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Posts Tagged ‘immune system’

Ever since the H1N1 swine flu scare a few years ago, I make it a point to get a flu vaccine every autumn. When receiving a regular physical exam from my general practitioner last week, the doctor suggested that a pneumococcal polysaccharide vaccine be added…

To check out the rest of this post, go to the newly launched website rheumatoidarthritis.net. I will be writing posts for this site periodically as a Patient Advocate and will continue to make regular posts at this personal blog.

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PrednisoneIt seems that many RA patients have this love-hate relationship with prednisone. For me, it’s all hate. Every time RA symptoms seem out of control, my rheumatologist mentions taking some prednisone at least short term to knock down the symptoms. I understand the rationale. If a powerful anti-inflammatory like prednisone can be used, the disease modifying and biological drugs have an easier and quicker time impacting the disease. And the suggestion is given out of compassion in an effort to make me feel better. For that I’m appreciative. But my response tends to be, “I’d rather live with the symptoms of RA than with the side effects of prednisone”.

For me, even taking 1 mg of of prednisone brings about side effects with which are difficult to deal. I get so wired that sleep is impossible. A couple days of that and nobody wants to be around me. I get this constant jacked-up feeling making it difficult to relax. This makes me want to run around and keep busy with projects contributing to joint pain and fatigue. There’s a vicious cycle of mood swings that my family can easily see. I also get a voracious appetite causing me to eat anything that is not nailed down.

I also refuse to start long term treatment with prednisone. I’ve seen what it’s done to a colleague at work in terms of weight gain (also hard on the joints). The other long term side effects sound pretty nasty and include high blood sugar, increased risk of infections, thinning bones, impact on adrenal gland hormone production, and slower wound healing (see the Mayo Clinic’s site). There is a risk of glaucoma in the eyes and with my mother’s difficult case of glaucoma, that is something I should probably avoid. I remember 9 years ago when I had my first autoimmune symptom, uveitis in both eyes, the ophthalmologist prescribed a strong dosing regimen of prednisone drops. It was every two hours and I was to get up in the middle of the night and put in drops. He was adamant about doing this in order to save my eyes from long term damage. But he also cautioned me that I couldn’t take it for more than a month since steroid induced glaucoma was a real danger. Adding to these long term side effects is the fact that it’s difficult to wean off of corticosteroids (check out RA Guy’s recent post).

Yes, I keep a bottle of prednisone pills in the cabinet. But I try to avoid using them like the plague.

Photo credit: By D4duong (Own work) [GFDL (http://www.gnu.org/copyleft/fdl.html) or CC-BY-SA-3.0 (http://creativecommons.org/licenses/by-sa/3.0)%5D, via Wikimedia Commons

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Money_closeupThere are many diseases in the world that impact people’s lives. According to the United States Centers for Disease Control (CDC), the most common chronic diseases include heart disease, cancer, stroke, arthritis, and diabetes.[i] It is estimated that over 12 million Americans have some form of cancer[ii], 25 million with diabetes[iii], and 25 million with diagnosed heart disease[iv]. The CDC also claims that,

Arthritis is the most common cause of disability, with nearly 19 million Americans reporting activity limitations.[v]

Of course, those 19 million Americans include people with the more common osteoarthritis which is caused by mechanical processes in the joints and is usually associated with age. It is estimated that rheumatoid arthritis, an autoimmune disease which can strike all ages, impacts over 1.5 million Americans.[vi] Of the 81 million Americans diagnosed with one of the major chronic diseases noted above, all forms of arthritis accounts for 24% and rheumatoid arthritis (RA) accounts for almost 2% of the population This prompted me to investigate research funding priorities.

The National Institutes of Health (NIH) is the federal government agency designated by the United States government to address health research and policy. According to their information,

The National Institutes of Health (NIH), a part of the U.S. Department of Health and Human Services , is the nation’s medical research agency—making important discoveries that improve health and save lives. More than 80% of the NIH’s budget goes to more than 300,000 research personnel at over 2,500 universities and research institutions. In addition, about 6,000 scientists work in NIH’s own Intramural Research laboratories, most of which are on the NIH main campus in Bethesda, Maryland.[vii]

The NIH awards billions of dollars every year for research into a wide variety of health related issues. Dr. Francis Collins, the famous scientist who led the Human Genome Project, is the current NIH Director. Funding from the NIH does not include research funding in other countries, research funded by corporations like pharmaceutical companies, or research funded by non-profit organizations or foundations. Clearly, pharmaceutical companies have large research and development departments whose goal is to develop new drugs and bring them to market for profit purposes. Non-profit agencies such as the Arthritis National Research Foundation (http://curearthritis.org/) dole out donated funds to researchers. The Bill and Melinda Gates Foundation is the largest private foundation in the world and one of their areas of emphasis is global health. But their main focus is on infectious diseases, family planning, and nutrition in developing countries.[viii]

NIH data can provide some measure of the emphasis put on various diseases. The NIH publishes annual lists of projects funded by disease category.[ix] The grants are awarded competitively – researchers submit proposal and they are peer reviewed for worthiness. According to their report of the latest actual numbers in 2011, the NIH funded $231 million in projects targeted at arthritis which includes osteoarthritis, rheumatoid arthritis, and other related diseases like lupus and gout. Of the numerous grant projects funded in 2011 for arthritis research, some were focused on osteoarthritis and others on RA. It’s a difficult process to wade through the hundreds of projects and some knowledge of the topic would be required to determine exactly which is RA focused. For example, a project called IL-10 Regulates Mast Cell Function and Survival was funded for $354,622 to Virginia Commonwealth University. This is probably RA related because IL-10 is one of the immune system regulatory chemicals involved in RA. The project Attenuation of Pain in Men and Women: Mechanisms of Exercise-Induced Analgesia funded to the University of Wisconsin for $157,028 is related to all forms of arthritis.[x]

The NIH gave another $869 million for projects categorized as autoimmune diseases which includes many diseases other than RA. There are many RA related projects funded in this category such as Effect of Chronic Inflammation on Atherosclerosis Outcomes in RA for $744,283 to the University of Texas Health Science Center. There are many projects funded in this category that are connected to general autoimmune processes that may or may not be involved with RA. For example, the project Innate Immune Signal Transduction Specificity in Inflammatory Disease was funded to Case Western Reserve University for $315,446.

The amount of funding given to arthritis and autoimmune diseases has held steady since 2008. There were some upward bumps in funding in 2009 and 2010 but that is because of extra stimulus funding from the American Recovery & Reinvestment Act. It appears that most disease categories maintained a level of funding over the past few years. There have been no dramatic increases of decreases in arthritis funding by the NIH.

According the NIH report, heart disease received a combined $1.673 billion of funding for 2011, diabetes received $1.076 billion, and all cancers combined received $7.413 billion in grants. Clearly cancer is the top policy priority of the national government. Given the actual impact to populations as a whole and its impact on disability, it seems that arthritis should receive a larger proportion of funding. That case could also be made for heart disease and diabetes. But it is heartening to see a large proportion of funding going to arthritis in general and RA in particular.

Creative Commons Photo Credit: By Pen Waggener (Flickr: Economic Landscape) [CC-BY-2.0

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5195232402_d7914561e0_nThe past few weeks have been a real pain in the neck literally. The lymph nodes under my jaws and neck are swollen and quite painful. This is not uncommon when fighting a cold or flu but I have no symptoms of any such infection. The pain was bad enough that it woke me up early this morning. I’m not too concerned as I’ve been down this road before.

About a year and a half ago, while taking Humira, a series of lymph nodes from under the jaw, down the neck, across the chest, and under the armpits were swollen and at times, quite painful. My rheumatologist called it lymphadenopathy which simply means “disease of the lymph nodes.”[i] This rather general definition doesn’t get at the cause of the changes in the lymph nodes. After a physical exam, my rheumatologist said that I probably had some sort of infection caused by the immune-suppressing medications used to treat RA. This made sense at the time since the lymph system is part of the immune system and includes liquid containing white blood cells that attack foreign invaders like bacteria and viruses.[ii]He called for a chest x-ray to rule out sarcoidosis[iii] which is an autoimmune disease of the lymph system and commonly shows up as many swollen lymph nodes deep in the chest. The x-rays were negative and he told me to keep an eye on the nodes. After a few months, I returned to the rheumatologist and told him that the nodes were the same. He found some nodes that were rather large including one being 3 centimeters. He called for an ultrasound to image the culprit. The ultrasound technician could not find it and she called in the radiologist on staff that day. She poked and prodded and moved the ultrasound wand all over the place without finding anything. She mentioned that a 3 centimeter node was rather large and wanted to be sure that she didn’t miss it. I went away not thinking about it much anymore. After another 6 months, I mentioned them again to my rheumatologist and this time he recommended that I see a hematologist since they are experts on blood and lymph system disorders. Little did I know that hematologists are also oncologists…doctors who treat cancers. That sent the stress level up a bit since I knew that Humira and other immune-suppressing treatments for RA were linked to higher levels of lymphoma. The oncologist was wonderful and very reassuring stating this is was likely not lymphoma but he wanted to rule it out. He ordered a CT scan with contrast and ran a large amount of blood tests…9 vials in all! At the follow-up, he told me the good news that he could not find anything and didn’t want to do a biopsy of the nodes. He did find an increased level of rheumatoid factor (RF) in my blood and said that I was probably experiencing an increase of disease activity and that lymph nodes can be impacted like this in RA patients. According to rheumatology researchers,

“Lymph node enlargement is
an important physical finding associated with RA and SLE
[lupus] disease activity. Atypical locations and unusually
large lymph nodes should raise clinical suspicion of another
underlying disease.”
[iv]

So it seems that lymphadenopathy is common with autoimmune diseases and that makes sense given the fact that the lymph nodes are part of the immune system. I’ve been down this road before and won’t think too much about it. But I’ll keep an eye on things since starting a new combination of Actemra and Imuran both of which impact the immune system. I just wish it wasn’t such a pain in the neck!

Creative Commons Photo Credit: http://www.bartleby.com/107/illus602.html

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4880117233_085f24e9b3_nThe sun was out in full force in Seattle today. In fact, it’s been a good week of sunshine and the extended forecast is for more sun. It’s a rare event when a high pressure takes control in January and blesses us with extended sunshine and cool, crisp Canadian air. During such events, Seattlites’ behavior changes with more energy, outdoor activities and improved moods. The snow speckled Cascade and Olympic mountains are visible making a nice contrast in colors. Mt. Rainier, that 14,400 foot volcano, shows itself to the south. We know that the weather won’t stay this way forever as the usual pattern in the winter is clouds with only periodic sun-breaks  But we know that spring and summer are coming with wonderful weather and a beautiful landscape.

This experience is much like living with rheumatoid arthritis. It’s been a long and draining “rainy season” as various medications failed to provide relief. I’ve tried various DMARD and biological treatments (Enbrel, Humira, Cimzia, Orencia) over the past four years. There were times of relief and times of bad flares. The past year seemed particularly bad as the combination of Orencia and Arava failed to make much of a dent in RA symptoms. After an extended time period like this, I begin to forget what it’s like to be “normal”. In December I began a new combination of Actemra infusions and Imuran as a DMARD. After about 2-3 weeks I began to notice a change. By the time of the second infusion I felt about 30-40% better. Two months into this treatment I feel like I haven’t in several years! I have almost a full day of energy, sleep is more restful, joint pain is reduced, and stiffness decreased. I forgot what it was like to feel this way. The sun is shining at the moment and I’m going to take advantage of it because you never know when the clouds will roll back in. Those clouds could be a failure of the medications over time, side effects, or long term tissue damage not stopped by the treatment.

Actemra acts on Interleukin 6 which is a unique cytokine that has a dual role in the immune system as both anti and pro-inflammatory. It’s also the first biological that raises the cholesterol levels of some patients and we’ve already noticed a spike in my recent blood test. Dietary changes were in order…watch fat and cholesterol consumption, eat foods that lower LDL and raise HDL, and exercise. I haven’t been able to exercise in almost three years. But this week I felt good enough to start some low level sessions on our elliptical.

I have hope that this combination will provide strong and long term relief. For the time being, I’m enjoying this time of sun-breaks. But with RA, those hopes are always tempered by the reality that RA is a sneaky beast.

Creative Commons Photo Credit: http://www.flickr.com/photos/okadayoichi/4880117233/

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B Cells and Antigens

A group of researchers at Duke University, with funding from the National Institutes of Health, have been working with a special type of B lymphocyte cell that they believe could eventually be used to treat autoimmune diseases. Their work was recently reported in the journal Nature.[i]

After reading this story, I had to get a refresher in the immune system. I have a degree in biology and this system remains difficult for me to fully understand. And full time researchers live in a complex world of their own nomenclature and symbols so off to the internet I went. When a foreign substance or germ enters the body, the immune system kicks into gear and recognizes the enemy and attacks it. This system is really amazing given the constant barrage of foreign invaders coming at us every day. Here’s a great website called KidsHealth that gives a nice overview of the immune system and the National Institutes of Health provides a more detailed explanation. When the system goes haywire and attacks itself, it’s called autoimmunity.

Central to the immune system are cells called lymphocytes. There are two types of lymphocytes, B Cells and T Cells. Many rheumatoid arthritis treatments are targeted at biochemical processes involved with these cells. To quote KidsHealth,

B lymphocytes are like the body’s military intelligence system, seeking out their targets and sending defenses to lock onto them. T cells are like the soldiers, destroying the invaders that the intelligence system has identified.

But some special types of B cells called regulatory B cells actually serve to suppress or dampen the immune system so it doesn’t get out of check. They turn off T cells keeping them from damaging one’s own tissues. Since they give off a signaling protein called interleukin 10, these cells are called B10 cells and they are quite rare in the body. This role in regulating autoimmunity garnered the interest of the researchers at Duke University as a possible avenue to treat autoimmune diseases like lupus, type 1 diabetes, and rheumatoid arthritis. Their first hurdle was to isolate and reproduce B10 cells. They discovered that they could create millions of B10 cells in the lab. They then put the cultured B10 cells into diseased mice. According to a press release from Duke University,

When a small amount of B10 cells were introduced into mice with multiple sclerosis-like autoimmune disease, their symptoms were significantly reduced, essentially turning off the disease. B10 cells will only shut off what they are programmed to shut off. If you have rheumatoid arthritis, you would want cells that would only go after your rheumatoid arthritis.[ii]

Such a treatment of injecting cells into the body in order to shut off autoimmune responses sounds like a wonderful thing. But the researchers point out that the immune system and autoimmune diseases are very complex and they are a ways off from making this a reality in humans.

Of course, one can’t get hopes up too high when reports like this appear. Thirty years ago the miracle of stem cells was touted as being able to cure all sorts of diseases. Yet it remains to become reality. But the notion of cellular therapy for rheumatoid arthritis is an interesting one and it brings hope that a cure may become a reality someday.

Creative Commons Image Credit: http://commons.wikimedia.org/wiki/File:Different-b-cells-with-antigen-receptors-and-antigen-molecules.svg

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One thing that RA patients learn over the long run is that there are all sorts of collateral issues that arise from both the disease and the treatments.  Every health care provider I visit, including doctors, dentists, physical therapists, ophthalmologists, etc. is aware of my conditions and treatments. And they understand the wide-ranging impact of the disease. For example, my ophthalmologist is aware of my history of eye inflammation (iritis) caused by RA and he regularly checks for that. He also knows of my medicines and the potential impact on the eyes. My dentist knows that RA patients may suffer gum disease and jaw bone problems. So I have regular cleanings and checkups.

 The strong medicines used to treat RA also cause collateral damage via side effects. My rheumatologist likes to quip “we treat the RA and then have to treat the side effects from the powerful medicines.” But she’s adamant that there is no way she would recommend not treating the RA. The impact of RA without treatment is too great to consider that. A recent side effect battle that I’ve been waging is chronic sinus infections most certainly exacerbated by a suppressed immune system caused by Orencia and Arava. Yes, I had sinus infections over the years probably due to anatomical issues in my sinuses. But the combination of anatomy and a suppressed immune system was too much for me to handle. So, in addition to dealing with RA symptoms, I have to also deal with sinus issues and an upcoming sinus surgery next week.

 All of this goes to demonstrate that RA patients must be persistent in dealing with the primary and secondary issues of the disease and its treatments. It’s a life-long battle and like with any battle, there’s bound to be collateral damage.  

Photo credit: http://commons.wikimedia.org/wiki/File:XM982_Excalibur.jpg

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