It may be best to refer to an ophthalmologist who specializes in inflammatory eye diseases when managing patients with spondyloarthritis (SpA) who have uveitis. However, many rheumatologists today face significant barriers because there is currently a lack of available uveitis expert consultants, according to uveitis specialist Jae Kim, MD, an Associate Professor in Ophthalmology at Vanderbilt Eye Institute, Nashville, Tennessee.

“There are barriers in terms of time and availability.  There is a problem in terms of access and not enough care providers,” Dr Kim said in a telephone interview with Rheumatology Advisor.  “Only a small fraction of patients have severe disease and have to be sent to a uveitis specialists, but [when consultation with a specialist is needed] there are only a few. There are about 50 to 100 uveitis specialists in the country.”

Uveitis is the inflammation of the middle layer of pigmented vascular structures of the eye (the uvea).  The uvea includes the iris, ciliary body, and choroid.  Diseases associated with uveitis include ankylosing spondylitis (AS), Behcet’s syndrome, cytomegalovirus retinitis, herpes zoster infection, histoplasmosis, Kawasaki disease, multiple sclerosis, psoriasis, reactive arthritis, rheumatoid arthritis, sarcoidosis, syphilis, toxoplasmosis, tuberculosis, ulcerative colitis and Vogt Koyanagi Harada’s disease, according to the National Institutes of Health.


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Uveitis can be separated into three types based on its clinical features – anterior uveitis, intermediate uveitis and posterior uveitis.  These conditions can overlap, and those cases are classified as pan uveitis. 

A French study that included 902 patients with SpA (61% men) with a mean age of 45.3 years found that uveitis prevalence was 32.2%.2 The study showed that factors independently associated with uveitis were HLA–B27 positivity (adjusted odds ratio of 2.97) and disease duration (adjusted odds ratio of 1.28).

As many as 25% of patients with AS may have uveitis.  Early referral and treatment are important for lowering morbidity associated with disease progression.  Rheumatologists, after taking a careful history and physical exam, and conducting other routine laboratory tests, should consider referral to an ophthalmologist to establish optimal treatment.  

“You are dealing with a problem that potentially is very severe, but [severe debilitating disease, including blindness] is not common,” said Dr Kim.  “This makes referring every single patient with a rheumatologic condition problematic because most of them you are going to be referring are not going to have any severe problems at all.  So the challenge is that, yes, it can lead to blindness but it is very uncommon.”

He said it is important that rheumatologists explain to their patients why potential blindness as a side effect of severe untreated uveitis cannot be ignored.  He said that creates another barrier for rheumatologists because it becomes time consuming in educating and counseling patients with SpA about their risk for uveitis.

Working in Collaboration

“[Uveitis] should be co-managed by a rheumatologist and an ophthalmologist.  It [ideally should be an ophthalmologist] who specializes in it, but there are not many who specialize in it, so a general ophthalmologist should be co-managing,” said Dr Sergio Schwartzman, MD, who is an Associate Attending Rheumatologist as the Hospital for Special Surgery and an Associate Professor, Weill Cornell Medical College, New York, New York.  

He said because uveitis may occur in patients with AS, juvenile rheumatoid arthritis, Behcet’s disease, and all of the HLA B-27 associated seronegative SpA, collaboration between rheumatologists and ophthalmologists must be ongoing.  He said that ophthalmological examination can actually quantify uveitis by counting cells that reflect disease activity.  Dr Schwartzman said anterior uveitis tends to be mild and it is treated mainly with topical agents.

“There are different types of the disease,” Dr Schwartzman said in a telephone interview with Rheumatology Advisor.  “Anterior uveitis is treated with topical steroids and cycloplegic agents. For intermediate and posterior uveitis, we use systemic medications, corticosteroids, methotrexate, mycophenolate, and cyclosporine.  If they work, that is all we use.”

He said for those who fail therapy the next step is to try a biological agent, such as adalimumab and infliximab.  Adalimumab has been the most studied and it has shown significant benefits in patients who have uveitis.  One study that included 88 patients showed that infliximab could induce a high rate of complete clinical remission in recalcitrant uveitis and was well tolerated by most patients.3  The study showed that 72 patients (81.8%) achieved clinical remission with infliximab and 42 patients (58.3%) required additional immunomodulatory medications.

“There has been the completion of trials with adalimumab which have shown dramatic improvements compared to the placebo arm,” said Dr Schwartzman.

Some of the treatments may result in an increased risk for cataracts and glaucoma, so while clinicians have a growing armamentarium, they are still limited by the risks and benefits associated with topical corticosteroids, prednisone, steroid-sparing immunosuppressive agents, and biologics.

“All these medications have potentially severe side effects. Topical corticosteroids can cause cataract and glaucoma. Prednisone causes a host of side effects including weight gain, osteoporosis, diabetes, hypertension, and heart disease. Steroid-sparing agents are associated with liver toxicity and anemia, and often cause stomach upset and nausea. Biologics can cause severe allergic reactions, increase infections, and potentially blood cancers years later,” said Dr Kim.

Disclosures

Dr Schwartzman is a consultant for AbbVie, Amgen, Genentech, Hospira, Pfizer, UCB, and XianJanssen.

References

1.  National Institutes of Health National Eye Institute (NEI) Website. Last updated online August 2011. Accessed May 10, 2016.  Source code.

2.  Canouï-poitrine F, Lekpa FK, Farrenq V, et al. Prevalence and factors associated with uveitis in spondylarthritis patients in France: results from an observational survey. Arthritis Care Res (Hoboken). 2012;64(6):919-24.

3.  Kruh JN, Yang P, Suelves AM, Foster CS. Infliximab for the treatment of refractory noninfectious Uveitis: a study of 88 patients with long-term follow-up. Ophthalmology. 2014;121(1):358-64.