Since the early 1960s almost a dozen different criteria for Sjögren’s syndrome (SS) have been published, both for classifying and for diagnosing that autoimmune disease. Recently, an international team of rheumatologists has published new classification criteria for Sjögren’s syndrome. In the April issue of the Arthritis Care & Research journal the authors propose clear and carefully worded guidelines.
Without question, these “new 2012 classification criteria for Sjögren’s syndrome” are urgently needed to better support etiologic and genetic research and therapeutic trials for Sjögren’s syndrome. Indeed, the new criteria are the first to be based solely on objective clinical tests!
Many other criterions have permitted various testing subjectivity to enable the classification of the disorder. In consequence, subjectivity has made standardisation of clinical trial inclusion something of a moving target, limiting comparability of research data across studies and impeding the needed robust clinical evaluation of possible new treatments. But criteria used for enrollment into clinical trials need to be clear, be easy to apply. And the new 2012 criteria agree to that demand.
Criteria based on objective clinical tests
However, the development of new biologic immunomodulationg agents (“biologicals”) that are being considered in the treatment of Sjögren’s syndrome increases the need and importance of developing stringent classification criteria that can be used in the context of clinical trials. Criteria badly need to have high specificity, considering the potentially serious adverse effects and comorbidities of biologic agents. The consequence of misclassifying someone without Sjögren’s syndrome as a case would be serious given the potentially toxic side effects of these agents!
This Sjögren’s syndrome criteria has been approved by the American College of Rheumatology (ACR) Board of Directors as Provisional […].
from the ACR classification criteria for Sjögren’s syndrome
The new criteria come from the Sjögren’s International Collaborative Clinical Alliance, or: SICCA for short. Importantly, the American College of Rheumatology (ACR) voted to accept the SICCA criteria, and they “[…] approved these Sjögren criteria as provisional […]”. This formulation cited from the original article signifies that the criteria set has been quantitatively validated using patient data, but it has not yet undergone validation based on an external data set. Furthermore, it is noted in the guideline that all ACR-approved criteria sets are expected to undergo intermittent updates.
The next step will be to present the Sjögren’s syndrome classification criteria to representatives of the EULAR.
Caroline Shiboski, Ph.D, co-lead author of the study
Actually, this guideline marks the first time ever that the ACR has approved classification criteria for Sjögren’s syndrome. And, in doing so, the ACR recognized the need for rheumatologists, ophthalmologists, and oral medicine practitioners to collaborate in research studies to diagnose the condition. Now, the next step will be to present the criteria to representatives of the EULAR. The abbreviation EULAR stands for the European League Against Rheumatism, which is the European equivalent of the American Congress of Rheumatism (ACR).
How the experts proceeded
In the “SICCA study” a panel of international experts began by compiling a consensus list of existing diagnostic tests to assess the various components of Sjögren’s syndrome, which are oral, ocular, and systemic. Using the various tests, the rheumatologists, ophthalmologists, oral medicine experts and pathology specialists performed comprehensive clinical evaluations on more than 1,600 participants enrolled in the so called so called SICCA registry. All of them had possible signs and/or symptoms of Sjögren’s syndrome typical of those of patients seen in a clinical practice.
Combining the expert consensus and data that have been collected from study participants, the SICCA scientists developed a set of preliminary criteria for classifying Sjögren’s syndrome. According to the authors, validation of the new criteria and comparison to alternatives resulted in high sensitivity and specificity, and the results showed high agreement with the American-European Consensus Group, the so called “AECG criteria”. These criteria have been published in 2002, and are currently the most frequently cited in Sjögren’s syndrome studies and a kind of “gold standard”.
Based on the intensive process of evaluation, the new Sjögren’s criteria emerged. They stipulate that to be classified with Sjögren’s syndrome, research participants must be positive for at least two of three objective diagnostic tests:
- A. positive serum anti-SS-A/Ro and/or positive serum anti-SS-B/La OR
B. positive rheumatoid factor (RF) and ANA titer ≥ 1:320
- labial salivary gland biopsy exhibiting focal lymphocytic sialadenitis with a focus score ≥ 1 focus /4 mm²
- Keratoconjunctivitis sicca with ocular staining score ≥ 3 (assuming that individual is not currently using daily eye drops for glaucoma and has not had corneal surgery or cosmetic eyelid surgery in the last 5 years)
Uniform classification criteria are vital for research
Consistent classification criteria based on objective tests are vital to ensure that participants in clinical studies and treatment trials are correctly classified as having Sjögren’s syndrome. This is especially important with respect to treatment trials to avoid exposing individuals to new investigational drugs and any potential toxicity if they don’t have the disease. That is why uniform criteria for classification are vital for clinical studies and research on SS.
Our data showed […] the tremendous complexity of Sjögren’s syndrome and the true value of assembling more objective classification criteria moving forward.
Dr. Troy Daniels, senior author on the classification paper
The analyses done by the Sjögren’s International Collaborative Clinical Alliance also reinforced that the subjective may not always be as informative as it at first seems. Dry mouth and eyes long have been associated with SS. But the data of the classification paper showed that although patients may complain of dry mouth and eyes, these symptoms lack a statistically significant association with positive antibodies (such as anti-SS-A/Ro, anti-SS-B/La, and antinuclear antibodies, ANA), ocular staining, and/or salivary biopsy. This shows the tremendous complexity of Sjögren’s syndrome and the true value of assembling more objective classification criteria moving forward.
Author of this article: Tobias Stolzenberg
Shiboski SC, Shiboski CH, Criswell LA et al. for the Sjögren’s International Collaborative Clinical Alliance (SICCA) Research Groups. American College of Rheumatology classification criteria for Sjögren’s syndrome: A data-driven, expert consensus approach in the Sjögren’s International Collaborative Clinical Alliance Cohort. Arthritis Care & Research 2012;64:475-487