Zeitschrift für Rheumatologie

, Volume 65, Issue 6, pp 505–519 | Cite as

Sjögren-Syndrom

Aktuelle Aspekte aus rheumatologischer Sicht
CME Weiterbildung · Zertifizierte Fortbildung

Zusammenfassung

Das Sjögren-Syndrom ist eine autoimmune Erkrankung der exokrinen Drüsen mit den Leitsymptomen Keratokonjunktivitis und Stomatitis sicca auf Grundlage einer komplexen Pathogenese. Die Prävalenz beträgt ca. 0,5–1%, wobei ein primäres Sjögren-Syndrom von einem sekundären Sjögren-Syndrom bei anderen Autoimmunerkrankungen differenziert wird. Die Diagnose wird durch die subjektiven Beschwerden und den objektiven Nachweis von Sicca-Symptomen, Anti-Ro(SS-A)/La(SS-B)-Antikörpern und/oder einer fokalen lymphozytären Infiltration der Drüsengewebe gestellt. Neben der typischen Sicca-Symptomatik, die symptomatisch durch Substitutions- und Stimulationstherapie behandelt wird, weisen einige Patienten extraglanduläre Manifestationen auf. Dominierend finden sich Beschwerden am Bewegungsapparat und an inneren Organen, die durch den Rheumatologen behandelt werden. Die Indikation zur Basistherapie wird individuell gestellt; deren Wirksamkeit ist jedoch nicht durch Studien belegt. Etwa 5–10% der Patienten mit einem primären Sjögren-Syndrom entwickeln ein Non-Hodgkin-Lymphom der B-Zell-Reihe. Die Erkrankung erfordert eine interdisziplinäre Betreuung mit Augen-, Zahn-, HNO- und anderen Kollegen in Abhängigkeit vom klinischen Bild.

Schlüsselwörter

Sjögren-Syndrom Sicca-Symptomatik Extraglanduläre Manifestationen Non-Hodgkin-Lymphom Therapie 

Sjögren’s syndrome

Current aspects from a rheumatological point of view

Abstract

Sjögren’s syndrome is an autoimmune disease of the exocrine glands characterized by the leading symptoms of keratoconjunctivitis and stomatitis sicca based on a complex pathogenesis. The prevalence is about 0.5–1%; primary Sjögren’s syndrome is differentiated from secondary Sjögren’s syndrome associated with other autoimmune disorders. The diagnosis is established by the presence of subjective complaints and objective evidence of sicca symptoms, anti-Ro(SSA)/La(SSB) antibodies, and/or focal lymphocytic infiltration of the glandular tissue. In addition to the typical sicca symptomatology, which is managed symptomatically by substitution and stimulation therapy, some patients exhibit extraglandular manifestations. Complaints involving the musculoskeletal system and inner ear dominate and are treated by the rheumatologist. The indication for base therapy is tailored to individual needs, but the efficacy of this approach has not been established in studies. About 5–10% of the patients with primary Sjögren’s syndrome develop a B-cell non-Hodgkin’s lymphoma. The disease requires interdisciplinary management including, among others, ophthalmologists, dentists, and otorhinolaryngologists, depending on the clinical picture.

Keywords

Sjögren’s syndrome Sicca symptomatology Extraglandular manifestations Non-Hodgkin’s lymphoma Therapy 

Literatur

  1. 1.
    Ackerman LS (2006) Sex hormones and the genesis of autoimmunity. Arch Dermatol 142(3): 371–376CrossRefPubMedGoogle Scholar
  2. 2.
    Al-Hashimi I (2005) Xerostomia secondary to Sjögren’s syndrome in the elderly. Drugs Aging 22(11): 887–899CrossRefPubMedGoogle Scholar
  3. 3.
    Aragona P, Di Pietro R, Spinella R, Mobrici M (2006) Conjunctival epithelium improvement after systemic pilocarpine in patients with Sjogren’s syndrome. Br J Ophthalmol 90(2): 166–170CrossRefPubMedGoogle Scholar
  4. 4.
    Asmussen K, Oxholm P (1999) Disease activity in primary Sjögren’s syndrome – can it be defined and assessed? State of the art lectures on Sjögren’s syndrome. Hygiea 108 (part 1) http://www.sjogrensyndrom.se/100-site/index100.html
  5. 5.
    Asmussen KH, Bowman SJ (2001) Outcome measures in Sjögren’s syndrome. Rheumatology 40: 1085–1088CrossRefPubMedGoogle Scholar
  6. 6.
    Bernatsky S, Ramsey-Goldman R, Clarke A (2006) Malignancy and autoimmunity. Curr Opin Rheumatol 18(2): 129–134CrossRefPubMedGoogle Scholar
  7. 7.
    Bloch KJ, Buchanan WW, Wohl MJ, Bunim JJ (1965) Sjögren’s syndrome, a clinical, pathological and serological study of sixty-two cases. Medicine 44: 187–231PubMedGoogle Scholar
  8. 8.
    Bolstad AI, Jonsson R (2002) Genetic aspects of Sjögren’s syndrome. Arthritis Res 4: 353–359CrossRefPubMedGoogle Scholar
  9. 9.
    Bowman SJ, Booth DA, Platts RG (2004) Measurement of fatigue and discomfort in primary Sjögren’s syndrome using a new questionnaire tool. Rheumatology 43: 758–764CrossRefPubMedGoogle Scholar
  10. 10.
    Bowman SJ, Pillemer S, Jonsson R et al. (2001) Revisiting Sjögren’s syndrome in the new millennium: perspectives on assessment and outcome measures. Report of a workshop held on 23 March 2000 at Oxford, UK. Rheumatology 40: 1180–1188CrossRefPubMedGoogle Scholar
  11. 11.
    Bredberg A, Henriksson G, Larsson Å et al. (2004) Sjögren’s syndrome and the Danger model. Rheumatol 44: 965–970CrossRefGoogle Scholar
  12. 12.
    Bredberg A, Manthorpe R, Henriksson G (2005) Recent findings shed light on the aethiopathogenesis of Sjögren’s syndrome. Akt Rheumatol 30: 1–4CrossRefGoogle Scholar
  13. 13.
    Brennan MT, Sankar V, Leakan RA et al. (2003) Sex steroid hormones in primary Sjogren’s syndrome. J Rheumatol 30(6): 1267–1271PubMedGoogle Scholar
  14. 14.
    Bron AJ, Tiffany JM, Gouveia SM et al. (2004) Functional aspects of the tear film lipid layer. Exp Eye Res 78(3): 347–360CrossRefPubMedGoogle Scholar
  15. 15.
    Callaghan R, Prabu A, Allan RB et al. (2006) Direct healthcare costs and predictors of costs in patients with primary Sjögren’s syndrome. Rheumatology 25 (Epub ahead of print)Google Scholar
  16. 16.
    Cha S, Singson E, Cornelius J et al. (2006) Muscarinic acetylcholine type-3 receptor desensitization due to chronic exposure to Sjogren’s syndrome-associated autoantibodies. J Rheumatol 33(2): 296–306PubMedGoogle Scholar
  17. 17.
    Champey J, Corruble E, Gottenberg JE et al. (2006) Quality of life and psychological status in patients with primary Sjogren’s syndrome and sicca symptoms without autoimmune features. Arthritis Rheum 55(3): 451–457CrossRefPubMedGoogle Scholar
  18. 18.
    Chisholm DM, Mason DK (1968) Labial salivary gland biopsy in Sjögren’s disease. J Clin Pathol 21: 656–660PubMedGoogle Scholar
  19. 19.
    Cimaz R, Casadei A, Rose C et al. (2003) Primary Sjogren syndrome in the paediatric age: a multicentre survey. Eur J Pediatr 162(10): 661–665CrossRefPubMedGoogle Scholar
  20. 20.
    Cummins MJ, Papas A, Kammer GM, Fox PC (2003) Treatment of primary Sjögren’s syndrome with low-dose human interferon-α administered by the oromucosal route: combined phase III results. Arthritis Rheum 49:585–593CrossRefPubMedGoogle Scholar
  21. 21.
    Cutolo M, Sulli A, Capellino S et al. (2004) Sex hormones influence on the immune system: basic and clinical aspects in autoimmunity. Lupus 13(9): 635–638CrossRefPubMedGoogle Scholar
  22. 22.
    Dalavanga YA, Detrick B, Hooks JJ et al. (1987) Effect of cyclosporin A (CyA) on the immunopathological lesion of the labial minor salivary glands from patients with Sjogren’s syndrome. Ann Rheum Dis 46(2): 89–92PubMedGoogle Scholar
  23. 23.
    Dartt DA (2002) Regulation of mucin and fluid secretion by conjunctival epithelial cells. Progress Retinal Eye Res 21: 555–576CrossRefGoogle Scholar
  24. 24.
    Davidson BK, Kelly CA, Griffiths ID (1999) Primary Sjogren’s syndrome in the North East of England: a long-term follow-up study. Rheumatology (Oxford) 38(3): 245–253Google Scholar
  25. 25.
    Dawson LJ, Stanbury J, Venn N et al. (2006) Antimuscarinic antibodies in primary Sjogren’s syndrome reversibly inhibit the mechanism of fluid secretion by human submandibular salivary acinar cells. Arthritis Rheum 54(4): 1165–1173CrossRefPubMedGoogle Scholar
  26. 26.
    Diener HC, Putzki N, Berlit P et al. (2005) Diagnostik und Therapie der vaskulitischen Neuropathien und Neuropathien bei Kollagenosen; Leitlinien für Diagnostik und Therapie in der Neurologie, 3. überarbeitete Aufl. Georg Thieme, Stuttgart, http://www.uni-duesseldorf.de/awmf/ll/030–068.htm
  27. 27.
    Dörner T (2001) Neonatale Lupussyndrome. In: Zeidler H, Zacher J, Hiepe F (Hrsg) Interdisziplinäre klinische Rheumatologie. Springer, Berlin Heidelberg New York Tokyo, S 865–894Google Scholar
  28. 28.
    Dörner T (2001) Sjögren Syndrom. In: Zeidler H, Zacher J, Hiepe F (Hrsg) Interdisziplinäre klinische Rheumatologie. Springer, Berlin Heidelberg New York Tokyo, S 922–928Google Scholar
  29. 29.
    Dörner T, Gromnica-Ihle E (2006) Sjögren-Syndrom, Kapitel 4.1. In: Rationelle Diagnostik und Therapie in der Inneren Medizin. Elsevier/Urban Fischer, München JenaGoogle Scholar
  30. 30.
    Dörner T, Lipsky PE (2002) Abnormalities of B cell phenotype, immunoglobulin gene expression and the emergence of autoimmunity in Sjögren’s syndrome. Arthritis Res 4: 360–371CrossRefPubMedGoogle Scholar
  31. 31.
    Drosos AA, Andonopoulos AP, Costopoulos JS et al. (1988) Prevalence of primary Sjögren’s syndrome in an elderly population. Rheumatology 27: 123–127Google Scholar
  32. 32.
    Drosos AA, Skopouli FN, Costopoulos JS et al. (1986) Cyclosporin A (CyA) in primary Sjogren’s syndrome: a double blind study. Ann Rheum Dis 45(9): 732–735PubMedGoogle Scholar
  33. 33.
    Drosos AA, Skopouli FN, Galanopoulou VK et al. (1986) Cyclosporin a therapy in patients with primary Sjogren’s syndrome: results at one year. Scand J Rheumatol Suppl 61: 246–249PubMedGoogle Scholar
  34. 34.
    Fife RS, Chase WF, Dore RK et al. (2002) Cevimeline for the treatment of xerostomia in patients with Sjögren syndrome: a randomized trial. Arch Internal Med 162: 1293–1300CrossRefGoogle Scholar
  35. 35.
    Fox PC, Datiles M, Atkinson JC et al. (1993) Prednisone and Piroxicam for treatment of primary Sjögren’s syndrome. Clin Exp Rheumatol 11: 149–156PubMedGoogle Scholar
  36. 36.
    Fox RI, Chan E, Benton L (1986) Treatment of primary Sjögren’s syndrome with hydroxychloroquine. Am J Med 85 [Suppl 4A]: 62–70Google Scholar
  37. 37.
    Fox RI, Dixon R, Guarrasi V, Krubel S (1996) Treatment of primary Sjögren’s syndrome with hydroxychloroquin: a retrospective, open-label study. Lupus 5 [Suppl 1]: S31–S36Google Scholar
  38. 38.
    Godaert GLR, Hartkamp A, Geenen R et al. (2002) Fatigue in daily life in patients with primary Sjögren’s syndrome and systemic lupus erythematosus. Ann NY Acad Sci 966: 320–326PubMedGoogle Scholar
  39. 39.
    Waterman SA, Gordon TP, Rischmueller M (2000) Inhibitory effects of muscarinic receptor autoantibodies on parasympathetic neurotransmission in Sjogren’s syndrome. Arthritis Rheum 43(7): 1647–1654CrossRefPubMedGoogle Scholar
  40. 40.
    Gottenberg JE, Guillevin L, Lambotte O et al. (2005) Tolerance and short term efficacy of rituximab in 43 patients with systemic autoimmune diseases. Ann Rheum Dis 64(6): 913–920CrossRefPubMedGoogle Scholar
  41. 41.
    Groom J, Kalled SL, Cutler AH et al. (2002) Association of BAFF/BLyS overexpression and altered B cell differentiation with Sjogren’s syndrome. J Clin Invest 109(1): 59–68CrossRefPubMedGoogle Scholar
  42. 42.
    Gudbjörnsson B, Broman JE, Hetta J, Hällgren R (1993) Sleep disturbances in patients with primary Sjögren’s syndrome. Rheumatology 32: 1072–1076Google Scholar
  43. 43.
    Hamilton JB (1943) A new conception of Keratoconjunctivitis sicca (keratitis filiformis in hypofunction of the lacrimal glands). Australasian Medical Publishing Company, SydneyGoogle Scholar
  44. 44.
    Hansen A, Gosemann M, Pruss A et al. (2004) Abnormalities in peripheral B cell memory of patients with primary Sjögren’s syndrome. Arthritis Rheum 50: 1897–1908CrossRefPubMedGoogle Scholar
  45. 45.
    Hansen A, Hoffmann A, Dörner T (2005) Sjögren-Syndrom – können wir das Lymphomrisiko stratifizieren? Akt Rheumatol 30: 46–49CrossRefGoogle Scholar
  46. 46.
    Hansen A, Lipsky PE, Dorner T (2005) Immunopathogenesis of primary Sjogren’s syndrome: implications for disease management and therapy. Curr Opin Rheumatol 17(5): 558–565CrossRefPubMedGoogle Scholar
  47. 47.
    Hansen A, Odendahl M, Reiter K et al. (2002) Disturbed B cell homeostasis in Sjögren’s syndrome: indication for the accumulation of memory B cells in the salivary glands. Arthritis Rheum 46: 2160–2171CrossRefPubMedGoogle Scholar
  48. 48.
    Hansen A, Reiter K, Pruss A et al. (2006) Dissemination of a Sjögren‘s syndrome-associated extranodal marginal zone B cell lymphoma. Arthritis Rheum 54: 127–137CrossRefPubMedGoogle Scholar
  49. 49.
    Höld KM, de Boer D, Zuidema J, Maes RAA (1995) Saliva as an analytical tool in toxicology. Int J Drug Testing 1(1): 1–36 (http://www.criminology.fsu.edu/journal/hold.pdf)Google Scholar
  50. 50.
    Ioannidis JP, Vassiliou VA, Moutsopoulos HM (2002) Long-term risk of mortality and lymphoproliferative disease and predictive classification of primary Sjögren’s syndrome. Arthritis Rheum 46(3): 741–747CrossRefPubMedGoogle Scholar
  51. 51.
    Isenberg DA (2006) B cell targeted therapies in autoimmune diseases. J Rheumatol Suppl 77: 24–28PubMedGoogle Scholar
  52. 52.
    Ittah M, Miceli-Richard C, Eric Gottenberg J et al. (2006) B cell-activating factor of the tumor necrosis factor family (BAFF) is expressed under stimulation by interferon in salivary gland epithelial cells in primary Sjögren’s syndrome. Arthritis Res Therapy 8: R51CrossRefGoogle Scholar
  53. 53.
    Kassan SS, Thomas TL, Moutsopoulos HM et al. (1978) Increased risk of lymphoma in sicca syndrome. Ann Intern Med 89(6): 888–892PubMedGoogle Scholar
  54. 54.
    Kassi E, Moutsatsou P, Sekeris CE et al. (2003) Oestrogen receptors in cultured epithelial cells from salivary glands of Sjögren’s syndrome patients. Rheumatology 42: 1120–1122CrossRefPubMedGoogle Scholar
  55. 55.
    Kauppi M, Pukkala L, Isomäki H (1997) Elevated incidence of hematologic malignancies in patients with Sjögren’s syndrome compared with patients, with rheumatoid arthritis (Finland). Cancer Causes Control 8: 201–214CrossRefPubMedGoogle Scholar
  56. 56.
    Kruize AA, Héne RJ, Kallenberg CGM et al. (1993) Hydroxychloroquine treatment for primary Sjögren’s syndrome: a two-year, double-blind cross-over trial. Ann Rheum Dis 52: 360–364PubMedGoogle Scholar
  57. 57.
    Lazarus MN, Robinson D, Mak V et al. (2006) Incidence of cancer in a cohort of patients with primary Sjögren’s syndrome. Rheumatology, Advance Access published on February 20, 2006. doi: 10.1093/rheumatology/kei281Google Scholar
  58. 58.
    Leng XM, Zhao Y, Zhou DB et al. (2005) A pilot trial for severe, refractory systemic autoimmune disease with stem cell transplantation. Chin Med Sci J 20(3): 159–165 (abstract)PubMedGoogle Scholar
  59. 59.
    Lipsky PE, Diamond B (2006) Autoimmunity and autoimmune diseases, Chapter 8. In: Fauci AS (ed) Harrison’s rheumatology. McGraw-Hill Medical Publishing Division, New York, p 63Google Scholar
  60. 60.
    Manthorpe R (2005) Wie klassifizieren wir Patienten, bei den wir ein Sjögren-Syndrom vermuten? Geschichtliche Entwicklung verschiedener Klassifikationen und vermutliche Weiterentwicklung. Akt Rheumatol 30: 32–37CrossRefGoogle Scholar
  61. 61.
    Manthorpe R, Benoni C, Jacobsson L et al. (2000) Lower frequency of focal lip sialadenitis (focus score) in smoking patients. Can tobacco diminish the salivary gland involvement as judged by histological examination and anti-SSA/Ro and anti-SSB/La antibodies in Sjogren’s syndrome? Ann Rheum Dis 59(1): 54–60CrossRefPubMedGoogle Scholar
  62. 62.
    Manthorpe R, Manthorpe T (2005) Das primäre Sjögren-Syndrom – Epidemiologie und Prognose. Akt Rheumatol 30: 27–31CrossRefGoogle Scholar
  63. 63.
    Mariette X, Ravaud P, Steinfeld S et al. (2004) Inefficacy of infliximab in primary Sjogren’s syndrome: results of the randomized, controlled Trial of Remicade in Primary Sjogren’s Syndrome (TRIPSS). Arthritis Rheum 50(4): 1270–1276CrossRefPubMedGoogle Scholar
  64. 64.
    Masaki Y, Sugai S (2004) Lymphoproliferative disorders in Sjogren’s syndrome. Autoimmun Rev 3(3): 175–182CrossRefPubMedGoogle Scholar
  65. 65.
    Messmer EM (2005) Differenzierte Therapie der Keratoconjunctivitis sicca beim Sjögren-Syndrom. Akt Rheumatol 30: 59–65CrossRefGoogle Scholar
  66. 66.
    Mitsias DI, Tzioufas G, Veiopoulou C et al. (2002) The Th1/Th2 cytokine balance changes with the progress of the immunological lesion of Sjogren’s syndrome. Clin Exp Immunol 128: 562–568CrossRefPubMedGoogle Scholar
  67. 67.
    Moutsopoulos HM (2006) Sjögren’s syndrom, Chapter 8. In: Fauci AS (ed) Harrison’s rheumatology. McGraw-Hill Medical Publishing Division, New York, pp 133–138Google Scholar
  68. 68.
    Niederkorn JY, Stern ME, Pflugfelder SC et al. (2006) Desiccating stress induces T cell-mediated Sjogren’s Syndrome-like lacrimal keratoconjunctivitis. J Immunol 176(7): 3950–3957PubMedGoogle Scholar
  69. 69.
    Noble BA, Loh RSK, MacLennan S et al. (2004) Comparison of autologous serum eye drops with conventional therapy in a randomised controlled crossover trial for ocular surface disease. Br J Opthalmol 88: 647–652CrossRefGoogle Scholar
  70. 70.
    Ono M, Takamura E, Shinozaki K et al. (2004) Therapeutic effect of cevimeline on dry eye in patients with Sjogren’s syndrome: a randomized, double-blind clinical study. Am J Ophthalmol 138(1): 6–17CrossRefPubMedGoogle Scholar
  71. 71.
    Palombi G, the Study Group for SjS of the Italian Society of Rheumatology (2006) Sjögren’s syndrome Disease Damage Index (SjSDDI) a scoring system for the quantification of damage in SjS, derived by the analysis of a cohort of Italian patients. Posterpräsentation IX. International Symposium on Sjogren’s Syndrom Washighton DC 27.–29.4.2006Google Scholar
  72. 72.
    Paulsen FP, Schaudig U, Thale AB (2003) Drainage of tears: impact on the ocular surface and lacrimal system. Clin Sci 1(4): 180–191Google Scholar
  73. 73.
    Pertovaara M, Antonen J, Hurme M (2006) Th2 cytokine genotypes are associated with a milder form of primary Sjogren’s syndrome. Ann Rheum Dis 65(5): 666–670CrossRefPubMedGoogle Scholar
  74. 74.
    Pertovaara M, Pukkala E, Laippala P et al. (2001) A longitudinal cohort study of Finnish patients with primary Sjögren’s syndrome: clinical, immunological, and epidemiological aspects. Ann Rheum Dis 60: 467–472CrossRefPubMedGoogle Scholar
  75. 75.
    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): 2740–2750CrossRefPubMedGoogle Scholar
  76. 76.
    Pillemer SR, Brennan MT, Sankar V et al. (2004) Pilot clinical trial of dehydroepiandrosterone (DHEA) versus placebo for Sjogren’s syndrome. Arthritis Rheum 51(4): 601–604CrossRefPubMedGoogle Scholar
  77. 77.
    Pleyer U, Dörner T (2001) Sjögren Syndrom – systemische und ophthalmologische Manifestationen. Uni-Med Taschenbuch Augenheilkunde, 1. Aufl. Uni-Med, Bremen, S 80–89, 103–104Google Scholar
  78. 78.
    Prause JU, Frost-Larsen K, Hoj L et al. (1984) Lacrimal and salivary secretion in Sjogren’s syndrome: the effect of systemic treatment with bromhexine. Acta Ophthalmol (Copenh) 62(3): 489–497Google Scholar
  79. 79.
    Price EJ, Rigby SP, Clancy U, Venables PJ (1998) Double blind placebo controlled trial of azathioprine in the treatment of primary Sjogren’s syndrome. J Rheumatol 25(5): 896–899PubMedGoogle Scholar
  80. 80.
    Ramos-Casals M, Font J (2005) Primary Sjögren’s syndrome: current and emergent aetiopathogenic concepts. Rheumatology 44: 1354–1367CrossRefPubMedGoogle Scholar
  81. 81.
    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): 312–321CrossRefPubMedGoogle Scholar
  82. 82.
    Reinikainen LM, Jaakkola JJ (2003) Significance of humidity and temperature on skin and upper airway symptoms. Indoor Air 13(4): 344–352CrossRefPubMedGoogle Scholar
  83. 83.
    Rosenthal P, Cotter J (2003) The Boston Scleral Lens in the management of severe ocular surface disease. Ophthalmol Clin North Am 16(1): 89–93CrossRefPubMedGoogle Scholar
  84. 84.
    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 Sjögren’s syndorm. Arthritis Rheum 48(11): 3187–3201CrossRefPubMedGoogle Scholar
  85. 85.
    Sánchez-Guerrero J, Pérez-Dosal MR, Cárdenas-Velázquez F et al. (2005) Prevalence of Sjögren’s syndrome in ambulatory patients according to the American-European Consensus Group criteria. Rheumatology 44: 235–240PubMedGoogle Scholar
  86. 86.
    Sankar V, Brennan MT, Kok MR et al. (2004) Etanercept in Sjögren’s syndrome: a twelve-week randomized, double-blind, placebo-controlled pilot clinical trial. Arthritis Rheum 50: 2240–2245CrossRefPubMedGoogle Scholar
  87. 87.
    Scott D, Hiepe F, Hummel M et al. (1998) Antigen-driven clonal proliferation of B cells within the target tissue of an autoimmune disease. The salivary glands of patients with Sjogren’s syndrome. J Clin Invest 102(5): 938–946PubMedGoogle Scholar
  88. 88.
    Sharpe M, Wilks D (2002) ABC of psychological medicine: Fatigue. BMJ 325: 480–483CrossRefPubMedGoogle Scholar
  89. 89.
    Sjögren HSC (1933) Zur Kenntnis der Keratoconjunctivitis sicca (Keratitis filiformis bei Hypofunktion der Tränendrüsen). Acta Ophthalmologica, Copenhagen [Suppl II]: 1–151Google Scholar
  90. 90.
    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): 296–304CrossRefPubMedGoogle Scholar
  91. 91.
    Skopouli FN, Jagiello P, Tsifetaki N, Moutsopoulos HM (1996) Methotrexate in primary Sjogren’s syndrome. Clin Exp Rheumatol 14(5): 555–558PubMedGoogle Scholar
  92. 92.
    Stangel M, Gold Rolf für die IVIg-Konsensusgruppe: Einsatz intravenöser Immunglobuline in der Neurologie – ein evidenzbasierter Konsens, S. 29. http://www.dgn.org/fileadmin/leitl/ivigkonsensgruppe.pdf
  93. 93.
    Steinfeld SD, Demols P, Appelboom T (2002) Infliximab in primary Sjogren’s syndrome: one-year followup. Arthritis Rheum 46(12): 3301–3303CrossRefPubMedGoogle Scholar
  94. 94.
    Steinfeld SD, Demols P, Salmon I et al. (2001) Infliximab in patients with primary Sjogren’s syndrome: a pilot study. Arthritis Rheum 44(10): 2371–2375CrossRefPubMedGoogle Scholar
  95. 95.
    Steinfeld SD, Tant L, Burmester GR et al. (2006) Epratzumab (humanized anti-CD22 antibody) in primary Sjogren’s syndrome: an open-label Phase I/II study. Arthritis Res Ther 8: R129 (http://arthritis-research.com/content/pdf/ar2018.pdf)CrossRefPubMedGoogle Scholar
  96. 96.
    Stern ME, Beuerman RW, Fox RI et al. (1998) The pathology of dry eye: the interaction between the ocular surface and lacrimal glands. Cornea 17(6): 584–589CrossRefPubMedGoogle Scholar
  97. 97.
    Stiller M (2005) Die orale Komponente des Sjögren-Syndroms – diagnostische Aspekte und zahnmedizinisch-therapeutische Konsequenzen. Akt Rheumatol 30: 41–45CrossRefGoogle Scholar
  98. 98.
    Stroehmann A, Dörner T, Lukowsky A et al. (2002) Cutaneous T cell lymphoma in a patient with primary biliary cirrhosis and secondary Sjögren’s syndrome. J Rheumatol 29: 1326–1330PubMedGoogle Scholar
  99. 99.
    Strömbeck B (2006) Women with primary Sjögren’s syndrome; assessment and treatment; a physiotherapeutic perspective. Doctoral Thesis, Lund UniversityGoogle Scholar
  100. 100.
    Sullivan DA, Sullivan BD, Ullman MD et al. (2000) Androgen influence on the Meibomian gland. Invest Ophthalmol Vis Sci 41: 3732–3742PubMedGoogle Scholar
  101. 101.
    Sutcliffe NN, Inanc M, Speight P, Isenberg D (1998) Predictors of lymphoma development in primary Sjögren’s syndrome. Semin Arthritis Rheum 28: 80–87CrossRefPubMedGoogle Scholar
  102. 102.
    Szodoray P, Jonsson R (2005) The BAFF/APRIL system in systemic autoimmune diseases with a special emphasis on Sjögren’s syndrome. Scand J Immunol 62(5): 421–428CrossRefPubMedGoogle Scholar
  103. 103.
    Tabbara KF, Frayha RA (1993) Alternate-day steroid therapy for patients with primary Sjögren’s syndrome. Ann Ophthal 15: 358–361Google Scholar
  104. 104.
    Talal N, Bunim JJ (1964) The development of malignant lymphoma in the course of Sjögren’s syndrome. Am J Med 36: 529–540CrossRefPubMedGoogle Scholar
  105. 105.
    Theander E (2005) Living and dying with primary Sjögren’s syndrome. Studies on aetiology, treatment, lymphoma, survival and predictors. Thesis. Lund University, Malmö, pp 1–144Google Scholar
  106. 106.
    Theander E, Andersson SI, Manthorpe R, Jocobsson LTH (2005) Proposed core set of outcome measures in patients with primary Sjögren’s syndrome. A 5 years follow-up. J Rheumatol 32: 1495–1502PubMedGoogle Scholar
  107. 107.
    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): 796–803CrossRefPubMedGoogle Scholar
  108. 108.
    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): 1262–1269CrossRefPubMedGoogle Scholar
  109. 109.
    Tishler M, Yaron I, Shirazi I, Yaron M (1999) Hydroxychloroquine treatment for primary Sjogren’s syndrome: its effect on salivary and serum inflammatory markers. Ann Rheum Dis 58: 253–256PubMedGoogle Scholar
  110. 110.
    Tsifetaki N, Kitsos G, Paschides CA et al. (2003) Oral pilocarpine for the treatment of ocular symptoms in patients with Sjogren’s syndrome: a randomised 12 week controlled study. Ann Rheum Dis 62(12): 1204–1207CrossRefPubMedGoogle Scholar
  111. 111.
    Valesini G, Priori R, Bavoillot D et al. (1997) Differential risk of non-Hodgkin’s lymphoma in Italian patients with primary Sjogren’s syndrome. J Rheumatol 24(12): 2376–2380PubMedGoogle Scholar
  112. 112.
    Valimaa H, Savolainen S, Soukka T et al. (2004) Estrogen receptor-beta is the predominant subtype in human oral epithelium and salivary glands. J Endocrinol 180(1): 55–62CrossRefPubMedGoogle Scholar
  113. 113.
    Valtiýsdóttir ST, Gudjbjörnsson B, Hällgren R, Hetta J (2000) Psychological well-being in patients with primary Sjögren’s syndrome. Clin Exp Rheumatol 18: 597–600PubMedGoogle Scholar
  114. 114.
    van Woerkom J, Kruize AA, Jacobs KMG et al. (2006) Clinical efficacy of leflunomide in the treatment of primary Sjögren’s syndrome correlates with a decrease in pro-inflammatory cytokine production. SAT0105 EULAR 2006Google Scholar
  115. 115.
    van Woerkom J, Kruize AA, Jacobs KMG et al. (2005) Safety and efficacy of leflunomide in primary Sjögren’s syndrome: preliminary results of a pilot study. FRI0172 EULAR 2005Google Scholar
  116. 116.
    Vitali C, Bombardieri S, Jonsson R et al. (2002) Classification criteria for Sjögren’s syndrome: a revised version of the European criteria proposed by the America-European-Consensus Group. Ann Rheum Dis 61: 554–558CrossRefPubMedGoogle Scholar
  117. 117.
    Vitali C, Palombi G, the Study Group for SjS of the Italian Society of Rheumatology (2006) Sjögren’s syndrome Disease Activity Measurement (SjSDAM): a scoring system fort he assessment of disease acitivty in SjS, derived by the analysis of a cohort of Italian patients. Posterpräsentation IX. International Symposium on Sjogren’s Syndrom Washighton DC 27.–29.4.2006Google Scholar
  118. 118.
    Vivino FB, Al-Hashimi I, Khan Z et al. (1999) Pilocarpine tablets for the treatment of dry mouth and dry eye symptoms in patients with Sjögren syndrome: a randomized, placebo-controlled, fixed-dose, multicenter trial. Arch Internal Med 159: 174–181CrossRefGoogle Scholar
  119. 119.
    Voulgarelis M, Giannouli S, Tzioufas AG, Moutsopoulos HM (2005) Long-term remission of Sjogren’s syndrome-associated aggressive B-cell non-Hodgkin’s lymphomas following administration of combined B-cell depletion therapy and CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone). Ann Rheum Dis published Online First: 1 December 2005. doi: 10.1136/ard.2005.046193Google Scholar
  120. 120.
    Youinou P, Moutsopoulos HM, Pennec YL (1990) Clinical features of Sjogren’s syndrome. Curr Opin Rheumatol 2(5): 687–693PubMedGoogle Scholar
  121. 121.
    Zandbelt MM, Blokx WA, DeJong EM et al. (2006) Expression of estrogen receptors alpha and beta in skin and salivary gland biospy specimens of Sjögren’s syndrome patients. Posterpräsentation EULAR-Kongress Amsterdam SAT 0110Google Scholar
  122. 122.
    Zandbelt MM, de Wilde P, van Damme P et al. (2004) Etanercept in the treatment of patients with primary Sjogren’s syndrome: a pilot study. J Rheumatol 31(1): 96–101PubMedGoogle Scholar
  123. 123.
    Zintzaras E, Voulgarelis M, Moutsopoulos HM (2005) The risk of lymphoma development in autoimmune diseases: a meta-analysis. Arch Intern Med 165(20): 2337–2344CrossRefPubMedGoogle Scholar

Copyright information

© Springer Medizin Verlag 2006

Authors and Affiliations

  1. 1.Reha-Zentrum Bad Aibling, Deutsche Rentenversicherung BundRheumazentrum – AHBBad AiblingDeutschland
  2. 2.Charite Universitätsmedizin Berlin & Deutsches Rheumaforschungszentrum BerlinBerlinDeutschland

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