Advertisement

Zeitschrift für Rheumatologie

, Volume 68, Issue 4, pp 305–311 | Cite as

Vaskulopathien bei Sjögren-Syndrom

Leitthema

Zusammenfassung

Das Sjögren-Syndrom ist eine systemische Autoimmunerkrankung mit im Vordergrund stehender Beteiligung der exokrinen Drüsen und resultierender Sicca-Symptomatik. Darüber hinaus kommt es in etwa 40% der Fälle zu extraglandulären Manifestationen mit Beteiligung der Haut, des muskuloskelettalen Systems, des peripheren und zentralen Nervensystems sowie auch innerer Organe. Das Auftreten einer systemischen Vaskulitis bei Sjögren-Syndrom kann bei etwa 5–10% der Patienten angenommen werden. Eine klassische vaskulitische Manifestation des Sjögren-Syndroms stellen die leukozytoklastische und kryoglobulinämische Vaskulitis dar, wobei in der Pathogenese insbesondere B-Zell-vermittelte Autoimmunreaktionen bei Nachweis von Autoantikörpern gegen Ro/SS-A und La/SS-B sowie Kryoglobuline eine Rolle spielen. Im Allgemeinen können das Auftreten einer Vaskulitis bei Sjögren-Syndrom sowie der Nachweis von Kryoglobulinen, eine Komplementerniedrigung, das Auftreten eines Non-Hodgkin-Lymphoms und eine Glomerulonephritis als ungünstige prognostische Faktoren angesehen werden. Bei Vaskulitis können verschiedene immunsuppressive Therapieansätze in der Regel in Komedikation mit Glukokortikoiden eingesetzt werden. Für therapieresistente Verläufe kann darüber hinaus die Option einer B-Zell-gerichteten Therapie unter Einsatz von Rituximab erwogen werden.

Schlüsselwörter

Sjögren-Syndrom Vaskulitis Vaskulopathie Extraglanduläre Manifestation 

Vasculopathy in Sjögren’s syndrome

Abstract

Sjögren’s syndrome is a systemic autoimmune disease with a predominant involvement of exocrine glands leading to sicca symptoms. Extraglandular involvement occurs in about 40% of patients with skin, musculoskeletal, neurological and organ manifestations. Systemic vasculitic manifestations of Sjögren’s syndrome can be assumed in approximately 5%–10% of patients. Leukocytoclastic or cryoglobulinemic vasculitis represent classic vasculitic manifestations of Sjögren’s syndrome. In the pathogenesis of vasculitis, B-cell-driven autoimmune processes play a major role by producing autoantibodies against the Ro/SS-A and La/SS-B antigens and cryoglobulins. In patients with Sjögren’s syndrome, manifestation of vasculitis, non-Hodgkin’s lymphoma and glomerulonephritis, as well as positive cryoglobulins and decreased levels of complement factors, are considered negative prognostic markers. Various immunosuppressive strategies, usually in co-medication with glucocorticoids, are used for the treatment of vasculitis in Sjögren’s syndrome. For refractory and severe manifestations, a B-cell-targeted therapy with Rituximab should be also considered.

Keyword

Sjögren’s syndrome Vasculitis Vasculopathy Extraglandular manifestation 

Notes

Interessenkonflikt

Der korrespondierende Autor gibt an, dass kein Interessenkonflikt besteht.

Literatur

  1. 1.
    Brito-Zeron P, Ramos-Casals M, Bove A et al (2007) Predicting adverse outcomes in primary Sjogren’s syndrome: identification of prognostic factors. Rheumatology (Oxford) 46(8):1359–1362Google Scholar
  2. 2.
    Ramos-Casals M, Anaya JM, Garcia-Carrasco M et al (2004) Cutaneous vasculitis in primary Sjogren syndrome: classification and clinical significance of 52 patients. Medicine (Baltimore) 83(2):96–106Google Scholar
  3. 3.
    Theander E, Henriksson G, Ljungberg O et al (2006) Lymphoma and other malignancies in primary Sjogren’s syndrome: a cohort study on cancer incidence and lymphoma predictors. Ann Rheum Dis 65(6):796–803PubMedCrossRefGoogle Scholar
  4. 4.
    Horvath IF, Szodoray P, Zeher M (2008) Primary Sjogren’s syndrome in men: clinical and immunological characteristic based on a large cohort of Hungarian patients. Clin Rheumatol 27(12):1479–1483PubMedCrossRefGoogle Scholar
  5. 5.
    Skopouli FN, Dafni U, Ioannidis JP, Moutsopoulos HM (2000) Clinical evolution, and morbidity and mortality of primary Sjogren’s syndrome. Semin Arthritis Rheum 29(5):296–304PubMedCrossRefGoogle Scholar
  6. 6.
    Tzioufas AG, Voulgarelis M (2007) Update on Sjogren’s syndrome autoimmune epithelitis: from classification to increased neoplasias. Best Pract Res Clin Rheumatol 21(6):989–1010PubMedCrossRefGoogle Scholar
  7. 7.
    Ramos-Casals M, Solans R, Rosas J et al (2008) Primary Sjogren syndrome in Spain: clinical and immunologic expression in 1010 patients. Medicine (Baltimore) 87(4):210–219Google Scholar
  8. 8.
    Salomonsson S, Jonsson MV, Skarstein K et al (2003) Cellular basis of ectopic germinal center formation and autoantibody production in the target organ of patients with Sjogren’s syndrome. Arthritis Rheum 48(11):3187–3201PubMedCrossRefGoogle Scholar
  9. 9.
    Aziz KE, McCluskey PJ, Wakefield D (1996) Expression of selectins (CD62 E,L,P) and cellular adhesion molecules in primary Sjogren’s syndrome: questions to immunoregulation. Clin Immunol Immunopathol 80(1):55–66PubMedCrossRefGoogle Scholar
  10. 10.
    Alexander EL, Arnett FC, Provost TT, Stevens MB (1983) Sjogren’s syndrome: association of anti-Ro(SS-A) antibodies with vasculitis, hematologic abnormalities and serologic hyperreactivity. Ann Intern Med 98(2):155–159PubMedGoogle Scholar
  11. 11.
    Terrier B, Lacroix C, Guillevin L et al (2007) Diagnostic and prognostic relevance of neuromuscular biopsy in primary Sjogren’s syndrome-related neuropathy. Arthritis Rheum 57(8):1520–1529PubMedCrossRefGoogle Scholar
  12. 12.
    Alexander EL, Provost TT, Stevens MB, Alexander GE (1982) Neurologic complications of primary Sjogren’s syndrome. Medicine (Baltimore) 61(4):247–257Google Scholar
  13. 13.
    Buyon JP (1996) Neonatal lupus: bedside to bench and back. Scand J Rheumatol 25(5):271–276PubMedCrossRefGoogle Scholar
  14. 14.
    Farris AD, Yaciuk JC, Maier SM et ak, (2008) OMRF, Oklahoma City, OK. Anti-La Autoimmunity Associates with Lung Disease in Mouse and Man. ACR 2008, Presentation 2001<<<bitte prüfen, im Text in Klammer zitiert>>> Google Scholar
  15. 15.
    Dankof A, Morawietz L, Feist E (2006) Labial salivary gland biopsy in Sjogren’s syndrome. Pathologe 27(6):416–421PubMedCrossRefGoogle Scholar
  16. 16.
    Vitali C, Bombardieri S, Jonsson R et al (2002) Classification criteria for Sjogren’s syndrome: a revised version of the European criteria proposed by the American-European Consensus Group. Ann Rheum Dis 61(6):554–558PubMedCrossRefGoogle Scholar
  17. 17.
    Chisholm DM, Mason DK (1968) Labial salivary gland biopsy in Sjogren’s disease. J Clin Pathol 21(5):656–660PubMedCrossRefGoogle Scholar
  18. 18.
    Meister P (2003) Vasculitides: classification, clinical aspects and pathology. A review. Pathologe 24(3):165–181PubMedGoogle Scholar
  19. 19.
    Tzioufas AG, Boumba DS, Skopouli FN, Moutsopoulos HM (1996) Mixed monoclonal cryoglobulinemia and monoclonal rheumatoid factor cross-reactive idiotypes as predictive factors for the development of lymphoma in primary Sjogren’s syndrome. Arthritis Rheum 39(5):767–772PubMedCrossRefGoogle Scholar
  20. 20.
    Ioannidis JP, Vassiliou VA, Moutsopoulos HM (2002) Long-term risk of mortality and lymphoproliferative disease and predictive classification of primary Sjogren’s syndrome. Arthritis Rheum 46(3):741–747PubMedCrossRefGoogle Scholar
  21. 21.
    Theander E, Manthorpe R, Jacobsson LT (2004) Mortality and causes of death in primary Sjogren’s syndrome: a prospective cohort study. Arthritis Rheum 50(4):1262–1269PubMedCrossRefGoogle Scholar
  22. 22.
    Tsokos M, Lazarou SA, Moutsopoulos HM (1987) Vasculitis in primary Sjogren’s syndrome. Histologic classification and clinical presentation. Am J Clin Pathol 88(1):26–31PubMedGoogle Scholar
  23. 23.
    Garcia-Carrasco M, Siso A, Ramos-Casals M (2002) Raynaud’s phenomenon in primary Sjogren’s syndrome. Prevalence and clinical characteristics in a series of 320 patients. J Rheumatol 29(4):726–730PubMedGoogle Scholar
  24. 24.
    Grant IA, Hunder GG, Homburger HA, Dyck PJ (1997) Peripheral neuropathy associated with sicca complex. Neurology 48(4):855–862PubMedGoogle Scholar
  25. 25.
    Mori K, Iijima M, Koike H et al (2005) The wide spectrum of clinical manifestations in Sjogren’s syndrome-associated neuropathy. Brain 128:2518–2534PubMedCrossRefGoogle Scholar
  26. 26.
    Delalande S, de Seze J, Fauchais AL et al (2004) Neurologic manifestations in primary Sjogren syndrome: a study of 82 patients. Medicine (Baltimore) 83(5):280–291Google Scholar
  27. 27.
    Andonopoulos AP, Lagos G, Drosos AA, Moutsopoulos HM (1990) The spectrum of neurological involvement in Sjogren’s syndrome. Br J Rheumatol 29(1):21–23PubMedCrossRefGoogle Scholar
  28. 28.
    Alexander EL, Craft C, Dorsch C et al (1982) Necrotizing arteritis and spinal subarachnoid hemorrhage in Sjogren syndrome. Ann Neurol 11(6):632–635PubMedCrossRefGoogle Scholar
  29. 29.
    Alexander GE, Provost TT, Stevens MB, Alexander EL (1981) Sjogren syndrome: central nervous system manifestations. Neurology 31(11):1391–1396PubMedGoogle Scholar
  30. 30.
    Ramos-Casals M, Brito-Zeron P, Font J (2007) The overlap of Sjogren’s syndrome with other systemic autoimmune diseases. Semin Arthritis Rheum 36(4):246–255PubMedCrossRefGoogle Scholar
  31. 31.
    Manoussakis MN, Georgopoulou C, Zintzaras E et al (2004) Sjogren’s syndrome associated with systemic lupus erythematosus: clinical and laboratory profiles and comparison with primary Sjogren’s syndrome. Arthritis Rheum 50(3):882–891PubMedCrossRefGoogle Scholar
  32. 32.
    Nossent JC, Swaak AJ (1998) Systemic lupus erythematosus VII: frequency and impact of secondary Sjogren’s syndrome. Lupus 7(4):231–234PubMedCrossRefGoogle Scholar
  33. 33.
    Uhlig T, Kvien TK, Jensen JL (1999) Sicca symptoms, saliva and tear production, and disease variables in 636 patients with rheumatoid arthritis. Ann Rheum Dis 58(7):415–422PubMedCrossRefGoogle Scholar
  34. 34.
    Mattey DL, Gonzalez-Gay MA, Hajeer AH et al (2000) Association between HLA-DRB1*15 and secondary Sjogren’s syndrome in patients with rheumatoid arthritis. J Rheumatol 27(11):2611–2616PubMedGoogle Scholar
  35. 35.
    Ramos-Casals M, Nardi N, Brito-Zeron P et al (2006) Atypical autoantibodies in patients with primary Sjogren syndrome: clinical characteristics and follow-up of 82 cases. Semin Arthritis Rheum 35(5):312–321PubMedCrossRefGoogle Scholar
  36. 36.
    Radaelli F, Meucci G, Spinzi G et al (1999) Acute self-limiting jejunitis as the first manifestation of microscopic polyangiitis associated with Sjogren’s disease: report of one case and review of the literature. Eur J Gastroenterol Hepatol 11(8):931–934PubMedCrossRefGoogle Scholar
  37. 37.
    Vaudo G, Bocci EB, Shoenfeld Y et al (2005) Precocious intima-media thickening in patients with primary Sjogren’s syndrome. Arthritis Rheum 52(12):3890–3897PubMedCrossRefGoogle Scholar
  38. 38.
    Lodde BM, Sankar V, Kok MR et al (2006) Serum lipid levels in Sjogren’s syndrome. Rheumatology (Oxford) 45(4):481–484Google Scholar
  39. 39.
    van Woerkom JM, Kruize AA, Geenen R et al (2007) Safety and efficacy of leflunomide in primary Sjogren’s syndrome: a phase II pilot study. Ann Rheum Dis 66(8):1026–1032CrossRefGoogle Scholar
  40. 40.
    Pijpe J, van Imhoff GW, Spijkervet FK et al (2005) Rituximab treatment in patients with primary Sjogren’s syndrome: an open-label phase II study. Arthritis Rheum 52(9):2740–2750PubMedCrossRefGoogle Scholar
  41. 41.
    Dass S, Bowman SJ, Vital EM et al (2008) Reduction of fatigue in Sjogren syndrome with rituximab: results of a randomised, double-blind, placebo-controlled pilot study. Ann Rheum Dis 67(11):1541–1544PubMedCrossRefGoogle Scholar
  42. 42.
    Isaksen K, Jonsson R, Omdal R (2008) Anti-CD20 treatment in primary Sjogren’s syndrome. Scand J Immunol 68(6):554–564PubMedGoogle Scholar
  43. 43.
    Voulgarelis M, Giannouli S, Anagnostou D, Tzioufas AG (2004) Combined therapy with rituximab plus cyclophosphamide/doxorubicin/vincristine/prednisone (CHOP) for Sjogren’s syndrome-associated B-cell aggressive non-Hodgkin’s lymphomas. Rheumatology (Oxford) 43(8):1050–1053Google Scholar

Copyright information

© Springer Medizin Verlag 2009

Authors and Affiliations

  1. 1.Klinik für Rheumatologie und Klinische ImmunologieCharité-Universitätsmedizin BerlinBerlinDeutschland
  2. 2.Institut für RadiologieCharité-Universitätsmedizin BerlinBerlinDeutschland
  3. 3.Institut für PathologieCharité-Universitätsmedizin BerlinBerlinDeutschland

Personalised recommendations