Prognostic Factors and Survival

  • Andreas V. Goules
  • Fotini N. Skopouli


The histological hallmark of primary Sjögren’s syndrome (pSS) is the focal lymphocytic infiltrates that slowly and steadily replace the epithelium of salivary and lacrimal glands and produce exocrine gland dysfunction, manifested mainly by xerostomia and xerophthalmia [1]. These two clinical manifestations are determinants for the term “exocrinopathy” in SS. Studies in the last 20 years have delineated the type and spectrum of other organ involvement in SS. Lungs, liver and the kidneys are usually affected in pSS. The histology and the evolution of the lesion in the above parenchymal tissues do not differ from that observed in salivary and lacrimal glands. These extragrandular manifestations are mild in severity in most cases, evolve slowly, and do not appear to respond to glucocorticoids or other immunosuppressive agents. The central role of the epithelial cell as the main target of the immune injury in the exocrine glands as well as in the lungs, the liver and the kidneys has led to the introduction of the term “autoimmune epithelitis” [1].


Interstitial Lung Disease Lacrimal Gland Standardize Mortality Ratio Standardize Incidence Ratio Mucosa Associate Lymphoid Tissue Lymphoma 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. 1.
    Moutsopoulos HM. Sjogren’s syndrome: autoimmune epithelitis. Clin Immunol Immunopathol. 1994;72:162–5.PubMedCrossRefGoogle Scholar
  2. 2.
    Skopouli FN, Dafni U, Ioannidis JP, Moutsopoulos HM. Clinical evolution, and morbidity and mortality of primary Sjogren’s syndrome. Semin Arthritis Rheum. 2000;29:296–304.PubMedCrossRefGoogle Scholar
  3. 3.
    Tzioufas AG, Boumba DS, Skopouli FN, Moutsopoulos HM. 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. 1996;39:767–72.PubMedCrossRefGoogle Scholar
  4. 4.
    Voulgarelis M, Dafni UG, Isenberg DA, Moutsopoulos HM. Malignant lymphoma in primary Sjogren’s syndrome: a multicenter, retrospective, clinical study by the European Concerted Action on Sjogren’s syndrome. Arthritis Rheum. 1999;42:1765–72.PubMedCrossRefGoogle Scholar
  5. 5.
    Ioannidis JP, Vassiliou VA, Moutsopoulos HM. Long-term risk of mortality and lymphoproliferative disease and predictive classification of primary Sjogren’s syndrome. Arthritis Rheum. 2002;46:741–7.PubMedCrossRefGoogle Scholar
  6. 6.
    Voulgarelis M, Giannouli S, Anagnostou D, Tzioufas AG. Combined therapy with rituximab plus cyclophosphamide/doxorubicin/vincristine/prednisone (CHOP) for Sjogren’s syndrome-associated B-cell aggressive non-Hodgkin’s lymphomas. Rheumatology (Oxford). 2004;43:1050–3.CrossRefGoogle Scholar
  7. 7.
    Voulgarelis M, Giannouli S, Tzioufas AG, Moutsopoulos HM. Long term remission of Sjogren’s syndrome associated aggressive B cell non-Hodgkin’s lymphomas following combined B cell depletion therapy and CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone). Ann Rheum Dis. 2006;65:1033–7.PubMedCrossRefGoogle Scholar
  8. 8.
    Voulgarelis M, Moutsopoulos HM. Mucosa-associated lymphoid tissue lymphoma in Sjögren’s syndrome: risks, management, and prognosis. Rheum Dis Clin North Am. 2008;34:921–33, viii.PubMedCrossRefGoogle Scholar
  9. 9.
    Rothman S, Block M, Hauser FV. Sjogren’s syndrome associated with lymphoblastoma and hypersplenism. AMA Arch Derm Syphilol. 1951;63:642–3.PubMedGoogle Scholar
  10. 10.
    Talal N, Bunim JJ. The development of malignant lymphoma in the course of Sjogren’s syndrome. Am J Med. 1964;36:529–40.PubMedCrossRefGoogle Scholar
  11. 11.
    Kassan SS, Thomas TL, Moutsopoulos HM, Hoover R, Kimberly RP, Budman DR, et al. Increased risk of lymphoma in sicca syndrome. Ann Intern Med. 1978;89:888–92.PubMedGoogle Scholar
  12. 12.
    Zintzaras E, Voulgarelis M, Moutsopoulos HM. The risk of lymphoma development in autoimmune diseases: a meta-analysis. Arch Intern Med. 2005;165:2337–44.PubMedCrossRefGoogle Scholar
  13. 13.
    Kauppi M, Pukkala E, Isomaki H. Elevated incidence of hematologic malignancies in patients with Sjogren’s syndrome compared with patients with rheumatoid arthritis (Finland). Cancer Causes Control. 1997;8:201–4.PubMedCrossRefGoogle Scholar
  14. 14.
    Pariente D, Anaya JM, Combe B, Jorgensen C, Emberger JM, Rossi JF, et al. Non-Hodgkin’s lymphoma associated with primary Sjogren’s syndrome. Eur J Med. 1992;1:337–42.PubMedGoogle Scholar
  15. 15.
    Baimpa E, Dahabreh IJ, Voulgarelis M, Moutsopoulos HM. Hematologic manifestations and predictors of lymphoma development in primary Sjogren syndrome: clinical and pathophysiologic aspects. Medicine (Baltimore). 2009;88:284–93.CrossRefGoogle Scholar
  16. 16.
    Mariette X. Lymphomas in patients with Sjogren’s syndrome: review of the literature and physiopathologic hypothesis. Leuk Lymphoma. 1999;33:93–9.PubMedGoogle Scholar
  17. 17.
    Royer B, Cazals-Hatem D, Sibilia J, Agbalika F, Cayuela JM, Soussi T, et al. Lymphomas in patients with Sjogren’s syndrome are marginal zone B-cell neoplasms, arise in diverse extranodal and nodal sites, and are not associated with viruses. Blood. 1997;90:766–75.PubMedGoogle Scholar
  18. 18.
    Theander E, Henriksson G, Ljungberg O, Mandl T, Manthorpe R, Jacobsson LT. Lymphoma and other malignancies in primary Sjogren’s syndrome: a cohort study on cancer incidence and lymphoma predictors. Ann Rheum Dis. 2006;65:796–803.PubMedCrossRefGoogle Scholar
  19. 19.
    Ambrosetti A, Zanotti R, Pattaro C, Lenzi L, Chilosi M, Caramaschi P, et al. Most cases of primary salivary mucosa-associated lymphoid tissue lymphoma are associated either with Sjogren syndrome or hepatitis C virus infection. Br J Haematol. 2004;126:43–9.PubMedCrossRefGoogle Scholar
  20. 20.
    Coiffier B, Lepage E, Briere J, Herbrecht R, Tilly H, et al. CHOP chemotherapy plus rituximab compared with CHOP alone in elderly patients with diffuse large-B-cell lymphoma. N Engl J Med 2002;346:235–42.PubMedCrossRefGoogle Scholar
  21. 21.
    Kruize AA, Hene RJ, van der Heide A, Bodeutsch C, de Wilde PC, van Bijsterveld OP, et al. Long-term followup of patients with Sjogren’s syndrome. Arthritis Rheum. 1996;39:297–303.PubMedCrossRefGoogle Scholar
  22. 22.
    Martens PB, Pillemer SR, Jacobsson LT, O’Fallon WM, Matteson EL. Survivorship in a population based cohort of patients with Sjogren’s syndrome, 1976-1992. J Rheumatol. 1999;26:1296–300.PubMedGoogle Scholar
  23. 23.
    Pertovaara M, Pukkala E, Laippala P, Miettinen A, Pasternack A. A longitudinal cohort study of Finnish patients with primary Sjogren’s syndrome: clinical, immunological, and epidemiological aspects. Ann Rheum Dis. 2001;60:467–72.PubMedCrossRefGoogle Scholar
  24. 24.
    Theander E, Manthorpe R, Jacobsson LT. Mortality and causes of death in primary Sjogren’s syndrome: a prospective cohort study. Arthritis Rheum. 2004;50:1262–9.PubMedCrossRefGoogle Scholar
  25. 25.
    Alamanos Y, Tsifetaki N, Voulgari PV, Venetsanopoulou AI, Siozos C, Drosos AA. Epidemiology of primary Sjogren’s syndrome in north-west Greece, 1982-2003. Rheumatology (Oxford). 2006;45:187–91.CrossRefGoogle Scholar
  26. 26.
    Brito-Zeron P, Ramos-Casals M, Bove A, Sentis J, Font J. Predicting adverse outcomes in primary Sjogren’s syndrome: identification of prognostic factors. Rheumatology (Oxford). 2007;46:1359–62.CrossRefGoogle Scholar
  27. 27.
    Goules A, Masouridi S, Tzioufas AG, Ioannidis JP, Skopouli FN, Moutsopoulos HM. Clinically significant and biopsy-documented renal involvement in primary Sjogren syndrome. Medicine (Baltimore). 2000;79:241–9.CrossRefGoogle Scholar
  28. 28.
    Aygen B, Dursun FE, Dogukan A, Ozercan IH, Celiker H. Hypokalemic quadriparesis associated with renal tubular acidosis in a patient with Sjogren’s syndrome. Clin Nephrol. 2008;69:306–9.PubMedGoogle Scholar
  29. 29.
    Dowd JE, Lipsky PE. Sjogren’s syndrome presenting as hypokalemic periodic paralysis. Arthritis Rheum. 1993;36:1735–8.PubMedCrossRefGoogle Scholar
  30. 30.
    Zimhony O, Sthoeger Z, Ben David D, Bar Khayim Y, Geltner D. Sjogren’s syndrome presenting as hypokalemic paralysis due to distal renal tubular acidosis. J Rheumatol. 1995;22:2366–8.PubMedGoogle Scholar
  31. 31.
    Tsokos M, Lazarou SA, Moutsopoulos HM. Vasculitis in primary Sjogren’s syndrome. Histologic classification and clinical presentation. Am J Clin Pathol. 1987;88:26–31.PubMedGoogle Scholar
  32. 32.
    Anderson LG, Talal N. The spectrum of benign to malignant lymphoproliferation in Sjogren’s syndrome. Clin Exp Immunol. 1972;10:199–221.PubMedGoogle Scholar
  33. 33.
    Tzioufas AG, Costello R, Manoussakis MN, Papadopoulos NM, Moutsopoulos HM. Cryoglobulinemia in primary Sjogren’s syndrome: a monoclonal process. Scand J Rheumatol Suppl. 1986;61:111–3.PubMedGoogle Scholar
  34. 34.
    Ramos-Casals M, Brito-Zeron P, Yague J, Akasbi M, Bautista R, Ruano M, et al. Hypocomplementaemia as an immunological marker of morbidity and mortality in patients with primary Sjogren’s syndrome. Rheumatology (Oxford). 2005;44:89–94.CrossRefGoogle Scholar

Copyright information

© Springer-Verlag London Limited 2011

Authors and Affiliations

  • Andreas V. Goules
    • 1
  • Fotini N. Skopouli
    • 2
  1. 1.Department of Pathophysiology, School of MedicineUniversity of AthensAthensGreece
  2. 2.Department of Dietetics and Nutritional ScienceHarokopio University of AthensAthensGreece

Personalised recommendations