Understanding, Diagnosing, and Treating Sjogren Syndrome
Understanding, Diagnosing, and Treating Sjogren Syndrome
The goal of improved diagnostic biomarkers is early and more specific diagnosis, but at the same time it is important to understand their sensitivity in predicting symptomatic disease. One study of a Scandinavian healthcare database found that only a minority (18%) of anti-SS-A antibody-positive individuals developed clinical features of SS during a median of 6 years of follow-up. There was even much lower risk for participants who were antinuclear antibody (ANA) or rheumatoid factor (RF) positive but SS-A or SS-B antibody negative.
Similar results were reported by Rasmussen and colleagues among a cohort of 467 anti-SS-A antibody-positive individuals, termed "incomplete SS." In the pediatric population, Tomiita and colleagues reported that among 17 pediatric patients with primary SS, 3 patients developed anti-DNA antibodies and possible juvenile SLE during 10-year follow-up. Overall, it appears that about 18%-25% of patients who are positive for SS-A antibodies will progress to clinical SS over a median of 6-10 years. Thus, we must be very careful in not giving asymptomatic patients a label of SS that may lead to substantial psychological distress.
In order to replace the minor salivary gland biopsy, several groups presented updates on the use of salivary gland ultrasound(SGUS), which included a review of over 167 publications that showed sensitivities ranging from 45.8% to 91.6% and specificities from 73.0% to 98.1%. This high degree of variation in validity was even reported in centers that had extensive experience in both SS and ultrasound. However, SGUS requires a great deal of skill in both performing and interpreting. Caution needs to be exercised before SGUS is used routinely in either diagnosis or clinical follow-up. Perhaps if SGUS is performed by properly trained ultrasonographers (which might increase its validity), this noninvasive method could be useful in both clinical practice and in research.
The actual histologic changes being detected by current SGUS methods remain unclear because our routine histology is derived from the minor salivary gland, while SGUS evaluates the parotid and submandibular glands. For example, the SGUS scoring methods currently score "fibrosis," but the histology of the active SS minor salivary gland biopsy may show lymphocytic infiltration and ductal cell dysfunction. Clearly, the histologic basis of SGUS findings must be clarified. Delli and colleagues in The Netherlands reported performing a biopsy of the major salivary gland (ie, tail of the parotid). Although this might sound risky to the practicing rheumatologist, they reported virtually no adverse side effects and have avoided severing the minor labial nerve, which can occur when the minor salivary gland biopsy is not done correctly. The parotid biopsy is more expensive to perform because it requires at least 2 clinicians, a sterile environment, surgical instruments and sutures, and is unlikely to have widespread use except in clinical trials. However, it will be able to provide information on the correlation between SGUS, histology, and flow rates. Seror and colleagues reported that in the European SS Disease Activity Index, parotid biopsy will be used for measurement of outcomes in clinical trials. Continued refinement of this important outcome measure accompanies the new consensus criteria and development of separate clinical domain and "biologic" domains for use in evaluation of therapeutic response. This new measurement will allow evaluation of specific biomarkers in response to therapy.
Identifying Biomarkers
The goal of improved diagnostic biomarkers is early and more specific diagnosis, but at the same time it is important to understand their sensitivity in predicting symptomatic disease. One study of a Scandinavian healthcare database found that only a minority (18%) of anti-SS-A antibody-positive individuals developed clinical features of SS during a median of 6 years of follow-up. There was even much lower risk for participants who were antinuclear antibody (ANA) or rheumatoid factor (RF) positive but SS-A or SS-B antibody negative.
Similar results were reported by Rasmussen and colleagues among a cohort of 467 anti-SS-A antibody-positive individuals, termed "incomplete SS." In the pediatric population, Tomiita and colleagues reported that among 17 pediatric patients with primary SS, 3 patients developed anti-DNA antibodies and possible juvenile SLE during 10-year follow-up. Overall, it appears that about 18%-25% of patients who are positive for SS-A antibodies will progress to clinical SS over a median of 6-10 years. Thus, we must be very careful in not giving asymptomatic patients a label of SS that may lead to substantial psychological distress.
In order to replace the minor salivary gland biopsy, several groups presented updates on the use of salivary gland ultrasound(SGUS), which included a review of over 167 publications that showed sensitivities ranging from 45.8% to 91.6% and specificities from 73.0% to 98.1%. This high degree of variation in validity was even reported in centers that had extensive experience in both SS and ultrasound. However, SGUS requires a great deal of skill in both performing and interpreting. Caution needs to be exercised before SGUS is used routinely in either diagnosis or clinical follow-up. Perhaps if SGUS is performed by properly trained ultrasonographers (which might increase its validity), this noninvasive method could be useful in both clinical practice and in research.
The actual histologic changes being detected by current SGUS methods remain unclear because our routine histology is derived from the minor salivary gland, while SGUS evaluates the parotid and submandibular glands. For example, the SGUS scoring methods currently score "fibrosis," but the histology of the active SS minor salivary gland biopsy may show lymphocytic infiltration and ductal cell dysfunction. Clearly, the histologic basis of SGUS findings must be clarified. Delli and colleagues in The Netherlands reported performing a biopsy of the major salivary gland (ie, tail of the parotid). Although this might sound risky to the practicing rheumatologist, they reported virtually no adverse side effects and have avoided severing the minor labial nerve, which can occur when the minor salivary gland biopsy is not done correctly. The parotid biopsy is more expensive to perform because it requires at least 2 clinicians, a sterile environment, surgical instruments and sutures, and is unlikely to have widespread use except in clinical trials. However, it will be able to provide information on the correlation between SGUS, histology, and flow rates. Seror and colleagues reported that in the European SS Disease Activity Index, parotid biopsy will be used for measurement of outcomes in clinical trials. Continued refinement of this important outcome measure accompanies the new consensus criteria and development of separate clinical domain and "biologic" domains for use in evaluation of therapeutic response. This new measurement will allow evaluation of specific biomarkers in response to therapy.
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