(un)Realistic Expectations

“My health may fail, and my spirit may grow weak, but God remains the strength of my heart: he is mine forever.” Psalm 73:26

I hope that everyone had a wonderful Thanksgiving holiday. My oldest came home from college and we were joined by a few friends from church. Other than the 18 hours of cooking over two days, it was a pretty relaxing affair. The highlights are the pumpkin, pecan, and sweet potato pies. But for some reason, everyone but me takes a special liking to the pumpkin torte that my wife makes.

I’m taking a break from the RA Weapons series to discuss how RA causes adjustments in expectations.

On Friday after Thanksgiving, the Christmas lights were installed on the house. It’s a fairly straightforward task being that the design hasn’t changed in five years and three children joined in to help. After the lights were up, the snowboards and skis were pulled down from storage for adjustments, tuning, and waxing. The kids learned to wax their own equipment. It’s fun to watch the kids embrace this lifelong sport. There are numerous mountains within an hour or so that have wonderful ski runs.

waxing skis http://www.flickr.com/photos/a2c_s_1980/

After the few hours on these responsibilities, the body made it clear that it had enough. The next couple of days resulted in much rest and joint pain. And of course, the ski/snowboard work got me thinking about how realistic (or unrealistic) my expectations are for future activities. Of all physical activities, snow skiing ranks the highest for me. My skis were waxed the other day but I have no idea if/when skiing will be a reality. But the time will come very soon when we’ll load up the equipment and head to the slopes. I’ll try to ski but my expectations are quite low at the time given the fact that a simple job of hanging Christmas lights kicked me pretty hard. Fellow RA bloggers Terry and Kelly recently spoke about how RA caused them to adjust their expectations for life activities.

This leads to a broader reflection on changes in expectations as RA takes a toll and medication changes are tried. In October, my doctor switched me from Enbrel to Cimzia. The last monthly dose of Cimzia was injected on November 4^th. The next injection is scheduled for this Wednesday. This will be the 3^rd injection since switching over from Enbrel.

Fellow bloggers Terry, Kelly, and I are in the process of trying new medications and we all seem to be attempting to come to grips about what to expect in terms of effectiveness. All three of us can point to a time when we were completely off major medications and can attest to the fact that symptoms were worse during those periods than we were on the “ineffective” previously used meds. But what can we expect with the new medications? In order help track impact and attempt to answer this question, I decided to keep a daily journal of RA symptoms starting in early November. This journal will be taken to my upcoming rheumatologist appointment.

In addition to listing specific symptoms, I created a scale of 1-10 for both energy level and overall joint health. Overall joint health included pain, stiffness, and swelling. A high number is positive and a low number is negative. I also tracked the number of days with headaches since I suspect Cimzia was causing these regularly. A simple spreadsheet was used to track the daily scores. A graph (see below) was produced to display a pattern over time.

The first thing I noticed was that everyday seems to be different. The second pattern is that energy and joint health appears to be related. And finally, there is a slight downward trend over the month since taking the Cimzia injection. This is not surprising since the effects wear off over time. The expectation is that the upcoming injection will bring some relief (and maybe more headaches). Relief is my hope.

I’m considering creating some sort of tracking tool based on this process so that RA patients can easily track changes over time. Feedback from readers would be appreciated. You can contact me via email or leave a comment on the blog.

Will Cimzia work long term? Will snow skiing be in store? These are questions that can’t be answered right now and expectations must be tempered.

Chemical Weapons

“Chemical warfare (CW) involves using the toxic properties of chemical substances as weapons to kill, injure, or incapacitate an enemy.” Wikipedia[i]

http://en.wikipedia.org/wiki/File:WMD-chemical.svg

Many of the first medical treatments for RA were chemical drugs that were actually developed for other diseases. Disease-modifying anti-rheumatic drugs, or DMARDs, are the hallmark chemical treatments for RA.[ii] These chemicals attack or incapacitate the enemy of RA, inflammation, using various processes. Many of these processes are not fully understood by scientists but suppression of the immune system resulting in less inflammation is suspected.

Methotrexate, plaquenil, sulfasalazine, Arava, cyclosporine, Imuran, Cytoxan, and gold salts are commonly used to treat RA. All of these are rather simple chemicals in terms of design, development, and production. This also tends to make them less costly relatively speaking. In heavier doses, some of these drugs are used as chemotherapies for various cancers. Plaquenil is used to treat malaria. If you ever want to help the uninformed really understand the seriousness of RA, let them know that you are taking a chemotherapy drug! Because they are somewhat harsh chemicals, the lists of side effects are rather lengthy.

Sulfasalazine was originally used as an antibiotic. But it is also thought to impact inflammation in the gastrointestinal tract. As mentioned in an earlier post, it is thought that 2/3 of the immune system lies around the intestines so it makes sense that sulfasalazine may reduce inflammation by impacting this area. This was the very first drug prescribed for my RA. No chance was given to see its impact because about 7 days into popping these large pills, I developed a severe allergic reaction. This occurred over the weekend and I was very close to heading to the emergency room. It took over a week for the sulfa to get out of my system. Also during this time, the symptoms of RA stepped it up many levels…that’s when methotrexate was prescribed.

I like to call methotrexate (MTX) the “chemical weapon” of choice against RA. At higher doses, it serves as a chemotherapy drug for some forms of cancer. In this use, it actually acts as a cell killer…attacking cells that divide quickly (like cancer cells). At lower doses, MTX acts as an anti-inflammatory by affecting T-lymphocytes. Methotrexate is probably used by more RA patients than any other treatment and is regularly used in combination with biological treatments (a future post).

http://www.flickr.com/photos/psyberartist/

My experience with MTX was short-lived. I took the first dose (7.5mg) on a Saturday as many do in an effort to fight the common side effects of nausea and headaches. By week three, it was clear that I couldn’t tolerate it at all. Besides the constant nausea and headaches, my brain was in a state of fog, my body hurt (not just from the RA), and I was totally nonfunctional. My rheumatologist said that a portion of patients cannot tolerate MTX. I knew it would be me because of my sensitively to every medicine under the sun. That’s when Enbrel was started.

Even though I’m no longer taking any “chemical weapons” for RA, I’m glad that they exist and provide relief for many. But the side effects are many and patients need to be fully aware of them in an effort to weigh benefits and costs.

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[i] http://en.wikipedia.org/wiki/Chemical_warfare

[ii] http://www.webmd.com/rheumatoid-arthritis/modifying-medications

Nuclear Weapons – Steroids

The first thing one must discuss when the topic of steroids and RA comes up is that there is a big difference between anabolic and corticosteroids. The former are associated with muscle mass gain popularized by illegal use in athletes. The later are connected with metabolism and immunity. Now that we’ve cleared up that little issue, we can delve into the use of steroids in the treatment of RA.

http://www.flickr.com/photos/denn/

Corticosteroids are powerful anti-inflammatory medicines and they are regularly used for all sorts of inflammatory problems. The most common forms of administration in RA patients are joint site injections and oral pills. But this effectiveness of fighting inflammation comes with side effects. The most common side effects of corticosteroid use include the following:

• Elevated pressure in the eyes (glaucoma)
• Fluid retention, causing swelling in your lower legs
• Increased blood pressure
• Mood swings
• Weight gain, with fat deposits in your abdomen, face and the back of your neck
• Cataracts
• High blood sugar, which can trigger or worsen diabetes
• Increased risk of infections
• Loss of calcium from bones, which can lead to osteoporosis and fractures
• Menstrual irregularities
• Suppressed adrenal gland hormone production
• Thin skin, easy bruising and slower wound healing [i]

Other side effects I would like to add to this list are difficulty sleeping and redness of the skin. For joint injections, patients will often overuse the joint because it feels so good resulting in further damage to tissue. There are probably other side effects and I hope readers chime in with their stories. This long list of side effects is why I categorize steroids as the Nuclear Weapon against RA. While they do an excellent job of fighting the enemies of RA-inflammation-they impact the entire body.

http://www.flickr.com/photos/scfiasco/

Most RA patients have experienced the famous Medrol Dose Pack. This handy package starts with 6 pills the first day and ends with one pill on day six. The first time I was prescribed Medrol was a weekend when I had a terrible reaction to methotrextate. My doctor pulled me off methotrexate and immediately put me on a dose pack in an effort knock down the RA symptoms until I could get into his office to begin Enbrel. The dose pack really helped me feel better until Enbrel started working. But because of the side effects, I try to avoid them as much as possible.

This was not my first experience with corticosteroids. Five years ago, before even being formally diagnosed with RA, a major case of iritis (inflammation of the eye) hit both eyes. It finally took a visit to an Ophthalmologist to figure out what was happening. He immediately prescribed regular doses of prednisone eye drops. They started out every two hours (all night long) and eventually tapered off over the next month. One interesting side note…this episode was the first sign of RA. The Ophthalmologist started asking me strange questions about joint problems and told me that iritis in both eyes simultaneously is an indicator of autoimmune disorders. No blood tests were run and I quickly forgot about it until other symptoms cropped up later. 

Just like superpower countries, a stockpile of corticosteroids remains stashed away just in case things get out of hand and the inflammation enemy strikes with a vengeance. Currently though, there seems to be détente between the enemy and my body. Other medicines seem to be doing the trick. But my finger remains ready to push the button releasing a nuclear war if needed.

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[i] http://www.mayoclinic.com/health/steroids/HQ01431

Arthritis Foundation Drug Chart

What timing! The Arthritis Foundation publishes a comprehensive drug chart. This will be a great tool to go along with my series of blogs on weapons against RA.

http://www.arthritistoday.org/DrugGuide/drug-chart.php

Weapons in the War Against RA Inflammation

RA is an autoimmune inflammatory disease meaning that your immune system attacks itself causing inflammation resulting in pain, heat, swelling, fatigue, malaise, and permanent joint destruction (described in an earlier blog post). Historically, medical treatments against RA are designed to reduce inflammation. I will use a war analogy to describe this battle, discuss the weapons used, and describe some of the battle scars I’ve experienced thus far. This war against inflammation is multifaceted and anyone diagnosed with RA long enough will likely experience most of the weapons from the doctor’s arsenal. Here’s how I categorize the weapons using military terminology.

• Conventional – NSAIDs
• Nuclear – Steroids
• Chemical – Methotrexate and others
• Biochemical – biological drugs
• Natural – diet

In this post, I will start with conventional weapons. Subsequent posts will systematically address the other categories.

http://www.flickr.com/photos/exalthim/

I liken non-steroidal anti-inflammatory drugs ( NSAIDs) to conventional weapons. Thousands of years ago it was noticed that chewing on the bark of willow trees reduced fever and pain. Aspirin was eventually developed in the 1800s and it is now the most widely used medicine in the world. Many other chemicals over the years joined the conventional weapon arsenal including ibuprofen, naproxen, celebrex, and vioxx (removed from the market). NSAIDs work by inhibiting enzymes that promote inflammation. They have provided much relief for many arthritis sufferers over the years. But if taken over long periods of time for chronic pain, NSAIDs leave collateral damage including stomach problems and elevated risk of heart attacks and strokes.

I occasionally took NSAIDs over the years mostly for headache or fever. After ankle surgery in 2007, my orthopedic doctor recommended that I take up to 1,600mg of ibuprofen a day.  Two to three days later my stomach was burning up. I had experienced regular heartburn over the past 10 years and even had my stomach scoped at one time (nothing was found). It was no surprise that ibuprofen caused stomach upset. After my second ankle surgery, I tried Celebrex since it supposedly did not cause as many problems. Stomach upset eluded me but Celebrex did not seem to have much anti-inflammatory impact. After 30 days, the insurance company sent a terse letter indicating that they were not going to cover Celebrex unless my doctor had a good reason. They argued that over-the-counter NSAIDs are just as effective and cheaper.

This is where my use of NSAIDs ended until recently when my rheumatologist prescribed Mobic (meloxicam). Enbrel stopped working for me and joint pain and damage was increasing. The first signs of finger bending were noticed. He felt that while I was waiting for my new biological medicine, Cimzia, to take effect, I should take a NSAID. He knew about my intolerance of NSAIDs but thought Mobic was worth a try since people typically display less problems with it. After two doses (taken twice a day), I could tell that my stomach didn’t like it either. I stopped taking it. I think about pulling it out and giving it another try; especially on those days when joints are screaming at me. But the thought of those stomach juices churning inside keep from reaching for those little yellow pills. While conventional warfare against RA via NSAIDs works for some, many cannot tolerate the side effects.

Next post…nuclear weapons

Cimzia Update

A second dose of Cimzia (certolizumab pegol) was injected Wednesday evening. Since Enbrel was no longer working well, my rheumatologist recommended trying a new medication. Cimzia, which was recently approved by the FDA, is designed to stay in the body longer thereby making it more effective. The nurse stated that about 15-20 patients in their office switched to Cimzia after Enbrel and Humira stopped working for them.

Below is a photo showing all the paraphernalia associated with self-administration of the antibody treatment. I do “enjoy” the ergonomically designed syringes!

I noticed less fatigue last month after the first injection although joint pain and inflammation continued. The first clear evidence of finger joint bending was noticable. My knee was bothering me after swimming a little (so much for swimming as a good exercise for RA). The fatigue returned over the past few days. Since swine flu made a visit to our house last week (my son had it), I debated whether I should wait to take the second dose. Cimzia lowers the immune system increasing vulnerability to infections. We were still in the incubation period for the flu. But I realized that the toll of RA on my body trumped anything else and I gave myself the second injection. The day after the 2nd injection brought an obvious increase in energy, less “brain fog”, and less joint stiffness and pain.

My rheumy said to give it a good 3-4 months before making any long-term judgements about the efficacy of Cimzia.  Since the pain was still present and finger bending noticeable, my rheumy suggested that I try Mobic (meloxicam) which is a non-steroidal anti-inflammatory (NSAID). I can’t tolerate ibuprofen so we’ll see how this goes. Thus, another weapon is added to the chemical arsenal designed to fight RA in my body.

Inflammation – the Good, the Bad, and the Ugly

On a long plane trip from Orlando back home to Seattle, an article in the November 2009 issue of Scientific American grabbed my attention. In the article, called “New Culprits in Chronic Pain”, the author discusses chronic pain that is not alleviated by traditional medications like morphine.[i] The offender appears to be overactive nerve cells called glia that help regulate nerve messenger chemicals. As I flipped to a diagram showing the processes involved, I was surprised to see that familiar enemy of RA patients called tumor necrosis factor (TNFα) listed as an inflammatory cytokine being released by the glia. The first thing that came to mind was that TNF blockers like Enbrel may help. A turn of the page revealed a table listing potential medicines being tested to help fight chronic pain…Etanercept (Enbrel) was listed as being in human trials. Excess inflammation seems to be connected to numerous diseases and medical problems.

Inflammation is normally a good thing. It’s part of an immune response when an infection or invader gets inside the body.[ii] My son recently had the flu (probably swine flu since it’s running rampant around here right now). His body was fighting the virus through inflammation which included fever, chills, fatigue, headaches, loss of appetite, and muscle pain. [iii] My son’s reaction to the flu is an example of acute or short term inflammation. He’s better now and fortunately no one else in the family shows signs of the flu but we’re still in the incubation period for a few more days. (By the way…anyone out there get an H1N1 vaccine yet?)

Chronic or long term inflammation is bad and is linked to all sorts of ugly diseases including RA, inflammatory bowel disease, psoriasis, lupus, scleroderma, polymyositis, vasculitis, rosacea, celiac disease, multiple sclerosis, asthma, and even arthrosclerosis leading to heart attacks and strokes.[iv] [v] [vi] And now chronic pain is associated with inflammation.

http://commons.wikimedia.org/wiki/File:Psoriatic_arthritis_ankle_ar1934-3.gif

As mentioned in an earlier post, inflammation results in messenger proteins called cytokines being released by cells. [vii] In autoimmune diseases like RA, the system is out of whack and too many of these cytokines are released resulting in ongoing inflammation. Most widely used medical treatments for RA are targeted at reducing the inflammatory impact of cytokines.

One of the least publically understood aspects of inflammation is chronic fatigue. This is way beyond just being tired – I refer to this feeling as being run over by a truck. Other than permanent joint damage, for me this is the hardest aspect of dealing with RA. Malaise, lack of interest in social interaction, brain fog, and depression are regularly linked to inflammatory diseases. The causes for this escaped scientists. But now researchers are beginning to unravel possible connections between inflammation and the brain.[viii] Interestingly, this recently discovered connection brings us back to the research about chronic pain – the glia nerve cells are implicated. Perhaps these connections will lead to new treatments that will keep RA sufferers from being “run over by the truck” as a result of chronic inflammation!

In the meantime, the multifaceted fight against inflammation continues (my next blog topic).

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[i] http://www.scientificamerican.com/

 

[ii] http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/I/Inflammation.html

[iii] http://my.clevelandclinic.org/symptoms/Inflammation/hic_Inflammation_What_You_Need_To_Know.aspx

[iv] http://www.crccid.com.au/www/119/1001127/displayarticle/1001196.html

[v] http://www.cibliga.com/en/index.html

[vi] http://www.rosaceatoday.com/RoleofInflammation.asp

[vii] http://nic.sav.sk/logos/books/scientific/node32.html

[viii] http://www.sciencedaily.com/releases/2009/02/090217173034.htm

Warmth 3-Ways

Yesterday brought three forms of warmth. Two were welcome – the other came in spite of objections.

RA is a disease of inflammation. As mentioned in an earlier post, inflammation is heat, redness, swelling, and pain brought about by an immune response. “Cold-bloodedness” was a hallmark of my life. My extremities were always cold. Right or wrong, this was attributed to circulation. But RA brought inflammation to the hands and mysteriously they started feeling warm. Sometimes they were downright hot. Placing my hands on my wife’s face demonstrated the change. While warm hands are preferrable to cold, it is a sign that inflammation is at work and that is unwelcome because with it brings joint damage and bone erosion.

http://www.flickr.com/photos/edeninchina/

The other two forms of warmth that came yesterday were quite welcome. Since cutting back on some church leadership activities over the past month due to RA, some close friends banded together to bring meals every Monday. We enjoyed a fine meal of chicken tetrazinni, broccoli, and peanut butter pie. That brough warmth to our stomachs and hearts.

The third form of warmth experienced yesterday was one that occurs several times a week. We are blessed to have a hot tub in the backyard (a nice thing to have in the Pacific Northwest). Even though it’s 25 years old, it works beautifully. Spending about 15 minutes in the hot tub with the children brought warmth to the achy joints and muscles. Even though the relief is short-lived, it’s a great way to end a day before jumping in bed.

Droplets and Deluges of Life Changes

Two workers were busy installing new gutters and gutter covers on my house today. Autumn and Winter in the Pacific Northwest means that more air comes off the ocean bringing with it moisture. Much of that moisture falls to the ground on the eastside of the Cascade Mountains (rain shadow effect). Our home is actually somewhat protected from the Olympic Mountains across Puget Sound, but about 40-45 inches of precipitation falls annually. Only 10 miles east of us, the rainfall increases to 90 or more inches a year as the Olympic Mountain rain shadow is not as much in effect and the air moves up in altitude. The rain usually comes slowly but it is critical that houses have good gutter systems to collect and divert the water away in order to avoid damage. Thus, good gutters are vital.

http://www.flickr.com/photos/elvispayne/

Once Autumn arrives, the sounds of leaf blowers can be heard almost every day. More often than not, those blowers are on a roof being used to clean gutters in order to maintain flow. That was my weekly routine for the past five years. But that practice was interrupted by a visit from rheumatoid arthritis. Don’t get me wrong, I’m thrilled to not have to clean gutters anymore. But hiring a professional gutter installer brings home the point that RA has changed my life. Here’s a partial list of some activities that have changed over the past year since RA decided to kick it up a notch.

• Lawn mowing and gardening
• Snow skiing
• Long walks with the dog
• Visiting the recreation center
• Missing evening events because of fatigue
• Stopping short that awesome Hawaiian snorkel tour
• Learning how to navigate medical systems
• Cutting back on service activities

Sometimes RA brings changes in small increments…droplets. Sometimes the change is more rapid…deluges. RA patients must have good gutter systems to capture the changes and channel it away. Such systems include family, friends, others who are experiencing RA, good doctors, and most importantly, faith and hope in God. My gutter today came in the form of a handwritten card from a family who thanked me for all I had done at church over the past few years. They knew I was in pain and was cutting back on my activities. And the father of this family offered to clean out my gutters a few weeks back. That note, coupled with the offer to crawl on my roof, helped me stay “warm and dry” today.

Genetic Treatments for RA

* update to post on 10-19-09. The American College of Rheumatology at their annual conference announced a recent focus on genetic research. See the following links: http://www.nxtbook.com/nxtbooks/tristar/acr09-day2/#/2, http://www.nxtbook.com/nxtbooks/tristar/acr09-day2/#/6

As mentioned in an earlier post, three factors, environmental, genetic, and a “leaky gut”, are suspected to play some role in rheumatoid arthritis. When in the process of being diagnosed, patients complete massive amounts of paperwork. Embedded within these forms are questions about family medical history. These questions are attempting to establish genetic propensity for autoimmune diseases. Doctors will ask new RA patients if anyone else in the family has a history of autoimmune diseases since there appears to be a connection. There is even a database designed to track these connections.[i]  My mother had Hashimoto’s disease (hypothyroidism), my grandmother had psoriasis, and my great uncle was suspected of having ankylosing spondylitis. Whether or not there is any familial link is not certain but the fact that these disorders were present in my family increases the risk. For RA, the risk of closely related family members having the disease is about 4%.[ii]

http://www.flickr.com/photos/25731575@N04/

Since the recent mapping of the human genome in 2003, scientists are starting to unravel genetic connections to a variety of diseases.[iii] There are 23 chromosomes, about 25,000 human genes, and over 3 billion chemical base pairs in the human genome. These base pairs contain the code for all of our characteristics. For the most part, all of us are strikingly similar genetically. Anytime there is a slight change in a genetic base pair sequence, it’s called a singular nucleotide polymorphism or SNP. This YouTube video provides a short and simple overview for the scientifically challenged. SNPs are what make all of us different. Hair color, height, and other characteristics (both external and internal) are determined by these slight genetic differences or SNPs.

http://www.flickr.com/photos/ethanhein/

A variety of SNPs have been linked with RA. Scientists in the UK and at MIT found a SNP called PTPN22 connected to a variety of autoimmune diseases including RA.[iv] [v] Other SNPs connected with RA include rs6920220 and rs5029937. [vi] [vii] [viii] Another group reported that a SNP on chromosome 17 is linked to proteins in the thymus gland which are connected to psoriasis, rheumatoid arthritis and systemic lupus erythematosus.[ix]

So what does this mean for the future of RA treatment? At this point it doesn’t mean much. But the fact that some genetic markers for RA are being identified brings hope that future treatments can be targeted at these SNPs. In an earlier post I mentioned that scientists at the University of Rochester identified that the NF-kappaB signaling pathway is involved with tumor necrosis factor (TNF). TNF is the target of many of the biological treatments like Enbrel, Humira, Remicade, Cimzia and Simponi. An article published in May 2009 suggests that genetic SNPs related to this pathway are of interest in RA and that scientists should “translate these discoveries to improve care of patients with RA.”[x] Initial experiments in transferring genes into the joints of RA patients show promise. [xi] [xii] [xiii] But time will tell and I wonder if those of us living with RA now will benefit from this work. In the meantime, we can marvel in our genetic differences.

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[i] http://www.biomedcentral.com/1471-2105/7/325

[ii] http://genetics.emory.edu/pdf/Emory_Human_Genetics_Autoimmune_Disorders.pdf

[iii] http://www.ornl.gov/sci/techresources/Human_Genome/home.shtml

[iv] http://www.ncbi.nlm.nih.gov/pubmed/15934099

[v] http://medgadget.com/archives/2007/01/unravelling_gen.html

[vi] http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2674282/

[vii] http://www.snpedia.com/index.php/Rs6920220

[viii] http://rheumatology.oxfordjournals.org/cgi/content/abstract/48/6/618

[ix] http://www.nytimes.com/2003/11/10/us/3-autoimmune-diseases-share-a-genetic-defect-scientists-find.html

[x] http://www.ncbi.nlm.nih.gov/pubmed/19365266

[xi] http://www.pnas.org/content/102/24/8698.full

[xii] http://www.reuters.com/article/healthNews/idUSTRE5124AT20090203

[xiii] http://www.harvardscience.harvard.edu/medicine-health/articles/gene-therapy-demonstrates-benefit-patients-with-rheumatoid-arthritis