Sjogren syndrome is a chronic inflammatory autoimmune disease that most commonly occurs in middle-aged women. Primary Sjogren syndrome is idiopathic; Sjogren syndrome that occurs concomitantly with another autoimmune disease (e.g., rheumatoid arthritis, systemic sclerosis) is classified as secondary Sjogren syndrome. Sjogren syndrome most commonly manifests with sicca syndrome but can also manifest with systemic symptoms such as arthritis, Raynaud phenomenon, and GI involvement as a result of lymphocytic infiltration of glandular and nonglandular organs. The diagnosis is confirmed by the detection of autoantibodies (anti-Ro/SSA or anti-La/SSB antibodies) in patients with sicca syndrome. Salivary gland biopsy is the gold standard test but is often only performed in patients with atypical presentations. Management focuses on supportive measures and, in patients with severe systemic disease, immunosuppressive therapy.
- Primary Sjogren syndrome: idiopathic (association with HLA-DR52) 
- Secondary Sjogren syndrome: associated with another autoimmune disease, e.g., rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis, polymyositis, or primary biliary cirrhosis 
Clinical presentation varies widely, from isolated sicca syndrome to systemic involvement. See “Complications” for other clinical presentations.
Sicca syndrome 
- Ocular symptoms
- Oral symptoms
- Other glandular symptoms
Systemic disease 
- Arthralgias and/or arthritis (most common systemic symptom)
- Raynaud phenomenon
- Constitutional symptoms: fever, weight loss, fatigue
- GI involvement, e.g., dysphagia , dyspepsia, reflux esophagitis
- Pulmonary involvement:
- Autoimmune thyroiditis
- Neurological involvement, e.g., peripheral neuropathy, myelitis
- In patients with secondary Sjogren syndrome: features of a concomitant autoimmune condition, e.g., malar rash in patients with SLE
Systemic symptoms are present in 50–60% of patients with Sjogren syndrome. 
General principles 
- Consider Sjogren syndrome in patients with features of sicca syndrome without a known cause.
- The following are needed to confirm the diagnosis:
- Classification criteria can help support the diagnosis.
- Further studies may be obtained depending on suspected organ involvement.
Laboratory studies 
Obtain routine studies and autoantibodies for all patients. Prognostic markers may be ordered by a specialist.
- Routine studies: may show nonspecific supportive findings
- Anti-Ro/SSA antibodies ; (positive in ∼ 70% of cases) and anti-La/SSB antibodies; (positive in ∼ 50% of cases): target ribonucleoprotein antigens (Ro/La) in epithelial cells, especially in the salivary glands 
- Antinuclear antibodies (positive in up to 80% of cases) 
- Rheumatoid factor (positive in 50% of cases of primary Sjogren syndrome) 
- Prognostic markers: associated with a poor prognosis
Assessment of xerostomia
Salivary gland function studies 
Unstimulated salivary flow (preferred)
- Method: Saliva is collected for 5 minutes.
- Supportive finding: salivary flow ≤ 0.1 mL/minute 
- Salivary scintigraphy
- Stimulated salivary flow
Biopsy of minor labial salivary gland 
- Gold standard test, but not routinely required
- Consider if clinical presentation is atypical.
- Supportive findings
Assessment of xerophthalmia 
- : shows decreased tear production
- Slit lamp examination
Salivary gland imaging studies 
- Ultrasound of the parotid gland
- MRI of the parotid gland: The glandular parenchyma may have a honeycomb or cloud-like structure.
- Systemic autoimmune diseases
- Chronic viral infections
- Atopic disease: e.g., allergic conjunctivitis
Age-related sicca syndrome 
- Definition: xerophthalmia and xerostomia in older patients without evidence of Sjogren syndrome
- Risk factors: older age, female sex, medication use (e.g., anticholinergics)
- Clinical features: See “ ” above.
- Diagnostics: Consider in older patients with sicca syndrome and no evidence of underlying Sjogren syndrome. (See “Diagnostics” above.)
- Uncontrolled diabetes mellitus
- Graft-versus-host disease
- Age-related sicca syndrome 
The differential diagnoses listed here are not exhaustive.
General principles 
- Management should be guided by a rheumatologist and other specialists as required.
- Symptomatic management of sicca syndrome is the mainstay of treatment.
- For patients with active systemic disease, immunosuppressants may be considered.
- Monitor patients for the development of complications, e.g., lymphoma, and associated autoimmune diseases.
Patients with Sjogren syndrome have an increased risk of developing MALT lymphoma.
Management of sicca syndrome 
- Frequent water intake
- Caries prophylaxis, e.g., regular dental hygienist visits, topical fluoride or chlorhexidine
- Avoidance of irritants (e.g., coffee, alcohol) and acidic beverages (e.g., herbal tea, cola) 
- Preferred treatment for patients without residual glandular function
- May be considered for all patients
Patient with residual glandular function: stimulation of salivary flow
- First line: nonpharmacological stimulants, e.g., sugar-free lozenges or gum, acidic candy, xylitol
- Second line: oral muscarinic agonists
Advise all patients to maintain adequate eye lubrication and avoid dry environments (e.g., shield eyes from wind, increase indoor humidity).
- First line: artificial tears for volume replacement and lubrication
- Second-line therapies: usually reserved for refractory or severe disease because of their potential adverse effects
Management of systemic disease 
Management depends on the specific manifestation and should always be guided by a specialist.
- Inflammatory musculoskeletal pain
- Regular exercise
- Hydroxychloroquine may be considered. 
- Other manifestations of systemic disease : Systemic immunosuppressants (e.g., glucocorticoids, cyclosporine, rituximab) may be considered for severe symptoms.
TNF-α inhibitors can cause serious adverse effects (e.g., serious infections, cytopenias) and increase the risk of developing non-Hodgkin lymphoma, and therefore should be avoided in patients with Sjogren syndrome. 
- Development of associated conditions
- Corneal scarring, ulcer, rupture, and infection
- Pregnancy: fetal loss, infant with neonatal lupus syndrome and associated complete heart block
We list the most important complications. The selection is not exhaustive.