Mischkollagenose, Overlap-Kollagenose und undifferenzierte Kollagenose

Zusammenfassung

Neben den klassifizierbaren Kollagenosen gibt es eine Gruppe ehemals unklassifizierbarer Erkrankungen, die sich klinische und serologische Gemeinsamkeiten mit den klassifizierbaren Kollagenosen teilen. In den letzten Jahren wurden diese „unklassifizierbaren“ Kollagenosen, nämlich die Mischkollagenose, die Overlap-Kollagenose und die undifferenzierte Kollagenose epidemiologisch und teilweise auch pathogenetisch aufgearbeitet. Wir umreißen in diesem Artikel aktuelle Erkenntnisse in der Pathogenese, die neuere Literatur zu Klassifikation und Diagnose sowie die noch geringe Evidenz zu therapeutischen Möglichkeiten.

Abstract

Next to the classifiable connective tissue diseases, there is a group of formerly not classifiable diseases that share clinical and serological features with the classifiable connective tissue diseases. During the course of the last years, these ‚unclassifiable‘ connective tissue diseases, namely mixed, overlap and undifferentiated connective tissue disease, were epidemiologically and, in part, pathogenetically investigated. We here summarize the current insights in pathogenesis, the novel literature on classification and diagnosis as well as the still limited evidences about therapeutic measures.

Schlüsselwörter

Mischkollagenose - Overlap-Kollagenose - undifferenzierte Kollagenose

Key words

mixed connective tissue disease - overlap connective tissue disease - undifferentiated connective tissue disease

• Literatur

• 1 Kastner B, Kornstadt U, Bach M. et al. Structure of the small nuclear RNP particle U1: identification of the two structural protuberances with RNP-antigens A and 70K. J Cell Biol 1992; 116: 839-849
• 2 Hoffman RW, Takeda Y, Sharp GC. et al. Human T cell clones reactive against U-small nuclear ribonucleoprotein autoantigens from connective tissue disease patients and healthy individuals. J Immunol 1993; 151: 6460-6469
• 3 Okubo M, Yamamoto K, Kato T. et al. Detection and epitope analysis of autoantigen-reactive T cells to the U1-small nuclear ribonucleoprotein A protein in autoimmune disease patients. J Immunol 1993; 151: 1108-1115
• 4 Greidinger EL, Casciola-Rosen L, Morris SM. et al. Autoantibody recognition of distinctly modified forms of the U1-70-kd antigen is associated with different clinical disease manifestations. Arthritis Rheum 2000; 43: 881-888
• 5 Flam ST, Gunnarsson R, Garen T. et al. The HLA profiles of mixed connective tissue disease differ distinctly from the profiles of clinically related connective tissue diseases. Rheumatology (Oxford, England) 2015; 54: 528-535
• 6 Paradowska-Gorycka A, Jurkowska M, Czuszynska Z. et al. IL-10, IL-12B and IL-17 gene polymorphisms in patients with mixed connective tissue disease. Mod Rheumatol 2015; 25: 487-489
• 7 Washio M, Fujii T, Kuwana M. et al. Lifestyle and other related factors for the development of mixed connective tissue disease among Japanese females in comparison with systemic lupus erythematosus. Mod Rheumatol 2014; 24: 788-792
• 8 Bodolay E, Aleksza M, Antal-Szalmas P. et al. Serum cytokine levels and type 1 and type 2 intracellular T cell cytokine profiles in mixed connective tissue disease. The Journal of rheumatology 2002; 29: 2136-2142
• 9 Holyst MM, Hill DL, Hoch SO. et al. Analysis of human T cell and B cell responses against U small nuclear ribonucleoprotein 70-kd, B, and D polypeptides among patients with systemic lupus erythematosus and mixed connective tissue disease. Arthritis Rheum 1997; 40: 1493-1503
• 10 Arbuckle MR, McClain MT, Rubertone MV. et al. Development of autoantibodies before the clinical onset of systemic lupus erythematosus. N Engl J Med 2003; 349: 1526-1533
• 11 Greidinger EL, Hoffman RW. The appearance of U1 RNP antibody specificities in sequential autoimmune human antisera follows a characteristic order that implicates the U1-70 kd and B'/B proteins as predominant U1 RNP immunogens. Arthritis Rheum 2001; 44: 368-375
• 12 Hoet RM, Koornneef I, de Rooij DJ. et al Changes in anti-U1 RNA antibody levels correlate with disease activity in patients with systemic lupus erythematosus overlap syndrome. Arthritis Rheum 1992; 35: 1202-1210
• 13 Ikeda K, Takasaki Y, Hirokawa K. et al. Clinical significance of antibodies to TS1-RNA in patients with mixed connective tissue disease. The Journal of rheumatology 2003; 30: 998-1005
• 14 Hof D, Cheung K, de Rooij DJ. et al. Autoantibodies specific for apoptotic U1-70K are superior serological markers for mixed connective tissue disease. Arthritis Res Ther 2005; 7: R302-R309
• 15 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 1972; 52: 148-159
• 16 Cappelli S, Bellando Randone S, Martinovic D. et al. "To be or not to be," ten years after: evidence for mixed connective tissue disease as a distinct entity. Semin Arthritis Rheum 2012; 41: 589-598
• 17 Tani C, Carli L, Vagnani S. et al. The diagnosis and classification of mixed connective tissue disease. J Autoimmun 2014; 48-49: 46-49
• 18 Hajas A, Szodoray P, Nakken B. et al. Clinical course, prognosis, and causes of death in mixed connective tissue disease. The Journal of rheumatology 2013; 40: 1134-1142
• 19 Vegh J, Szodoray P, Kappelmayer J. et al. Clinical and immunoserological characteristics of mixed connective tissue disease associated with pulmonary arterial hypertension. Scand J Immunol 2006; 64: 69-76
• 20 Gunnarsson R, Aalokken TM, Molberg O. et al. Prevalence and severity of interstitial lung disease in mixed connective tissue disease: a nationwide, cross-sectional study. Ann Rheum Dis 2012; 71: 1966-1972
• 21 Szodoray P, Hajas A, Kardos L. et al. Distinct phenotypes in mixed connective tissue disease: subgroups and survival. Lupus 2012; 21: 1412-1422
• 22 Kawano-Dourado L, Baldi BG, Kay FU. et al. Pulmonary involvement in long-term mixed connective tissue disease: functional trends and image findings after 10 years. Clinical and experimental rheumatology 2015; 33: 234-240
• 23 Ungprasert P, Wannarong T, Panichsillapakit T. et al. Cardiac involvement in mixed connective tissue disease: a systematic review. International journal of cardiology 2014; 171: 326-330
• 24 Usuba FS, Lopes JB, Fuller R. et al. Sjogren's syndrome: An underdiagnosed condition in mixed connective tissue disease. Clinics (Sao Paulo, Brazil) 2014; 69: 158-162
• 25 Hoffmann-Vold AM, Gunnarsson R, Garen T. et al. Performance of the 2013 American College of Rheumatology/European League Against Rheumatism Classification Criteria for Systemic Sclerosis (SSc) in large, well-defined cohorts of SSc and mixed connective tissue disease. The Journal of rheumatology 2015; 42: 60-63
• 26 Iaccarino L, Gatto M, Bettio S. et al. Overlap connective tissue disease syndromes. Autoimmun Rev 2013; 12: 363-373
• 27 Baer AN, Maynard JW, Shaikh F. et al. Secondary Sjogren's syndrome in systemic lupus erythematosus defines a distinct disease subset. The Journal of rheumatology 2010; 37: 1143-1149
• 28 Mosca M, Tani C, Vagnani S. et al. The diagnosis and classification of undifferentiated connective tissue diseases. J Autoimmun 2014; 48-49: 50-52
• 29 Costenbader KH, Schur PH. We need better classification and terminology for "people at high risk of or in the process of developing lupus". Arthritis Care Res (Hoboken) 2015; 67: 593-596
• 30 Valentini G. Undifferentiated Connective Tissue Disease at risk for systemic sclerosis (SSc) (so far referred to as very early/early SSc or pre-SSc). Autoimmun Rev 2015; 14: 210-213
• 31 Koenig M, Joyal F, Fritzler MJ. et al. Autoantibodies and microvascular damage are independent predictive factors for the progression of Raynaud's phenomenon to systemic sclerosis: a twenty-year prospective study of 586 patients, with validation of proposed criteria for early systemic sclerosis. Arthritis Rheum 2008; 58: 3902-3912
• 32 Fischer A, Antoniou KM, Brown KK. et al. An official European Respiratory Society/American Thoracic Society research statement: interstitial pneumonia with autoimmune features. Eur Respir J 2015; 46: 976-987
• 33 Ferri C, Manfredi A, Sebastiani M. et al. Interstitial pneumonia with autoimmune features and undifferentiated connective tissue disease: Our interdisciplinary rheumatology-pneumology experience, and review of the literature. Autoimmun Rev 2016; 15: 61-70
• 34 Kuroki M, Okayama A, Kuwata G. et al. A case of mixed connective tissue disease with lupus-like manifestations of the central nervous system, successfully treated with cyclophosphamide combined with prednisolone. Ryumachi 2000; 40: 627-632
• 35 Wise CM, Vuyyuru S, Roberts WN. Methotrexate in nonrenal lupus and undifferentiated connective tissue disease--a review of 36 patients. The Journal of rheumatology 1996; 23: 1005-1010
• 36 Oddis CV, Reed AM, Aggarwal R. et al. Rituximab in the treatment of refractory adult and juvenile dermatomyositis and adult polymyositis: a randomized, placebo-phase trial. Arthritis Rheum 2013; 65: 314-324
• 37 Bauhammer J, Blank N, Max R et al. Rituximab in the Treatment of Jo1 Antibody-associated Antisynthetase Syndrome: Anti-Ro52 Positivity as a Marker for Severity and Treatment Response. The Journal of rheumatology 2016
• 38 Cavagna L, Caporali R, Abdi-Ali L. et al. Cyclosporine in anti-Jo1-positive patients with corticosteroid-refractory interstitial lung disease. The Journal of rheumatology 2013; 40: 484-492
• 39 Moskowitz RW, Lesko M, Hooper M. Open-label study of clarithromycin in patients with undifferentiated connective tissue disease. Semin Arthritis Rheum 2006; 36: 82-87
• 40 Ritterhouse LL, Crowe SR, Niewold TB. et al. Vitamin D deficiency is associated with an increased autoimmune response in healthy individuals and in patients with systemic lupus erythematosus. Ann Rheum Dis 2011; 70: 1569-1574
• 41 Antico A, Tampoia M, Tozzoli R. et al. Can supplementation with vitamin D reduce the risk or modify the course of autoimmune diseases? A systematic review of the literature. Autoimmun Rev 2012; 12: 127-136
• 42 Zold E, Szodoray P, Nakken B. et al. Alfacalcidol treatment restores derailed immune-regulation in patients with undifferentiated connective tissue disease. Autoimmun Rev 2011; 10: 155-162
• 43 Zold E, Szodoray P, Kappelmayer J. et al. Impaired regulatory T-cell homeostasis due to vitamin D deficiency in undifferentiated connective tissue disease. Scand J Rheumatol 2010; 39: 490-497