Overview
Sjögren’s Syndrome is a chronic, systemic autoimmune disorder characterized by lymphocytic infiltration and destruction of exocrine glands, primarily affecting the salivary and lacrimal glands, leading to dry mouth (xerostomia) and dry eyes (keratoconjunctivitis sicca). It commonly affects middle-aged women, with a female:male ratio of approximately 9:1. It can be primary (isolated) or secondary (associated with other autoimmune diseases like RA or SLE).
Definition
Sjögren’s Syndrome (SS): Autoimmune disease targeting exocrine glands, especially lacrimal and salivary.
Xerostomia: Dry mouth due to decreased salivary flow.
Keratoconjunctivitis sicca: Dry eyes from decreased tear production.
Extraglandular manifestations: Systemic features such as arthritis, neuropathy, ILD, and vasculitis.
Anatomy and Physiology
Lacrimal glands produce tears to lubricate the eye and protect the cornea.
Salivary glands (parotid, submandibular, sublingual) produce saliva for digestion and oral health.
Exocrine glands are regulated by parasympathetic nervous system and rely on intact glandular epithelium for secretion.
Aetiology and Risk Factors
Aetiology:
• Unknown, likely multifactorial
• Genetic predisposition (HLA-DR52, HLA-DR3)
• Environmental triggers (e.g. viral infections: EBV, CMV, HTLV-1)
• Aberrant activation of innate and adaptive immune system
Risk Factors:
• Female sex (90% of cases)
• Age 40–60
• Family history of autoimmune disease
• Coexisting autoimmune diseases (RA, SLE, scleroderma)
Pathophysiology
- Environmental/genetic trigger activates innate immune response
- Activation of autoreactive B and T cells leads to lymphocytic infiltration of exocrine glands
- Destruction of acinar cells in lacrimal/salivary glands → ↓ secretions
- Formation of autoantibodies (anti-Ro/SSA, anti-La/SSB)
- Potential development of ectopic germinal centers and B-cell lymphoma
- Extraglandular involvement via systemic immune activation and vasculitis
Clinical Manifestations
Glandular
• Xerostomia – difficulty swallowing, speaking, dental caries
• Keratoconjunctivitis sicca – gritty eye sensation, redness, photophobia
• Parotid enlargement – often bilateral and non-tender
Extraglandular (systemic)
• Arthralgia/arthritis – non-erosive, symmetric
• Interstitial lung disease
• Raynaud’s phenomenon
• Peripheral neuropathy
• Cutaneous vasculitis (palpable purpura)
• Renal involvement (distal RTA, interstitial nephritis)
• Fatigue
Triad: Xerostomia, Keratoconjunctivitis sicca, Parotid gland swelling
Remember
Sjogrens causes RTA Type I: A urine pH >5.5 in the setting of metabolic acidosis and hypokalemia is highly suggestive of type 1 RTA.
Diagnosis
2016 ACR/EULAR Classification Criteria (score ≥4 = diagnosis):
| Feature | Points |
| Positive anti-Ro/SSA antibodies | 3 |
| Labial salivary gland biopsy (focal lymphocytic sialadenitis with focus score ≥1) | 3 |
| Ocular staining score ≥5 (or van Bijsterveld ≥4 in at least one eye) | 1 |
| Schirmer’s test ≤5 mm/5 min in at least one eye | 1 |
| Unstimulated salivary flow rate ≤0.1 mL/min | 1 |
Investigations
- Serology: ANA, RF, anti-Ro/SSA, anti-La/SSB
- Schirmer’s test (dry eyes)
- Salivary flow testing
- Salivary gland imaging – ultrasound, sialography, scintigraphy
- Lip biopsy (minor salivary glands) for histology
- Ophthalmologic tests: Rose Bengal or lissamine green staining
Differential diagnoses
- Dry eyes/mouth from drugs (e.g. anticholinergics)
- Sarcoidosis
- Hepatitis C
- IgG4-related disease
- HIV
| Feature | Anti-Ro (SSA) | Anti-La (SSB) |
| Prevalence in Sjögren’s | 60–75% | 40–50% |
| Sensitivity | Higher | Lower |
| Specificity | Moderate | Higher |
| Seen in other diseases | Yes (SLE, neonatal lupus) | Mostly limited to Sjögren’s |
| Clinical associations | ILD, vasculitis, neonatal lupus | Milder disease course |
Side note
Ro52 is found in autoimmune ILD conditions (SSc, RA) and typically associated with a poor prognostic factor.
Remember
Anti-Ro is highly sensitive, anti-La is more specific.
Classification
- Primary Sjögren’s Syndrome: Occurs alone without another autoimmune disease
- Secondary Sjögren’s Syndrome: Associated with RA, SLE, systemic sclerosis
Treatment
Glandular symptoms
- Artificial tears/saliva substitutes regularly
- Good oral hygiene and fluoride to prevent caries
- Pilocarpine or cevimeline (muscarinic agonists)
- Topical cyclosporine for dry eyes (e.g. Restasis)
Systemic/extraglandular
- Hydroxychloroquine for arthralgia, fatigue
- Steroids for vasculitis, ILD, renal involvement
- Immunosuppressants (e.g. MTX, MMF, rituximab) for organ-threatening disease
Remember
Tailor treatment to manifestations — not all patients need immunosuppression.
Complications and Prognosis
Complications
- Dental caries and oral infections
- Corneal ulcers and keratitis
- Non-Hodgkin B-cell lymphoma (especially MALT) – 5% lifetime risk
- Interstitial lung disease and pulmonary hypertension
- Fatigue and reduced quality of life
- Cryoglobulinemic vasculitis
Poor Prognostic Factors
- Low C4 levels
- Cryoglobulinemia
- Purpura
- Parotid enlargement
- Lymphadenopathy
Think
Any new lymphadenopathy or weight loss in SS → evaluate for lymphoma.
References
- Shiboski CH, et al. 2016 ACR/EULAR classification criteria for primary Sjögren’s syndrome. Ann Rheum Dis. 2017;76(1):9–16.
- Fox RI. Sjögren’s syndrome. Lancet. 2005;366(9482):321–331.
- Ramos-Casals M, et al. Primary Sjögren syndrome: clinical and immunologic disease patterns in a cohort of 400 patients. Medicine (Baltimore). 2005;84(4):231–239.
- Rischmueller M, et al. Pathogenesis of Sjögren syndrome. Rheum Dis Clin North Am. 2016;42(3):485–500.
- Brito-Zerón P, et al. Sjögren syndrome. Nat Rev Dis Primers. 2016;2:16047.
Discussion