Arthritis Rheumatol 2016 Oct 26
2016 American College of Rheumatology/European League Against Rheumatism Classification Criteria for Primary Sjögren's Syndrome: A Consensus and Data-Driven Methodology Involving Three International Patient Cohorts.
Abstract
Objective
To develop and validate an international set of classification criteria for primary Sjögren's syndrome (SS) using guidelines from the American College of Rheumatology (ACR) and the European League Against Rheumatism (EULAR). These criteria were developed for use in individuals with signs and/or symptoms suggestive of SS.
Methods
We assigned preliminary importance weights to a consensus list of candidate criteria items, using multi-criteria decision analysis. We tested and adapted the resulting draft criteria using existing cohort data on primary SS cases and non-SS controls, with case/non-case status derived from expert clinical judgment. We then validated the performance of the classification criteria in a separate cohort of patients.
Results
The final classification criteria are based on the weighted sum of 5 items: anti-SSA/Ro antibody positivity and focal lymphocytic sialadenitis with a focus score of ≥1 foci/4 mm2 , each scoring 3; an abnormal ocular staining score of ≥5 (or van Bijsterveld score of ≥4), a Schirmer's test result of ≤5 mm/5 minutes, and an unstimulated salivary flow rate of ≤0.1 ml/minute, each scoring 1. Individuals with signs and/or symptoms suggestive of SS who have a total score of ≥4 for the above items meet the criteria for primary SS. Sensitivity and specificity against clinician-expert-derived case/non-case status in the final validation cohort were high, i.e., 96% (95% confidence interval [95% CI] 92-98%) and 95% (95% CI 92-97%), respectively.
Conclusion
Using methodology consistent with other recent ACR/EULAR-approved classification criteria, we developed a single set of data-driven consensus classification criteria for primary SS, which performed well in validation analyses and are well-suited as criteria for enrollment in clinical trials.
Related Questions
Is there any value in nonspecific inflammation seen on a salivary gland biopsy for making a clinical diagnosis of Sjogren’s disease in a seronegative patient with sicca symptoms (ie. chronic sialoadenitis with focus score 0)?
Unfortunately, nonspecific inflammation is unhelpful. In patients classified as having Sjogren's, the minor salivary gland biopsy will have a focus score of 0 in about 20% (Sharma et al., PMID 31092717). So you cannot rule out Sjogren's with a negative/non-specific biopsy. To meet the 2016 ACR/EULAR...
How do you approach the management of a patient with strongly positive SSA antibodies and an extraglandular feature such as ILD or peripheral neuropathy, but without sicca symptoms or parotid abnormalities?
The ACR/EULAR 2016 criteria are clear that a patient with a +SSA antibody needs to also have some degree of measurable sicca in order to be clinically diagnosed with SjD. In my experience, many patients may not perceive that they are dry because they have been able to tolerate the symptoms over time...
In a patient with sicca symptoms and SS-B antibodies only, can a minor salivary gland lip biopsy with lymphoid aggregates, but also scattered areas of acute neutrophilic inflammation be consistent with Sjogren's Disease?
I agree with @Dr. First Last and cannot speculate on the neutrophils.I'd also like to point out that a French study showed that only 1% of isolated anti-SSB patients had Sjogren's disease, SjD (Jardel et al., PMID 28931060); all others had other autoimmune diseases, neoplasia, infection, and solitar...
In patients with sicca symptoms and positive SSA/SSB how often do you perform other diagnostic testing such as salivary gland ultrasound, biopsy, Shirmers, ocular staining, stimulated salivary flow, etc?
It depends on the clinical context, insurance coverage for procedures, availability of Sjogren's knowledgeable referrals, and patient preferences. I always have patients see optometry/ophthalmology in order to prevent ocular surface damage and assess the causes of dry eye (meibomian gland etc), and ...
In what circumstances do you pursue labial salivary gland biopsy in an asymptomatic patient with high titer ANA and positive SSA?
I seldom, if ever, suggest a lip biopsy in the work-up of patients with Sjogren's syndrome. It is invasive, and even the histo-pathological interpretation is often open to question. I typically refer patients to an ophthalmologist for a diagnosis of keratoconjunctivitis sicca, if present, and if nec...
Do you assess baseline salivary gland function before starting treatment in patients with Sjogren's syndrome?
No. Visual assessment of salivary pool and oral mucosa is routinely done. In the initial consultation and management plan, most always, referral to Sjogren's Oral Medicine Specialist is made where whole salivary flow is measured, usually by Unstimulated Whole Salivary Flow Rate (abnormal, less than/...
What baseline work-up or "staging" do you do in patients with a new diagnosis of Sjogren's (i.e., PFT, cryoglobulins, complement, RF, UA)?
The baseline workup I like to do in patients newly diagnosed with Sjogren's are the following lab tests with rationale: ANA (almost all patients have a high titer ANA that is positive - typically it is a speckled pattern Extractable nuclear antigen (ENA) testing looking for SSA (anti-Ro antibody) +/...