Diseases and Conditions RheumDoctor Learning Center

What is the Link Between HLA-B27 and Uveitis Explained

February 15, 2024

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

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Diseases and Conditions Journal Club

Exploring New Ways to Keep ANCA Vasculitis in Check

February 12, 2024

ANCA Vasculitis is a rare but serious condition where the body’s immune system mistakenly attacks its own blood vessels, causing inflammation. This falls into a group of illnesses known as autoimmune diseases. Each year, about 3 out of every 100,000 people get diagnosed with it, mainly those who are between 50 and 70 years old. One of the biggest hurdles in treating ANCA Vasculitis is preventing it from coming back, which calls for some creative solutions to keep the disease in remission.

A groundbreaking study titled “Maintenance of Remission of ANCA Vasculitis by Rituximab Based on B Cell Repopulation Versus Serological Flare: A Randomised Trial” sheds light on a novel tactic for tackling this challenge. It zeroes in on the drug Rituximab, which helps calm the immune system’s overreaction that’s at the heart of this condition.

Why Focus on Rituximab for ANCA vasculitis?

Rituximab targets B cells, which play a big part in the body’s overactive immune response seen in ANCA Vasculitis. Doctors usually give this medication when they notice B cells coming back after treatment or when there’s a spike in ANCA levels, which can mean the disease is flaring up.

The Two Approaches Explained

The study looks at two ways of deciding when to give extra doses of Rituximab:

The first way is based on whether B cells are starting to show up again after being knocked down by treatment.
The second way relies on monitoring ANCA levels in the blood, even if the patient isn’t showing any symptoms, to catch any potential flare-ups.

What the Study Found

This research offers new insights by comparing these two strategies. It found that using Rituximab based on the return of B cells leads to fewer relapses than waiting for ANCA levels to rise, over an average follow-up of 4.1 years. This result supports the idea that tailoring treatment to each patient’s specific situation can really make a difference in managing complex autoimmune diseases like ANCA Vasculitis.

However, both methods have their challenges, such as predicting disease flares accurately and the feasibility of frequent testing. The study also closely monitored safety, noting similar side effects in both groups but a slightly higher risk of serious issues related to COVID-19 in those treated based on B cell repopulation.

Personalized Care for ANCA Vasculitis is Key

The findings highlight that there’s no one-size-fits-all answer to treating ANCA Vasculitis. Some patients might do better with one approach over the other, emphasizing the importance of customizing treatment plans.

Looking Ahead

This study is a significant step forward in improving how we maintain remission in ANCA Vasculitis. It encourages us to keep asking questions and searching for better ways to care for those affected by this disease.

Even though the medical terms might sound complex, they’re part of understanding how to best manage ANCA Vasculitis. As we work to unravel these complexities, it’s crucial to keep learning, adapting, and showing compassion for those living with this condition.

This research marks an important progress in our journey, and we’re committed to sharing the latest and most accurate information to help make informed health decisions. Our dedication to understanding and empathizing with your health challenges stands firm.

References

Zonozi R, Cortazar FB, Jeyabalan A, Sauvage G, Nithagon P, Huizenga NR, Rosenthal JM, Sipilief A, Cosgrove K, Laliberte KA, Rhee EP, Pendergraft WF 3rd, Niles JL. Maintenance of remission of ANCA vasculitis by rituximab based on B cell repopulation versus serological flare: a randomised trial. Ann Rheum Dis. 2023 Dec 11:ard-2023-224489. doi: 10.1136/ard-2023-224489. Epub ahead of print. PMID: 38123922.

Medical Disclaimer

Patient Advocacy

The Methotrexate Shortage – What Can We Do Now?

January 30, 2024

Introduction

Although other newer biologics are available, methotrexate remains a cornerstone treatment for rheumatoid arthritis today.

When the Shortage Began

The current shortage of methotrexate began in late 2022, according to the American Society of Health-Systems Pharmacists (ASHP). It was primarily caused by manufacturing delays and supply chain issues impacting several major methotrexate suppliers, including Pfizer, Teva, and Fresenius Kabi. This led to intermittent supply disruptions and backorders for both the injectable and oral forms of the drug.

The methotrexate shortage has been further exacerbated by increased demand for the drug during the COVID-19 pandemic. Rheumatoid arthritis patients have been seeking additional prescriptions to manage worsening pain and inflammation while staying home. This spike in demand made the limited supply even more scarce for those dependent on methotrexate.

Expected Duration of the Methotrexate Shortage

The exact end date of the methotrexate shortage is still unclear. Manufacturers have indicated the shortage could potentially last through much of 2023, depending on how quickly they can resolve the underlying manufacturing and supply issues.

According to the American Society of Health-System Pharmacists (ASHP), the shortage is expected to continue through at least June 2023 for injection formulations from suppliers like Fresenius Kabi and Hikma [1]. The timeline is less certain for oral formulations, with some manufacturers like Teva unable to provide estimates on resolution.

Ultimately, the duration of the methotrexate shortage is highly dependent on pharmaceutical companies bringing their manufacturing capabilities back to normal levels. Some progress is being made, with Accord Healthcare restarting production in late 2022 after facility issues [2]. However, until all manufacturers have fully resumed stable methotrexate production and replenished inventory, the shortage is likely to persist.

Impacts on Rheumatology Patients

The methotrexate shortage has had significant impacts on rheumatology patients who rely on the drug to manage their conditions. Many patients are reporting difficulty filling their methotrexate prescriptions as pharmacies face short supply. This forces some patients to skip doses or take smaller doses than prescribed, which can lead to increased joint pain, stiffness, and swelling as their condition flares up. One survey found that 76% of pediatric cancer centers had patients miss or delay methotrexate doses due to the shortage.

In some cases, rheumatology patients may be forced to switch to more expensive biologic drugs instead of methotrexate to manage their symptoms. However, these drugs can cost thousands of dollars per dose, resulting in much higher out-of-pocket medical expenses. The financial strain adds further hardship for patients already dealing with increased joint inflammation and pain from the lack of methotrexate.

Alternatives During the Shortage

With the methotrexate shortage, rheumatology patients and their doctors need to explore alternatives to manage symptoms. Some options include:

Other DMARDs (disease-modifying antirheumatic drugs) like sulfasalazine or leflunomide may be substituted, depending on the patient’s condition. These work in a similar way to methotrexate and can help control inflammatory arthritis.

Biologics like Humira (adalimumab) or Enbrel (etanercept) target specific parts of the immune system. They can be very effective for rheumatoid arthritis but are more expensive.

Corticosteroids like prednisone reduce inflammation and pain quickly. But long-term use can cause side effects, so they are typically used as a bridge until other treatments start working.

Lifestyle measures like rest, exercise, diet, and stress management may also help patients manage symptoms during the shortage. But they should not replace disease-modifying medications.

Ultimately, it is important to have a conversation with your physician to discuss your personalized treatment plan.

Efforts to Resolve the Methotrexate Shortage

There are ongoing efforts to improve the methotrexate supply and end the shortage as soon as possible. Major manufacturers like Teva and Mylan have been working to resolve the issues that led to the shortage at their facilities (source). Teva restarted production at one facility in November 2022, which has helped stabilize the supply somewhat.

The FDA has also worked to increase available supply by reaching agreements to import methotrexate from abroad. The regulatory agency is engaging with manufacturers around the world to facilitate greater imports to meet US demand (source).

In addition, the FDA has allowed compounding pharmacies to help close the gap by producing compounded methotrexate products. While compounded drugs carry greater risk, this temporary measure expands supply while issues limiting manufacturing persist.

Preparing for Future Shortages

To prevent shortages in the future, steps must be taken to improve the resilience of the pharmaceutical supply chain. According to the AMA, diversifying suppliers is key to avoiding disruptions when a single company faces manufacturing issues (AMA, 2023). The FDA also recommends increasing stockpiles and reserves of essential medications that are at risk of shortage (Shuman, 2020). Finally, end-to-end supply chain transparency and information sharing between manufacturers, wholesalers, pharmacies, and regulators can identify potential shortages earlier and mobilize responses (Pharma News Intel, 2023).

By taking a proactive, collaborative approach, the pharmaceutical industry can build a more resilient supply chain and ensure patients have access to vital medications during public health emergencies. Regulators must also be empowered to act quickly when shortages arise to minimize disruptions to patient care.

Conclusion

In summary, the methotrexate shortage that began in late 2022 has had significant impacts on rheumatology patients who rely on this critical medication. Patients have struggled to access their usual methotrexate doses, resulting in increased symptoms and reduced quality of life. Rheumatologists have worked hard to find alternatives, but options are limited. This highlights the importance of ensuring consistent supply and production of key medications.

Solutions require collaboration across the pharmaceutical industry and government regulators. Manufacturing and supply chain improvements are needed to prevent future shortages and ensure access. With luck this shortage will be resolved quickly, but work remains to build a more resilient prescription drug supply system.

There is hope the manufacturers will resolve the issues causing this shortage in the coming months. However, the impacts have shown the vulnerability of relying on just a few suppliers for essential medications. Rheumatology patients and providers will continue advocating for reliable access to the treatments they need.

Medical Disclaimer

This information is offered to educate the general public. The information posted on this website does not replace professional medical advice, but for general information purposes only. There is no Doctor – Patient relationship established. We strongly advised you to speak with your medical professional if you have questions concerning your symptoms, diagnosis

Overcoming Inflammation When to see a rheumatologist

How to prepare for your rheumatology consultation

October 3, 2017

Rheumatologists treat well over 100 different types of diseases. These diseases are complex and affect many organ systems. Diagnosing a rheumatic disease is like solving a complex puzzle. Every first consultation includes a detailed history, a physical examination, and a review of past blood work, x-rays, and documentation from your other doctors. All these help your rheumatologist solve the puzzle.

Preparing for a rheumatology consultation is a bit like preparing for a meeting with your accountant. You want everything organized in advance: W-2, investment income statements, IRA/pensions distributions, child care costs, etc. You want everything neatly laid out in advance, so that your consultation is as productive as possible.

Laying the groundwork

Make sure your rheumatologist has all the information at his or her disposal well before your appointment.

The progress note from your referring physician. What is the question that’s being asked?
Your primary care physician’s (PCP) last progress note.
The results of any blood tests.
The results of any x-rays or any other imaging.
If you had a biopsy that relates to your symptoms (e.g., skin biopsy, kidney biopsy, lung biopsy), your rheumatologist will want to see the pathologist’s interpretation.
If you are transferring care from another rheumatologist, your current rheumatologist will definitely want to see that information.

Bring an updated list of your medications and allergies

It’s always a good idea to have a written updated list of all your medications and allergies. Make sure you bring this along to your first consultation. Do not assume that your PCP’s updated medication list is up-to-date. Some people see more than one doctor and they’re all making changes independently.

Anticipate questions your doctor may ask

Rheumatologists certainly have access to high specialized blood tests and imaging, but the medical history is by far the most important part of the consultation. Before your visit, try to expect some questions your doctor may ask and then write them down. Here are a few that may help you get started.

When did you first notice something was wrong or had changed?
Describe your symptoms.
Has this ever happened before? If so when?
Do the symptoms come and go or are they continuous?
Is there a particular time of day where they are worse?
What makes your symptoms worse? What makes them better?
Have you taken any over-the-counter medications for your symptoms? If so, which ones and did they help?
Do you think you have other symptoms besides joint or muscle pain that seem connected?
Have your symptoms caused you to make changes to your daily routine?

Anticipate questions you may have for your doctor

Based on what you know, what could be causing my symptoms?
What tests do I need to have done to help decide what my diagnosis is?
Are there any symptoms that I should be looking out for?
What kind of interventions could I do now, to help ease some of my symptoms?
What kind of activities should I avoid at this time? (e.g, get pregnant, run a marathon, prolonged travel, etc.)

Actively listen and participate

You may feel overwhelmed when your doctor is giving you a new diagnosis, let alone giving you a complex set of recommendations. You’re not alone. A study looked at how much information (when prescribing a new medication) patients retained after their doctor’s appointment. They found that only 64% of people were able to recall all the information that they discussed during the visit[1]. Not bad, but not great.

We know that recall of information improves health outcomes in people suffering from chronic diseases like rheumatoid arthritis and lupus. Another study looked at aspects of doctor-patient communication that lead to higher recall. They found that active patient engagement and explicit conversations about medications improved recall.[2] Here are a few tips about becoming a better active listener.

Pay attention
Show that you’re listening
Provide feedback
Defer judgement
Be candid, open, and honest in your response.

You may also want to write things down in a journal (highly recommended) or maybe you may want to bring an advocate to your consultation. This could be a trusted friend or family member.

Conclusion

Being ready for your appointment, active listening, and asking questions to understand your symptoms is central to not only making the most of your rheumatology consultation but also, becoming an empowered patient.

Please follow this link to request a rheumatology consultation.

[1] Tarn DM, Flocke SA, New prescriptions: How well do patients remember important information? Fam Med. 2011 Apr; 43(4): 254–259.

[2] Richard C, Glaser E, Lussier MT. Communication and patient participation influencing patient recall of treatment discussions. Health Expect. 2017 Aug; 20(4): 760–770.

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Diseases and Conditions Featured

Guide to living with rheumatoid arthritis: Part 2

August 2, 2017

People that suffer from rheumatoid arthritis need to exercise on a daily basis, eat healthy, and find ways to reduce stress in their lives

If you missed Part 1 of Guide to living with rheumatoid arthritis please follow the link. In part 1 we covered the basics: what is rheumatoid arthritis, the cause, symptoms, diagnosis, and treatment. In part 2, I’ll be covering how rheumatoid arthritis (RA) can affect your day-to-day living, habits that worsen RA, exercise, food, and stress reduction techniques. Without further adieu, here is Part 2 of the Guide to living with rheumatoid arthritis. I hope you enjoy!

How will rheumatoid arthritis affect my life?

Rheumatoid arthritis changes your life. Depression, anxiety, feeling overwhelmed, these are all emotions that are perfectly natural when you get diagnosed with rheumatoid arthritis or any chronic illness. These should improve with time as you learn more about the illness and with the help of family and friends.

The Arthritis Foundation is a national non-profit organization who’s mission is to help, “conquer everyday battles through life-changing information and resources, access to optimal care, advancements in science and community connections. Our goal is to chart a winning course, guiding families in developing personalized plans for living a full life – and making each day another stride towards a cure. We also publish Arthritis Today, the award-winning magazine that reaches 4.2 million readers”.

They definitely are a good group to check out and they have chapters across the country.

The physical aspect

Other than, psychological and emotional impact of the illness, there is also the physical part. There will be good days and bad days. It’s very important to work closely with your rheumatologist when you suffer from RA. It is of utmost importance to go into remission as quickly and safely as possible. There are many medications used to treat RA. Some may work for you and some may not. By working together, you can help your rheumatologist tailor the best possible treatment plan for you.

The goal is to get you back doing what you used to do with the least amount of limitations as possible.

Be aware, even in the best of situations, expect flares. Stress, infections, the weather, and hormonal changes can precipitate a flare. Another goal is to make flares a rare event. Not the norm.

The financial aspect

Finally, although no one likes to talk about it, another important impact that rheumatoid arthritis has on your life is its impact on your wallet. Rheumatoid arthritis is expensive. Frequent doctor’s appointments. Not only do you need to see your rheumatologist on a regular basis, but you may also need to see other specialists such as an ophthalmologist, nephrologist, pulmonologist, etc. So many co-pays.

Medication costs can get very expensive. Even with health insurance the out-of-pocket costs can be enormous. In my clinic, this is a daily problem. In fact, I’m lucky to work in a practice that has a dedicated patient advocate that helps my patients find solutions to get access to care without breaking the bank. I call her my “health insurance whisperer”. She kindly agreed to impart some of her knowledge in Part 3 of Guide to Living with Rheumatoid Arthritis. It’s going to be a real treat!

Other costs

These medications tend to have a long list of potential side effects. These require routine bloodwork. Yet another co-pay.

Lost work days. The less you work, the less you make.

Time. One of the most, and arguably THE most important financial costs.

I do realize that I seem to be painting a very bleak picture, but I want to make it very clear that YOU are in control. Your experience with RA will depend on how much you let it affect you. It will change you for sure but not conquer you.

Will I be able to work? How do I tell my boss?

I won’t lie. Rheumatoid arthritis can lead to work disability, abseeteeism, and presenteeism (at-work productivity loss) at a high cost to you but also to your employer. You’ve had the conversation with your family and friends but now it’s time to tell your boss.

First, you’re not legally required to disclose your RA to your employer. However, as an employer myself, I would appreciate it if my employee would disclose this information. What if your job requires heavy lifting or standing around for a very long time? Maybe I can help you and re-arrange your work duties to better accommodate you? Maybe you need a better chair or a better mouse? Every situation is different. Not everyone with RA has horrible disease but on the flip side not everyone’s employer is accommodating.

There’s also the situation with doctor’s appointments. Most people with RA see their rheumatologist every 3 to 6 months for regular checkups. Some people may need medications that only come as infusions. These infusions are given in clinic and last between 1.5 hours to half a day. That’s more time off work.

By informing your employer, you are entitled to certain legal rights, as outlined in the Americans with Disabilities Act and the Family and Medical Leave Act. For more information, please click on the following link[1].

Ultimately, the choice to tell your boss or not is yours. You are in control.

What habits worsen rheumatoid arthritis?

Smoking

At this point, I hope everyone understands that smoking is a terrible habit associated with a multitude of negative health outcomes. But did you know that smoking can also predispose people to develop antibody positive rheumatoid arthritis (seropositive)?

Costenbader et al. prospectively studied 103 818 women from 1976 to 2002. Of those women 680 developed rheumatoid arthritis. The researchers found that both past and current cigarette smoking was associated with a 40% increased risk of developing seropositive rheumatoid arthritis. Here are some of the other findings:

Increasing duration and intensity of cigarette smoking increases the risk of RA.
Greater than 10 pack years of smoking increases the risk of RA in a dose-dependent way.
It takes about 20 years of smoking cessation for the risk to return to the “never smoker” category.[2]

What if you already have rheumatoid arthritis?

Does smoking have any impact on active rheumatoid arthritis? Anecdotally, it’s a lot more difficult to control rheumatoid arthritis when someone smokes cigarettes. We end up having to cycle through more medications and use more medications at high doses. However, when you think about it, it makes logical sense.

The current paradigm of RA pathogenesis is that people with certain genetic risk factors first are exposed to environmental triggers that cause local inflammation. These people then produce autoantibodies and with time some of these people go on to develop full-blown rheumatoid arthritis. Cigarette smoking is thought to be one of these triggers by causing local inflammation in the lungs[3].

If someone already has RA and continues smoking, well that’s like trying to put out a fire with gasoline. You’re trying to put out the fire with DMARDs but you’re also adding to the fire by smoking cigarettes.

Another great reason to stop smoking when diagnosed with RA, is the fact that rheumatoid arthritis is well-known to increase the risk of cardiovascular disease.[4] Other traditional cardiovascular risk factors include high blood pressure, high cholesterol, diabetes, obesity, and physical inactivity. This brings me to my next point, “not moving”.

Not moving

Sedentary behavior is defined as any waking behavior characterized by an energy expenditure of ≤ 1.5 METs and a sitting or reclining posture. It is associated with poor health outcomes in rheumatoid arthritis. Although adopting a sedentary lifestyle won’t necessarily directly cause increased disease activity, this lifestyle can worsen muscle density, functional disability, bone mass, and cardiovascular risk.[5]

Everyone knows that life can get really busy sometimes, and going out to the gym sometimes is the last thing on your “to-do” list. Believe me, I don’t have a gym membership because getting into my car, driving to the gym, changing into workout gear, hopping on a boring treadmill, changing back into my regular clothing, and driving back home is the last thing I want to do after a long day at work.

But being active doesn’t necessarily mean going to the gym. A 30 minute walk around your neighborhood 5 days week is enough. Does walking sound boring? How about catching up on your reading while strolling about. Amazon has a ton of audiobooks via Audible. This is NOT affiliate marketing. I simply use this service on regularly during my daily walks. I walk at least 30 minutes a day AND read about a book a week. Win-win!

Now if you tend to forget to get active and need a little nudge to get you going, check out these free IFTTT recipes I made to help you stay active 30 minutes a day. You need to have a Fitbit, cell phone, and an IFTTT account (which is free) for it to work.

Periodontal disease

In recent years researchers have found a correlation between rheumatoid arthritis and periodontal disease more specifically Porhyromonas gingivalis.[6] Now the question is whether treatment of periodontal disease have any effect on rheumatoid arthritis? The answer is yes. A recent systematic review meta-analysis showed that there was a reduction in DAS 28 (this is a scale that we use to measure RA activity) in patients with rheumatoid arthritis after periodontal treatment.[7] Interestingly, treatment with DMARDs does not improve periodontal disease in people with rheumatoid arthritis.[8]

To keep up with good oral health, the American Dental Association (ADA) recommends brushing your teeth twice a day for two minutes and flossing once a day. They also recommend eating a healthy diet, limiting snacks, and of course, regular dental check-ups.[9]

Which exercises are safe with rheumatoid arthritis?

This is a very frequent question. What exercises are “good” and which exercises are “bad”. Personally, I don’t think that there are any good or bad exercises for rheumatoid arthritis. What really matters is whether you are you moving. You should try being active for about 30 minutes a day. Choose an activity that you enjoy and stick with it. If someone tells you swimming is excellent for RA but you really don’t like swimming, chances are you won’t stick with the program. Be active in a way that brings you joy. Here are some examples.

Walking
Swimming
Yoga
Tai chi
Jogging
Rowing
Etc

Have fun!

What types of food should I eat with rheumatoid arthritis?

This is a very common question yet there is very little quality evidence-based research about this topic. Most studies with robust quality controls focus on cardiovascular disease as opposed to rheumatoid arthritis. There is very little quality evidence to support a specific diet for RA.

What is Epigenetics?

Everyone is born with genes. Some of these genes are active and some remain dormant. Your genotype is the entire makeup of your genes. Your phenotype is the result of how your genetic material is expressed. For example, you may have the genes for blue eyes and brown eyes. If the genetic material for brown eyes is dominant, you’ll have brown eyes.

This is where it gets really interesting. Over the course of your lifetime, some of your genes are turned on and off. This is influenced by factors like aging, the environment, and lifestyle. Epigenetics is the study of how genes are turned on and off based on external influences.

Epigenetic changes can be good but can also cause harm. We think that some of these changes can result in autoimmune diseases. It’s important to remember that epigenetics is in its infancy. Researchers still are not 100% sure how this happens, let alone, how to specifically manipulate the environment to cause favorable epigenetic change.

What types of foods are good for people with rheumatoid arthritis?

First, listen to your body. If you find that your arthritis worsens when you eat nightshades, then stop eating nightshades. Look for patterns. Journaling is helpful in finding these patterns.

Since there isn’t great data supporting a specific diet for RA, I typically recommend a diet that is good for overall health. For this I recommend adhering to the principles of the Blue Zone Project, more specifically the Power 9. The Blue Zones Project initially began as a research project funded by the National Geographic. They sought to find regions in the world where people tend to live to 100 years of age and be healthy. They identified 5 zones:

Ikaria, Greece
Okinawa, Japan
Ogliastra region, Sardinia
Loma Linda, California
Nicoya Peninsula, Costa Rica

All these regions have very different cultures and geography, yet they all live by these 9 common attributes. They called them the Power 9.

Move Naturally

People that live to 100 years don’t necessarily run marathons or go the gym. They are always on the go and they move naturally. For example, they tend a garden, they walk to the market, and they use stairs instead of the elevator.

Purpose

People that live in the Blue Zones live with purpose. They wake up every morning, and they know “why I wake up in the morning”. Having a clear purpose in life can add an extra 7 years of life expectancy.

Down Shift

We all know that stress can cause inflammation. I often see people in my clinic who’s rheumatoid arthritis was in perfect control until something really bad happened, like a divorce, job loss, or a death in the family. Chronic stress leads to chronic inflammation. People in the Blue Zones develop daily habits to help reduce stress.

80% Rule

The Japanese have a saying “Hara hachi bu”. This is a mantra that Okinawans say before every meal, reminding them to stop eating when they feel about 80% full. There is a delay between feeling full and actually being full. When you feel 80% full, you are actually full. So if you stop eating when you feel full, you are overeating. People living in the Blue Zones tend to eat their largest meal at breakfast and their smallest meal at dinner.

Plant Slant

Although not all regions of the Blue Zones eat meat, their diets all mainly consist of fresh veg and beans. Lot’s of beans: fava, soy, lentils, etc. They eat meat very sparingly and servings are small, “about the size of a deck of cards”.

Wine @ 5

Thank goodness for this one! People in the Blue Zones, except for Adventists, drink alcohol moderately and regularly. Typically, they drink 1-2 glasses of wine per day with friends and family at the end of the work day. They found that people who drink regularly and moderately tend to live longer than those who don’t.

Belong

Almost all people who live until 100 tend to belong to some sort of faith-based community. They found that attending a service 4 times a month can add up to 4 – 14 years of life expectancy.

Loved Ones First

People living in Blue Zones tend to live close to their families. It’s common to have children, parents, and grandparents living under the same roof. They also tend to commit to a life partner.

Right Tribe

People in the Blue Zones keep strong social networks. Not only are these social strong, but they also foster healthy behaviors. Women in Okinawa create “moais” early on in life. These are groups of 5 friends that are completely committed to each other for life.

Does stress affect rheumatoid arthritis?

Psychological stress can trigger RA flares. A recent study looked at 274 people with RA. They found that the most frequent reasons for joint symptoms were psychological stress/mood disorder (86.1%) followed by infection.[10] Other studies have also shown similar [11] findings and I do regularly see this in clinic.

Techniques to reduce stress

Everyone experiences stress in a different way and everyone has different stress thresholds. When it comes to the best way to reduce stress in people with rheumatoid arthritis, well the data is very poor. There are a many studies that look at different methods but they have poor quality standards.

The Mayo clinic has a page on their website dedicated to stress management and techniques[12]. It’s quite good. Some techniques include:

Autogenic relaxation
Progressive muscle relaxation
Visualization
Deep breathing
Massage
Meditation
Tai chi
Yoga
Biofeedback therapy
Music and art therapy
Aromatherapy
Hydrotherapy

Try a few and see what works for you. Remember, consistency is key.

Conclusion

Thus concludes Part 2 of a Guide to living with rheumatoid arthritis. In part 3 I’ll be covering the financial aspect of rheumatoid arthritis with some help from my “health insurance whisperer”. Since you are reading this article, there’s a good chance you just were diagnosed with rheumatoid arthritis. Now the question that I know must be on your mind, “How am I going to pay for these expensive medications?”

Medical Disclaimer

References

[1] https://www.dol.gov/general/topic/benefits-leave/fmla

[2] Costenbader KH, Feskanich D, Mandl LA, Karlson EW. Smoking intensity, duration, and cessation, and the risk of rheumatoid arthritis in women. Am J Med. 2006 Jun;119(6):503.e1-9.

[3] Sparks JA, Karlson EW. The roles of cigarette smoking and the lung in the transitions between phases of preclinical rheumatoid arthritis. Curr Rheumatol Rep. 2016 Mar;18(3):15. doi: 10.1007/s11926-016-0563-2.

[4] Balsa A, et al. Prevalence of comorbidities in rheumatoid arthritis and evaluation of their monitoring in clinical practice: the Spanish cohort of the COMORA study. Reumatol Clin. 2017 Jul 12. pii: S1699-258X(17)30134-1. doi: 10.1016/j.reuma.2017.06.002. [Epub ahead of print].

[5] Fenton SA, Veldhuijzen van Zanten JJ, Duda JL, Metsios GS, Kitas GD. Sedentary behaviour in rheumatoid arthritis: definition, measurement and implications for health. Rheumatology (Oxford). 2017 Apr 7. doi: 10.1093/rheumatology/kex053. [Epub ahead of print]

[6] Azzi L, et al. Periodontal microbioma and rheumatoid arthritis: The role of Porhyromonas gingivalis. J Biol Regul Homeost Agents. 2017 Apr-Jun;31(2 Suppl 1):97-103.

[7] Calderaro DC, Correa JD, Ferreira GA, Barbosa IG, Martins CC, Silva TA, Teixeira AL. Influence of periodontal treatment on rheumatoid arthritis: a systematic review and meta-analysis. Rev Bras Reumatol Engl Ed. 2017 May – Jun;57(3):238-244. doi: 10.1016/j.rbre.2016.11.011. Epub 2017 Jan 4.

[8] Ayravainen L, Leirisalo-Repo M, Kuuliala A, Ahola K, Koivuniemi R. Meurman JH, Heikkinen AM. Periodontitis in early and chronic rheumatoid arthritis: a prospective follow-up study in Finnish population. BMJ Open. 2017 Jan 31;7(1):e011916. doi: 10.1136/bmjopen-2016-011916.

[9] http://www.ada.org/en/science-research/science-in-the-news/periodontal-disease-affects-nearly-half-us-population

[10] Yilmaz V, Umay E, Gundogdu I, Karaahmet ZO, Ozturk AE. Rheumatoid arthritis: are psychological factors effective in disease flare. Eur J Rheumatol. 2017 Jun;4(2):127-132. doi: 10.5152/eurjrheum.2017.16100. Epub 2017 Jun 1.

[11] Nagano J, Sudo N, Nagaoka S. Yukioka M, Kondo M. Life events, emotional responsiveness, and the functional prognosis of patients with rheumatoid arthritis. Biopsychosoc Med. 2015 Jun 23;9:15. doi: 10.1186/s13030-015-0043-3. eCollection 2015.

[12] http://www.mayoclinic.org/healthy-lifestyle/stress-management/basics/stress-basics/hlv-20049495

Diseases and Conditions

Can small fiber neuropathy mimic fibromyalgia?

July 19, 2017

Can small fiber neuropathy (SFN) mimic fibromyalgia? The simple answer is yes, but it’s more complicated… So why does a rheumatologist care about small fiber neuropathy? The answer is very simple. Many people get referred to a rheumatologist for fibromyalgia, which is a disease that causes widespread pain, brain fog, non-restorative sleep, and various other unexplained symptoms such as headaches. While fibromyalgia IS NOT an autoimmune disease, small fiber neuropathy can present very similarly but CAN BE caused by autoimmune diseases.

There’s a lot of controversy in the medical community about fibromyalgia. One group believes that it’s a separate entity, some do not believe in its existence, and some people are somewhere in the middle. Personally, I believe that fibromyalgia likely represents many diseases that we haven’t identified yet. Until we can categorize them into distinct entities, we’re going to have a hard time understanding them, let alone come up with effective treatments.

First, let’s review the clinical criteria that doctors use to make a diagnosis of fibromyalgia.

2010 ACR criteria for fibromyalgia

Criteria A patient satisfies diagnostic criteria for fibromyalgia if the following 3 conditions are met:

Widespread pain index (WPI) ≥ 7 and symptom severity (SS) scale score ≥5 or WPI 3–6 and SS scale score ≥ 9.
Symptoms have been present at a similar level for at least 3 months.
The patient does not have a disorder that would otherwise explain the pain.

Number #1 are various validated pain scores. These are rarely used in clinic but are often used for clinical trials. It helps researchers objectively quantify pain levels at any given time. As you can see, we don’t use trigger points to check for fibromyalgia anymore.

Small fiber neuropathy in people with fibromyalgia

So is small fiber neuropathy a feature of fibromyalgia, just like it is for diseases like Sjogren’s syndrome or are patient’s with small fiber neuropathy mistakenly diagnosed with fibromyalgia?

In one study, 46 patients with fibromyalgia and 34 normal controls were tested for small fiber neuropathy with a specialized skin biopsy. I’ll talk more about this later on. The researchers measured pain intensity with a survey called the Neuropathic Pain Symptom Inventory. They found that 32.6% of patients with fibromyalgia had reduced nerve fiber density on their biopsy, i.e, they had small fiber neuropathy. Interestingly, they also didn’t find any correlation between pain scores and nerve density.

This implies three things. First of all, the level of pain and symptoms experienced by people with fibromyalgia was the same as those with small fiber neuropathy. So you can’t distinguish between fibromyalgia and small fiber neuropathy based on symptoms alone. Second, about 1/3 of people diagnosed with fibromyalgia have small fiber neuropathy. Finally, having worse nerve density doesn’t necessarily mean you’ll experience more pain. Other studies have also found similar results.

Now this still doesn’t answer all our questions but I think it’s safe to say that testing for small fiber neuropathy should happen when there is a clinical diagnosis of fibromyalgia. Now let’s talk about small fiber neuropathy.

What is Small Fiber Neuropathy?

Small fiber neuropathy results from damage to the small, unmyelinated nerve fibers that send pain and temperature and control autonomic functions like sweating. The following are some of the symptoms caused by SFN:

Burning pain
Numbness and tingling
Pain that is out of proportion
Cramping
Unexplained itching
Lack of sweating
Temperature dysregulation
Dryness

How to diagnose small fiber neuropathy?

The first step to diagnose small fiber neuropathy is taking a care history, reviewing risk factors, and performing a detailed physical examination. On physical exam, deep tendon reflexes (e.g., knee jerk reflex) are normal and there’s no loss of strength. If there is a suspicion for SFN your doctor may send you for electrodiagnostic tests (EMGs). These are colloquially called nerve conduction tests.

Small fiber neuropathy affects small myelinated A-delta and unmyelinated C fibers, NOT large fibers. This means that EMGs are typically negative because these are good for looking for problems affecting large fibers like carpal tunnel syndrome.

One way to diagnose small fiber neuropathy is with a skin biopsy, more specifically epidermal nerve fiber density testing (ENFD). This technique allows direct visualization, quantification, and morphologic assessment of small sensory fibers innervating the skin. This technique has a sensitivity of 88% and a specificity of 95 – 97%. In layman’s terms, the test will miss 12% of cases of small fiber neuropathy, but if the test is positive, there’s a 3 – 5% chance that it’s a mistake (false positive). These are actually pretty good values. A report by the European Federation of Neurological Societies states that ENFD is a reliable and efficient tool to assess for SFN.

How is epidermal fiber density testing done?

Epidermal fiber density testing is done by taking 2-4 three mm punch biopsies. This test happens in clinic. It’s quick and safe. Your doctor can only do these in areas that have been validated: near the ankle, upper thigh, the foot, near the wrist, and the upper arm.

The biopsy is then sent to a specialized pathologist and stained with anti-protein gene product 9.5 antibody (PGP 9.5), which stains all the axons. The pathologist can then painstakingly count all the nerves and calculate the density. The density is then compared to age and sex matched control values to decide whether it’s abnormal.

Common causes of small fiber neuropathy

Once your doctor makes a diagnosis of small fiber neuropathy, then the question is whether there is an underlying cause. About 50% of small fiber neuropathy cases are idiopathic, meaning that doctors can’t find an underlying cause. As a result that leaves us with the other 50%. Of those cases, the most common cause is diabetes mellitus. In fact, autoimmune diseases make a relatively small proportion of cases, so it’s important to look for other causes first. There are MANY other causes but these are some of the more common conditions that can cause small fiber neuropathy.

Non-autoimmune causes

Diabetes mellitus
Lyme disease
Hepatitis C infection
HIV
Celiac disease
Chronic kidney disease
Hypo/hyperthyroidism
Alcohol abuse
Medications, especially chemotherapy
Vitamin B12, B6, B1 deficiency
Paraneoplastic syndromes
Amyloidosis
Exposure to heavy metals

Autoimmune causes

Sjögren’s syndrome
Systemic lupus erythematosus
Sarcoidosis
Rheumatoid arthritis
Scleroderma
Inflammatory bowel disease (Crohn’s disease and ulcerative colitis)
Vasculitis
Psoriasis and psoriatic arthritis

Some genetic conditions can also cause small fiber neuropathy, like Fabry’s, but these are very rare.

Treatment

I won’t talk too much about treatment because it really depends on the underlying cause. If you’re dealing with an autoimmune disease… treat it. Sometimes symptomatic treatment is also necessarily. The following are some medications that are often used:

Tricyclic antidepressants
Serotonin norephinephrine re-uptake inhibitors (SNRIs)
Pregabalin
Gabapentin
Topical lidocaine
Topical capsaicin

Doctors sometimes use intravenous immunoglobulin (IVIG) in extreme situation, particularly in situations where an autoimmune disease is the culprit. The evidence supporting this type of treatment isn’t great. Sometimes it works, sometimes it doesn’t. Moreover, there are no large randomized controlled studies looking at IVIG treatment for small fiber neuropathy.

Ultimately, we’re going to need to understand why and how small fiber neuropathy happens to come up with effective treatments.

Conclusion

I hope this helps explain how small fiber neuropathy (SFN) mimics fibromyalgia and why it’s important to distinguish between both. For those who want to learn more about small fiber neuropathy and how to live with it, I’ve included a link to a great YouTube video.

Please leave your comments below!

References

Lauria G, Devigili G. Skin biopsy as a diagnostic tool in peripheral neuropathy. Nature Clinical Practice Neurology. 2007 Oct 3;3(10):546-57.

Devigili G, Tugnoli V, Penza P, Camozzi F Lombordi R, Milli G, Broglio , Granieri E, Lauria G. The diagnostic criteria for small fibre neuropathy : from symptoms to neuropathology. Brain 2008; 131; 1912-19.

Lauria G, Hsieh ST, Johansson O, Kennedy WR, Leger JM, Mellgren SI, Nolano M, Merkies IS, Polydefkis M, Smith AG, Sommer C, Valls-Sole J. European Federation of Neurological Societies/Peripheral Nerve Society Guideline on he use of skin biopsy in the diagnosis of small fiber neuropathy. Report of a joint task force of the European Federation of Neurological Societies and the peripheral nerve society. J Peripher Nerv Syst. 2010 Jun;15(2):79-92.

Giannoccaro MP, DonadioV, Incensi A, Avoni P, Liguori R. Small nerve fiber involvement in patients referred for fibromyalgia. Muscle Nerve. 2014 May;49(5):757-9.

Kosmidis ML, Koutsogeorgopoulou L, Alexopoulos H, Mamali I, Vlachoyiannopoulos PG, Voulgarelis M, Moutsopoulos HM, Tzioufas AG, Dalakas MC. Reduction of intraepidermal nerve fiber density (IENFD) in the skin biopsies of patients with fibromyalgia: a controlled study. J Neurol Sci. 2014 Dec 15;347(1-2):143-7.

Chan AC, Wilder-Smith EP. Small fiber neuropathy: getting bigger! Muscle Nerve. 2016 Feb 13. [Epub ahead of print]

UpToDate 2017

Uceyler N, Zeller D, Kahn AK, Kewenig S, Kittel-Schneider A, Casanova-Molla J, Reiners K, Sommer C. Small fibre pathology in patients with fibromyalgia syndrome. Brain. 2013 Jun;136(Pt 6):1857-67.

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