Guide to living with rheumatoid arthritis: Part 1

July 5, 2017

Have you recently been diagnosed with rheumatoid arthritis? RheumDoctor presents a guide to living with rheumatoid arthritis

Rheumatoid arthritis… Your rheumatologist diagnosed you with rheumatoid arthritis and you have a lot questions. What’s rheumatoid arthritis? Can I get rid of it or will I live with this disease for the rest of my life? What should I expect? How do I fight it? This week I’ll present to you Part 1 of a Guide to living with rheumatoid arthritis. I’m going to present this as a three-part series. Part 1 will cover the basics: what is rheumatoid arthritis, the cause, symptoms, diagnosis, treatment, etc. In Part 2 I’ll cover prognosis, what to expect, diet and exercise. In Part 3, I’ll be covering the financial side of rheumatoid arthritis: How to get access to medications and how to deal with insurance companies.

I hope you find this information useful. Be strong, be brave, and know that you’re not alone.

What is rheumatoid arthritis?

Rheumatoid arthritis is an autoimmune disease that causes inflammation throughout the body but mainly affect joints. Without treatment, rheumatoid arthritis can eventually lead to permanent joint destruction. Autoimmune diseases occur when the immune system loses “tolerance to self”. What this means is that the immune system can no longer distinguish between healthy cells and cells that don’t belong like bacteria or cancerous cells.

According to the CDC, about 1% of people living in the US suffer from rheumatoid arthritis. It tends to occur 2-3 times more often in women and tends to start in your sixties but it can start at any age. [1]

Some common signs and symptoms include:

Pain and swelling in the joints. Particularly small joints like the knuckles, wrists, and toes.
Morning stiffness that lasts more than one hours
Having difficulty opening jars. Weakness in the hands.
Fatigue, fevers, unintentional weight loss.

What causes rheumatoid arthritis?

We’re actually unsure. We do know that in certain cases there is a genetic link. People that have a certain HLA class II genotype (shared epitope) tend to get rheumatoid arthritis more often. Especially, if they smoke cigarettes. Moreover, we know that rheumatoid arthritis tends to run in families. However, most cases of RA happen spontaneously and not everyone who has a genetic risk factor develops RA.

There’s still a lot of work that needs to be done to fully understand what causes rheumatoid arthritis. Like most autoimmune diseases, our best guess is that people who have RA probably were born with some sort of genetic predisposition for the disease. Then they get exposed to something in the environment like a virus, trauma, stress, hormonal change, which then triggers the disease to come online.

What are the symptoms of rheumatoid arthritis?

Usually rheumatoid arthritis presents with pain, swelling, and prolonged stiffness involving small joints, like the ones in your hands or feet. When I mean prolonged, I mean more than one hour. But RA can present in many ways. These can be divided into typical (90% of cases) and atypical presentations (10% of cases).

Typical

Insidious (55% – 65%): People develop pain, swelling, and prolonged stiffness mainly involving small joints like the toes and knuckles. This progressively worsens over months.

Subacute (15% – 20%): Again small joints are painful, swollen, and stiff but the this develops over weeks. Usually people experience some fatigue.

Acute (10%): Joints suddenly become swollen and tender over days. Some people have a fever, drenching night sweats, and sometimes can lose weight without trying.

Atypical (10% of cases)

Palindromic pattern: This type of presentation isn’t technically considered rheumatoid arthritis. It’s just that 33% to 50% of people with this type of presentation progress to full-blown rheumatoid arthritis. Typically, one joint is involved. It becomes tender and swollen for a few days then gets better on its own. Then a few weeks to a few months later it happens again. The flare can happen in the same joint but not necessarily. Treatment with hydroxychloroquine can decrease the risk of developing full-blown rheumatoid arthritis, so it’s important to start treatment as this stage.

Insidious onset of the elderly: As the name suggests this type of presentation occurs in the elderly, so people aged greater than 65 years. People experience extreme pain and stiffness shoulders and the hips. Sometimes you can see whole hand or foot swelling. Sometimes it’s very difficult to differentiate from polymyalgia rheumatica or remitting seronegative symmetrical synovitis with pitting edema (RS3PE). People with polymyalgia rheumatica and RS3PE typically do NOT have any positive antibodies.

Rheumatoid nodulosis: Rheumatoid arthritis can cause nodules and bone cysts on radiographs. Usually people also have joint pain and swelling but sometimes all they have are nodules.

Arthritis robustus: This is rather rare. I’ve only seen it once. It typically occurs in men. Essentially the person develops horrible rheumatoid arthritis hand deformities but experiences little or no pain. I know it’s hard to believe, but it’s possible!

By James Heilman, MD (Own work) [CC BY-SA 3.0 (http://creativecommons.org/licenses/by-sa/3.0) or GFDL (http://www.gnu.org/copyleft/fdl.html)], via Wikimedia Commons

How is rheumatoid arthritis diagnosed?

The diagnosis of rheumatoid arthritis, contrary to popular belief, is primarily a clinical diagnosis. Having a positive antibodies like a rheumatoid factor (RF) does not necessarily mean that you have rheumatoid arthritis because MANY conditions can have a positive rheumatoid factor. Some of these include:

Rheumatoid arthritis, mixed cryoglobulinemia types II and III, sarcoidosis, and other autoimmune diseases like Sjogren’s syndrome. Other non-rheumatology diseases that can cause someone to have a positive rheumatoid factor include infections most notably hepatitis C, tuberculosis, syphilis, HIV, and endocarditis. People suffering from cancer and people with chronic pulmonary and liver diseases, can also have a positive rheumatoid factor.

It’s also important to mention that about 5 – 25% of people aged 60 years and older have a positive rheumatoid factor without any underlying causative disease.

This is why my job as a rheumatologist is so interesting 🙂

The American College of Rheumatology classification criteria for rheumatoid arthritis is as follows:

The 2010 American College of Rheumatology/European League Against Rheumatism classification criteria for rheumatoid arthritis[2]

Who to test?

People that have at least 1 joint with definite swelling.
And the swelling cannot be better explained by another disease.

Classification criteria for RA (a score of ≥ 6/10 is needed for someone to have definite RA)

Category

Score

Joint involvement

1 large joint

2 – 10 large joints

1 – 3 small joints

4 – 10 small joints

> 10 joints (at least one small joint)

Antibodies

Negative RF and negative CCP antibodies

Low positive RF or low positive CCP antibodies *

High-positive RF or high positive CCP antibodies #

Inflammation markers

Normal CRP and normal ESR

Abnormal CRP or abnormal ESR

Duration of symptoms

< 6 weeks

≥ 6 weeks

* Low positive antibodies means any value that is above normal but less than 3 standard deviations above the upper limit of normal.

# High positive antibodies means any value that is 3 standard deviations above the upper limit of normal.

It’s important to note that these criteria were NOT meant for clinical practice but rather, were really meant for research trials. Sometimes, rheumatologists do deviate. Other conditions should be ruled out and let’s face it, not everyone fits perfectly into the mold. The criteria also does not account for musculoskeletal ultrasound testing. This imaging test can detect very subtle inflammation of a joint.[3]

Positive antibodies without RA

Now sometimes the workup is completely negative including x-rays. This is not uncommon. It can mean many things. It could mean that the rheumatoid factor is not clinically significant. 5–25% of the population can have a positive rheumatoid factor without any underlying condition or any symptoms. Typically the rheumatoid factor levels are low. It could also mean that you will develop rheumatoid arthritis in the future. Studies have shown that antibodies associated with rheumatoid arthritis can be present over a decade before onset of clinical disease. [4]Unfortunately, we don’t have the tools to precisely determine who will convert and who will not. In this situation, your rheumatologist can help you watch for any change in your condition.

How is rheumatoid arthritis treated?

We treat rheumatoid arthritis with medications called disease modifying anti-rheumatic drugs (DMARDs). These medications slow down or stop the natural progression of rheumatoid arthritis.

Except for a few special situations, EVERYONE should with rheumatoid arthritis should be treated with a DMARD as soon as possible because permanent joint damage can happen in as little as 3 months after symptoms start.[5]

The following are the medications used to treat rheumatoid arthritis in the United States. It’s important to work closely with your rheumatologist because they all have possible risks and what may be good for your neighbor may not be safe for you.

I’ve broken them down into conventional DMARDs, biologic DMARDs, and pipeline medications that have not been approved as of yet.

Conventional

Methotrexate
Leflunomide
Sulfasalazine
Hydroyxchloroquine

Biologics

Etanercept, TNF inhibitor
Adalimumab, TNF inhibitor
Golimumab, TNF inhibitor
Certolizumab pegol, TNF inhibitor
Infliximab, TNF inhibitor
Abatacept, Co-stimulation inhibitor
Tocilizumab, IL-6 inhibitor
Sarilumab, IL-6 inhibitor
Tofacitinib – JAK inhibitor
Rituximab – B cell depletion

Pipeline

ABT 494, a new JAK inhibitor
Baricitinib, another JAK inhibitor
Sirukumab, another IL-6 inhibitor

Biosimilars

It’s also important to note that we are starting to see biosimilar medications in the States. These are medications that are sort of copied from existing biologic medications. They are NOT generic medications. The problem with biosimilars is that because of their complexity, it literally is impossible to exactly copy a biologic medication. If you want to learn more about biosimilar medications, please check this article.

Supplements

If you’re interested in supplementing, there is some research that suggests high dose turmeric/curcuma and high dose fish oil/omega-3 fatty acids may also be helpful.[6][7] However, supplementation should be used in combination with FDA approved medications that I listed above.

Is there a cure for rheumatoid arthritis?

I honestly wish I had better news for you. Unfortunately there is no cure for rheumatoid arthritis. Treatment primarily focuses on arresting the natural progression of the disease with the use of disease modifying anti-rheumatic agents (DMARDs). Conventional DMARDs such as methotrexate, leflunomide, sulfasalazine, and hydroxychloroquine, modulate the immune system to decrease rheumatoid arthritis activity. Biologic medications like etanercept use a targeted approach, i.e., suppress a specific cytokine.

The goal of treatment is to put rheumatoid arthritis into remission and decrease the frequency of flares.

This may seem very pessimistic, but recent advances have really improved the prognosis of people living with rheumatoid arthritis.

Nevertheless, DMARDs do not cure rheumatoid arthritis.

How do we win the war against rheumatoid arthritis? Before we can win the war and find a cure, we need to know exactly what causes rheumatoid arthritis in the first place and we need to understand its exact pathophysiology. Believe it or not, despite all our advances, we still cannot answer these two questions. Don’t despair, researchers are actively trying to answer these questions.

Can rheumatoid arthritis become fatal?

Rheumatoid arthritis is a systemic autoimmune mediated disease that primarily affect the joints. Note the primarily bit. It can affect a host of different organs including the eyes, lungs, heart, skin, and bone marrow to name a few.

Untreated or poorly controlled rheumatoid arthritis can cause serious conditions such as interstitial lung disease (i.e., inflammation of the lungs), pericarditis (i.e., inflammation of the “sac” surrounding the heart), as well as something called Felty’s syndrome (i.e., a hematologic condition that can cause white cells to dramatically decrease and causes the spleen to enlarge). These severe manifestations of rheumatoid arthritis that can lead to death are hardly ever seen anymore mainly because we have many highly effective medications called disease modifying anti-rheumatic medications (DMARDs). These medications have completely changed people’s prognosis.

Cardiovascular disease and infection

The most common cause of death in people with rheumatoid arthritis these days includes cardiovascular disease and infection – primarily from medications.[8]

Rheumatoid arthritis increases cardiovascular risk via the interplay of inflammation and lipid metabolism. Studies have shown that people who receive treatment with methotrexate and or tumor necrosis factor inhibitors reduce their cardiovascular risk.[9] A British study also demonstrated that cardiovascular was not increased regardless of the choice of DMARD provided that rheumatoid arthritis was well controlled.[10]

Infection remains an ever-present problem in the world of rheumatology. To treat autoimmunity you need to suppress the immune system. Not too much, not too little, but just right. In some cases this has the unfortunate result in causing serious infections that can lead to death in extreme cases.

Rheumatoid arthritis can become fatal in many other ways, however, for the most part it is medication induced – although the pharmaceutical companies don’t really want you to know that. Just read a package insert. They’re terrifying.

However, I’ve been talking about rheumatoid arthritis fatalities. Untreated or undertreated rheumatoid arthritis is HIGHLY debilitating leading to a significant drop in your quality of life. Early treatment with a DMARD is the best way to improve your odds. You have to fight fire with fire!

Can I stop my medications if I’m feeling better?

No. Rheumatoid arthritis is a life-long disease. If you’re feeling better, great! However, it’s probably your medications that are keeping you that way. If you stop your medications the rheumatoid arthritis will come back. Maybe not now but soon. Rheumatoid arthritis subsides spontaneously in a VERY small subset of people.

If your medication is making you feel sick, talk to your rheumatologist. They’re there to make you feel better and they want to find the perfect treatment plan tailored for you.

Do not stop your medications without consulting your rheumatologist.

Next steps

We’ve covered a lot of material today and there’s a lot more coming your way! Stay tuned for Part 2. I’ll be covering topics such as what to expect, what to eat, how to exercise, and strategies on how to reduce stress. Please leave your comments below.

References

[1] https://www.cdc.gov/arthritis/basics/rheumatoid-arthritis.html

[2] https://www.rheumatology.org/Portals/0/Files/2010_revised_criteria_classification_ra.pdf

[3] Horton SC, et al. Ultrasound-detectable grey scale synovitis predicts future fulfilment of the 2010 ACR/EULAR RA classification criteria in patients with new-onset undifferentiated arthritis. RMD Open. 2017 Mar 30;3(1):e000394. doi: 10.1136/rmdopen-2016-000394. eCollection 2017.

[4] Brink M, et al. Rheumatoid factor isotypes in relation to antibodies against citrullinated peptides and carbamylated proteins before the onset of rheumatoid arthritis. Arthritis Res Ther. 2016 Feb 9;18:43. doi: 10.1186/s13075-016-0940-2.

[5] Raza K, et al. Treating very early rheumatoid arthritis. Best Pract Res Clin Rheumatol. 2006 Oct;20(5):849-63.

[6] van der Tempel H, et al. Effects of fish oil supplementation in rheumatoid arthritis. Ann Rheum Dis. 1990 Feb; 49(2): 76–80.

[7] Ramadan G Al-Kahtani MA, El-Sayed WM. Anti-inflammatory and anti-oxidant properties of Curcuma longa (turmeric) versus Zingiber officiale (ginger) rhizomes in rat adjuvant-induced arthritis. Inflammation. 2011 Aug;34(4):291-301. doi: 10.1007/s10753-010-9278-0.

[8] https://www-ncbi-nlm-nih-gov.elibrary.amc.edu/pubmed/26472415

[9] https://www-ncbi-nlm-nih-gov.elibrary.amc.edu/pubmed/28455580

[10] https://www-ncbi-nlm-nih-gov.elibrary.amc.edu/pubmed/28160488

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 and treatment.

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Recipes

Buckwheat pancake: galettes de sarrasin

June 28, 2017

A picture of the moulin Legare the oldest functional water powered mill in North America. The mill produces 4 tons of wheat and buckwheat flour annually.

Last weekend I took some much needed time off and spent it celebrating la Fête de la Saint-Jean-Baptiste with my family up in my hometown of Saint-Eustache, Quebec. This is akin to the 4th of July for French Canadians. Saint-Eustache was founded in 1770 and boasts two famous historical sites: the church and the buckwheat water mill.

Historical Sites

The church gained notoriety for its significance during the battle of the Lower Canada Rebellion on December 14th, 1837. After rebelling against the English following multiple failures at political reform, seventy rebels were shot or burnt alive inside the church while the English bombarded its facade. The English then pillaged the city and burnt the majority of the city to the ground. Many see the rebellion of the Patriotes Canadiens as an example of what could have happened in the United States had the American Revolutionary War failed.

By Vincent Poirier (Own work) [CC BY-SA 3.0 (http://creativecommons.org/licenses/by-sa/3.0)], via Wikimedia Commons

Every June 24th the entire province gathers to celebrate our independence and express our gratitude for those who made the ultimate sacrifice.

Now the second famous historical site in Saint-Eustache is the moulin Légaré. It was built in 1762 and has been in constant operation since then. In fact, it’s the oldest functional water-powered mill in North America. The mill, to this day, produces about 40 tons of wheat and buckwheat flour annually!

What’s buckwheat and how do I use it?

Contrary to popular belief, buckwheat is NOT a grain. It just has grain-like seeds which are milled into a flour. That being said, buckwheat flour is gluten-free and has many trace minerals as well as vitamin B6, pantothenic acid, niacin, folate, thiamine, and choline. Moreover, you will find 4 grams of soluble fiber, 8 grams of protein, and 15% of your daily iron requirements in 1/3 of a cup of buckwheat flour. Needless to say buckwheat is very healthy and should be part of your diet.

In Quebec, we use buckwheat in our traditional cooking. This is probably because we have a shorter growing season. Buckwheat likes cold weather, acidic and low fertility soil.

One of the most popular ways to use buckwheat flour is to make pancakes. We call them galettes de sarrasin. Essentially it’s a thin pancake, more like a Parisian crêpe. It’s cooked on a sizzling hot cast iron pan and then drizzled with molasses or maple syrup. But really you can dress it with almost anything: swiss cheese, a fried egg, bechamel, etc. Sweet or savory, whatever you fancy.

Buckwheat Pancake – Galette de sarrasin

Adapted from Recettes de la famille Légaré

2 cups of buckwheat flour

1 tsp of baking powder

1/2 tsp of salt

2 cups of water

Butter

Instructions

In a large bowl, whisk together the water, buckwheat flour, baking powder, and salt.
Heat a cast iron pan on medium heat. When hot, add about 1/2 tsp of butter. If you want to be ultra traditional, use lard.
Ladle a spoonful of batter onto the sizzling hot pan. Flip the pancake once you see holes forming but only for a few seconds. Serve immediately.

RheumDoctor Learning Center

RheumDoctor Learning Center: What is a cytokine?

May 31, 2017

A picture of interleukin 6 a cytokine thought to be involved in giant cell arteritis

A cytokine is a type of protein in the body that helps cells communicate. Here are some types of cytokines:

Lymphokines: Cytokines produced by lymphocytes
Monokines: Cytokines produced by monocytes
Chemokines: Cytokines that attract other cells
Interleukin (IL-): Cytokines produced by leukocytes that help regulate the immune system.

Sometimes cells make cytokines and those cytokines directly affect them. This is autocrine action. If the cell makes a cytokine and it affects a nearby cell, this is paracrine action. Finally, if a cell makes a cytokine and it affects distant cells, this is endocrine action.

How are cytokines and autoimmune diseases related?

Researchers have identified many cytokines such as IL-1β, IL-6, IL-17, and TNF-α that play an important role in autoimmune diseases. This information is then used to make biologic medications that specifically block problematic cytokines.

References

MedicineNet.com

Image of interleukin 6 molecule by Ramin Herati [Public domain], via Wikimedia Commons

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Diseases and Conditions

Will hydroxychloroquine hurt my eyes?

May 24, 2017

I love hydroxychloroquine. Honestly, I really do. It’s simple, easy, it works, and for the most part it’s benign especially when compared to the rest of the medications I prescribe. Rheumatologists use hydroxychloroquine (Plaquenil) to treat of lupus, mild cases of rheumatoid arthritis, and many other autoimmune diseases.

Now I said benign. Well I actually said, “for the most part it’s benign”. Allergic reactions are always a concern but the main concern I have with hydroxychloroquine is the possibility of developing eye toxicity. More specifically, hydroxychloroquine maculopathy. But before I continue, I think it’s important to go through some anatomy.

Anatomy of the Eye

The following is a simplified version of the human eye. The cornea is the clear part of the eye that lets you focus light into your eye. The iris regulates the amount of light you let into your eye. The pupil is the dark part of the eye. This is where light actually goes into the eye. The lens focuses light so that it hits the retina just right and the retina actually senses light. This info is then condensed onto the optic disc and then sent to the optic nerve then into your brain.

Where does hydroxychloroquine fit in?

Now this is the important part because this is where hydroxychloroquine can cause problems: the macula. The macula is a specialized place on your retina that has cells that enable you to see fine details with high acuity. We call these specialized cells cones and they are found in high density in this area. The macula is then made up of the fovea, foveal avascular zone, parafovea, and the perifovea. The following is a real life example courtesy of Danny Hope.

By Photograph: Danny Hope from Brighton & Hove, UK Diagram: User:Zyxwv99 [CC BY 2.0 (http://creativecommons.org/licenses/by/2.0)], via Wikimedia Commons

Now the prospect of losing the ability to see things clearly sounds absolutely terrible. I’ve been wearing glasses since I was 13. Without them, everything is blurry. I can’t even imagine the blow to my quality of life, if I didn’t have my glasses. Hydroxychloroquine is kind of like that. Your vision becomes blurry, except glasses won’t help, and the vision loss is permanent.

So why would anyone go on this medication and why would your doctor even suggest it?

Well… because it’s actually a pretty good medication. Just like most medications, you need to take it as safely as possible. The American Academy of Ophthalmology released a statement last year about monitoring hydroxychloroquine. Let’s go over these recommendations together!

Recommendations on Screening for Hydroxychloroquine Retinopathy (2016 Revision)

First of all, it’s still unclear how exactly hydroxychloroquine causes eye toxicity. In a nutshell the outer layer of the retina gets damaged and then it deepens and spreads around the fovea. People tend not to notice anything at this stage. Over time, if the medication is not stopped, the fovea becomes involved and visual acuity drops. It’s also important to note that hydroxychloroquine can worsen even after stopping the medication. If it’s caught early on, it probably won’t affect vision. If there already was a lot of damage to begin with, then the risk is higher. So the real question is what is the real risk of developing toxicity, what are the factors that increase that risk, and how often should you get screened by an ophthalmologist?

What is the real risk of developing hydroxychloroquine eye toxicity?

In the past, we thought the risk of developing eye toxicity from hydroxychloroquine was very low. New data suggests otherwise. Although the risk is still low, we were probably underestimating the risk. Researchers following 2,361 people using hydroxychloroquine, found that about 7.5% of those people had eye toxicity. The most important risk factors included the daily dose of hydroxychloroquine and duration of use.

People who took 4 to 5 mg/kg/day of hydroxychloroquine had a much lower cumulative risk as compared to people you took a higher dose: 1% risk in the first 5 years and less than 2% up to 10 years. After 20 years the risk dramatically increased to 20%.

When I mean mg/kg/day, I mean the amount of drug for every kilogram of body weight over a 24 hour period. To calculate the dosage of hydroxychloroquine you need to use your real weight, NOT your ideal weight. For some medications, it’s the opposite. Let’s say you were taking hydroxychloroquine 200 mg twice a day and then you started dieting and exercising, and then you shed a lot of weight. You now may need to decrease your daily dose of hydroxychloroquine because your real weight decreased. In the study, the researchers found that thin people tended to have more eye toxicity because they tended to get more than 4 – 5 mg/kg/day of hydroxychloroquine.

FYI When calculating your body weight to verify your hydroxychloroquine dose, you need to use metric. This is not optional.

1 kilogram = 2.2 pounds

Other Significant Risks

Initially we thought hydroxychloroquine gets stored in fat cells. In actuality, recent lab studies show that the medication is mostly stored in melanotic tissue, liver, and in the kidneys. Muscle, fat, and other organs not so much. That being said, people with severe kidney disease are at higher risk of developing eye toxicity. These people may need more frequent eye testing and they may not need as high of a dose.

Other significant risks includes concurrent use of tamoxifen, which is a medication commonly used to help treat breast cancer. The researchers found that there was a 5-fold increase of toxicity in people taking tamoxifen and hydroxychloroquine. Why? Tamoxifen itself can affect the retina, so maybe having both on board simultaneously isn’t such a great idea.

Finally, people with macular or retinal issues, like having macular degeneration, may also be at higher risk. There wasn’t enough results to confirm this, but it kind of makes sense. If he retina isn’t too hot to begin with, it’ll probably be difficult for the ophthalmologist to decide whether future changes are medication-related versus disease-related, in this case macular degeneration. Do you need to stop hydroxychloroquine? Or do you need to start ranibizumab (i.e., a medication FDA approved for macular degeneration)?

Screening Schedule

As I mentioned before, hydroxychloroquine eye toxicity is not reversible. Once it happens, it happens. So the trick is to catch it early. Fortunately, the changes occur VERY slowly. The American Academy of Ophthalmology recommends the following:

Obtain a baseline eye exam within the first year of starting hydroxychloroquine to document any complicating eye problem.
Annual screening beginning after 5 years of use.
Sooner if there are major risk factors.
Check the dose of hydroxychloroquine based on your weight at your doctor’s appointment.
Inform your doctor if there’s been any significant change in your health: significant weight loss (intentional or unintentional), kidney disease, or if you’ve been prescribed tamoxifen.

Now you may wonder why your rheumatologist insists on annual eye checks even though you’ve been on hydroxychloroquine for less than 5 years. This is probably a matter of style. Personally, I’m one of those rheumatologists that insists on annual eye checks. I wouldn’t feel comfortable NOT seeing my ophthalmologist if I was taking a medication that had retinal toxicity.

Screening Tests

There are many different techniques to screen for toxicity. I won’t go into specifics because, well, I’m not an ophthalmologist. However, here is a list of techniques that the American Academy of Ophthalmology approved to screen for hydroxychloroquine eye toxicity.

Automated visual fields
Spectral-domain optical coherence tomography
Multifocal electroretinogram
Fundus autofluorescence
Microperimetry – newer test, possible value in future
Adaptive optics retinal imaging – newer test, possible value in future

These tests are not recommended for screening

Fundus examination
Time-domain optical coherence tomography
Fluorescein angiography
Full-field electroretinogram
Amsler grid
Color testing
Electro-oculogram

If you have any questions about these tests, please ask you ophthalmologist.

Conclusion

Hydroxychloroquine is truly wonderful and useful medication for the treatment of multiple different types of autoimmune diseases. Although eye toxicity is a real danger, the risk is usually small especially in the short-term. But like I said at the beginning, like medications you need to take it safely and responsibly. To learn more about medication safety, please read my article regarding the 10 most frequently asked questions when starting methotrexate.

Please leave your comments below!

By Jessica Chapman, M.D.

References

https://commons.wikimedia.org/wiki/File:Schematic_diagram_of_the_human_eye_en.svg

https://commons.wikimedia.org/wiki/File:Macula.svg

Marmor MF, Kellner U, Lai TY, Melles RB, Mieler WF, American Academy of Ophthalmology. Recommendations on screening for chloroquine and hydroxychloroquine retinopathy (2016 revision). Ophthalmology. 2016 Jun;123(6):1386-94.

UpToDate

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RheumDoctor Learning Center

RheumDoctor Learning Center: What is the microbiome?

May 17, 2017

How the microbiome affects the immune system

The microbiome refers to the combined genetic material of a group of microorganisms found in a certain body part such as the gut, respiratory tract, skin, or genitourinary system.

Symbiosis refers to a relationship between organisms that are beneficial for one another.

Dysbiosis refers to an imbalance of different microorganisms. It is the opposite of a state of symbiosis.

How the microbiome and autoimmune diseases relate?

There appears to be an association between autoimmune dieaseses and dysbiosis, such as inflammatory bowel disease, spondyloarthritis, psoriasis, and rheumatoid arthritis. It is still unclear whether autoimmune diseases cause dysbiosis or whether dysbiosis causes autoimmune diseases, let alone how we can use this information to treat and prevent autoimmune diseases.

Ultimately we need more research. We live in interesting times! Please leave your comments below!

References

National Human Genome Research Institute

Diseases and Conditions

How to prepare for pregnancy with an autoimmune disease

April 5, 2017

Pregnancy can be a major concern for women living with an autoimmune disease. How will it affect baby? How will if affect mommy? If you so happen to be one of those women and you thought that pregnancy was out of the question for you because of your illness… think again.

Pregnancy with an autoimmune disease

Pregnancy with an autoimmune disease requires careful planning. First, it’s extremely important to have an open and honest discussion with your rheumatologist before thinking about conceiving, preferably 6 to 12 months before. In fact, you should have a similar discussion with everyone on your care team: primary care provider, hematologist, nephrologist, pulmonologist, cardiologist, etc. It’s also important to establish care with a high-risk OB-GYN, preferably someone who has experience caring for people with your condition and who delivers in a hospital staffed by rheumatologists.

During this time your care team plan will work with you to:

Make sure your disease is well controlled on a stable regimen for at least 6 months.
Remove medications that could potentially cause problems for your baby and replace them with safe alternatives.
Identify and anticipate for potential risks that could negatively affect your pregnancy.

High risk medications

Because it would be completely unethical to conduct a randomized controlled study on pregnancy outcomes and exposure to disease modifying agents (DMARDs), the vast majority of evidence regarding the safety of medications during pregnancy comes from animal models and registries such as OTIS: autoimmune diseases in pregnancy project. The following are considered safe to use during pregnancy:

Hydroxychloroquine
Azathioprine

What about biologics?

Again, available data is limited due to the fact that you can’t recruit people into studies to answer these sort of questions. Mounting evidence suggests that TNF-inhibitors are probably safe. However, if I were to choose one biologic, I would probably go with certolizumab for the simple reason that very little if any of it crosses the placenta.

Follow this link from the American College of Rheumatology regarding medication safety during pregnancy.

What about breastfeeding?

The NIH maintains a database called LactMed that contains information about medications and how they affect breastfeeding. The information is free and available to the public.

What does it mean to be high-risk?

Previous pregnancy with complications
Kidney disease
Heart disease
Lung disease (including pulmonary hypertension), very high risk
Flare of a rheumatic illness
A history of previous blood clot
Presence of SSA and SSB antibodies
Presence of antiphospholipids
IVF (in vitro fertilization)
Pregnancy with twins, triplets, etc.
Mother being over 40

SSA and SSB antibodies

SSA and SSB increase the risk of neonatal lupus. The risk is small, 1-2% of cases but the risk significantly increases in women who have already borne a child with neonatal lupus.

Children that are born with neonatal lupus may have a rash, liver problems, and low blood cell counts but thankfully, these symptoms disappear completely after about six months. Having neonatal lupus does NOT increase the risk systemic lupus erythematosus (SLE).

The most dreaded complication of neonatal lupus is complete heart block, which typically occurs at weeks 20 – 22. Your high risk OB-GYN will conduct frequent fetal cardiac tests during the “high risk period” +/- a few weeks. While it’s currently not recommended to use prophylactic steroids to prevent this from happening, if congenital heart block does occur, your doctor will most likely use steroids and in utero pacing.

Antiphospholipid antibodies

There are three types of antiphospholipids: lupus anticoagulant, anticardiolipin antibodies, and beta-2 glycoproteins. The presence of these antibodies, particularly at high titers, are associated with something called the antiphospholipid syndrome. People that have this condition have a higher risk of developing blood clots. Hence, they tend to get DVTs and pulmonary embolisms. Moreover, women tend to get miscarriages, stillbirths, pre-term deliveries, and preeclampsia. Since antiphosplipid antibodies increase the risk of clots, to prevent complications, women that have antiphospholipids should take “pregnancy-safe” blood thinners.

How does pregnancy affect disease activity?

It all depends on the disease. Typically SLE becomes more active during pregnancy, whereas rheumatoid arthritis and psoriatic arthritis tends to improve.

Lupus nephritis

HOWEVER, there are a few notable circumstances where pregnancy is risky for both the mother and the child. It’s generally not safe to conceive during a period of very high disease activity. This includes lupus nephritis. It’s generally discouraged to conceive when lupus nephritis is active, but when things are controlled it’s okay with very close monitoring. Patients with lupus nephritis commonly flare, are at higher risk of preeclampsia, and HELLP syndrome.

Pulmonary hypertension

Another very important high risk situation is pulmonary hypertension. This happens in systemic sclerosis, SLE, myositis, mixed connective tissue disease, Sjogren’s syndrome, and rheumatoid arthritis. When pulmonary hypertension is caused by an autoimmune disease, we call it connective tissue disease-related pulmonary arterial hypertension. Symptoms include:

Shortness of breath, particularly with exertion
Fatigue
Dizziness, passing out.
Chest pain
Swollen legs or swollen abdomen (ascites)
Palpitations
Bluish color

So why is this especially important for pregnancy-related matters?

A study by Qian et al. aimed to evaluate the survival of patient with SLE-associated pulmonary arterial hypertension. This was a systematic review and meta-analysis. They identified 6 studies which included a total of 323 patients. They found that 1-, 3-, and 5-year survival rates were 88%, 81%, and 68% respectively. The more severe the pulmonary hypertension, the worse the outcome.

However, high pulmonary hypertension peripartal mortality is not an isolated incident related to SLE alone. It is elevated for all connective tissue disease-related caused of pulmonary arterial hypertension.

Conclusion

In conclusion, we’ve come a long way when it comes to rheumatic diseases and pregnancy. Way back when, it was generally discouraged in practically all circumstances. But things have changed. With careful planning and monitoring, many women with autoimmune diseases can now have safe pregnancies.

Medical Disclaimer

References

Kelley and Firestein’s Textbook of Rheumatology, tenth edition

American College of Rheumatology

Pasut G. Pegylation of biological molecules and potential benefits: pharmacological properties of certolizumab pegol.BioDrugs. 2014 Apr;28 Suppl 1:S15-23.

Moroni G, et al. Maternal outcome in pregnancy women with lupus nephritis. A prospective multicenter study. J Autoimmun. 2016 Nov;74:194-200.

Thakkar V, Lau EM. Connective tissue disease-related pulmonary arterial hypertension. Best Pract Res Clin Rheumatol. 2016 Feb;30(1):22-38.

Qian J, et al. Survival and prognostic factors of systemic lupus erythematosus-associated pulmonary arterial hypertension: A PRISMA-compliant systematic review and meta-analysis. Autoimmun Rev. 2016 Mar;15(3):250-7.

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