Sjögren’s Syndrome

Notes

Connective Tissue Diseases | Rheumatology

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.