Key Facts

Sjogren syndrome is one of the most common autoimmune diseases, often under-diagnosed. Systemic involvement can be significant and the lymphoma risk requires long-term monitoring.

Epidemiology

• Prevalence: 0.1-0.5% (varies by criteria used)
• F:M 9:1; peak onset 40-60 years
• Often under-diagnosed: average delay to diagnosis ~7 years
• Secondary Sjogren more common than primary

Aetiology

• Genetic: HLA-DR3, HLA-B8, IRF5, STAT4
• Environmental: viral triggers (EBV, HTLV-1)
• Hormonal: oestrogen deficiency may contribute

Pathophysiology

• Lymphocytic infiltration (CD4+ T cells, B cells) of exocrine glands
• Autoantibodies: anti-Ro, anti-La target ribonucleoprotein complexes
• Glandular destruction → reduced saliva and tear production
• B-cell hyperactivation → hypergammaglobulinaemia, RF production
• Chronic B-cell stimulation → risk of B-cell lymphoma (MALT → DLBCL)
• Extraglandular involvement: immune complex deposition and lymphocytic infiltration in lungs, kidneys, nerves

Sicca Symptoms

• Dry eyes (keratoconjunctivitis sicca): gritty sensation, burning, photosensitivity, recurrent conjunctivitis
• Dry mouth (xerostomia): difficulty swallowing dry foods, dental caries, oral candidiasis, voice changes
• Parotid gland enlargement: episodic or persistent bilateral swelling

Systemic Manifestations (30-40%)

• Arthralgia/arthritis: non-erosive, similar to SLE
• Fatigue: often the most debilitating symptom
• Skin: purpura (hypergammaglobulinaemic or vasculitic), Raynaud (30%)
• Lungs: ILD (NSIP most common), lymphocytic interstitial pneumonia (LIP)
• Renal: type 1 (distal) RTA, interstitial nephritis
• Neurological: peripheral neuropathy (sensory > motor), cranial neuropathy (especially trigeminal), CNS involvement (rare)
• Haematological: lymphopenia, hypergammaglobulinaemia, cryoglobulinaemia

Lymphoma Risk

• 5-10% lifetime risk of B-cell NHL (predominantly MALT lymphoma of parotid)
• Warning signs: persistent parotid swelling, falling immunoglobulins, new lymphadenopathy, splenomegaly
• Risk factors: low C4, cryoglobulinaemia, vasculitis, lymphopenia

Red Flags

• Persistent unilateral parotid swelling → exclude lymphoma
• Falling immunoglobulins in previously hypergammaglobulinaemic patient → lymphoma
• New neurological symptoms → CNS Sjogren or lymphoma
• Severe systemic disease → consider rituximab

Bloods

• Anti-Ro (SSA): positive in ~70% of primary Sjogren
• Anti-La (SSB): positive in ~40% (more specific)
• ANA: positive in 70-80%
• RF: positive in 60-70%
• Immunoglobulins: polyclonal hypergammaglobulinaemia
• C3/C4: may be low (immune complex disease)
• ESR: often elevated (high Ig levels)
• CRP: usually normal (distinguishes from infection)
• FBC: lymphopenia
• Cryoglobulins: if vasculitis suspected

Ocular Assessment

• Schirmer test: filter paper in lower fornix; <5mm wetting in 5 minutes = abnormal
• Ocular surface staining (Rose Bengal, lissamine green, fluorescein): corneal/conjunctival epithelial damage
• Tear break-up time: <10 seconds = abnormal

Salivary Assessment

• Unstimulated salivary flow rate: <0.1 mL/min is abnormal
• Salivary gland USS: inhomogeneous echotexture, hypoechoic areas
• Sialography: ductal ectasia (rarely performed now)

Biopsy

• Labial salivary gland biopsy: minor salivary glands from inner lip; focal lymphocytic sialadenitis with focus score ≥1 (≥50 lymphocytes per 4mm²) – most specific test

Screening

• Dental assessment: increased caries risk
• Pulmonary function tests: if respiratory symptoms (ILD)
• Renal function + urine pH: RTA screening

Symptomatic (Sicca)

Dry eyes:

• Artificial tears (hypromellose drops): first-line; preservative-free if used >6×/day
• Carbomer gel (Viscotears): for night-time use
• Ciclosporin 0.1% eye drops (Ikervis): for moderate-severe keratoconjunctivitis sicca
• Punctal plugs: reduce tear drainage

Dry mouth:

• Saliva substitutes (Glandosane spray, Biotene products)
• Pilocarpine 5mg TDS-QDS (muscarinic agonist): stimulates residual salivary function; side effects include sweating
• Cevimeline: alternative cholinergic agonist (not widely available in UK)
• Dental hygiene: regular dental check-ups, fluoride rinses
• Sugar-free chewing gum: stimulates saliva
• Treat oral candidiasis: nystatin or fluconazole

Systemic Disease

• Hydroxychloroquine 200-400mg daily: for arthralgia, fatigue, skin involvement
• Corticosteroids: for acute flares of systemic disease (serositis, vasculitis)
• Methotrexate/azathioprine: for arthritis, ILD
• Rituximab: for severe systemic disease (vasculitis, neuropathy, ILD); off-label but evidence from TRACTISS trial (limited efficacy for fatigue/dryness but may help systemic)
• Mycophenolate: for renal involvement

Monitoring

• Annual ophthalmology: if on hydroxychloroquine (>5 years)
• Dental review: 6-monthly
• Lymphoma surveillance: clinical monitoring; investigate persistent parotid swelling, falling Ig levels, new lymphadenopathy

Referral Criteria

• Suspected Sjogren → rheumatology
• Severe dry eyes → ophthalmology
• Suspected lymphoma → haematology urgently
• ILD → respiratory medicine

• Life expectancy: near-normal for primary Sjogren without systemic involvement
• 5-10% lifetime risk of B-cell lymphoma (most commonly MALT lymphoma of parotid gland)
• Systemic disease: occurs in 30-40%; ILD and renal involvement carry worse prognosis
• Quality of life: significantly affected by fatigue and sicca symptoms
• Dental caries: accelerated; major morbidity if inadequate prevention
• Predictors of lymphoma: low C4, cryoglobulinaemia, palpable purpura, parotid enlargement, lymphopenia

ACR/EULAR 2016 Classification Criteria

Applicable if at least 1 domain of ocular or oral dryness. Score ≥4 classifies as Sjogren syndrome:

Primary vs Secondary Sjogren