Corticosteroids significantly worsening apparent immunological symptoms

[spinachhands]

Hoping there are people much smarter than me here than can help me understand what is happening.

My partner has ME/long COVID, they became very severe in 2023 and have been bedbound since. With rest and time their energy, fatigue, and PEM were all improving. Midway through 2024 they began experiencing new symptoms that were not present when their ME/LC was at its worst, that have only continued to worsen with time even as their core ME/LC symptoms continued to improve.

After a LOT of investigations, doctors, treatment trials and dead ends, we are now working with two doctors who both believe this is severe immune-mediated autonomic dysfunction.

There's more research going on in the US about this than here in the UK, but essentially it's believed that the long term damage to their immune system from the LC has led to autoimmunity, which has been damaging their autonomic nervous system. It's not responding to any usual treatments for POTS, MCAS, etc. Both doctors think they need IVIG, or possibly plasmapheresis.

While this is being arranged, they were prescribed prednisolone to see if it could in any way dampen their severe immune responses (their symptoms worsen from any input- food, water, vitamins, medicines).

After just two doses they've had to stop as it has severely worsened all of their symptoms. This isn't side effects, but their same symptoms magnified 1000x. Until I can get a hold of their doctors to talk this through, I'm trying to figure out why this could happen, and why the steroids would have the opposite effect they're supposed to.

I've been reading how in some circumstances, corticosteroids can have a pro-inflammatory effect, especially if there is already microglia or endothelial dysfunction. It can also exacerbate vascular issues, which may be having an effect on their autonomic issues?

It's been nearly 24hrs since their second dose, and even drinking a glass of water left them unable to move, struggling to breathe, dizzy and faint, immense pressure in their head, pain all throughout their body. I just want to understand, if their immune system is the problem, why would immunosuppressants make it worse? And what could help it? Getting IVIG, or feeling any benefit from it, could still be months away and we need to figure out something in the meantime as they can't live like this. All they can eat is white rice, and even that makes them worse.

Any ideas on what could be happening, and what could be done instead that I can ask the doctors about, would be greatly appreciated.

 

[Jonathan Edwards]

Any ideas on what could be happening, and what could be done instead that I can ask the doctors about, would be greatly appreciated.

If the person concerned is very unwell then they need medical help, not advice from here. We try hard not to give advice on treatments for individuals, as much as anything because the diagnosis may be wrong and without all clinical details it would be irresponsible.

All I can really say is that the explanations you give do not make much sense and I would question that anyone here knows what is going on. (As you probably know I am a professor of immnology with a particular interest in autoimmunity. There is no reason to think Covid would induce autoimmunity as far as I know.)

If I had more details on where you are and who the physicians are I might be able to make more useful comments. I don't think there is any point in trying to explain why steroids have been associated with worsening without some understanding of what is actually happening.

I am pretty sure that there is no evidence for IVIG being relevant in this sort of situation, nor any reason to think it would be.

Send me a direct message if you prefer.

 

[Colleen Steckel]

Hoping there are people much smarter than me here than can help me understand what is happening.

My partner has ME/long COVID, they became very severe in 2023 and have been bedbound since. With rest and time their energy, fatigue, and PEM were all improving. Midway through 2024 they began experiencing new symptoms that were not present when their ME/LC was at its worst, that have only continued to worsen with time even as their core ME/LC symptoms continued to improve.

After a LOT of investigations, doctors, treatment trials and dead ends, we are now working with two doctors who both believe this is severe immune-mediated autonomic dysfunction.

There's more research going on in the US about this than here in the UK, but essentially it's believed that the long term damage to their immune system from the LC has led to autoimmunity, which has been damaging their autonomic nervous system. It's not responding to any usual treatments for POTS, MCAS, etc. Both doctors think they need IVIG, or possibly plasmapheresis.

While this is being arranged, they were prescribed prednisolone to see if it could in any way dampen their severe immune responses (their symptoms worsen from any input- food, water, vitamins, medicines).

After just two doses they've had to stop as it has severely worsened all of their symptoms. This isn't side effects, but their same symptoms magnified 1000x. Until I can get a hold of their doctors to talk this through, I'm trying to figure out why this could happen, and why the steroids would have the opposite effect they're supposed to.

I've been reading how in some circumstances, corticosteroids can have a pro-inflammatory effect, especially if there is already microglia or endothelial dysfunction. It can also exacerbate vascular issues, which may be having an effect on their autonomic issues?

It's been nearly 24hrs since their second dose, and even drinking a glass of water left them unable to move, struggling to breathe, dizzy and faint, immense pressure in their head, pain all throughout their body. I just want to understand, if their immune system is the problem, why would immunosuppressants make it worse? And what could help it? Getting IVIG, or feeling any benefit from it, could still be months away and we need to figure out something in the meantime as they can't live like this. All they can eat is white rice, and even that makes them worse.

Any ideas on what could be happening, and what could be done instead that I can ask the doctors about, would be greatly appreciated.

So sorry for what you are both going through. None of this is easy! I have a lot of experience with mast cell activation syndrome - dysfunctional immune system since the 90s. I can relate to having to limit foods to manage symptoms. I have also had trouble with steroids. If you are interested in what I've experienced, please feel free to reach out to me - I can be found on most social medial platforms.

 

[spinachhands]

If the person concerned is very unwell then they need medical help, not advice from here. We try hard not to give advice on treatments for individuals, as much as anything because the diagnosis may be wrong and without all clinical details it would be irresponsible.

All I can really say is that the explanations you give do not make much sense and I would question that anyone here knows what is going on. (As you probably know I am a professor of immnology with a particular interest in autoimmunity. There is no reason to think Covid would induce autoimmunity as far as I know.)

If I had more details on where you are and who the physicians are I might be able to make more useful comments. I don't think there is any point in trying to explain why steroids have been associated with worsening without some understanding of what is actually happening.

I am pretty sure that there is no evidence for IVIG being relevant in this sort of situation, nor any reason to think it would be.

Send me a direct message if you prefer.

Thanks for your reply, and yes I do understand that I can't be given medical advice. I'm mainly looking to try and figure out why steroids might make the symptoms they're supposed to be helping, worse. I will be speaking to their doctors as well, but want to go into the appointments with some thoughts and understanding.

The concept of long COVID leading to immune mediated, widespread severe dysautonomia is a fairly new one, I think at this year's dysautonomia international conference it was Novak who discussed results of trials with IVIG, and a few others presented on immune effects on the autonomic nervous system, and well as newer thoughts around cerebral hypoperfusion. Although it doesn't show on your traditional tests for inflammation and autoimmunity, more advanced testing and scans have shown it in patient studies. My partner does have low white cell count, low lymphocytes, and low T Cells across CD3, 4 and 8.
Two different doctors separately came to the same conclusion on hearing their full history, symptoms and test results, one cardiologist/dysautonomia specialist, and one infectious diseases/immunology specialist. Both are now working together hopefully to arrange either ivig or plasmapheresis.

Their symptoms' lack of response to classic mast cell treatments (literally...all of them), suggests their severe worsening of symptoms in reaction to food, water, IVs, vitamins, medicines, basically anything is immune/autonomic but not just mast cell mediated. Gastro involvement has been ruled out, MRIs have ruled out structural neuro issues. Traditional POTS treatments have also proven essentially ineffective, which the drs suggest is because there is still too much damage being done to their ANS from their immune system for it to be effective.

No worries if you don't agree with the diagnosis or idea of autoimmunity in LC/dysautonomia. Honestly would welcome any alternate suggestions for routes to look down. I have a list complied of every blood test result from this year and it's at nearly 400 lines so have managed to rule out quite a lot! I just need to get them some help really, it's what I've dedicated the past two years of my life to and still, even as their ME/LC improved, this all began and has just gotten worse no matter what we do.

As you can imagine, the NHS have been close to useless. Just writing us off as hypochondriacs while my partner lies paralyzed and wracked with pain, unable to think and in torment from sipping some water. They've gone into hospital twice this year in acute care and still the doctors just want to fob them off to do CBT and mindfulness.

 

[Jonathan Edwards]

The concept of long COVID leading to immune mediated, widespread severe dysautonomia is a fairly new one, I think at this year's dysautonomia international conference it was Novak who discussed results of trials with IVIG, and a few others presented on immune effects on the autonomic nervous system, and well as newer thoughts around cerebral hypoperfusion.

With due respect, I have no confidence that this sort of 'new concept' is based on any real science. I would be very wary of Dysautonomia International. As indicated before, none of this makes much sense to me as an immunologist. We discuss this sort of issue regularly here and I thinkmy scepticism is shared by most who are interested in getting to the bottom of the science. Sadly, there is far too much half-baked stuff around even within establishment immunology labs.

Reactions to food, supplements and water are very unlikely to be immunologically mediated. I also think it unlikely to have anything to do with mast cells. I cannot establish from what you say why anyone should think steroids would help. Steroids do not even necessarily help immune problems - it depends on what mediators we think are involved.

POTS is not about damage to the ANS. It shows an active ANS response for reasons presumably from elsewhere.

Sorry to be negative, but there is a huge amount of disinformation out there on these things, and there are also a lot of 'influencers' ready to spread the words.

The NHS is a disaster but as far as I know nobody knows what is best to do in these situations other than provide support. Unless of course the diagnosis is wrong - which is where I emphasise that none of us should not give personal advice.