What are the markers for Sjögren's syndrome and Ehlers-Danlos syndrome?

From the Guidelines

Sjögren's syndrome and Ehlers-Danlos syndrome (EDS) have distinct diagnostic markers that help identify these conditions, with Sjögren's syndrome primarily marked by anti-SSA (Ro) and anti-SSB (La) antibodies, and EDS diagnosed clinically based on the Beighton score and genetic testing for certain subtypes. For Sjögren's syndrome, the primary markers include anti-SSA (Ro) and anti-SSB (La) antibodies in blood tests, which are present in about 70% of patients, as noted in the study by 1. Additional testing includes salivary gland biopsy, Schirmer's test to measure tear production, and lip biopsy to detect lymphocytic infiltration. The latest classification criteria for Sjögren's syndrome, as proposed in the study by 1, are based on the 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.

Some key points to consider in the diagnosis and management of Sjögren's syndrome include:

• The importance of suspecting Sjögren's syndrome in patients with clinically significant dry eye and dry mouth symptoms, as noted in the study by 1
• The need for comanagement with a rheumatologist due to the many possible comorbid systemic conditions, as emphasized in the study by 1
• The use of objective parameters such as tear film stability, tear osmolarity, and ocular surface damage to stage the severity of dry eye syndrome, as recommended in the study by 1
• The availability of treatment options such as tear supplementation, control of inflammation, and possible stimulation of tear production, as discussed in the study by 1

In contrast, Ehlers-Danlos syndrome is diagnosed primarily clinically, based on the Beighton score for joint hypermobility, skin hyperextensibility, and tissue fragility, with genetic testing available for several EDS subtypes, particularly for the vascular type (COL3A1 gene) and classical type (COL5A1 and COL5A2 genes), as noted in the study by 1. While there's no single definitive test for either condition, these markers help establish diagnosis when combined with clinical symptoms. Both conditions often require evaluation by specialists such as rheumatologists for Sjögren's and geneticists for EDS, as they can present with overlapping symptoms like joint pain and fatigue, making differential diagnosis important.

From the Research

Sjogren's Syndrome Markers

• The diagnostic tests for primary Sjögren's syndrome (pSS) are generally highly reliable when performed twice with a one year interval 2.
• The highest reliability was obtained for the sensation of dry mouth (98.2%) and sensation of dry eyes (96.4%), and anti-SSA/SSB antibodies (93.3%) 2.
• A non-invasive model for diagnosis of primary Sjögren's disease based on salivary biomarkers, serum autoantibodies, and Schirmer's test has been established 3.
• The model includes salivary biomarkers such as complement factor B (CFB), clusterin (CLU), and neutrophil elastase (NE), serum autoantibodies (anti-SSA/Ro60 and anti-SSA/Ro52), and Schirmer's test 3.
• The 2016 American College of Rheumatology/European League Against Rheumatism Classification Criteria for Primary Sjögren's Syndrome include anti-SSA/Ro antibody positivity, focal lymphocytic sialadenitis, abnormal ocular staining score, Schirmer's test result, and unstimulated salivary flow rate 4.

Ehlers-Danlos Syndrome Markers

• The diagnosis of vascular Ehlers-Danlos syndrome is challenging, and patient selection for genetic testing relies on diagnostic criteria, which have never been evaluated 5.
• The Villefranche criteria provide accurate detection of symptomatic probands in specialized practice but have limited specificity 5.
• The revised diagnostic criteria for vascular Ehlers-Danlos syndrome have increased specificity, but its overall performance is poorer 5.
• There is no specific marker mentioned in the studies for Ehlers-Danlos syndrome, but the Villefranche criteria and revised diagnostic criteria are used for diagnosis 5.

Comparison of Sjogren's and Ehlers-Danlos Syndrome Markers

• Sjogren's syndrome has specific markers such as anti-SSA/SSB antibodies, salivary biomarkers, and Schirmer's test, whereas Ehlers-Danlos syndrome relies on diagnostic criteria such as the Villefranche criteria and revised diagnostic criteria 2, 5, 3, 4.
• The diagnosis of Sjogren's syndrome is more established and has a higher sensitivity and specificity compared to Ehlers-Danlos syndrome 2, 3, 4.