M (1987) Classification and diagnostic criteria for mixed connective tissue disease. In: Kasukawa R, Sharp GC (Eds) Mixed Connective Tissue Disease and Antinuclear Antibodies. Elsevier, Amsterdam, pp 33–40

    Google Scholar 

  • Alarcon-Segovia D, Cardiel MH (1989) Comparison between three diagnostic criteria for mixed connective tissue disease. Studies of 593 patients. J Rheumatol 16:328–334

    PubMed  CAS  Google Scholar 

  • Amigues JM, Cantagrel A, Abbal M, Mazieres B, and the Autoimmunity Group of the Hospitals of Toulouse (1996) Comparative study of 4 diagnosis criteria sets in mixed connective tissue disease in patients with anti-RNP antibodies. J Rheumatol 23:2055–2062 (see comments)

    PubMed  CAS  Google Scholar 

  • Becker H, Langrock A, Federlin K (1992) Imbalance of CD4+ lymphocyte subsets in patients with mixed connective tissue disease. Clin Exp Immunol 88:91–95

    Article  PubMed  CAS  Google Scholar 

  • Black C, Isenberg DA (1992) Mixed connective tissue disease — goodbye to all that. Br J Rheumatol 31:695–700 (see comments)

    Article  PubMed  CAS  Google Scholar 

  • Burdt MA, Hoffman RW, Dertscher SL, Wang GS, Johnson JC, Sharp GC (1999) Long-term outcome in mixed connective tissue disease: longitudinal clinical and serological findings. Arthritis Rheum 42:899–909

    Article  PubMed  CAS  Google Scholar 

  • Dahl M, Chalmers A, Wade J, Calverley D, Munt B (1992) Ten year survival of a patient with advanced hypertension and mixed connective tissue disease treated with immunosuppressive therapy. J Rheumatol 19:1807–1809

    PubMed  CAS  Google Scholar 

  • Dong RP, Kimura A, Hashimoto H, Akizuki M, Nishimura Y, Sasazuki T (1993) Difference in HLA-linked genetic background between mixed connective tissue disease and systemic lupus erythematosus. Tissue Antigens 41:21–25

    Article  Google Scholar 

  • Doria A, Ghirardello A, de Zambiasi P, Ruffatti A, Gambari PF (1992) Japanese diagnostic criteria for mixed connective tissue disease in Caucasian patients. J Rheumatol 19:259–264

    PubMed  CAS  Google Scholar 

  • Esther JH, Sharp GC, Agia G, Hurst DJ, Maricq HR (1981) Pulmonary hypertension in a patient with connective tissue disease and antibody to nuclear ribonucleoprotein. Arthritis Rheum 24:2105

    Google Scholar 

  • Filep JG, Bodolay E, Sipka S, Gyimesi E, Csipoe I, Szegedi G (1995) Plasma endothelin correlate with antiendothelial antibodies in patients with mixed connective tissue disease. Circulation 92:2969–2974

    PubMed  CAS  Google Scholar 

  • Fritzler MJ, Ali R, Tan EM (1984) Antibodies from patients with mixed connective tissue disease react with heterogeneous nuclear ribonucleoprotein or ribonucleic acid (hn RNP/RNA) of the nuclear matrix. J Immunol 132:1216–1222

    PubMed  CAS  Google Scholar 

  • Gendi NS, Welsh KI, van Venrooij WJ, Vancheeswaran R, Girloy J, Black CM (1995) HLA type as a predictor of mixed connective tissue disease differentiation: ten-year clinical and immunologic follow up of 46 patients. Arthritis Rheum 38:259–266

    Article  PubMed  CAS  Google Scholar 

  • Graziano FM, Friedman LCV, Grossmaen J (1983) Pulmonary hypertension in a patient with mixed connective tissue disease. Clin Exp Rheumatol 1:251–255

    PubMed  CAS  Google Scholar 

  • Hassfeld W, Steiner G, Studinicka-Benke A, Skriner K, Graninger W, Fisher I, Smolen JS (1995) Autoimmune response to the spliceosome: an immunologic link between rheumatoid arthritis, mixed connective tissue disease, and systemic lupus erythematosus. Arthritis Rheum 38:777–785

    Article  PubMed  CAS  Google Scholar 

  • Hishikawa T, Ogasawara H, Kaneko H, Shirasawa T, Matsuura Y, Sekigawa I, Takasaki Y, Hashimoto H, Hirose S, Handa S, Nagasawa R, Maruyama N (1997) Detection of autoantibodies to a recombinant gag protein derived from human endogenous retrovirus clone 4-1 in autoimmune diseases. Viral Immunol 10:137–147

    Article  PubMed  CAS  Google Scholar 

  • Hoffman RW, Rettenmaier LJ, Takeda Y, Hewette JE, Pettersson I, Nyman U, Luger AM, Sharp GC (1990) Human autoantibodies against the 70-kd polypeptide of U1 small nuclear RNP are associated with HLA-DR 4 among connective tissue disease patients. Arthritis Rheum 33:666–673

    Article  PubMed  CAS  Google Scholar 

  • Holyst MM, Hill DL, Hoch SO, Hoffman RW (1997) Analysis of human T cell and B cell response against U small nuclear ribonucreoprotein 70-kd, B, and D polypeptides among patients with systemic lupus erythematosus and mixed connective tissue disease. Arthritis Rheum 40:1493–1503

    Article  PubMed  CAS  Google Scholar 

  • Hosoda Y (1994) Pathology of pulmonary hypertension: A human and experimental study. Pathol Int 44:241–267

    Article  PubMed  CAS  Google Scholar 

  • Ikaeheimo H, Tiilikainen AS, Hameenkorpi R, Silvennoinen-Kassinen SH (1994) Different distribution of T cell receptor beta-chain haplotypes in mixed connective tissue disease and systemic lupus erythematosus. Ann Med 26:129–132

    Article  Google Scholar 

  • Kasukawa R, Tojo T, Miyawaki S, Yoshida H, Tanimoto K, Nobunaga M, Suzuki T, Takasaki Y, Tamura T (1987) Preliminary diagnostic criteria for classification of mixed connective tissue disease: In: Kasukawa R, Sharp GC (Eds) Mixed Connective Tissue Disease and Antinuclear Antibodies. Elsevier, Amsterdam, pp 41–47

    Google Scholar 

  • Kasukawa R, Nishimaki T, Takagi T, Miyawaki S, Yokohari R, Tsunematsu T (1990) Pulmonary hypertension in connective tissue disease. Clinical study of sixty patients in multi-institutional study. Clin Rheum 9:56–62

    Article  CAS  Google Scholar 

  • Klemperer P, Pollack AD, Baehr G (1942) Diffuse collagen diseases, acute disseminated lupus erythematosus and diffuse scleroderma. JAMA 119:331–332

    Google Scholar 

  • Komatireddy GR, Wang GS, Sharp GC, Hoffman RW (1997) Antiphospholipid antibodies among anti-U1-70 kda autoantibody positive patients with mixed connective tissue disease. J Rheumatol 24:319–322 (see comments)

    PubMed  CAS  Google Scholar 

  • Le Roy EC, Maricq HR, Kahaleh MB (1980) Undifferentiated connective tissue syndromes. Arthritis Rheum 23:341–343

    Article  Google Scholar 

  • Lerner MR, Steitz JA (1979) Antibodies to small nuclear RNAs complexed with proteins are produced by patients with systemic lupus erythematosus. Proc Natl Acad Sci USA 76:5495–5499

    Article  PubMed  CAS  Google Scholar 

  • Lundberg I, Antohi S, Takeuki K, Arnett F, Steiner G, Brumeanu TD, Klareskog L, Bona C (2000) Kinetics of anti-fibrillin-1 autoantibodies in MCTD and CREST syndrome. J Autoimmun 14:267–274

    Article  PubMed  CAS  Google Scholar 

  • Mairesse N, Kahn MF, Appelboom T (1993) Antibodies to the constitutive 73-kd heat shock protein: A new marker for mixed connective tissue disease? Am J Med 95:595–600

    Article  PubMed  CAS  Google Scholar 

  • Miyata M, Kida S, Kanno T, Suzuki K, Watanabe H, Kaise S, Nishimaki T, Hosoda Y, Kasukawa R (1992) Pulmonary hypertension in MCTD: Report of two cases with anticardiolipin antibody. Clin Rheumatol 11:195–201

    Article  PubMed  CAS  Google Scholar 

  • Miyata M, Suzuki K, Sakuma F, Watanabe H, Kaise S, Nishimaki T, Kasukawa R (1993) Anticardiolipin antibodies are associated with pulmonary hypertension in patients with mixed connective tissue disease or systemic lupus erythemotosus. Int Arch Allergy Immunol 100:351–354

    Article  PubMed  CAS  Google Scholar 

  • Miyawaki S, Kasukawa R, Nishimaki T, Onodera H (1988) Treatment and prognosis of patients with mixed connective tissue disease. A multi-center co-operative study. In: Kasukawa R (ed) 1987 Annual Report of The Research Committee of Japanese Ministry of Health and Welfare for Mixed Connective Tissue Disease pp 31–41 (in Japanese, Abstract in English)

    Google Scholar 

  • Nimelstein SH, Brody S, Mc Shane D, Holman HR (1980) Mixed connective tissue disease: a subsequent evaluation of the original 25 patients. Medicine (Baltimore) 59:239–248

    CAS  Google Scholar 

  • Nishimaki T, Aotsuka S, Kondo H, Yamamoto K, Takasaki Y, Sumiya M, Yokohari R (1999) Immunological analysis of pulmonary hypertension in connective tissue disease. J Rheumatol 26:2357–2362

    PubMed  CAS  Google Scholar 

  • Okawa-Takatsuji M, Aotsuka S, Uwatoko M, Sumiya M, Yokohari R (1994) Enhanced synthesis of cytokines by peripheral blood monocytes cultured in the presence of autoantibodies against U1-ribonucreoprotein and/or negatively charged molecules: implication in the pathogenesis of pulmonary hypertension in mixed connective tissue disease (MCTD). Clin Exp Immunol 98:427–433

    Article  PubMed  CAS  Google Scholar 

  • Okubo M, Kurokawa M, Ohto H, Nishimaki T, Nishioka K, Kasukawa R, Yamamoto K (1994) Clonotype analysis of peripheral blood T cells and autoantigen-reactive T cells from patients with mixed connective tissue disease. J Immunol 153:3784–3790

    PubMed  CAS  Google Scholar 

  • Ozawa T, Ninomiya Y, Honma T, Kikuchi M, Sato T, Nakano M, Arakawa M (1995) Increased serum angiotensin-1 converting enzyme activity in patients with mixed connective tissue disease and pulmonary hypertension. Scand J Rheumatol 24:38–43

    Article  PubMed  CAS  Google Scholar 

  • Pepke-Zaba J, Higenbottam TW, Dinh-Xuan AT, Stone D, Wallwork J (1991) Inhaled nitric oxide as a cause of selective pulmonary vasodilatation in pulmonary hypertension. Lancet 338:1173–1174

    Article  PubMed  CAS  Google Scholar 

  • Query CC, Keene JD (1987) A human autoimmune protein associated with U1 RNA contains a region of homology that is cross reactive with retroviral p30gag antigen. Cell 51:211–220

    Article  PubMed  CAS  Google Scholar 

  • Reichlin M (1976) Problems in differentiating SLE and mixed connective tissue disease. N Engl J Med 295:1194–1195

    Article  PubMed  CAS  Google Scholar 

  • Ruuska P, Hameenkorpi R, Forsberg S, Julkunen H, Maekitalo R, Ilonen J, Tilikainen A (1992) Differences in HLA antigens between patients with mixed connective tissue disease and systemic lupus erythematosus. Ann Rheum Dis 51:52–55

    Article  PubMed  CAS  Google Scholar 

  • Sato S, Hasegawa M, Ihn H, Kikuchi K, Takehara K (2000) Clinical significance of antinuclear matrix antibody in serum from patients with anti-U1 RNP antibody. Arch Dermatol Res 292:55–59

    Article  PubMed  CAS  Google Scholar 

  • Sawai T, Murakami K, Kasukawa R, Kyogoku M (1997) Histopathological study of mixed connective tissue disease for 32 autopsy cases in Japan. Jpn J Rheumatol 7:279–292

    Article  Google Scholar 

  • Sharp GC, Irvin WS, Tan EM, Gould RG, Holman HR (1972) Mixed connective tissue disease: an apparently distinct rheumatic disease syndrome associated with a specific antibody to an extractable nuclear antigen (ENA). Am J Med 52:148–159

    Article  PubMed  CAS  Google Scholar 

  • Sharp GC (1987) Diagnostic criteria for classification of MCTD. In: Kasukawa R, Sharp GC (Eds) Mixed Connective Tissue Disease and Antinuclear Autoantibodies. Elsevier, Amsterdam, pp 23–32

    Google Scholar 

  • Skriner K, Sommergruber WH, Tremmel V, Fischer I, Barta A, Smolen JS, Steiner G (1997) Anti-A2/RA33 autoantibodies are directed to the RNA binding region of A2 protein of the heterogeneous nuclear ribonucleoprotein complex: differential epitope recognition in rheumatoid arthritis, systemic lupus erythematosus and mixed connective tissue disease. J Clin Invest 100:127–135

    Article  PubMed  CAS  Google Scholar 

  • Smolen JS, Steiner G (1998) Mixed connective tissue disease. To be or not to be? Arthritis Rheum 41:768–777

    Article  PubMed  CAS  Google Scholar 

  • Steiner G, Skriner K, Smolen JS (1996) Autoantibodies to the A/B proteins of the heterogeneous nuclear ribonucleoprotein complex: Novel tools for the diagnosis of rheumatic diseases. Int Arch Allergy Immunol 111:314–319

    Article  PubMed  CAS  Google Scholar 

  • Sullivan WD, Hurst DJ, Harmon CE, Esther JH, Agia GA, Maltby JD, Lillard SB, Held CN, Wolfe JF, Sunderrajan EV, Maricq HR, Sharp GC (1984) Prospective evaluation emphasizing pulmonary involvement in patients with mixed connective tissue disease. Medicine 63:92–107

    Article  PubMed  CAS  Google Scholar 

  • Talken BL, Lee DR, Caldwell CW, Quinn TP, Schaefermeyer KR, Hoffman RW (1999) Analysis of T cell receptors specific for U1-70 kD small nuclear ribonucleoprotein autoantigen: The alpha chain complementary determining region three is highly conserved among connective tissue disease patients. Human Immunol 60:200–208

    Article  CAS  Google Scholar 

  • Tan FK, Arnett FC, Antohi S, Saito S, Mirarchi A, Spiera H, Sasaki T, Shoichi O, Takeuchi K, Pandy JP, Silver RM, LeRoy C, Postlethwaite AE, Bona CA (1999) Autoantibodies to the extracellular matrix microfibrillar protein, fibrillin-1, in patients with scleroderma and other connective tissue diseases. J Immunol 163:1066–1072

    PubMed  CAS  Google Scholar 

  • Tojo T, Ogasawara T, Aotsuka S, Yokohari R (1991) Major causes of death and five year survival rates in mixed connective tissue disease. In: Yokohari R (ed) 1999 Annual Report of The Research Committee of Japanese Ministry of Health and Welfare for Mixed Connective Tissue Disease. pp 10–13 (in Japanese, Abstract in English)

    Google Scholar 

  • van den Hoogen FH, Spronk PE, Boerbooms AM, Bootsma H, de Rooij DJ, Kallenberg CG, van de Putte LB (1994) Long-term follow up of 46 patients with anti-(U1) sn RNP antibodies. Br J Rheumatol 33:1117–1120

    Article  PubMed  Google Scholar 

  • Weckmann AL, Granados J, Cardiel MH, Andrede F, Vargas-Alarcon G, Alcocer-Varela J, Alarcon-Segovia D (1999) Immunogenetics of mixed connective tissue disease in Mexican Mestizo population. Clin Exp Rheumatol 17:91–94

    PubMed  CAS  Google Scholar 

  • Wiemann C, Bodenbach L, Pyerin W (1993) Antibodies to casein kinase II in sera of patients with mixed connective tissue disease: Evaluation with recombinant protein. Clin Chem 39:2492–2494

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Institute of Rheumatic Diseases, Ohta General Hospital Foundation, 5-25, Nakamachi, Koriyama, 963-8004, Japan

    Reiji Kasukawa MD

Authors
  1. Reiji Kasukawa MD
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Michael Hertl

Rights and permissions

Reprints and permissions

Copyright information

© 2011 Springer-Verlag/Wien

About this chapter

Cite this chapter

Kasukawa, R. (2011). Mixed Connective Tissue Disease. In: Hertl, M. (eds) Autoimmune Diseases of the Skin. Springer, Vienna. https://doi.org/10.1007/978-3-211-99225-8_12

Download citation

  • DOI: https://doi.org/10.1007/978-3-211-99225-8_12

  • Publisher Name: Springer, Vienna

  • Print ISBN: 978-3-211-99224-1

  • Online ISBN: 978-3-211-99225-8

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation