Could there be an on/off switch for ME/CFS and if there is, what would that tell us??

[SNT Gatchaman]

Recording in this thread: I noticed a new blog on HealthRising which describes one of these switch offs - although in this case not totally instantaneous, occurring on a rebound from a (risky) immune modulator (a JAK1 inhibitor). The person had ME/CFS for 18 years, to severe levels, on a background of EDS. They appear to have a strong family history too.

After two months of complete misery without any sign of improvement, a CBC showed my white blood cell count had dropped to dangerously low levels, leading me to discontinue the medication. To my surprise, the follow-up cytokine panel showed that most of my elevated cytokines had returned to normal levels – the first time I had witnessed such a change in four years of tracking. Even so, I didn’t feel any better.

A few weeks after I stopped taking Rinvoq, once my body had time to recover from the side effects and my white blood cell levels returned to normal, I felt an undeniable shift, the crushing weight of ME was lifted. The switch that had been flipped in January 2006 that sent my body to the depths of hell was flipped back in March 2024. I was alive again; it felt like a miracle. The most debilitating of my symptoms – PEM/PENE, POTS/dysautonomia, profound weakness, and paralyzing exhaustion – disappeared.

For the first time in over 18 years, they were just gone, and eight months later they have not returned. Recent panels show my cytokine levels have continued to normalize many months after stopping Rinvoq, suggesting long-term benefits from the treatment. My body had a cytokine storm raging for years and a JAK1 inhibitor ended it when nothing else could. It fixed something. I am in remission. Rinvoq made my body work the way it worked before I got sick, which is to say I still have significant connective tissue disease symptoms (EDS) that I’ve had lifelong, but the ME is gone. This is important to differentiate because ME and CTDs are sometimes seen as one and the same.

 

[Michelle]

I have begun to wonder if there might be multiple switches that cause a similar response (i.e. ME/CFS). About a week after one of my last periods I felt that icky, flu-like feeling begin to lift about 9pm on a Friday. By Sunday I was out on my balcony repotting plants--something I'd struggled to do for years. Within a few months I went from being almost completely bedbound to days where I could do simple DIY projects around my apartment. I stopped crashing as severely as I used to. I can actually go for a doctor's appointment and not spend 3 weeks recovering. It's not been a complete remission but definitely a marked improvement.* However, since beginning Estradiol treatment for hot flashes/prevention of osteoporosis, my PEM is back. It's harder to move. I'm crashing more severely, etc.

I had a substitute caregiver several years ago who had near total remission in her mid 50s and I've long wondered about the role sex hormones may have played in that. But obviously, that would not be the switch in others (notably, men!). So, are there multiple switches causing ME/CFS?

*There may be more improvement to come. A chance hematology consult noted past low ferritin levels so had it checked again. It was 4ng/ml. Which might explain the crushing fatigue I've had that has lacked the flu-like quality I'm used to with ME/CFS. As we all like to say over and over again, ME/CFS is not just fatigue and I've just had first-hand experience of that.

 

[obeat]

@Michelle the onset of the menopause triggered a severe decline in my symptoms so I ended up having to use an electric wheelchair indoors. 8 years later I have finally noticed an improvement. HRT relieved hot flushes but did not change my MEsymptoms

 

[alex3619]

He thought it was related to blood collection and processing/freezing and wanted to retry with fresh samples.

This might fit the vesicle speculation. What happens to vesicles that are frozen like that? I don't know, but I think we need to know. It may be nothing, or it may be important.

 

[Michelle]

@Michelle the onset of the menopause triggered a severe decline in my symptoms so I ended up having to use an electric wheelchair indoors. 8 years later I have finally noticed an improvement. HRT relieved hot flushes but did not change my MEsymptoms

Yeah it's been a real mixed bag for me. I started having missed/late periods in 2019 and by Christmas was actually able to enjoy myself at my sister's. But my periods returned with train table regularity in 2020 and by August was getting sicker. Then the worst crash I've ever had happened in October: had to remain flatter than flat, struggled to get 250 calories a day down, couldn't speak much or tolerate the blinds open, biology of sleep at times just stopped, etc. But as my periods have declined, my PEM has lessened and I improved to better than before the crash--until starting Estradiol. In my case, there does seem to be a significant correlation between Estradiol levels and PEM. I have wondered if that horrible crash was due to a spike in Estradiol as levels will apparently spike and plummet wildly during perimenopause.

It's why I do wonder if there is no One True Trigger for ME/CFS but rather multiple triggers that are interacting with other individual feedback loops in pwME that all create a similar clinical picture. Could it be multiple little triggers in each person or, say, five main triggers in the population as a whole--sex hormones being one of them? Or maybe sex hormones are co-factors in one of the main triggers? Certainly a lot of women complain that their symptoms are worse during the luteal phase of their cycle. Then again, it's not like menopause is curing ME/CFS in most female patients. I dunno (insert should-shrugging emoji that I can't find here). Curious what @Jonathan Edwards might think.

 

[Peter T]

I suspect that any theory of ME will have to explain its variability and even the variability in its variability.

In the first decade of my ME there were times when the idea of an on/off switch seemed to relate the some of my experience of my ME. Even in the next decade the possibility of full recovery did not seem implausible as there were times when my brain functioning gave me a taste of what it had been pre-morbidly and times when it was possible to walk in the Himalayas or go swimming in Antarctica. I had the hope that if the right treatment was found it would still be possible to switch off this condition.

However the last decade of my ME has been more consistently severe and it feels that there has been deterioration in my brain function and in my physical condition, such that even if there was a treatment for ME, even allowing for aging, full recovery is no longer an option. Now it is a decade since I have been able to read a book from cover to cover or even visit the nearest seaside.