Sjogren's syndrome is an autoimmune disease characterized by lymphocytic infiltration of the exocrine glands resulting in dry eyes and mouth. It predominantly affects middle-aged women. Approximately one-third of patients experience systemic manifestations such as arthritis, lung involvement, or vasculitis. Pulmonary manifestations include airway disease, interstitial lung disease such as nonspecific interstitial pneumonia, lymphocytic interstitial pneumonitis, and usual interstitial pneumonia. Treatment involves managing dryness symptoms and suppressing inflammation.

1. Sjogrens syndrome
Dr. Vipin Aggarwal
Under Guidance –Dr. Gauri Godbole

2. Sjogren's Syndrome

3. •Sjögren's syndrome was in 1933 by Swedish eye specialist Henrik Sjögren
•Mikulich syndrome
•Sjögren's syndrome is a chronic, slowly progressive autoimmune disease
characterized by lymphocytic infiltration of the exocrine glands resulting in
xerostomia and dry eyes.
•Approximately one-third of patients present with systemic manifestations.

5. • Middle-aged women
• female:male ratio, 9:1
• Primary Sjögren's syndrome is approximately 0.5–1%,
• 30% of patients with autoimmune rheumatic diseases suffer from secondary
Sjögren's syndrome
• Approx. 1/3rd
of pts present with systemic manifestations
• HLA-B8, DR3 & DRw52 are prevalent in pts with primary sjogren’s

6. Sjögren syndrome:
Etiopathology
Etiology -not well understood
Characterised by:
◦Lymphocytic (T cells ,B cells) infiltration of exocrine glands
◦T cells infiltration –mild lesion
◦B cells –severe lesions
◦IL-18 macrophages-parotid gland involvement
◦Low levels of Compliment C4 prone to lymphoma
◦B lymphocyte hyper-reactivity

7. ◦ Expresses
non-organ-specific antigens such as immunoglobulins
(rheumatoid factors) -25%
extractable nuclear and cytoplasmic antigens (Ro/SS-A, La/SS-B)
fodrin (120 kDa), a salivary gland–specific protein,
muscarinic receptor 3 (M3R)
water-channel protein aquaporin-5

8. Clinical manifestations
• Majority of pts have symptoms related to diminished lacrimal & salivary gland
function
• In most pts the primary syndrome runs a slow & benign course.8 -10 years to
develop full blown disease
• Predominant Glandular manifestations:
 xerostomia
 keratoconjunctivitis sicca
• other less frequent glandular manifestations:
• xerotrachea,atrophic gastritis,subclinical pancreatitis

9. Oral manifestation
 Difficulty in swallowing dry food,
 inability to speak continuously,
 a burning sensation,
 increase in dental caries,
 problems in wearing complete dentures
On physical examination
 atrophy of filiform papillae on the dorsum of the tongue,
 saliva from the major glands is either not expressible or cloudy.
 Enlargement of the parotid -occurs in two-thirds of patients with primary Sjögren's syndrome

10. Keratoconjuctivitis sicca
•sandy or gritty feeling under the eyelids.
•burning, accumulation of thick strands at the inner canthi,
•decreased tearing,
•redness, itching,
•eye fatigue, and increased photosensitivity.
•These symptoms are attributed to the destruction of corneal and bulbar conjunctival epithelium

11. • Respiratory gland atrophy - dry nose, throat, and trachea (xerotrachea),
• GI gland atrophy -esophageal mucosal atrophy, atrophic gastritis, and subclinical pancreatitis.
• Dyspareunia due to dryness of the external genitalia and dry skin also may occur

12.  Extra-glandular manifestations are seen in one-third of pts:
Clinical Manifestation Percent
Arthralgias/arthritis 60
Raynaud's phenomenon 37
Lymphadenopathy 14
Lung involvement 14
Vasculitis 11
Kidney involvement 9
Liver involvement 6
Lymphoma 6
Splenomegaly 3
Peripheral neuropathy 2
Myositis 1

13.  Most pts with primary sjogrens experience atleast one episode
of nonerosive arthritis
 renal involvement – interstitial nephritis clinically manifesting
as hypoasthenuria and renal tubular dysfunction
 SN hearing loss was found in one-half of pts with sjogrens
 Vasculitis – purpura, recurrent urticaria, skin ulcers
 Lung involvement

14. Clinical.
A small but significant patients develop malignant lymphoma.
persistent parotid enlargement
purpura
leukopenia
Cryoglobulinemia
Low c4 counts
Most lymphomas are extra-nodal marginal zone B cell lymphomas
usually detected incidentally during evaluation of labial biopsy
Survival is decreased in patients with B symptoms, lymph node mass >7 cm in diameter,
and high or intermediate histologic grade.

15. Revised International Classification
Criteria for Sjögren's Syndrome
I. Ocular symptoms: a positive response to at least one of the following questions:
•Have you had daily, persistent, troublesome dry eyes for more than 3 months?
•Do you have a recurrent sensation of sand or gravel in the eyes?
•Do you use tear substitutes more than 3 times a day?
II. Oral symptoms: a positive response to at least one of the following questions:
•Have you had a daily feeling of dry mouth for more than 3 months?
•Have you had recurrently or persistently swollen salivary glands as an adult?
•Do you frequently drink liquids to aid in swallowing dry food?

16. criteria
III. Ocular signs-that is, objective evidence of ocular involvement defined as a positive
result for at least one of the following two tests:
• Schirmer's I test, performed without anaesthesia (</=5 mm in 5 minutes)
• Rose bengal score or other ocular dye score (>/=4 according to van Bijsterveld's
scoring system)
IV. Histopathology: In minor salivary glands (obtained through normal-appearing
mucosa) focal lymphocytic sialoadenitis, evaluated by an expert histopathologist,
with a focus score >/=1, defined as a number of lymphocytic foci (which are
adjacent to normal-appearing mucous acini and contain more than 50 lymphocytes)
per 4 mm2
of glandular tissue

17. CRITERIA
V. Salivary gland involvement: objective evidence of salivary gland involvement
defined by a positive result for at least one of the following diagnostic tests:
• Unstimulated whole salivary flow (</=1.5 ml in 15 minutes)
• Parotid sialography showing the presence of diffuse sialectasias (punctate,
cavitary or destructive pattern), without evidence of obstruction in the major
ducts
• Salivary scintigraphy showing delayed uptake, reduced concentration and/or
delayed excretion of tracer
VI. Autoantibodies: presence in the serum of the following autoantibodies:
Antibodies to Ro(SSA) or La(SSB) antigens, or both

18. Revised Rules for Classification
For primary SS
In patients without any potentially associated disease, primary SS may be defined as
follows:
The presence of any 4 of the 6 items is indicative of primary SS, as long as either item
IV (Histopathology) or VI (Serology) is positive
The presence of any 3 of the 4 objective criteria items (that is, items III, IV, V, VI)
The classification tree procedure represents a valid alternative method for
classification, although it should be more properly used in clinical-epidemiological
survey
For secondary SS
In patients with a potentially associated disease (for instance, another well defined
connective tissue disease), the presence of item I or item II plus any 2 from among
items III, IV, and V may be considered as indicative of secondary SS


19. Exclusion criteria:
Past head and neck radiation treatment
Hepatitis C infection
Acquired immunodeficiency disease (AIDS)
Pre-existing lymphoma
Sarcoidosis
Graft versus host disease
Use of anticholinergic drugs

20. DD of sjogren’s
HIV infection & sicca
syndrome
sjogren’s syn. sarcoidosis
Age predominantly young
males
predominantly in middle-
aged women
invariable
Auto-antibodies - Presence of
autoantibodies to Ro/SS-
A and/or La/SS-B
-
Histology lymphoid infiltrates of
salivary glands by CD8+
lymphocytes
Lymphoid infiltrates of
salivary glands by CD4+
lymphocytes
granulomas in salivary
glands
Genetics Associated with HLA-DR5 Associated with HLA-DR3
& DRw52
unknown
Serology Positive tests for HIV Neg. tests Neg. tests

21. HIV & Sjogren’s
Immunologic & rheumatologic disorders are common in HIV pts
Drug allergies are the most significant allergic reactions in HIV + , more common as the disease
progresses(upto 65% for TMP/SMX)
SLE & RA are ameliorated by the concomitant HIV inf.
The one autoimmune disease that may occur with increased frequency in HIV inf. Is A
VARIANT of PRIMARY SJOGREN’S
This syn. Consists of parotid gland enlargement,dry eyes & dry mouth
These pts donot have anti-SS-A or anti-SS-B
Less common with increased use of ARV
The term DIFFUSE INFILTRATIVE LYMPHOCYTOSIS SYNDROME(DILS) is used to describe this
entity

22. Treatment
Glandular manifestations:
Dry eyes:
1.Artificial tears without preservatives
2.Avoidance of drugs that decrease lacrimal & salivary secretion such as diuretics,
antihypertensive drugs,anticholinergics & antidepressants.
3.Systemic stimulation with oral pilocarpine 5 mg TID,oral cevimeline 30 mg TID
4. Severe dry eyes: NL duct occlusion ,soft contact lenses, corneal transplantation
5.If corneal ulcerations are present, eye patching and boric acid ointments are recommended

23. Treatment
• Xerostomia:
1. Lubrication – water( the best replacement)
2. Local stimulation- flavoured lozenges or gum
3. Systemic stimulation – as for dry eyes
4. Topical application of fluoride
5. Oral candidiasis – topical nystatin or clotrimazole lozenges
• Parotid enlargement :
1. Treat superinfection- antibiotics,analgesics
2. Hard, persistent – r/o lymphoma

24. Treatment
• Extraglandular manifestations:
1. Arthritis/arthralgia : Hydroxychloroquine 200-400 mg/day
2. Raynaud’s : cold protection with gloves & T.Nifedipine 10 mg TDS
3. RTA : sodium bicarbonate orally (0.5–2 mmol/kg in four divided doses).
4. Lymphoma : CHOP regimen + anti-CD20
5. Systemic vasculitis: glucocorticoids 1 mg/kg per day

25. Secondary sjogren’s
When it presents in association with other autoimmune rheumatic diseases
The common autoimmune diseases associated with sjogren’s are:
1. Rheumatoid arthritis
2. SLE
3. Scleroderma
4. MCTD
5. Primary biliary cirrhosis
6. vasculitis
7. chronic active hepatitis

26. Pulmonary
menifestation in
sjogrens

27. Pulmonary manifestations of Sjögren’s syndromeThoracic manifestations Prevalence Peculiar aspects in
Sjögren’s syndrome
Treatment
Airway disease
1.cough 41–61%# Secretagogues
(pilocarpine)
Nebulised saline
Solution
Bronchial
hyperresposivness
42–60%# Inhaled corticosteroids
Bronchiolitis 12–24%# Mainly follicular
bronchiolitis
Steroids
Rituximab
Macrolides
Bronchiectasis 7–54%# Mainly cylindrical
Bronchiectasis
Pulmonary infections 10–35%#

28. Thoracic manifestations Prevalence Peculiar aspects in
Sjögren’s syndrome
Treatment
Interstitial lung disease
Nonspecific interstitial
pneumonia
45%¶ Steroids
Hydroxychloroquine
Azathioprine
Cyclophosphamide
Rituximab
Usual interstitial pneumonia 16%¶ No benefit of immunosuppressive
Drugs
Lymphocytic interstitial
pneumonitis
15%¶ Steroids
Azathioprine
Cyclophosphamide
Chlorambucil
Rituximab
Organising pneumonitis 11%# Steroids
Azathioprine
Cyclosporine
Infliximab
Rituximab
Tocilizumab

29. Pulmonary amyloidosis rare female Steroids
Pulmonary lymphoma 2% Specific haematological
treatment
Pulmonary embolism
and
pulmonary hypertension
Rare Risk of venous
thrombosis
or pulmonary embolism
in
Sjögren’s syndrome
patients
is greater than in the
general population

30. risk factors of lung involvement
1. male,
2. smoking,
3. late onset
4. long evolution of disease
Pulmonary involvement is mostly associated with systemic manifestations,
hypergammaglobulinaemia and anti-SSA and anti-SSB antibodies

31. PFT in sjogrens disease
1.Generally shows restrictive disorder
2.Reduced DLCo
Airway disorder
Most common disorder manifesting as cough and bronchiolitis. cough treated by nebulised
saline and secretagogues.
Bronchiolits is mainly follicular :in Follicular bronchiolitis is characterised by the presence of
hyperplastic lymphoid follicles with reactive germinal centres distributed along bronchovascular
bundles.Treated with steroids , rituximab , or macrolides though with a low level of scientific
evidence

32. ILD in Sjögren’s syndrome
The first association between Sjögren’s syndrome and ILD, described in 1973, was lymphocytic
interstitial pneumonitis (LIP)
However, nonspecific interstitial pneumonitis (NSIP) seems to be the most common
pathological subtype revealed by lung biopsy
Ct scan shows interstitial abnormalities
ground-glass opacities (92%)
nonseptal linear opacities (75%) ,
interlobular septal thickening (55%)
Cysts (30%) , reticulation and fibrosis
often associated with airway disease (centrilobular nodules in 78% of Sjögren’s syndrome ILD).

33. Multiple thin wall air cysts randomly distributed 0.5/0.7cm in size are rare in other disorders
and may be a crucial factor in diagnosing Sjögren’s syndrome. often downstream of thickened
bronchi. The suspected mechanisms are the trapping of a check-valve”mechanism upstream
and destruction of the alveolar wall. D/D - LIP ,amyloidosis or lymphoma, particularly when they
are associated with nodules.
BAL studies have found lymphocytic alveolitis in the majority of Sjögren’s syndrome
asymptomatic patients (64%)(essentially with T-cells),
Require greater need for therapy and higher mortality, without systematically developing
respiratory disease

34. NSIP
Most common –fibrosing variant
Ct scan-
•bibasal and symmetrically predominant reticular abnormalities
•traction bronchiectasis, peri-bronchovascular extension (frequently associated with ground-
glass attenuation)
•sub-pleural sparing and pulmonary consolidations
Corticosteroids (ranging 0.5–1 mg·kg−1·day−1 with azathioprine or cyclophosphamide) are
usually prescribed for NSIP patients, but with no evidence of efficacy

35. Lymphocyitic interstitial pneumonitis
First association
Considered as a progression of follicular bronchiolitis
Accounts for 15% of cases
Reversible but progressive disease
diffuse proliferation of polyclonal lymphocytes and plasma cells in the pulmonary parenchymal
interstitium, with lymphoid follicles and germinal centres
Ct scan –
•thickened bronchovascular bundles (evoking association with follicular bronchiolitis),
•nodules and ground-glass opacities, and thickening of interlobular septa
• cysts in 68–82% of patients

36. Treatment of LIP
1.corticosteroids
2.immunosuppressive –variable response

37. UIP
In approx. 16 % of patients
Female >male
Older age
Ct scan-
•bilateral areas of intralobular reticular attenuation
•Traction bronchiectasis and small cystic changes
•basal and peripheral predominance and temporal heterogeneity
Sjögren’s syndrome patients have more interstitial inflammation, lymphoid follicles with
germinal centres and cysts

38. Organising pneumonia
11% of patients
CT scans
•multiple patchy areas of consolidation
•subpleural or peribronchovascular distribution, often bilateral,
•areas of ground-glass attenuation or fine centrilobular nodules
Ultimately proresses to NSIP
Corticosteroids
Immunosupressive drugs in resistant cases
Toclizumab under trial

39. Pulmonary lymphoma
16- to 44-fold increased risk of non-Hodgkin lymphoma
1–2% in patients with primary Sjögren’s syndrome
Most common-
•Marginal zone B-cell lymphoma
•mucosa-associated lymphoid tissue.
associated
•parotidomegaly,
• hypocomplementemia,
•type IIcryoglobulinaemia,
•cutaneous vasculitis,
•CD4 cytopenia and a low CD4/CD8 ratio

40. Thank you