Sjogren Syndrome for General Practitioners

Introduction

Sjögren syndrome (SS) is a chronic systemic autoimmune disease characterized by lymphocytic infiltration of exocrine glands leading to sicca symptoms, with potential multisystem involvement. It is frequently underdiagnosed in primary care due to its insidious onset and nonspecific features. A patient with hypokalaemic periodic paralysis? deaths of babies in the neonatal period or by intra uterine foetal death? Edentulous in a younger than expected age are clinical scenarios of Sjogren syndrome. This condition has been increasingly recognized nowadays, thanks to increased awareness of practising clinicians and availability of immunological tests countrywide. This review is an overview for general practitioners with Recent European Alliance of Associations for Rheumatology (EULAR) recommendations are integrated.

• Definition

  Sjögren syndrome is a systemic autoimmune disease primarily affecting salivary and lacrimal glands, resulting in xerostomia and keratoconjunctivitis sicca. It may occur as primary disease or secondary to other autoimmune disorders such as rheumatoid arthritis or systemic lupus erythematosus.

• Epidemiology
  

  The prevalence of SS ranges from 0.1% to 1% globally. It predominantly affects women (female-to-male ratio approximately 9:1), with peak onset between 40 and 60 years of age. Underdiagnosis is common due to gradual symptom development and overlap with other conditions.

• Chronic dry eyes and/or mouth (sicca)  for >3 months
• Recurrent parotitis is typically a more dominant symptom than sicca in children.

• Clinical Presentation
  3.1Glandular Manifestations
  

  • Dry eyes: irritation, burning, foreign body sensation
  • Dry mouth: difficulty swallowing dry food, dental caries
  • Parotid gland and lacrimal gland enlargement
    
    3.2Extra-glandular Manifestations
    
  • Musculoskeletal: arthralgia, non-erosive arthritis
  • Cutaneous: xerosis with or without pruritus, vasculitis
  • Pulmonary: interstitial lung disease
  • Renal: tubulointerstitial nephritis, glomerulonephritis, renal tubular acidosis
  • Neurological: peripheral neuropathy, cranial neuropathy, mononeuritis multiplex
  • Haematological: cytopenias
  • Gynaecologic manifestations: vulvovaginal dryness, pruritus, and dyspareunia
  • Foetal: congenital heart block, neonatal lupus

   

  4. Diagnostic Approach and Investigations
  

  Step 1: Clinical suspicion
  

• Chronic dry eyes and/or mouth (sicca)  for >3 months
• Recurrent parotitis is typically a more dominant symptom than sicca in children.
• Examination – oral dryness, parotid or lacrimal gland enlargement, cervical lymph adenopathyStep 2: Exclude common causes of sicca
• Medications (anticholinergics), dehydration, diabetes mellitus, hepatitis C, post head and neck radiation therapyStep 3: Initial investigationsLaboratory testingBaseline laboratory tests
  1. Full blood count: leukopenia, thrombocytopenia, and anaemia
  2. ESR – can be high
  3. Total and differential protein in serum – hyperglobulinemia (Serum protein electrophoresis: usually polyclonal gamma globulinaemia)
  4. Urinalysis: proteinuria and/or haematuria, urine pH ≥7 in the face of a metabolic acidosis
  5. Liver function tests and renal function tests
  6. Infection screening: Hepatitis B Combo, Anti HCV antibody, HIV
  7. Screening for comorbidity: Blood glucose, serum lipids
  8. Complement C 3 and C 4 – low in active disease

Immunological tests:

• ANA (Indirect Immunofluorescent), anti-SSA/Ro, Anti-SSB/La, Rheumatoid Factor
• SS should not be diagnosed based solely upon the presence of antibodies to SSA/Ro and/or SSB/La, as these antibodies can be found not only in patients with SS, but in other rheumatic/connective diseases, as well as in healthy individuals.

Step 4: Objective testing of sicca

• Ophthalmologic evaluation – All patients should be evaluated by an ophthalmologist, for the presence of dry eye on a formal eye examination. The examination should include Schirmer testing, a slit-lamp examination for assessment of tear break-up time (TBUT) and ocular surface staining.
• Unstimulated salivary flow ≤0.1 mL/min
• Minor salivary gland biopsy if indicated

Step 5: Additional investigations (case based)

1. Cryoglobulins
2. Chest x ray, High resolution CT of the lungs, pulmonary function test – interstitial lung disease
3. Urine protein quantity tests – E.g. urine for protein creatinine ratio
4. Nerve conduction and electromyography testing
5. Lymph node biopsy

Step 6: Apply classification criteria

Classification Criteria (2016 ACR/EULAR) ¹

5. Disease Activity Assessment

EULAR Sjögren’s syndrome disease activity index (ESSDAI) 2015 ⁴

Physician-reported index assessing systemic activity across organ domains.

6. Management 2,5

Management emphasizes symptom control and organ-based therapy.

6.1 General Measures

• Patient education
• Avoid xerogenic drugs
• Hydration

6.2 Sicca Symptom Management

Ocular: artificial tears, topical cyclosporine, surgical means

Oral: saliva substitutes, pilocarpine

6.3 Systemic Therapy

• Hydroxychloroquine for musculoskeletal symptoms
• Corticosteroids short course for initial control of organ involvement
• Immunosuppressants (methotrexate, azathioprine, mycophenolic acid )
• Biologics (rituximab in selected cases)
• Intravenous immunoglobulins

Lymphoma Risk and Red Flags

Patients with SS have an increased risk of non-Hodgkin lymphoma.

Red flags:

• Persistent parotid enlargement
• Lymphadenopathy
• Splenomegaly
• Unexplained cytopenias
• Low C4 or cryoglobulinemia
• Weight loss or fever

8. Referral Criteria

Urgent Referral

• Suspicion of lymphoma
• Significant organ involvement (renal, pulmonary, neurological)

Routine Referral

• Diagnostic uncertainty
• Persistent symptoms despite treatment
• Special situations: infection, surgery, severe comorbid conditions, pregnancy and lactation

9. Considerations in Resource-Limited Settings

• Emphasize clinical diagnosis and basic serology
• Use Schirmer’s test as primary objective tool
• Hydroxychloroquine as cost-effective systemic therapy
• Prioritize referral for severe or atypical disease

10. Conclusion

Sjögren’s syndrome is a multisystem autoimmune disease with significant morbidity. Early recognition in primary care is essential. A structured diagnostic and management approach, adapted to available resources and shared care between primary care physicians and Rheumatologists can improve patient outcomes.

References

1. Aringer, M. et al. (2017) ‘2016 ACR/EULAR classification criteria for primary Sjögren’s syndrome’, Annals of the Rheumatic Diseases, 76(1), pp. 9–16.
2. Brito-Zerón, P. et al. (2020) ‘EULAR recommendations for the management of Sjögren’s syndrome with topical and systemic therapies’, Annals of the Rheumatic Diseases, 79(1), pp. 3–18.
3. Ramos-Casals, M. et al. (2020) ‘Sjögren syndrome’, Nature Reviews Disease Primers, 6(1), pp. 1–20.
4. Seror, R. et al. (2010) ‘EULAR Sjögren’s Syndrome Disease Activity Index (ESSDAI)’, Annals of the Rheumatic Diseases, 69(6), pp. 1103–1109.
5. Price, E.J. et al. (2017) ‘The British Society for Rheumatology guideline for the management of adults with primary Sjögren’s syndrome’, Rheumatology, 56(10), pp. e24–e48.

Author Information

Cho Mar Lwin

Professor and Head, Department of Rheumatology

University of Medicine 1, Yangon