How to diagnose Sjögren's (Sjögren's syndrome)?

From the Guidelines

Diagnosing Sjögren's syndrome requires a comprehensive approach combining clinical evaluation, laboratory tests, and sometimes tissue biopsy, with the latest classification criteria based on a weighted sum of five items, including anti-SSA/Ro antibody positivity, focal lymphocytic sialadenitis, abnormal ocular staining score, Schirmer's test result, and unstimulated salivary flow rate, as outlined in the most recent study from 2024 1. The diagnosis typically begins with a thorough assessment of symptoms such as dry eyes, dry mouth, joint pain, and fatigue. Specific tests include blood work to detect autoantibodies like anti-SSA (Ro) and anti-SSB (La), which are present in many Sjögren's patients, as well as rheumatoid factor and antinuclear antibody tests 1. Eye tests are crucial, including Schirmer's test to measure tear production and ocular surface staining to assess damage, with a Schirmer test result of ≤5 mm/5 minutes without anesthesia being one of the criteria for diagnosis 1. Oral evaluation may involve measuring salivary flow rates and performing a lip biopsy to examine minor salivary glands for characteristic lymphocytic infiltration, which is considered the gold standard for diagnosis, with a focus score of ≥1 foci/4 mm2 being one of the criteria for diagnosis 1. Additional tests might include salivary gland ultrasonography or scintigraphy to evaluate gland function. Diagnosis often follows classification criteria established by rheumatology organizations, which require a combination of subjective symptoms and objective findings, with individuals having a total score of ≥4 meeting the criteria for primary Sjögren's syndrome 1. Since Sjögren's can mimic other conditions, differential diagnosis to rule out other autoimmune diseases, medication side effects, or infections is essential, with a panel of experts recommending a comprehensive evaluation including symptoms, objective parameters of tear film stability, tear osmolarity, degree of lid margin disease, and ocular surface damage 1. Early diagnosis is important as it allows for proper management of symptoms and monitoring for potential complications like lymphoma, with studies showing that patients with decreased C4 levels at the time of diagnosis of Sjögren's syndrome had a higher risk of developing lymphoma 1. Some key points to consider in the diagnosis of Sjögren's syndrome include:

• The prevalence of Sjögren's syndrome is approximately 0.4%, with a female-to-male ratio of 20:1 1
• Sjögren's syndrome should be suspected if intrinsic tear-production deficiency is detected in nonelderly women, especially if it is rapid in onset and/or marked in severity 1
• Patients with Sjögren's syndrome are at increased risk for potentially life-threatening vasculitic or lymphoproliferative disorders, with about 5% of patients developing some form of lymphoid malignancy 1
• A low threshold for serological work-up for diagnostic purposes is recommended for patients with clinically significant dry eye, given the increased risk of lymphoma in patients with Sjögren's syndrome 1.

From the Research

Evaluation of Sjögren's Syndrome

To evaluate for Sjögren's syndrome, the following steps can be taken:

• Initial evaluation requires establishment of a dry eye diagnosis using a combination of patient questionnaires and objective ocular tests, including inflammatory biomarker testing 2
• Additional work-up using the Schirmer test and tear film break-up time can differentiate between aqueous-deficient dry eye (ADDE) and evaporative dry eye 2
• The presence of ADDE should trigger further work-up to differentiate between SS-ADDE and non-SS-ADDE 2
• Examination of classic SS biomarkers (SS-A/Ro, SS-B/La, antinuclear antibody, and rheumatoid factor) is a convenient and non-invasive way of evaluating patients for the presence of SS 2
• Recently, newer biomarkers have been identified, including autoantibodies to salivary gland protein-1, parotid secretory protein, and carbonic anhydrase VI, and may allow for earlier diagnosis of SS 2

Diagnostic Criteria

Diagnostic criteria for Sjögren's syndrome include:

• Detection of autoantibodies in patient serum 3
• Histological analysis of biopsied salivary gland tissue 3
• A positive minor salivary gland biopsy is mandatory to fulfill the 2016 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) classification criteria for primary Sjögren syndrome in patients who are seronegative for anti-SSA/Ro antibodies 4

Diagnostic Tests

Diagnostic tests for Sjögren's syndrome include:

• Tear function tests 2
• Serological tests for autoantibody biomarkers 2
• Minor salivary gland and lacrimal gland biopsies 2
• Schirmer test and tear film break-up time 2
• A diagnostic test kit is commercially available (Sjö(®)), incorporating new biomarkers along with the classic autoantibodies 2

Patient Evaluation

Patients with clinically significant ADDE should be considered for serological assessment for SS, given the availability of new serological diagnostic tests and the potentially serious consequences of missing the diagnosis 2 Patients with a negative anti-SSA antibody test who undergo minor salivary gland biopsy to assess suspected Sjögren syndrome have a high diagnostic value, with 93.3% sensitivity, 100% specificity, 100% positive predictive value, and 97% negative predictive value 4