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Treatment of systemic and extraglandular manifestations of Sjögren’s syndrome

Authors
Robert Fox, MD, PhD
Paul Creamer, MD
Section Editor
Peter H Schur, MD
Deputy Editor
Paul L Romain, MD

INTRODUCTION

Sjögren’s syndrome (SS) is a chronic multisystem inflammatory disorder characterized by diminished lacrimal and salivary gland function. This results in the “sicca complex,” a combination of dry eyes (xerophthalmia) and dry mouth (xerostomia). A variety of other disease manifestations may also be present, including systemic signs and extraglandular features.

SS occurs in a primary form not associated with other diseases and in a secondary form associated with other autoimmune rheumatic conditions, including rheumatoid arthritis and systemic lupus erythematosus (SLE).

The treatment and prognosis of systemic and extraglandular manifestations of SS will be reviewed here. Other issues in SS are discussed separately, including the clinical manifestations and diagnosis; the treatment of dry eyes, dry mouth (including the use of muscarinic agonists such as pilocarpine and cevimeline), and other nonocular sicca symptoms is presented separately. (See "Clinical manifestations of Sjögren's syndrome: Exocrine gland disease" and "Clinical manifestations of Sjögren's syndrome: Extraglandular disease" and "Diagnosis and classification of Sjögren's syndrome" and "Treatment of dry mouth and other non-ocular sicca symptoms in Sjögren's syndrome" and "Treatment of dry eye in Sjögren's syndrome".)

GENERAL PRINCIPLES

Both local and systemic medical therapies are used in the treatment of Sjögren’s syndrome (SS) [1]. These include:

Preventive therapies and attention to other conditions, medications, and environments that may exacerbate dryness complaints

                         

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Literature review current through: Nov 2016. | This topic last updated: Fri Dec 04 00:00:00 GMT+00:00 2015.
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References
Top
  1. Thanou-Stavraki A, James JA. Primary Sjogren's syndrome: current and prospective therapies. Semin Arthritis Rheum 2008; 37:273.
  2. Ruiz-Irastorza G, Ramos-Casals M, Brito-Zeron P, Khamashta MA. Clinical efficacy and side effects of antimalarials in systemic lupus erythematosus: a systematic review. Ann Rheum Dis 2010; 69:20.
  3. A randomized study of the effect of withdrawing hydroxychloroquine sulfate in systemic lupus erythematosus. The Canadian Hydroxychloroquine Study Group. N Engl J Med 1991; 324:150.
  4. Fox RI, Dixon R, Guarrasi V, Krubel S. Treatment of primary Sjögren's syndrome with hydroxychloroquine: a retrospective, open-label study. Lupus 1996; 5 Suppl 1:S31.
  5. Fox RI, Chan E, Benton L, et al. Treatment of primary Sjögren's syndrome with hydroxychloroquine. Am J Med 1988; 85:62.
  6. Tishler M, Yaron I, Shirazi I, Yaron M. Hydroxychloroquine treatment for primary Sjögren's syndrome: its effect on salivary and serum inflammatory markers. Ann Rheum Dis 1999; 58:253.
  7. 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.
  8. Mavragani CP, Moutsopoulos HM. Conventional therapy of Sjogren's syndrome. Clin Rev Allergy Immunol 2007; 32:284.
  9. Mavragani CP, Moutsopoulos NM, Moutsopoulos HM. The management of Sjögren's syndrome. Nat Clin Pract Rheumatol 2006; 2:252.
  10. Kruize AA, Hené RJ, Kallenberg CG, et al. Hydroxychloroquine treatment for primary Sjögren's syndrome: a two year double blind crossover trial. Ann Rheum Dis 1993; 52:360.
  11. Skopouli FN, Jagiello P, Tsifetaki N, Moutsopoulos HM. Methotrexate in primary Sjögren's syndrome. Clin Exp Rheumatol 1996; 14:555.
  12. Vitali C, Palombi G, Cataleta P. Treating Sjögren's Syndrome: Insights for the Clinician. Ther Adv Musculoskelet Dis 2010; 2:155.
  13. Fox RI, Liu AY. Sjögren's syndrome in dermatology. Clin Dermatol 2006; 24:393.
  14. Ng WF, Bowman SJ. Biological therapies in primary Sjögren's syndrome. Expert Opin Biol Ther 2011; 11:921.
  15. Mariette X, Ravaud P, Steinfeld S, et al. Inefficacy of infliximab in primary Sjögren's syndrome: results of the randomized, controlled Trial of Remicade in Primary Sjögren's Syndrome (TRIPSS). Arthritis Rheum 2004; 50:1270.
  16. Zandbelt MM, de Wilde P, van Damme P, et al. Etanercept in the treatment of patients with primary Sjögren's syndrome: a pilot study. J Rheumatol 2004; 31:96.
  17. Sankar V, Brennan MT, Kok MR, et al. Etanercept in Sjögren's syndrome: a twelve-week randomized, double-blind, placebo-controlled pilot clinical trial. Arthritis Rheum 2004; 50:2240.
  18. Steinfeld SD, Demols P, Salmon I, et al. Infliximab in patients with primary Sjögren's syndrome: a pilot study. Arthritis Rheum 2001; 44:2371.
  19. Steinfeld SD, Demols P, Appelboom T. Infliximab in primary Sjögren's syndrome: one-year followup. Arthritis Rheum 2002; 46:3301.
  20. Steinfeld SD, Demols P, Salmon I, et al. Notice of retraction of two articles (“Infliximab in patients with primary Sjögren’s syndrome: a pilot study” and “Infliximab in patients with primary Sjögren’s syndrome: one-year followup”). Arthritis Rheum 2013; 65:814.
  21. FDA statement on the voluntary withdrawal of raptiva from the U.S. market http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/2009/ucm149561.htm (Accessed on April 09, 2009).
  22. Pelletier D, Hafler DA. Fingolimod for multiple sclerosis. N Engl J Med 2012; 366:339.
  23. Cohen PL, Traisak P. Biological treatment for Sjogren's syndrome. In: Sjogren's Syndrome: Practical Guidelines to Diagnosis and Therapy, Fox RI, Fox CM. (Eds), Springer, New York 2012. p.459.
  24. Meiners PM, Vissink A, Kallenberg CG, et al. Treatment of primary Sjögren's syndrome with anti-CD20 therapy (rituximab). A feasible approach or just a starting point? Expert Opin Biol Ther 2011; 11:1381.
  25. Meijer JM, Meiners PM, Vissink A, et al. Effectiveness of rituximab treatment in primary Sjögren's syndrome: a randomized, double-blind, placebo-controlled trial. Arthritis Rheum 2010; 62:960.
  26. Gottenberg JE, Guillevin L, Lambotte O, et al. Tolerance and short term efficacy of rituximab in 43 patients with systemic autoimmune diseases. Ann Rheum Dis 2005; 64:913.
  27. Brah S, Chiche L, Fanciullino R, et al. Efficacy of rituximab in immune thrombocytopenic purpura: a retrospective survey. Ann Hematol 2012; 91:279.
  28. Pijpe J, van Imhoff GW, Spijkervet FK, et al. Rituximab treatment in patients with primary Sjögren's syndrome: an open-label phase II study. Arthritis Rheum 2005; 52:2740.
  29. Seror R, Sordet C, Guillevin L, et al. Tolerance and efficacy of rituximab and changes in serum B cell biomarkers in patients with systemic complications of primary Sjögren's syndrome. Ann Rheum Dis 2007; 66:351.
  30. Gorson KC, Natarajan N, Ropper AH, Weinstein R. Rituximab treatment in patients with IVIg-dependent immune polyneuropathy: a prospective pilot trial. Muscle Nerve 2007; 35:66.
  31. Bryce AH, Dispenzieri A, Kyle RA, et al. Response to rituximab in patients with type II cryoglobulinemia. Clin Lymphoma Myeloma 2006; 7:140.
  32. Ring T, Kallenbach M, Praetorius J, et al. Successful treatment of a patient with primary Sjögren's syndrome with Rituximab. Clin Rheumatol 2006; 25:891.
  33. Devauchelle-Pensec V, Morvan J, Pennec Y, et al. Rituximab (anti-CD20) in the treatment of primary Sjögren's syndrome: Results of an open label study. Ann Rheum Dis 2005; 64:S309.
  34. Ahmadi-Simab K, Lamprecht P, Nölle B, et al. Successful treatment of refractory anterior scleritis in primary Sjogren's syndrome with rituximab. Ann Rheum Dis 2005; 64:1087.
  35. Ramos-Casals M, López-Guillermo A, Brito-Zerón P, et al. Treatment of B-cell lymphoma with rituximab in two patients with Sjögren's syndrome associated with hepatitis C virus infection. Lupus 2004; 13:969.
  36. Harner KC, Jackson LW, Drabick JJ. Normalization of anticardiolipin antibodies following rituximab therapy for marginal zone lymphoma in a patient with Sjogren's syndrome. Rheumatology (Oxford) 2004; 43:1309.
  37. Botez SA, Herrmann DN. Prolonged remission of a demyelinating neuropathy in a patient with lymphoma and Sjögren's syndrome after Rituximab therapy. J Clin Neuromuscul Dis 2010; 11:127.
  38. Mekinian A, Ravaud P, Hatron PY, et al. Efficacy of rituximab in primary Sjogren's syndrome with peripheral nervous system involvement: results from the AIR registry. Ann Rheum Dis 2012; 71:84.
  39. Terrier B, Launay D, Kaplanski G, et al. Safety and efficacy of rituximab in nonviral cryoglobulinemia vasculitis: data from the French Autoimmunity and Rituximab registry. Arthritis Care Res (Hoboken) 2010; 62:1787.
  40. Ramos-Casals M, García-Hernández FJ, de Ramón E, et al. Off-label use of rituximab in 196 patients with severe, refractory systemic autoimmune diseases. Clin Exp Rheumatol 2010; 28:468.
  41. Meiners PM, Arends S, Brouwer E, et al. Responsiveness of disease activity indices ESSPRI and ESSDAI in patients with primary Sjögren's syndrome treated with rituximab. Ann Rheum Dis 2012; 71:1297.
  42. Hadjinicolaou AV, Nisar MK, Parfrey H, et al. Non-infectious pulmonary toxicity of rituximab: a systematic review. Rheumatology (Oxford) 2012; 51:653.
  43. Leonard JP, Coleman M, Ketas JC, et al. Epratuzumab, a humanized anti-CD22 antibody, in aggressive non-Hodgkin's lymphoma: phase I/II clinical trial results. Clin Cancer Res 2004; 10:5327.
  44. Furman RR, Coleman M, Leonard JP. Epratuzumab in non-Hodgkin's lymphomas. Curr Treat Options Oncol 2004; 5:283.
  45. Goldenberg DM. Epratuzumab in the therapy of oncological and immunological diseases. Expert Rev Anticancer Ther 2006; 6:1341.
  46. Haas KM, Sen S, Sanford IG, et al. CD22 ligand binding regulates normal and malignant B lymphocyte survival in vivo. J Immunol 2006; 177:3063.
  47. Leonard JP, Coleman M, Ketas J, et al. Combination antibody therapy with epratuzumab and rituximab in relapsed or refractory non-Hodgkin's lymphoma. J Clin Oncol 2005; 23:5044.
  48. Manoussakis MN, Moutsopoulos HM. Antimalarials in Sjögren's syndrome--the Greek experience. Lupus 1996; 5 Suppl 1:S28.
  49. Easterbrook M. An ophthalmological view on the efficacy and safety of chloroquine versus hydroxychloroquine. J Rheumatol 1999; 26:1866.
  50. Biyajima S, Osada T, Daidoji H, et al. Pulmonary hypertension and antiphospholipid antibody in a patient with Sjögren's syndrome. Intern Med 1994; 33:768.
  51. Bridges AJ, Burns RP. Acute iritis associated with primary Sjögren's syndrome and high-titer anti-SS-A/Ro and anti-SS-B/La antibodies. Treatment with combination immunosuppressive therapy. Arthritis Rheum 1992; 35:560.
  52. Friedman J, Larson W, Sorenson E, Ike R. How should peripheral neuropathy associated with primary Sjögren's syndrome be treated? (abstract). Arthritis Rheum 1996; 39:S63.
  53. Fife RS, Chase WF, Dore RK, et al. Cevimeline for the treatment of xerostomia in patients with Sjögren syndrome: a randomized trial. Arch Intern Med 2002; 162:1293.
  54. Sheikh SH, Shaw-Stiffel TA. The gastrointestinal manifestations of Sjögren's syndrome. Am J Gastroenterol 1995; 90:9.
  55. Tishler M, Alosachie I, Barka N, et al. Primary Sjögren's syndrome and primary biliary cirrhosis: differences and similarities in the autoantibody profile. Clin Exp Rheumatol 1995; 13:497.
  56. Jorgensen C, Legouffe MC, Perney P, et al. Sicca syndrome associated with hepatitis C virus infection. Arthritis Rheum 1996; 39:1166.
  57. García-Carrasco M, Ramos M, Cervera R, et al. Hepatitis C virus infection in 'primary' Sjögren's syndrome: prevalence and clinical significance in a series of 90 patients. Ann Rheum Dis 1997; 56:173.
  58. Verbaan H, Carlson J, Eriksson S, et al. Extrahepatic manifestations of chronic hepatitis C infection and the interrelationship between primary Sjögren's syndrome and hepatitis C in Swedish patients. J Intern Med 1999; 245:127.
  59. Caron P, Lassoued S, Dromer C, et al. Prevalence of thyroid abnormalities in patients with rheumatoid arthritis. Thyroidology 1992; 4:99.
  60. Pérez B, Kraus A, López G, et al. Autoimmune thyroid disease in primary Sjögren's syndrome. Am J Med 1995; 99:480.
  61. Delalande S, de Seze J, Fauchais AL, et al. Neurologic manifestations in primary Sjögren syndrome: a study of 82 patients. Medicine (Baltimore) 2004; 83:280.
  62. Mori K, Iijima M, Koike H, et al. The wide spectrum of clinical manifestations in Sjögren's syndrome-associated neuropathy. Brain 2005; 128:2518.
  63. Takahashi Y, Takata T, Hoshino M, et al. Benefit of IVIG for long-standing ataxic sensory neuronopathy with Sjögren's syndrome. IV immunoglobulin. Neurology 2003; 60:503.
  64. Levy Y, Uziel Y, Zandman GG, et al. Intravenous immunoglobulins in peripheral neuropathy associated with vasculitis. Ann Rheum Dis 2003; 62:1221.
  65. Andonopoulos AP, Ballas C. Autonomic cardiovascular neuropathy in primary Sjögren's syndrome. Rheumatol Int 1995; 15:127.
  66. de Seze J, Delalande S, Fauchais AL, et al. Myelopathies secondary to Sjögren's syndrome: treatment with monthly intravenous cyclophosphamide associated with corticosteroids. J Rheumatol 2006; 33:709.
  67. Vaudo G, Bocci EB, Shoenfeld Y, et al. Precocious intima-media thickening in patients with primary Sjögren's syndrome. Arthritis Rheum 2005; 52:3890.
  68. Tensing EK, Solovieva SA, Tervahartiala T, et al. Fatigue and health profile in sicca syndrome of Sjögren's and non-Sjögren's syndrome origin. Clin Exp Rheumatol 2001; 19:313.
  69. Bonafede RP, Downey DC, Bennett RM. An association of fibromyalgia with primary Sjögren's syndrome: a prospective study of 72 patients. J Rheumatol 1995; 22:133.
  70. Tishler M, Barak Y, Paran D, Yaron M. Sleep disturbances, fibromyalgia and primary Sjögren's syndrome. Clin Exp Rheumatol 1997; 15:71.
  71. Kraus A, Cifuentes M, Villa AR, et al. Myositis in primary Sjögren's syndrome. Report of 3 cases. J Rheumatol 1994; 21:649.
  72. Pijpe J, Meijer JM, Bootsma H, et al. Clinical and histologic evidence of salivary gland restoration supports the efficacy of rituximab treatment in Sjögren's syndrome. Arthritis Rheum 2009; 60:3251.
  73. Belenguer R, Ramos-Casals M, Brito-Zerón P, et al. Influence of clinical and immunological parameters on the health-related quality of life of patients with primary Sjögren's syndrome. Clin Exp Rheumatol 2005; 23:351.
  74. Ioannidis JP, Vassiliou VA, Moutsopoulos HM. Long-term risk of mortality and lymphoproliferative disease and predictive classification of primary Sjögren's syndrome. Arthritis Rheum 2002; 46:741.
  75. Thomas E, Symmons DP, Brewster DH, et al. National study of cause-specific mortality in rheumatoid arthritis, juvenile chronic arthritis, and other rheumatic conditions: a 20 year followup study. J Rheumatol 2003; 30:958.
  76. Ramos-Casals M, Font J, Garcia-Carrasco M, et al. Primary Sjögren syndrome: hematologic patterns of disease expression. Medicine (Baltimore) 2002; 81:281.
  77. Ramos-Casals M, Anaya JM, García-Carrasco M, et al. Cutaneous vasculitis in primary Sjögren syndrome: classification and clinical significance of 52 patients. Medicine (Baltimore) 2004; 83:96.
  78. Voulgarelis M, Dafni UG, Isenberg DA, Moutsopoulos HM. Malignant lymphoma in primary Sjögren's syndrome: a multicenter, retrospective, clinical study by the European Concerted Action on Sjögren's Syndrome. Arthritis Rheum 1999; 42:1765.
  79. Ramos-Casals M, Brito-Zerón P, Yagüe J, et al. Hypocomplementaemia as an immunological marker of morbidity and mortality in patients with primary Sjogren's syndrome. Rheumatology (Oxford) 2005; 44:89.