Are You Missing the Early Signs of Sjögren’s Syndrome?

>> What you need to know to help your patients

Kelly Nichols, OD, MPH, PhD: As many as 4 million people in the United States are believed to be affected by Sjögren’s Syndrome, a chronic, systemic, progressive, autoimmune inflammatory disease. It’s estimated that only 1 million people have been diagnosed, which means up to 75% of those who have the disease may remain undiagnosed.^1-3 While these statistics may be surprising to many eyecare practitioners (ECPs), others are even more surprising. For example, it currently takes 4.7 years for a person with Sjögren’s Syndrome to receive an accurate diagnosis.⁴ This is significant because Sjögren’s is a precursor to other diseases, including lymphoma,^5,6 and complications affecting the liver, lungs and thyroid.⁷ The results of a study conducted at the University of Ioannina School of Medicine in Greece indicated that one in five deaths among patients with primary Sjögren’s Syndrome can be attributed to lymphoma.⁸

Because the immune response associated with this disease is largely directed at the salivary and lacrimal glands, ocular symptoms are frequently the first to present. Research shows that 1 in 10 people with clinically significant dry eye also have Sjögren’s Syndrome.⁹ We’re all familiar with the large numbers of patients who come to us seeking relief from the symptoms of dry eye. Many of them may also have Sjögren’s Syndrome, likely undiagnosed. This gives ECPs a unique opportunity to identify patients with this disease early and not only treat its ocular manifestations but also enable patients to seek earlier treatment for its systemic manifestations, which can be multi-system, progressive and debilitating (Figure 1).

Figure 1. Areas of the body that may be affected by Sjögren’s Syndrome.

Do you think our colleagues have a good understanding of Sjögren’s and its manifestations?

Douglas Devries, OD: I think there’s a lack of in-depth understanding throughout eye care.

Arthur Epstein, OD, FAAO: I think there’s an understanding at a basic level that the condition exists, but it has not progressed beyond that. The ramifications aren’t fully understood. I think everyone knows about Sjögren’s, but no one fully understands it.

Dry Eye in the Context of Undiagnosed Sjögrens Syndrome

Dr. Nichols: As we know, a precise determination of the prevalence of dry eye has been elusive. However, an estimated 12.5 million people in the United States, and that may be a conservative estimate, have clinically significant dry eye. Among those, as many as 4 million may have Sjögren’s Syndrome, and most are undiagnosed. As mentioned previously, those numbers translate to one out of every 10 dry eye patients having Sjögren’s. What are your thoughts on this?

Dr. Devries: I find the numbers startling. They tell me that I’m not treating a large percentage of my patients who have Sjögren’s and will experience the consequences but haven’t been diagnosed.

Katherine Mastrota, MS, OD, FAAO: The diagnosis of dry eye is a common one, and perhaps we’re all a bit guilty of lumping all ocular surface disease into the same box, so to speak. We attempt to manage dry eye in a palliative manner, but often don’t think of taking the next step to try and understand whether the cause is something underlying — something more core.

Dr. Epstein: Clearly, a much greater percentage of dry eye patients have Sjögren’s than we tend to believe. It’s tragic that we don’t go to that next level of suspecting it because these patients often progress and become significantly impacted by their dry eye, and then they begin to show the other signs of Sjögren’s.

Dr. Mastrota: Glaucoma patients, too, come to mind. We tend to attribute dry eye in those cases to the medications and the preservatives instead of reminding ourselves that patients can have two conditions at once.

Dr. Devries: I would imagine many early Sjögren’s patients get dismissed as being perimenopausal.

Dr. Nichols: That is possible given that 9 out of 10 Sjögren’s Syndrome patients are women.¹⁰ Can you recall a male patient with Sjögren’s in your practice? They do exist.

Dr. Epstein: It’s rare, but I also wonder if their presentation is milder than in females, perhaps a more delayed onset, which could make the disease more likely to be missed.

Dr. Nichols: I had a male patient who had cancer, so his cancer treatments very likely caused his dry eye. But he could just as easily have had Sjögren’s. He said to me at one point, “I’m a firefighter, and I beat cancer, but this dry eye is going to bring me down.”

Dr. Epstein: The patients I’ve had with diagnosed Sjögren’s Syndrome have had severe ocular manifestations and were miserable.

Dr. Mastrota: Also, dry eye patients often travel from practice to practice searching for relief when treatments aren’t working. They continue to be uncomfortable and unhappy. It begins a cycle of misery for these individuals. Being able to make a diagnosis earlier can empower patients to better manage their condition.

Dr. Epstein: We recognize the complexity of dry eye patients more than ever before, which enables us to better address their problems. It would be great if they could be diagnosed and managed properly at any doctor’s office.

Reducing Time to Diagnosis

Dr. Nichols: Earlier detection of Sjögren’s could certainly help reduce the distress, both ocular and systemic, that patients experience. The Sjögren’s Syndrome Foundation has a goal to reduce the time to diagnosis, currently 4.7 years,⁴ by half in the next 5 years. What can ECPs do?

Dr. Devries: Our history/intake forms are a good place to start. They could include questions related to dry mouth and systemic problems that manifest with Sjögren’s, such as aches and pains and extreme fatigue. Incidentally, in my experience, many of my Sjögren’s patients also have conjunctival chalasis.

Dr. Epstein: I take a structured approach with dry eye patients, looking for associated rheumatoid conditions, which is part of my intake form.

Dr. Nichols: Do you find patients are aware of words like Sjögren’s, rheumatoid arthritis, lymphoma, lupus, and so on?

Dr. Epstein: Yes. Those who’ve been through the system are much more self-educated than they’ve been in the past. I also think it’s important to pay attention to how patients present. Do they appear to have arthritis? About half of Sjögren’s patients have another autoimmune disorder, such as rheumatoid arthritis, lupus or systemic scleroderma.³ How do they shake your hand? Do their hands seem to be extremely cold, which could be an indication of Sjögren’s-related Raynaud’s disease? Did they bring a cup of water into the exam?

Dr. Nichols: Patients with those types of symptoms are already advanced in the Sjögren’s disease process. We would like to be able to determine earlier which patients are likely to go down that road — before they do.

Dr. Epstein: As the first point of contact for many of these patients, ECPs can be the first to recognize something more significant is going on in connection with their ocular status and direct them to the proper specialist.

In addition, it’s important to recognize that the classic presentation of Sjögren’s in the eyecare office is typically aqueous-deficient dry eye. However, both aqueous-deficient and evaporative dry eye can be associated with inflammation affecting all layers of the tear film.⁷ Meibomian gland disease can be present, too. Being cognizant of this opens up more possibilities for us in terms of patient management. Dry eye is a complex, challenging diagnostic entity, and we need to keep an open mind throughout the process.

Dr. Mastrota: Part of the challenge is that dry eye symptoms may improve or worsen in cycles or remain stable.

Dr. Nichols: Yes, and Sjögren’s is a dynamic disease as well. Symptoms don’t always present concurrently and tend to be cyclical.⁵ Patients may have periods during which they experience significant pain and irritation and periods where they feel normal and appear clinically normal.

New Test Improves Diagnostic Sensitivity and Specificity

Dr. Nichols: Unfortunately, the serology testing traditionally used to diagnose Sjögren’s doesn’t have very high sensitivity and specificity, so it isn’t likely to detect disease early.¹¹ New research has identified additional biomarkers — salivary protein-1 (SP-1), carbonic anhydrase (CA6) and parotid secretory protein (PSP) — that appear to improve the speed and consistency of diagnosis (Table 1).¹¹ This new knowledge has been incorporated into the Sjö test, which was approved by the FDA in November 2013. The test includes the traditionally used biomarkers plus (SP-1), (CA6) and (PSP), and has exhibited high sensitivity and specificity of more than 95%.¹² The Sjö test can be administered in-office via a blood sample obtained with a finger prick.

How do you think this test could be incorporated into optometric practice?

Dr. Epstein: The increased sensitivity and specificity is a major step forward, and the test is far more accessible to us as clinicians, which I think is a massively important step. I could see it easily becoming part of my armamentarium for patients who have moderate to severe dry eye, and perhaps even for those who have mild but progressive dry eye. The test represents a change in standard of care that centers around optometry, which is something that’s happening in a number of different areas.

Dr. Mastrota: Patients would absolutely welcome a test whose result could help them understand the basis of their symptoms. I know this assay would easily fit into any mode of practice.

Dr. Devries: Absolutely. My feeling is that point-of-care testing in general is going to be the standard of care within primary care optometry in the future.

Strategies for Patients with Sjögren’s Syndrome

Dr. Nichols: Current Preferred Practice Pattern guidelines include treatment options for Sjögren’s-associated dry eye such as topical lubricants, topical cyclosporine, autologous serum, topical corticosteroids, punctal occlusion and systemic secretagogues.¹³ As with other forms of dry eye, the overall goal of therapy is to normalize the tear film, decrease inflammation, improve lacrimal function and facilitate epithelial healing. Treating the ocular symptoms of Sjögren’s can help to prevent lacrimal gland degradation.³

Do you treat dry eye patients differently if you know they have Sjögren’s?

Dr. Mastrota: Yes, and I surmise intuitively we all would. We know what is likely coming down the line, and we want to slow down that train any way we can. The earlier we can intercede in order to break the cycle of inflammation, the better.

Dr. Devries: Referral to a rheumatologist is important, too, and the Preferred Practice Pattern notes that.

Dr. Nichols: When you’re managing patients who have dry eye and known Sjögren’s, what are some of the strategies you use?

Dr. Devries: I tend to be aggressive. I put patients on cyclosporine (Restasis, Allergan) the first time I see them. I recommend they use moisture chamber goggles to manage the environmental conditions. For many patients, I also utilize compounded androgen ointment and have them use omega-3 creams. I frequently use autologous serum as well. That involves a blood draw, which is spun down into a serum and sent to a compounding pharmacy to be mixed with balanced salt solution and put into small eye drop vials. Patients use the drops every few hours over an 8-week period, which gives the eye a chance to heal by utilizing the growth factors and trans-growth factors in the serum. It’s not a panacea, but it’s rare that I don’t see some kind of a positive result. For patients with severe, unresolving punctate epithelial keratitis, I may use an amniotic membrane.

Even though these measures are aggressive, patients with Sjogren’s and severe dry eye are very good with compliance because they’ve been so uncomfortable and their symptoms have affected their lives so dramatically.

Dr. Epstein: Scleral lenses and bandage contact lenses can also be helpful. Mindful of meibomian gland function, I think preserving whatever aqueous is left on the eyes is critically important. Interestingly, I use very little Restasis for most patients, but for this group I use it fairly frequently.

Dr. Nichols: We mentioned the importance of referring patients with a diagnosis of Sjögren’s to a rheumatologist. Perhaps a dental referral is something that also shouldn’t be overlooked.

Dr. Epstein: I wonder whether most optometrists co-manage directly with dentists or whether the rheumatologist coordinates it?

Dr. Nichols: The dental loop is definitely an interesting concept. Why wouldn’t we be working with the dentists in our communities on this? It seems like an easy connection to make.

A New Way to Help Our Dry Eye Patients

Dr. Nichols: We’ve learned a great deal about dry eye in the past 10 years. We’re putting together a much more global picture of how best to manage this group of patients. A key component is ruling in or ruling out potential underlying etiologies, and the new Sjö test should be a big help in regard to Sjögren’s and therefore a great service to our patients.

Dr. Devries: I’m very excited about this test. Immediately, it makes me think of my most challenging cases of dry eye, where, for example, patients just aren’t responding to treatment like I would expect or are progressing for no apparent reason. The test will give them a quick answer, which is what they need and want. When doctor and patient are armed with that information, we can move on to setting expectations and doing what we need to do to provide relief to our patients and protect them as much as possible from further damage.

Dr. Epstein: Sjögren’s patients pretty much define what I feel I’ve dedicated most of my life to. They’re among the patients who need us the most. Anything I can do to recognize what they need, initiate treatment earlier, and be part of a team that can help them more effectively is very exciting to me.

Dr. Nichols: Further improving our care of dry eye patients is a common goal for all of us. Being able to also identify patients in our practices who have undiagnosed Sjögrens Syndrome is a step of major importance.

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