Advertisement

Drugs & Aging

, Volume 25, Issue 1, pp 19–33 | Cite as

Sjögren’s Syndrome

Diagnosis and Therapeutic Challenges in the Elderly
  • Kristine P. Ng
  • David A. Isenberg
Therapy In Practice

Abstract

Sjögren’s syndrome (SS) is a chronic autoimmune rheumatic disease characterized by keratoconjunctivitis sicca and xerostomia as a result of lymphocytic infiltration of the lacrimal and salivary glands. Extra-glandular manifestations occur in about one-third of patients with SS. The diagnosis of SS in the geriatric population is not straightforward and consideration needs to be given to exclusion of other conditions that may have similar presenting symptoms. The presence of autoantibodies, in particular anti-Ro and anti-La antibodies, may aid in the diagnosis of SS. Salivary gland biopsy findings represent one of the objective criteria included in the widely accepted American-European classification diagnostic criteria. However, SS-like histological changes can also be present in the healthy elderly, adding to the dilemma in diagnosing this condition in the geriatric population. Management of SS involves local treatment of dry eyes and mouth with replacement and stimulation therapies. Patients with more serious systemic involvement may require immunosuppressive therapy. Medications that are routinely used in the treatment of patients with SS often have limited use in the elderly population because patients in the latter group may have complex comorbid conditions and be taking multiple medications. Recently, use of newer targeted therapies has been explored in SS. This article provides an update on recent developments in the diagnosis and management of SS, with emphasis on issues that may arise when treating elderly patients with this condition.

Keywords

Salivary Gland Keratoconjunctivitis Sicca Sicca Symptom Cevimeline Minor Salivary Gland Biopsy 
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.

Notes

Acknowledgements

No sources of funding were used to assist in the preparation of this article. Dr Kristine P. Ng is a recipient of the New Zealand Rose Hellaby medical scholarship.

The authors have no conflicts of interest that are directly relevant to the content of this article.

References

  1. 1.
    Manthorpe R, Asmussen K, Oxholm P. Primary Sjogren’s syndrome: diagnostic criteria, clinical features and disease activity. J Rheumatol Suppl 1997 Sep; 50: 8–11PubMedGoogle Scholar
  2. 2.
    Sanchez-Guerrero J, Perez-Dosal MR, Cardenas-Velazquez F, et al. Prevalence of Sjogren’s syndrome in ambulatory patients according to the American-European Consensus Group criteria. Rheumatology (Oxford) 2005 Feb; 44(2): 235–40CrossRefGoogle Scholar
  3. 3.
    Alamanos Y, Tsifetaki N, Voulgari PV, et al. Epidemiology of primary Sjogren’s syndrome in north-west Greece, 1982–2003. Rheumatology (Oxford) 2006 Feb; 45(2): 187–91CrossRefGoogle Scholar
  4. 4.
    Drosos AA, Andonopoulos AP, Costopoulos JS, et al. Prevalence of primary Sjogren’s syndrome in an elderly population. Br J Rheumatol 1988 Apr; 27(2): 123–7PubMedCrossRefGoogle Scholar
  5. 5.
    Whaley K, Williamson J, Wilson T, et al. Sjogren’s syndrome and autoimmunity in a geriatric population. Age Ageing 1972 Nov; 1: 197–206PubMedCrossRefGoogle Scholar
  6. 6.
    Tapinos NI, Polihronis M, Tzioufas AG, et al. Sjogren’s syndrome: autoimmune epithelitis. Adv Exp Med Biol 1999; 455: 127–34PubMedCrossRefGoogle Scholar
  7. 7.
    McArthur C, Wang Y, Veno P, et al. Intracellular trafficking and surface expression of SS-A (Ro), SS-B (La), poly(ADP-ribose) polymerase and alpha-fodrin autoantigens during apoptosis in human salivary gland cells induced by tumour necrosis factor-alpha. Arch Oral Biol 2002 Jun; 47(6): 443–8PubMedCrossRefGoogle Scholar
  8. 8.
    Venables PJ, Rugby SP. Viruses in the etiopathogenesis of Sjogren’s syndrome. J Rheumatol Suppl 1997 Sep; 50: 3–5PubMedGoogle Scholar
  9. 9.
    Sawalha AH, Potts R, Schmid WR, et al. The genetics of primary Sjogren’s syndrome. Curr Rheumatol Rep 2003 Aug; 5(4): 324–32PubMedCrossRefGoogle Scholar
  10. 10.
    Manthorpe R, Oxholm P, Prause JU, et al. The Copenhagen criteria for Sjogren’s syndrome. Scand J Rheumatol Suppl 1986; 61: 19–21PubMedGoogle Scholar
  11. 11.
    Vitali C, Bombardieri S, Moutsopoulos HM, et al. Preliminary criteria for the classification of Sjogren’s syndrome: results of a prospective concerted action supported by the European Community. Arthritis Rheum 1993 Mar; 36(3): 340–7PubMedCrossRefGoogle Scholar
  12. 12.
    Vitali C, Bombardieri S, Jonsson R, et al. Classification criteria for Sjogren’s syndrome: a revised version of the European criteria proposed by the American-European Consensus Group. Ann Rheum Dis 2002 Jun; 61(6): 554–8PubMedCrossRefGoogle Scholar
  13. 13.
    Price EJ, Venables PJ. Dry eyes and mouth syndrome: a subgroup of patients presenting with sicca symptoms. Rheumatology (Oxford) 2002 Apr; 41(4): 416–22CrossRefGoogle Scholar
  14. 14.
    Schein OD, Hochberg MC, Munoz B, et al. Dry eye and dry mouth in the elderly: a population-based assessment. Arch Intern Med 1999 Jun 28; 159(12): 1359–63PubMedCrossRefGoogle Scholar
  15. 15.
    Hochberg MC, Tielsch J, Munoz B, et al. Prevalence of symptoms of dry mouth and their relationship to saliva production in community dwelling elderly: the SEE project. Salisbury Eye Evaluation. J Rheumatol 1998 Mar; 25(3): 486–91PubMedGoogle Scholar
  16. 16.
    Hermann GA, Vivino FB, Goin JE. Scintigraphic features of chronic sialadenitis and Sjogren’s syndrome: a comparison. Nucl Med Commun 1999 Dec; 20(12): 1123–32PubMedCrossRefGoogle Scholar
  17. 17.
    Kalk WW, Vissink A, Spijkervet FK, et al. Morbidity from parotid sialography. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2001 Nov; 92(5): 572–5PubMedCrossRefGoogle Scholar
  18. 18.
    Kalk WW, Vissink A, Spijkervet FK, et al. Parotid sialography for diagnosing Sjogren syndrome. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2002 Jul; 94(1): 131–7PubMedCrossRefGoogle Scholar
  19. 19.
    Radfar L, Kleiner DE, Fox PC, et al. Prevalence and clinical significance of lymphocytic foci in minor salivary glands of healthy volunteers. Arthritis Rheum 2002 Oct 15; 47(5): 520–4PubMedCrossRefGoogle Scholar
  20. 20.
    Xu KP, Katagiri S, Takeuchi T, et al. Biopsy of labial salivary glands and lacrimal glands in the diagnosis of Sjogren’s syndrome. J Rheumatol 1996 Jan; 23(1): 76–82PubMedGoogle Scholar
  21. 21.
    de Wilde PC, Baak JP, Slootweg PJ, et al. Morphometry in the diagnosis of Sjogren’s syndrome. Anal Quant Cytol Histol 1986 Mar; 8(1): 49–55PubMedGoogle Scholar
  22. 22.
    Pennec YL, Leroy JP, Jouquan J, et al. Comparison of labial and sublingual salivary gland biopsies in the diagnosis of Sjogren’s syndrome. Ann Rheum Dis 1990 Jan; 49(1): 37–9PubMedCrossRefGoogle Scholar
  23. 23.
    Fox PC. Simplified biopsy technique for labial minor salivary glands. Plast Reconstr Surg 1985 Apr; 75(4): 592–3PubMedCrossRefGoogle Scholar
  24. 24.
    Daniels TE. Labial salivary gland biopsy in Sjogren’s syndrome: assessment as a diagnostic criterion in 362 suspected cases. Arthritis Rheum 1984 Feb; 27(2): 147–56PubMedCrossRefGoogle Scholar
  25. 25.
    Chisholm DM, Mason DK. Labial salivary gland biopsy in Sjogren’s disease. J Clin Pathol 1968 Sep; 21(5): 656–60PubMedCrossRefGoogle Scholar
  26. 26.
    Daniels TE, Whitcher JP. Association of patterns of labial salivary gland inflammation with keratoconjunctivitis sicca: analysis of 618 patients with suspected Sjogren’s syndrome. Arthritis Rheum 1994 Jun; 37(6): 869–77PubMedCrossRefGoogle Scholar
  27. 27.
    Greenspan JS, Daniels TE, Talal N, et al. The histopathology of Sjogren’s syndrome in labial salivary gland biopsies. Oral Surg Oral Med Oral Pathol 1974 Feb; 37(2): 217–29PubMedCrossRefGoogle Scholar
  28. 28.
    Kikuchi M, Inagaki T, Ogawa K, et al. Histopathological investigation of salivary glands in the asymptomatic elderly. Arch Gerontol Geriatr 2004 Mar–Apr; 38(2): 131–8PubMedCrossRefGoogle Scholar
  29. 29.
    Larsson A, Bredberg A, Henriksson G, et al. Immunohistochemistry of the B-cell component in lower lip salivary glands of Sjogren’s syndrome and healthy subjects. Scand J Immunol 2005 Jan; 61(1): 98–107PubMedCrossRefGoogle Scholar
  30. 30.
    Adamson 3rd TC, Fox RI, Frisman DM, et al. Immunohistologic analysis of lymphoid infiltrates in primary Sjogren’s syndrome using monoclonal antibodies. J Immunol 1983 Jan; 130(1): 203–8PubMedGoogle Scholar
  31. 31.
    Manthorpe R, Benoni C, Jacobsson L, et al. 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 2000 Jan; 59(1): 54–60PubMedCrossRefGoogle Scholar
  32. 32.
    Morimoto Y, Habu M, Tomoyose T, et al. Dynamic magnetic resonance sialography as a new diagnostic technique for patients with Sjogren’s syndrome. Oral Dis 2006 Jul; 12(4): 408–14PubMedCrossRefGoogle Scholar
  33. 33.
    Hocevar A, Ambrozic A, Rozman B, et al. Ultrasonographic changes of major salivary glands in primary Sjogren’s syndrome: diagnostic value of a novel scoring system. Rheumatology 2005 Jun; 44(6): 768–72PubMedCrossRefGoogle Scholar
  34. 34.
    Niemela RK, Takalo R, Paakko E, et al. Ultrasonography of salivary glands in primary Sjogren’s syndrome: a comparison with magnetic resonance imaging and magnetic resonance sialography of parotid glands. Rheumatology 2004 Jul; 43(7): 875–9PubMedCrossRefGoogle Scholar
  35. 35.
    Manoussakis MN, Tzioufas AG, Silis MP, et al. High prevalence of anti-cardiolipin and other autoantibodies in a healthy elderly population. Clin Exp Immunol 1987 Sep; 69(3): 557–65PubMedGoogle Scholar
  36. 36.
    Haga HJ, Jonsson R. The influence of age on disease manifestations and serological characteristics in primary Sjogren’s syndrome. Scand J Rheumatol 1999; 28(4): 227–32PubMedCrossRefGoogle Scholar
  37. 37.
    Tishler M, Yaron I, Shirazi I, et al. Clinical and immunological characteristics of elderly onset Sjogren’s syndrome: a comparison with younger onset disease. J Rheumatol 2001 Apr; 28(4): 795–7PubMedGoogle Scholar
  38. 38.
    Garcia-Carrasco M, Cervera R, Rosas J, et al. Primary Sjogren’s syndrome in the elderly: clinical and immunological characteristics. Lupus 1999; 8(1): 20–3PubMedCrossRefGoogle Scholar
  39. 39.
    Asmussen K, Andersen V, Bendicen G, et al. A new model for classification of disease manifestations in primary Sjogren’s syndrome: evaluation in a retrospective long term study. J Int Med 1996 Jun; 239(6): 475–82CrossRefGoogle Scholar
  40. 40.
    Daniels TE, Silverman Jr S, Michalski JP, et al. The oral component of Sjogren’s syndrome. Oral Surg 1975 Jun; 39(6): 875–85PubMedCrossRefGoogle Scholar
  41. 41.
    Fox RI. Clinical features, pathogenesis, and treatment of Sjogren’s syndrome. Curr Opin Rheumatol 1996 Sep; 8(5): 438–45PubMedCrossRefGoogle Scholar
  42. 42.
    Freeman SR, Sheehan PZ, Thorpe MA, et al. Ear, nose, and throat manifestations of Sjogren’s syndrome: retrospective review of a multidisciplinary clinic. J Otolaryngol 2005 Feb; 34(1): 20–4PubMedCrossRefGoogle Scholar
  43. 43.
    Haga HJ, Gjesdal CG, Irgens LM, et al. Reproduction and gynaecological manifestations in women with primary Sjogren’s syndrome: a case-control study. Scand J Rheumatol 2005; 34(1): 45–8PubMedCrossRefGoogle Scholar
  44. 44.
    Wright SA, Convery RP, Liggett N. Pulmonary involvement in Sjogren’s syndrome. Rheumatology (Oxford) 2003 May; 42: 697–8CrossRefGoogle Scholar
  45. 45.
    Parambil JG, Myers JL, Lindell RM, et al. Interstitial lung disease in primary Sjogren syndrome. Chest 2006 Nov; 130(5): 1489–95PubMedCrossRefGoogle Scholar
  46. 46.
    Papiris SA, Maniati M, Constantopoulos SH, et al. Lung involvement in primary Sjogren’s syndrome is mainly related to the small airway disease. Ann Rheum Dis 1999 Jan; 58(1): 61–4PubMedCrossRefGoogle Scholar
  47. 47.
    Davidson BK, Kelly CA, Griffiths ID. Ten year follow up of pulmonary function in patients with primary Sjogren’s syndrome. Ann Rheum Dis 2000 Sep; 59(9): 709–12PubMedCrossRefGoogle Scholar
  48. 48.
    Soy M, Piskin S. Cutaneous findings in patients with primary Sjogren’s syndrome. Clin Rheumatol 2006; 26(8): 1350–2PubMedCrossRefGoogle Scholar
  49. 49.
    Bernacchi E, Amato L, Parodi A, et al. Sjogren’s syndrome: a retrospective review of the cutaneous features of 93 patients by the Italian Group of Immunodermatology. Clin Exp Rheumatol 2004 Jan–Feb; 22(1): 55–62PubMedGoogle Scholar
  50. 50.
    Ramos-Casals M, Anaya JM, Garcia-Carrasco M, et al. Cutaneous vasculitis in primary Sjogren syndrome: classification and clinical significance of 52 patients. Medicine (Baltimore) 2004 Mar; 83(2): 96–106CrossRefGoogle Scholar
  51. 51.
    Pease CT, Shattles W, Barrett NK, et al. The arthropathy of Sjogren’s syndrome. Br J Rheumatol 1993 Jul; 32(7): 609–13PubMedCrossRefGoogle Scholar
  52. 52.
    Gottenberg JE, Mignot S, Nicaise-Rolland P, et al. Prevalence of anti-cyclic citrullinated peptide and anti-keratin antibodies in patients with primary Sjogren’s syndrome. Ann Rheum Dis 2005 Jan; 64(1): 114–7PubMedCrossRefGoogle Scholar
  53. 53.
    Ostuni P, Botsios C, Sfriso P, et al. Fibromyalgia in Italian patients with primary Sjogren’s syndrome. Joint Bone Spine 2002 Jan; 69(1): 51–7PubMedCrossRefGoogle Scholar
  54. 54.
    Giles I, Isenberg D. Fatigue in primary Sjogren’s syndrome: is there a link with the fibromyalgia syndrome? Ann Rheum Dis 2000 Nov; 59(11): 875–8PubMedCrossRefGoogle Scholar
  55. 55.
    Lindvall B, Bengtsson A, Ernerudh J, et al. Subclinical myositis is common in primary Sjogren’s syndrome and is not related to muscle pain. J Rheumatol 2002 Apr; 29(4): 717–25PubMedGoogle Scholar
  56. 56.
    Binder A, Snaith ML, Isenberg D. Sjogren’s syndrome: a study of its neurological complications. Br J Rheumatol 1988 Aug; 27(4): 275–80PubMedCrossRefGoogle Scholar
  57. 57.
    Govoni M, Padovan M, Rizzo N, et al. Neurological involvement in primary Sjogren’s syndrome: prevalence, clinical aspects, diagnostic assessment and therapeutic approach. CNS Drugs 2001; 15(8): 597–607PubMedCrossRefGoogle Scholar
  58. 58.
    Lafitte C, Amoura Z, Cacoub P, et al. Neurological complications of primary Sjogren’s syndrome. J Neurol 2001 Jul; 248(7): 577–84PubMedCrossRefGoogle Scholar
  59. 59.
    Goransson LG, Herigstad A, Tjensvoll AB, et al. Peripheral neuropathy in primary Sjogren syndrome: a population-based study. Arch Neurol 2006 Nov; 63(11): 1612–5PubMedCrossRefGoogle Scholar
  60. 60.
    Lopate G, Pestronk A, Al-Lozi M, et al. Peripheral neuropathy in an outpatient cohort of patients with Sjogren’s syndrome. Muscle Nerve 2006 May; 33(5): 672–6PubMedCrossRefGoogle Scholar
  61. 61.
    Barendregt PJ, van den Bent MJ, van Raaij-van den Aarssen VJ, et al. Involvement of the peripheral nervous system in primary Sjogren’s syndrome. Ann Rheum Dis 2001 Sep; 60(9): 876–81PubMedGoogle Scholar
  62. 62.
    Andonopoulos AP, Christodoulou J, Ballas C, et al. Autonomic cardiovascular neuropathy in Sjogren’s syndrome: a controlled study. J Rheumatol 1998 Dec; 25(12): 2385–8PubMedGoogle Scholar
  63. 63.
    Alexander EL. Neurologic disease in Sjögren’s syndrome: mononuclear inflammatory vasculopathy affecting central/peripheral nervous system and muscle: a clinical review and update of immunopathogenesis. Rheum Dis Clin North Am 1993 Nov; 19(4): 869–908PubMedGoogle Scholar
  64. 64.
    Coates T, Slavotinek JP, Rischmueller M, et al. Cerebral white matter lesions in primary Sjogren’s syndrome: a controlled study. J Rheumatol 1999 Jun; 26(6): 1301–5PubMedGoogle Scholar
  65. 65.
    de Leeuw FE, de Groot JC, Achten E, et al. Prevalence of cerebral white matter lesions in elderly people: a population based magnetic resonance imaging study. The Rotterdam Scan Study. J Neurol Neurosurg Psychiatry 2001 Jan; 70(1): 9–14PubMedCrossRefGoogle Scholar
  66. 66.
    Bossini N, Savoldi S, Franceschini F, et al. Clinical and morphological features of kidney involvement in primary Sjogren’s syndrome. Nephrol Dial Transplant 2001 Dec; 16(12): 2328–36PubMedCrossRefGoogle Scholar
  67. 67.
    Goules A, Masouridi S, Tzioufas AG, et al. Clinically significant and biopsy-documented renal involvement in primary Sjogren syndrome. Medicine (Baltimore) 2000 Jul; 79(4): 241–9CrossRefGoogle Scholar
  68. 68.
    Leppilahti M, Tammela TL, Huhtala H, et al. Interstitial cystitislike urinary symptoms among patients with Sjogren’s syndrome: a population-based study in Finland. Am J Med 2003 Jul; 115(1): 62–5PubMedCrossRefGoogle Scholar
  69. 69.
    Wotherspoon AC, Doglioni C, Diss TC, et al. Regression of primary low-grade B-cell gastric lymphoma of mucosa-associated lymphoid tissue type after eradication of Helicobacter pylori. Lancet 1993 Sep 4; 342(8871): 575–7PubMedCrossRefGoogle Scholar
  70. 70.
    Raderer M, Osterreicher C, Machold K, et al. Impaired response of gastric MALT-lymphoma to Helicobacter pylori eradication in patients with autoimmune disease. Ann Oncol 2001 Jul; 12(7): 937–9PubMedCrossRefGoogle Scholar
  71. 71.
    Kaplan MJ, Ike RW. The liver is a common non-exocrine target in primary Sjogren’s syndrome: a retrospective review. BMC Gastroenterol 2002 Sep 13; 2: 21PubMedCrossRefGoogle Scholar
  72. 72.
    Miller EB, Shichmanter R, Friedman JA, et al. Granulomatous hepatitis and Sjogren’s syndrome: an association. Semin Arthritis Rheum 2006 Dec; 36(3): 153–8PubMedCrossRefGoogle Scholar
  73. 73.
    Reichlin M. Antibodies to Ro and La. Ann Med Interne (Paris) 1998 Feb; 149(1): 34–41Google Scholar
  74. 74.
    Ramos-Casals M, Nardi N, Brito-Zeron P, et al. Atypical auto-antibodies in patients with primary Sjogren syndrome: clinical characteristics and follow-up of 82 cases. Semin Arthritis Rheum 2006 Apr; 35(5): 312–21PubMedCrossRefGoogle Scholar
  75. 75.
    Ramos-Casals M, Font J, Garcia-Carrasco M, et al. Primary Sjogren syndrome: hematologic patterns of disease expression. Medicine (Baltimore) 2002 Jul; 81(4): 281–92CrossRefGoogle Scholar
  76. 76.
    Stewart A, Blenkinsopp PT, Henry K. Bilateral parotid MALT lymphoma and Sjogren’s syndrome. Br J Oral Maxillofac Surg 1994 Oct; 32(5): 318–22PubMedCrossRefGoogle Scholar
  77. 77.
    Kassan SS, Thomas TL, Moutsopoulos HM, et al. Increased risk of lymphoma in sicca syndrome. Ann Intern Med 1978 Dec; 89(6): 888–92PubMedGoogle Scholar
  78. 78.
    Theander E, Henriksson G, Ljungberg O, et al. Lymphoma and other malignancies in primary Sjogren’s syndrome: a cohort study on cancer incidence and lymphoma predictors. Ann Rheum Dis 2006 Jun; 65(6): 796–803PubMedCrossRefGoogle Scholar
  79. 79.
    Lazarus M, Robinson D, Mak V, et al. Incidence of cancer in a cohort of patients with primary Sjogren’s syndrome. Rheumatology 2006; 45: 1012–5PubMedCrossRefGoogle Scholar
  80. 80.
    Voulgarelis M, Dafni UG, Isenberg DA, et al. Malignant lymphoma in primary Sjogren’s syndrome: a multicenter, retrospective, clinical study by the European Concerted Action on Sjogren’s Syndrome. Arthritis Rheum 1999 Aug; 42(8): 1765–72PubMedCrossRefGoogle Scholar
  81. 81.
    Bernatsky S, Ramsey-Goldman R, Clarke A. Malignancy and autoimmunity. Curr Opin Rheumatol 2006 Mar; 18(2): 129–34PubMedCrossRefGoogle Scholar
  82. 82.
    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 Mar; 46(3): 741–7PubMedCrossRefGoogle Scholar
  83. 83.
    Anaya JM, Tobon GJ, Vega P, et al. Autoimmune disease aggregation in families with primary Sjogren’s syndrome. J Rheum 2006 Nov; 33(11): 2227–34PubMedGoogle Scholar
  84. 84.
    Lazarus M, Isenberg D. Development of additional autoimmune diseases in a population of patients with primary Sjogren’s syndrome. Ann Rheum Dis 2005 Jul; 64: 1062–4PubMedCrossRefGoogle Scholar
  85. 85.
    Vivino FB, Al-Hashimi I, Khan Z, et al. Pilocarpine tablets for the treatment of dry mouth and dry eye symptoms in patients with Sjogren syndrome: a randomized, placebo-controlled, fixed-dose, multicenter trial. P92-01 Study Group. Arch Intern Med 1999 Jan 25; 159(2): 174–81PubMedCrossRefGoogle Scholar
  86. 86.
    Tsifetaki N, Kitsos G, Paschides CA, et al. Oral pilocarpine for the treatment of ocular symptoms in patients with Sjogren’s syndrome: a randomised 12 week controlled study. Ann Rheum Dis 2003 Dec; 62(12): 1204–7PubMedCrossRefGoogle Scholar
  87. 87.
    Petrone D, Condemi JJ, Fife R, et al. A double-blind, randomized, placebo-controlled study of cevimeline in Sjogren’s syndrome patients with xerostomia and keratoconjunctivitis sicca. Arthritis Rheum 2002 Mar; 46(3): 748–54PubMedCrossRefGoogle Scholar
  88. 88.
    Fife RS, Chase WF, Dore RK, et al. Cevimeline for the treatment of xerostomia in patients with Sjogren syndrome: a randomized trial. Arch Intern Med 2002 Jun 10; 162(11): 1293–300PubMedCrossRefGoogle Scholar
  89. 89.
    Cummins M, Papas A, Kammer G, et al. Treatment of primary Sjogren’s syndrome with low dose human interferon alpha administered by the oromucosal route: combined phase III results. Arthritis Rheum 2003; 49(4): 585–93PubMedCrossRefGoogle Scholar
  90. 90.
    Fox RI, Dixon R, Guarrasi V, et al. Treatment of primary Sjogren’s syndrome with hydroxychloroquine: a retrospective, open-label study. Lupus 1996 Jun; 5Suppl. 1: S31–6PubMedCrossRefGoogle Scholar
  91. 91.
    Kruize AA, Hene RJ, Kallenberg CG, et al. Hydroxychloroquine treatment for primary Sjogren’s syndrome: a two year double blind crossover trial. Ann Rheum Dis 1993 May; 52(5): 360–4PubMedCrossRefGoogle Scholar
  92. 92.
    Skopouli FN, Jagiello P, Tsifetaki N, et al. Methotrexate in primary Sjogren’s syndrome. Clin Exp Rheumatol 1996 Sep–Oct; 14(5): 555–8PubMedGoogle Scholar
  93. 93.
    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 May; 25(5): 896–9PubMedGoogle Scholar
  94. 94.
    Drosos AA, Skopouli FN, Galanopoulou VK, et al. Cyclosporin A therapy in patients with primary Sjogren’s syndrome: results at one year. Scand J Rheumatol Suppl 1986; 61: 246–9PubMedGoogle Scholar
  95. 95.
    Kizawa M, Mori K, Iijima M, et al. Intravenous immunoglobulin treatment in painful sensory neuropathy without sensory ataxia associated with Sjogren’s syndrome. J Neurol Neurosurg Psychiatry 2006 Aug; 77(8): 967–9PubMedCrossRefGoogle Scholar
  96. 96.
    de Seze J, Delalande S, Fauchais AL, et al. Myelopathies secondary to Sjogren’s syndrome: treatment with monthly intravenous cyclophosphamide associated with corticosteroids. J Rheumatol 2006 Apr; 33(4): 709–11PubMedGoogle Scholar
  97. 97.
    Delalande S, de Seze J, Fauchais AL, et al. Neurologic manifestations in primary Sjogren syndrome: a study of 82 patients. Medicine (Baltimore) 2004 Sep; 83(5): 280–91CrossRefGoogle Scholar
  98. 98.
    Miyawaki S, Nishiyama S, Matoba K. Efficacy of low dose prednisolone maintenance for saliva production and serological abnormalities in patients with primary Sjogren’s syndrome. Intern Med 1999 Dec; 38(12): 938–43PubMedCrossRefGoogle Scholar
  99. 99.
    Sankar V, Brennan MT, Kok MR, et al. Etanercept in Sjogren’s syndrome: a twelve-week randomized, double-blind, placebo-controlled pilot clinical trial. Arthritis Rheum 2004 Jul; 50(7): 2240–5PubMedCrossRefGoogle Scholar
  100. 100.
    Mariette X, Ravaud P, Steinfeld S, et al. Inefficacy of infliximab in primary Sjogren’s syndrome: results of the randomized, controlled Trial of Remicade in Primary Sjogren’s Syndrome (TRIPSS). Arthritis Rheum 2004 Apr; 50(4): 1270–6PubMedCrossRefGoogle Scholar
  101. 101.
    Pijpe J, van Imhoff GW, Spijkervet FK, et al. Rituximab treatment in patients with primary Sjogren’s syndrome: an open-label phase II study. Arthritis Rheum 2005 Sep; 52(9): 2740–50PubMedCrossRefGoogle Scholar
  102. 102.
    Steinfeld SD, Tant L, Burmester GR, et al. Epratuzumab (humanised anti-CD22 antibody) in primary Sjogren’s syndrome: an open-label phase I/II study. Arthritis Res Ther 2006; 8(4): R129PubMedCrossRefGoogle Scholar
  103. 103.
    Aragona P, Stilo A, Ferreri F, et al. Effects of the topical treatment with NSAIDs on corneal sensitivity and ocular surface of Sjogren’s syndrome patients. Eye 2005 May; 19(5): 535–9PubMedCrossRefGoogle Scholar
  104. 104.
    Marsh P, Pflugfelder SC. Topical nonpreserved methyl-prednisolone therapy for keratoconjunctivitis sicca in Sjogren syndrome. Ophthalmology 1999 Apr; 106(4): 811–6PubMedCrossRefGoogle Scholar
  105. 105.
    Hong S, Kim T, Chung S, et al. Recurrence after topical non-preserved methylprednisolone therapy for keratoconjunctivitis sicca in Sjogren’s syndrome. J Ocul Pharm Therapeut 2007; 23: 78–82CrossRefGoogle Scholar
  106. 106.
    Sall K, Stevenson O, Mondorf T, et al. Two multicenter randomized studies of the efficacy and safety of cyclosporine ophthalmic emulsion in moderate to severe dry eyes: CsA Phase 3 Study Group. Ophthalmology 2000 Apr; 107(4): 631–9PubMedCrossRefGoogle Scholar
  107. 107.
    Tatlipinar S, Akpek E. Topical ciclosporin in the treatment of ocular surface disorders. Br J Ophthalmol 2005 Oct; 89(10): 1363–7PubMedCrossRefGoogle Scholar
  108. 108.
    Gunduz K, Ozdemir O. Topical cyclosporin treatment of keratoconjunctivitis sicca in secondary Sjogren’s syndrome. Acta Ophthalmol (Copenh) 1994 Aug; 72(4): 438–42CrossRefGoogle Scholar
  109. 109.
    Al-Hashimi I. Xerostomia secondary to Sjögren’s syndrome in the elderly: recognition and management. Drugs Aging 2005; 22(11): 887–99PubMedCrossRefGoogle Scholar
  110. 110.
    van der Reijden WA, van der Kwaak H, Vissink A, et al. Treatment of xerostomia with polymer-based saliva substitutes in patients with Sjogren’s syndrome. Arthritis Rheum 1996 Jan; 39(1): 57–63PubMedCrossRefGoogle Scholar
  111. 111.
    Mulherin D, Ainsworth JR, Hamburger J, et al. Survey of artificial tear and saliva usage among patients with Sjogren’s syndrome [letter]. Ann Rheum Dis 2001 Nov; 60(11): 1077PubMedCrossRefGoogle Scholar
  112. 112.
    Venables PJ. Management of patients presenting with Sjogren’ syndrome. Best Pract Res Clin Rheumatol 2006 Aug; 20(4): 791–807PubMedCrossRefGoogle Scholar
  113. 113.
    Khurshudian AV. A pilot study to test the efficacy of oral administration of interferon-alpha lozenges to patients with Sjogren’s syndrome. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2003 Jan; 95(1): 38–44PubMedCrossRefGoogle Scholar
  114. 114.
    Ship JA, Fox PC, Michalek JE, et al. Treatment of primary Sjogren’s syndrome with low-dose natural human interferon-alpha administered by the oral mucosal route: a phase II clinical trial. IFN Protocol Study Group. J Interferon Cytokine Res 1999 Aug; 19(8): 943–51PubMedCrossRefGoogle Scholar
  115. 115.
    Shiozawa S, Tanaka Y, Shiozawa K. Single-blinded controlled trial of low-dose oral IFN-alpha for the treatment of xerostomia in patients with Sjogren’s syndrome. J Interferon Cytokine Res 1998 Apr; 18(4): 255–62PubMedCrossRefGoogle Scholar
  116. 116.
    Ferraccioli GF, Salaffi F, De Vita S, et al. Interferon alpha-2 (IFN alpha 2) increases lacrimal and salivary function in Sjogren’s syndrome patients: preliminary results of an open pilot trial versus OH-chloroquine. Clin Exp Rheumatol 1996 Jul–Aug; 14(4): 367–71PubMedGoogle Scholar
  117. 117.
    Kastrup O, Maschke M, Diener HC. Pulse-cyclophosphamide in the treatment of ataxic sensory and cranial nerve neuropathy associated with Sjogren’s syndrome. Clin Neurol Neurosurg 2005 Aug; 107(5): 440–1PubMedCrossRefGoogle Scholar
  118. 118.
    Levy Y, Uziel Y, Zandman G, et al. Intravenous immunoglobulins in peripheral neuropathy associated with vasculitis. Ann Rheum Dis 2003 Dec; 62(12): 1221–3PubMedCrossRefGoogle Scholar
  119. 119.
    Steinfeld SD, Demols P, Salmon I, et al. Infliximab in patients with primary Sjogren’s syndrome: a pilot study. Arthritis Rheum 2001 Oct; 44(10): 2371–5PubMedCrossRefGoogle Scholar
  120. 120.
    Voulgarelis M, Giannouli S, Tzioufas AG, et al. 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 Aug; 65(8): 1033–7PubMedCrossRefGoogle Scholar

Copyright information

© Adis Data Information BV 2008

Authors and Affiliations

  1. 1.Centre for Rheumatology Research, Division of MedicineUniversity College LondonLondonUK

Personalised recommendations