Sjögren's syndrome

Red Flags

Persistent unilateral parotid swelling, palpable mass, or rapidly enlarging gland — exclude lymphoma (5-fold lifetime risk in primary Sjögren's); imaging and biopsy^[1]
Severe extraglandular disease (interstitial lung disease, vasculitis, peripheral neuropathy, glomerulonephritis, severe cytopenia) — admit and immunosuppression^[1]
Cryoglobulinaemic vasculitis — palpable purpura, neuropathy, glomerulonephritis; investigate hepatitis C; rituximab consideration^[1]
Pregnancy with anti-Ro/anti-La positive — fetal echocardiography 16–28 weeks; risk of congenital heart block; multidisciplinary care^[1]

First-line treatment

Interventions

Symptomatic management of sicca^[1]
Eyes: artificial tears, lubricating gels at night, ciclosporin 0.05% drops, punctal plugs, autologous serum drops in severe disease. Mouth: frequent sips of water, sugar-free gum/lozenges, saliva substitutes, fluoride toothpaste, regular dental review
Patient education and lifestyle^[1]
Avoid smoking, dry environments; hydration; dental hygiene; fatigue management; manage comorbidities; physiotherapy for fatigue and musculoskeletal symptoms
Stepped pharmacotherapy for sicca^[1]
Step 1: lubricants. Step 2: pilocarpine or cevimeline if residual function. Step 3: corticosteroid topical for severe inflammation. Step 4: systemic immunosuppression for severe refractory glandular disease
Vaccination and infection prevention^[1]
Pneumococcal, influenza annual, recombinant zoster, HPV, hepatitis B; defer live vaccines once on biologic; counsel about increased infection susceptibility

First-line drug therapy

Drug	Class	Adult	Paediatric	Notes
Pilocarpine^[1]	Muscarinic agonist (cholinergic)	5 mg PO QDS	—	Stimulates residual salivary and lacrimal function; sweating, GI upset; contraindicated in narrow-angle glaucoma, asthma, severe COPD
Cevimeline (where available)^[1]	Muscarinic M3-selective agonist	30 mg PO TDS	—	Alternative cholinergic agonist; more M3-selective than pilocarpine; better cardiac tolerability
Hydroxychloroquine^[1]	Antimalarial / immunomodulator	200–400 mg PO daily (max 5 mg/kg actual body weight)	—	Useful for arthralgia, fatigue, cutaneous lupus features; safety established; baseline retinal exam and annual screening from year 5
Prednisolone (severe extraglandular)^[1]	Systemic corticosteroid	0.5–1 mg/kg/day with rapid taper to ≤7.5 mg/day; preceded by IV pulse 250–500 mg × 3 days for severe organ disease	—	Bridge to immunosuppressant; minimise duration; bone protection (calcium, vitamin D, bisphosphonate per fracture risk)
Rituximab^[1]	Anti-CD20 monoclonal antibody	1 g IV × 2 doses 2 weeks apart, repeat at 6 months by clinical response	—	First-line biologic for severe refractory extraglandular disease (cryoglobulinaemic vasculitis, peripheral neuropathy, ILD); HBV screen and prophylaxis; vaccinate before
Mycophenolate mofetil^[1]	Inosine monophosphate dehydrogenase inhibitor	1–3 g/day PO in divided doses	—	Useful for ILD, neurological, glomerulonephritis; teratogenic — strict contraception

Pilocarpine^[1]

Muscarinic agonist (cholinergic)

Adult: 5 mg PO QDS
Paediatric: —

Stimulates residual salivary and lacrimal function; sweating, GI upset; contraindicated in narrow-angle glaucoma, asthma, severe COPD

Cevimeline (where available)^[1]

Muscarinic M3-selective agonist

Adult: 30 mg PO TDS
Paediatric: —

Alternative cholinergic agonist; more M3-selective than pilocarpine; better cardiac tolerability

Hydroxychloroquine^[1]

Antimalarial / immunomodulator

Adult: 200–400 mg PO daily (max 5 mg/kg actual body weight)
Paediatric: —

Useful for arthralgia, fatigue, cutaneous lupus features; safety established; baseline retinal exam and annual screening from year 5

Prednisolone (severe extraglandular)^[1]

Systemic corticosteroid

Adult: 0.5–1 mg/kg/day with rapid taper to ≤7.5 mg/day; preceded by IV pulse 250–500 mg × 3 days for severe organ disease
Paediatric: —

Bridge to immunosuppressant; minimise duration; bone protection (calcium, vitamin D, bisphosphonate per fracture risk)

Rituximab^[1]

Anti-CD20 monoclonal antibody

Adult: 1 g IV × 2 doses 2 weeks apart, repeat at 6 months by clinical response
Paediatric: —

First-line biologic for severe refractory extraglandular disease (cryoglobulinaemic vasculitis, peripheral neuropathy, ILD); HBV screen and prophylaxis; vaccinate before

Mycophenolate mofetil^[1]

Inosine monophosphate dehydrogenase inhibitor

Adult: 1–3 g/day PO in divided doses
Paediatric: —

Useful for ILD, neurological, glomerulonephritis; teratogenic — strict contraception

Safety-net

Dental review every 6 months — Sjögren's accelerates dental caries; fluoride toothpaste, mouthwash, frequent water sips and sugar-free gum reduce damage^[1]
Persistent gland enlargement, especially unilateral, deserves evaluation — small lymphoma risk warrants vigilance^[1]
Plan pregnancy with rheumatologist — anti-Ro positivity needs fetal cardiac surveillance to detect heart block early^[1]

Referral criteria

All suspected Sjögren's syndromeRheumatology; combined with ophthalmology and dental input^[1]
Severe extraglandular disease (ILD, vasculitis, neuropathy, glomerulonephritis, severe cytopenia)Tertiary rheumatology and relevant subspecialty^[1]
Suspected lymphoma (persistent unilateral parotid mass, B symptoms, monoclonal protein)Haematology / oncology with imaging and biopsy^[1]
Pregnancy with anti-Ro/anti-La positivityJoint rheumatology and fetal medicine clinic^[1]

Clinical summary

Diagnosis and stepwise management of sicca symptoms and systemic manifestations of primary Sjögren's syndrome in adults.

References

1.EULAR Recommendations for the Management of Sjögren's Syndrome (2020); ACR/EULAR 2016 Classification Criteria; British Society of Rheumatology 2017 (2020)