PMRGCAuk
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Steroids Don't Suppress All The Inflammation in GCA

I am an RN in the USA; have a biopsy, blood work, symptom diagnosis of GCA & PMR since late 2/2017. The article I'm referencing is considered scholarly. So, it maybe difficult to understand. What was a surprise to me is that there are chemical cytokines which are found in GCA that cause inflammation & they are NOT suppressed by glucocorticoids ( the steroids we take). The article found this Rheumatoid Arthritis drug Tofacitinib, did stop the "over growth inside the artery walls" that occur in GCA.

This article was on a link to the American Heart Association Professional site. The title is "Inhibition of JAK-STAT Signaling Suppresses Pathogenic Immune Responses in Medium and Large Vessel Vasculitis".

circ.ahajournals.org/conten...

When I spoke with my internist about this recently, he said that's why we have you on aspirin & will add a statin. I said no way will I take a statin. Seems if we're not blinded by GCA, my Rheum & Internist are content with smoldering inflammation affecting the inside of my arteries.

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Thanks for this - I am no medical expert but like you I find it interesting that our inflammation is not fully controlled by coticosteroids - but the point I guess is as to whether it is generally 'adequately' controlled. I hadn't heard of Tofacitinib and see now it is sometimes used in conjunction with Tocilizumab - for people with RA but assuming there's still more work to do in this area before this is regarded as 'good' for people with GCA.

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'corticosteroids'

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Hi,

Interesting. I note this is coming from a “Heart” organisation and refers to condition of the aorta and it’s large branches. That’s a slightly different slant than the usual studies on GCA.

I would say that your Rheumy and Internist are obviously not “content with smouldering inflammation...” if they are recommending aspirin and a statin!

Aspirin used to be prescribed as a matter of course alongside Pred, but now it’s recommended on a case by case basis.

Just as a matter of interest why so anti a statin?

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My brother who was 10 years older than me, died in 2014. Zocor, a statin, wasted his muscles. He had good insurance, but his doctor was for the birds. His legs were like toothpicks & could hardly carry his 6' 2" frame by the time I saw him. It was a chiropractor who told him the Zocor maybe the problem & not his doctor. Although we spoke on the phone, I didn't see him until our summer vacation in the Adirondack Mountains of NY State.

His kids warned me that his appearance was so changed.

In the hospital that I worked, the minute there are muscle problems with statins, the patients are switched or taken off statins. They can cause muscle breakdown leading to kidney failure. I believe statins killed him in the end. He wound up in an assisted living facility. From there they found him on the floor next to his bed a few times, which sent him to the hospital. Then Albany Medical Center finally got him & diagnosed him with a rapidly progressive neurological dysfunction from which he would need a feeding tube. So, he went into hospice & died within 2 weeks.

I also follow a cardiologist, Dr. Steven Sinatra. He is no fan of statins especially for women. And he grew up around the corner. I remain friends with his sister as we are the same age. And my other brother & him were in the same grade & fraternities. drsinatra.com/about-dr-sinatra

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Ok,

Sorry to hear about your brother, and his doctor didn’t sound the best, but people react very differently to medication- and we all know there is an element of risk. I guess we just have to trust the medical profession will check to ensure those risks are minimised.

Dr Sinatra may be a family friend, but I see he is also selling his version of medication.

As the saying goes - you pays your money and you takes your choice!

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I don't buy from him. I like the the vitamin company Bluebonnet. They source their stuff in the US. The man who started this company, did so after he sold his company Schiff, he didn't like how they changed. Here's a link to how Bluebonnet sources bluebonnetnutrition.com/abo...

Dr. Sinatra has co authored a book "Health Revelations from Heaven and Earth". The other author, Tommy Rosa, had a near death experience. I'm a vegetarian since my son died 8 years ago. It's a sacrifice for me. I like meat. But, at this point I'm not eating anything with eyes or a mouth. Dr. Sinatra says meats OK, but grass-fed. I eat the gifts of the animals, egg whites, low salt Lacey Swiss Cheese, plain Greek yogurt, good sourced whey protein. I don't think Dr. Sinatra would advocate these things. So as with all things, I take what I want & leave the rest of what he has to offer.

I may look at Bluebonnet's Cellular Active® CoQ10 Ubiquinol 100 mg Vegetarian Softgels.

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From Dr. Sinatra's website:

"Disease Risk and the Cholesterol Myth

Many doctors are still prescribing cholesterol lowering statin drugs in record numbers. But the odds are good that you’re not realizing any benefit from that cholesterol medication you’re taking—because cholesterol is not a serious risk factor for heart disease. Taking steps to reduce inflammation—including eliminating dietary sugar—is the best way to protect yourself.

Dr. Sinatra was also one of the first to say that saturated fat is not the enemy. Instead, saturated fats help to raise your beneficial HDL cholesterol, improving your triglyceride/HDL ratio—a key marker of cardiovascular health. Plus, foods high in saturated fat also help to change your LDL cholesterol pattern, from small dense particles that can clog your arteries to large “fluffy” harmless LDL particles."

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The most recent guidelines for management of GCA actually have removed the aspirin recommendation as not having more benefits than risks in terms of bleeding risk.

This is in vitro work - will it be the same in humans? There are other large vessel vasculitides which are treated with other drugs - mostly chemotherapy ones - to induce remission and which then require to be used at intervals if and when it flares. It is pretty likely that there could be a mix - but you would also expect left-over symptoms and lack of response to corticosteroids would also suggest that whatever is going on is not pure "GCA".

In GCA and PMR the corticosteroids never do suppress the cytokines by modifying the disease process - they relieve the inflammation and suppress the symptoms. The autoimmune disorder chugs away in the background until it decides to go into remission. A great deal of the longterm damage is due to the inflammation which is why it is important to take ENOUGH pred for long enough. On the other hand - tocilizumab DOES appear to target the actual cytokine pathway and modifies the disease mechanism. Whether it can kick it to reset over a long period without ongoing treatment remains to be seen.

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Thanks PMRpro. Is this referenced somewhere as I am still taking my daily dose of 75mgms if soluble aspirin?

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keepandshare.com/doc/819279...

is the slide presentation about it which Prof Dasgupta gave at the Scottish meeting nearly 18 months ago - the aspirin and statin advice is in Recommendations 9 and 10, just a few slides from the end of the presentation. There are a few random slides about TB in the middle - no idea why!! But as far as I know the new Recommendations have not been published yet.

I'm sure your husband will like it. Interestingly - there are comments about shared decision making between patient and physician and adjusting tapering to suit the individual patient! Hope springs eternal...

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That’s really helpful.

I expect you know that GPs in the UK have to undertake an annual endurance test called Appraisal which leads to relicensing every five years. All the older ones like mine absolutely hate it and struggle to determine what they are going to do for their next Personal Development Plan. Guess what mine is going to do? PMR and GCA, there is so much lovely clinical information on this site that he will astound them with his knowledge, starting with this 76 page handout.

Cheers🥂🥂

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Oh terrific!!!! If there's anything anyone from the charities can do to help just say. Some are involved in developing the guidelines, others have worked closely to develop other stuff.

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Any guidelines would be useful. They each need to have a GP Appraiser attached to the University so it will get into the system

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I suspect if he contacts Lorna Neill at the Scottish group she can provide him with a lot of links to suitable info - she is on a range of guideline committees and a patient research partner with the Leeds group.

pmrandgca.org.uk/

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Thanks I can do that and he can read them 🥂

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I've just emailed her to ask if I can give you her direct email address.

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Thank you

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She's delighted to help any GP who wants to increase his knowledge of PMR and GCA!! Will pm the email address.

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There are 8 of them in the Practice with some bright young things eager to learn so the word can be spread

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That's what I like to hear :-)

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The more I read about these expensive arthritis/ psoriasis drugs, the more I know I don't want to be on them. At 15mg/day of Prednisone, many of the skin growths I got at higher doses are abating. I also have Blepharitis (An inflammation of the eyelid that affects the eyelashes or tear production.) which has gotten so much worse on Prednisone. I have had at least 3 eyelid infections requiring oral antibiotics in one year. It is when I'm on antibiotics that any cuts & abrasions (my skin splits open at minor brushing against something since on Prednisone) begin to heal. So, despite having a low carbohydrate diet, on steroids, I heal like someone diagnosed with diabetes. And having an infection is one reason not to take these other drugs. Since at higher doses I begin to get grayish bumps all over my skin, I'd also be afraid of the lymphomas they talk about getting with these drugs.

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I hear you on the aspirin. I am on Evista to prevent bone loss. Blood clots are a potential side effect. I am pursuing the energy healing called Reiki through adult ed classes. The teacher impressed me as 30 years ago she had Lupus. Her treatment had her hair falling out & more. So, her rheumatologist at the time, didn't discourage her from trying Reiki. Her sister was diagnosed with stage IV non Hodgkin's lymphoma, too. Both of them were successfully returned to good health with Reiki healing. Can't hurt to try.

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No objection to TRYING anything - but not in isolation.

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First off thank you for this great info. You being a RN have more medical understanding of all of this. Since according to this study that Prednisone does not suppress inflammation in the arteries then how does it work? Someone else mentioned this too that we don't know to the full extent how Prednisone works. I don't understand how some people have gone into remission while being on Prednisone. The mechanism of Tofacitinib makes sense as it PARTIALLY prevents cytokine production which equates to less inflammation. There is still inflammation but less so how much of an effect does Tofacitinib have on GCA? I don't know but the downside is when you're on this drug all the time and you get sick, catch a bacteria or virus, then you are in trouble because pro-inflammatory is blocked and we need pro-inflammation to fight the bacteria or virus or whatever is making us sick. The question arises which one is worth the risks; Prednisone vs Tofacitinib.

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Yes, it is a dilemma. I'm glad that I was put on Prednisone once I was diagnosed. I was covered at 60 mg & the headaches stopped. It's been a year of trying to decrease. This week I'm down to 14 mg/ day.

Going forward, I want to try alternative therapies in addition to Prednisone. As I said, I don't want any of those other powerful immunosuppressive drugs.

I have had short (15 minute) healings at Psychic Fairs which were terrific. I plan on seeing the last one I saw again privately. And I just started the cellular active Ubicquinol for what the steroids are doing to me.

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The purpose/point of using pred is that it reliably suppresses the effects of the inflammation - irrespective of the underlying cause. That has been known for many years and that is why it is the mainstay of immediate management of suspected GCA. The basic science seems to suggest there are at least 3 different mechanisms of inflammation in GCA, due to B-cells, T-cells and monocytes and macrophages. all of which have been shown to be present in temporal artery biopsies.

Tofacitinib and Actemra each seem to work on one aspect of the creation of the inflammation - but not necessarily all. Which is why pred will probably remain part of the management of the disease for some time to come. Not all patients are able to stop taking pred even while on Actemra - so maybe there is more than one mechanism at work. That certainly seems to be the case in PMR and the links between GCA and PMR are very close.

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I agree I would not go on statins either nor will I take aspirin but I did take Actemra and it did a wonderful job. If you have read any of my posts you know I have been on steroids for a very long time and they had done a lot of damage. I think the Actemra finally got rid of the major inflammation because it brought my CRP and ESR way down which prednisone could not do. I have just taken myself off the drug and I am living with 8.5 mg of prednisone for newly discovered Addison’s disease until I see my endocrinologist. I to live in the USA and presently in Florida on my way back to New Jersey in May. Good luck to you I hope your journey is a little easier than mine has been.

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The prednisone works on my numbers (sed rate & CPR). There was a month in Dec that I didn't have any jaw pain. My shoulders are always sore when I lift my arms like during folding of sheets. I did want Acterma. But, in the last year I have had 4 infections. Three related to my eyelid requiring antibiotics & one from my cat's nail going into my cheek when she tried to wake me up with her paw. I can't cut them as they are former feral cats. Other skin manifestations I get are easy abrasions that need topical antibiotics, growths all over my skin (seems these can come off if my dose is below 20 mg). I also have seborrheic dermatitis which is controlled with antifungal topicals & shampoos.

When my cat got me with her nail, I put a prescription topical antibiotic on the scratches on my face. Normally, any deeper infection from an animal will show up in 12-14 hours. It was a day & a half before the side of my face was swollen & red. Steroids delay healing as well. Whenever, I'm on antibiotics, all my cuts on my legs & arms stop being red & begin to heal. Acterma & all the other drugs that suppress the immune response can suppress response to infection.

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I understand. But here’s the thing and maybe I’m wrong but if you are getting these infections anyway perhaps Actemra will not make them worse.. I don’t know. I was not on it for long. From August to February 2018. That’s 7 months and I started every other week a month ago. So far so good. My next blood test will tell me more. If the CRP and ESR don’t exceed the norm then I’m good. Or it may take a week or two longer to tell. Are you on steroids for adrenals? You probably told me and it’s late and I am too tired to look it up. Also remind me how much steroid you are on.

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Hi Nap1, I know my fatigue comes out of the blue, so plans are often changed. I am on 14 mg/day of Prednisone split to be 5 AM & 5 PM as that works better for me. I am going down 1 mg every 3 weeks as the first week is often hard awful leg & foot cramps that wake me up, requiring me to stand up and walk, fatigue that comes out of the blue and once I lay down, I can hardly get up. It's like the muscles are paralyzed. This passes. I've never gone below 15 mg without a flair, which for my Rheumatologist didn't count as a flair until he saw the Sed Rate go from 3 to 21 to 42. Oh, now he believes my symptoms. Because although he didn't think 21 was bad, that was on high dose steroids. My scalp hurt behind the temples, my jaw pain returned. And when I get one of these infections, I don't feel so well all around & won't decrease until the antibiotics are out of my system. And we traveled in January and I won't decrease, I don't have another appointment since their system was down to make one. I'm decreasing as we had discussed. If I get a flair, I'll call them. We have discussed Acterma & only with more flairs will he consider it.

As far as my adrenals, they are in all likelihood asleep, so to speak. I have the moon face, male pattern loss of hair, my blood work shows that I an in a catabolic state per my internist (steroids cause muscle wasting ncbi.nlm.nih.gov/pubmed/104... My weight has decreased by 30 #s as I keep my diet low salt & low carb. Now my BMI is normal, but the weight in the abdomen persists to a degree.

I started an adult ed Tai Chi class, to help with my balance. But, I'm not doing it when there is no class. I took ReikI Level I in adult ed class, but I'm not practicing it daily as we were taught.

I get outside everyday, but my 7 hours of gardening days seem to be gone. Three hours is a lot.

Are you a snow bird? Although I'm 67, I've been working one day a month teaching Infant CPR. Love it, when I do it. After 45 years of acute care nursing, these are expectant couples, grandparents and some who have their babies in the neonatal ICU, so those before me are healthy. But, it does require that I maintain all my certifications and learn new things.

I am so happy Acterma has worked for you. Infection is one contraindication for Acterma. And each time I got these infections, I had to go to either the eye doctor, the internist, or Urgent Care to get treated. I think I'd have to go to a different Rheumatologist to go on it. He doesn't monitor any other blood work like the markers for cholesterol, glucose or even the changes that could be going on in my bones and major vessels. The first thing he said when I brought Acterma up was that it could perforate my stomach. So can Prednisone. I have seen pancreatitis reported, but I'd be more concerned with liver enzyme elevation. My liver enzymes were a little elevated when I was diagnosed with GCA. And a nurse educator I worked with had to come off Acterma for Rheumatoid arthritis due to her liver enzymes increasing.

I don't think they want to be bothered monitoring all these things carefully. He once asked me who was following me. I said I thought it was you.

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"my blood work shows that I an in a catabolic state"

What markers are abnormal? Just interested to learn.

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Mostly it's my anion gap which is around 2 last it was checked. And my BUN is always about 10 points higher than normal (The creatinine is fine.) And the RDW was abnormal I can't remember the number, but that's OK last CBC. Without a search of all the paper work, I don't have the exact numbers as it was done in the Emergency Room after my doctor was worried that I had facial cellulitis from the cat scratch infection. So, later that week I went to see him to interpret these findings. In the ED they thought nothing of it as they were just making sure I wasn't headed toward sepsis. Certainly sepsis causes acidosis. Anyway, the only thing I found about a low anion gap was multiple myeloma. So, I wanted him to tell me why. He said because your catabolic (from muscle breakdown). ncbi.nlm.nih.gov/pubmed/104...

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