One step forward, two steps back: treating inflammation and HPA axis

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This should perhaps serve as an update to anyone curious about how my last year has gone, what I've understood, what I've learned. Perhaps it's a way for me to get feedback from PR.

Yesterday, Cort Johnson posted a very interesting article about the mechanisms of long Covid in the context of what researchers have observed. He summarized a preliminary finding: there is no specific "signature," or pattern of autoimmunity in long Covid patients. He draws a parallel with ME/CFS patients: there is no clear-cut autoimmune presentation, no signature of auto-antibodies, but an "array of autoimmune antibodies," mimicking the predisposition and susceptibility in each individual and rendering a 'singular sick pattern' of ME/CFS for every patient.

I spent the last year in France trying getting through a one-year program in a nursing school. I specialized in caring for the disabled. This included practicums in order to build professional experience. Until I was put on prednisone, my decade-long symptoms were inevitable.

In the mornings, I suffered from dry eye, body-wide weakness, stiff muscles, and fatigue. Throughout the day, the hours upon hours of classroom energy sent me into a crash. As was also expected, I had more erratic bowel movements (IBS), dermatological flares (seborrheic dermatitis), and poorer blood circulation. I might also add recurring, aggressive episodes of torticolis, frozen shoulder, and joint displacements due to CCI and / or unspecified connective tissue disease.

From the moment I was put on prednisone, most, or the totality of my symptoms were abated. I was re-reading French medical literature on treating ME/CFS and Fibromyalgia and noticed a section where they say that corticosteroids do nothing for fibromyalgia pain. It was striking to reconcile this with the diagnosis of ME/CFS and Fibromyalgia that a rheumatologist finally gave me one month ago, upon finding nothing on my scans or labs to indicate a specific autoimmune or rheumatic condition.

Striking until one juxtaposes the observation that long covid, or ME/CFS, or post-viral fatigue are non-specific autoimmune conditions (syndromes) with symptoms that present relative to any one person's particular health risks and health predisposition. If ME/CFS is autoimmune, then we each acquire different presentations of the same syndrome.

-----

In attempting to treat myself, what did I learn so far?

On a urinary (catabolites) analysis, I learned a few things:
  1. Neurotransmitters: abnormal serotonin (below range) ; very low dopamine ; abnormal noradrenaline (below range) ; abnormal HVA and VMA (below range).
  2. Lymphocytes: normal CD4 count ; abnormal CD8 count (below range) ; abnormal IL2R (above range).
  3. Microbiome: rather healthy with exceptions -- abnormal indican (above range) -- a metabolite produced by tryptophan-dependent flora / bacteria.

On whole genome sequencing, I "might have two short-form 5-HTTLPR" (at gs290, in SLC6A4). This is a degenerate, repeat polymorphic region that plays into the way the body handles serotonin (apparently it is a sped-up, serotonin-transporting enzyme).


In a very costly but state-covered extensive stool analysis, no abnormal bacteria, clostridium, or parasite was found. A gastroenterologist recommended a colonoscopy anyway, which I will have early next year. I have mild pancreatic insufficiency -- this was corroborated with a Genova amino acids analysis.

-----

Through treatment with two medications so far, two notions have a strong basis in my test results and symptomatic experience.

Inflammation: doctor is weaning me off prednisone after one year on it. I was at high levels at the beginning of the year. Toward the second half of the year, I remained at a daily dose of 5mg prednisone:
  1. In terms of pain, stiffness, muscular exertion, blood circulation, energy and cognitive capacity, the prednisone eliminated all of my symptoms.
  2. Now that I have had to replace it with hydrocortisone (a strength-equivalent dose of 20mg, split throughout the day), the entirety of my symptoms have returned: energy problems, pain, and stiffness

HPA axis: the other piece of the puzzle for me. A second doctor suggested I try an SSRI (Lexapro).
  1. Last year, I attempted Lexapro but struggled so badly in terms of gut reactivity that I quit.
  2. I attempted it again this year and adjusted of my own accord to a low dose of 5mg.
  3. I've been taking it for one month now. It did nothing noticeable when taken during the day.
  4. Like I've noticed before, when taken at night prior to going to sleep, it made me a decisively very noticeable difference. I woke up far more 'responsive' the next day (e.g. early morning rise for work).
  5. This ties into what seems in my case to be an endemic deficiency in serotonin transportation.
-----

When these two medications were taken together, I had effectively abated most of my ME/CFS and Fibromyalgia symptoms, including IBS.

Once I was forced off one half of the protocol, the inflammation returned. The lexapro at that dose became ineffective.

I am once again left to my own devices, tending to a body replete with problems: absolutely unrefreshing and non-recuperative sleep ; muscle fatigue and stiffness throughout the day ; poor adrenal function ; a hypersensitive immune system.

At this point in time, it is nice to have state-covered health insurance, but paired with a shy, non-progressive medical system, it does not make much of a difference.

-----

I have to figure out a way to continue to wean off corticosteroids if this is what is asked of me. In the meantime, I am considering raising my dose to 10mg lexapro.

In anticipation of a work contract next year and more early morning rises, I am throwing more at the wall to see what sticks, because I know the mornings will be a struggle. I am not waiting to see my psychiatrist in one month's time. I have ordered 10mg amitriptyline based off positive feedback on Fibromyalgia Facebook groups: it appears to help with neuropathic pain.

Lastly, I am attempting whatever I can to replicate the undeniable anti-inflammatory effects of prednisone: I am trying to order low-dose naltrexone through the UK (online consultation). They absolutely do not offer it in France... nor do they conceive of its off-label use.

-----

Something about addressing inflammation (prednisone) as well as the HPA-axis (serotonin) has been undeniably and verifiably efficient for my ME/CFS and Fibromyalgia. I cling to the diagnosis not only because I believe that it manifests differently in each of us. I also cling to it because I got there through sound exclusion: no consistently elevated CRP, no positive ANA nor ANCA, no HLA B27, no joint inflammation, no obvious viral titers (I have yet to check for enterovirus). No obvious Lyme.

In the meantime, don't hesitate to leave feedback if any of you have some. I am still effectively bouncing between doctors who are too timid to properly handle the complexity of my situation -- I have been bouncing between medical systems and countries for well over a decade.

In the meantime, I am chelating (Andy Cutler). I am trying to figure out ways to raise my rock-bottom cortisol in the morning (Genova 4 pt salivary test confirms this). I am ordering 100 mg pregenolone to trial it. DHEA is not allowed into the country here.

Thanks for reading this extremely long post. I have no idea what to expect because electing to trial medication on my own is a scary position to be in (amitriptyline ; LDN if I get it).
 
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xebex

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I don't really have anything to contribute other than I admire your thought process throughout this. I have also been thinking of taking steroids - do you think florinef could have similar results? I'm not sure about taking prednisone as it can damage dura and I have a suspected spinal fluid leak that could be caused by weak dura, i'm not 100% on this it was just a suggestion by a doc so i'm not entirely throwing it out the window.

Also i tried LDN 2 years ago and it very much helped my brain fog - over time i got physically worse so i quit (and resumed more activity) but the brain fog is still considerably better even after quitting LDN (though i have to keep my sugar load down), and although very physically limited, my daily cognitive functioning is very good apart from when in a crash,
 
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I have also been thinking of taking steroids - do you think florinef could have similar results? I'm not sure about taking prednisone as it can damage dura and I have a suspected spinal fluid leak that could be caused by weak dura, i'm not 100% on this it was just a suggestion by a doc so i'm not entirely throwing it out the window.
I haven't researched fludrocortisone quite enough. Of course, the major concern is the following: prednisone was strong enough to mop up my inflammation, but hydrocortisone wasn't...?

Does this mean that I should hope to find something as strong as prednisone? And if so will there always be side-effects to a medication that is as strong as prednisone? By extension, will LDN even be enough? It's all a bit concerning, but I have to remain hopeful.
 

xebex

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i think LDN is just a huge unknown, it could perform miracles it could do nothing - such a weird potion. I think its worth trying, but its going to feel different than steroids for sure.
 

Wishful

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Lastly, I am attempting whatever I can to replicate the undeniable anti-inflammatory effects of prednisone:
Prednisone gave me full temporary remission the first two times I tried it, then it stopped working. However, cumin (cuminum cyminum) worked just as well for a couple of weeks, then it too stopped having that effect. Later, cumin worked for me for blocking PEM. No one else has reported benefits from cumin, but it's cheap, safe, and easy to buy, if it's not already in your kitchen. Think of it as a lottery ticket: the chances of winning might be tiny, but imagine if you're one of those few lucky ones that wins... :thumbsup:

LDN worked great for me for blocking the neuropathic pains I got from ME, but did nothing for my other ME symptoms.
 
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In the meantime, I am chelating (Andy Cutler). I am trying to figure out ways to raise my rock-bottom cortisol in the morning (Genova 4 pt salivary test confirms this). I am ordering 100 mg pregenolone to trial it. DHEA is not allowed into the country here.
For information on raising cortisol and treating HPA axis dysfunction, I would suggest a book by a naturopath who is a leading proponent of using diet and supplements. Dr. James L Wilson is the author. It is called "Adrenal Fatigue, The 21st Century Stress Syndrome".
 

Wishful

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@Wishful - may I ask how much cumin do you find therapeutic? In ground form?
A level tsp seemed to be the optimum amount for me, at least as a PEM blocker. Three heaping tsps wasn't more effective (can't go over 100% blocking), and only lasted slightly longer. When I first tried it and got the remission, I think I used a tsp or so. If it does do anything for you, search for my thread about PEM blocker cumin. I don't understand why something that was so effective for me doesn't work for anyone else, so I keep hoping someone will benefit from it.
 

Heartl

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A level tsp seemed to be the optimum amount for me, at least as a PEM blocker. Three heaping tsps wasn't more effective (can't go over 100% blocking), and only lasted slightly longer. When I first tried it and got the remission, I think I used a tsp or so. If it does do anything for you, search for my thread about PEM blocker cumin. I don't understand why something that was so effective for me doesn't work for anyone else, so I keep hoping someone will benefit from it.
Thank you- I will experiment with this:)
 

EddieB

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HPA axis: the other piece of the puzzle for me. A second doctor suggested I try an SSRI (Lexapro).
  1. Last year, I attempted Lexapro but struggled so badly in terms of gut reactivity that I quit.
  2. I attempted it again this year and adjusted of my own accord to a low dose of 5mg.
  3. I've been taking it for one month now. It did nothing noticeable when taken during the day.
  4. Like I've noticed before, when taken at night prior to going to sleep, it made me a decisively very noticeable difference. I woke up far more 'responsive' the next day (e.g. early morning rise for work).
  5. This ties into what seems in my case to be an endemic deficiency in serotonin transportation.
Hello, can you tell me more about your initial startup of lexapro? At a gastrologist insistence, I tried it last week for my severe ibs. Three days of 2.5 mg I had to stop because the stomach pain was excruciating.
 
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Hello, can you tell me more about your initial startup of lexapro? At a gastrologist insistence, I tried it last week for my severe ibs. Three days of 2.5 mg I had to stop because the stomach pain was excruciating.
My starting dose was 10mg for a couple days during the day. When I realized that it was not "sitting well with me" and that it reminded me of a bad reaction to it at the same dose last year, I decided of my own accord to take it at night (before going to bed) and not during the day, where I also reduced the dose to 5mg.

This helped a lot. Over about two months now, I steadily raised to 15mg. In part because I was compelled to: I was asked to wean off prednisone and replace with HC (a bad decision by a doctor). I decided to raise my Lexapro dose hoping it would counter-act the unpleasant flare up of my pain / fatigue symptoms.

I am now steady on both prednisone and Lexapro.
 
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pattismith

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In the mornings, I suffered from dry eye, body-wide weakness, stiff muscles, and fatigue. Throughout the day, the hours upon hours of classroom energy sent me into a crash. As was also expected, I had more erratic bowel movements (IBS), dermatological flares (seborrheic dermatitis), and poorer blood circulation. I might also add recurring, aggressive episodes of torticolis, frozen shoulder, and joint displacements due to CCI and / or unspecified connective tissue disease.
My ME/CFS + fibro symptoms are quite similar to yours.

From the moment I was put on prednisone, most, or the totality of my symptoms were abated. I was re-reading French medical literature on treating ME/CFS and Fibromyalgia and noticed a section where they say that corticosteroids do nothing for fibromyalgia pain. It was striking to reconcile this with the diagnosis of ME/CFS and Fibromyalgia that a rheumatologist finally gave me one month ago, upon finding nothing on my scans or labs to indicate a specific autoimmune or rheumatic condition.
My fibro too was fixed by Prednisolone during that year. A significant portion of fibro patients have polyentesitis (about 30%), so I bet these ones respond well to corticosteroids or NSAI as well.

There is no inflammatory markers in the blood for Polyentesitis, because entheses are not much vascularised.
The best way to diagnose it is Ultrasound.

I have polyenthesitis and I also respond well to piroxicam 20 mg a day. Unfortunately my kidneys got injured by both corticosteroids and NSAI and I had to stop them all.

In attempting to treat myself, what did I learn so far?

On a urinary (catabolites) analysis, I learned a few things:
  1. Neurotransmitters: abnormal serotonin (below range) ; very low dopamine ; abnormal noradrenaline (below range) ; abnormal HVA and VMA (below range).
  2. Lymphocytes: normal CD4 count ; abnormal CD8 count (below range) ; abnormal IL2R (above range).
  3. Microbiome: rather healthy with exceptions -- abnormal indican (above range) -- a metabolite produced by tryptophan-dependent flora / bacteria.

On whole genome sequencing, I "might have two short-form 5-HTTLPR" (at gs290, in SLC6A4). This is a degenerate, repeat polymorphic region that plays into the way the body handles serotonin (apparently it is a sped-up, serotonin-transporting enzyme).
Do you mean you have an abnormal low blood CD8? I have that too. Still low for 3 years now.
I think the abnormal CD4/CD8 ratio (mine is 5) is responsible for some auto-immune predisposition, and possibly immune deficiency even though doctors consider it only if CD8 falls under 100..

I also have typical central dopamine circuit damages, with headache + restless legs + central pain.

Did you check your MBL genotype in your WGS?

In the meantime, I am chelating (Andy Cutler). I am trying to figure out ways to raise my rock-bottom cortisol in the morning (Genova 4 pt salivary test confirms this). I am ordering 100 mg pregenolone to trial it. DHEA is not allowed into the country here.

Thanks for reading this extremely long post. I have no idea what to expect because electing to trial medication on my own is a scary position to be in (amitriptyline ; LDN if I get it).
Thank you for sharing your journey with this disease. I hope you will get access to the meds you wish to get
 
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EddieB

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I am now steady on both prednisone and Lexapro.
Thanks for responding, glad this is helping you.

Curious, did you have gut issues prior to the lexapro, and are you taking PPI’s? Apparently PPI’s have an enzyme CYP450 that slows the break down of lexapro (Escitalopram) and doses should be reduced...
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4297217/

I’m seeing the gastrologist later today, I’ll have to decide whether or not to give lexapro another try. Since 2.5 mg caused problems, I may consider splitting to 1.25 mg to test.
 

EddieB

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I have ordered 10mg amitriptyline
I was on low dose amitriptlyne (10 mg) for several years. It didn’t do much, but I became dependent on it to sleep. Overall it made me more fatigued. Higher doses slowed digestion, couldn’t pee or poop. But maybe it will help you, there’s a lot of claims it does work.
 
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@pattismith Im sorry it took this long to respond. I wanted to try and be concise when I answered. I did look at MBL2 and I have two heterozygous SNPs there. Not for the well studied rs1800450.

On selfdecode.com they usually have mini “fixes” or things one can do to reduce or raise a given gene’s activity, but this gene was one of the ones that kind of didn’t lead anywhere specific (meaning I didn’t know what to make of this deleterious SNP). For some reason MBL does not show up. Still, based on my two SNPs, my mannose binding lectin may be reduced.

My low CD8 are 296 (minimum low range is 350). I guess I should be reassured based on the “below 100” comment.

Aside for the muscle pain, concentration issues, and fatigue (mostly in remission but not entirely), I noticed I do not tolerate high dose B1 (100mg thiamin). Not sure why as I thought this would do wonders for my peripheral neuropathy. I injured my knee in an accident years ago. Although I have no permanent issues, it seems that my foot sometimes gets numb in spots for days. I ought to remedy this with exercise. Instead I considered that vitamin because it gets recommended for neuropathy. I won’t take it again, as I feel it aggravated everything (the numb spot appeared after taking B1, plus return of cervical dystonia type pains, bit of exhaustion and fatigue).
 

pattismith

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@pattismith

My low CD8 are 296 (minimum low range is 350). I guess I should be reassured based on the “below 100” comment.
Thank you for answering.
Well CD8 = 296 is not high, mine is 200 (but I am older so the number fade with age). Where did you find that minimum low range at 350? The minimum normal is usually 150 to 200 depending on labs.
How much is your CD4/CD8?
Did you get tested for enthesopathy?
 
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pattismith

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@pattismith Im sorry it took this long to respond. I wanted to try and be concise when I answered. I did look at MBL2 and I have two heterozygous SNPs there. Not for the well studied rs1800450.

On selfdecode.com they usually have mini “fixes” or things one can do to reduce or raise a given gene’s activity, but this gene was one of the ones that kind of didn’t lead anywhere specific (meaning I didn’t know what to make of this deleterious SNP). For some reason MBL does not show up. Still, based on my two SNPs, my mannose binding lectin may be reduced.
I do have the homozygous variant at the major locus, so I am currently investigating my full MBL genotype and phenotype to see if it could explain some of my immunodeficiency symptoms.
Be careful with immunosuppressive drugs like corticosteroids, you may experience (like I did) some infectious recurrence on the long run.
 
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@pattismith I figured this might be easier. I have spent over a year trying to decipher this because the functional doctor here wasn't of much help in analyzing it. I deduced low CD25, CD57, and low CD8. I'm actively trying to tie it into it anything supplement-wise or diagnostic-wise that could give me a lead in healing:

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