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Sjögren Syndrome. ARUP Consult®. Retrieved December 02, 2020, https://arupconsult.com/content/sjogren-syndrome

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Sjögren Syndrome

Sjögren syndrome is an autoimmune disease characterized by lymphocytic infiltration of exocrine glands that results in dry eyes and dry mouth; other common symptoms include fatigue and joint pain.  The disease may affect as many as four million people in the United States and is one of the more prevalent connective tissue ​or systemic autoimmune rheumatic diseases (SARDs).  Sjögren syndrome may occur alone (referred to as primary Sjögren syndrome) or in conjunction with other systemic autoimmune diseases (eg, rheumatoid arthritis or systemic lupus erythematosus [SLE]) or organ-specific autoimmune diseases (eg, thyroiditis or primary biliary cholangitis).  Although no laboratory test is specific for the diagnosis of Sjögren syndrome, tests for antinuclear antibodies (ANAs), antibodies against Sjögren syndrome-related antigen A and B (anti-SSA [Ro], anti-SSB [La]), and rheumatoid factor (RF) may aid in the diagnostic evaluation of Sjögren syndrome. 

Quick Answers for Clinicians

Who should be tested for Sjögren syndrome?

Patients with dry mouth and dry eyes should be considered for testing, especially if these symptoms accompany fatigue, joint pain, and/or signs of systemic complications (30-40% of patients with primary Sjögren syndrome have systemic complications). 

Which laboratory tests are most useful for Sjögren syndrome?

A first step in evaluating a patient with a possible systemic autoimmune condition is antinuclear antibody (ANA) testing; however, ANAs can be found in a variety of conditions, so these tests are best used in patients with a high pretest probability of a connective tissue or systemic autoimmune rheumatic disease (SARD) such as Sjögren syndrome.  Additional autoimmune laboratory tests include anti-SSA (Ro), specifically SSA-52 (Ro52) and/or SSA-60 (Ro60), anti-SSB (La), and rheumatoid factor (RF) tests. Positivity for anti-SSA (Ro) is a key component of the diagnostic criteria for primary Sjögren syndrome.  (See Criteria for Diagnosis.)

What kind of monitoring is recommended for patients with Sjögren syndrome?

Surveillance (clinical screening) for B-cell lymphoma is important because its incidence in patients with Sjögren syndrome is 15-20 times that in the general population.  For general monitoring, the European League Against Rheumatism (EULAR) Patient Reported Index can be used to assess mouth and ocular dryness, fatigue, and pain, and relies on patient self-reporting. A second, more extensive index for monitoring patients with Sjögren syndrome has been developed by EULAR for use in clinical trials.  (See Monitoring.)

Which testing algorithms are related to this topic?
Antinuclear Antibody Disease Testing Algorithm
Antinuclear Antibody Disease Testing Algorithm - Nuclear Patterns
Antinuclear Antibody Disease Testing Algorithm - Cytoplasmic Patterns

Criteria for Diagnosis

The American College of Radiology (ACR) and European League Against Rheumatism (EULAR) classification criteria for primary Sjögren syndrome  are listed in the table below. These criteria apply to patients considered to have oral or ocular dryness according to the ACR/EULAR definition.  The classification does not apply to patients with another rheumatologic diagnosis with overlapping symptoms or to patients with conditions such as active hepatitis C virus with polymerase chain reaction (PCR) confirmation, AIDS, sarcoidosis, amyloidosis, IgG4-related disease, graft-versus-host disease, or history of head and neck radiation.  These criteria are not yet validated for secondary Sjögren syndrome. 

ACR/EULAR Classification Criteria for Primary Sjögren Syndrome
Criteria Scorea

Anti-SSA (Ro) positivity

3

Labial salivary gland with focal lymphocytic sialadenitis and focus score ≥1 foci/4 mm2

3

Whole saliva flow rate (unstimulated) ≤1 mL/minb

1

Ocular staining score ≥5 or van Bijsterveld score ≥4b,c

1

Schirmer’s test rate ≤5 mm/5 minb,c

1

aScore of ≥4 designates individual as having primary Sjögren syndrome.

bPatients receiving anticholinergic drugs should be assessed only after a period without these drugs for an accurate evaluation.

cIn at least 1 eye.

Source: Shiboski, 2017 

Indications for Testing

Testing for Sjögren syndrome should be considered for patients with dry mouth and dry eyes, especially if these symptoms are accompanied by fatigue, joint pain, and/or signs of systemic complications. As many as 30-40% of patients with primary Sjögren syndrome have systemic complications. 

Laboratory Testing

Diagnosis

Antinuclear Antibody Tests

ANAs are not specific to Sjögren syndrome but are seen in a variety of other SARDs, as well as in organ-specific autoimmune diseases and some infections or malignancies. They may also be found in elderly patients and even in some healthy individuals.  For that reason, ANA testing is best used in patients with a strong likelihood of having Sjögren syndrome or another SARD. 

ANA tests may show a speckled pattern in patients with Sjögren syndrome.  Cytoplasmic patterns (eg, speckled, discrete dots/GW body-like, golgi/polar) and other nuclear patterns (eg, nucleolar)  (For comprehensive information on patterns and their clinical associations, refer to the International Consensus on ANA Patterns website. )

The gold standard for ANA testing is the indirect fluorescent antibody (IFA) assay.  Methods other than IFA to detect ANAs are considered less sensitive for particular disorders but can be more specific and have faster turnaround times. 

Extractable Nuclear Antibody Tests

Extractable nuclear antibody (ENA) testing is used to follow up on positive ANA results. ENA test results can help to differentiate between various SARDs, for instance, Sjögren syndrome and SLE. Panels that test for several ENAs can be helpful for identifying these disorders. The presence of anti-SSA (Ro) (SSA-52 and SSA-60) and anti-SSB (La) is useful for distinguishing Sjögren syndrome. Anti-SSA antibodies are found in two thirds of patients with Sjögren syndrome,  and anti-SSA (Ro) positivity is an important component of the ACR/EULAR classification criteria for primary Sjögren syndrome.  (See Criteria for Diagnosis above.)

Rheumatoid Factor Test

RF testing is commonly used as part of the workup for Sjögren syndrome because RF is found in approximately half of patients with the disease. 

Additional Tests

Sjögren syndrome diagnosis requires tests in addition to antibody and RF tests (see Criteria for Diagnosis above). Suggested tests include the measurement of unstimulated whole saliva flow rate to assess oral dryness, ocular staining to evaluate damage to the ocular surface caused by eye dryness, Schirmer’s test to measure tear production, and a labial salivary gland biopsy to detect focal lymphocytic sialadenitis and determine a focus score. 

Monitoring

Surveillance for B-cell lymphoma is particularly important in patients with Sjögren syndrome because the incidence of B-cell lymphoma is 15-20 times higher in those with Sjögren syndrome than in the general population. 

ENA testing can also be used for monitoring patients with Sjögren syndrome (see Extractable Nuclear Antibody Tests above).

A tool called the EULAR Patient Reported Index is useful for general monitoring to evaluate mouth and eye dryness as well as fatigue and pain. A second index for Sjögren syndrome, the EULAR Sjögren’s Syndrome Disease Activity Index (ESSDAI), assesses 12 organ domains, but is used primarily in clinical trials.  )

ARUP Laboratory Tests

Antinuclear Antibody Tests

Preferred ANA screening test

Positive nuclear patterns reported include homogeneous, speckled, centromere, nucleolar, or nuclear dots; positive cytoplasmic patterns reported include reticular/AMA, discrete/GW body-like, polar/golgi-like, rods and rings, or cytoplasmic speckled patterns

Enzyme-linked immunosorbent assay (ELISA) has lower sensitivity than IFA for SARDs; if ELISA detects ANAs, then IFA will be performed

Components: ELISA screen is designed to detect anti-SSA (Ro) and anti-SSB (La), among other antibodies

Extractable Nuclear Antibody Tests

Secondary screening test if ANA is positive, or if ANA IFA is negative but Sjögren syndrome is strongly suspected

Recommended to distinguish Sjögren​ syndrome and SLE

First-line testing for connective tissue disease

Panel includes dsDNA, IgG; Smith/RNP, IgG; Smith (ENA), IgG; SSA 52 and 60, IgG; SSB, IgG; Jo-1, IgG; Scl-70, IgG

Confirmatory test for specific connective tissue disease or SARD

Rheumatoid Factor Test

Medical Experts

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References

  1. Nuclear Patterns ICAP

    International Consensus on Antinuclear Antibody Patterns. Nuclear patterns. International Consensus on ANA Patterns. Gainesville, FL. [Updated: 2019; Accessed: Jun 2020]

    Online
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