Myriad symptoms and three different sets of classification criteria make Sjögren’s syndrome a challenging diagnosis, according to a presenter at the Congress of Clinical Rheumatology East.

“Sjögren’s is an oft-neglected topic in rheumatology,” Fredrick B. Vivino, MD, MS, of Penn Presbyterian Medical Center, in Philadelphia, said in his presentation.

Despite its neglected status, Vivino noted that the disease has meanwhile become the second most common autoimmune disease. As many as 20 million Americans report dry eyes, while some 4.5 million Americans have “clinically significant” dry eyes, according to findings from the Women’s Health Study and Physicians Health Study.

“We have gone from being very rare now to being considered quite common,” Vivino said.

Regarding demographics, because the disease was initially described in Scandinavian women, the “typical patient” has historically been a middle-aged white woman, according to Vivino. However, it can now be seen in younger women and those with different racial and ethnic backgrounds, notably including tennis star Venus Williams.

Vivino stressed that some 80% of patients present with sicca syndrome.

“Far and away, dry eyes is the most common presenting manifestation,” he said.

That said, this manifestation is not always present.

“You can diagnose Sjögren’s in the absence of sicca symptoms,” Vivino said. “Please, please keep that in mind.”

Other symptoms at presentation may include seropositive polyarthritis, polymyalgia rheumatica, leukocytoclastic vasculitis, demyelinating disease, peripheral neuropathy, inflammatory myositis, salivary gland swelling or accelerated caries.

“The diagnostic algorithm for Sjögren’s can be quite challenging,” Vivino said.

In addition, the differential diagnosis can range from chronic sialadenitis to IgG4 syndrome, medication-related dryness to sarcoidosis.

“The most common cause of sicca in this country is medication-related dryness,” Vivino said.

Turning to diagnosis and classification, Vivino first urged rheumatologists to assess patients for the objective presence of salivary gland involvement and proof of autoimmunity. Sialometry or abnormal ultrasound may be used to assess dry mouth and salivary glands.

Vivino then offered a tip for proving autoimmunity: “At the present time, the most reliable way is to test for the presence of anti-SSA, or anti-Ro, antibodies,” he said.

A lip biopsy also may aid in diagnosis. According to Vivino, biopsies should be graded for the presence of lymphoepithelial lesions.

“Lip biopsies are frequently misread,” Vivino said, noting that this occurs when a clinician fails to calculate a focus score, cite QNS/sampling error, measure tissue surface area or describe chronic sialadenitis.

“It behooves us to work with a pathologist,” he said.

According to Vivino, classification of Sjögren’s has been difficult because there are currently three sets of criteria being used. The 2002 American European Consensus Group (AECG) classification criteria still maintain some relevance, as do the 2012 ACR-SICCA criteria and an ACR-EULAR document from 2016, he added.

Vivino acknowledged that with three different classification criteria and such an uncertain array of symptoms, it can be difficult to diagnose Sjögren’s.

“I get confused myself from time to time,” he said. “If you rely strictly on classification criteria, you are going to miss some diagnoses.”

With this in mind, Vivino described the what he called the “physician gold standard” of diagnosis, which he defined as three of the following four criteria: Objective evidence of dry eyes, objective evidence of salivary gland involvement, anti-SSA positivity and/or focal lymphocytic sialadenitis, based on a Focus score greater than 0.25 mm².

“You need to take a reasonable, common-sense approach to diagnosis,” he said. “If you do that, you will miss very few diagnoses.”