Classic Immunosuppressive and Immunomodulatory Drugs

  • Clio P. Mavragani
  • Stuart S. Kassan


Symptoms of Sjögren’s syndrome (SS) are chronic and can sometimes be devastating, compromising patients’ quality of life to a major degree. Despite the advances in our understanding of the pathogenesis of SS, its therapy remains largely empiric, symptomatic, and focused on alleviating sicca symptoms. Eye lubricants, saliva substitutes, and stimulators of the glandular secretion are the cornerstones of therapy in SS. Despite the autoimmune nature of the disorder, evidence for the use of immunosuppressive agents, the mainstay of therapy of diseases of autoimmune origin, is scarce. In an attempt to alleviate the symptoms of SS by altering the natural disease process, a number of immunosuppressive agents have been tested in clinical studies, mostly with unsatisfactory or questionable results (Table 38.1).


Interstitial Lung Disease Musculoskeletal Complaint Saliva Substitute Sicca Symptom Parotid Gland Enlargement 


  1. 1.
    Tishler M, Yaron I, Shirazi I, et al. Hydroxychloroquine treatment for primary Sjogren’s syndrome: its effect on salivary and serum inflammatory markers. Ann Rheum Dis. 1999;58:253–6.PubMedCrossRefGoogle Scholar
  2. 2.
    Manoussakis MN, Moutsopoulos HM. Antimalarials in Sjogren’s syndrome – the Greek experience. Lupus. 1996;5 Suppl 1:S28–30.PubMedCrossRefGoogle Scholar
  3. 3.
    Groom J, Kalled SL, Cutler AH, et al. Association of BAFF/BLyS overexpression and altered B cell differentiation with Sjogren’s syndrome. J Clin Invest. 2002;109:59–68.PubMedGoogle Scholar
  4. 4.
    Mariette X, Roux S, Zhang J, et al. The level of BLyS (BAFF) correlates with the titre of autoantibodies in human Sjogren’s syndrome. Ann Rheum Dis. 2003;62:168–71.PubMedCrossRefGoogle Scholar
  5. 5.
    Yavuz S, Asfuroglu E, Bicakcigil M, et al. Hydroxychloroquine improves dry eye symptoms of patients with primary Sjogren’s syndrome. Rheumatol Int. 2011;31:1045–9. Epub Mar 23, 2010.PubMedCrossRefGoogle Scholar
  6. 6.
    Dawson LJ, Caulfield VL, Stanbury JB, et al. Hydroxychloroquine therapy in patients with primary Sjogren’s syndrome may improve salivary gland hypofunction by inhibition of glandular cholinesterase. Rheumatology (Oxford). 2005;44:449–55.CrossRefGoogle Scholar
  7. 7.
    Mavragani CP, Moutsopoulos NM, Moutsopoulos HM. The management of Sjogren’s syndrome. Nat Clin Pract Rheumatol. 2006;2:252–61.PubMedCrossRefGoogle Scholar
  8. 8.
    Okan G, Karaaslan M, Büyükbabani N. Systemic vasculitis developing after hydroxychloroquine interruption in a patient with Sjögren’s syndrome. Clin Exp Dermatol. 2010;35:442–3. Epub Nov 3, 2009.PubMedCrossRefGoogle Scholar
  9. 9.
    Zandbelt MM, van den Hoogen FH, de Wilde PC, et al. Reversibility of histological and immunohistological abnormalities in sublabial salivary gland biopsy specimens following treatment with corticosteroids in Sjogren’s syndrome. Ann Rheum Dis. 2001;60:511–3.PubMedCrossRefGoogle Scholar
  10. 10.
    Fox PC, Datiles M, Atkinson JC, et al. Prednisone and piroxicam for treatment of primary Sjogren’s syndrome. Clin Exp Rheumatol. 1993;11:149–56.PubMedGoogle Scholar
  11. 11.
    Kaufman I, Schwartz D, Caspi D, et al. Sjogren’s syndrome – not just Sicca: renal involvement in Sjogren’s syndrome. Scand J Rheumatol. 2008;37:213–8.PubMedCrossRefGoogle Scholar
  12. 12.
    Hawley RJ, Hendricks WT. Treatment of Sjogren syndrome myelopathy with azathioprine and steroids. Arch Neurol. 2002;59:875; author reply 876.PubMedCrossRefGoogle Scholar
  13. 13.
    Linardaki G, Moutsopoulos HM. The uncertain role of immunosuppressive agents in Sjogren’s syndrome. Cleve Clin J Med. 1997;64:523–6.PubMedGoogle Scholar
  14. 14.
    Yeoman CM, Franklin CD. The treatment of Sjogren’s disease in NZB/NZW F1 hybrid mice with azathioprine: a two-stage study. Clin Exp Rheumatol. 1994;12:49–53.PubMedGoogle Scholar
  15. 15.
    Price EJ, Rigby SP, Clancy U, et al. A double blind placebo controlled trial of azathioprine in the treatment of primary Sjogren’s syndrome. J Rheumatol. 1998;25:896–9.PubMedGoogle Scholar
  16. 16.
    Moutsopoulos HM, Balow JE, Lawley TJ, et al. Immune complex glomerulonephritis in sicca syndrome. Am J Med. 1978;64:955–60.PubMedCrossRefGoogle Scholar
  17. 17.
    Skopouli FN, Dafni U, Ioannidis JP, et al. Clinical evolution, and morbidity and mortality of primary Sjogren’s syndrome. Semin Arthritis Rheum. 2000;29:296–304.PubMedCrossRefGoogle Scholar
  18. 18.
    Boumba D, Skopouli FN, Moutsopoulos HM. Cytokine mRNA expression in the labial salivary gland tissues from patients with primary Sjogren’s syndrome. Br J Rheumatol. 1995;34:326–33.PubMedCrossRefGoogle Scholar
  19. 19.
    Skopouli FN, Jagiello P, Tsifetaki N, et al. Methotrexate in primary Sjogren’s syndrome. Clin Exp Rheumatol. 1996;14:555–8.PubMedGoogle Scholar
  20. 20.
    Skopouli FN, Fox PC, Galanopoulou V, et al. T cell subpopulations in the labial minor salivary gland histopathologic lesion of Sjogren’s syndrome. J Rheumatol. 1991;18:210–4.PubMedGoogle Scholar
  21. 21.
    Drosos AA, Skopouli FN, Costopoulos JS, et al. Cyclosporin A (CyA) in primary Sjogren’s syndrome: a double blind study. Ann Rheum Dis. 1986;45:732–5.PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag London Limited 2011

Authors and Affiliations

  • Clio P. Mavragani
    • 1
  • Stuart S. Kassan
    • 2
  1. 1.Department of Experimental Physiology, School of MedicineUniversity of AthensAthensGreece
  2. 2.University of Colorado Health Sciences CenterDenverUSA

Personalised recommendations