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Nandakumar
Peterson
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 (e.g., rheumatoid arthritis or systemic lupus erythematosus [SLE]) or organ-specific autoimmune diseases (e.g., 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
The initial evaluation of a patient with a possible systemic autoimmune condition should include 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 tests for antibodies against Sjögren syndrome-related antigen A (anti-SSA [Ro]), specifically SSA-52 (Ro52) and/or SSA-60 (Ro60), antibodies against Sjögren syndrome-related antigen B (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.)
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, but it is primarily used in clinical trials. (See Monitoring.)
Criteria for Diagnosis
The American College of Rheumatology (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, immunoglobulin G4 (IgG4)-related disease, graft-versus-host disease, or history of head and neck radiation. A classification criteria score of ≥4 designates a patient as having primary Sjögren syndrome. These criteria are not yet validated for secondary 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 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. | |
Indications for Testing
Testing for Sjögren syndrome should be considered for patients with dry mouth and dry eyes, particularly 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 healthy individuals, particularly those who are elderly. 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 (e.g., speckled, discrete dots/GW body-like, golgi/polar) and other nuclear patterns (e.g., nucleolar) may also be associated with Sjögren syndrome. , (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 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 help identify these disorders. The presence of anti-SSA (Ro) (SSA-52 and SSA-60) and anti-SSB (La) is useful to distinguish 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.)
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). 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, a Schirmer 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 to monitor patients with Sjögren syndrome (see Extractable Nuclear Antibody Tests).
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
Semi-Quantitative Indirect Fluorescent Antibody (IFA)
Qualitative Enzyme-Linked Immunosorbent Assay/Semi-Quantitative Indirect Fluorescent Antibody
Qualitative Enzyme-Linked Immunosorbent Assay/Semi-Quantitative Indirect Fluorescent Antibody/Semi-Quantitative Multiplex Bead Assay/Semi-Quantitative Enzyme-Linked Immunosorbent Assay
Reflex pattern: If ANA IgG is detected by ELISA, then ANA, HEp-2, IgG by IFA will be added; if ANA, IgG by IFA is confirmed positive with a titer of 1:80 or greater, then a titer and pattern will be reported; samples positive for ANA, IgG by IFA will reflex to ENA confirmation for the particular antibody
Semi-Quantitative Multiplex Bead Assay
Semi-Quantitative Multiplex Bead Assay
Quantitative Enzyme-Linked Immunosorbent Assay/Quantitative Multiplex Bead Assay
Semi-Quantitative Enzyme-Linked Immunosorbent Assay/Semi-Quantitative Indirect Fluorescent Antibody (IFA)/Semi-Quantitative Multiplex Bead Assay
Components: dsDNA, IgG; Smith/RNP, IgG; Smith (ENA), IgG; SSA 52 and 60, IgG; SSB, IgG; Jo-1, IgG; Scl-70, IgG
Semi-Quantitative Enzyme-Linked Immunosorbent Assay/Semi-Quantitative Multiplex Bead Assay
Quantitative Immunoturbidimetry
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Reflex pattern: If ANA IgG is detected by enzyme-linked immunosorbent assay (ELISA), then ANA, HEp-2, IgG by IFA will be added