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Diagnosis and classification of Sjögren's syndrome

INTRODUCTION

Sjögren’s syndrome (SS) is a chronic autoimmune inflammatory disorder characterized by diminished lacrimal and salivary gland function. The diminished exocrine gland function leads to the “sicca complex,” a combination of dry eyes and dry mouth [1,2]. In addition, a variety of other disease manifestations affecting multiple organs and organ systems may occur, and the clinical features of SS can be divided into the two broad categories of exocrine glandular features and extraglandular features [3]. (See "Clinical manifestations of Sjögren's syndrome: Exocrine gland disease" and "Clinical manifestations of Sjögren's syndrome: Extraglandular disease".)

Disease severity can vary over a wide range:

At the mild to moderate end of the spectrum are patients with symptoms of dry eyes, dry mouth, a low titer of antinuclear antibody, and symptoms of fatigue, myalgia, and mild cognitive dysfunction. At times, such patients may be difficult to distinguish clinically from patients with fibromyalgia or depression who have ocular and/or oral dryness caused or exacerbated by medications with anticholinergic side effects.

A severely affected patient may have florid salivary gland enlargement, adenopathy, antibodies to the Ro/SSA and La/SSB antigens, cryoglobulinemia, hypocomplementemia, a propensity to develop non-Hodgkin lymphoma, and other extraglandular disease manifestations.

A small group of patients have primarily extraglandular manifestations and positive testing for antinuclear and Ro/SSA antibodies without significantly dry eyes or dry mouth. The laboratory findings may be found during evaluation of neuropathies, nephropathies, interstitial pneumonitis, hematologic abnormalities, lymphoproliferative changes, or abnormalities of other organs with a pattern of extraglandular disease suggestive of either SS or systemic lupus erythematosus.

                                  

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Literature review current through: Sep 2014. | This topic last updated: Oct 20, 2014.
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References
Top
  1. Ramos-Casals M, Tzioufas AG, Font J. Primary Sjögren's syndrome: new clinical and therapeutic concepts. Ann Rheum Dis 2005; 64:347.
  2. Pertovaara M, Korpela M, Uusitalo H, et al. Clinical follow up study of 87 patients with sicca symptoms (dryness of eyes or mouth, or both). Ann Rheum Dis 1999; 58:423.
  3. Asmussen K, Andersen V, Bendixen G, et al. A new model for classification of disease manifestations in primary Sjögren's syndrome: evaluation in a retrospective long-term study. J Intern Med 1996; 239:475.
  4. Sjögren H. Zur Kenntnis der Keratoconjunctivitis sicca. Acta Ophthalomol 1933; 11(suppl II):1.
  5. Behrens A, Doyle JJ, Stern L, et al. Dysfunctional tear syndrome: a Delphi approach to treatment recommendations. Cornea 2006; 25:900.
  6. The definition and classification of dry eye disease: report of the Definition and Classification Subcommittee of the International Dry Eye WorkShop (2007). Ocul Surf 2007; 5:75.
  7. Stern ME, Schaumburg CS, Pflugfelder SC. Dry eye as a mucosal autoimmune disease. Int Rev Immunol 2013; 32:19.
  8. Mikulicz JH. Uber eine eigenartige symmetrische Erkrankung der Tranen- und Mundspeicheldrusen. In: Beitr. Chir. Fortschr, Billroth GT (Ed), Stuttgart, 1892. p.610.
  9. Schaffer AJ, Jacobsen AW. Mikulicz’s syndrome: a report of ten cases. Am J Dis Child 1927; 34:327.
  10. Yamamoto M, Takahashi H, Ohara M, et al. A new conceptualization for Mikulicz's disease as an IgG4-related plasmacytic disease. Mod Rheumatol 2006; 16:335.
  11. Ihrler S, Harrison JD. Mikulicz's disease and Mikulicz's syndrome: analysis of the original case report of 1892 in the light of current knowledge identifies a MALT lymphoma. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2005; 100:334.
  12. Pillemer SR, Matteson EL, Jacobsson LT, et al. Incidence of physician-diagnosed primary Sjögren syndrome in residents of Olmsted County, Minnesota. Mayo Clin Proc 2001; 76:593.
  13. Qin B, Wang J, Yang Z, et al. Epidemiology of primary Sjögren's syndrome: a systematic review and meta-analysis. Ann Rheum Dis 2014.
  14. Thomas E, Hay EM, Hajeer A, Silman AJ. Sjögren's syndrome: a community-based study of prevalence and impact. Br J Rheumatol 1998; 37:1069.
  15. Maldini C, Seror R, Fain O, et al. Epidemiology of primary Sjögren's syndrome in a French multiracial/multiethnic area. Arthritis Care Res (Hoboken) 2014; 66:454.
  16. Liew MS, Zhang M, Kim E, Akpek EK. Prevalence and predictors of Sjogren's syndrome in a prospective cohort of patients with aqueous-deficient dry eye. Br J Ophthalmol 2012; 96:1498.
  17. Kang HI, Fei HM, Saito I, et al. Comparison of HLA class II genes in Caucasoid, Chinese, and Japanese patients with primary Sjögren's syndrome. J Immunol 1993; 150:3615.
  18. Jacobsson LT, Axell TE, Hansen BU, et al. Dry eyes or mouth--an epidemiological study in Swedish adults, with special reference to primary Sjögren's syndrome. J Autoimmun 1989; 2:521.
  19. Strickland RW, Tesar JT, Berne BH, et al. The frequency of sicca syndrome in an elderly female population. J Rheumatol 1987; 14:766.
  20. Schein OD, Hochberg MC, Muñoz B, et al. Dry eye and dry mouth in the elderly: a population-based assessment. Arch Intern Med 1999; 159:1359.
  21. 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; 25:486.
  22. Vitali C, Moutsopoulos HM, Bombardieri S. The European Community Study Group on diagnostic criteria for Sjögren's syndrome. Sensitivity and specificity of tests for ocular and oral involvement in Sjögren's syndrome. Ann Rheum Dis 1994; 53:637.
  23. Percival RS, Challacombe SJ, Marsh PD. Flow rates of resting whole and stimulated parotid saliva in relation to age and gender. J Dent Res 1994; 73:1416.
  24. Puderbach S, Stolze HH. Tear ferning and other lacrimal tests in normal persons of different ages. Int Ophthalmol 1991; 15:391.
  25. Drosos AA, Andonopoulos AP, Costopoulos JS, et al. Prevalence of primary Sjögren's syndrome in an elderly population. Br J Rheumatol 1988; 27:123.
  26. Fox PC, Busch KA, Baum BJ. Subjective reports of xerostomia and objective measures of salivary gland performance. J Am Dent Assoc 1987; 115:581.
  27. Bournia VK, Diamanti KD, Vlachoyiannopoulos PG, Moutsopoulos HM. Anticentromere antibody positive Sjögren's Syndrome: a retrospective descriptive analysis. Arthritis Res Ther 2010; 12:R47.
  28. Scott J. Qualitative and quantitative observations on the histology of human labial salivary glands obtained post mortem. J Biol Buccale 1980; 8:187.
  29. Botsios C, Furlan A, Ostuni P, et al. Elderly onset of primary Sjögren's syndrome: clinical manifestations, serological features and oral/ocular diagnostic tests. Comparison with adult and young onset of the disease in a cohort of 336 Italian patients. Joint Bone Spine 2011; 78:171.
  30. Ramos-Casals M, García-Carrasco M, Brito MP, et al. Autoimmunity and geriatrics: clinical significance of autoimmune manifestations in the elderly. Lupus 2003; 12:341.
  31. MORGAN WS, CASTLEMAN B. A clinicopathologic study of Mikulicz's disease. Am J Pathol 1953; 29:471.
  32. Bridges AJ, England DM. Benign lymphoepithelial lesion: relationship to Sjögren's syndrome and evolving malignant lymphoma. Semin Arthritis Rheum 1989; 19:201.
  33. Leban SG, Stratigos GT. Benign lymphoepithelial sialoadenopathies. The Mikulicz/Sjögren controversy. Oral Surg Oral Med Oral Pathol 1974; 38:735.
  34. Ma Q, Song H. Diagnosis and management of lymphoepithelial lesion of the parotid gland. Rheumatol Int 2011; 31:959.
  35. Hsi ED, Zukerberg LR, Schnitzer B, Harris NL. Development of extrasalivary gland lymphoma in myoepithelial sialadenitis. Mod Pathol 1995; 8:817.
  36. Ellis GL. Lymphoid lesions of salivary glands: malignant and benign. Med Oral Patol Oral Cir Bucal 2007; 12:E479.
  37. Baughman RP, Teirstein AS, Judson MA, et al. Clinical characteristics of patients in a case control study of sarcoidosis. Am J Respir Crit Care Med 2001; 164:1885.
  38. GREENBERG G, ANDERSON R, SHARPSTONE P, JAMES DG. ENLARGEMENT OF PAROTID GLAND DUE TO SARCOIDOSIS. Br Med J 1964; 2:861.
  39. Johns CJ, Michele TM. The clinical management of sarcoidosis. A 50-year experience at the Johns Hopkins Hospital. Medicine (Baltimore) 1999; 78:65.
  40. Obenauf CD, Shaw HE, Sydnor CF, Klintworth GK. Sarcoidosis and its ophthalmic manifestations. Am J Ophthalmol 1978; 86:648.
  41. Ramos-Casals M, Brito-Zerón P, García-Carrasco M, Font J. Sarcoidosis or Sjögren syndrome? Clues to defining mimicry or coexistence in 59 cases. Medicine (Baltimore) 2004; 83:85.
  42. Ramos-Casals M, Loustaud-Ratti V, De Vita S, et al. Sjögren syndrome associated with hepatitis C virus: a multicenter analysis of 137 cases. Medicine (Baltimore) 2005; 84:81.
  43. Carrozzo M. Oral diseases associated with hepatitis C virus infection. Part 1. sialadenitis and salivary glands lymphoma. Oral Dis 2008; 14:123.
  44. Basu D, Williams FM, Ahn CW, Reveille JD. Changing spectrum of the diffuse infiltrative lymphocytosis syndrome. Arthritis Rheum 2006; 55:466.
  45. Kazi S, Cohen PR, Williams F, et al. The diffuse infiltrative lymphocytosis syndrome. Clinical and immunogenetic features in 35 patients. AIDS 1996; 10:385.
  46. Imanguli MM, Atkinson JC, Mitchell SA, et al. Salivary gland involvement in chronic graft-versus-host disease: prevalence, clinical significance, and recommendations for evaluation. Biol Blood Marrow Transplant 2010; 16:1362.
  47. Cheuk W, Chan JK. IgG4-related sclerosing disease: a critical appraisal of an evolving clinicopathologic entity. Adv Anat Pathol 2010; 17:303.
  48. Liu SY, Vlantis AC, Lee WC. Bilateral parotid and submandibular gland enlargement: rare features of Wegener's granulomatosis. J Laryngol Otol 2003; 117:148.
  49. Feinstein AJ, Ciarleglio MM, Cong X, et al. Parotid gland lymphoma: prognostic analysis of 2140 patients. Laryngoscope 2013; 123:1199.
  50. Afonso AA, Monroy D, Stern ME, et al. Correlation of tear fluorescein clearance and Schirmer test scores with ocular irritation symptoms. Ophthalmology 1999; 106:803.
  51. Vitali C, Bombardieri S, Jonsson R, et al. Classification criteria for Sjögren's syndrome: a revised version of the European criteria proposed by the American-European Consensus Group. Ann Rheum Dis 2002; 61:554.
  52. Methodologies to diagnose and monitor dry eye disease: report of the Diagnostic Methodology Subcommittee of the International Dry Eye WorkShop (2007). Ocul Surf 2007; 5:108.
  53. Whitcher JP, Shiboski CH, Shiboski SC, et al. A simplified quantitative method for assessing keratoconjunctivitis sicca from the Sjögren's Syndrome International Registry. Am J Ophthalmol 2010; 149:405.
  54. Bron AJ, Evans VE, Smith JA. Grading of corneal and conjunctival staining in the context of other dry eye tests. Cornea 2003; 22:640.
  55. van Bijsterveld OP. Diagnostic tests in the Sicca syndrome. Arch Ophthalmol 1969; 82:10.
  56. Nichols KK, Foulks GN, Bron AJ, et al. The international workshop on meibomian gland dysfunction: executive summary. Invest Ophthalmol Vis Sci 2011; 52:1922.
  57. Aung W, Yamada I, Umehara I, et al. Sjögren's syndrome: comparison of assessments with quantitative salivary gland scintigraphy and contrast sialography. J Nucl Med 2000; 41:257.
  58. Hermann GA, Vivino FB, Goin JE. Scintigraphic features of chronic sialadenitis and Sjögren's syndrome: a comparison. Nucl Med Commun 1999; 20:1123.
  59. Kohler PF, Winter ME. A quantitative test for xerostomia. The Saxon test, an oral equivalent of the Schirmer test. Arthritis Rheum 1985; 28:1128.
  60. Niemelä RK, Pääkkö E, Suramo I, et al. Magnetic resonance imaging and magnetic resonance sialography of parotid glands in primary Sjogren's syndrome. Arthritis Rheum 2001; 45:512.
  61. Niemelä RK, Takalo R, Pääkkö 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 (Oxford) 2004; 43:875.
  62. Jungehülsing M, Fischbach R, Schröder U, et al. Magnetic resonance sialography. Otolaryngol Head Neck Surg 1999; 121:488.
  63. Tonami H, Ogawa Y, Matoba M, et al. MR sialography in patients with Sjögren syndrome. AJNR Am J Neuroradiol 1998; 19:1199.
  64. Heverhagen JT, Kalinowski M, Rehberg E, et al. Prospective comparison of magnetic resonance sialography and digital subtraction sialography. J Magn Reson Imaging 2000; 11:518.
  65. Eracleous E, Kallis S, Tziakouri C, et al. Sonography, CT, CT sialography, MRI and MRI sialography in investigation of the facial nerve and the differentiation between deep and superficial parotid lesions. Neuroradiology 1997; 39:506.
  66. Cornec D, Jousse-Joulin S, Pers JO, et al. Contribution of salivary gland ultrasonography to the diagnosis of Sjögren's syndrome: toward new diagnostic criteria? Arthritis Rheum 2013; 65:216.
  67. Milic VD, Petrovic RR, Boricic IV, et al. Diagnostic value of salivary gland ultrasonographic scoring system in primary Sjogren's syndrome: a comparison with scintigraphy and biopsy. J Rheumatol 2009; 36:1495.
  68. Sun Z, Zhang Z, Fu K, et al. Diagnostic accuracy of parotid CT for identifying Sjögren's syndrome. Eur J Radiol 2012; 81:2702.
  69. Kalk WW, Vissink A, Spijkervet FK, et al. Morbidity from parotid sialography. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2001; 92:572.
  70. Daniels TE, Benn DK. Is sialography effective in diagnosing the salivary component of Sjögren's syndrome? Adv Dent Res 1996; 10:25.
  71. Chan EK, Tan EM, Ward DC, Matera AG. Human 60-kDa SS-A/Ro ribonucleoprotein autoantigen gene (SSA2) localized to 1q31 by fluorescence in situ hybridization. Genomics 1994; 23:298.
  72. Tan EM. Antinuclear antibodies: diagnostic markers for autoimmune diseases and probes for cell biology. Adv Immunol 1989; 44:93.
  73. Ben-Chetrit E, Chan EK, Sullivan KF, Tan EM. A 52-kD protein is a novel component of the SS-A/Ro antigenic particle. J Exp Med 1988; 167:1560.
  74. Harley JB, Sestak AL, Willis LG, et al. A model for disease heterogeneity in systemic lupus erythematosus. Relationships between histocompatibility antigens, autoantibodies, and lymphopenia or renal disease. Arthritis Rheum 1989; 32:826.
  75. Shen L, Suresh L, Lindemann M, et al. Novel autoantibodies in Sjogren's syndrome. Clin Immunol 2012; 145:251.
  76. Lee M, Rutka JA, Slomovic AR, et al. Establishing guidelines for the role of minor salivary gland biopsy in clinical practice for Sjögren's syndrome. J Rheumatol 1998; 25:247.
  77. Varela Centelles P, Sánchez-Sánchez M, Costa-Bouzas J, et al. Neurological adverse events related to lip biopsy in patients suspicious for Sjögren's syndrome: a systematic review and prevalence meta-analysis. Rheumatology (Oxford) 2014; 53:1208.
  78. Daniels TE. Labial salivary gland biopsy in Sjögren's syndrome. Assessment as a diagnostic criterion in 362 suspected cases. Arthritis Rheum 1984; 27:147.
  79. Daniels TE, Fox PC. Salivary and oral components of Sjögren's syndrome. Rheum Dis Clin North Am 1992; 18:571.
  80. Greenspan JS, Daniels TE, Talal N, Sylvester RA. The histopathology of Sjögren's syndrome in labial salivary gland biopsies. Oral Surg Oral Med Oral Pathol 1974; 37:217.
  81. Daniels TE, Whitcher JP. Association of patterns of labial salivary gland inflammation with keratoconjunctivitis sicca. Analysis of 618 patients with suspected Sjögren's syndrome. Arthritis Rheum 1994; 37:869.
  82. Vitali C, Bombardieri S, Moutsopoulos HM, et al. Preliminary criteria for the classification of Sjögren's syndrome. Results of a prospective concerted action supported by the European Community. Arthritis Rheum 1993; 36:340.
  83. Shiboski SC, Shiboski CH, Criswell L, et al. American College of Rheumatology classification criteria for Sjögren's syndrome: a data-driven, expert consensus approach in the Sjögren's International Collaborative Clinical Alliance cohort. Arthritis Care Res (Hoboken) 2012; 64:475.
  84. Daniels TE, Cox D, Shiboski CH, et al. Associations between salivary gland histopathologic diagnoses and phenotypic features of Sjögren's syndrome among 1,726 registry participants. Arthritis Rheum 2011; 63:2021.
  85. Vivino FB, Gala I, Hermann GA. Change in final diagnosis on second evaluation of labial minor salivary gland biopsies. J Rheumatol 2002; 29:938.
  86. Baimpa E, Dahabreh IJ, Voulgarelis M, Moutsopoulos HM. Hematologic manifestations and predictors of lymphoma development in primary Sjögren syndrome: clinical and pathophysiologic aspects. Medicine (Baltimore) 2009; 88:284.
  87. Theander E, Henriksson G, Ljungberg O, et al. Lymphoma and other malignancies in primary Sjögren's syndrome: a cohort study on cancer incidence and lymphoma predictors. Ann Rheum Dis 2006; 65:796.
  88. Radfar L, Kleiner DE, Fox PC, Pillemer SR. Prevalence and clinical significance of lymphocytic foci in minor salivary glands of healthy volunteers. Arthritis Rheum 2002; 47:520.
  89. Christodoulou MI, Kapsogeorgou EK, Moutsopoulos HM. Characteristics of the minor salivary gland infiltrates in Sjögren's syndrome. J Autoimmun 2010; 34:400.
  90. Theander E, Vasaitis L, Baecklund E, et al. Lymphoid organisation in labial salivary gland biopsies is a possible predictor for the development of malignant lymphoma in primary Sjögren's syndrome. Ann Rheum Dis 2011; 70:1363.
  91. Fox RI. The importance of minor salivary gland biopsy in prediction of lymphoma in Sjögren's syndrome: should we be obtaining more information about prognosis from minor salivary gland samples? Ann Rheum Dis 2011; 70:1351.
  92. Van Mello NM, Pillemer SR, Tak PP, Sankar V. B cell MALT lymphoma diagnosed by labial minor salivary gland biopsy in patients screened for Sjögren's syndrome. Ann Rheum Dis 2005; 64:471.
  93. Baer AN, Gourin CG, Westra WH, et al. Rare diagnosis of IgG4-related systemic disease by lip biopsy in an international Sjögren syndrome registry. Oral Surg Oral Med Oral Pathol Oral Radiol 2013; 115:e34.
  94. Vitali C. Classification criteria for Sjögren's syndrome. Ann Rheum Dis 2003; 62:94.
  95. Daniels TE. Do we need new diagnostic criteria for Sjögren's syndrome? Presse Med 2012; 41:e441.
  96. Theander E, Jacobsson LT. Relationship of Sjögren's syndrome to other connective tissue and autoimmune disorders. Rheum Dis Clin North Am 2008; 34:935.