Methotrexate

[kushami]

How foolish would it be to try methotrexate under my own steam?

I discussed it last year with my rheumatologist, and he said it would be appropriate for me to try but I am “not sick enough” to justify the risks.*

The thing is, I am sick enough. And on top of that my sole support person has had a major health setback, which may be permanent. This is what is precipitating my thoughts of going it alone.

I could order my own monitoring blood tests. I would be taking the dose and doing the same blood tests as I would if the rheumatologist was prescribing it.

* He did prescribe two lower-risk treatments, for which I am grateful. But so far they aren’t doing anything spectacular. Oddly, one got rid of wrist pain that I’ve had for 15 years, really the least of my problems. They can both be combined with methotrexate, so I wouldn’t have to stop them.

 

[manasi12]

Can you please share what other two low risk treatments helped you ? I have Sjogren's and rheumatologist wants to try methotrexate next.

 

[kushami]

I am taking hydroxychloroquine (Plaquenil), which is what resolved my wrist pain, and LDN, which I have only just started this week, so too early to say.

I have an unknown autoimmune disease, i.e. they know it’s autoimmune, but nobody has looked for the antibodies yet. I doubt anybody ever will, as only about 300 people have been diagnosed with it and it is not life threatening.

It causes vasoconstriction in the cerebral arterioles (the next branch down from arteries), so that means I have low blood flow to the brain. Main symptoms are fatigue, orthostatic intolerance, cognitive problems, exercise intolerance.

I wish you all the best with your treatment for Sjögren’s. (I suspect my mum had undiagnosed SS, so I have read a bit about it.)

Have you seen this lecture? (Click on “Learn more” and it will play, despite appearances.)

Can you please share what other two low risk treatments helped you ? I have Sjogren's and rheumatologist wants to try methotrexate next.

 

[kushami]

P.S. I am hoping that hydroxychloroquine (HCQ) will do something for my main condition, but I only managed to get in three months before having to stop it temporarily. It fixed the wrist pain in a matter of weeks during those three months. But you need to to persist for six months to get full effects, which is what I am doing now.

However, my living situation has become insecure, and I no longer feel comfortable trying it for six months in case it helps. Methotrexate also takes a while to work, but is stronger and more likely to work in my case than HCQ, But that comes with increased risks.

 

[hapl808]

I have an unknown autoimmune disease, i.e. they know it’s autoimmune, but nobody has looked for the antibodies yet. I doubt anybody ever will, as only about 300 people have been diagnosed with it and it is not life threatening.

That's interesting - how was it diagnosed as a specific thing?

 

[kushami]

That's interesting - how was it diagnosed as a specific thing?

The symptoms were described as a disorder in 2016, and the doctor who discovered the disorder believes it is autoimmune. He has treated some of his sicker patients with non-specific autoimmune treatments with good results.

There are quite a few well-known diseases that are suspected to be autoimmune, or at least to have autoimmune involvement, but for which the antibodies or specific mechanism are yet to be discovered. Plus there are some diseases for which some antibodies are known, but don’t tell the whole story. Scientists only know that patients tend to get better when given non-specific immune-modulating or immune-suppressing treatments, but they don’t know exactly what the drugs are doing to the immune system.

This is all the stuff I am learning, anyhow

 

[pattismith]

@kushami

what kind of testing allowed your doctor to make this diagnosis?

 

[kushami]

@kushami

what kind of testing allowed your doctor to make this diagnosis?

No confirmatory testing for me, unfortunately, only testing that ruled out other possibilities, plus a lot of differential diagnosis.

(I was on the verge of getting confirmatory testing, after a year of trying, but my incompetent specialist sabotaged it. I may try again in the future, but with my support person unwell, I don’t know how I would get there. Plus I was so fed up of waiting that, when the testing fell through, I took a course of steroids that I had in reserve knowing it would make me feel better but also interfere with testing for some months.)

But for anyone who lives in a country with an autonomic lab that has Doppler ultrasound equipment, that testing done in conjunction with a tilt table test will confirm OCHOS (my condition).

Description of OCHOS:
https://pubmed.ncbi.nlm.nih.gov/26909037/

(Note that, in this initial description Dr Novak doesn’t refer to autoimmune causes, but he does in later papers and conference lectured.)

Then, if the autonomic specialist considers you have autoimmune involvement, I imagine you would have tests to look for other common autoimmune diseases associated with orthostatic intolerance and autonomic dysfunction, e.g. Sjogren’s syndrome. Then, if none of those are found, it would be assumed you that you have whatever the as-yet-unidentified autoimmune thing is that causes some cases of OCHOS.

It must be an antibody or similar that interferes with cerebral blood flow. Dr Novak says he believes it acts on the cerebral arterioles, which are the next branch after the arteries. It causes abnormal vasoconstriction. He treats all patients with vasodilators, and some, the very sick ones, and perhaps those that have raised nonspecific AI markers, with nonspecific immune treatments.

Having other autoimmune diseases and a family history of autoimmune diseases would also factor in to treatment decisions. Plus if you’ve ever felt better while taking steroids, and, importantly, had a period of remission after stopping them.

I live in Australia so I have had to scrabble to approximate any/all of this. Most of my diagnosis happened by chance, plus my scouring medical journals and patient forums and watching lectures, plus kind researchers answering questions that I emailed them.

In the US, there would be a long wait to get into one of the autonomic centres, but, once you are a patient, it might all happen fairly quickly.

The other route to diagnosis would be to become very unwell with obvious and life-threatening autoimmune and autonomic symptoms. Then you would get to see the top specialists quickly and have lots of high-level autoimmune testing, such as samples being sent around the country in the US, or from Australia to the UK. And even if they couldn’t identify the exact autoimmune problem, you would probably be given higher-risk nonspecific or at least less-specific autoimmune treatments.

At least, that’s what I’ve gathered so far. I think there are a few people here who have (not voluntarily!) gone down the “become very unwell” path and know much more than I do.

 

[kushami]

Is nobody going to tell me that taking methotrexate without medical supervision is foolish

I am starting to reconsider it after reading about the possible GI side effects. I’ve just had bad GI reactions to three medications in a row. Ugh.

 

[pattismith]

Is nobody going to tell me that taking methotrexate without medical supervision is foolish

I am starting to reconsider it after reading about the possible GI side effects. I’ve just had bad GI reactions to three medications in a row. Ugh.

I tried it and couldn't tolerate it (depression, burning feet and hands).
Even a low dose and taking B9 and B12 didn't helped me to tolerate it.
My mother took it and couldn't tolerate it either.

 

[kushami]

Sorry to hear that, @pattismith .

Every time we try a medication, we have to wonder what the side effects will be – will they outweigh any positive effects, and will they go away again quickly if we stop the medication.

Then there’s the cost and the time to try each one, especially hard with those that take weeks or months to possibly show an effect.

A roll of the dice each time.

 

[cfs since 1998]

Fluge and Mella have said their patients reacted poorly to methotrexate.

 

[manasi12]

@kushami ..thank you for answering. I have tried plaquenil in 2017 and to my surprise, I realised that I was in so much pain before that. But I was so focused on my OI that didn't care about pain. I stopped it as I was scared for my vision as tlit is associated with retinal damage. I know that was foolish but didn't realise how much worse pain I had to endure after my TMJD and neck issues. Now it is hot mess with whole myofacial pain syndrome affecting my whole right side.

Now I just don't tolerate It at all since having COVID twice . I guess it exacerbated my pre existing long Qt syndrome. Couldn't even tolerate half tablet. It caused very scary palpitations n near syncope.

I have heard good reviews about methotrexate. Of course GI issues n hair fall may be the cons. Good luck to you for trying it.

 

[Zebra]

Is nobody going to tell me that taking methotrexate without medical supervision is foolish

Hi, Kushami!

Many, many years ago, I was prescribed Methotrexate for a presumed flare of an autoimmune disease.

I believe I took it once a week. What I found is that it made me quite ill the day *after* I took it. So, I learned to take it on Saturday and plan to stay in my PJs, in bed, all day Sunday.

I only took it for 8 to 10 weeks before my physician decided I should stop. Her rationale, at the time, was "it doesn't seem to be doing anything for you" which seemed hasty to me. Previously we had trialed meds for 3 to 6 months.

I don't think you are "crazy" to try it unsupervised if you regularly order your own CBC and CMP, as you said you will.

I would, however, caution against purchasing a large amount, just in case you can't tolerate it.

I hope this is somewhat helpful to you.

You are a gem to graciously respond to all the questions folks lobbed at you while patiently awaiting responses to the question you posted.

 

[kushami]

@Zebra , that’s a good point about not ordering too much.

I am not embarrassed to admit here that I stay in my PJs all day, every day. My daytime look is the addition of a cardigan, dressing gown and slippers. The Arthur Dent look.

I will prepare myself for a day in bed afterwards.

Everyone here is so kind, and I am happy to blab on about my diagnosis history in case it helps someone else.

I feel sure, judging by the research from Visser et al, that a decent subset of people with ME/CFS have abnormal vasoconstriction to the brain like me, even if I have it “solo” as opposed to part of a bigger picture.

If I win the lottery, I would love to donate a blood volume measurement machine and a transcranial Doppler set-up to a few major population centres around the world. Funnily enough, they are both reasonably priced and don’t cost much to run, apart from hiring the sonographer.

 

[kushami]

@manasi12 , I’m sorry to hear that you couldn’t restart Plaquenil. I don’t know whether I already said this, but I am trying to restart it too.

I did have a bit of GI upset the first time I started it, but I took a low dose and had it with porridge or mashed potato, and after a few weeks I was up to the full dose and feeling fine.

This time I had to put it aside after losing 5kg in a week. Eek. (I could actually do with losing 5kg, bit not through diarrhoea!)

I will try again in a week or two.

The possible eye damage is not to be taken lightly. I’m hoping a regular eye check will alert me in time if anything starts to go wrong. If it makes me feel great after six months, is that an acceptable pay-off for the risk of vision loss? I suppose I will review that at the six-month mark, if I can get back on it.

Lucky porridge is cheap

 

[manasi12]

Wish you the best for trying both drugs. I hope plaquenil is better this time. Losing 5 kg in a week is too bad.

Of course, take a few days gap between two . I guess GI upset will be common for both. I have been prescribed methotrexate weekly and folic acid by my rheumatologist. But due to oral infection, I'm not able to take it yet.

I'm also in the same subset regarding cerebral vasoconstriction. I thought about it few years ago as it gives distinct sensation of getting so congested in head. My POTS is hyperadrenergic type. I haven't tried vasodilator yet. Currently low dose atenolol and extremely low dose of fludrocortisone.

 

[kushami]

Also, in case anyone is about to ask – because this was my next question – can we measure or image this kind of cerebral vasoconstriction?

The answer seems to be no, at least not for regular medical imaging. Dr Novak has hypothesised that the vasoconstriction takes place in the cerebral arterioles. Arterioles are the next branch “down” after arteries, and are very small.

Arteries are 5–10mm in diameter, and can be imaged. Arterioles are 10–50 micrometers.

So it would be a two-step process of measuring a proxy for cerebral blood flow using transcranial or carotid Doppler ultrasound, and then seeing whether the patient feels any improvement on a vasodilator.

(There are scans that look at cerebral perfusion and oxygenation, but they can only be done lying down.)

* Remembering that in classical orthostatic intolerance, not enough blood makes it up to the head; but in abnormal cerebral vasoconstriction, plenty of blood is available to the head but not enough can get in. Different disease mechanisms, both resulting in cerebral hypoperfusion, but needing different treatment approaches. Although both are possibly caused by autoimmune stuff, so maybe ultimately both will be treated with autoimmune strategies.

 

[kushami]

Just for fun, here’s an article about arterioles:
https://my.clevelandclinic.org/health/body/23377-arterioles

I had never heard of the term until Dr Novak mentioned it, and yet they are the heavy lifters in regulating our blood supply.