Future Treatments Hold Promise
Editor’s note: ACR on Air, the official podcast of the ACR, dives into topics important to the rheumatology community, such as the latest research, solutions for practice management issues, legislative policies, patient care and more. Twice a month, host Jonathan Hausmann, MD, a pediatric and adult rheumatologist in Boston, interviews healthcare professionals and clinicians on the rheumatology front lines. In a series for The Rheumatologist, we provide highlights from these relevant conversations. Listen to the podcast online at acronair.org, or download and subscribe to ACR on Air wherever you get your podcasts. Here we highlight episode 88, “Sjögren’s Disease,” which aired on Oct. 22, 2024.
Sjögren’s disease is evolving as physicians and researchers better understand its causes and types.
One recent change has been a renaming, from Sjögren’s syndrome to Sjögren’s disease, said Sara McCoy, MD, PhD, a rheumatologist, physician-scientist and the director of the University of Wisconsin Health Sjögren’s Disease Clinic, Madison.
“Patients just didn’t like the concept of a syndrome being an ill-defined pathologic process when we have moved toward understanding the pathogenic process driving Sjögren’s,” said Dr. McCoy, who is co-chair for the Sjögren’s OMERACT working group and is on the Board of Directors for the Sjögren’s Foundation.1
Dr. McCoy
Dr. McCoy described Sjögren’s as causing the characteristic dry eye and dry mouth with, sometimes, other organ involvement. “Ultimately, it’s a severe dryness due to autoimmune exocrinopathy,” she said.
In addition to primary Sjögren’s, some patients may be diagnosed with associated Sjögren’s—the type of Sjögren’s that occurs along with another autoimmune disease.
Identifying patients who may need further testing for Sjögren’s can get tricky, Dr. McCoy acknowledged, because it’s not always clear at first if dryness is caused by Sjögren’s or something else.
If a patient endorses dryness, Dr. McCoy outlined some basic questions you can ask. If you get affirmative answers to these questions, your suspicion of Sjögren’ disease should increase.
For patients with dry eye:
- Do you have a recurrent sensation of sand or gravel in the eye? “That’s what patients will feel a lot of times upon wakening,” she said.
- Have you had dry eye daily for more than three months?
- Do you have to use tear substitutes more than three times a day?
For patients with dry mouth:
- Have you had dry mouth for more than three months?
- Do you have to take a sip of water to swallow a saltine cracker?
- Have you ever had recurrent or persistent swelling of the salivary glands?
Drilling Down a Diagnosis
If a patient comes to Dr. McCoy’s clinic with dryness, she will perform a Schirmer’s test and a salivary flow test at the same time. A Schirmer’s test involves the use of special paper to test tear production in the eye over five minutes. An unstimulated salivary flow test measures the amount of saliva passively produced by a patient within five minutes after clearing out their mouth in advance. Passive saliva collection is akin to drooling for five minutes. Dr. McCoy will have patients do both tests at the same time for efficiency.
It can be harder to diagnose Sjögren’s disease if a patient does not have strong symptoms of dryness and dryness only becomes apparent during testing. “Some of the patients who say they’re dry aren’t necessarily as dry as you might think and vice versa,” she said.
When it comes to antibody testing, Dr. McCoy will order an SS-A test (anti-Ro 52/60 antibody), both to check for a positive result and to find the patient’s actual SS-A level.
Although using other antibodies for a Sjögren’s diagnosis, such as an early antigen panel or carbonic anhydrase VI, has been discussed, not enough evidence supports their use for a Sjögren’s diagnosis, she noted.
If a patient is SS-A negative but still exhibiting symptoms of Sjögren’s disease, Dr. McCoy orders a labial salivary gland biopsy. However, she said it can be challenging to find an ENT provider or dentist who can perform this procedure.
Another challenge can be getting an accurate pathologic interpretation from the biopsy, as less tissue can lead to a higher likelihood of misdiagnosis.2 “You actually need to pay attention to how much tissue there is and then find a good pathologist,” she said. The pathologist will report a focus score, which involves looking for mononuclear cell infiltrates on the gland.
Other diagnostic tools for Sjögren’s are not as widely used, including the use of special stains or different cell markers.
Sjögren’s Treatment
Dr. McCoy characterizes patients with Sjögren’s disease as having both dryness but also fatigue, pain and brain fog that dramatically affect quality of life. For now, treatments are still mostly just supportive.
For dry mouth, sugar-free gum and candies, wetting agents and sialogogues are available. “The first patient described in the literature in the 1880s was treated with the same thing we’re using now or a derivative of it. That’s nuts,” Dr. McCoy said.
For dry eye, preservative-free wetting agents, as well as punctal plugs, moisture chamber eyewear and environmental modifications—such as staying out of windy areas—are typical. “It’s all largely supportive unless you have end-organ involvement. That’s where you reach for off-label immunomodulators,” she said.
If patients don’t respond well to the initial ocular treatments outlined above, they should be referred to ophthalmology. Topical drugs, such as cyclosporine ophthalmic emulsion (Restasis) or lifitegrast ophthalmic solution (Xiidra), may be prescribed with mixed response, Dr. McCoy said.
Although hydroxychloroquine had been used frequently in the past, the 2014 JOQUER trial did not show that it was effective at six months to treat symptoms of Sjogren’s disease, leading to providers moving away from it as general symptom treatment of Sjögren’s.3
The use of endotyping, or grouping patients by pathobiologically similar subtypes, has begun to help patients with Sjögren’s disease by identifying which patients have a phenotype that’s more likely to respond to certain therapies than others, Dr. McCoy said.
The use of endotyping is likely to usher in more treatments going forward. Several drugs have met primary end points in phase 2 studies. “That’s likely because we’ve learned from our failed trials. Not all Sjögren’s patients will respond to a drug. So you might select your Sjögren’s patient by who should respond,” she said.
Endotyping may help identify which patients could benefit from certain drugs, such as hydroxychloroquine, using endotyping techniques, such as stratifying by symptom burden.4
Although the dryness from Sjögren’s disease tends to get worse over time, future treatments hold promise, and resources that rheumatologists can share with patients are available, Dr. McCoy said. These resources include the patient support group from the Sjögren’s Foundation. The foundation also has a monthly meeting called Sjö-Net geared toward clinicians interested in Sjögren’s disease.
Vanessa Caceres is a medical writer in Bradenton, Fla.
References
- Baer AN, Hammitt KM. Sjögren’s disease, not syndrome. Arthritis Rheumatol. 2021 Jul;73(7):1347–1348.
- Fisher BA, Jonsson R, Daniels T, et al. Standardisation of labial salivary gland histopathology in clinical trials in primary Sjögren’s syndrome. Ann Rheum Dis. 2017 Jul;76(7):1161–1168.
- Gottenberg JE, Ravaud P, Puéchal X, et al. Effects of hydroxychloroquine on symptomatic improvement in primary Sjögren syndrome: The JOQUER randomized clinical trial. JAMA. 2014 Jul 16;312(3):249–258.
- Collins A, Lendrem D, Wason J, et al. Revisiting the JOQUER trial: Stratification of primary Sjögren’s syndrome and the clinical and interferon response to hydroxychloroquine. Rhematol Int. 2021 Sep;41(9):1593–1600.
