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. 1994 Oct;53(10):637–647. doi: 10.1136/ard.53.10.637

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.

C Vitali 1, H M Moutsopoulos 1, S Bombardieri 1
PMCID: PMC1005429  PMID: 7979575

Abstract

AIM--To establish a definitive set of diagnostic criteria in a multicentre European study a selected number of oral and ocular tests were performed on a large number of patients with Sjögrens Syndrome (SS) and controls. The diagnostic accuracy of each test for patients with primary and secondary SS and for controls at different ages, was studied. METHODS--Each centre received a clinical chart describing the series of tests to be conducted. The tests included: questionnaires for dry eye and dry mouth symptoms, Schirmer's-I-test (ScT), tear fluid lactoferrin level (TFLL), break-up time (BUT) and rose Bengal score (RBS) for the eye evaluation; unstimulated and stimulated whole saliva collection (UWSC and SWSC), salivary gland scintigraphy (SGS), parotid sialography (PS) and minor salivary gland biopsy (MSGB) for oral involvement. RESULTS--Data from 22 centres and 11 countries was collected on a total of 447 patients with SS (246 with primary SS and 201 with secondary SS) and 246 controls (of whom 113 had a connective tissue disease without SS). Among the ocular symptoms, the feeling of dry eye and 'sand in the eye' were the ones most commonly recorded in patients with SS. Similarly, the feeling of dry mouth, appearing either spontaneously or when the patient was eating or breathing, was the most frequent subjective oral symptom. Among the ocular tests, ScT showed the best balance between sensitivity and specificity (76.9% and 72.4% respectively), while RBS was the most specific test (81.7%). ScT and RBS gave also sufficiently concordant results. TFLL and BUT gave considerably less reliable results, which were not concordant with each other or with the other ocular tests. The quantitative lacrimal tests ScT and TFLL produced significantly different results in elderly controls, while RBS did not. Abnormal results for all of the ocular tests were less marked and less frequent in patients with secondary SS than in those with primary SS. The oral tests (except SWSC) were generally more reliable than the ocular tests in diagnosing SS. In particular, PS was the most specific diagnostic tools (100%), while MSGB (where the presence of at least one inflammatory focus was considered as indicative for the diagnosis) showed a good balance between sensitivity and specificity (82.4% and 86.2%, respectively). The tests showed a good degree of agreement, and, with the exception of UWSC, were not influenced by age. In the oral, as in the ocular tests, abnormal results were less frequent and less marked in patients with secondary SS. CONCLUSIONS--The results clearly show that ScT and RBS (for the eye evaluation), and SGS, PS, MSGB and UWSC (for salivary gland involvement) are the most reliable tests for the diagnosis of SS. The clinician should be aware, however, that the test results may vary depending on the age of the patient and the type of SS (primary or secondary).

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Anderson L. G., Cummings N. A., Asofsky R., Hylton M. B., Tarpley T. M., Jr, Tomasi T. B., Jr, Wolf R. O., Schall G. L., Talal N. Salivary gland immunoglobulin and rheumatoid factor synthesis in Sjögren's syndrome. Natural history and response to treatment. Am J Med. 1972 Oct;53(4):456–463. doi: 10.1016/0002-9343(72)90141-6. [DOI] [PubMed] [Google Scholar]
  2. Andonopoulos A. P., Skopouli F. N., Dimou G. S., Drosos A. A., Moutsopoulos H. M. Sjögren's syndrome in systemic lupus erythematosus. J Rheumatol. 1990 Feb;17(2):201–204. [PubMed] [Google Scholar]
  3. Arnett F. C., Edworthy S. M., Bloch D. A., McShane D. J., Fries J. F., Cooper N. S., Healey L. A., Kaplan S. R., Liang M. H., Luthra H. S. The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum. 1988 Mar;31(3):315–324. doi: 10.1002/art.1780310302. [DOI] [PubMed] [Google Scholar]
  4. Bodeutsch C., de Wilde P. C., Kater L., van Houwelingen J. C., van den Hoogen F. H., Kruize A. A., Hené R. J., van de Putte L. B., Vooijs G. P. Quantitative immunohistologic criteria are superior to the lymphocytic focus score criterion for the diagnosis of Sjögren's syndrome. Arthritis Rheum. 1992 Sep;35(9):1075–1087. doi: 10.1002/art.1780350913. [DOI] [PubMed] [Google Scholar]
  5. Bohan A., Peter J. B. Polymyositis and dermatomyositis (second of two parts). N Engl J Med. 1975 Feb 20;292(8):403–407. doi: 10.1056/NEJM197502202920807. [DOI] [PubMed] [Google Scholar]
  6. Chisholm D. M., Mason D. K. Labial salivary gland biopsy in Sjögren's disease. J Clin Pathol. 1968 Sep;21(5):656–660. doi: 10.1136/jcp.21.5.656. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Chisholm D. M., Waterhouse J. P., Mason D. K. Lymphocytic sialadenitis in the major and minor glands: a correlation in postmortem subjects. J Clin Pathol. 1970 Nov;23(8):690–694. doi: 10.1136/jcp.23.8.690. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Couderc L. J., D'Agay M. F., Danon F., Harzic M., Brocheriou C., Clauvel J. P. Sicca complex and infection with human immunodeficiency virus. Arch Intern Med. 1987 May;147(5):898–901. [PubMed] [Google Scholar]
  9. Daniels T. E. Labial salivary gland biopsy in Sjögren's syndrome. Assessment as a diagnostic criterion in 362 suspected cases. Arthritis Rheum. 1984 Feb;27(2):147–156. doi: 10.1002/art.1780270205. [DOI] [PubMed] [Google Scholar]
  10. Daniels T. E. Salivary histopathology in diagnosis of Sjögren's syndrome. Scand J Rheumatol Suppl. 1986;61:36–43. [PubMed] [Google Scholar]
  11. De Wilde P. C., Baak J. P., van Houwelingen J. C., Kater L., Slootweg P. J. Morphometric study of histological changes in sublabial salivary glands due to aging process. J Clin Pathol. 1986 Apr;39(4):406–417. doi: 10.1136/jcp.39.4.406. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Drosos A. A., Pennec Y. L., Elisaf M., Lamour A., Acritidis N. C., Jouquan J. R., Moutsopoulos H. M., Youinou P. Sjögren's syndrome in patients with the CREST variant of progressive systemic scleroderma. J Rheumatol. 1991 Nov;18(11):1685–1688. [PubMed] [Google Scholar]
  13. Fox R. I., Robinson C. A., Curd J. G., Kozin F., Howell F. V. Sjögren's syndrome. Proposed criteria for classification. Arthritis Rheum. 1986 May;29(5):577–585. doi: 10.1002/art.1780290501. [DOI] [PubMed] [Google Scholar]
  14. Franco A., Valesini G., Barnaba V., Silvagni C., Tiberti A., Balsano F. Class II MHC antigen expression on epithelial cells of salivary glands from patients with Sjögren's syndrome. Clin Exp Rheumatol. 1987 Jul-Sep;5(3):199–203. [PubMed] [Google Scholar]
  15. Greenspan J. S., Daniels T. E., Talal N., Sylvester R. A. The histopathology of Sjögren's syndrome in labial salivary gland biopsies. Oral Surg Oral Med Oral Pathol. 1974 Feb;37(2):217–229. doi: 10.1016/0030-4220(74)90417-4. [DOI] [PubMed] [Google Scholar]
  16. HALBERG G. P., BERENS C. Standardized Schirmer tear test kit. Am J Ophthalmol. 1961 May;51:840–842. doi: 10.1016/0002-9394(61)91827-x. [DOI] [PubMed] [Google Scholar]
  17. Hansen B. U., Lindgren S., Eriksson S., Henricsson V., Larsson A., Manthorpe R., Warfvinge G. Clinical and immunological features of Sjögren's syndrome in patients with primary biliary cirrhosis with emphasis on focal sialadenitis. Acta Med Scand. 1988;224(6):611–619. doi: 10.1111/j.0954-6820.1988.tb19634.x. [DOI] [PubMed] [Google Scholar]
  18. Heft M. W., Baum B. J. Unstimulated and stimulated parotid salivary flow rate in individuals of different ages. J Dent Res. 1984 Oct;63(10):1182–1185. doi: 10.1177/00220345840630100101. [DOI] [PubMed] [Google Scholar]
  19. Heintze U., Birkhed D., Björn H. Secretion rate and buffer effect of resting and stimulated whole saliva as a function of age and sex. Swed Dent J. 1983;7(6):227–238. [PubMed] [Google Scholar]
  20. Holly F. J. Physical chemistry of the normal and disordered tear film. Trans Ophthalmol Soc U K. 1985;104(Pt 4):374–380. [PubMed] [Google Scholar]
  21. Janssen P. T., van Bijsterveld O. P. A simple test for lacrimal gland function: a tear lactoferrin assay by radial immunodiffusion. Graefes Arch Clin Exp Ophthalmol. 1983;220(4):171–174. doi: 10.1007/BF02186663. [DOI] [PubMed] [Google Scholar]
  22. Lindahl G., Hedfors E. Lymphocytic infiltrates and epithelial HLA-DR expression in lip salivary glands in connective tissue disease patients lacking sicca: a prospective study. Br J Rheumatol. 1989 Aug;28(4):293–298. doi: 10.1093/rheumatology/28.4.293. [DOI] [PubMed] [Google Scholar]
  23. Lindahl G., Lefvert A. K., Hedfors E. Periductal lymphocytic infiltrates in salivary glands in myasthenia gravis patients lacking Sjögren's syndrome. Clin Exp Immunol. 1986 Oct;66(1):95–102. [PMC free article] [PubMed] [Google Scholar]
  24. Lindahl G., Lönnquist B., Hedfors E. Lymphocytic infiltrations of lip salivary glands in bone marrow recipients. A model for the development of the histopathological changes in Sjögren's syndrome? J Autoimmun. 1989 Aug;2(4):579–583. doi: 10.1016/0896-8411(89)90191-1. [DOI] [PubMed] [Google Scholar]
  25. Mackie I. A., Seal D. V. The questionably dry eye. Br J Ophthalmol. 1981 Jan;65(1):2–9. doi: 10.1136/bjo.65.1.2. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Manthorpe R., Oxholm P., Prause J. U., Schiødt M. The Copenhagen criteria for Sjögren's syndrome. Scand J Rheumatol Suppl. 1986;61:19–21. [PubMed] [Google Scholar]
  27. Marx R. E., Hartman K. S., Rethman K. V. A prospective study comparing incisional labial to incisional parotid biopsies in the detection and confirmation of sarcoidosis, Sjögren's disease, sialosis and lymphoma. J Rheumatol. 1988 Apr;15(4):621–629. [PubMed] [Google Scholar]
  28. Moutsopoulos H. M., Karsh J., Wolf R. O., Tarpley T. M., Tylenda A., Papadopoulos N. M. Lysozyme determination in parotid saliva from patients with Sjögren's syndrome. Am J Med. 1980 Jul;69(1):39–42. doi: 10.1016/0002-9343(80)90497-0. [DOI] [PubMed] [Google Scholar]
  29. Moutsopoulos H. M., Klippel J. H., Pavlidis N., Wolf R. O., Sweet J. B., Steinberg A. D., Chu F. C., Tarpley T. M. Correlative histologic and serologic findings of sicca syndrome in patients with systemic lupus erythematosus. Arthritis Rheum. 1980 Jan;23(1):36–40. doi: 10.1002/art.1780230107. [DOI] [PubMed] [Google Scholar]
  30. Moutsopoulos H. M., Mann D. L., Johnson A. H., Chused T. M. Genetic differences between primary and secondary sicca syndrome. N Engl J Med. 1979 Oct 4;301(14):761–763. doi: 10.1056/NEJM197910043011405. [DOI] [PubMed] [Google Scholar]
  31. Moutsopoulos H. M., Webber B. L., Vlagopoulos T. P., Chused T. M., Decker J. L. Differences in the clinical manifestations of sicca syndrome in the presence and absence of rheumatoid arthritis. Am J Med. 1979 May;66(5):733–736. doi: 10.1016/0002-9343(79)91110-0. [DOI] [PubMed] [Google Scholar]
  32. Norn M. S. Tear secretion in diseased eyes. Keratoconjunctivitis sicca, diseases of the lacrimal system, ectropion, lagophthalmos, conjunctivitis, etc., studied by a new method: lacrimal streak dilution test. Acta Ophthalmol (Copenh) 1966;44(1):25–32. doi: 10.1111/j.1755-3768.1966.tb06427.x. [DOI] [PubMed] [Google Scholar]
  33. Osial T. A., Jr, Whiteside T. L., Buckingham R. B., Singh G., Barnes E. L., Pierce J. M., Rodnan G. P. Clinical and serologic study of Sjögren's syndrome in patients with progressive systemic sclerosis. Arthritis Rheum. 1983 Apr;26(4):500–508. doi: 10.1002/art.1780260408. [DOI] [PubMed] [Google Scholar]
  34. Paschides C. A., Kitsios G., Karakostas K. X., Psillas C., Moutsopoulos H. M. Evaluation of tear break-up time, Schirmer's-I test and rose bengal staining as confirmatory tests for keratoconjunctivitis sicca. Clin Exp Rheumatol. 1989 Mar-Apr;7(2):155–157. [PubMed] [Google Scholar]
  35. Pease C. T., Shattles W., Charles P. J., Venables P. J., Maini R. N. Clinical, serological, and HLA phenotype subsets in Sjögren's syndrome. Clin Exp Rheumatol. 1989 Mar-Apr;7(2):185–190. [PubMed] [Google Scholar]
  36. Pennec Y. L., Leroy J. P., Jouquan J., Lelong A., Katsikis P., Youinou P. Comparison of labial and sublingual salivary gland biopsies in the diagnosis of Sjögren's syndrome. Ann Rheum Dis. 1990 Jan;49(1):37–39. doi: 10.1136/ard.49.1.37. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Preliminary criteria for the classification of systemic sclerosis (scleroderma). Subcommittee for scleroderma criteria of the American Rheumatism Association Diagnostic and Therapeutic Criteria Committee. Arthritis Rheum. 1980 May;23(5):581–590. doi: 10.1002/art.1780230510. [DOI] [PubMed] [Google Scholar]
  38. RUBIN P., HOLT J. F. Secretory sialography in diseases of the major salivary glands. Am J Roentgenol Radium Ther Nucl Med. 1957 Apr;77(4):575–598. [PubMed] [Google Scholar]
  39. Schall G. L., Anderson L. G., Wolf R. O., Herdt J. R., Tarpley T. M., Jr, Cummings N. A., Zeiger L. S., Talal N. Xerostomia in Sjögren's syndrome. Evaluation by sequential salivary scintigraphy. JAMA. 1971 Jun 28;216(13):2109–2116. [PubMed] [Google Scholar]
  40. Schiødt M., Greenspan D., Daniels T. E., Nelson J., Leggott P. J., Wara D. W., Greenspan J. S. Parotid gland enlargement and xerostomia associated with labial sialadenitis in HIV-infected patients. J Autoimmun. 1989 Aug;2(4):415–425. doi: 10.1016/0896-8411(89)90170-4. [DOI] [PubMed] [Google Scholar]
  41. Schiødt M., Thorn J. Criteria for the salivary component of Sjögren's syndrome. A review. Clin Exp Rheumatol. 1989 Mar-Apr;7(2):119–122. [PubMed] [Google Scholar]
  42. Scott J. Qualitative and quantitative observations on the histology of human labial salivary glands obtained post mortem. J Biol Buccale. 1980 Sep;8(3):187–200. [PubMed] [Google Scholar]
  43. Scully C. Oral parameters in the diagnosis of Sjögren's syndrome. Clin Exp Rheumatol. 1989 Mar-Apr;7(2):113–117. [PubMed] [Google Scholar]
  44. Seal D. V. The effect of ageing and disease on tear constituents. Trans Ophthalmol Soc U K. 1985;104(Pt 4):355–362. [PubMed] [Google Scholar]
  45. Skopouli F. N., Siouna-Fatourou H. I., Ziciadis C., Moutsopoulos H. M. Evaluation of unstimulated whole saliva flow rate and stimulated parotid flow as confirmatory tests for xerostomia. Clin Exp Rheumatol. 1989 Mar-Apr;7(2):127–129. [PubMed] [Google Scholar]
  46. Speight P. M., Cruchley A., Williams D. M. Quantification of plasma cells in labial salivary glands: increased expression of IgM in Sjögren's syndrome. J Oral Pathol Med. 1990 Mar;19(3):126–130. doi: 10.1111/j.1600-0714.1990.tb00810.x. [DOI] [PubMed] [Google Scholar]
  47. Syrjänen S. Age-related changes in structure of labial minor salivary glands. Age Ageing. 1984 May;13(3):159–165. doi: 10.1093/ageing/13.3.159. [DOI] [PubMed] [Google Scholar]
  48. Takeda Y., Komori A. Focal lymphocytic infiltration in the human labial salivary glands: a postmortem study. J Oral Pathol. 1986 Feb;15(2):83–86. doi: 10.1111/j.1600-0714.1986.tb00582.x. [DOI] [PubMed] [Google Scholar]
  49. Talal N., Asofsky R., Lightbody P. Immunoglobulin synthesis by salivary gland lymphoid cells in Sjögren's syndrome. J Clin Invest. 1970 Jan;49(1):49–54. doi: 10.1172/JCI106221. [DOI] [PMC free article] [PubMed] [Google Scholar]
  50. Tan E. M., Cohen A. S., Fries J. F., Masi A. T., McShane D. J., Rothfield N. F., Schaller J. G., Talal N., Winchester R. J. The 1982 revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum. 1982 Nov;25(11):1271–1277. doi: 10.1002/art.1780251101. [DOI] [PubMed] [Google Scholar]
  51. Vanley G. T., Leopold I. H., Gregg T. H. Interpretation of tear film breakup. Arch Ophthalmol. 1977 Mar;95(3):445–448. doi: 10.1001/archopht.1977.04450030087010. [DOI] [PubMed] [Google Scholar]
  52. Vitali C., Bombardieri S., Moutsopoulos H. M., Balestrieri G., Bencivelli W., Bernstein R. M., Bjerrum K. B., Braga S., Coll J., de Vita S. Preliminary criteria for the classification of Sjögren's syndrome. Results of a prospective concerted action supported by the European Community. Arthritis Rheum. 1993 Mar;36(3):340–347. doi: 10.1002/art.1780360309. [DOI] [PubMed] [Google Scholar]
  53. Vitali C., Tavoni A., Simi U., Marchetti G., Vigorito P., d'Ascanio A., Neri R., Cristofani R., Bombardieri S. Parotid sialography and minor salivary gland biopsy in the diagnosis of Sjögren's syndrome. A comparative study of 84 patients. J Rheumatol. 1988 Feb;15(2):262–267. [PubMed] [Google Scholar]
  54. Whaley K., Blair S., Low P. S., Chisholm D. M., Dick W. C., Buchanan W. W. Sialographic abnormalities in Sjogren's syndrome, rheumatoid arthritis, and other arthritides and connective tissue diseases. A clinical and radiological investigation using hydrostatic sialography. Clin Radiol. 1972 Oct;23(4):474–482. doi: 10.1016/s0009-9260(72)80019-9. [DOI] [PubMed] [Google Scholar]
  55. Whaley K., Williamson J., Chisholm D. M., Webb J., Mason D. K., Buchanan W. W. Sjogren's syndrome. I. Sicca components. Q J Med. 1973 Apr;42(166):279–304. [PubMed] [Google Scholar]
  56. de Wilde P. C., Kater L., Baak J. P., van Houwelingen J. C., Hené R. J., Slootweg P. J. A new and highly sensitive immunohistologic diagnostic criterion for Sjögren's syndrome. Arthritis Rheum. 1989 Oct;32(10):1214–1220. doi: 10.1002/anr.1780321005. [DOI] [PubMed] [Google Scholar]
  57. van Bijsterveld O. P. Diagnostic tests in the Sicca syndrome. Arch Ophthalmol. 1969 Jul;82(1):10–14. doi: 10.1001/archopht.1969.00990020012003. [DOI] [PubMed] [Google Scholar]
  58. van Bijsterveld O. P., Mackor A. J. Sjögren's syndrome and tear function parameters. Clin Exp Rheumatol. 1989 Mar-Apr;7(2):151–154. [PubMed] [Google Scholar]
  59. van Bijsterveld O. P. Standardization of the lysozyme test for a commercially available medium. Its use for the diagnosis of the sicca syndrome. Arch Ophthalmol. 1974 Jun;91(6):432–434. doi: 10.1001/archopht.1974.03900060446002. [DOI] [PubMed] [Google Scholar]

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