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Sangye
05-20-2009, 03:49 AM
Someone on the Yahoo Wegs group posted this article. I would just post the link (http://www.mdconsult.com/das/news/body/138254759-2/mnfp/0/208214/1.html?nid=208214&date=week&general=true&mine=true)ordinarily, but it requires a subscription to see the entire article. Dr Seo is my JHU Wegs doc. I thought the article would be a good springboard for discussion and may help each of us sort out "disease vs damage."

(I have no idea why Dr Seo's name always get underlined on this forum)


Sorting out vasculitis damage from disease

CHICAGO (EGMN) – Vasculitis is less likely to kill affected patients than are complications arising from the drugs used to treat it. So thinking about vasculitis in terms of disease activity and disease damage may help avoid overtreatment.

In vasculitis, damage occurs in two peaks. The first is the direct result of the vasculitis itself, such as pulmonary fibrosis and renal insufficiency that are the direct consequence of disease flare. The second peak is due to the untoward effects of therapies such as cyclophosphamide and glucocorticoids that accumulate in patients over time, Dr. Philip Seo said at a symposium sponsored by the American College of Rheumatology.

This accumulation of damage actually predicts increased mortality and is important in the way clinicians think about their patients when deciding what to do next, said Dr. Seo, codirector of the Johns Hopkins Vasculitis Center, Baltimore.

“It’s important to recognize in patients that there are manifestations that are clearly due to vasculitis that are not going to be amenable to immunosuppressive therapy and really should not be treated as such,” he said. “Because the more immunosuppressive therapy you use, the more likely they are to accrue damage as a consequence, and that just becomes an endless cycle.”

Data from the European Vasculitis Study Group (EUVAS) show that only 73% of patients with vasculitis were alive at 5 years. Impaired kidney function was a significant predictor of poor outcomes, while younger age was a clear benefit. Notably, vasculitis was not the No. 1 killer. The top three causes of death were infection, cardiovascular events, and malignancy, “all of which can relate back to the drugs we use to treat these patients,” said Dr. Seo, who reported no relevant conflicts of interest.

The WeCLOT (Wegener’s Clinical Occurrence of Thrombosis) trial highlighted the increased risk of venous thromboembolism (VTE), reporting a VTE incidence rate of 7 per 100 person-years in 167 patients enrolled with active Wegener’s granulomatosis and no prior VTE events (Ann. Intern Med. 2005;142:620-5). To put this in context, patients with Wegener’s are 23 times more likely than the general population to have a venous thromboembolic event and 7 times more likely to do so than patients with lupus, which is traditionally considered to be the prothrombotic disease, he said.

Perhaps less well known is the increased risk for solid malignancies. Five-year follow-up data reported in 2008 from WGET (Wegener’s Granulomatosis Etanercept Trial) showed a 4.4-fold increased risk of solid malignancies in patients with Wegener’s treated with etanercept (Enbrel) and cyclophosphamide.

It has been unclear whether this finding can be generalized beyond this population, but new unpublished data from 469 of 554 patients enrolled in the EUVAS Long-Term Follow-Up Study (LTFU) are moving in the same direction, Dr. Seo said. EUVAS investigators identified 31 solid malignancies (6.6%) including 8 prostate, 5 lung, and 4 bladder cancers, as well as 22 skin malignancies (3.8%).

Dr. Seo highlighted a short list of other common forms of damage to monitor in patients with Wegener’s based on 6-year prevalence rates in WGET. They were nasal blockade/chronic discharge/crusting (32%), hypertension (22%), hearing loss (20%), chronic sinusitis (12%), and osteoporosis (10%).

Hearing loss is often ignored because patients and physicians tend not to bring it up. “This is a mistake because it affects quality of life more than we realize,” he said. Patients will report being able to converse well with an individual, but will begin to restrict their activities because they have trouble picking out conversations in large groups where there is a lot of ambient noise.

Dr. Seo acknowledged that it is not always easy to differentiate disease activity from disease damage. To make that call, he suggests applying three tests. The first test is to examine chronicity, or how long the manifestation has been present. The second is to look for evidence of inflammation, which can mean going back for a second biopsy when the evidence is unclear.

“I would much rather subject someone to a second biopsy of the sinus or the kidneys than put them on another year or two of cyclophosphamide or steroids because I know that’s what is going to cause them the most trouble in the end,” he said.

The third test is to observe the response to immunosuppression. A short course of immunosuppression might help show which disease manifestations are due to damage, and are unlike to respond to prolonged immunosuppression.

“Sometimes things aren’t clear cut,” he said. “But I think this is a reasonable strategy that works well for many patients.”

Jack
05-20-2009, 05:14 AM
A very interesting article and I have to agree with every word. During at least the past 10 years all my problems have been due to drug side effects and these are becoming increasingly serious. It won't be the Wegener's that kills me, it will be the treatment! :rolleyes:

Just came back from having some electrical tests on my nerves and muscles today. They all seem to work OK so it looks like the pain and problems I am having with my legs is down to long term steroids. My consultant is considering a drop from the 10 mg I currently take and starting a regime of 5 one day and 10 the next. Anyone heard of this?

Sangye
05-20-2009, 05:22 AM
I thought of you as I read the article, Jack.

I saw a physiatrist yesterday (an MD who specializes in physical medicine and rehab). She recommended two things for Weggies : aquatic physical therapy and a consultation with an endocrinologist. The endocrinologist is to help with the ongoing weakness/fatigue/hitting the wall.

I'm feeling much better since we increased Cellcept by 50% on Friday. The pain has gone down, and I think it's actually better than it's been for many months. I was able to stay in the pool longer today and get groceries afterwards.

Jack
05-20-2009, 06:15 AM
Glad to hear you are feeling a bit better Sangye. :)
There is always the wish to minimise our medication, but sometimes the compromise has to be shifted a little. Even now, my medication requirements continue to change, I think the trick is to realise this and be prepared to go with it. I thought I would be on 10 mg of pred for ever, but perhaps not.

I was going to edit my last post. I said that the treatment would kill me, but of course, I might get run over by a bus or something. ;)

Sangye
05-20-2009, 06:36 AM
There you go, always looking on the bright side. :D

Doug
05-20-2009, 10:26 AM
Hey, feel blessed! He gave me bunny ears!

No, kidding Jack, this article does speak to your issues a lot. A very lot. I don't know about anyone else, but my doctors will get a copy of this article.

My primary care doctor and the University of Colorado-Denver rheumatologists consult often on this serious issue of not harming this patient with therapies, and my apparent good recovery and remission speak to their skill. I hope! I am in that same training hospital environment Jack talks about, and you quickly come to understand that you are a guinea pig only to the degree you don't actively involve yourself in your treatment. Why not? You have the most to gain, and doctors appreciate a patient who understands the disease, disease process, and treatments in a solid lay way, where they don't have to spend lots of time explaining what they are doing.

That Dr. Seo is associated with Johns Hopkins helps a lot, too. Thanks again, Sangye. It's a bit chilling to note 73% of weggies surviving at five years. Having reached that point, I feel good that I feel good.

Derek
05-20-2009, 11:23 PM
I was browsing round the internet and came across an interesting article at the following web site. Click below
JAMA -- Treatment of Antineutrophil Cytoplasmic Antibody Associated Vasculitis: A Systematic Review, August 8, 2007, Bosch et al. 298 (6): 655 (http://jama.ama-assn.org/cgi/content/full/298/6/655)

Also has some interesting pictures with the article.

I am seeing my doc on Friday and hope there is something else he can
try to take away the joint and muscle pain. I try not to take painkillers
due to an impaired liver function. Any way enough of my whinging.

Hope you are all ok

Derek

Doug
05-21-2009, 12:16 AM
I was browsing round the internet and came across an interesting article at the following web site. Click below
JAMA -- Treatment of Antineutrophil Cytoplasmic Antibody Associated Vasculitis: A Systematic Review, August 8, 2007, Bosch et al. 298 (6): 655 (http://jama.ama-assn.org/cgi/content/full/298/6/655)

Also has some interesting pictures with the article.

I am seeing my doc on Friday and hope there is something else he can
try to take away the joint and muscle pain. I try not to take painkillers
due to an impaired liver function. Any way enough of my whinging.

Hope you are all ok

Derek

Derek- No kidding. The PowerPoint slides alone make this worth the time. It will take some time to digest it all (and a good dictionary!). I find it difficult to describe why WG wipes weggies out if untreated, and this helps my understanding. Thanks for posting the link. :confused::)

I just came back from a second look and to save the PowerPoint slides for later digestion. I took a look at credentials and lists sources at the end. An article in the LANCET looked interesting, and it noted the full article was available. All the better! Usually, you get a summary and a hand sticking out wanting money for access to the full article. Sadly, this turned out to be such a place. Oh, if you were a healthcare practitioner or a short list of other such people, you could have the full copy. Everyone else better have their VISA ready and whatever else they required.


I note that this is a common thing for medical papers, the kinds of things that get into deep detail of the sort weggies need to have and try to understand. At that moment, the one where the hand comes out, it struck me that people like us, who have been the guinea pigs (gladly, thank you!) in WG studies and as patients, oftentimes in training hospitals because the family GP didn't have the resources to do the job, should be included on the list for gratis copies of these papers.

Why not? We're stuck with needles; we're crammed into MRI machines; we're processed in catscans; have our blood sucked out one end, run through dialysis and/or plasmapheresis machines, then put back in on the other end; have kidneys, hearts, eyes, throats, lungs, skin wiped out by the formation of granulomas in our medium and small blood vessels; have our peace of mind wiped out by the bizarre effects of Prednisone on our bodies (what doesn't kill us makes us stronger....); and generally suffer a damn lot so that those papers can be written!

Yes, I wonder why we can't have a free copy of the full texts of papers related to our disease?

A less brazen alternative might be to allow people like Andrew to attach full copies to an on-line library in their websites, making this in-depth information available to those of us afflicted with WG, who like to dig as deep as we can, to wallow in knowledge.:mad:



p.s. I see my pulmonologist in June. Perhaps I should pin him to the wall and ask him. He's used to forward questions, respectfully asked.

Jack
05-21-2009, 12:27 AM
Thanks for that link Derek, another interesting article.:)
I'm glad to say that my own treatment ties in very closely with the results reported so it looks like I've been getting the best available.

Doug
05-21-2009, 12:57 AM
I felt the same when I read it. :):)

Sangye
05-21-2009, 01:23 AM
Derek, about the journals charging to read the full article : Medical journals are not big money makers. They barely get by, actually, and because their online versions don't have advertising, they charge small amounts for subscriptions, individual papers, etc....

Researchers (not the ones working for pharm. companies) make very little money, too. They spend their lives immersed in research, working way more hours than you can imagine, all to help patients. They rarely get any glory. I did biomedical research in my early twenties, so I know what their lives are like, and what the world of research publishing is like, too.

If it weren't for their work, we would all be dead. We wouldn't have anything but pred to treat us, which was only 50% effective at keeping Weggies alive for one year.

Since you're interested in reading numerous journal articles, you might try the following : If you live near a university, you can use their library (medical or otherwise) for free. You can photocopy any journal article. Also, you can ask your doctor for copies of any articles s/he has authored. I think PubMed has a way of purchasing a subscription that allows you to download full articles from any journal. I'm sure you can fish around on their site and find out. Or call a University library and ask them how. I'm sorry I don't know more about getting online research-- the internet didn't exist when I was involved in research.

Doug
05-21-2009, 04:33 AM
Oops! Derek was not the one ranting about free medical journal articles. I'm afraid I have to take credit for that, Sangye. Thanks, at any rate, for the perspective. Doug :o

Sangye
05-21-2009, 07:25 AM
(Sorry Derek! )

Doug, let me know what you find out about subscriptions, etc... It would help me to know how to get the full article (or at least the full abstract), too.

Cindy M
05-21-2009, 04:45 PM
Great article but very scary. If it's not the disease that will get us it's the medication. What a choice.

Jack
05-21-2009, 05:12 PM
Or it could be one of the hundreds of things that get "normal" people. ;)

Sangye
05-21-2009, 11:48 PM
Yeah, I bet a banana peel takes me out in the end....

I think the article can also be interpreted as positive, too. When Dr Seo has explained these things to me, that's his attitude about it. The concept of sorting out disease from damage is new. Most docs keep us on drugs for the "standard" amount of time without considering what that's creating for us down the road. Any symptoms we have are labeled as "Wegs" and not fallout from Wegs or the drugs.

I think it's because for decades there weren't alternatives. The docs couldn't worry about drug toxicity down the road, just keeping someone alive today. Now we're living longer with Wegs, and there are less-toxic drugs to help. My first docs were unconcerned about the long-term consequences of the drugs. I was freaked out but they said, "There's no alternative." They also had no clue about when to stop a drug or change it.

Doug
05-22-2009, 07:55 AM
(Sorry Derek! )

Doug, let me know what you find out about subscriptions, etc... It would help me to know how to get the full article (or at least the full abstract), too.

Sangye- Serves me right! This is not for amateurs, I guarantee! I've been tied up with executor business on my father's estate and hospital visits with my mother (she's doing just fine, thank you!), so I haven't had more than a few minutes to play around in the site. I am registered there now, so I guess that means I can go back any time I want and wallow in the zillions of publications they seem to have available! I can't believe how many sort variables they allow. So far, I haven't found anything that tells me dollar amounts for any publication. Never mind. I'm pretty snoopy when I get the chance.