Introduction to HLA-B27

HLA-B27 is a gene that provides instructions for making a protein called major histocompatibility complex, class I, B 27 (MHC Class 1 B 27). This protein plays an important role in the immune system by presenting antigens to T-cells. Approximately 6-8% of the general population carries the HLA-B27 gene, though prevalence varies among different ethnic groups. HLA-B27 positivity is closely associated with a group of inflammatory joint conditions known as seronegative spondyloarthropathies. The most well-known of these is ankylosing spondylitis, where up to 90% of patients test positive for HLA-B27. Other associated conditions include reactive arthritis, psoriatic arthritis, inflammatory bowel disease, and acute anterior uveitis. While the exact mechanism is unclear, it is believed that HLA-B27 may present self-antigens to T-cells, triggering an autoimmune response that leads to chronic inflammation in the joints and eyes.

HLA-B27 and the Eye

The main ocular manifestation of HLA-B27 is uveitis, which is inflammation of the middle layer of the eye called the uvea. Up to 50% of cases of acute anterior uveitis are associated with HLA-B27. Although HLA-B27 is strongly linked to acute anterior uveitis, which involves the iris and ciliary body, it can also be associated with intermediate, posterior and panuveitis.

The exact mechanism for how HLA-B27 leads to increased uveitis risk is not fully understood. One theory is molecular mimicry, where HLA-B27 is similar in structure to molecules found in the eye, leading to cross-reactivity of the immune system. Another theory suggests HLA-B27 misfolds and elicits an inflammatory response. Regardless of the mechanism, HLA-B27 positive individuals have a greatly increased lifetime risk for developing recurrent uveitis.

Types of HLA-B27 Uveitis

The most common type of uveitis associated with HLA-B27 is acute anterior uveitis, which involves inflammation of the iris and ciliary body in the front of the eye. Up to 50% of all cases of acute anterior uveitis are linked to HLA-B27 positivity [1]. Anterior uveitis leads to redness, pain, and blurred vision.

While anterior uveitis is most typical, HLA-B27 positive individuals can also develop inflammation involving the posterior segment of the eye, including intermediate uveitis, posterior uveitis, and panuveitis [2]. Posterior inflammation is less common but can lead to more severe visual complications if not treated promptly.

Symptoms of HLA-B27 Uveitis

The most common symptoms of HLA-B27 associated uveitis are:

• Acute onset of redness in one eye
• Eye pain and discomfort, often severe
• Blurred vision or reduced visual acuity
• Photophobia or increased sensitivity to light
• Tearing and discharge

Patients often describe a sudden onset of symptoms including severe pain, redness, and light sensitivity in one eye. Vision becomes blurred or cloudy. Discharge and tearing may occur as inflammation sets in. The symptoms arise rapidly and reach peak intensity over the course of a few days. Attacks often recur periodically in the same eye.

The acute anterior uveitis associated with HLA-B27 has a classic presentation but posterior uveitis involving the retina or choroid can also occur. Symptoms help differentiate anterior versus posterior inflammation. Vision loss, floaters, and photopsias point more to posterior segment issues.

In summary, the typical symptoms of HLA-B27 uveitis are unilateral red eye with blurred vision, pain, and tearing. The acute onset and recurrent nature helps differentiate it from other types of uveitis. Prompt diagnosis and treatment is key to prevent complications from repeated bouts of inflammation.

Diagnosis

Diagnosing HLA-B27 uveitis involves a comprehensive eye examination, medical history assessment, and laboratory tests. Ophthalmologists may use several methods to evaluate the type and severity of uveitis:

Slit lamp exam – This allows close inspection of the front structures of the eye. Signs of inflammation in the anterior chamber such as flair and inflammatory cells can be observed. The architecture of the iris and lens are also examined for abnormalities.

Intraocular pressure measurement – Increased pressure may indicate inflammation of the trabecular meshwork or steroid response. Low pressure can occur with severe inflammation.

Dilated pupil exam – Drops are used to open up the pupil so the ophthalmologist can thoroughly inspect the posterior segment with an ophthalmoscope. Active inflammation of the retina or choroid may be visible.

Optical coherence tomography (OCT) – This non-invasive imaging technique can reveal subtle changes in the retina and measure areas of macular edema.

Fluorescein angiography – A dye injected into the arm travels to the blood vessels in the eye. This allows detailed visualization of retinal vasculitis, vascular leakage, and macular edema.

Lab tests – HLA-B27 blood testing confirms the genetic marker. Complete blood count, inflammatory markers, syphilis testing, and x-rays may be ordered to rule out other potential causes of uveitis.

Treatment

Treatment for HLA-B27 uveitis focuses on controlling acute flare ups and preventing recurrent episodes of inflammation. The main treatments include:

• Topical corticosteroid eye drops such as prednisolone or dexamethasone are used to rapidly decrease inflammation and symptoms during an acute attack. High potency drops may be given frequently (up to every hour) upon onset of a flare up.
• Immunomodulatory medications can be used to reduce the body’s autoimmune response and prevent recurrent episodes of uveitis. Common options include methotrexate, mycophenolate mofetil, cyclosporine, and newer biologic agents like adalimumab or infliximab. These are often used along with low-dose corticosteroid drops to maintain remission.

According to research, “Treatment for HLA-B27 uveitis can range from local corticosteroids to immunosuppressive drugs, and now numerous studies have highlighted the benefits of tumor necrosis factor alpha inhibitors in the management of HLA-B27-associated uveitis” (Source)

The treatment plan is tailored to the individual patient based on the severity and recurrence pattern of their inflammation. The goal is to find the lowest effective doses needed to control the uveitis long-term.

Monitoring

Ongoing monitoring by an ophthalmologist is important for HLA-B27 uveitis patients to screen for potential complications and recurrent inflammation. According to the American Academy of Ophthalmology, patients should be examined 1-2 weeks after an acute attack and then every 3-6 months indefinitely if the condition is chronic. More frequent follow-up is required if ocular complications develop.

During monitoring exams, the ophthalmologist will perform a slit lamp exam to carefully inspect the anterior chamber for signs of recurrent inflammation. Intraocular pressure will also be checked to screen for steroid-induced glaucoma. Dilated fundus exam and optical coherence tomography may be done to check for cystoid macular edema and other posterior segment complications. Patients are instructed to contact their ophthalmologist immediately if symptoms of recurrent uveitis flare up between scheduled visits.

Regular monitoring aims to achieve quiescence of inflammation and prevent permanent vision loss from complications. Studies show that 60-90% of patients respond well to proper management and maintain 20/20 visual acuity long-term. However, ongoing adherence to treatment and follow-up care is imperative.

Complications

Chronic inflammation due to HLA-B27 uveitis can lead to several complications that threaten vision and eye health. The most common complications include:

Posterior Synechiae

Up to 40% of patients develop posterior synechiae, which are adhesions between the iris and lens [1]. These adhesions can permanently damage the drainage system and cause angle closure glaucoma.

Cataract

Around 20% of HLA-B27 uveitis cases result in cataract formation, particularly with repeated inflammation [2]. Cataracts cause blurred vision and eventual blindness if left untreated.

Glaucoma

Increased eye pressure is common in HLA-B27 uveitis. Glaucoma develops in up to 10% of patients and can lead to optic nerve damage and vision loss if uncontrolled [3].

Cystoid Macular Edema (CME)

Chronic inflammation can also result in CME, which is fluid accumulation in the macula causing blurred central vision. Regular eye exams are key to detecting CME early.

Prognosis

With timely diagnosis and proper management of HLA-B27 associated uveitis, the prognosis for vision is generally good. Studies show that with consistent steroid and immunomodulatory treatment to control inflammation, most patients can maintain useful vision and experience minimal complications.

According to a 10-year study published in Ocular Immunology and Inflammation, 95% of HLA-B27 positive uveitis patients achieved complete remission or only rare episodic inflammation when treated with systemic immunosuppression along with steroid eye drops. The study concluded that recurrent HLA-B27 anterior uveitis responds well to therapy and monitoring.

Patients need to work closely with their ophthalmologist for regular exams and screenings to detect recurrences early. With vigilant monitoring and treatment compliance, most can retain 20/20 vision despite having a chronic uveitis condition.

Conclusion – the importance of recognizing HLA-B27 uveitis and controlling inflammation

HLA-B27 associated uveitis can lead to significant ocular complications and vision loss if left uncontrolled. However, with prompt diagnosis and proper management, the prognosis for maintaining good vision is favorable. It is critical for both patients and physicians to be aware of the connection between HLA-B27 and uveitis.

Patients who test positive for HLA-B27 should have regular dilated eye exams to screen for signs of uveitis, even in the absence of symptoms. At the first sign of inflammation, aggressive treatment is needed to eliminate active disease and prevent recurring attacks. Though challenging to manage, chronic uveitis in HLA-B27 patients can typically be well-controlled with corticosteroid therapy and secondary immunosuppressive medications as needed.

Close monitoring for elevated eye pressure, cataracts, macular edema and other complications is also essential. Early intervention with surgery may be required in some cases. With a tailored treatment approach and ongoing care, most HLA-B27 positive patients can achieve lasting remission and preserve their vision.

Medical Disclaimer

The information in this video is not intended nor implied to be a substitute for professional medical advice, diagnosis or treatment. All content, including text, graphics, images, and information, contained in this article is for general information purposes only and does not replace a consultation with your own doctor/health professional