Selling the Ferrari

Infusion reactions are super fun, high speed adventures. Wheee!

Imagine this. You hop into your cushy Remicade lounge chair, get strapped up to the drippy machine and get on with your morning - checking email, snacking on a tootsie-pop and waiting for that mousie to make you feel better. (At least that's how my infusions start - don't yours?)

Then, out of the blue your face turns red, and your stomach starts to feel green (no pun intended). The room starts to look like it's been designed by Dr. Seuss and then - best of all - Horton comes and sits his big elephant butt down on your lungs. (At least that's how my infusion reactions start - don't yours?) In short, you can't breathe.

The Remicade team I know and love is fabulous - I have never seen two nurses move as fast as mine did that day when I waved and hooted and tried to scare the Grinch away. They shut my IV off, doped me up with Claritin, added a saline bag and hovered. And we waited.

This was last December. Like most reactions, mine went away within a few minutes, leaving me breathless and insecure.

I've come to rely on Remicade to work it's magic on my Psoriatic Arthritis. 2.5 hours in a chair with a movie, and I felt like gold for 5 weeks. My denial about the power of this drug has gone hand in hand with my denial about being sick at all. Fab Rheumy has been telling me not to play with fire - that I need to take this drug seriously. But I felt too good to be serious. Lalala and all that.

Apparently in clinical trials, 20% of people had an infusion reaction to Remicade, as opposed to 10% with a placebo. I could not find the study backing this data up - but the link made me sit up in my chair. Nearly as scary - a recent single center study of people on Remicade (for Crohn's) showed that 15% had serious infusion "events". That's a good enough number for me.

(an aside - I like the word "event". I certainly had the attention of the entire Remicade room for a morning - I felt like a bride).

I successfully had my infusion, and had one more infusion in January that went swimmingly. But it's hard to sit there to get doped up in order to trick your body into accepting a high powered drug. Every time I've thought about what I was doing to myself, it just felt... bad. My body is saying no for a reason, right? Why did I keep trying to force the stuff in? I guess because I like feeling better.

Long story short - a few weeks ago I got a visit from that damned blue elephant again, and we had to shut 'er down. And now I'm off Remicade.

(By now I know many of you don't care about my reactions - all you want to know about is my super duper Italian car! Ok. I'll tell you about it.)

Right about the time my doctor and I decided to take me off of Remicade, I saw this article. In it, Dr. Francisco Kerdel (a dermatologist from the University of Miami) is quoted as saying that inflixumab is a Ferrari. He warns other physicians:

"This is a high-performance vehicle, but you need to know what you’re doing... keep safety in mind from the start."

Then, Dr. Kerdel dragged me down to the used car lot, and showed me a car I might like better. Enbrel, the station wagon of biologics.

"Etanercept is like a Volvo. It’s not a fast car, it’s not a flashy car, but it’s a good, solid car that will probably work for you."

This metaphor, goofy as it is, was another reminder to me that I can take none of these drugs for granted. None of us can. Who ever thought putting boiled up mousie bits into our bodies was smart? It works... a lot of the time. And that is glorious. But what else can and does it do? I don't think anyone knows.

Sometimes I think I see Horton, off in the distance, driving his Ferrari into the sunset. I kind of want him to come back. I'm anxious about starting a new drug, especially after my experiences with Leflunomide and Remicade. Better the devil you know - right? Or no devil at all. But I can't imagine life without a biologic.

A sad state of affairs. Sounds like time for a new car. I guess this time it's a Volvo.

I'm going on a diet, and here's why...

An article in the New York Times caught my eye today. It inspired me to get out of my back to school and so much to catch up on so why the heck did I get that puppy when the cat died funk, and start writing again.

(yes, we got a puppy. By the way: puppy + psoriatic arthritis = really achy joints, a few second thoughts and lots of laughing. Back to the science - more on puppy later.)

The NYT's front page story was on autophagy, which was described as:

Our cells ... perpetually devouring themselves, shredding their own complex molecules to pieces and recycling them for new parts.

Apparently, we all have proteasomes and lysosomes, two types of small structures inside of cells that are recycling machines. They work day and night eating cells and spitting out the remains, which are used to build new cells. One scientist was quoted saying that we get an entirely new heart every 3 days due to the continual cell destruction and re-creation. WOW.

Scientists are now starting to believe that autophagy (or the lessening of autophagy as we get older) has a lot to do with the development of Alzheimer's and cancer. While autophagy doesn't necessarily cease as we age, it slows down, causing more and more cells to live longer and therefore mutate, leading to illness. The current thinking is that if we can control autophagy, we may live longer.

OK, fellow autoimmune specialists... doesn't "autophagy" remind you of another cellular process we're all really familiar with? Isn't autoimmune disease caused when our immune system (different cells, I know, but...) destroys our own cells mistakenly? Couldn't autoimmune disease be related to autophagy? And, could this slew of new research also support research in autoimmune disease?

It turns out that scientists are starting to connect the dots between autophagy and autoimmunity. While the NYT article doesn't mention autoimmune disease, there is some great work out along these lines:

The connection between autophagy and immunity should be emphasized in that autophagy contributes to the defense against microbial agents [5, 12], promotes antigen presentation through MHC class II [13, 14], is induced by cytokines [5, 15, 16], may regulate T lymphocyte survival and function [17], and may be stimulated by serum autoantibodies [18].

This is from an article by a ton of docs (Ana Lleo, MD, Pietro Invernizzi, MD PhD, Carlo Selmi, MD PhD, Ross L. Coppel, MD, Gianfranco Alpini, PhD, Mauro Podda, MD, Ian R. Mackay, MD, and M. Eric Gershwin, MD) linking autoimmunity and autophagy in the Journal of Autoimmunity (2007). The article is long and complex, so I'll cut to the chase. They conclude:

In the context of immunity, there is clear evidence for participation of autophagy in intracellular defense against infectious agents and also perhaps, in disposal of unwanted e.g. misfolded self proteins, although there is no evidence yet for an ensuing inflammatory response to such disposal.

As always, lots to learn on this topic, but there are some smart people out there trying to put all these pieces together. I'll keep watching, and will write more when I learn more.

OK, so I can hear you asking: "why the diet?".

Here's why. Autophagy kicks in when our bodies have fewer new proteins coming in... you've all heard of the process where our body starts "eating" itself when it has less food. And it is well documented that people on permanently lower calorie diet are healthier... turns out semi-starvation is kinda good for you. Scientists think that inducing this "cannibalism" increases the destruction of older, dysfunctional cells - those that cause Alzheimer's and cancer. So I wonder if the same is true of autoimmunity. In short:

Would a lower calorie diet induce autophagy, and help our bodies destroy those cells that are mis-firing and causing our immune systems to act up?

BTW, because of the dog, I've lost 3 pounds, just from walking. I look fabulous. And if I just stop eating, I'll apparently be able to walk the dog 'til I'm 150.

Where's the leash?

Is Psoriatic Arthritis underdiagnosed?

We all know the numbers - it is estimated that only 10-30% of people with Psoriasis will be diagnosed with Psoriatic Arthritis. But is the low rate of co-incidence because people with P(soriasis) don't usually develop Ps(oriatic) A(rthritis), or because many people with P don't realize they also have PsA? I tend to think the latter, and I think research is starting to back me up.

A recent Canadian research survey on people with Psoriasis (not Psoriatic Arthritis), called the SKIN study (cute) suggests that PsA could be widely underdiagnosed. The article I read about the study states:

The SKIN survey reveals that half of all respondents [with Psoriasis] reported that they had developed joint pain or stiffness, but only 18 per cent of these respondents had ever received a diagnosis of psoriatic arthritis.

and...

Respondents reporting no psoriatic arthritis diagnosis indicated that they experienced stiffness in the knees, shoulders and hips (48 per cent), followed by pain or stiffness in the finger joints (38 per cent) and toe joints (23 per cent).

Underdiagnosis concerns me for two reasons - firstly, of course, I don't want anyone else to experience the pain I experience. But secondly, fewer people diagnosed with PsA means the research community will be less likely to study PsA.

A while back I wrote about the lack of research and basic information about Psoriatic Arthritis, as compared to Rheumatoid Arthritis and Psoriasis. Here's the link.

Here's my point: fewer scholarly articles on PsA will lead doctors to make fewer diagnoses, AND, the lack of PsA diagnoses certainly has an effect on how much research is undertaken.

So if you're out there with P, and think you have PsA, please consider getting a definitive diagnosis.

You know what they say about the squeaky wheel, after all. I'm up for some grease (and I'm not talking another ointment).

Psoriatic Arthritis, Menstruation, and Remicade

My periods are funky. I'm just to go ahead and say it "outloud", after months of avoiding the topic for fear of grossing y'all out (yes, I'm talking about you, dear squeamish reader - you know who you are!)

But it can't be avoided now. The story of my "little visitor" has become too compelling, personally and scientifically, to make light of. So here goes:

For about three and a half years (from just before the time I developed psoriatic arthritis), I've had very heavy, and LONG, menstrual bleeding. My visitor was a terrible guest. Stayed too long (two weeks or more) and didn't clean up after herself.

Then came Remicade. I started Remicade (Infliximab) about 6 weeks ago, and missed my period a week later. Please note: I never miss a period (except when pregnant). Of course I ran off to RiteAid for a pregnancy test, which came back negative. So I waited.

About 4 weeks after my first Remicade treatment, I had a visit, finally, and she was an easier houseguest than I've had in years. Not heavy, not long, just...normal. She practically did the dishes for me.

Now, here's the kicker. The bleeding started again, 4 days ago, right when the second Remicade dose wore off and I started feeling the arthritic aches and fatigue again. This was just two weeks after my last, very late, period. Is it coincidence that Remicade delayed and then "normalized" my period, and the absence of Remicade made me bleed? I think not.

So, as always, I'm turning to the research journals. First, I must give credit to the KickAS website and support group, which had a bunch of useful information in this thread.

It turns out that TNF-alpha has been linked to endometriosis, and is probably involved in the development of ovarian follicles. A fascinating 2004 review article by Sakumoto and Okuda (Journal of Reproduction and Development) states (italic mine):

3. Although the physiological significance of TNF-alpha regulating CL (corpus luteum) function during gestation is still obscure, TNF-alpha may play physiological roles in regulating CL function in the gestation period as well as in the estrous cycle.

Good golly I wish I was a research scientist and understood all of this better. But what I'm getting is: the corpus luteum is a little blister-like object that is formed when the ovary pops out an egg halfway through the menstrual cycle (here's a good diagram about the cycle). It produces hormones that support a potential pregnancy, and it decays towards the end of the cycle if the egg isn't fertilized. What these researchers believe is that the CL formation, and perhaps the entire estrous cycle, are partially regulated by TNF-alpha.

And of course, as we all know, TNF-Alpha is what the Remicade blocks. It's a lead factor in inflammatory arthritis, as well as other autoimmune diseases.

So by my reckoning, for the last three years my little visitor has arrived at the end of my menstrual cycle... she arrives early and dances in the front yard lightly for about a week, but then moves in and trashes the house at about the time I would normally be expecting guests. But possibly, the Remicade has shortened her stay.

(Translated, I think I bleed lightly for the last week of my cycle, when the CL is disintegrating, and then I bleed heavily when my period should start. But with remicade, somehow the TNF-alpha blocking is shortening dear Aunt Flo's visit).

I don't know what to think here, except to feel grateful for a better understanding of why I've had these nasty periods for so long. I don't really know why TNF-alpha affects me in so many ways, but at least I can blame it for my heavy bleeding. And I now have a new topic for reading and speculation about autoimmune illness. Just think...some researchers now think some endometriosis is caused by flaws in the immune system!

I'm also quite curious as to what Remicade has in store for me and my bad house guest - maybe I can close up the B&B for a while.

Aloe Vera treats Plaque Psoriasis

This just in - a study in Thailand demonstrated that topical aloe vera was possibly a better treatment for plaque psoriasis than topical steroids. Here's the link, and here's a quote from the investigators:

"Although contrary results were reported from two previous placebo-controlled studies, our study showed that aloe very cream was more effective than 0.1% triamcinolone acetonide cream after eight weeks of treatment".

Now, keep in mind that these results did not reach statistical significance. However, the aloe did beat out the steroid in only 8 weeks.

I wonder if my psoriatic arthritis would go away if I started drinking the stuff. Here's a link to a post claiming it would. (this is not a study, though, just an opinion).

I have been feeling like a big chemical cess-pit lately, so this study certainly caught my attention. I like when research proves that natural remedies work - it makes my scientific preferences feel at peace with my hippie soul.

Universities, beef, and some education on the side...

In the last few days two articles have come out in the New York Times that I think are relevant to this blog, despite the fact that neither of them is about psoriatic arthritis or psoriasis. Humor me... I do have a point...

The first is an opinion piece called End the University as We Know It, by Mark C. Taylor. It calls for a systemic reorganization of the university system, most specifically in graduate education, because:

Most graduate programs in American universities produce a product for which there is no market (candidates for teaching positions that do not exist) and develop skills for which there is diminishing demand (research in subfields within subfields and publication in journals read by no one other than a few like-minded colleagues), all at a rapidly rising cost (sometimes well over $100,000 in student loans).

Why is this relevant to PsA, you might ask? It was these paragraphs that hit me:

Responsible teaching and scholarship must become cross-disciplinary and cross-cultural.

Just a few weeks ago, I attended a meeting of political scientists who had gathered to discuss why international relations theory had never considered the role of religion in society. Given the state of the world today, this is a significant oversight. There can be no adequate understanding of the most important issues we face when disciplines are cloistered from one another and operate on their own premises.

It would be far more effective to bring together people working on questions of religion, politics, history, economics, anthropology, sociology, literature, art, religion and philosophy to engage in comparative analysis of common problems. As the curriculum is restructured, fields of inquiry and methods of investigation will be transformed.

Ok, so sub out the words "religion, politics, history, economics, anthropology, sociology" etc. etc. and put in "rheumatology, dermatology, immunology, gastroenterology" etc. etc. The more I learn about how deeply connected autoimmune diseases are, the more I wish that these, and other, fields of medicine were working more closely together.

Now I know I have it really good - my rheumatologist consults with my dermatologist on almost everything she does, and visa versa. But I'm assuming that that is not true for many of you, and certainly neither of them has talked to my gastroenterologist. I do like the idea of a new area of clinical (meaning, not in a lab- they see patients) specialization - autoimmunology - but boy folks in that field had better have great communication skills.

Anyway, go read the article. It really makes you think.

That second article? Here - Paying a Price for Loving Red Meat, written by Jane E. Brody. Apparently, a new study demonstrates that the more red meat consumed, the more likely you are to die early.

This article struck me because of the increased risk for heart disease that psoriasis patients (and, in theory, psoriatic arthritis patients) have. Here's my thinking - I'm already at increased risk for heart disease... and red meat consumption increases that risk further! I want to protect my body, and I want all of my readers to, too. So I thought I'd share this data...

For lunch today, I'll be eating lentils while reading the paper. What about you?

The business behind the disease

Was I the only one who was surprised, when starting Humira, that you could get a payment plan to reduce the cost of co-pays to pretty much nothing for the first 6 months on the drug? It came in the form of a card, given to my rheumatologist to give to me, which I could then use with the pharmacy to get that co-pay covered by Abbott, who makes Humira. Was Abbott encouraging me through that plan to use their drug?

In the words of my favorite Alaskan Governor - "You betcha".

The business behind big-pharma and biotech is fascinating. As I noted in a recent post, we've come a long way in our genomic research, (which leads to the development of effective biologic drugs) but we still have a long way to go. It's easy to think about a set of good-willed researchers in their white coats worrying about our joints and striving for the good of science to cure us. I know many of these researchers (I'm married to someone who used to be one). I'm grateful to them.

It's also easy to forget that good science is also about good business.

Today, I found a European news article online that links to a report called: The Autoimmune Market Outlook to 2013: Competitive landscape, pipeline analysis and growth opportunities. I couldn't get access to the whole report, because it looks to cost a bundle. But here are some excerpts on the page describing the report:

-The global autoimmune market generated sales of $31.9bn in 2007, an increase of 14.4% over 2006 sales. The market is forecast to grow at a CAGR of 8.1% to reach a total value of $51.0bn in 2013.
-Immunosuppressant drugs dominate the automimnune [sic] market, with four products from this class accounting for 40.3% of total market sales. The highest selling immunosuppressant drug was J&J/Schering-Plough's Remicade, with 42.1% of total sales in this class.

and:

Use this report to:

- Assess patient potential, treatment trends and sales patterns of major autoimmune indications over the period 2009-13, with this report's coverage of osteoarthritis, rheumatoid arthritis, crohn's disease, systemic lupus erythematosus, ulcerative colitis and multiple sclerosis markets across Japan, France, Germany, Italy, Spain, the UK and the US.
- Discover the market dynamics of the autoimmune area and understand the impact of recent events by assessing key market trends, growth drivers and the latest issues affecting product development.

I'm glad there are market analyses being done regarding both autoimmune diseases and the drugs that treat them. And, of course, I worry whenever big money is involved, esp given our economic climate. Mostly, though, it is important for those of us who are health consumers to understand the multiple motivations behind good science. Money talks.

Make 'em laugh, doc!

We all know psoriatic arthritis is no laughing matter, but it appears that if we can find the funny side of our disease, we'll do better.

The Bio-Medicine website has a great article today about a research study showing that laughter can affect your disease course. Researchers took a group of diabetics, put them all on the same medication, but made only half of the diabetics watch a humorous video (of their choice) for a half an hour each day. The other half were not prescribed humor.

The folks who watched the funny videos:

had lower epinephrine and norepinephrine levels by the second month, suggesting lower stress levels. They had increased HDL (good) cholesterol. The laughter group also had lower levels of TNF-α, IFN-γ, IL-6 and hs-CRP levels, indicating lower levels of inflammation.

Crazy cool - laughter may reduce inflammation. Now I have to figure out what TV show makes me laugh for 30 minutes straight... finding one may be harder than giving myself that methotrexate shot!

Genomic research update - we've got a ways to go.

The New England Journal of Medicine published several articles this week about the current state of research on the human genome. The articles were especially focused on whether greater understanding of the genome will lead to greater understanding of how humans develop certain diseases.

(If you, like me, need to run to the dictionary every time you hear the word "genome" to find out why it is different from "gene" or "chromosome" - here's a good link. In short - the genome is the complete set of genes in a particular organism).

Kraft and Hunter, in an article they title "Genetic Risk Prediction: Are we there yet?", state pessimistically:

We are still too early in the cycle of discovery for most tests that are based on newly discovered associations to provide stable estimates of genetic risk for many diseases. Although the major findings are highly unlikely to be false positives, the identified variants do not contribute more than a small fraction of the inherited predisposition. ...Estimates are poor predictors of risk, both in absolute terms and in relation to risk estimators that will be available when more of the remaining locus associations are discovered.

In other words, to answer their title question - no, we're not there yet. The New York Times has a great review today about the NEJM series of articles that explains this far better than I can. But, basically - researchers and drug companies thought that if we could examine the genomes of people with illnesses and compare them with genomes of people who are well, one or two genes in the genome would essentially "light up" as the key genes causing these diseases. Drugs could then be made that would alter these genetic sequences, thus curing those diseases.

Turns out we're more complicated than that - much more complicated. When one or a few genes are implicated in a disease, usually these genes can only predict the disease some of the time, for some people. There seems to be a lot more going on in our bodies besides genes in the development of a disease. AND, often, there are hundreds, instead of tens, of genes involved in a disease, which makes the development of a targeted drug really difficult.

It's very smart for these scientists to be taking a step back to think about whether or not the genomic research they are doing is going to pay off in the short run (or long run). If you look at the NEJM articles, you can see some differing of opinions - some folks sound more optimistic than others... some are wisely watching their wallets, and some are ambitiously still looking into the future.

I fear we have a long way to go.

Celiac Disease and Psoriatic Arthritis

I was trolling around PubMed today and came across this topic... frankly, I'm surprised at myself for not looking at it before, considering my history.

A study was published in the Journal Rheumatology in 2002 linking psoriatic arthritis to celiac disease. The researchers found that there was a higher rate of celiac disease in their PsA patients. They state:

An increased prevalence of coeliac disease in patients with PsoA has not been reported previously. Among our patients, 4.4% had coeliac disease (ascertained by the presence of villous atrophy) compared with 0.4% in a large Swedish adult population of blood donors.

also:

Patients with PsoA have an increased prevalence of raised serum IgA AGA and of coeliac disease. Patients with raised IgA AGA seem to have more pronounced inflammation than those with a low IgA AGA concentration.

Celiac Disease (or coeliac disease, if you live in Europe), is an autoimmune disease in which the body confuses gluten (a protein found in wheat, barley and rye, as well as some other grains) with toxins. If a "celiac" ingests gluten, the body produces antibodies to break down the intestinal wall, destroying the villi which are used to digest food, in a flawed effort to save itself from toxins. When you lose those villi, you get super sick - anemic, weak, skinny. The only known treatment is complete adherence to a gluten free diet.

What this study is saying is that people with psoriatic arthritis are more likely to have celiac disease, and that patients with more acute inflammation in their psoriatic arthritis could possible also have worse celiac disease.

I have had celiac disease and have been on a gluten-free diet for 16 years. I continually struggle with the autoimmune diet (no dairy, alcohol, sugar, etc - boring!) but the gluten-free part of the autoimmune diet has been easy. Gluten makes me very, very ill, and I'm never tempted to cheat. Its not worth it. When we're better friends I'll describe what happens to my gut when I eat wheat. But not yet. I don't know you well enough.

The researchers state, at the end of their article:

Studies of the gastrointestinal mucosa in PsoA patients are therefore needed. Controlled studies of the effects of a gluten-free diet on the severity of PsoA are also required.

In short, more psoriatic arthritics should go on gluten-free diets to see if they get better. In a research setting, with control subjects eating gluten, etc. etc.

Of course, the plot thickens. Here in the U.S.A, another study was conducted which looked at the prevalence of IgA antibodies to gliadin (in other words, celiac disease) in folks with psoriasis and psoriatic arthritis. Their results found no increase in these antibodies in psoriasis and psoriatic arthritis patients. They state:

We found no support for the results of prior studies showing that elevated AGAs occur with increased frequency in patients with psoriasis.

I'm not convinced. Look at this abstract if you want to have your mind blown. It lists many, many skin manifestations in auto-immune diseases - from Grave's to Crohn's to celiac disease. It is apparent our skin, as one of the organs of our bodies, is greatly affected by our immune system, especially when it is in havoc. I'm continually astounded by the links between all of these autoimmune diseases, and by how so much of this science is still in its infancy. And it appears that our skin disease, and our joint disease, may be related to a gut disease.

Hm. I meant for this to be a short blog post. But isn't this stuff fascinating? And here's another piece in my puzzle:

I have no idea if a gluten-free diet would work on my PsA, because guess what... the year I developed celiac disease was the year my knees first showed signs of arthritis. Autoimmune diseases can be triggered by something in the environment, and in 2003 I had just come back from Tonga with a bad case of giardia, a parasite. We think it triggered the celiac disease, and I know now what I didn't realize then - I was developing two diseases back in 2003 instead of one. At the time I had some physical therapy, but ended up ignoring my knees in order to focus on my gut. After a while, the knee pain was pretty manageable.

So here's my question: Did the giardia trigger two diseases, and did the new gluten free diet slow the disease process in my knees?

A final note: I've not had a single bout of ... um... unmentionable gastrointestinal troubles ... since I went on Humira for my arthritis. Go figure.

Are autoimmune diseases connected? I think yes!

A fellow Psoriatic Arthritis patient asked me to explain whether (and why) if someone has one autoimmune disease, they are more likely to get a second one. For example, in my case, is there some reason other than chance that I have both Psoriatic Arthritis and Celiac Disease?

To tell the truth... if I could answer that question I could win the Nobel prize and run a whole lot of people out of work. The immune system is incredibly complex, and a layperson like me can only skim the surface of understanding it.

Here's what I do know, however, after doing some sleuthing.

Yes, autoimmune diseases come in multi-packs, like underwear from Target. If you have one, you're likely to get two or three. This is called co-morbidity, btw. Just last month, an article in the American Journal of Epidemiology discussed some researchers' attempts to demonstrate autoimmune co-morbidity. The authors used public records to see how often rheumatoid arthritis, multiple sclerosis, autoimmune thyroiditis and insulin-dependent diabetes mellitus were present in the same individual. And they found that there was a high co-occurrence between rheumatoid arthritis, insulin-dependent diabetes mellitus and autoimmune thyroiditis. BUT... they found that there was an inverse relationship between RA and MS - which means that if you had one, you were LESS likely to have the other! Go figure. This reverse relationship does speak to a relationship... but what kind of relationship?

Dr. Noel Rose wrote an essay called The Common Thread discussing the etiology (the cause) of autoimmune diseases and the need for more research on the links between them. You can find the paper on the American Autoimmune Related Diseases Association website. Dr. Rose states:

Autoimmunity is an etiology: it is a cause of disease. Anatomically, autoimmune disease is very diverse; and that's why we see specialists in so many areas of medicine studying autoimmunity. They may be rheumatologists who are interested in joints; they may be dermatologists who are interested in skin; they may be cardiologists who are interested in the heart; they may be gastroenterologists who are interested in the gastrointestinal tract. But the common etiology for all of these disease--for Crohn's disease of the gut; for lupus of the skin; for rheumatoid arthritis of the joint--the common etiology that brings together all of these diseases is autoimmunity.

Dr. Rose doesn't necessarily say that one disease can cause another, but that's not what we're talking about. We're talking about whether they occur at the same time, and whether autoimmune diseases are all just one disorder with multiple symptoms. It does make sense that if you are having a problem with your immune system in general, that the problem won't always limit itself to one organ or region, but can be systemic. But how do we prove that all of these autoimmune diseases are related, or perhaps one underlying disease?

Here's one data point that suggests a connection: many different autoimmune diseases can be treated by the same medication - and I'm not just talking about diseases that look similar, like psoriatic arthritis and rheumatoid arthritis. For example, my husband and I could get Abbott labs to give us a bulk discount - Humira treats PsA and Crohn's Disease. Humira is a TNF-alpha blocker - and both of our diseases can be linked to an excess of TNF-alpha. On the other hand, so far, Humira doesn't seem to treat every auto-immune disease.

In their book "The Autoimmune Connection" Rita Baron-Faust, Jill P. Buyon, M.D. hypothesize about some of the reasons autoimmune diseases may co-occur, or may perhaps be one disease with multiple symptoms. They say:

While autoimmune diseases may target different areas of the body, the genes that affect immune responses may be the same. For example, genes that govern cytokines may have a mutation that causes too many inflammatory molecules to be released. Defective genes common to autoimmune diseases may also affect the way T-cells are programmed to recognize antigens, the number of receptors they carry, the number of T-cells with a faulty memory, or how many defective T-cells are eliminated.

Researchers are now trying to demonstrate, on a genetic level, that many autoimmune diseases are related. A group of researchers looked across 42 separate studies of 11 autoimmune diseases to see if they could find underlying genetic links. They found that several diseases shared some common genetic fingerprints (the HLA region of chromosome 6 lit up for many autoimmune diseases, as did many parts of chromosome 16). On the other hand, there were several genes that seemed to be involved with only one disease. This is from the Feb 2009 issue of the European Journal of Human Genetics - you can read the abstract here.

So, ok, what do we know about autoimmune co-morbidity? What do we think? Here's what I've learned:

• Many autoimmune diseases are likely to co-occur in the same person, but some aren't.
• Many researchers think that separate autoimmune diseases have a shared etiology, or cause, and may possibly be one disease. Some evidence supports this, but some doesn't.
  
• Many autoimmune diseases share similar genetic links, but not in all cases.

What does this mean? Folks, it means that we need more research. And of course, this means we need more funding for research. If you haven't yet, find some way to support research on your disease(s), or autoimmune disease in general. Go to the NPF website, or the AARDA website. Do something, and keep talking.

It also speaks to something I've discussed before in my blog - the fact that humans' compulsions to put things in boxes - to categorize - may limit how we understand disease. Maybe autoimmune diseases are all just one disease... maybe they aren't, but they just share a lot of qualities or root causes. Do the diagnostics get in the way of knowledge? I think yes, sometimes. Perhaps a more holistic approach to research, diagnosis, and treatment would help use understand these symptoms (not diseases) better.

It also means I have a lot more to learn before I ever attempt to write a logical post about this topic again. This is complicated stuff.

Are psoriasis and psoriatic arthritis different diseases?

Maryanne Kazanis, a research fellow at Harvard and a med student, presented a paper in Japan last summer suggesting that psoriasis and psoriatic arthritis could possibly be different diseases. Check this out:

Support for the one-disease concept comes from the observation that arthritis occurs more frequently in patients with cutaneous psoriasis than in nonpsoriatic controls.

On the other hand, the fact that a drug such as cydosporine is effective for the skin manifestations of psoriasis but provides little benefit for psoriatic joint symptoms has caused many physicians to lean toward the view that psoriasis and psoriatic arthritis are two diseases, albeit possibly sharing some immunopathogenetic elements, Ms. Kazanis said.

The heart of the article goes on to discuss Kazanis' research, which demonstrates that different diseases co-occur with psoriasis vs. psoriatic arthritis. The article also highlights some of the measurement issues in this study. It's worth a read...

My two cents? I'm again struck with the similarities between psoriatic arthritis and rheumatoid arthritis, both in symptoms and the types of treatment that work. We really are just beginning to learn about these diseases, and anything is possible. What if psoriatic arthritis and rheumatoid arthritis are the same disease, with a few different symptoms? What if rheumatoid factor is just a symptom that some folks develop? And... what if psoriasis is a different disease that occurs a lot in people with PsA/RA type arthritis? What do you think?

I really gotta go get my M.D. This armchair speculation is making me woozy.

Humor me, but don't kiss me

My dog-eared copy of The Autoimmune Epidemic has me in its clutches again today. I'm bursting with hypotheses, but I'm realizing that my lack of a PhD in biochemistry or genomics or super-brainiac-science-chickness is getting in my way. Nevertheless, I will persevere in my attempt to be the psoriatic Sherlock Holmes.

In "The Autoimmune Epidemic" (starting on page 127) Jackson Nakazawa introduces the work of Drs. John Harley and Judi James. These two maverick researchers discovered a strong link between Epstein-Barr Virus (EBV) (which causes mononucleosis - the kissing disease) and the onset of lupus, which is another autoimmune disease. Jackson Nakazawa discusses how Harley and James were able to:

...travel back in time and show that the autoimmune reaction in lupus patients was a slow-brew reaction to an Epstein-Barr exposure that had occurred months, years or even decades before. (page 134)

Why did this tickle my brain, you may ask?

As I mentioned in an earlier post, my husband and I both suffered from a strange bout of sickness about 4 years ago. Our doctors at first thought it was lymphoma, but then settled on Epstein-Barr/mono (our test results were equivocal).

About 2 years after my husband had mono, he had his first Crohn's disease flare (Crohn's is an autoimmune illness). Also, about 2 years after I had mono, my knees, hands, and wrists flared with psoriatic arthritis.

I haven't had time yet to do a thorough scan of the the research journals, but at first glance there is not a lot out there about PsA and EBV. However, I did find this recent article about the possible link between EBV and our sister disease, Rheumatoid Arthritis. There's something to this, I think.

BTW, 95% of people will have EBV by the time they are 35-40. But most people get EBV, and mono, in their teens (I guess neither of us got enough action in high school). Did our late exposure to EBV trigger our bad genetics, and cause an autoimmune reaction?

More to come. But 'til then... be careful who you kiss, Watson.

Burn, baby, burn

Just a quick note... I'm going to be starting laser treatment for my psoriasis soon, if my insurance allows. Here's an article on it from the WSJ. This is extremely exciting new technology. My dermatologist said during each of the 10 treatments, they will only use the laser 'til my skin turns red. They have to be careful that my skin doesn't blister (although she also said that blistering works faster... eeeewwww).

I can't imagine not feeling embarrassed about my elbows this summer.

Our little club is getting bigger

After writing so much about the increased incidence of autoimmune diseases, and also about potential triggers for Psoriatic Arthritis, I wanted to make sure I wasn't barking up a non-existent tree. Are Psoriatic Arthritis incidence rates really on the rise?

The answer is... most probably yes.

In this opinion article from the Feb 2009 issue of the Journal of Rheumatology, Dr. Vinod Chandran from Toronto Western Hospital discusses a current study (in the same issue) that demonstrates that PsA rates are in the rise. He also devotes a bunch of page space to the diagnostic challenges of PsA, which profoundly affect how well we can measure incidence rates.

Here's a summary quote from the article, but I recommend going in and reading the whole piece:

...the prevalence of both psoriasis and PsA is increasing, and environmental rather than genetic factors are probably responsible.

So, why do I state above that the rates are "probably" rising? Because of the nature of research and available data. The quoted study was done only on people in one smallish area in Minnesota - so while we can assume this increase is true across the country, we can't be sure. Maybe there is something in Minnesota that is causing an increase - something not present elsewhere. The author also refers to our inability to truly understand why these rates are rising:

Genetic or ethnicity related factors are unlikely to be responsible for the observed change since there has not been any significant immigration or emigration from this “captive” population. It would be interesting to study how environmental factors have changed over the years to give us an explanation. However, such studies are best done prospectively.

(prospectively meaning: not after-the-fact)

I admire Dr. Chandran's analysis of the frustrations preventing true understanding of the prevalence rates of PsA. He cites weaknesses in diagnostics or "classification criteria", which is a reflection of how recently scientists have begun studying Psoriatic Arthritis. Until doctors and scientists nationwide agree on what PsA signs and symptoms really are, it is hard to compare epidemiological studies from different regions. And, of course, it's financially challenging to develop a nation-wide study.

Once again, I'm struck with how much PsA remains the "ugly stepsister" to Psoriasis and Rheumatoid Arthritis. I wish the science behind this disease wasn't still so hit-and-miss. I admire, and appreciate, those scientists and doctors dedicated to this disease, but I wish there were more of them. It may take more and more of us being diagnosed to generate more PsA researchers.

And unfortunately or fortunately, my wishes may be coming true.

Morbidity and comorbidity

The National Psoriasis Foundation recently headlined a news article about the long term risks of psoriasis because of its highly inflammatory nature. At the recent Annual Meeting of the American Academy of Dermatology, Dr. Joel M. Gelfand (a dermatologist) explained:

that for the last two decades, research has shown that excessive inflammation is a critical feature of psoriasis... Excess inflammation also is present in other common conditions, such as hardening of the arteries, heart attacks, stroke, obesity and diabetes - which may explain why some psoriasis patients may be at an increased risk for developing these other serious conditions.

He goes on to say that people with severe psoriasis are likely to die 5-7 years earlier than those without.

Upon reading this, I went racing off to PubMed to try to locate some of this comorbidity research that Gelfand is talking about (especially the stuff that says I'm gonna croak soon), and ran across this 2008 article. Here are some highlights from the abstract (italics mine):

The risk factors of cardiovascular disease and other disease comorbidities appear to be more common in patients with psoriasis compared with the general population. To support this concept, the association between psoriasis and cardiovascular disease and other comorbidities was analyzed... from 1127 patients with psoriasis and a matched cohort of nonpsoriasis patients. Psoriasis patients were significantly more likely to have cardiovascular comorbidities... compared with nonpsoriasis patients. Other comorbidities significantly associated with psoriasis were arthritis, depression, sleep disorder/insomnia, chronic obstructive pulmonary disease, and gastroesophageal reflux disease. Responses to this large survey confirm that patients with psoriasis have a higher rate of cardiovascular risk factors and other comorbidities compared with patients without psoriasis.

Wait, wait... now I'm confused. Because I have psoriasis, I'm more likely to have arthritis? So...am I a patient with psoriasis, and the psoriasis is manifesting itself through the comorbidity of arthritis?

Or, am I a patient with psoriatic arthritis, which is an inflammatory condition similar to rheumatoid arthritis, but I also have some skin stuff going on too??

It's all just so blurry, and leads me back to questioning the diagnostic process again. I think I'm going to go back to reading those autoimmune books. While there's still time.

Take your medicine, folks!

A recent article in the Journal "Arthritis Research and Therapy" demonstrated, unsurprisingly, that folks with Rheumatoid Arthritis who were more consistent at taking their DMARDs (Disease Modifying Anti-Rheumatic Drugs) do have better prognoses - they feel better sooner, and have less structural damage. The subjects in this study had just been diagnosed, and were followed over two years.

The key point of this article was that younger patients were more likely to stay on their drugs than older patients.

My two cents - have any of you been on methotrexate? Many rheumatologists and patients love this drug, but it was my personal nightmare. I took it weekly for 6 weeks, and for three days each week I was nauseated, dizzy, exhausted, and had rampant diarrhea. I'm in my early 40s, and not frail by any means. I can imagine that for folks with compromised health already some of these drugs are worse than the disease. I think about my grandparents, who as they have gotten older are more forgetful and less tolerant of side effects. The article calls for more investigation into how to increase medication compliance - and this is especially true for older people.

So, if you can, don't give up on your meds too quickly. Build a support system to get yourself through the first few months, when both the pain and side effects are the worst. Many of these drugs do work. Just give them time...

Good news re: a new drug

One of the psoriasis and psoriatic arthritis drugs currently in clinical trials (ustekinumab) seems to be doing well - here's the article.

I'm still waiting for the drug that is helping 90% of people who try it, however. The fact that these drugs only help 60% reinforces my belief that this disease is a tricky one, and there is more than meets the eye in understanding all the underlying processes involved.

BTW - according to Wikipedia, Ustekinumab targets IL-12 and IL-23 - some of our genes to watch out for.

A rose by any other name... would be something else?

The New York Times had a fascinating article in their magazine this weekend about the Undiagnosed Diseases Program sponsored by the N.I.H. The article focused on a 31 year old woman named Summer Stiers in declining health, who has spent the last 20 being undiagnosed or misdiagnosed by well-intentioned physicians. She was frequently misdiagnosed with autoimmune conditions, because her symptoms just scream "autoimmune".

The article followed her disease progression, and her experiences in Bethesda, MD being examined by a constellation of specialists from the N.I.H.

There were countless fascinating aspects of this article - I recommend you take the time to read through it. However, what stood out most to me was the difficulty physicians have in making accurate diagnoses, even now, with all of our tools and experience. The article highlights how the N.I.H. is trying to advance knowledge about both specific illnesses and the diagnostic process through the Undiagnosed Diseases Program, and it brings home how complicated the jobs of physicians AND patients are when addressed a complicated array of symptoms.

A few weeks ago I wrote about how fractured and fragmented our current of system of diagnostics are, and the article on Summer Stiers included a great discussion of this problem. Forgive the long quote - this is from page 5 - but I found this so interesting, esp in light of diagnostics in the field of autoimmunology (italics mine):

The balkanization of medicine accounts for an increasingly constrained approach to diagnosis — an approach that... is defined by a specialist’s focused knowledge rather than by some broader understanding of the patient. “This is partly because of how medicine is taught — how it has to be taught,” said Kathryn Montgomery, professor of medical humanities and bioethics and of medicine at the Northwestern University medical school in Chicago, when we spoke by telephone. “Doctors get educated to solve problems in their own terms. They’ve got only a certain set of information and experience at their disposal.”

Few physicians are trained to look at the patient as a whole, Montgomery says, with the exception of generalists like internists and pediatricians. ...

But the problem is not just overspecialization, Montgomery says; it’s the complex nature of diagnosis itself, and the difficulty of trying to teach the process in medical school. Because diagnosis involves so many intersecting and often incompatible parts, medical students have traditionally been taught to do opposite things at once when they meet a new patient: suspend judgment, but form an initial impression; look for a single diagnosis to explain all symptoms, but watch for co-morbidities; avoid the anecdotal, but pay attention to stories; expect the diagnosis to be a common disease, but don’t forget the rare ones. This dissonant approach was recently modified in some medical schools, according to Montgomery, with students now taught to begin with a “working diagnosis” that they refine as they accumulate data that either confirm or refute their first guess. But while the working-diagnosis method might clarify some things, Montgomery worries about what might be lost: a sense, as she wrote in her 2006 book, “How Doctors Think: Clinical Judgment and the Practice of Medicine,” of an alternative pathway. Because of the inherent contradictions traditionally taught in medical school, she wrote, new doctors have been able to achieve “a certain balance, a consciousness that, no matter which way they may work through a diagnosis, there is another way.”

As patients, we see similar contradictions in our roles of finding the right doctors. Do I find an older doctor... someone with lots of clinical experience? Or should I turn to someone who is fairly new out of school, who has fresh knowledge on the most modern techniques and research? Do I find a generalist or a specialist? Do I look to someone who is alternative in their approach, or have two separate doctors, one representing the "western" approach and one representing an alternative approach? When meeting a doctor for the first time, do I tell them my whole complicated history, or just focus on the day's issues?

This makes me more and more convinced that I am my own boss re: my health (see "I'm canceling everybody"). Doctors, by the very fact that they are human with limited brain-space, are fallible. We have to be our own agents, and rely on our doctors as we would rely on consultants. We have to be our own Chief Information Officers.

Itchy itchy scratchy

Yesterday US News and World Report published an article about the link between shingles and some of the common biologics used to treat Psoriatic Arthritis. Apparently it's been demonstrated that older folks with Rheumatoid Arthritis who were on anti-TNF drugs (Humira being one, and also Remicade) were twice as likely to develop herpes zoster (aka shingles). The link to the news article is here.

Now, N=1 of course, I can report that since being on Humira I've had 4 cold sores. 4 cold sores in 4 months. My usual rate of cold sores is about 1 every two years. Herpes in the mouth is herpes simplex 1 (usually), and herpes zoster is herpes type 3... they are slightly different viruses in the Herpesviridae family. But I think I can say that because I am now immunosuppressed, my body is less likely to be able to control a "creepy" virus like herpes (the Greek word herpein means "to creep").

What I was pleased to see is the news article I cite above is that the FDA is going to commit a lot more time to studying these Anti-TNF drugs so many of us are using. They are life-savers for many, but we need to be sure they are safe.