Sjögren's Syndrome
Summary
Sjögren's Syndrome (SS) is a chronic autoimmune exocrinopathy characterised by lymphocytic infiltration of the exocrine glands, primarily the lacrimal and salivary glands, causing dry eyes (keratoconjunctivitis sicca) and dry mouth (xerostomia). It can occur as Primary Sjögren's (isolated) or Secondary Sjögren's (in association with another autoimmune disease, most commonly RA or SLE). The hallmark autoantibodies are Anti-Ro (SSA) and Anti-La (SSB). The major concern is a significantly increased lifetime risk of Non-Hodgkin Lymphoma (5-10%). [1,2]
Clinical Pearls
The Lymphoma Shadow: Sjögren's carries a 15-20x increased risk of B-cell Non-Hodgkin Lymphoma (especially MALT lymphoma of the parotid). Any persistent, hard, or unilateral parotid swelling warrants investigation. Suspect if low C4, Cryoglobulins, or worsening RF.
It's Not Just Dry Eyes and Mouth: Sjögren's is a systemic disease. Extra-glandular manifestations include fatigue (nearly universal), arthralgia, interstitial lung disease, renal tubular acidosis, and vasculitis.
Anti-Ro in Pregnancy: Women with Anti-Ro antibodies (even if asymptomatic) can have babies with Neonatal Lupus or Congenital Heart Block. Screen pregnant women if known positive.
Schirmer's Test: A simple bedside test. A strip of filter paper is placed in the lower conjunctival sac. less than 5mm wetting in 5 minutes indicates dry eye.
Demographics
- Prevalence: 0.5-1% of the general population.
- Sex: 9:1 Female predominance.
- Age: Peak onset 40-60 years (but can occur at any age).
- Association: 30% of RA patients and 10-20% of SLE patients develop Secondary Sjögren's.
Risk Factors
- Genetic: Strong HLA association (DRB10301, DQB10201).
- Viral Trigger: Postulated role for EBV, HTLV-1.
Mechanism
- Genetic Predisposition + Environmental Trigger: Viral infection or other trigger initiates immune response in genetically susceptible individuals.
- Epithelial Cell Activation: Salivary and lacrimal ductal epithelial cells become targets of autoimmune attack. They express HLA Class II and co-stimulatory molecules, presenting autoantigens.
- Lymphocytic Infiltration (Focal Lymphocytic Sialadenitis): CD4+ T-cells and B-cells infiltrate the glands, forming organised lymphoid structures (tertiary lymphoid organs).
- Autoantibody Production: Polyclonal B-cell activation produces Anti-Ro (SSA) targeting Ro52/Ro60 ribonucleoproteins and Anti-La (SSB).
- Glandular Destruction: Progressive destruction of acinar cells leads to reduced secretion (Sicca syndrome).
- Extra-Glandular Disease: Immune complex deposition and vasculitis cause systemic manifestations.
- Lymphomagenesis: Chronic B-cell stimulation predisposes to monoclonal transformation and Non-Hodgkin Lymphoma.
| Condition | Key Features |
|---|---|
| Age-Related Dry Eye | Common in elderly. No systemic features or autoantibodies. |
| Medication-Induced | Anticholinergics, Antihistamines, Diuretics, TCAs, SSRIs. |
| Dehydration / Mouth Breathing | Contextual. |
| Diabetes Mellitus | Polyuria/Polydipsia. Autonomic neuropathy. |
| Sarcoidosis | Bilateral parotid swelling (Heerfordt's syndrome). Bilateral Hilar Lymphadenopathy. Non-caseating granulomas. |
| IgG4-Related Disease | Painless gland swelling. Elevated IgG4. Responds to steroids. |
| HIV-Associated Sicca (DILS) | Diffuse Infiltrative Lymphocytosis Syndrome. CD8+ lymphocyte infiltration. HIV positive. |
| Amyloidosis | May cause gland infiltration (Macroglossia). Congo Red stain. |
Glandular (Sicca) Manifestations
Extra-Glandular (Systemic) Manifestations (~40-50%)
Classification Criteria (ACR/EULAR 2016 - Score ≥4)
| Item | Score |
|---|---|
| Positive Lip Biopsy (Focal Lymphocytic Sialadenitis, Focus Score ≥1) | 3 |
| Anti-SSA/Ro Positive | 3 |
| Ocular Staining Score ≥5 (Rose Bengal/Lissamine Green/Fluorescein) | 1 |
| Schirmer's Test ≤5mm/5min | 1 |
| Unstimulated Salivary Flow ≤0.1 ml/min | 1 |
Serology
- Anti-Ro (SSA): Positive in 60-70% of Primary SS.
- Anti-La (SSB): Positive in 30-40%. More specific.
- Rheumatoid Factor (RF): Often positive (up to 50%).
- ANA: Positive in 80%.
- Hypergammaglobulinaemia: Polyclonal IgG elevation.
Eye Assessment
- Schirmer's I Test: less than 5mm wetting in 5 mins is positive.
- Ocular Surface Staining: Slit lamp with Rose Bengal/Lissamine Green.
Salivary Gland Assessment
- Labial Salivary Gland Biopsy (Minor Gland Biopsy): Gold standard. Focus Score ≥1 (Aggregates of ≥50 lymphocytes per 4mm²).
- Ultrasound / MRI Salivary Glands: Parenchymal heterogeneity.
Systemic Screening
- LFTs, U&Es, Urinalysis (Renal tubular acidosis).
- Complement C3/C4 (Low C4 is a lymphoma risk factor).
- Cryoglobulins (Lymphoma risk factor).
- PFTs / HRCT Chest (If respiratory symptoms).
Management Algorithm
SJÖGREN'S SYNDROME DIAGNOSED
(ACR/EULAR Criteria ≥4 or Clinically)
↓
ASSESS MANIFESTATIONS
┌──────────┴───────────┐
SICCA ONLY EXTRA-GLANDULAR
↓ ↓
SYMPTOMATIC SYSTEMIC
TREATMENT TREATMENT
↓ ↓
- Artificial Tears - Hydroxychloroquine
- Saliva Substitutes (Fatigue, Arthralgia)
- Pilocarpine - DMARDs (e.g., MTX)
(Severe disease)
- Rituximab
(Refractory vasculitis, etc.)
- Steroids
(Short-term for flares)
↓
LYMPHOMA SURVEILLANCE
- Monitor for persistent swelling
- Check C4, Cryoglobulins
1. Sicca Symptom Management
- Dry Eyes:
- Artificial Tears (Preservative-free for frequent use).
- Lubricating Eye Ointments (Night-time).
- Ciclosporin Eye Drops (Restasis/Ikervis) for severe cases.
- Punctal Plugs (Block tear drainage).
- Dry Mouth:
- Saliva Substitutes (Gels, Sprays).
- Pilocarpine (Muscarinic agonist - stimulates secretion). S/E: Sweating, Flushing.
- Sugar-free gum.
- Aggressive dental hygiene (high caries risk).
2. Systemic Treatment
- Hydroxychloroquine: First-line for fatigue, arthralgia, mild systemic disease. (Annual eye screen for retinopathy).
- Corticosteroids: Short-term for flares. Avoid long-term.
- Methotrexate / Azathioprine: For arthritis or significant systemic involvement.
- Rituximab (Anti-CD20): For severe extra-glandular manifestations (Vasculitis, Cryoglobulinaemia, ILD).
3. Lymphoma Surveillance
- Watch for persistent/hard parotid swelling.
- Monitor: C4 (declining), Cryoglobulins (new), Monoclonal Gammopathy.
- Low threshold for biopsy if suspicious.
Glandular
- Corneal Ulceration / Perforation (Severe dry eye).
- Dental Caries (Accelerated due to reduced saliva).
- Oral Candidiasis.
- Recurrent Parotitis.
Non-Hodgkin Lymphoma
- Risk: 5-10% lifetime (15-20x general population risk).
- Type: Most commonly Marginal Zone B-cell Lymphoma (MALT lymphoma of parotid gland).
- Risk Factors: Low C4, Cryoglobulinaemia, Palpable Purpura, Lymphadenopathy, Splenomegaly.
Other Systemic
- Interstitial Lung Disease.
- Renal Tubular Acidosis (Hypokalaemia, Nephrocalcinosis).
- Peripheral Neuropathy.
- Generally good prognosis for glandular disease with symptomatic treatment.
- Prognosis worsens with extra-glandular involvement and development of lymphoma.
- Mortality: Increased mainly due to lymphoma and severe systemic vasculitis.
Key Guidelines
| Guideline | Organisation | Key Recommendations |
|---|---|---|
| Primary Sjögren's | EULAR (2020) | Hydroxychloroquine for fatigue/arthralgia. Rituximab for severe systemic. Pilocarpine for xerostomia. |
| Classification | ACR/EULAR (2016) | Scoring system requiring ≥4 points. |
Landmark Evidence
1. TEARS Trial (Rituximab)
- Rituximab vs Placebo for primary SS.
- Mixed Results: Did not meet primary endpoint (fatigue VAS) but showed some benefit in secondary outcomes. Rituximab is reserved for severe/refractory disease.
What is Sjögren's Syndrome?
It is an autoimmune condition where your immune system attacks the glands that make tears and saliva. This leads to very dry eyes and a very dry mouth.
Is it serious?
For most people, the main problem is the dryness, which is uncomfortable but manageable. However, it can affect other parts of the body (lungs, kidneys, nerves). The most important thing we watch for is a type of cancer called lymphoma, which affects some patients. If you notice persistent swelling in your salivary glands (near your ears or jaw), please tell us.
How is it treated?
- For dry eyes: Artificial tears, special eye drops.
- For dry mouth: Saliva sprays, gum, or tablets (Pilocarpine) to stimulate saliva.
- For body-wide symptoms: Medications like Hydroxychloroquine.
What about pregnancy?
If you have certain antibodies (Anti-Ro/SSA), there is a small risk they can affect your baby's heart. We monitor pregnancies closely.
Primary Sources
- Ramos-Casals M, et al. EULAR recommendations for the management of Sjögren's syndrome with topical and systemic therapies. Ann Rheum Dis. 2020.
- Shiboski CH, et al. 2016 American College of Rheumatology/European League Against Rheumatism classification criteria for primary Sjögren's syndrome. Ann Rheum Dis. 2017.
Common Exam Questions
- Antibody: "Specific antibody for Sjögren's?"
- Answer: Anti-La (SSB) is more specific. Anti-Ro (SSA) is more sensitive.
- Complication: "Major long-term risk?"
- Answer: Non-Hodgkin B-cell Lymphoma (5-10% lifetime risk).
- Investigation: "Gold standard diagnostic test?"
- Answer: Labial (Minor) Salivary Gland Biopsy showing Focal Lymphocytic Sialadenitis (Focus Score ≥1).
- Treatment: "Drug for xerostomia?"
- Answer: Pilocarpine (Muscarinic agonist).
Viva Points
- Schirmer's Test: Describe methodology. less than 5mm in 5 minutes is positive.
- Neonatal Lupus / CHB: Explain the transplacental passage of Anti-Ro and its effects on the fetus (rash, cytopenias, heart block).
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