Sjögren Syndrome

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

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

Antinuclear Antibody Testing Algorithm

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

Indications for Laboratory Testing

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

Additional Tests Available

Sedimentation Rate, Westergren (ESR) 0040325
Method: Visual Identification

Comments

Nonspecific test used to detect inflammation associated with infections, cancers, and autoimmune diseases

Often elevated in Sjögren syndrome

Connective Tissue Diseases Profile 0051668
Method: Semi-Quantitative Multiplex Bead Assay

Comments

Confirmatory tests for specific connective tissue disease

Panel consists of Smith (ENA), RNP, SSA, SSB, Jo-1, RPP, centromere and Scl-70 antibodies

Systemic Sclerosis Panel 2012057
Method: Semi-Quantitative Indirect Fluorescent Antibody/Semi-Quantitative Multiplex Bead Assay/ Semi-Quantitative Enzyme-Linked Immunosorbent Assay

Comments

Recommended panel for the diagnosis of systemic sclerosis

Components include anti-nuclear antibody (ANA); scleroderma (Scl-70); and RNA polymerase III

SSA 52 and 60 (Ro) (ENA) Antibodies, IgG 2012074
Method: Semi-Quantitative Multiplex Bead Assay

Comments

Order as secondary screen based on results of ANA test or if ANA IFA is negative and  Sjögren's syndrome, SLE, or myositis is strongly suspected

SSB (La) (ENA) Antibody, IgG 0050692
Method: Semi-Quantitative Multiplex Bead Assay

Comments

Order as secondary screen based on results of ANA test

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

Kruszka P, O'Brian R. 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 L, Fritzler M. 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 S, Giles R, Jaskowski T, Gardiner A, Wilson A, Hill H. 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 T, Schroder C, Martins T, Mouritsen L, Hill H. 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 D, Bennett A, Mahajan D, Bronner M. 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: December 2015