Term
| What epidemiological factors define Sjogren's Syndrome? |
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Definition
1) 55-60 peak incidence
2) >9:1 women: men
3) 0.6% prevalence (1.3 million adults)
4) Secondary Sjogren's (25-30% of the number of primary cases) |
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Term
| What are the 6 primary diagnostic criteria for Sjogren's syndrome? |
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Definition
1) Ocular symptoms-grit sensation-
2) Oral-need liquids to swallow food
3) Ocular signs-Shirmer's test (tear), Rose-Bengal score(stain for damage to cornea and lens)
4) Histopathology-focal lymphocytic sialoadenitis (salivary inflammation)
5) Salivary gland- flow, sialography, scintigraphy
6) Autoantibodies (SSA/B (Ro/La)) |
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Term
| How can you determine if someone has primary Sjogren's Syndrome? |
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Definition
1) 4 of 6 diagnostic criteria with either (+) Histopathalogy for lymphocytic sialoadenitis or (+) Autoantibody test.
2) 3 of 4 objective criteria (Shirmer's, HIstopathology, Salivary gland involvement, Autoantibodies) |
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Term
A patient presents with focal lymphocytic sialoadenitis, an abnormal Shirmer's test and ocular grit sensation.
Do they have primary Sjogren's Syndrome? |
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Definition
Not necessarily
You need either 4 of 6 criteria with 4 or 6 (+), or 3 of 4 objective criteria.
This patient has 2 objective criteria (Shirmer's and sialoadenitis), but to be definitive, they must also have either (+) autoantibodies or salivary gland involvement.
Alternatively, they could also have oral symptoms, which would make 4 of 6 with histopathology (4) being (+) |
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Term
| When might you see secondary Sjogren's syndrome? |
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Definition
Usually I and II with 2 of III, IV, and V
1) Connective tissue diseases such as SLE, SSC, RA, MCTD, myositis, thyroid disease ect.
2) One item indicative of ocular or oral dryness (usually both)
3) 2 of the following: Ocular signs (III), positive salivary gland biopsy (IV), abnormal tests of salivary gland function (V) |
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Term
| How might you exclude Sjogren's Syndrome in a differential diagnosis? |
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Definition
MANY CAUSES OF SALIVARY GLAND ISSUES-SPECIFICS DONT MATTER
1) Prior head/neck irradiation
2) Hep C
3) AIDS
4) Lymphoma
5) Sarcoidosis
6) GVHD
7) Anticholinergic medication use
8) Other causes of sialadenitis: salivary stones, actue bacterial sialadenitis, |
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Term
| What are the primary disease features to look for in Sjogren's Syndrome? |
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Definition
1) Glandular- ocular, oral
2) Extraglandular (25% of patients)- Skin , joints, muscles, lungs, heart ect. with GENERALIZED FATIGUE |
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Term
| What diagnostic tests are available for Sjogren's Syndrome? |
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Definition
1) Ocular- Schirmer (tear), Rose bengal staining (eye damage)
2) Histopathology- lymphoid foci in salivary tissue
3) Salivary gland involvement- Ultrasounds, unstimulated flow, parotid sialography, salivary scintigraphy. |
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Term
| How do you treat "Xeroistomia" associated with Sjogren's? |
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Definition
1) Replacement of oral secretions (water, gum, spray)
2) Stimulation of salivary flow (Pilocarpine and Cevimelene (M3 stimulation)
3) Dental caries (biotene tooth paste)
4) Oral candidiasis (anti-fungals) |
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Term
| How might you treat the "Keratoconjunctivitis Sicca" in Sjogren's |
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Definition
1) Replacement with artifical treats (Retesin)
2) Cyclosporin and Tacrolimus (inhibit NFAT to reduce inflammation that prevents tear formation- RESTOSIS)
3) Diqualfosol (P2Y2 receptor to treat dry eye)
4) Punctal occlusion or cauterize (retain tears for longer periods) |
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Term
| What immunosuppresive therapies are available for Sjogren's? |
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Definition
1) Glandular
Hydroxychloroquine and Rituximab (dryness)
2) Extraglandular
Hydroxichloriquine and Methotrexate (arthritis)
Cyclophosphamide (neurologic)
Azathioprine (ILD)- may increase risk for lymphoma
Cyclosprone (interstitial cystitis)
Rituximab (lymphoma, fatigue) |
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Term
| What are 4 clinical associations seen with Sjogren's |
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Definition
1) Neonatal Lupus (anti-Ro (SSA) autoantibodies)
2) Lymphoma (pseudolymphomas; non-Hodgkin's: MALT lymphomas)
3) Dental caries/Oral thrush (lack of saliva is cause)
4) Other connective tissue diseases. |
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Term
| How does autoimmune epithelitis arise in Sjorgen's? |
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Definition
1) Salivary epithelial cells serve as APC
2) APCs activate T-cells (via VCAM, MHC, B7, CD40, ICAM1)
3) T-cells activate B-cells via CXCL13 (chemokines)
4) B cells make auto-antibodies against BAFF and SSA/B and form germinal centers |
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Term
| What is the role of CXCL13 is Sjorgen's pathophysiology? |
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Definition
| Chemokine released by T-cells to activate B-cells which make autoantibodies in Autoimmune Epithelitis of Salivary gland. |
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Term
| How do salivary lymph foci relate to Sjorgen's pathophysiology? |
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Definition
1) They contain B cells which form tertiary lymphoid organs with germinal centers
2) They form aggregates with transitional and marginal zone B cells |
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Term
| What does Blys overproduction have to do with Sjorgen's Syndrome? |
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Definition
1) Antigens activate monocytes which release Blys
2) Overproduction of Blys in B cells of salivary glands.
3) Blys is cleaved and soluble form activates B cells and leads to overproduction of autoantibodies
** This is seen in mouse models as well ** |
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Term
| How does Candidacidal activity of saliva develop with Sjogren's syndrome? |
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Definition
Decreased saliva leads to lower protein levels (histatins and beta-defensins) that are important for resistance against oral candidiasis
NORMAL
1) Candida binds C-type Lectin R on APC leading to production of IL-1, IL-6 and IL-23
2) These cytokines activate Th17 differentiation, which produces IL-17 to produce antimicrobial peptides (histatin/beta-defensin) and CXC chemokines to attract neutrophils. |
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Term
| How does the prevalence of Sjogren's relate to RA? |
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Definition
| They are about the same, but Sjogren's is handled more easily with minimal treatment |
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Term
| What are the most typical features to look for in a case presentation of Sjogren's? |
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Definition
Older women with dry eyes/mouth and parotid gland swelling.
They might have recurrent pleuritis and will probably have a (+) ANA with a speckled pattern. |
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Term
| What are the 6 important Extraglandular features to look for in Sjogren's? |
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Definition
1) Skin (Raynaud's)
2) Joints (arthralgias/arthritis)
3) Lungs (interstitial lung disease)
4) Kidney (interstitial nephritis)
5) Nerve/Brain (peripheral neuropathy)
6) General fatigue (really bad) |
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Term
True or False:
It is common to see Glomerulonephritis in Sjogren's |
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Definition
FALSE
You do often see extraglandular, renal involvement, but it is INTERSTITIAL NEPTHRITIS
(You see glomeruloneprhitis in SLE) |
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Term
| What are Pilocarpine and Cevimelene used for? |
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Definition
| To stimulate salivary flow by activating M3 receptors. |
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Term
| How can you test for salivary gland involvement in Sjogren's |
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Definition
1) Ultrasound
2) Unstimulated Flow
3) Parotid sialography (contrast with x-ray)
4) Salivary scintigraphy (Radio-labeled with imaging. Lemon juice should empty them) |
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Term
| What is the cut-off for tear travel distance in a Schirmer's test? |
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Definition
| <5mm (remember, <4mm is severe!) |
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Term
True or False
TNF is not thought to be involved in Sjogren's |
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Definition
True!
TNF-a is a pro-inflammatory cytokine, but it is not thought to be involved, as anti-TNF agents are ineffective |
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Term
| How does Rituximab work to treat Lymphoma and fatigue in Sjogren's? |
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Definition
Acts against CD20+ B cells, but leaves plasmablasts and memory cells
Older patients don't respond as well! |
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Term
| What is the basic idea behind Sjogrens pathogensis as it relates to BAFF and lymphoma? |
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Definition
1) BAFF is overproduced in B cells of salivary glands
2) Overproduction of BAFF activates B cells (plasmablasts) to make auto-antibodies against SSA/SSB
** Positive feedback loop** |
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