Sjögren Syndrome

  • Diagnosis
  • Algorithms
  • Background
  • Lab Tests
  • References
  • Related Topics

Indications for Testing

  • Dry eyes and mouth

Criteria for Diagnosis

  • International consensus criteria

Laboratory Testing

  • Nonspecific tests – not specific for Sjögren syndrome; abnormal results may be seen in other connective tissue diseases
    • C-reactive protein (CRP)
    • Immunoglobulins – marked hypergammaglobulinemia (IgG>IgA>IgM)
    • Total protein – elevated
    • CBC – usually normal
    • IgM rheumatoid factor may be positive
  • Antibody testing
    • Initial testing – ANA followed by extractable nuclear antibody (ENA) if positive
    • SS antibodies – although not specific for Sjögren syndrome, antibodies are relatively sensitive; may be useful to order panel screening for connective tissue diseases if Sjögren is not high probability
      • Strong association between SSA antibodies and vasculitis in Sjögren syndrome
      • Several studies identify SSB antibodies as serological marker for SS-sicca complex
        • SSB antibodies detected in approximately 60% of SS-sicca complex patients

Histology

  • Labial gland biopsy – predominate lymphocytic infiltration
    • Should contain >50 lymphocytes with normal appearing acini per 4 mm2 of glandular tissue
    • Sjögren syndrome focus score = number of lymphocyte aggregates x 4 ÷ area of salivary gland parenchyma
      • Focus score ≥1 considered diagnostic

Other Testing

  • Objective ocular involvement – Schirmer test or Rose bengal staining
  • Objective salivary gland involvement – sialography, scintigraphy or sialometry

Differential Diagnosis

Sjögren syndrome is a slowly progressive autoimmune disease characterized by lymphocytic infiltration of exocrine glands resulting in dry eyes and dry mouth.

Epidemiology

  • Prevalence – 2-4/100,000 in U.S.
    • Second most common autoimmune disease
  • Age – peak is 40-60 years
  • Sex – M<F, 1:9

Risk Factors

  • Genetic predisposition (multigenetic factors)
    • Family history of Sjögren syndrome

Pathophysiology

  • Mononuclear infiltrate with loss of ductal cells and relative preservation of acinar cells in secretory glands
  • Leads to loss of secretory capacity of the gland
  • Infiltration of cells may also be systemic, causing multi-organ disease

Clinical Presentation

  • Head, eyes, ears, nose and throat (HEENT)
    • Dry eye (xerophthalmia, keratoconjunctivitis sicca)
    • Dry mouth (xerostomia) – increased incidence of dental caries
    • Enlargement of salivary glands
  • Musculoskeletal – arthritis, arthralgias, myalgias
  • Dermatologic – palpable purpura, cryoglobulinemia, Raynaud phenomena, alopecia
  • Endocrine – autoimmune thyroiditis
  • Neurologic – peripheral neuropathy, cranial neuropathies
  • Pulmonary – interstitial pneumonitis, tracheobronchial sicca
  • Complications

Treatment

  • Xerophthalmia – artificial tears, topical cyclosporine
  • Xerostomia – pilocarpine or cevimeline derivatives

Tests generally appear in the order most useful for common clinical situations. Click on number for test-specific information in the ARUP Laboratory Test Directory.

Anti-Nuclear Antibodies (ANA), IgG by ELISA with Reflex to ANA, IgG by IFA 0050080
Method: Qualitative Enzyme-Linked Immunosorbent Assay/Semi-Quantitative Indirect Fluorescent Antibody

Limitations

Low titer ANA common with advancing age; certain drugs may also cause low titer ANA

ANA ELISA assays have been reported to have lower sensitivities for antibodies associated with nucleolar and specked ANA-IFA patterns

Follow Up

Recommend cutaneous direct immunofluorescence testing of active edge of new lesion (lesional biopsy) if dermatologic manifestations are present

Anti-Nuclear Antibodies (ANA), IgG by ELISA with Reflexes to ANA, IgG by IFA and to dsDNA, RNP, Smith, SSA 52, SSA 60, and SSB Antibodies, IgG 0050317
Method: Qualitative Enzyme-Linked Immunosorbent Assay/Semi-Quantitative Indirect Fluorescent Antibody/Semi-Quantitative Multiplex Bead Assay

Extractable Nuclear Antigen Antibodies (RNP, Smith, SSA 52, SSA 60, and SSB) 0050652
Method: Semi-Quantitative Multiplex Bead Assay

C-Reactive Protein 0050180
Method: Quantitative Immunoturbidimetry

Immunoglobulins (IgA, IgG, IgM), Quantitative 0050630
Method: Quantitative Nephelometry

Protein, Total, Serum or Plasma 0020029
Method: Quantitative Spectrophotometry

CBC with Platelet Count and Automated Differential 0040003
Method: Automated Cell Count/Differential

Related Tests

Guidelines

American Society for Clinical Pathology. Choosing Wisely - Five Things Physicians and Patients Should Question. An initiative of the ABIM Foundation. [Last revision Feb 2015; Accessed: Jan 2016]

Seror R, Ravaud P, Bowman SJ, Baron G, Tzioufas A, Theander E, Gottenberg J, Bootsma H, Mariette X, Vitali C, EULAR Sjögren's Task Force. EULAR Sjogren's syndrome disease activity index: development of a consensus systemic disease activity index for primary Sjogren's syndrome. Ann Rheum Dis. 2010; 69(6): 1103-9. PubMed

General References

Amarasena R, Bowman S. Sjögren's syndrome. Clin Med. 2007; 7(1): 53-6. PubMed

Fox PC. Autoimmune diseases and Sjogren's syndrome: an autoimmune exocrinopathy. Ann N Y Acad Sci. 2007; 1098: 15-21. PubMed

Kruszka P, O'Brian RJ. Diagnosis and management of Sjögren syndrome. Am Fam Physician. 2009; 79(6): 465-70. PubMed

Ramos-Casals M, Brito-Zerón P, Sisó-Almirall A, Bosch X. Primary Sjogren syndrome. BMJ. 2012; 344: e3821. PubMed

Stinton LM, Fritzler MJ. A clinical approach to autoantibody testing in systemic autoimmune rheumatic disorders. Autoimmun Rev. 2007; 7(1): 77-84. PubMed

References from the ARUP Institute for Clinical and Experimental Pathology®

Copple SS, Giles R, Jaskowski TD, Gardiner AE, Wilson AM, Hill HR. Screening for IgG antinuclear autoantibodies by HEp-2 indirect fluorescent antibody assays and the need for standardization. Am J Clin Pathol. 2012; 137(5): 825-30. PubMed

Jaskowski TD, Schroder C, Martins TB, Mouritsen L, Hill HR. Comparison of three commercially available enzyme immunoassays for the screening of autoantibodies to extractable nuclear antigens. J Clin Lab Anal. 1995; 9(3): 166-72. PubMed

Patil DT, Bennett AE, Mahajan D, Bronner MP. Distinguishing Barrett gastric foveolar dysplasia from reactive cardiac mucosa in gastroesophageal reflux disease. Hum Pathol. 2013; 44(6): 1146-53. PubMed

Medical Reviewers

Last Update: April 2016