Sjögren’s Syndrome: An Autoimmunity Underdog

March 18, 2019

Sjögren’s Syndrome is a frequently misunderstood and misdiagnosed illness. Relatively speaking, and compared to other autoimmune rheumatic diseases such as rheumatoid arthritis and lupus, Sjögren’s Syndrome lacks in research funding and specialized centers adept at diagnosing, managing, and studying the condition, particularly in the United States.

“I typically refer to Sjögren’s as the underdog of autoimmune rheumatic diseases,” says Ghaith Noaiseh, MD, assistant professor of medicine and director of the UPMC Sjögren’s Syndrome clinic. Dr. Noaiseh specializes in the treatment and research of Sjögren’s Syndrome, with a particular interest in caring for complex patients who have the disorder and exhibit severe, systemic (extraglandular) manifestations.

Dr. Noaiseh arrived at UPMC in 2012 after completing a fellowship in rheumatology at the University of Pennsylvania where he developed an interest in studying Sjögren’s.

“There are very few centers in the United States that have dedicated clinics and research programs for Sjögren’s Syndrome, even though the disorder is more common in occurrence than lupus, and much more common in occurrence than scleroderma,” says Dr. Noaiseh.

Since arriving at UPMC, Dr. Noaiseh has established and expanded the Sjögren’s Syndrome clinic, which resides within the UPMC Lupus Center of Excellence. In 2014, Dr. Noaiseh began the UPMC Sjögren’s Registry, which is a biorepository that collects tissue and blood-based data samples from patients in order to facilitate research and promote collaborative investigations with researchers at other institutions with similar interest.

Sjögren’s Syndrome: Beyond Dry Eyes and Mouth

Sjögren’s Syndrome is a frequently misdiagnosed disorder. Somewhat similar to lupus, the hall marks of the disorder are dry eyes and dry mouth, as well as other complications such as fatigue and chronic pain. In some patients, the disease can lead to serious and potentially life-threatening manifestations such as nerve, lung, and kidney inflammation.

“Additionally, about five percent of Sjogren’s patients develop non-Hodgkin’s Lymphoma, a risk profile that is higher than any other autoimmune disease,” says Dr. Noaiseh.

“This is a very important point to make and a reason why these patients need to be regularly evaluated in the rheumatology clinic. There are certain predictors of lymphoma development with which the clinician has to be familiar. Patients who have several of these predictors have the highest risk.”

One of the most severe complications in the disease is the development of interstitial lung disease (ILD). For this reason, one of Dr. Noaiseh’s frequent collaborators in patient care is the Dorothy P. and Richard P. Simmons Center for Interstitial Lung Disease at UPMC.

“Symptoms, as well as laboratory testing of Sjögren’s, frequently overlap with other autoimmune disorders. For example, most Sjogren’s patients have a positive ANA and symptoms of joint pain and rashes, which is a similar presentation at lupus. This can sometimes account for its misdiagnosis and classification. Additionally, objective testing for dry eyes and mouth, an important step in establishing the diagnosis, is seldom done in the rheumatology clinic, which may delay the diagnosis. We need to have a more heightened awareness of the disease, both in primary care clinics and within rheumatology,” says Dr. Noaiseh.

Sjögren’s: Moving Away From Primary and Secondary Designations

Sjögren’s Syndrome used to be designated as being either a primary or secondary disorder, but as Dr. Noaiseh explains, the secondary designation is no longer a favorable scientific term to use. The field has migrated away from classifying it as such for several reasons.

“This older, secondary designation implies that, for example, in a case or presence of lupus and Sjogren’s in the same patient, that Sjögren’s is a secondary phenomenon — that lupus led to the Sjögren’s. However, this is not really how autoimmunity works. What is really happening is much more of an overlap type of scenario. It is much more appropriate to view Sjögren’s as a distinct disorder that overlaps at times with other rheumatic diseases.

The idea here is to reinforce that Sjögren’s Syndrome can and does co-occur with other autoimmune diseases,” says Dr. Noaiseh.

Developing New Clinical Guidelines for Sjögren’s Syndrome

Dr. Noaiseh was recently invited to chair a panel of experts through the Sjögren’s Syndrome Foundation (SSF) to develop new clinical practice guidelines for the diagnosis and management of vasculitis in Sjögren’s Syndrome. The clinical guidelines project began several years ago and has since progressed through several phases of development.

Research and Clinical Trials

Dr. Noaiseh is the site principal investigator for numerous phase 2 and 3 randomized clinical trials assessing the efficacy of different novel biological therapies in the management of Sjögren’s Syndrome and SLE. “Since there are virtually no FDA-approved therapies for Sjögren’s, we are essentially left with empirical treatment options, experience, and intuition to try to help the patient in front of us manage their disease. There is a significant amount of unmet need in the care of these patients. These kinds of trials are vitally important to our goals of expanding our treatment armamen-tarium and developing classes of effective, potent medication therapies,” says Dr. Noaiseh.

Further Reading

St Clair EW, Baer AN, Wei C, Noaiseh G, Parke A,Coca A, Utset TO, Genovese MC, Wallace DJ, McNamara J, Boyle K, Keyes-Elstein L, Browning JL, Franchimont N, Smith K, Guthridge JM, et al. The Clinical Efficacy and Safety of Baminercept, a Lymphotoxin-ß Receptor Fusion Protein, in Primary Sjögren’s Syndrome: Results from a Randomized, Double-Blind, Placebo-Controlled Phase II Trial. Arthritis Rheumatol. 2018.