sjogren syndrome

1. BY DR SUMAN ROY
MD PGT

4. 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.

5. EPIDEMIOLOGY
 MIDDLE-AGED WOMEN (FEMALE-TO-
MALE RATIO, 9:1) ARE PRIMARILY
AFFECTED
 ALTHOUGH SJÖGREN’S SYNDROME
MAY OCCUR AT ANY AGE, INCLUDING
CHILDHOOD.

6.  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.

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

10. 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).

11. 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

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

13. 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

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

15. (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;

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

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

18. 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

19.  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

20. 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.

21.  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.

22. 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,

23.  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

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

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

35. 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?

36. 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

37. 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

38. 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.

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

40. . 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).

41. 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

47. 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

48. 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

49. 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

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

51. 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

52.  THANK YOU