Journal of Oral Medicine and Pain

Korean Academy of Orofacial Pain and Oral Medicine (대한안면통증구강내과학회)
권호 표지
DOI QR코드

DOI QR Code

An Update on Sjögren's Syndrome for Oral Medicine Specialists

  • Lee, Kyung-Eun (Department of Oral Medicine, Institute of Oral Bioscience, School of Dentistry, Jeonbuk National University) ;
  • Jung, Won (Department of Oral Medicine, Institute of Oral Bioscience, School of Dentistry, Jeonbuk National University)
  • Received : 2021.12.01
  • Accepted : 2021.12.09
  • Published : 2021.12.30
Download PDF
⟨ Previous Next ⟩

Abstract

Sjögren's syndrome (SjS) is a common autoimmune disorder characterized by lymphocytic infiltration in the salivary and lacrimal glands, resulting in severe dry mouth or eyes. The symptoms are complex and heterogeneous. Several diagnostic criteria have been proposed for SjS and its subsets over the years. However, on the other hands, great efforts have been made searching for reliable biomarkers able to ameliorate the diagnostic algorithm and the prognostic stratification of SjS patients. The aim of this article is to review biomarkers and treatments related to SjS for oral medicine specialists.

Keywords

References

  1. Fox RI. Sjogren's syndrome. Lancet 2005;366:321-331. https://doi.org/10.1016/S0140-6736(05)66990-5
  2. Ramos-Casals M, Tzioufas AG, Font J. Primary Sjogren's syndrome: new clinical and therapeutic concepts. Ann Rheum Dis 2005;64:347-354. https://doi.org/10.1136/ard.2004.025676
  3. Ramos-Casals M, Brito-Zeron P, Siso-Almirall A, Bosch X. Primary Sjogren syndrome. BMJ 2012;344:e3821. https://doi.org/10.1136/bmj.e3821
  4. 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;61:554-558. https://doi.org/10.1136/ard.61.6.554
  5. Shiboski SC, Shiboski CH, Criswell L, et al. American College of Rheumatology classification criteria for Sjogren's syndrome: a data-driven, expert consensus approach in the Sjogren's International Collaborative Clinical Alliance cohort. Arthritis Care Res (Hoboken) 2012;64:475-487. https://doi.org/10.1002/acr.21591
  6. Shiboski CH, Shiboski SC, Seror R, et al. 2016 American College of Rheumatology/European League Against Rheumatism classification criteria for primary Sjogren's syndrome: a consensus and data-driven methodology involving three international patient cohorts. Arthritis Rheumatol 2017;69:35-45. https://doi.org/10.1002/art.39859
  7. Chen W, Cao H, Lin J, Olsen N, Zheng SG. Biomarkers for primary Sjogren's syndrome. Genomics Proteomics Bioinformatics 2015;13:219-223. https://doi.org/10.1016/j.gpb.2015.06.002
  8. Baldini C, Ferro F, Elefante E, Bombardieri S. Biomarkers for Sjogren's syndrome. Biomark Med 2018;12:275-286. https://doi.org/10.2217/bmm-2017-0297
  9. Ko MY, Heo JY, Ok SM, Kim KH, Jeong SH, Ahn YW. The analysis and study of first visit outpatients in oral medicine. J Oral Med Pain 2013;38:137-142. https://doi.org/10.14476/jomp.2013.38.2.137
  10. Lee KE. Sjogren's syndrome: an update on diagnostic, clinical, and basic aspects for oral medicine specialists. J Oral Med Pain 2018;43:99-111. https://doi.org/10.14476/JOMP.2018.43.4.99
  11. Clark G, Reichlin M, Tomasi TB Jr. Characterization of a soluble cytoplasmic antigen reactive with sera from patients with systemic lupus erythmatosus. J Immunol 1969;102:117-122.
  12. Mattioli M, Reichlin M. Heterogeneity of RNA protein antigens reactive with sera of patients with systemic lupus erythematosus. Description of a cytoplasmic nonribosomal antigen. Arthritis Rheum 1974;17:421-429. https://doi.org/10.1002/art.1780170413
  13. Alspaugh MA, Tan EM. Antibodies to cellular antigens in Sjogren's syndrome. J Clin Invest 1975;55:1067-1073. https://doi.org/10.1172/JCI108007
  14. Alspaugh M, Maddison P. Resolution of the identity of certain antigen-antibody systems in systemic lupus erythematosus and Sjogren's syndrome: an interlaboratory collaboration. Arthritis Rheum 1979;22:796-798. https://doi.org/10.1002/art.1780220719
  15. Shen L, Suresh L. Autoantibodies, detection methods and panels for diagnosis of Sjogren's syndrome. Clin Immunol 2017;182:24-29. https://doi.org/10.1016/j.clim.2017.03.017
  16. Bournia VK, Vlachoyiannopoulos PG. Subgroups of Sjogren syndrome patients according to serological profiles. J Autoimmun 2012;39:15-26. https://doi.org/10.1016/j.jaut.2012.03.001
  17. Ingegnoli F, Castelli R, Gualtierotti R. Rheumatoid factors: clinical applications. Dis Markers 2013;35:727-734. https://doi.org/10.1155/2013/726598
  18. Fayyaz A, Kurien BT, Scofield RH. Autoantibodies in Sjogren's syndrome. Rheum Dis Clin North Am 2016;42:419-434. https://doi.org/10.1016/j.rdc.2016.03.002
  19. Muro Y. Antinuclear antibodies. Autoimmunity 2005;38:3-9. https://doi.org/10.1080/08916930400024612
  20. Nosal RS, Superville SS, Varacallo M. StatPearls. Biochemistry, antinuclear antibodies. Treasure Island: StatPearls; 2021.
  21. Whitcher JP, Shiboski CH, Shiboski SC, et al. A simplified quantitative method for assessing keratoconjunctivitis sicca from the Sjogren's Syndrome International Registry. Am J Ophthalmol 2010;149:405-415. https://doi.org/10.1016/j.ajo.2009.09.013
  22. Huo AP, Lin KC, Chou CT. Predictive and prognostic value of antinuclear antibodies and rheumatoid factor in primary Sjogren's syndrome. Int J Rheum Dis 2010;13:39-47. https://doi.org/10.1111/j.1756-185X.2009.01444.x
  23. Theander E, Jonsson R, Sjostrom B, Brokstad K, Olsson P, Henriksson G. Prediction of Sjogren's syndrome years before diagnosis and identification of patients with early onset and severe disease course by autoantibody profiling. Arthritis Rheumatol 2015;67:2427-2436. https://doi.org/10.1002/art.39214
  24. Haneji N, Nakamura T, Takio K, et al. Identification of alpha-fodrin as a candidate autoantigen in primary Sjogren's syndrome. Science 1997;276:604-607. https://doi.org/10.1126/science.276.5312.604
  25. Hu Q, Wang D, Chen W. The accuracy of the anti-α-fodrin antibody test for diagnosis of Sjogren's syndrome: a meta-analysis. Clin Biochem 2013;46:1372-1376. https://doi.org/10.1016/j.clinbiochem.2013.04.020
  26. Willeke P, Gaubitz M, Schotte H, et al. Clinical and immunological characteristics of patients with Sjogren's syndrome in relation to alpha-fodrin antibodies. Rheumatology (Oxford) 2007;46:479-483. https://doi.org/10.1093/rheumatology/kel270
  27. Qin Q, Wang H, Wang HZ, et al. Diagnostic accuracy of anti-alpha-fodrin antibodies for primary Sjogren's syndrome. Mod Rheumatol 2014;24:793-797. https://doi.org/10.3109/14397595.2013.865823
  28. Lee KE, Kang JH, Lee JW, et al. Anti-centromere antibody-positive Sjogren's syndrome: a distinct clinical subgroup? Int J Rheum Dis 2015;18:776-782. https://doi.org/10.1111/1756-185X.12684
  29. Li Y, Bookman AAM. Comparison of effect on sicca symptoms of anticentromere antibody-positive Sjogren syndrome and primary Sjogren syndrome alone. J Rheumatol 2020;47:876-880. https://doi.org/10.3899/jrheum.190462
  30. Park Y, Lee J, Koh JH, et al. Clinical influences of anticentromere antibody on primary Sjogren's syndrome in a prospective Korean cohort. Korean J Intern Med 2021;36:1492-1503. https://doi.org/10.3904/kjim.2020.146
  31. Shen L, Suresh L, Li H, et al. IL-14 alpha, the nexus for primary Sjogren's disease in mice and humans. Clin Immunol 2009;130:304-312. https://doi.org/10.1016/j.clim.2008.10.006
  32. Vishwanath S, Shen L, Suresh L, Ambrus JL Jr. Anti-salivary gland protein 1 antibodies in two patients with Sjogren's syndrome: two case reports. J Med Case Rep 2014;8:145. https://doi.org/10.1186/1752-1947-8-145
  33. Shen L, Kapsogeorgou EK, Yu M, et al. Evaluation of salivary gland protein 1 antibodies in patients with primary and secondary Sjogren's syndrome. Clin Immunol 2014;155:42-46. https://doi.org/10.1016/j.clim.2014.08.009
  34. Martin-Nares E, Hernandez-Molina G. Novel autoantibodies in Sjogren's syndrome: a comprehensive review. Autoimmun Rev 2019;18:192-198. https://doi.org/10.1016/j.autrev.2018.09.003
  35. Khovidhunkit W, Hachem JP, Medzihradszky KF, et al. Parotid secretory protein is an HDL-associated protein with anticandidal activity. Am J Physiol Regul Integr Comp Physiol 2005;288:R1306-R1315. https://doi.org/10.1152/ajpregu.00007.2004
  36. Cecchettini A, Finamore F, Puxeddu I, Ferro F, Baldini C. Salivary extracellular vesicles versus whole saliva: new perspectives for the identification of proteomic biomarkers in Sjogren's syndrome. Clin Exp Rheumatol 2019;37 Suppl 118:240-248.
  37. Deng C, Hu C, Chen S, et al. Meta-analysis of anti-muscarinic receptor type 3 antibodies for the diagnosis of Sjogren syndrome. PLoS One 2015;10:e0116744. https://doi.org/10.1371/journal.pone.0116744
  38. Zuo J, Williams AE, Park YJ, et al. Muscarinic type 3 receptor autoantibodies are associated with anti-SSA/Ro autoantibodies in Sjogren's syndrome. J Immunol Methods 2016;437:28-36. https://doi.org/10.1016/j.jim.2016.07.003
  39. Mona M, Mondello S, Hyon JY, et al. Clinical usefulness of anti-muscarinic type 3 receptor autoantibodies in patients with primary Sjogren's syndrome. Clin Exp Rheumatol 2021;39:795-803. https://doi.org/10.55563/clinexprheumatol/gy6udz
  40. Cui L, Elzakra N, Xu S, Xiao GG, Yang Y, Hu S. Investigation of three potential autoantibodies in Sjogren's syndrome and associated MALT lymphoma. Oncotarget 2017;8:30039-30049. https://doi.org/10.18632/oncotarget.15613
  41. He L, Hannon GJ. MicroRNAs: small RNAs with a big role in gene regulation. Nat Rev Genet 2004;5:522-531. https://doi.org/10.1038/nrg1379
  42. Reale M, D'Angelo C, Costantini E, Laus M, Moretti A, Croce A. MicroRNA in Sjogren's syndrome: their potential roles in pathogenesis and diagnosis. J Immunol Res 2018;2018:7510174. https://doi.org/10.1155/2018/7510174
  43. Sembler-Moller ML, Belstrom D, Locht H, Pedersen AML. Distinct microRNA expression profiles in saliva and salivary gland tissue differentiate patients with primary Sjogren's syndrome from non-Sjogren's sicca patients. J Oral Pathol Med 2020;49:1044-1052. https://doi.org/10.1111/jop.13099
  44. Ramos-Casals M, Brito-Zeron P, Bombardieri S, et al. EULAR recommendations for the management of Sjogren's syndrome with topical and systemic therapies. Ann Rheum Dis 2020;79:3-18. https://doi.org/10.1136/annrheumdis-2019-216114
  45. Strombeck B, Jacobsson LT. The role of exercise in the rehabilitation of patients with systemic lupus erythematosus and patients with primary Sjogren's syndrome. Curr Opin Rheumatol 2007;19:197-203. https://doi.org/10.1097/BOR.0b013e32801494e3
  46. Price EJ, Rauz S, Tappuni AR, et al. The British Society for Rheumatology guideline for the management of adults with primary Sjogren's syndrome. Rheumatology (Oxford) 2017;56:e24-e48. https://doi.org/10.1093/rheumatology/kex166
  47. van der Heijden EHM, Kruize AA, Radstake TRDJ, van Roon JAG. Optimizing conventional DMARD therapy for Sjogren's syndrome. Autoimmun Rev 2018;17:480-492. https://doi.org/10.1016/j.autrev.2018.03.003
  48. Fox RI, Fox CM, Gottenberg JE, Dorner T. Treatment of Sjogren's syndrome: current therapy and future directions. Rheumatology (Oxford) 2021;60:2066-2074. https://doi.org/10.1093/rheumatology/kez142
  49. Baldini C, Pepe P, Quartuccio L, et al. Primary Sjogren's syndrome as a multi-organ disease: impact of the serological profile on the clinical presentation of the disease in a large cohort of Italian patients. Rheumatology (Oxford) 2014;53:839-844. https://doi.org/10.1093/rheumatology/ket427
  50. Carsons SE, Vivino FB, Parke A, et al. Treatment guidelines for rheumatologic manifestations of Sjogren's syndrome: use of biologic agents, management of fatigue, and inflammatory musculoskeletal pain. Arthritis Care Res (Hoboken) 2017;69:517-527. https://doi.org/10.1002/acr.22968
  51. Rogers SJ, Williams CS, Roman GC. Myelopathy in Sjogren's syndrome: role of nonsteroidal immunosuppressants. Drugs 2004;64:123-132. https://doi.org/10.2165/00003495-200464020-00001
  52. Reina D, Roig Vilaseca D, Torrente-Segarra V, et al. Sjogren's syndrome-associated interstitial lung disease: a multicenter study. Reumatol Clin 2016;12:201-205. https://doi.org/10.1016/j.reumae.2015.09.009
  53. Enomoto Y, Takemura T, Hagiwara E, et al. Prognostic factors in interstitial lung disease associated with primary Sjogren's syndrome: a retrospective analysis of 33 pathologically-proven cases. PLoS One 2013;8:e73774. https://doi.org/10.1371/journal.pone.0073774
  54. Hattori N, Nakashima H, Usui T, et al. [Successful treatment with prednisolone for autoimmune myelofibrosis accompanied with Sjogren syndrome]. Rinsho Ketsueki 2007;48:1539-1543. Japanese.
  55. Williams CS, Butler E, Roman GC. Treatment of myelopathy in Sjogren syndrome with a combination of prednisone and cyclophosphamide. Arch Neurol 2001;58:815-819. https://doi.org/10.1001/archneur.58.5.815
  56. 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;38:938-943. https://doi.org/10.2169/internalmedicine.38.938
  57. Ramos-Casals M, Brito-Zeron P, Siso-Almirall A, Bosch X, Tzioufas AG. Topical and systemic medications for the treatment of primary Sjogren's syndrome. Nat Rev Rheumatol 2012;8:399-411. https://doi.org/10.1038/nrrheum.2012.53
  58. Lopez-Pintor RM, Fernandez Castro M, Hernandez G. Oral involvement in patients with primary Sjogren's syndrome. Multidisciplinary care by dentists and rheumatologists. Reumatol Clin 2015;11:387-394. https://doi.org/10.1016/j.reumae.2015.03.014
  59. Ben-Zvi I, Kivity S, Langevitz P, Shoenfeld Y. Hydroxychloroquine: from malaria to autoimmunity. Clin Rev Allergy Immunol 2012;42:145-153. https://doi.org/10.1007/s12016-010-8243-x
  60. Tishler M, Yaron I, Shirazi I, Yaron M. Hydroxychloroquine treatment for primary Sjogren's syndrome: its effect on salivary and serum inflammatory markers. Ann Rheum Dis 1999;58:253-256. https://doi.org/10.1136/ard.58.4.253
  61. 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;52:360-364. https://doi.org/10.1136/ard.52.5.360
  62. Gottenberg JE, Ravaud P, Puechal X, et al. Effects of hydroxychloroquine on symptomatic improvement in primary Sjogren syndrome: the JOQUER randomized clinical trial. JAMA 2014;312:249-258. https://doi.org/10.1001/jama.2014.7682
  63. Coy V. Granados C, Gil D, et al. Antimalarials for Sjogren's syndrome treatment in adults, meta-analysis. Paper presented at: 2012 ACR/ARHP Annual Meeting; 2012 Nov 9-14; Washington, D.C., USA. pp. 64.
  64. Brito-Zeron P, Siso-Almirall A, Kostov B, Bosch X, Tzioufas AG, Ramos-Casals M. B-cell targeted therapies in primary Sjogren syndrome. In: Bosch X, Ramos-Casals M, Khamashta MA, eds. Drugs targeting B-cells in autoimmune diseases. Basel: Springer; 2014. pp. 111-138.
  65. Kennedy T, McCabe C, Struthers G, et al. BSR guidelines on standards of care for persons with rheumatoid arthritis. Rheumatology (Oxford) 2005;44:553-556. https://doi.org/10.1093/rheumatology/keh554
  66. Wessels JA, Huizinga TW, Guchelaar HJ. Recent insights in the pharmacological actions of methotrexate in the treatment of rheumatoid arthritis. Rheumatology (Oxford) 2008;47:249-55. https://doi.org/10.1093/rheumatology/kem279
  67. Alarcon GS, Schrohenloher RE, Bartolucci AA, Ward JR, Williams HJ, Koopman WJ. Suppression of rheumatoid factor production by methotrexate in patients with rheumatoid arthritis. Evidence for differential influences of therapy and clinical status on IgM and IgA rheumatoid factor expression. Arthritis Rheum 1990;33:1156-1161.
  68. Wijngaarden S, van Roon JA, van de Winkel JG, Bijlsma JW, Lafeber FP. Down-regulation of activating Fcgamma receptors on monocytes of patients with rheumatoid arthritis upon methotrexate treatment. Rheumatology (Oxford) 2005;44:729-734. https://doi.org/10.1093/rheumatology/keh583
  69. Skopouli FN, Jagiello P, Tsifetaki N, Moutsopoulos HM. Methotrexate in primary Sjogren's syndrome. Clin Exp Rheumatol 1996;14:555-558.
  70. Bardek I, Milavec-Puretic V, Lipozencic J. Azathioprine in dermatology. Acta Dermatovenerol Croat 2007;15:264-268.
  71. Stocco G, Pelin M, Franca R, et al. Pharmacogenetics of azathioprine in inflammatory bowel disease: a role for glutathione-Stransferase? World J Gastroenterol 2014;20:3534-3541. https://doi.org/10.3748/wjg.v20.i13.3534
  72. Darrieutort-Laffite C, Andre V, Hayem G, et al. Sjogren's syndrome complicated by interstitial cystitis: a case series and literature review. Joint Bone Spine 2015;82:245-250. https://doi.org/10.1016/j.jbspin.2014.12.007
  73. Deheinzelin D, Capelozzi VL, Kairalla RA, Barbas Filho JV, Saldiva PH, de Carvalho CR. Interstitial lung disease in primary Sjogren's syndrome. Clinical-pathological evaluation and response to treatment. Am J Respir Crit Care Med 1996;154(3 Pt 1):794-799. https://doi.org/10.1164/ajrccm.154.3.8810621
  74. Kaufman I, Schwartz D, Caspi D, Paran D. Sjogren's syndrome-not just Sicca: renal involvement in Sjogren's syndrome. Scand J Rheumatol 2008;37:213-218. https://doi.org/10.1080/03009740701867323
  75. Hawley RJ, Hendricks WT. Treatment of Sjogren syndrome myelopathy with azathioprine and steroids. Arch Neurol 2002;59:875; author reply 876. https://doi.org/10.1001/archneur.59.5.875
  76. Price EJ, Rigby SP, Clancy U, Venables PJ. A double blind placebo controlled trial of azathioprine in the treatment of primary Sjogren's syndrome. J Rheumatol 1998;25:896-899.
  77. Meiners PM, Vissink A, Kroese FG, et al. Abatacept treatment reduces disease activity in early primary Sjogren's syndrome (open-label proof of concept ASAP study). Ann Rheum Dis 2014;73:1393-1396. https://doi.org/10.1136/annrheumdis-2013-204653
  78. Carubbi F, Cipriani P, Marrelli A, et al. Efficacy and safety of rituximab treatment in early primary Sjogren's syndrome: a prospective, multi-center, follow-up study. Arthritis Res Ther 2013;15:R172. https://doi.org/10.1186/ar4359
  79. Adler S, Korner M, Forger F, Huscher D, Caversaccio MD, Villiger PM. Evaluation of histologic, serologic, and clinical changes in response to abatacept treatment of primary Sjogren's syndrome: a pilot study. Arthritis Care Res (Hoboken) 2013;65:1862-1868. https://doi.org/10.1002/acr.22052
  80. Gottenberg JE, Cinquetti G, Larroche C, et al. Efficacy of rituximab in systemic manifestations of primary Sjogren's syndrome: results in 78 patients of the AutoImmune and Rituximab registry. Ann Rheum Dis 2013;72:1026-1031. https://doi.org/10.1136/annrheumdis-2012-202293
  81. St Clair EW, Levesque MC, Prak ET, et al. Rituximab therapy for primary Sjogren's syndrome: an open-label clinical trial and mechanistic analysis. Arthritis Rheum 2013;65:1097-1106. https://doi.org/10.1002/art.37850
  82. 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:R129. https://doi.org/10.1186/ar2018
  83. Pijpe J, van Imhoff GW, Spijkervet FK, et al. Rituximab treatment in patients with primary Sjogren's syndrome: an openlabel phase II study. Arthritis Rheum 2005;52:2740-2750. https://doi.org/10.1002/art.21260
  84. Delli K, Haacke EA, Kroese FG, et al. Towards personalised treatment in primary Sjogren's syndrome: baseline parotid histopathology predicts responsiveness to rituximab treatment. Ann Rheum Dis 2016;75:1933-1938. https://doi.org/10.1136/annrheumdis-2015-208304
  85. Srivastava A. Belimumab in systemic lupus erythematosus. Indian J Dermatol 2016;61:550-553. https://doi.org/10.4103/0019-5154.190107
  86. Mariette X, Seror R, Quartuccio L, et al. Efficacy and safety of belimumab in primary Sjogren's syndrome: results of the BELISS open-label phase II study. Ann Rheum Dis 2015;74:526-531. https://doi.org/10.1136/annrheumdis-2013-203991
  87. De Vita S, Quartuccio L, Salvin S, et al. Sequential therapy with belimumab followed by rituximab in Sjogren's syndrome associated with B-cell lymphoproliferation and overexpression of BAFF: evidence for long-term efficacy. Clin Exp Rheumatol 2014;32:490-494.
  88. Wang B, Chen S, Zheng Q, et al. Early diagnosis and treatment for Sjogren's syndrome: current challenges, redefined disease stages and future prospects. J Autoimmun 2021;117:102590. https://doi.org/10.1016/j.jaut.2020.102590
  89. Cartee DL, Maker S, Dalonges D, Manski MC. Sjogren's syndrome: oral manifestations and treatment, a dental perspective. J Dent Hyg 2015;89:365-371.
  90. Sutcliffe N, Recchioni A, Hilmi S, Rauz S, Tappuni AR. What's new in ocular and oral aspects of Sjogren's syndrome and do new treatments work? Rheumatology (Oxford) 2021;60:1034-1041. https://doi.org/10.1093/rheumatology/keaa854
  91. Chu LL, Cui K, Pope JE. Meta-analysis of treatment for primary Sjogren's syndrome. Arthritis Care Res (Hoboken) 2020;72:1011-1021. https://doi.org/10.1002/acr.23917
  92. Al Hamad A, Lodi G, Porter S, Fedele S, Mercadante V. Interventions for dry mouth and hyposalivation in Sjogren's syndrome: a systematic review and meta-analysis. Oral Dis 2019;25:1027-1047. https://doi.org/10.1111/odi.12952
  93. Cifuentes M, Del Barrio-Diaz P, Vera-Kellet C. Pilocarpine and artificial saliva for the treatment of xerostomia and xerophthalmia in Sjogren syndrome: a double-blind randomized controlled trial. Br J Dermatol 2018;179:1056-1061. https://doi.org/10.1111/bjd.16442
  94. Rhodus NL, Schuh MJ. Effects of pilocarpine on salivary flow in patients with Sjogren's syndrome. Oral Surg Oral Med Oral Pathol 1991;72:545-549. https://doi.org/10.1016/0030-4220(91)90491-T
  95. 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, fixeddose, multicenter trial. P92-01 Study Group. Arch Intern Med 1999;159:174-181. https://doi.org/10.1001/archinte.159.2.174
  96. Gil-Montoya JA, Silvestre FJ, Barrios R, Silvestre-Rangil J. Treatment of xerostomia and hyposalivation in the elderly: a systematic review. Med Oral Patol Oral Cir Bucal 2016;21:e355-e366.
  97. Watanabe M, Yamada C, Komagata Y, Kikuchi H, Hosono H, Itagaki F. New low-dose liquid pilocarpine formulation for treating dry mouth in Sjogren's syndrome: clinical efficacy, symptom relief, and improvement in quality of life. J Pharm Health Care Sci 2018;4:4. https://doi.org/10.1186/s40780-018-0099-x
  98. Furness S, Worthington HV, Bryan G, Birchenough S, McMillan R. Interventions for the management of dry mouth: topical therapies. Cochrane Database Syst Rev 2011;(12):CD008934.
  99. Mouly S, Salom M, Tillet Y, et al. Management of xerostomia in older patients: a randomised controlled trial evaluating the efficacy of a new oral lubricant solution. Drugs Aging 2007;24:957-965. https://doi.org/10.2165/00002512-200724110-00007
  100. Milgrom P, Ly KA, Tut OK, et al. Xylitol pediatric topical oral syrup to prevent dental caries: a double-blind randomized clinical trial of efficacy. Arch Pediatr Adolesc Med 2009;163:601-607. https://doi.org/10.1001/archpediatrics.2009.77
  101. Riley P, Moore D, Ahmed F, Sharif MO, Worthington HV. Xylitol-containing products for preventing dental caries in children and adults. Cochrane Database Syst Rev 2015;(3):CD010743.
  102. Murugesh J, Annigeri RG, Raheel SA, Azzeghaiby S, Alshehri M, Kujan O. Effect of yogurt and pH equivalent lemon juice on salivary flow rate in healthy volunteers - an experimental crossover study. Interv Med Appl Sci 2015;7:147-151. https://doi.org/10.1556/1646.7.2015.4.3