ACR: New Sjögren’s classification criteria on the way

SAN FRANCISCO – New classification criteria for Sjögren’s syndrome are ready for sign-off by the American College of Rheumatology and the European League Against Rheumatism, Dr. Caroline Shiboski said.

“We hope this will be the last iteration of the international classification criteria that we have proposed to ACR and EULAR,” said Dr. Shiboski, professor of orofacial sciences at the University of California San Francisco School of Dentistry.

The criteria will give researchers a single set of consensus diagnostic measures for Sjögren’s syndrome, replacing both the provisional 2012 ACR criteria (Arthritis Care Res (Hoboken). 2012 Apr;64[4]:475-87) and criteria from the American-European Consensus Group, added Dr. Shiboski, who led the led the ACR steering committee that helped to create the criteria. “These criteria aim to classify clinical trial participants,” she added. “That doesn’t mean we can’t use them for diagnostic purposes, but that was not the primary purpose.”

Dr. Alan Baer

Sjögren’s syndrome is complex, with differential diagnoses ranging from non-autoimmune sicca syndrome and IgG4-related disease to sarcoidosis, hematologic cancers, and amyloidosis, said Dr. Alan Baer, one of the clinician-experts who participated in the working group that led to the new criteria. Moreover, patients need care from rheumatologists, ophthalmologists, and oral medicine specialists to manage systemic symptoms and sequelae of sicca and xerostomia. The lack of consensus criteria has made it hard even to estimate the incidence and prevalence of the disease, researchers have noted (Clin Epidemiol. 2014;6:247-55). Furthermore, some rheumatologists criticized the provisional ACR criteria for requiring a salivary gland biopsy and ophthalmologic testing, both of which are time consuming and unavailable in many practices.

The new criteria help to solve some of those problems, Dr. Shiboski and her fellow experts said at the annual meeting of the American College of Rheumatology.* They add two simpler diagnostic options: the Schirmer tear test and the 5-minute salivary flow test. They also weight the various diagnostic tests, assigning 2 points each to the focus score for focal lymphocytic sialadenitis and the presence of anti–Sjögren’s syndrome antibody A; and 1 point each for a Schirmer test of 5 mm in less than 5 min, an ocular staining score of greater than 5, and salivary flow rate of less than 0.1 mL/min.

Patients need a total of 4 points for a confirmed diagnosis of Sjögren’s syndrome. Because diagnosis no longer requires mucosal dryness, the new criteria “are more flexible, and allow us to select patients in the earlier stages of Sjögren’s syndrome who are more likely to show improvement with treatment,” said Dr. Raphaèle Seror, a clinical rheumatologist at Hôpitaux universitaires Paris-Sud in France and a member of the EULAR Steering Committee for the criteria.

Nonetheless, the new criteria have “some recognizable limitations,” said Dr. Baer, director of the Johns Hopkins Jerome L. Greene Sjögren’s Syndrome Center in Baltimore. They are not validated for secondary or juvenile forms of Sjögren’s or for the subset of cases associated with anticentromere antibodies, he noted. They also exclude several established diagnostic tools, including CT, MRI, and sialography or scintigraphy, as well as several “emerging” tools such as parotid gland biopsy, ultrasonography, and tests for novel autoantibodies, he added.

Criteria aside, “when you go into the clinic, it’s important that you do a complete evaluation of the patient who comes to you complaining of dry eyes and a dry mouth,” Dr. Baer emphasized. “The way you ask these questions is really important. Look for daily, persistent, dry eyes and dry mouth.”

Diagnostic tests for Sjögren’s syndrome are imperfect, so clinicians should interpret them carefully. The Schirmer tear test is relatively unreliable and insensitive, and its values normally decline in older patients. Ocular surface staining results also are nonspecific and prone to inconsistent interpretation, according to Dr. Baer. The single most reliable test is a labial gland biopsy with a focus score of 1 or higher, meaning that a 4 mm² area has at least one cluster of at least 50 lymphocytes adjacent to salivary gland acini, he said.

To draft the criteria, Dr. Shiboski and her colleagues used 1000Minds decision-making software to show 55 experts dozens of fictive clinical vignettes. For each vignette, the experts were asked to use the existing ACR criteria to determine whether or not the patient had Sjögren’s syndrome; they also could say that they were unsure. Analyzing the vignettes on which experts’ agreed approach yielded a set of draft diagnostic criteria, which were then tested among 1,200 real-life patients with Sjögren’s from the real-life Sjögren’s International Collaborative Clinical Alliance (SICCA), Paris-Sud, and Oklahoma Medical Research Foundation (OMRF) cohorts, Dr. Shiboski said. Specificity received double the weight of sensitivity, because “in clinical trials, you want specificity to be as high as possible,” she added.