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Histopathological study of mixed connective tissue disease from 32 autopsy cases in Japan

  • Original Article
  • Published:
Japanese Journal of Rheumatology

Abstract

In order to identify the histological specificity of newly defined connective tissue disease, we examined 32 autopsy cases of mixed connective tissue disease (MCTD) which fulfilled the disease criteria proposed by the Japanese MCTD Committee. The age of the 32 cases ranged from 19 to 79 with an average age of 43 years. The male: female ratio was 3∶29. The duration of illness was 7.9 years on average. These tendencies were not so specific compared with other connective tissue diseases. In reference to the cause of death, pulmonary hypertension associated with severe pulmonary arterial lesions such as plexogenic arteriopathy and intimal thickening was found in 16 cases, which was 34% of all total autopsy cases. Totally pulmonary diseases including pulmonary hypertension, pulmonary fibrosis and interstitial pneumonitis amounted to half of all fatal cases. Following pulmonary disease, esophageal fibrosis, sialoadenitis and cardiac involvement succeeded. Although clinical signs such as dysphagia or hypomotility did not necessarily present before death, the frequency and severity of histological changes of the esophagus cannot be ignored. Accompanied with sicca syndrome, the salivary gland showed variable stages of inflammatory changes from slight lymphocytic infiltration in the periductal region to severe parenchymatous atrophy with severe fibrosis. Autopsy cases of MCTD disclosed myocardial damage in not a few cases, which were often accompanied with fibrosis, and these features were very similar to the those of esophageal lesions. On the other hand, involvement of the kidney, skin and muscle was very slight in MCTD compared with those of systemic lupus erythematosus, progressive systemic sclerosis and polymyositis/dermatomyositis. The kidney lesion was characterized by membranous glomerulonephritis. Skin continued to be scleroedematous in spite of long term illness. Muscle showed slight lymphocytic infiltration around small vessels and interstitium. In addition to serological and clinical features, histopathological study revealed specific features of MCTD different from other connective tissue diseases. In treatment and follow-up of the patients of MCTD, special care should be paid to the conditions of this disease which reflect the histological changes as presented here.

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References

  1. Sharp GC, Irvin WS, Tan EMet al.: Mixed connective tissue disease — an apparently distinct rheumatic disease syndrome associated with a specific antibody to extractable nuclear antigen (ENA).Am J Med 52: 148–159, 1972.

    Article  CAS  PubMed  Google Scholar 

  2. Nimelstein SH, Brody S, McShane Det al.: Mixed connective tissue disease: a subsequent evaluation of the original 25 patients.Medicine 59: 239–248, 1980.

    Article  CAS  PubMed  Google Scholar 

  3. Grant KD, Adams LE, Hess EV: Mixed connective tissue disease — a subset with sequential clinical and laboratory features.J Rheumatol 8: 587–598, 1981.

    CAS  PubMed  Google Scholar 

  4. Kasukawa R, Tojo T, Miyawaki Set al.: Mixed connective tissue disease — a preliminary diagnostic criteria.Jap J Rheumatol 1: 263–279, 1988.

    Google Scholar 

  5. Alarcon-Segovia, Cardiel MH: Comparison 3 diagnostic criteria for mixed connective tissue disease. Study of 593 patients.J Rheumatol 16: 328–334, 1989.

    CAS  PubMed  Google Scholar 

  6. Tan EM: Antinuclear antibody: diagnostic markers for autoimmune disease and probes for cell biology.Adv Immunol 44: 93–148, 1989.

    Article  CAS  PubMed  Google Scholar 

  7. Jones MB, Osterholm RK, Wiison RBet al.: Fatal pulmonary hypertension and resolving immunecomplex glomerulonephritis in mixed connective tissue disease. A case report and review of the literature.Am J Med 65: 855–863, 1978.

    Article  CAS  PubMed  Google Scholar 

  8. Graziano FM, Friedman LC, Grossman J: Pulmonary hypertension in a patients with mixed connective tissue disease: clinical and pathologic findings and review of literature.Clin Exp Rheumatol 1: 251–255, 1983.

    CAS  PubMed  Google Scholar 

  9. Hosoda Y, Suzuki Y, Takano Met al.: Mixed connective tissue disease with pulmonary hypertension: A clinical and pathological study.J Rheumatol 14: 826–830, 1987.

    CAS  PubMed  Google Scholar 

  10. Fuller TJ, Richman AV, Auerbach Det al.: Immune-complex glomerulonephritis in a patient with mixed connective tissue disease.Am J Med 62: 761–764, 1977.

    Article  CAS  PubMed  Google Scholar 

  11. Bennet RM, Spargo BH: Immune complex nephritis in mixed connective tissue disease.Am J Med 63: 534–541, 1977.

    Article  Google Scholar 

  12. Kobayashi S, Nagase M, Kimura Met al.: Renal involvement in mixed connective tissue disease. Report of 5 cases.Am J Nephrol 5: 282–289, 1985.

    Article  CAS  PubMed  Google Scholar 

  13. Kitridou RC, Akmal M, Turkel SBet al.: Renal involvement in mixed connective tissue disease: a longitudinal clinicopathologic study.Semin Arthritis Rheum 16: 135–145, 1986.

    Article  CAS  PubMed  Google Scholar 

  14. Harris GJ, Franson TR, Ryan LM: Recurrent aseptic meningitis as a manifestation of mixed connective tissue disease.Wis Med J 86: 31–33, 1987.

    CAS  PubMed  Google Scholar 

  15. Shiozawa S, Shiozawa K, Shimizu Set al.: Aseptic meningitis during the course of mixed connective tissue disease (MCTD) — a case report.Ryumachi 27: 16–22, 1987.

    CAS  PubMed  Google Scholar 

  16. Nunoda S, Mifune J, Ono Set al.: An adult case of mixed connective tissue disease associated with perimyocarditis and massive pericardial effusion.Jpn Heart J 27: 129–135, 1986.

    CAS  PubMed  Google Scholar 

  17. Lash AD, Wittman AL, Quismorio FP, Jr: Myocarditis in mixed connective tissue disease: clinical and pathologic study of three cases and review of the literature.Semin Arthritis Rheum 15: 288–296, 1986.

    Article  CAS  PubMed  Google Scholar 

  18. Alpert MA, Goldberg SH, Singsen BHet al.: Cardiovascular manifestation of mixed connective tissue disease.Circulation 68: 1182–1193, 1983.

    CAS  PubMed  Google Scholar 

  19. Whitlow PA, Gilliam JN, Chubick Aet al.: Myocarditis in mixed connective tissue disease. Association of myocarditis with antibody to nuclear riboprotein.Arthritis Rheum 23: 808–815, 1980.

    Article  CAS  PubMed  Google Scholar 

  20. Marshall JB, Ravendhran N: Liver disease in mixed connective tissue disease.Arch Intern Med 143: 1817–1818, 1983.

    Article  CAS  PubMed  Google Scholar 

  21. Alarcon-Segovia D, Chrdiel MH: Comparison between 3 diagnostic criteria for mixed connective tissue disease study of 593 patients.J Rheumatol 16: 328–334, 1989.

    CAS  PubMed  Google Scholar 

  22. Maeda M, Kanayama M, Hasuyama Yet al.: Case of mixed connective tissue disease associated with autoimmune hepatitis.Dig Dis Sci 33: 1487–1490, 1988.

    Article  CAS  PubMed  Google Scholar 

  23. Dantas RO, Villanova MG, de-Godoy RA: Esophageal dysfunction progressive systemic sclerosis and mixed connective tissue disease.Arq Gastroenterol 22: 122–126, 1985.

    CAS  PubMed  Google Scholar 

  24. Gutierrez F, Valenzuela JE, Ehresmann GRet al.: Esophageal dysfunction in patients with mixed connective tissue diseases.Dig Dis Sci 27: 592–597, 1982.

    Article  CAS  PubMed  Google Scholar 

  25. Bennet RM, O’Conenell DJ: Mixed connective tissue disease: a clinico-pathologic study 20 cases.Semin Arthritis Rheum 8: 587–598, 1980.

    Google Scholar 

  26. Weihrauuch TR, Rorty GW: Manometric assessment of esophageal involvement in progressive systemic sclerosis, morphea and Raynaud’s disease.Br J Dermatol 107: 325–332, 1982.

    Article  Google Scholar 

  27. Schneider HA, Yonker RA, Longley Set al.: Scleroderma esophagus: A non specific entity.Ann Intern Med 100: 848–850, 1984.

    CAS  PubMed  Google Scholar 

  28. Saitoh K, Sagawa K, Nishimaki Tet al.: Localization of nRNP antigen in mammalian cells stained with peroxidase-labeled IgG fraction of anti-U1RNP antibody obtained from a patients with mixed connective tissue disease (MCTD).Tohoku J Exp Med 15: 21–26, 1987.

    Article  Google Scholar 

  29. Singeson BH, Swanson VL, Bernstein BHet al.: A histologic evaluation of mixed connective tissue disease in childhood.Am J Med 68: 710–717, 1983.

    Article  Google Scholar 

  30. Alarcon-Segovia D: Symptomatic Sjögren syndrome in mixed connective tissue disease.J Rheumatol 3: 191–195, 1976.

    CAS  PubMed  Google Scholar 

  31. Wasner CK: Ibuprofen, meningitis and systemic lupus erythematosus.J Rheumatol 5: 162–164, 1978.

    CAS  PubMed  Google Scholar 

  32. Bernstein RF: Ibuprofen-associated aseptic meningitis.Clin Pharm 1: 561–566, 1982.

    Google Scholar 

  33. Frayha RA, Nasr FW, Mufarrij AA: Mixed connective tissue disease, Sjögren syndrome and abdominal pseudolymphoma.Br J Rheumatol 24: 70–73, 1985.

    Article  CAS  PubMed  Google Scholar 

  34. Manthorpe R, Elling H, van der Meullen JTet al.: Two fatal cases of mixed connective tissue disease — description of cases histories terminating progressive systemic sclerosis.Scand J Rheumatol 9: 7–10, 1980.

    Article  CAS  PubMed  Google Scholar 

  35. Oxenhandler R, Hart M, Corman Let al.: Pathology of skeletal muscle in mixed connective tissue disease.Arthritis Rheum 20: 985–988, 1977.

    Article  CAS  PubMed  Google Scholar 

  36. Gilliam JN, Prystowsky SD: Mixed connective tissue disease syndrome.Arch Dermatol 113: 583–587, 1977.

    Article  CAS  PubMed  Google Scholar 

  37. Ramos-Niembro F, Alarcon-Segovia D, Hernabdez-Ortis J: Articular manifestations of mixed connective tissue disease.Arthritis Rheum 22: 43–51, 1979.

    Article  CAS  PubMed  Google Scholar 

  38. Bennet RM, O’Connel DJ: The arthritis of mixed connective tissue disease.Ann Rheum Dis 37: 397–403, 1978.

    Article  Google Scholar 

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Authors and Affiliations

  1. Department of Pathology, Tohoku University Hospital, 1-1 Seiryo-machi, 980-77, Aoba-ku, Sendai, Japan

    Takashi Sawai & Masahisa Kyogoku

  2. Division of Clinical Pathology, Tohoku Welfare Pension Hospital, 1-2-1 Fukumuro, 983, Miyagino-ku, Sendai, Japan

    Kazuhiro Murakami

  3. The Second Department of Internal Medicine, Fukushima Medical College, 1 Hikarigaoka, 960-12, Fukushima, Japan

    Reiji Kasukawa

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  1. Takashi Sawai
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  2. Kazuhiro Murakami
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  3. Reiji Kasukawa
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  4. Masahisa Kyogoku
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Sawai, T., Murakami, K., Kasukawa, R. et al. Histopathological study of mixed connective tissue disease from 32 autopsy cases in Japan. Japanese Journal of Rheumatology 7, 279–292 (1997). https://doi.org/10.1007/BF03041330

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  • DOI: https://doi.org/10.1007/BF03041330

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