Comanagement a priority in patients with autoimmune disease

Optometry is in a unique position to detect autoimmune disease, as inflammatory markers can present early in the eye.

Tracy Doll, OD, FAAO, believes practitioners are waiting too long to test for underlying autoimmune conditions. She told Primary Care Optometry News that she is often the fourth or fifth doctor that a patient with ocular manifestations has visited for answers.

“By the time the patient gets to me they are already suffering, and they’ve been through all the basic interventions,” Doll, who is coordinator for Pacific Dry Eye Solutions, a dry eye specialty service/center of excellence within Pacific University College of Optometry, said. “It seems to me that you could detect a lot more cases if you asked patients complaining about dry eye if they have dry mouth and excessive fatigue, particularly when you see it in combination with anterior keratitis.”

Sjögren’s syndrome, celiac disease and other autoimmune diseases are increasing in both incidence and prevalence, according to Brian E. Mathie, OD, FAAO, adjunct faculty member with the Ohio State University College of Optometry and clinic director at the Roholt Vision Institute.

Celiac disease is now estimated to have a prevalence of more than 1% of the population, although the majority, as high as 87%, are undiagnosed, he told PCON.

“That translates to 40 patients with celiac disease a year for an average optometrist who sees 4,000 patients a year,” he said.

Researchers project that the prevalence of primary Sjögren’s syndrome is between two and 10 individuals per 10,000 citizens, according to a study of a population-based cohort in Minnesota.

Ninety percent of all Sjögren’s patients will be female, and the average age of onset is typically after 40 years, according to Mathie. He added that while 90% are female, that leaves more than 400,000 U.S. men who suffer from the disease. Patients also tend to be thinner in stature.

“I don’t think we are necessarily seeing more autoimmune disease; I think we are understanding the correlations better,” Carlo Pelino, OD, FAAO, a professor at The Eye Institute at Salus University, said in an interview. “The eye was made so that it should not have inflammation inside of it; the immune privilege means the internal eye should not have inflammation.”

In 10% to 20% of cases optometrists may be the first physician to see the autoimmune disease, which highlights the need for a good patient history, he said.

“These patients present to us, and it’s our responsibility to know how to order the lab work-up and get them better because, a lot of the time, ocular symptoms are the first thing they present with,” Julie Rodman, OD, MS, FAAO, associate professor at Nova Southeastern University, told PCON.

Barbara Caffery, OD, PhD, FAAO, who practices in Toronto and teaches at the University of Waterloo School of Optometry, said clinicians often may dismiss dry eye as a less important issue; however, it is of increased importance, especially when it impedes a patient’s daily function and quality of life.

Symptoms of autoimmune disease

Rheumatologist Lauren Kim, MD, in private practice in the Portland, Ore., area, outlined presenting symptoms of various autoimmune diseases.

She said the initial symptom of Sjögren’s syndrome is, “hands down, dryness, usually both in the eyes and mouth, although some patients complain of one before the other.”

She told PCON that systemic lupus erythematosus (SLE) is variable in terms of initial presentation.

“It could be a photosensitive rash, including the butterfly rash on the face; it could be hair loss; it could be renal failure, rarely hemoptysis, hematologic abnormalities and sometimes all of the above,” she continued. “Lupus is probably the most unpredictable of all of our diseases.”

Rodman added that patients severely affected by lupus can have chest pain and shortness of breath. Ocular presentation can include dry eye, conjunctivitis, episcleritis, scleritis, keratitis and optic neuritis, and in severe situations patients can have oculomotor abnormalities.

“The most urgent issue in SLE is probably infection,” Kim said. “They may be on strong immunosuppressive medications, putting them at higher risk.”

She added that optometrists may also see anterior uveitis and oral steroid-induced cataracts.

“Retinal diseases are more rare but can be seen,” she said, “such as vaso-occlusive retinopathy and, of course, toxic maculopathy from hydroxychloroquine.”

Rheumatoid arthritis (RA) is more predictable, Kim said.

“One would expect to see joint pain, typically polyarticular, typically starting in the small joints of the hands or feet, then going on to bigger joints. It’s usually bilateral and symmetric, with hours of morning stiffness,” she said.

Rodman said she sees RA regularly in her practice, and dry eye is common, while uveitis, episcleritis and scleritis may also occur.

Kim added that ocular infection is possible in patients with RA, “and should be checked, especially if patients are on strong immunosuppressive therapy. Cataracts would also be common in patients on long-term oral steroid therapy.”

While Crohn’s disease is usually first seen by a gastroenterologist, “ocular manifestations are fairly common in all of the seronegative spondyloarthropathies, including Crohn’s disease,” Kim continued. “Uveitis and episcleritis are the most common, and noninfectious conjunctivitis, blepharitis and optic neuritis can be seen.”

The ocular manifestations of inflammatory bowel disease (IBD) can present as primary, secondary or coincidental complications, according to Pelino.

Primary complications include uveitis, which may be anterior, intermediate or posterior; episcleritis, which is the most common manifestation; scleritis; and corneal disease such as keratopathy.

If uveitis is present, Pelino will ask if a patient has experienced any bloody stool, fever or cramps, especially in a patient between 15 and 35 years old.

Secondary ocular findings include vitamin A deficiency or postsurgical dry eye, cataract, glaucoma and scleromalacia, he said. The coincidental complications include conjunctivitis, corneal or marginal ulcers, and recurrent corneal erosions. Rare findings include optic neuritis, orbital inflammatory disease, retinal vascular occlusive disease and retinitis.

With IBD, the joints, skin, intestines, eye and peripapillary system can be affected, Pelino said.

Mathie said that patients with celiac disease will not have significant symptoms, especially early in the disease, “so it highlights the importance of a detailed case history that sometimes will include discussions about items that seem non-optometric, like diarrhea, bloating or stool characteristics.”

He said it is easier to find the multitude of symptoms that point to autoimmune disease in general, then the proper referral and testing can be initiated to determine specifically which disease is involved.

“Adults with celiac disease may have symptoms such as anemia, fatigue, arthritis, bloating, liver or biliary tract disorders, depression, migraines, missed menstrual periods and possibly even infertility,” Mathie said.

He noted that children are more likely to have symptoms than adults, and they may include chronic diarrhea, weight loss, fatigue, irritability, and delayed growth and puberty.

“First-degree relatives of patients with celiac disease should always be screened, even if they are not experiencing symptoms, as they have a one in 10 risk of developing the disease,” Mathie added.

Sjögren’s syndrome

Jennifer Coyle, OD, MS, FAAO, dean of the Pacific University College of Optometry, can speak about autoimmune disease from first-hand experience. She was recently diagnosed with Sjögren’s syndrome with the help of Doll.

Coyle said in an interview that she had the classic symptoms, such as dry eye and corneal erosions. At first, she assumed it might be computer-related or complications from laser refractive surgery.

“We are taught in optometry school that Sjögren’s is rare, but it’s diagnosed more often now because people are aware of the lifestyle and environmental effects and oral health manifestations,” Coyle said.

Mathie said symptoms can include dry mouth, with dryness or cracks at the corners of the mouth, and more severe dry eye findings, such as filaments, corneal epithelial defects and episcleritis.

However, patients with autoimmune disease often do not look sick, Doll said.

“Every patient I’ve seen that tests positive looks like your average person; they don’t look ill,” she said. “They tend to always carry water bottles if it’s Sjögren’s, which can be a good tip.”

Tear measurement tests and stains do not always match up with how severely the patient feels they are suffering, Caffery told PCON. A patient can have few symptoms and look terrible.

“Perhaps more complex are the patients who are suffering and not showing the signs. We have a lot to learn in dry eye disease,” she said.

Caffery recommended asking female patients with dry eye, a low Schirmer’s score and significant ocular staining about dry mouth, which correlates with Sjögren’s.

“Many times, the systemic disease that manifests in joints and vasculopathy is so extreme that they don’t acknowledge other parts of their disease like dry eye or mouth; those problems feel small,” she said.

Most of these patients are women fighting chronic fatigue, women that look but do not feel normal, Caffery added.

“They have to learn how to manage their lives with fatigue and dryness, and we can be essential in helping the patients understand the situation and helping rheumatology to understand the patient,” she said.

Diagnostic testing

Coyle said optometrists are in a position to order lab tests for autoimmune disease, which is also a way to build a practice.

“You become a part of an interprofessional team to manage your patients, including their systemic disorders,” she said.

Mathie’s practice has invested in training, marketing and technological purchases to diagnose and treat dry eye disease, including Sjögren’s. As a result, the number of Sjögren’s patients diagnosed in his clinic has increased dramatically.

Coyle and Doll recommend that optometrists use Bausch + Lomb’s Sjö Diagnostic Test in Sjögren’s syndrome suspects.

If the test is not covered by insurance, Doll said independent labs such as LabCorp and Quest can run the same diagnostics, and referring the patient for testing is fairly easy.

“The new proprietary markers, the earlier detectors, might not be covered by insurance, but the classic tests that they combine with it are,” she said.

When Kim sees patients with suspected Sjögren’s syndrome, she orders ANA, SSa and SSB antibodies.

For SLE, she orders antinuclear antibodies (ANA), anti-double stranded DNA antibody (anti-dsDNA), complements, SSa, SSB, and anti-Smith and RNP antibodies.

“Complete blood count (CBC) and comprehensive metabolic panel (CMP) are also important since there are many hematologic manifestations of SLE as well as concern for renal involvement,” Kim said. “Urinalysis complete with microscopic analysis is also important to assess for renal disease. Cell-mediated cytotoxicity (CMC) can also help detect autoimmune hepatitis.”

Kim said she orders rheumatoid factor and anti-cyclic citrullinated peptide (CCP) antibodies for RA and human leukocyte antigen (HLA)-B27 for Crohn’s disease.

Lab tests for celiac disease include Endomysial antibody IgA, tissue transglutaminase (tTG) IgA and total serum IgA, Mathie said.

“A referral to a gastroenterologist would be appropriate if celiac disease is suspected,” he said

“Other lab tests center on the inflammation associated with celiac disease,” Mathie continued. “There may be inflammation of the gallbladder and liver, increased liver enzymes and white cell counts, but the definitive and most accurate diagnosis is made following an upper endoscopy with direct observation and biopsy of the lining of the small intestine where microvilli are damaged in celiac disease.”

Management

“Today’s optometrists are comfortable not only in the diagnosis of ocular complications of autoimmune disease, but also in the treatment and management of these complications,” according to Joseph J. Pizzimenti, OD, FAAO, a faculty member at the University of the Incarnate Word, Rosenberg School of Optometry.

“Treatment may include conventional medical management, such as with corticosteroids, as well as counseling the patient about the importance of an anti-inflammatory, low-glycemic index and Mediterranean-type diet and lifestyle modifications such as smoking cessation and increasing physical activity,” he said in an interview.

Mathie recommends a diet that promotes hydration and limits sugar and omega-6 supplements, as they can promote inflammation.

Doll recommends 3,000 mg of omega-3 fatty acids daily, with each 1,000-mg capsule containing at least 600 mg of combined EPA and DHA. Marine sources, such as fish oil, are best, she said.

Because dry eye is so common in these groups, stressing proper blinking, using artificial tears and humidifiers, and limiting diuretics can be beneficial, Mathie added. Punctal plugs can also offer relief.

Restasis (cyclosporine ophthalmic emulsion, Allergan), Xiidra (lifitegrast ophthalmic solution, Shire) and autologous tears are beneficial in these situations, as is maximizing meibomian gland function through proper lid hygiene, warm compresses and lid treatments such as LipiFlow (TearScience), he said.

“Most importantly, these patients need to be monitored closely for the beginning or escalation of ocular sequelae from autoimmune disease,” Mathie said.

When Coyle found out she had Sjögren’s syndrome, she said she conducted exhaustive research on autoimmune disease.

“I read all the literature about leaky gut syndrome, specific syndromes that have a definitive cause and are autoimmune in nature, and I discovered that there are many ways to manage Sjögren’s with simple diet changes,” she said.

The biggest lifestyle trend in managing systemic disease is reducing inflammation in the body and shifting the focus from weight loss to wellness, Coyle said.

Changes to her diet helped tremendously, she said. She eliminated processed foods and white sugar, manages her salt intake and increased her intake of anti-inflammatory foods such as turmeric, cayenne pepper and ginger.

“If I stay close to the autoimmune protocol, I tend to have fewer symptoms, but this may not be the case for everyone,” Coyle said.

She encourages optometrists to become aware of the nutritional aspects of managing ocular symptoms.

Biologics

Biologics such as Humira (adalimumab, AbbVie) and Remicade (infliximab, Janssen) work to control the inflammation in patients with autoimmune disease, according to Pelino.

“I think these biologics are wonderful for the patient systemically, as well as for inflammation in the eye,” he said.

Pelino noted that treatment of ankylosing spondylitis patients with biologic agents directed against TNF- has been associated with a significant decrease in the number of anterior uveitis flares.

Given the high costs and limited long-term safety data, Pizzimenti said he does not routinely recommend biologics as first-line therapy for noninfectious uveitis; for those cases where biologics are indicated, he collaborates with fellowship-trained subspecialists in uveitis, rheumatology, immunology and gastroenterology.

Rodman said biologics can have quite a few side effects, “which is where our comanagement really fits in so that rheumatology, etc, knows what’s going on, and so do we.”

Pelino said perhaps the use of biologics will result in fewer ocular problems in these patients in the future.

Collaborative care most beneficial

Pizzimenti said optometrists should strive to practice full scope to provide a wide array of services for patients referred by nonophthalmic providers who wish to comanage.

“When it comes to effective comanagement, mutual respect, automatic return of each patient and a prompt, meaningful report to the other team members are the cornerstones,” he said. “Three decades of experience and research have shown that patients with chronic conditions benefit most from care that is collaborative among various professions and disciplines. Given the complexities of systemic immunomodulation, ODs need to work closely with internal medicine, rheumatology, immunology and even gastroenterology.”

If a patient with a diagnosed autoimmune disease comes in with episcleritis or uveitis, Pelino recommends speaking with the gastroenterologist, rheumatologist or primary care physician. Suggest that it could be a flare-up, he said, and that medication may need adjustment.

“Ask the physician what we should be doing as part of the team,” Pelino said.

Kim recommended that optometrists refer whenever they suspect systemic disease, “when the ocular disease is the heralding symptom. We frequently see referrals from ophthalmologists for patients with recurrent or bilateral anterior uveitis and almost always in cases of posterior uveitis where concomitant systemic disease is common. Good communication would be the most important aspect of a relationship between all of these providers. Sending each other copies of each visit would be helpful.”

One message Caffery hears from rheumatologists is how lucky optometrists are to be able to see the inflammation, the ocular surface, and the cells and flare in the anterior segment.

“We are glad to be heroic and fix vision, but it’s hard to manage chronic disease,” Caffery added. “Rheumatology doesn’t expect to cure, they expect to manage the disease. I think that’s a mentality for optometry: We need to learn to manage people who have chronic symptoms of discomfort in dry eye.” – by Abigail Sutton and Nancy Hemphill, ELS, FAAO

• References:
• Braun J, et al. Arthritis & Rheumatology. 28 July 2005;doi:10.1002/art.21197.
• Maciel G, et al. Arthritis Care Res. 2017;doi:10.1002/acr.23173.

• For more information:
• Barbara Caffery, OD, PhD, FAAO, practices in Toronto and teaches at the University of Waterloo School of Optometry. She can be reached at: dr.b.caffery@gmail.com.
• Jennifer Coyle, OD, MS, FAAO, is the dean of the Pacific University College of Optometry and a member of the PCON Editorial Board. She can be reached at: coylej@pacificu.edu.
• Tracy Doll, OD, FAAO, is coordinator for Pacific Dry Eye Solutions at Pacific University College of Optometry and an assistant professor and attending optometrist for third- and fourth-year students. She can be reached at: EyeDoll@pacificu.edu.
• Lauren Kim, MD, is in private rheumatologic practice in the Portland, Ore., area. She can be reached at: laurenhhkim@gmail.com.
• Brian E. Mathie, OD, FAAO, is an adjunct faculty member with the Ohio State University College of Optometry and clinic director at the Roholt Vision Institute. He can be reached at: bmathieod@aol.com.
• Carlo Pelino, OD, FAAO, is a professor at The Eye Institute at Salus University. He can be reached at: cpelino@salus.edu.
• Joseph J. Pizzimenti, OD, FAAO, is a faculty member at the University of the Incarnate Word, Rosenberg School of Optometry. He can be reached at: pizzimen@uiwtx.edu.
• Julie Rodman, OD, MS, FAAO, is an associate professor at Nova Southeastern University and a member of the PCON Editorial Board. She can be reached at: rjulie@nova.edu.

Disclosures: Caffery, Coyle, Kim, Mathie, Pelino and Pizzimenti report no relevant financial disclosures. Doll reports she is a dry eye consultant for Allergan and Shire. Rodman reports she is a speaker and consultant for CenterVue and Optovue.