Sjögren’s Syndrome

1. Sjögren’s Syndrome Classification Criteria Extraglandular Manifestations Clinical Follow-up Systemic Therapy Claudio Vitali, MD Dept. of Internal Medicine and Section of Rheumatology Piombino, Italy

2. Sjögren’s Syndrome - Definition • Sjögren's syndrome (SS) is defined as an autoimmune disease of the exocrine glands, involving in particular the salivary and lacrimal glands. • It may occur alone (primary SS), or in association with a variety of connective tissue diseases and autoimmune disorders (secondary SS). • The spectrum of presentation of the disorder is very broad, ranging from the local consequences of exocrine gland dysfunction to major, life-threatening systemic complications such as vasculitis, and renal or lung involvement.

3. Sjögren’s Syndrome - Associations • Rheumatoid arthritis • Systemic Lupus • Scleroderma • Mixed Connective Tissue Disease • Primary Biliary Cirrhosis • Myositis • Vasculitis • Thyroiditis • Chronic Active Hepatitis • Mixed Cryoglobulinaemia

4. Sjögren’s Syndrome Classification Criteria Extraglandular Manifestations Clinical Follow-up Systemic Therapy

5. Sjögren’s Syndrome Classification (Diagnostic) Criteria Extraglandular Manifestations Clinical Follow-up Systemic Therapy

9. Types of Criteria for Rheumatic Diseases(from Fries JF, et al.: Arthritis Rheum, 1994)

10. Classification Criteria for SjSIssues • Introductory Remarks • History • European/American classification criteria • Impact of different classification criteria on the Scientific Community • Performance of different classification criteria sets

11. Classification Criteria for Sjögren’s SyndromeIntroductory Remarks • Conceptually, classification criteria are the same as diagnostic criteria. This is particularly true when sensitivity and specificity of classification criteria were both close to 100%. • However, classification criteria are usually not perfect and a certain proportion of patients is always misclassified. • Thus, classification criteria do not have the medical standing of a diagnosis and the physician is the only one who can establish a diagnosis for an individual patient.

12. Classification Criteria are not aimed at the Diagnosis

13. Classification Criteria are a Communication Tool

15. Classification Criteria for Sjögren’s Syndrome Historical Overview

16. San Diego Classification Criteria for SjS (Fox RI et al., 1986) Histopathology of minor salivary (or lacrimal) glands (focus score ≥2) Salivary gland involvement Symptomatic xerostomia plus Decreased Unstimulated and Stimulated whole salivary gland flow Ocular involvement Positivity of Schirmer’s I test (<9 mm/5min) plus Increased Staining with Rose Bengal test (or fluorescin test) Autoantibodies Presence of anti-Ro/La antibodies or Presence of ANA or Presence of RF Exclusions: Pre-existing lymphoma Graft-versus-host disease Acquired Immunodeficiency disease Sarcoidosis

17. The Mosaic of Different Classification Criteria Sets included not included

18. The application of different diagnostic criteria over the years has led to a heterogeneous group of patients being given the diagnosis of SjS. There is an increasing need to establish internationally recognized criteria for the diagnosis of SjS, both to provide common basis for defining patients for studies and to clarify case-by-case clinical diagnosis. Proceedings of 2nd International Symposium on SS (San Antonio, Texas, 1989). J Autoimmun 1989; 2: 529-41

19. Pisa, September 1988 Meeting of the Experts

20. Preliminary criteria for the classification of Sjögren's syndrome. Results of a prospective concerted action supported by the European Community. Vitali C, Bombardieri S, Moutsopoulos HM, et al. Arthritis Rheum 1993; 36: 340-7

21. Assessment of the European classification criteria for Sjögren's syndrome in a series of clinically defined cases. Results of a prospective multicentre study. • Vitali C, Bombardieri S, Moutsopoulos HM, et al. • Ann Rheum Dis 1996; 55: 116-22.

22. Venice, December 1999 VIIth International Symposium on SjS

23. Classification Criteria for Sjögren’s Syndrome The European American Revision of the Classification Criteria

24. Classification Criteria for Sjögren’s Syndrome

26. Classification Criteria for Sjögren’s syndromeNew Rules for the Classification

27. Classification Tree for Primary SjS sensitivity 96.05% specificity 94.2%

28. Classification Criteria for Sjögren’s SyndromeAgreement on the Exclusion Criteria

29. Classification criteria for Sjögren's syndrome: a revised version of the European criteria proposed by the American-European Consensus Group. Vitali C, Bombardieri S, Jonsson R, Moutsopoulos HM, Alexander EL, Carsons SE, Daniels TE, Fox PC, Fox RI, Kassan SS, Pillemer SR, Talal N, Weisman MH. Ann Rheum Dis 2002; 61: 554-8.

30. Classification Criteria for Rheumatic Diseases

31. Classification Criteria for Sjögren’s Syndrome The Impact of the Different Classification Criteria Sets on the Scientific Community

32. Number of Citations in the Medical Journals of Different Classification Criteria Sets proposed for Sjögren’s SyndromeSource ISI-Web of Science (Jan 1990-May 2004)

33. Classification Criteria for Sjögren’s Syndrome The Performance of Different Classification Criteria Sets

34. Study Population 35 Patients with Clinically Defined Primary SjS (1 Male, mean age 58.9 yrs.) 54 Disease Controls: 20 Patients with other CTDs, without Secondary SjS (1 Male, mean age 49.0 yrs.) 34 Patients with Sicca Complaints, but without SjS (5 Males, mean age 50.8 yrs.)

35. Classification CriteriaSensitivity - Definition Prevalence of true patients which meet the criteria designed to correctly classify patients as having that disease. TP TP+FN x100

36. Sensitivity of the Different Classification Criteria Sets *p<.05 **p<.01 ***p<.001 % * ** *** *** ***

37. Classification CriteriaSpecificity - Definition Prevalence of normal (or disease) controls which do not meet the criteria designed to correctly classify patients as having a given disease. TN TN+FP x100

38. Specificity of the Different Classification Criteria Sets %

39. Classification CriteriaPositive Predictive Value - Definition Prevalence of cases which meet the criteria for a given disease, which are true patients with that disease. TP TP+FP x100

40. Positive Predictive Value of the Different Classification Criteria Sets %

41. Classification CriteriaNegative Predictive Value - Definition Prevalence of cases which do not meet the criteria for a given disease, which do not suffer from that disease. TN TN+FN x100

42. Negative Predictive Value of the Different Classification Criteria Sets *p<.05 **p<.01 ***p<.001 % * * ** *** ***

43. Classification CriteriaAccuracy - Definition TN+TP TN+TP+FN+FP x100

44. Accuracy of the Different Classification Criteria Sets *p<.05 **p<.01 ***p<.001 * * ** % *** ***

45. Concluding Remarks • American-European Classification Criteria are: • the only validated, • the most reliable, • and • the most widely accepted • tool presently available for the classification of patients with primary and secondary Sjögren’s syndrome.

46. Sjögren’s Syndrome Classification Criteria Extraglandular Manifestations Clinical Follow-up Systemic Therapy

47. Sjögren’s Syndrome Classification Criteria Extraglandular Manifestations Clinical Follow-up Systemic Therapy

48. SjS - Manifestazioni Cliniche Extraghiandolari

49. SjS - Alterazioni Sierologiche

50. Cutaneous involvement of patients with primary SjS • Cutaneous vasculitis • SS associated small vessel vasculitis •      Cryoglobulinaemic vasculitis •      Urticarial vasculitis •      Other leucocytoclastic vasculitis • SS associated medium vessel vasculitis • b) Other cutaneous processes • Ro associated, polycyclic, photosensitive cutaneous lesions (SCLE) • Erythema nodosum • Livedo reticularis • Thrombocytopenic purpura • Lichen planus • Vitiligo • Nodular vasculitis • Cutaneous amyloidosis • Annular granuloma • Granulomatous panniculitis