Has infection caused flare?

[Countrykitten]

I have Depomedrone injections for PMR every four weeks because I cannot take oral Pred..I had just tapered down to 40mg from 60 (I started on 120 and tapering over last year or so ) This dose did nothing for me, arms, shoulders, thighs,.hips etc..becoming more stiff and painful..Locum GP put dose back up.to 60 at next injection so I had a painful four week.wait..I then had the ,60mg dose but continued to have all usual symptoms..I had the next 60mg yesterday and told the nurse that the previous dose didn't help .She has arranged for a Dr to ring me on Monday. While all this has been going on I have had a nasty septic cyst on my back. It is finally cleared after two courses of antibiotics and weekly clearing out by nurse. I wonder if all the poison circulating in my blood has caused a flare and whether things will settle down again if I stay on 60mg for the next injection.I know few of you have experience of Depomedrone but have any of you had a flare caused by an infection and taken.a while to.settle down?

I am not looking forward to Dr's call because my nice GP has retired, helpful Locum no longer there and only two male Drs left at practice, each of whom have, in the past, decided to alter my medication without ever meeting me!! So I have little faith in either. (My 'proper' GP put me back on correct doses.)

Sorry to ramble on, feeling a bit lost at the moment. Thanks.

[PMRpro Ambassador]

You aren't reducing relentlessly, you are looking for the lowest dose that works and I suspect you may well have gone a bit low - it was a big change, But yes - your immune system has been under fire with the septic cyst and could well have triggered a flare. However - if you have had 2 months with symptoms, you will need to clear the accumulated inflammation out as well.

[DorsetLady PMRGCAuk volunteer]

Agree with PMRpro, you need to address the flare [if that’s what it is ,and agree very likely] - and it’s a bit difficult with your situation..

[SnazzyD]

Have you had your blood sugar tested over the last few months?

[Countrykitten in reply to SnazzyD]

No. Do you think I should?

[SnazzyD]

Yes. Depomedrone, like other potent steroids, will be forcing the liver to make the blood sugar rise. Persistent boils and reduced healing can be a sign of diabetes or persistently raised blood sugar. Your GP should be keeping an eye on it. You may be already doing so but a super low carb diet helps mitigate this effect.

[AtopicGuy]

I find it hard to see how your immune system can correct itself, or effectively taper off, 4-weekly injections of Depo-Medrol, whose active ingredient is methylprednisolone (see link below). Steroid injections are like a shock treatment to the immune system, the very opposite of what a taper is designed to achieve. Here's why:

Methylprednisolone is 25% more potent than prednisolone, so a 120mg injection is equivalent to a massive 150mg of prednisolone. However, the half-life in the blood is only 3.5 hours, so at the start of the second day there is only the equivalent of about 2mg of prednisolone left in your system. By the start of Day 3, it's all gone and there's still 26 days before the next shot.

The numbers are even more stark at a Depo-Medrol dose of 40mg. By 24 hours after the injection, only about 0.5mg of methylprednisolone remains in the blood, equivalent to just 0.4mg of prednisolone.

Who knows how your adrenal glands respond to being on such a steroid rollercoaster? Any benefit that continues after Day 1 is simply because the immune system is still reeling from the shock of the high dose. It's hard to see how chronic inflammation can stay healed under that regime.

drugs.com/compare/depo-medr...

[Countrykitten in reply to AtopicGuy]

I have been following Dr Dasgupta's regime, tapering by 20mg every 12weeks. It has been working very well until now.

[PMRpro Ambassador in reply to AtopicGuy]

You obviously don't understand the mechanism of depot medrone deep i.m. injections. You will find it discussed in the posts by Admiral06. The deep i.m. approach results in a slow release over the following few weeks/

healthunlocked.com/user/Adm...

They have been used in a clinical study by Prof Dasgupta and no-one here will dispute that he knows his stuff:

ncbi.nlm.nih.gov/pmc/articl...

and they are mentioned in the 2015 guidelines for the management of PMR. I know a few patients who used them successfully for PMR and one who even managed to control GCA using them.

[Countrykitten in reply to PMRpro]

Thanks for pointing that out to Atopic Guy..I've been pleased to follow Prof Dasgupta as approved by my old GP. Just worried what remaing Dr will want me to do..

[AtopicGuy in reply to PMRpro]

Indeed. I'd never heard of Depo-Medrol so I googled it. None of the medical sources I checked mentioned it being for intramuscular injection, or how that works. The link I copied only gave a half-life of 3.5 hours. Thank you for spotting the missing link in my reasoning. When I get a minute, I will dig deeper with my research.

[AtopicGuy in reply to AtopicGuy]

My research turned up this datasheet from NZ. It is for Depo-Medrol 40mg/ml used for intramuscular injections:

medsafe.govt.nz/profs/datas...

The name "Depo-" stems from the idea that the modified corticosteroid - methylprednisolone acetate - is injected into one or more 'depots' within the body. The acetate part is then slowly, naturally stripped off, and pure methylprednisolone circulates around the bloodstream.

It takes about 7.1 hours for the steroid level to reach its peak in the bloodstream. The level then decays with a half-life of about 69.3 hours (just under 3 days). So after a week, the level of steroid in the blood has fallen to just 20% of its peak. After 2 weeks, less than 4% remains. The drug has effectively run out while there's still weeks left until the next injection.

Two things mean the anti-inflammatory benefits of steroids do not end abruptly, of course. Firstly, the immune system stays suppressed for a while after the drug peters out. Secondly, the adrenal glands should quickly begin producing cortisol again, because the treatment is short-term. These effects extend what the experts call the "duration of hypothalmic-pituitary-adrenal axis suppression", or the "duration of HPA axis suppression" for short. Unfortunately, the datasheet says that this immunosuppression lasts only "4 to 8 days" depending on the number of doses. So I remain puzzled as to how monthly intramuscular injections can consistently relieve PMR symptoms for a whole month, and encourage the immune system to abandon autoimmunity, unless 'shock tactics' are involved. It seems to fly in the face of gentle tapering.

[PMRpro Ambassador in reply to AtopicGuy]

I did give you some links that describe it - and I assure you it DOES work.

[AtopicGuy in reply to PMRpro]

I don't question that it does what it does. What it doesn't do is replicate a daily dose which (if taken first thing in the morning) matches the rise and fall of the natural cortisol cycle. Nor does it provide a consistent dose from day-to-day, week-to-week, which is the aim of slow-tapering regimes.

[PMRpro Ambassador in reply to AtopicGuy]

It tapers itself naturally and it is claimed to have less effect on adrenal function and causes fewer adverse effects altogether. Which is the same as I have heard from people who tried it,

It is a fallacy to believe that morning pred mimics the natural rise and fall of corisol production - if it did then there would be less adrenal suppression which is in fact seen with use of depot-medrol.

[AtopicGuy in reply to PMRpro]

Indeed. As the datasheet from NZ shows: each injection is effectively a two-week-long course which tapers to zero well within the month. Adrenal suppression only happens when the glands have nothing to do for extended periods. I'd be surprised if a single dose of Depo-Medrol had that effect, but repeated injections might.

The paper below says the adrenal glands normally produce about 9.7mg of cortisol per day. This is equivalent to less than 2.5mg of prednisolone. So any sustained dose over this level might risk 'putting the adrenal glands to sleep'. How promptly they wake up is another matter. I've tapered off long courses beginning at 20 - 30 mg/dy three times without an issue.

ncbi.nlm.nih.gov/pmc/articl...

My point about the circadian rhythm is that, for the first few days after an injection, the steroid level stays high through both day and night. On a morning pill regime, the concentration in the blood has fallen by about 90% by bedtime. The later is much closer to the normal cortisol cycle than what Depo-Medrol produces.

[PMRpro Ambassador in reply to AtopicGuy]

Suppression takes several weeks - a few days is not enough.

Can you not accept that medics who know what they are talking about did the study?

[AtopicGuy in reply to PMRpro]

That's exactly what I said (assuming you mean adrenal suppression, not immunosuppression).

[Countrykitten in reply to AtopicGuy]

I don't understand why you seem determined to prove Depo doesn't work! As someone with PMR who cannot take oral Prednisolone I can assure you that it does. There is no alternative for people like me. 'The proof is in the pudding' as the old saying goes and eminent clinicians would not prescribe it if your arguments were correct!!

[AtopicGuy in reply to Countrykitten]

I'm not "determined to prove Depo doesn't work!" Your posts keep us informed of how things are progressing, and I know that steroid pills and liquids have been ruled out. All I am trying to do is understand what the injections are actually doing to the body, because that can provide insights into the disease.

[Countrykitten]

Just had my phone call from Dr. The nice helpful Locum is back at practice. I told him I thought my flare was caused by the cyst. He said that was what he was going to suggest to me..Also, I said I am definitely feeling much improved after last Thursday's injection and would like to carry on at 60mg for next twelve weeks ( three more injections) and again he said that was what he was going to suggest. He said I'm a very sensible person who knows her own body and what it needs! Hooray, a Dr who works with the patient and doesn't talk down to us. I just wish the practice would offer him a full time job. I actually managed to strip the bed this morning (cleaner puts fresh bedding on) That's the first time I've been able to lift my arms for two months. Looking back at the calendar I notice my cyst/flare happened shortly after Covid booster, so possible factor. But I'd rather put up with PMR symptoms than risk the dreaded Covid.!!!