Sjögren’s Syndrome (SS) is a chronic autoimmune disorder where the immune system mistakenly attacks the body’s moisture-producing glands. The condition is primarily defined by symptoms of severe dry eyes and dry mouth, known as sicca symptoms, which result from damage to the lacrimal and salivary glands. Making a definitive diagnosis of SS can be complex because these dryness symptoms often mimic those of other diseases or are side effects of common medications. Because no single finding can confirm the disorder, physicians rely on a combination of laboratory, functional, and tissue-based tests to accurately identify the presence of Sjögren’s Syndrome.
Screening with Serological Markers
The initial step in diagnosing Sjögren’s Syndrome often involves blood tests to screen for specific autoantibodies, which are proteins produced by the immune system that target the body’s own tissues. The most characteristic of these serological markers are Anti-Ro/SSA and Anti-La/SSB antibodies. Anti-Ro/SSA antibodies are present in approximately 70% of individuals with Sjögren’s Syndrome, while Anti-La/SSB antibodies are found in about 40% of patients.
The presence of these autoantibodies indicates active autoimmune processes, providing strong evidence to support a potential diagnosis. However, neither marker is exclusive to Sjögren’s Syndrome, as they can also be detected in patients with other connective tissue diseases, such as systemic lupus erythematosus. This overlap means the tests are considered highly sensitive for screening but possess lower specificity for Sjögren’s alone.
Other serological markers are routinely checked, including the Antinuclear Antibody (ANA) test, which is frequently positive in autoimmune disorders, and Rheumatoid Factor (RF). RF, an antibody often associated with rheumatoid arthritis, is present in over 50% of people with Sjögren’s Syndrome. While these additional markers further suggest a systemic autoimmune condition, they do not provide the specific confirmation needed to finalize the diagnosis of Sjögren’s Syndrome.
Objective Assessments of Glandular Function
Beyond blood work, the diagnostic process requires objective evidence of decreased tear and saliva production, which are the physical manifestations of the glandular damage. These functional tests quantify the severity of the sicca symptoms and are distinct from the serological screening.
For ocular assessment, the Schirmer test measures tear production by placing a small strip of filter paper under the lower eyelid for five minutes. A result of 5 millimeters or less of wetting, without anesthetic, indicates insufficient tear production. Another procedure is ocular surface staining, which involves applying specialized dye drops (such as Lissamine Green or Rose Bengal) to the eye. An ophthalmologist then uses a slit lamp to examine the eye’s surface for damage caused by chronic dryness.
Salivary function is typically assessed using sialometry, which measures the flow rate of saliva. This test is performed by collecting saliva in a container over a specific period, often 15 minutes, both before and after stimulation. An unstimulated whole salivary flow rate of 1.5 milliliters or less is considered an abnormal sign of glandular dysfunction. While these measurements confirm the severity of the dryness, they cannot definitively prove Sjögren’s Syndrome is the cause, as other conditions and medications can also depress tear and saliva output.
Histological Confirmation and Diagnostic Accuracy
The minor salivary gland biopsy is widely regarded as the most specific and definitive test for Sjögren’s Syndrome. This minimally invasive procedure involves removing a small sample of minor salivary glands, typically from the inner surface of the lower lip, for microscopic examination. Performed under local anesthesia, the procedure provides physical evidence of the disease process within the glandular tissue.
Pathologists analyze the tissue sample for a specific pattern of immune cell infiltration known as focal lymphocytic sialadenitis (FLS). This finding is characterized by the aggregation of 50 or more lymphocytes—a type of white blood cell—clustered around the ducts and blood vessels of the salivary glands. The severity of this infiltration is quantified by the focus score, where one or more foci of lymphocytes per four square millimeters of glandular tissue is considered a positive result.
The high specificity of the biopsy makes it the “gold standard” test, particularly when serological markers are negative or other test results are inconclusive. Many patients who do not have the characteristic Anti-Ro/SSA or Anti-La/SSB antibodies still receive a diagnosis based on a positive biopsy result. Ultimately, the diagnosis of Sjögren’s Syndrome is not based on any single test but on a comprehensive evaluation that integrates results from all three categories. Rheumatologists use established classification criteria, such as the American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) criteria, which require a certain score based on autoantibodies, functional deficits, and positive histology to confirm the diagnosis.