RAers, can you prevent Rheumatoid Arthritis in your children?

‘Doc, I have had rheumatoid arthritis (RA) since last 10 yrs. I know this terrible disease inside out. It has ruined my life. I do not want my daughter to suffer from this. Can I do anything to prevent rheumatoid arthritis in her? Does science have any answer? Are there any meds/ strategies to prevent rheumatoid arthritis?‘

The words of my patient are still echoing in my mind. ‘Does science have an answer?’ For a long time, we were grappling with the best strategy to control RA. Hence, majority of the research was directed at this.

However, importance of the ‘pre-RA’ phase has been understood. ‘Pre-RA phase’ is the phase before the symptoms of RA actually appear. This phase is important from the preventive perspective.

We do know about a few proven strategies to prevent RA.

These include:

1) Smoking cessation — The risk of developing RA is about two times higher for male smokers than for nonsmokers. For women, the risk for smokers is approximately 1.3 times greater than for non-smokers. (We have seen this in detail previously)

2) Dental hygiene—Periodontal disease is a proven risk factor for RA. (We have discussed this previously on the blog)

3) Optimal body weight. This is a recent finding. We would soon have a dedicated blog post for this. As of now, aim at a healthy body weight to reduce chances of developing RA.

4) Adequate vitamin D intake.

A study specifically looking at the various risk factors for evolution of RA in those with family history is underway & should provide further insight.

So, RAers; your daughters need not suffer the way you did. We do have these definite, easy strategies to prevent RA in those genetically predisposed.

Life of a #rheum patient: It is indeed a juggling act

We always keep complaining that most studies about Rheumatoid Arthritis (RA) focus only on the objective measures of inflammation & other factors rheumatologists are interested in. They hardly ever look at what a patient goes through, physically & mentally due to RA. Caroline Flurey & colleagues have just published a study that looks at Rheumatoid Arthritis from the patient’s perspective.

The study consisted of interviews of patients with Rheumatoid Arthritis to understand how they manage their day-to-day life & cope with their ailment.

The results have been startling. For us Rheumatologists, they are an eye-opener; letting us a sneak preview of what a RAer goes through. As a RAer, I am sure you can identify yourself as you go through the study results.

Here is what the study revealed. I have also added links about remedial actions.

1) Most RAers experience RA as a constant background reality, often being aware of its presence & the limitations it brings. Life is all about micromanaging & macromanaging their symptoms & daily life so that it remains in the background & does not interfere much with daily life.

2) Learning & developing proper coping strategies (details in resources at the bottom of the post) can do a lot good & help keep RA in the background. The aim of any rheumatologist is to keep the RA in remission (background) & minimize the chances of a flare.

3) RA can be & is unpredictable. It can intrude into life in the form of a flare without any notice. A flare can reach a magnum proportion by the time one sits trying to make sense of the fluctuation.

4) Once in a flare, coping strategies do matter. Some try to regain control on their own, some seek medical help right away while some Leave it as the final option.

5) One of the best ways to better manage a flare is to keep a self-help plan ready in consultation with your Rheumie. We have discussed this in the past here on the blog. Let it roll as soon as a flare is recognised & seek a Rheumie appointment in the mean time.

All in all, life of a #rheum patient is indeed a juggling act with a need to balance every aspect of life so as to keep RA & its impact in the background.

DMARDs/ biologics, positive attitude & the right coping strategies help in this regard.

In case, RA tends to overpower & come to forefront in form of a flare, there is no need to panic. Roll out the ‘flare plan’ immediately & push RA in the background again.

Resources:

1) Study- It’s like a juggling act: rheumatoid arthritis patient perspectives on daily life and flare while on current treatment regimes. Caroline A. Flurey & colleagues Rheumatology (2013) doi: 10.1093/rheumatology/ket416

2) How to plan a house cleaning job with RA?

3) How to arrange the kitchen if you have arthritis?

4) Tips for painless cooking.

image courtesy: http://www.openclipart.org

Steroids for Rheumatoid Arthritis: Misconceptions & the reality

Steroids……

More bad than good comes to one’s mind when steroids are mentioned, isn’t it? Steroids (Glucocorticoids) have been equated with all that allopathy has to offer for its arthritis patients. It is thought that each & every patient consulting a Rheumatologist would be on long-term steroids irrespective of his diagnosis & would invariably end up with side effects.

Glucocorticoids (popularly known as steroids) were discovered by Scientist Hench. It was a path-breaking discovery & Hench was awarded the Nobel Prize for this in 1950.
Steroids when introduced were used for Rheumatoid Arthritis (RA). As expected they had miraculous results. It was thought that a cure for Rheumatoid Arthritis was in the making. Variable doses were given for variable duration as everyone was on a learning curve. Soon, the side effects were realised. Search began for better medications. This resulted in the development of DMARDs & later biologics that have revolutionized the treatment & outcome of Rheumatoid Arthritis. Not just new drugs, but treatment strategies such as ‘treat to target’ were developed to ensure remission in RA.

So then, if not for steroids, how is RA treated now?
RA is now treated with a target of remission (absolute control of arthritis) right from day 1. Patients are started on DMARDs; generally a combination with Methotrexate as the anchor drug. The DMARD doses are stepped up with the aim of achieving remission asap. If the patient fails to show a good response by six months, biologics come into the picture.
What about steroids in that case? What is its role? Steroids are given to begin with as a bridge till the time DMARDs have their effect. This would mean a small dose of steroid for 4-6 weeks.

However, there a few situations in which steroids have to be given in the long run. These include
1) Rheumatoid Arthritis related Interstitial Lung Disease
2) Rheumatoid vasculitis – this can present as vasculitic ulcers
3) Rheumatoid Arthritis related mononeuritis multiplex (damage to multiple peripheral nerves)
4) Rheumatoid Arthritis related scleromalacia (an eye complication)
5) An occasional patient who has persistent active arthritis despite DMARDs & cannot afford biologics.
All in all, steroids have a well-defined role & use as far as Rheumatoid Arthritis is concerned & one does not have to be on long-term steroids unless for some specific indications.

Why are we Rheumatologists looking forward to Tofacitinib (Xeljanz) ?

Rheumatoid disease is a chronic disease predominantly involving the joints. We have come a long way as far as treatment & outcomes are concerned. We have been able to put life back into patient’s life.
However, not everyone is that lucky. We are still not able to achieve remission in each & every patient. Statistically, almost 20- 30% rheumatoid patients do not improve sufficiently with DMARDs & biologics. The retention rate of most biologics are low (retention rate is the proportion of patients continuing biologics on a long term basis). We have still not understood the rheumatoid pathogenesis completely. We have not yet located the master switch that can turn off the inflammation.

As Rheumatologists, we would like each & every patient to achieve remission & do well. That is precisely the reason why we are looking forward to further development in understanding of RA & new drugs to tame the inflammation.

Rheumatoid inflammation

In rheumatoid disease, immune cells in the synovium of the joints get activated. They secrete various chemicals called cytokines. These cytokines are absorbed in blood & circulate throughout the body. These in turn act on other immune cells; activate them. The activated immune cells start secreting more cytokines. Theses cytokines are responsible for the joint damage & other complications of Rheumatoid disease. So, our efforts are directed to block either these cytokines or the cells secreting them. This would not only reduce the chances of joint damage but also keep the inflammation in check by blocking activation of immune cells. We can block these cytokines & cells with DMARDs & biologics.

Let us consider an example to understand the rheumatoid inflammation & the mechanism of various medications. This is akin to the following plot.

There are 5 terrorists (cytokines ) who want to enter an island country (immune cell) to start a terrorist camp & train more terrorists (generate more cytokines). So, if they are able to enter this country, the number of terrorists will increase as also the chances of destructive activities. They can enter the country by air using multiple airlines ( Airline TNF- α, Airline IL-6, Airline B cell)

If a Rheumatologist is the police; using DMARDs is like using multiple contacts in various airlines asking them to block the entry to the terrorists. This may work if one has good contacts, but is not foolproof.

Biologics are more specific. They are like specific legal orders to specific airlines to block their entry. So if one blocks the TNF α Airline from carrying the terrorists, the island is safer. But then, this is not the only airline available. They can always take the other airlines & still manage to enter the country & succeed with their plans. The same way, a biologic works but then is not the final answer.

How about going a step further? One can also block their entry at the ports of entry. This will block the terrorists irrespective of the airline they use.

This is exactly where we are today.
We have taken the war against Rheumatoid to the ‘ port of entry- signal transduction’ level. Instead of blocking multiple different cytokines, we are now looking at blocking the cellular system that responds to multiple cytokines. This way, we can block the effect of multiple cytokines with a single medication & reduce activation of immune cells thus keeping the Rheumatoid inflammation under check.
Janus Kinase is an enzyme that works at the port of entry in the cell & helps the transduction of message (execution of the plot). We now have Tofacitinib (xeljanz), a Janus kinase blocker recently approved by FDA.

As we saw, this is clearly a step ahead in our battle against the Rheumatoid Disease. We would be looking how well this technological advance really translates in practice in the further blogposts.

How does Rheumatoid arthritis affect the cervical spine (neck joints)?

Rheumatoid disease can affect the cervical spine (neck vertebrae) joints as any other joint. What makes the cervical spine joints different is the fact that the spinal cord is in close vicinity & any pressure on the same by the rheumatoid synovium or the bone can lead to paralysis.

To understand this, we should understand the anatomy of these vertebrae. The 1 st vertebra is called Atlas & the 2 nd vertebra is called the Axis. These are ring shaped circular bones. The axis has a vertical structure called the odontoid process (Dens). The atlas sits on top of the Axis & the odontoid process.

The space enclosed by the atlas has the odontoid process & the spinal cord within. The swollen rheumatoid synovium destroys the ligament (Transverse Ligament) that holds the odontoid process in its position. Once this ligament is damaged, the odontoid starts pressing against the spinal cord. The cord in turn has nerve fibres that control the movements of the limbs.

Early symptoms would include weakness in the limbs, neckache, electric current like sensation when one bends the neck. This generally happens with chronic deformed Rheumatoid Arhtirits.

Prevention with tight control of Rheumatoid activity remains the best way to avoid this serious problem. However, once the dislocation occurs, surgery remains the best option to avoid damage to the spinal cord.

History Of Rheumatoid Arthritis- an infographic

Does One Need Anti Arthritis Meds After Knee Replacement Surgery (With Rheumatoid Arthitis) ?

Rheumatoid Arthritis (RA) is an inflammatory ailment that affects multiple joints. However, this is too simple a picture. RA has systemic manifestations & can involve other organs like eyes, lungs, nerves as well. In fact, we now call it Rheumatoid Disease as it is more than just arthritis.

Unchecked rheumatoid inflammation in the joints damages the joints (as seen previously on this blog). It can destroy the cartilage in the joints & leads to secondary osteoarthritis. This is common in the knee due to the weight bearing.

Surgical intervention like TKR (Total Knee replacement), THR (Total Hip replacement) are used to take care of the damaged joint. Once severely damaged, knee replacement surgery remains the best option. TKR, THR thus take care of the mechanical problem in the involved joint. It does not take care of the RA activity. Hence the surgery will have no implications on the inflammation in the other joints.

Hence, DMARDs (Anti Arthritis meds like Methotrtexate,Hydroxychloroquine, Leflunomide, Suphasalazine are a must even after surgery to take care of the other joints.

Time, tide & inflammation waits for nobody…

I recently blogged about the ‘drug free remission’ in Rheumatoid Arthritis.
Aggressive treatment with DMARDs, biologics & a targeted approach can help one achieve this.
But, is it really that simple? For the best results, what would one expect from Patients? Positive approach & compliance……
But, why am I thinking about all This?

Last week, I was going through my OPD appointment list. One of the names looked familiar; Mrs. K, but I could not recollect the patient.
A lady in wheel chair, with most of the joints swollen was brought in by 6 of her relatives! She was unable to walk on her own. As I went through her file, history unfolded.

I had seen her some two years back. A lively young lady, a doting mother had consulted me for her joint complaints. She did have rheumatoid arthritis & was started on DMARDs. She was given three DMARDs due to the high disease activity. However, unfortunately she continued to have persistent joint inflammation even after 6 months of therapy.

The inflammation then started interfering with her personal & family life as well. Frequent leaves were ruining her professional reputation, her son was doing badly at school & there were frustration & fights at home.

We were slowly moving towards a decision of starting biologics. The entire issue, need of biologics, effects, side effects were discussed. The family was alright with the idea of a more potent drug to control the inflammation, but wanted to wait for some more time. We waited for two months, DMARD doses further optimized; but in vain.
After three months, I discussed the issue again. However, they were scared by a pharmacist relative about the side effects of biologics.

That was the last I saw her then. Now, she started telling me what happened after the last meeting. She & her family were scared of the side effects of biologics, decided to try alternative medicine, stopped all her allopathic medicines. The Result? It was staring at me……

A crucial mistake of stopping all DMARDs at a crucial juncture had done a lot of damage. Her knees were badly damaged & hands were deformed. Time, tide & inflammation does not wait for anyone…..uncontrolled inflammation had inflicted enough of damage already & quite a bit was irreversible.

Suppose you are caught in a similar situation wherein you have to decide regarding a biologic/ new therapy advised by your Doctor, how would you go about?

Decision making made easy for patients

A few points to remember —

1) When you go for a second opinion, if the second consultant confirms the proposed line of treatment, go back to your primary consultant who already knows you & your disease. The second doctor would take some time to understand your arthritis & establish his own treatment strategy.

2) Use the internet, get more information. Be judicious in the choice of sites. You can also use the social media to connect with specialists & other patients to learn from their advice, experience.

3) Never stop the ongoing treatment in the mean time. Never go for the radical option of stopping all the medicines without medical advice.

4) Always know when to put a ‘stop- loss’ order. What is this ‘stop loss order’? It simply means that, you should know when to stop wasting time in taking crucial decisions. Your decision & the plan should not take more than 4- 6 weeks (preferably).

Let us not realize that ‘Time, tide & inflammation does not wait for anyone’ the hard way.

Do you take your arthritis meds with fruit Juice?

Do you take your arthritis med with fruit Juice?

If yes, think again. Fruit juice may not let you achieve remission…..
And why is that So?

Many fruits, especially grapefruit juice & possibly orange, starfish, Seville apple juice affect the absorption of methotrexate from the intestine.

Methotrexate is absorbed in the intestine by a pump called OATP. These juices contain chemicals that block this pump & decrease absorption of methotrexate. Grapefruit also blocks CY 350 which affects other meds.

So now that we know about this, what can we do?

1) Avoid taking methotrexate with any fruit juice.
2) Keep a gap of at least 2 hours between methotrexate fruit & any fruit juice.

Leflunomide (Arava) and Pregnancy

Leflunomide (available as Arava / Lefno / Lefumide / Rumalef) is a powerful DMARD used for Rheumatoid Arthritis.

In animal studies, Leflunomide has been found to be toxic to the embryo. In rats; malformations of the head, rump, vertebral column, ribs, and limbs were seen; while in rabbits, malformations of the head, spine were observed.
Studies of Leflunomide in humans are obviously not possible. Hence, whatever data we have about humans is either extrapolated from the animal studies or is from the accidental pregnancies while on Leflunomide.

In view of the known fetal toxicity, Leflunomide is avoided in women of childbearing age group. If it is prescribed, reliable contraceptive measures are advised.
Leflunomide has a long half-life & tends to remain in the body for up to 2 years after stopping therapy. Hence, planning pregnancy would mean waiting for 2 years once it is stopped. There is a washout therapy though, to washout Leflunomide from the body. It consists of taking cholestyramine 8 gm thrice daily for 11 days.

Organization of Teratology Information Specialists Collaborative Research Group studied 64 pregnant women with exposure to Leflunomide during pregnancy & compared them with other pregnant ladies with Rheumatoid Arthritis as well as normal pregnant ladies. A majority of these patients did receive a Cholestyramine washout therapy. The study did not find any significant differences in the overall rate of major structural defects in the exposed group.

These numbers are small & one cannot conclude that Leflunomide is safe in pregnancy. The only conclusion we can draw from the study is that cholestyramine therapy early in cases of accidental pregnancy may avert fetal damage. The risk is least if the washout therapy is started immediately on missing a period.

Leflunomide washout therapy—
1. Cholestyramine to be taken in the dose of 8 gm thrice daily for 11 days.
2. Blood is checked for Leflunomide levels to ensure adequate washout from the body. The levels should be less than 0.02 mg/L on two occasions 2 weeks apart.
3. If the levels are higher, further Cholestyramine course is essential.

Dos & don’ts for patients on Leflunomide
1. Leflunomide is not the first drug to be used for Rheumatoid Arthritis in the childbearing age group. Your Rheumatologist will start Leflunomide therapy only if your RA is not controlled with other DMARDs & after counseling regarding the fetal toxicity.
2. Practice contraception while on Leflunomide to avoid pregnancy.
3. In case of suspected pregnancy, stop Leflunomide & consult your Rheumatologist immediately.
4. You can take a decision regarding continuation of pregnancy in consultation with your Rheumatologist. In case you wish to continue the pregnancy, washout therapy has to begin immediately.
5. Take time out & register with the Leflunomide pregnancy registries at http://otispregnancy.org/otis_study_ra.asp & http://www.uktis.org/UKTIS_reporting_form.pdf Your information will help Rheumatologists & other patients in their knowledge about this medication.

References:
1. Birth outcomes in women who have taken Leflunomide during pregnancy. Chambers CD et al Arthritis Rheum. 2010 May; 62(5):1494-503
2. Teratogen Update: Reproductive risks of Leflunomide; A pyrimidine synthesis inhibitor: counseling women taking Leflunomide before or during pregnancy and men taking Leflunomide who are contemplating fathering a child. Brent RL Teratology 63:106–112 (2001)

Download the ebook: Successful pregnancy with Rheumatoid Arthritis.