2. INTRODUCTION
• Syn : Gougerot–Houwer–Sjögren syndrome /
Sicca Syn
• Swedish Ophthalmologist Henrik Sjögren who
first described it (1933) ; Mikulicz - 1888
• Defined as a systemic autoimmune disease
caused by an immune-mediated inflammation of
exocrine glands, and involves salivary, lacrimal
and sweat glands, as Sicca Syndrome or with
internal organ involvement.
3. CLINICAL TYPES
• PRIMARY SS - de novo ; assoc with
Malignant Lymphomas
• SECONDARY SS - associated rheumatic
disorder (RA / SLE / SSc / PBC)
• SICCA SYNDROME – Xerophthalmia +
Xerostomia – Internal Organ / Bone Inv
4. ETIOLOGY
• Female : Male = 9 : 1
• 4/5/6th decade
• Autoimmune ; HLA-B8 / DR3 / Complement
allele C4AQO [7] / HLA-DRw52 (Jap)
• Antibodies to the SSA / Ro in relatives
9. XEROPHTHALMIA
Aka DES
Dry eyes for more than 3 months
Gritty Sensation of sand or gravel in the eyes
Need for tear substitutes more than 3 times a day
Schirmer’s test, performed without anaesthesia (≤5 mm in 5 min)
Rose Bengal score or other ocular dye score (Lisamine Green)
Fluoroscine flow / Lactoferrin or Lysozyme estimation / Lacrimal Biopsy
43% - Keratoconjunctivitis Sicca with xerostomia
23% had associated CTD (RA)
Oral symptoms may precede ocular, or both may occur late in the disease.
10.
11. SCHIRMER’S TEST
• German Ophthalmologist Otto Schirmer
• determines whether the eye produces enough
tears to keep it moist
• This test is used when a person experiences
very dry eyes or excessive watering of the eyes
12. PROCEDURE / INFERENCE
• Schirmer's test places a small strip of filter paper inside the lower
eyelids (conjunctival sac). The eyes are closed for 5 minutes. The
paper is then removed and the amount of moisture is measured.
This technique measures basic tear function.
• A young person normally moistens 15 mm of each paper strip.
Because hypolacrimation occurs with aging, 33% of normal elderly
persons may wet only 10 mm in 5 minutes. Persons with Sjögren's
syndrome moisten less than 5 mm in 5 minutes.
• INTERPRETATION
1. Normal which is ≥15 mm wetting of the paper after 5 minutes
2. Mild which is 14-9 mm wetting of the paper after 5 minutes
3. Moderate which is 8-4 mm wetting of the paper after 5 minutes
4. Severe which is <4 mm wetting of the paper after 5 minutes.
16. XEROSTOMIA
• Saliva is at first thick and mucoid, but later salivary volume
decreases; requirement of liquids to swallow food
• Tongue is red, smooth and dry, and in severe cases there
may be difficulty in swallowing dry food.
• Parotid duct narrowing and web formation may develop.
Recurrent episodes of swelling of one or both parotid
glands or, less often, the submaxillary and sublingual
glands, may be due to autoimmune inflammation or
infection, which is common
• Dental caries - severe and progressive
• The lips are red, dry and scaly. There are frequently cracks
at the corners of the mouth.
• Chronic oral candidiasis is frequent
19. TESTING
Unstimulated whole salivary flow (>1.5 ml in 15 min)
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
Focal lymphocytic sialoadenitis (focus score ≥1) on HPE
(the number of mononuclear cell infiltrates containing at
least 50 inflammatory cells in a 4 mm2 glandular section)
21. OTHER MANIFESTATIONS
Arthralgia and arthritis
Myalgia and myositis
ENT : Sinusitis / Hearing Loss / TPRD / Atrophic Rhinitis
GI : GERD / Achlorhydria
Resp : Interstitial pneumonitis, pulmonary fibrosis and pulmonary
hypertension
Nephro : Interstitial nephritis, Renal Tubular Acidosis
Neuro : migraine, neuropathies, cerebral vasculitis
22. MISCELLANEOUS
• In patients without associated connective
tissue disease, mild articular symptoms occur
in 83%, with mild synovitis
• Cervical or generalized LAN
• Hepatosplenomegaly
24. American-EU Consensus Classification
Criteria : SS (1989 1996)
1. Ocular symptoms: at least one of:
1 Dry eyes for more than 3 months
2 Gritty Sensation of sand or gravel in the eyes
3 Need for tear substitutes more than 3 times a day
2. Oral symptoms: at least one of:
1 Dry mouth for more than 3 months
2 Recurrently or persistently swollen salivary glands as an adult
3 Need liquids to swallow dry food
3. Ocular signs—at least one of the following two tests positive:
1 Schirmer’s test, performed without anaesthesia (≤5 mm in 5
min)
2 Rose Bengal score or other ocular dye score
25. 4. Histopathology: in minor salivary glands, focal lymphocytic sialoadenitis
(focus score ≥1).
5. Salivary gland involvement: a positive result for at least one of the
following diagnostic tests:
1 Unstimulated whole salivary flow (≤1.5 ml in 15 min)
2 Parotid sialography showing the presence of diffuse sialectasias (punctate,
cavitary, or destructive pattern), without evidence of obstruction in the major
ducts
3 Salivary scintigraphy showing delayed uptake, reduced concentration and/or
delayed excretion of tracer
6. Autoantibodies – SSA (Ro) / SSB (La)
26. Criteria
For primary SS
• In patients without any potentially associated disease,
primary SS may be defined as follows:
• a. The presence of any four of the six items is indicative of
primary SS, as long as either item 4 (Histopathology) or 6
(Serology) is positive.
• b. The presence of any three of the four objective criteria
items (that is, items 3, 4, 5, 6)
For secondary SS
• In patients with a potentially associated disease, the
presence of item 1 or item 2 plus any two from among
items 3, 4, and 5 may be considered as indicative of
secondary SS
27. Proposed classification criteria for SS :
ACR (2012)
•
1. Positive serum anti-SSA/Ro and/or anti-SSB/La or (positive rheumatoid factor
and ANA titer 1:320)
•
2. Labial salivary gland biopsy exhibiting focal lymphocytic sialadenitis with a focus
score 1 focus/4 mm2
•
3. Keratoconjunctivitis sicca with ocular staining score 3 (assuming that individual
is not currently using daily eye drops for glaucoma and has not had corneal surgery
or cosmetic eyelid surgery in the last 5 years)
Prior diagnosis of any of the following conditions would exclude participation in SS
studies or therapeutic trials because of overlapping clinical features or interference
with criteria tests:
Head / Neck Radiation
HCV Inf
AIDS
Sarcoidosis
Amyloidosis
GVHD
29. DDx (SS)
• HIV infection diffuse infiltrative lymphocytosis
syndrome (DILS), which is characterized by
parotid enlargement; involvement of the renal,
lung, and gastrointestinal systems
• Chronic GVHD may mimic symptoms
• SLE might be considered, especially at onset of
the disease. Autoimmune thyroid dysfunction
may be present.
33. INVESTIGATIONS
• Se Globulin
• RA (52% Primary ; 98% Secondary)
• ANA (>50%) speckled, and nucleolar factor is only
occasionally found).
• Anti-dsDNA / Anti-RNP rarely found in the sicca syndrome
alone.
• Anti-Ro (also called SS-A) and anti-La (SS-B) are frequently
found (53%), associated with vasculitis, purpura, LAN
• Antibodies to Lupus Anticoagulant / APLA
• Antibodies to carbonic anhydrase 11 can be seen in
patients with Sjögren syndrome who have primary billiary
cirrhosis.
34. • Anti-La assoc with Annular Erythema
• Antibody to salivary duct epithelium can be
demonstrated in approximately 50%
• Thyroglobulin antibodies are present in 25% of
cases
• Leukopenia and eosinophilia may be seen. ESR
generally raised.
35. • Presence of anti–alpha-Fodrin antibody (reliable diagnostic
marker of juvenile Sjögren syndrome)
• Creatinine clearance may be diminished in up to 50% of
patients
• High alkaline phosphatase level – s/o Primary Biliary
Cirrhosis
• Elevated transaminase levels –s/o Chr Hepatitis
• Hypokalemia
37. TREATMENT
• Symptomatic treatment for the dryness of the
eyes is best accomplished by lubricating
agents, such as 0.5% Methylcellulose eye
drops instilled into the eyes four or five times
daily.
• Bromhexine 16 mg three times daily has been
found to increase the lacrimal secretion, but
has no effect on salivary flow
38. • Artificial saliva / Steam inhalation / Humidifier –
Respiratory Tract
• Systemic corticosteroids reducing parotid swelling, but
rarely increase parotid or lacrimal secretion.
• Ciclosporin improved subjective xerostomia and may
reduce histopathological progression.
• Nifedipine may help Raynaud’s phenomenon.
• Associated Polymyositis improved with monthly
intravenous pulse CPA therapy.
• Annular erythema in Japanese patients may be controlled
by prednisolone 10–20 mg/day or by dapsone.
• Graduated compression hosiery for hyperglobulinaemic
purpura
40. BIOLOGICS
• Reports on the use of Rituximab in patients
with primary Sjögren syndrome - improved
saliva flow rate, lacrimal gland function,
vasculitis, and peripheral neuropathy
• Eparazumab ?????
