Sjögren Syndrome

A chronic autoimmune exocrinopathy characterised by lymphocytic infiltration of exocrine glands, principally the lacrimal and salivary glands, producing the hallmark sicca symptoms of dry eyes and dry mouth, with systemic extraglandular manifestations and a markedly increased risk of lymphoma compared with the general population. It occurs as a primary condition or secondary to another connective tissue disease, most often systemic lupus erythematosus or rheumatoid arthritis.

Pathophysiology

Lymphocytic infiltration and destruction of exocrine glandular tissue, driven by activated B and T cells, autoantibody production (anti Ro and anti La), and a background of type I interferon pathway activation, produces progressive glandular dysfunction. Extraglandular disease reflects broader systemic immune dysregulation, with B cell hyperactivity underlying the substantially elevated lymphoma risk, particularly mucosa associated lymphoid tissue lymphoma arising within chronically inflamed salivary glands.

Dry eyes (keratoconjunctivitis sicca) present as a gritty, foreign body sensation, burning, photophobia and, in severe cases, corneal damage from inadequate tear film.

Dry mouth (xerostomia) causes difficulty swallowing dry food, altered taste, dental caries (often rampant and affecting unusual tooth surfaces), oral candidiasis and difficulty wearing dentures.

Parotid and other salivary gland swelling occurs episodically or persistently, and persistent unilateral swelling or a discrete mass warrants investigation for lymphoma.

Other sicca manifestations include dry skin, vaginal dryness (dyspareunia), and dryness of the respiratory tract mucosa contributing to chronic cough.

Fatigue and arthralgia are common and often significantly impact quality of life, frequently out of proportion to objective disease activity markers.

Extraglandular manifestations include non erosive arthritis, cutaneous vasculitis (palpable purpura), peripheral neuropathy, interstitial lung disease, renal tubular acidosis and interstitial nephritis, and Raynaud phenomenon.

Anti Ro positivity carries specific risk in pregnancy, associated with neonatal lupus and, most seriously, congenital heart block in the fetus, requiring specific antenatal monitoring.

Constitutional symptoms of low grade fever and weight loss, together with persistent salivary gland enlargement, lymphadenopathy or splenomegaly, should prompt evaluation for lymphoma.

Diagnosis integrates sicca symptoms, objective evidence of reduced glandular secretion, positive serology and, where needed, tissue confirmation.

Schirmer test quantifies tear production (reduced wetting of filter paper strips), and ocular staining assesses corneal and conjunctival damage from chronic dryness.

Unstimulated whole salivary flow rate quantifies xerostomia objectively.

Anti Ro (SSA) and anti La (SSB) antibodies are positive in the majority of patients and are central to diagnosis, alongside antinuclear antibody and rheumatoid factor, which are frequently positive even in the absence of overlapping rheumatoid arthritis.

Minor salivary gland (labial) biopsy showing focal lymphocytic sialadenitis with a focus score of one or more foci per four square millimetres is the histological reference standard, particularly valuable where serology is negative but clinical suspicion remains high.

Salivary gland ultrasound is an increasingly used, non invasive adjunct showing characteristic hypoechoic areas within affected glands.

Complement levels (low C4 and C3), cryoglobulins, and immunoglobulin levels (often elevated as part of polyclonal B cell activation, with a falling immunoglobulin level or new monoclonal band raising concern for evolving lymphoma) contribute to risk stratification.

Investigate persistent unilateral gland swelling, a discrete mass, unexplained lymphadenopathy or a falling complement/immunoglobulin level with imaging and biopsy given lymphoma risk.

Ocular dryness is managed with preservative free artificial tears used regularly, topical ciclosporin or lifitegrast for more significant disease, punctal plugs to reduce tear drainage, and ophthalmology review for corneal complications.

Oral dryness is managed with frequent sips of water, sugar free chewing gum or lozenges to stimulate residual salivary flow, saliva substitutes, and muscarinic agonists (pilocarpine, cevimeline) for patients with residual glandular function, used with caution given cholinergic adverse effects and contraindication in uncontrolled asthma or narrow angle glaucoma.

Meticulous dental care with regular review, fluoride application and prompt treatment of caries is essential given the markedly increased dental disease burden.

Hydroxychloroquine is commonly used for fatigue, arthralgia and constitutional symptoms, though evidence for its efficacy in this specific condition is less robust than in lupus.

Systemic immunosuppression (methotrexate, azathioprine, or biologic therapy such as rituximab) is reserved for significant extraglandular disease, particularly vasculitis, interstitial lung disease, neuropathy or renal involvement, under specialist rheumatology direction.

Vaginal dryness is managed with lubricants and, where appropriate, topical oestrogen.

Pregnancy planning in anti Ro positive women requires specialist obstetric and cardiology input with serial fetal echocardiography to monitor for congenital heart block, typically from sixteen to twenty six weeks gestation.

Lifelong surveillance for lymphoma given the substantially elevated risk, with prompt investigation of any new or changing gland swelling, lymphadenopathy or constitutional symptoms.