Sjogren syndrome

sjogren syndrome

1. Sjögren syndrome BY DR SUMAN ROY MD PGT

2. DEFINATION Sjögren’s syndrome is a chronic, slowly progressive autoimmune disease characterized by lymphocytic infiltration of the exocrine glands resulting in xerostomia and dry eyes.

3. EPIDEMIOLOGY Middle-aged women (female-to-male ratio, 9:1) are primarily affected although Sjögren’s syndrome may occur at any age, including childhood.

4. The prevalence of primary Sjögren’s syndrome is ~0.5–1%, while 30% of patients with autoimmune rheumatic diseases suffer from secondary Sjögren’s syndrome.

5. PATHOGENESIS Lymphocytic infiltration of the exocrine glands and B lymphocyte hyperreactivity .

6. Serum often contain : Autoantibodies to non-organ-specific antigens such as immunoglobulins (rheumatoid factors) and extractable nuclear and cytoplasmic antigens (Ro/SS-A, La/SS-B).

7. Autoantibodies to Ro/SS-A and La/SS-B antigens are usually detected at the time of diagnosis and are associated with earlier disease onset, longer disease duration, salivary gland enlargement, and more intense lymphocytic infiltration of minor salivary glands

8. The major infiltrating cells in the affected exocrine glands are: activated T and B lymphocytes Macrophages and dendritic cells also are found.

9. predictors for lymphoma development. The number of macrophages positive for interleukin (IL) 18 has been shown to correlate with parotid gland enlargement and low levels of the C4 component of complement BOTH ARE ADVERSE PREDICTORS OF LYMPHOMA DEVELOPMENT

10. Ductal and acinar epithelial cells appear to play a significant role in the initiation and perpetuation of autoimmune injury .

11. (1) express class II major histocompatibility complex (MHC) molecules, co-stimulatory molecules, and abberant expression of intracellular autoantigens on cell membranes and thus are able to provide signals essential for lymphocytic activation;

12. (2) inappropriately produce proinflammatory cytokines and lymphoattractant chemokines necessary for sustaining the autoimmune lesion AND

13. and allowing progression to more sophisticated ectopic germinal center formation ,

14. and (3) express functional receptors of innate immunity, particularly Toll-like receptors (TLRs) 3, 7, and 9, that may account for the perpetuation of the autoimmune response

15. Both infiltrating T and B cells have a tendency to be resistant to apoptosis. Levels of B cell–activating factor (BAFF) have been found to be elevated in patients with Sjögren’s syndrome, especially those with hypergammaglobulinemia , and probably accounts for this antiapoptotic effect

16. Glandular epithelial cells seem to have an active role in the production of BAFF, which may be expressed and secreted after stimulation with type I interferon as well as with viral or synthetic double- strandedRNA .

17. The triggering factor for epithelial activation appears to be a persistent enteroviral infection (possibly with coxsackievirus strains). Type I and type II interferon signatures have been described in ductal epithelial cells and T cells, respectively; their detection implies that interferons exert direct and cross-regulating effects on the pathogenic process.

18. A defect in cholinergic activity mediated through the M3 receptor and redistribution of the water-channel protein aquaporin 5, both leading to neuroepithelial dysfunction and diminished glandular secretions,

19. Molecular analysis of human leukocyte antigen (HLA) class II genes has revealed that Sjögren’s syndrome, regardless of the patient’s ethnic origin, is highly associated with the HLA DQA1*0501 allele. Genomewide association studies have disclosed an increased prevalence of single-nucleotide polymorphisms in genes of IRF-5 and STAT-4, which participate in the activation of the type I interferon pathway

20. SJ SYNDROME Cracked, peeling and atrophic appearance of the lips. Dry and fissured tongue

21. SJ SYNDROME Dry and smooth tongue. Hyposalivation-related dental caries.

22. Revised International Classification Criteria for Sjogren’s Syndrome I. Ocular symptoms: a positive response to at least one of three validated questions. 1. Have you had daily, persistent, troublesome dry eyes for more than 3 months? 2. Do you have a recurrent sensation of sand or gravel in the eyes? 3. Do you use tear substitutes more than three times a day?

23. II. Oral symptoms: a positive response to at least one of three validated questions. 1. Have you had a daily feeling of dry mouth for more than 3 months? 2. Have you had recurrent or persistently swollen salivary glands as an adult? 3. Do you frequently drink liquids to aid in swallowing dry foods

24. III. Ocular signs: objective evidence of ocular involvement defined as a positive result to at least one of the following two tests: 1. Shirmer’s I test, performed without anesthesia (≤5 mm in 5 min) 2. Rose Bengal score or other ocular dye score (≥4 according to van Bijsterveld’s scoring system

25. IV. Histopathology: In minor salivary glands focal lymphocytic sialoadenitis , with a focus score ≥1. V. Salivary gland involvement: objective evidence of salivary gland involvement defined by a positive result to at least one of the following diagnostic tests: 1. Unstimulated whole salivary flow (≤1.5 mL in 15 min) 2. Parotid sialography 3. Salivary scintigraphy VI. Antibodies in the serum to Ro/SS-A or La/SS-B antigens, or both.

26. Exclusion criteria: past head and neck radiation treatment, hepatitis C infection, AIDS, preexisting lymphoma, sarcoidosis , graft-versus-host disease, use of anticholinergic drugs

27. . Primary Sjögren’s syndrome : Any four of the six items, as long as item IV (histopathology) or VI (serology) is positive; or any three of the four objective-criteria items (III, IV, V, VI).

28. In patients with a potentially associated disease (e.g., another well-defined connective tissue disease), the presence of item I or item II plus any two from among items III, IV, and V may be considered indicative of secondary Sjögren’s syndrome

29. GLANDULAR MANIFESTATIONS DRY EYES Avoid Smoking areas, windy, low humidity environment, drugs with anticholinergic action, diuretics Lubrication Artificial tears without preservatives, bicarbonate-buffered electrolyte solutions Local stimulation Cyclic adenosine monophosphate , cyclosporine 2% olive solution

30. GLANDULAR MANIFESTATIONS DRY EYES Systemic stimulation Pilocarpine (5 mg thrice daily orally); cevimeline (30 mg thrice daily orally) Severe dry eyes Nasolacrimal duct occlusion (temporary or permanent); soft contact lenses; corneal transpla

31. GLANDULAR MANIFESTATIONS DRY MOUTH Oral hygiene after each meal Topical application of fluoride Lubrication Water Local Stimulation Sugar-free, flavored L Lozenges or gum Systemic Stimulation As for dry eyes Oral Candidiasis Topical nystatin or clotrimazole lozenges

32. Apply Local wet heat Treat Superinfection Antibiotics,analgesics Persistent, Hard Rule out lymphoma PAROTID GLAND ENLARGEMENT

33. EXTRAGLANDULAR MANIFESTATIONS: ARTHRITIS Hydroxychloroquine (200–400 mg/d) or Methotrexate (0.2–0.3 mg/kg body weight weekly) plus Prednisolone (<10 mg daily orally RAYNAUDS PHENOMENON RENAL TUBULAR Cold protection: gloves ACIDOSIS Bicarbonate replacement VASCULITIS LYMPHOMA Standard CHOP+ Anti CD20 Treatment

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