Anidulafungin (IV antifungal)

[Robert 1973]

Also, for what it is worth...I am not a doctor, but when I read Graham's account, I see a complex situation with a lot of different pathologies, medications and medication changes. It does not read to me like an account that suggests clear improvement in ME/CFS that can only be attributed to an antifungal.

I’m definitely not suggesting it that it’s the only explanation. I’m just speculating about whether it is a possible explanation that warrants further consideration or investigation.

 

[Yann04]

If someone with ME/CFS had a co-morbid immune deficiency which led to a more widespread fungal infection, would there be any reason for anyone treating them to link it to their ME/CFS? My guess is not as it would be perfectly normal to see a fungal infection in someone with immune deficiency, and most physicians aren’t interested in ME/CFS.

Even if a physician they did suspect a link, is it likely that they would publish it? Again, I suspect not.

Perhaps it would be different if it was a previously unidentified fungus but that’s not necessarily what I’m suggesting.

One thing that I’m not clear about is whether the type of overgrowth/infection that I’m hypothesising (whether commensal or otherwise) would be picked up on a scan or any other type of investigation that someone with ME/CFS might have for any reason.

My intuition is that if anti-fungal medication substantially improved a decent proportion of cases with ME we‘d probably know it? In the sense these aren’t particularly uncommon drugs and there has been „hype cycles“ in some ME-adjacent circles along the lines of „It‘s actually caused by candida, let‘s take antifungals“. I think there‘s an entire published book by a „doctor„ in french saying candida causes ME/CFS and going over all the diets and supplements needed to combat it.

 

[Evergreen]

I’m definitely not suggesting it that it’s the only explanation. I’m just speculating about whether it is a possible explanation that warrants further consideration or investigation.

I get that. To me, it doesn't seem probable.

Why link the antifungal directly to ME/CFS when there was long-term steroid use which would raise risk of fungal (and other) infections, which would potentially respond to an antifungal?

Some people have reported remission after other infections - why not link the improvement to covid, or indeed, sepsis?

Fluge & Mella had 7 cases in their own ward. From the 2019 phase III paper:

In our cancer ward, we have seen 7 patients since 2004 with long-standing ME/CFS who developed malignant disease (Hodgkin lymphoma, diffuse large B-cell lymphoma, or breast cancer). They independently reported alleviation of their ME/CFS symptoms
after chemotherapy with cyclophosphamide or ifosfamide, which are cytotoxic drugs, or after receiving the combination of chemotherapy and rituximab, an anti-CD20 monoclonal antibody.

I think we'd have some case studies.

 

[Jonathan Edwards]

If someone with ME/CFS had a co-morbid immune deficiency which led to a more widespread fungal infection, would there be any reason for anyone treating them to link it to their ME/CFS?

Fungal infections in the immunodeficient tend to be life threatening and either progress to fatality or are successfully eradicated. I don't see the relevance to ME/CFS really.

 

[Utsikt]

Nail fungus is often treated with terbinafine for up to a year. It accumulates in nail, hair, etc. so perhaps it won’t have much of a systemic effect?

I’m sure we would have known if it works for ME/CFS by now.

 

[Robert 1973]

My intuition is that if anti-fungal medication substantially improved a decent proportion of cases with ME we‘d probably know it?

There are anecdotal reports of improvement following courses of oral antifungals but as far as I’m aware there have never been any controlled trials.

I suspect very few people with ME/CFS have been given IV anidulafungin.

Why link the antifungal directly to ME/CFS when there was long-term steroid use which would raise risk of fungal (and other) infections, which would potentially respond to an antifungal?

Graham had been taking steroids for a prolonged period, since before sepsis. He was admitted to hospital for IV antibiotics with sepsis on multiple occasions over a many months.

He was only given IV anidulafungin once, after he contracted Covid-19 in hospital. Covid and anidulafungin are are the only known variables which correlate with his reported improvement in his ME/CFS symptoms. The data suggests that Covid-19 is highly unlikely to have led to an improvement in his ME/CFS symptoms.

[Edit: I originally wrote “CFS symptoms” for some unknown reason!]

Fluge & Mella had 7 cases in their own ward. From the 2019 phase III paper:

I think we are extremely fortunate that it was Fluge and Mella to whom this was reported. My guess is that most physicians wouldn’t have taken it any further.

 

[Robert 1973]

Fungal infections in the immunodeficient tend to be life threatening and either progress to fatality or are successfully eradicated. I don't see the relevance to ME/CFS really.

I get that. I was responding to:

If fungi were responsible they would have shown themselves in at one of tens of thousands of people with ME/CFS who has had medical attention. Just now and again at least they would have got out of hand enough to show.

I interpreted your comment to mean that it would have got out of hand in people with ME/CFS who are have a co-morbid condition which causes immunodeficiency.

Did you mean that you would expect a local fungal infection to get out of hand in some people who are not immunodeficient? I don’t know how that would present or whether it is a safe assumption but I would defer to your knowledge. That’s why I’m asking.

 

[Jonathan Edwards]

Did you mean that you would expect a local fungal infection to get out of hand in some people who are not immunodeficient?

Yes, or at least be overt enough to be readily identified.

 

[Evergreen]

Graham had been taking steroids for a prolonged period, since before sepsis. He was admitted to hospital for IV antibiotics with sepsis on multiple occasions over a many months.

He was only given IV anidulafungin once, after he contracted Covid-19 in hospital. Covid and anidulafungin are are the only known variables which correlate with his reported improvement in his ME/CFS symptoms.

My point was a different one, that long-term steroids can cause fungal infections. Those fungal infections could contribute to how bad someone feels, and they could be treated by antifungals, leading to the person feeling better. So even if the antifungal were directly involved in the feeling better, it could be by treating a chronic fungal infection that has gone untreated rather than treating ME/CFS.

I think we are extremely fortunate that it was Fluge and Mella to whom this was reported. My guess is that most physicians wouldn’t have taken it any further.

I agree, but fungal infections are so common that there would be other physicians like them to whom similar improvements after antifungals would be reported.

 

[Robert 1973]

My point was a different one, that long-term steroids can cause fungal infections. Those fungal infections could contribute to how bad someone feels, and they could be treated by antifungals, leading to the person feeling better. So even if the antifungal were directly involved in the feeling better, it could be by treating a chronic fungal infection that has gone untreated rather than treating ME/CFS.

Graham’s ME/CFS symptoms that improved following anidulafungin (including PEM) were symptoms he had had since the onset of his ME/CFS, before he started taking steroids. As far as I’m aware he didn’t notice any deterioration in symptoms after he started taking steroids – only some symptomatic relief.

However, I had a very marked deterioration in my ME/CFS symptoms – particularly the discomfort in my face and down the side of my head – after I was prescribed a high dose of steroids. The discomfort in my face improved significantly following a course of oral antifungals, which appeared to cause the discharge of an unidentified black stringy substance from my sinuses followed by weeks of bright yellow mucus. The improvement was limited but sustained.

If the improvement in Graham’s ME/CFS symptoms was due to the effect of anidulafungin treating an undiagnosed fungal infection in his sinuses, that would mean that such infections could be a cause of ME/CFS symptoms in some people, or at least an aggravating factor. That is what I have been hypothesising. It would be huge if there was anything more than anecdotal evidence to support that hypothesis, but as far as I understand there isn’t – and I acknowledge what Jonathan says above.

 

[Evergreen]

such infections could be a cause of ME/CFS symptoms in some people, or at least an aggravating factor

I don't see it that way. Chronic infections cause chronic symptoms that would overlap with ME/CFS symptoms. Think of "sickness behaviour". So I wouldn't say that a fungal infection causes ME/CFS, but it can certainly cause some of the symptoms that a person with ME/CFS has, because someone with ME/CFS has other things too.

An aggravating factor, yes, absolutely.

The symptoms wouldn't have to be new, just worse. Personally, I find that I often miss when something is causing pre-existing symptoms to get worse, because I'm used to them waxing and waning.

Anyway, I'll bow out because I think these points are not the crucial ones (Jonathan's) and probably not relevant to Graham's particular case.

 

[bobbler]

Not really. If fungi were responsible they would have shown themselves in at one of tens of thousands of people with ME/CFS who has had medical attention. Just now and again at least they would have got out of hand enough to show.

I actually think you can discount this.

But what medic is either picking these up (I didn’t get taken seriously for anything for decades and who knows if it was the people I saw and/or labels in notes which of course were written by same type of people)

And if they do then what person has told them they have me/cfs (getting anything else diagnosed is almost mutually exclusive to the person you are seeing knowing you have me/cfs)

And the records regarding me/cfs are terrible and designed so nothing is put together like that - it’s ’cfs’ with no designation normally if there, hidden, people are lucky if the diagnosis appears anywhere and isn’t the neuresthenia version and it’s set up to be assumed in all cases that it goes away, even if people had been going back regularly over those years to a GP specifically regarding that illness.

 

[bobbler]

My intuition is that if anti-fungal medication substantially improved a decent proportion of cases with ME we‘d probably know it? In the sense these aren’t particularly uncommon drugs and there has been „hype cycles“ in some ME-adjacent circles along the lines of „It‘s actually caused by candida, let‘s take antifungals“. I think there‘s an entire published book by a „doctor„ in french saying candida causes ME/CFS and going over all the diets and supplements needed to combat it.

Taking enough of it is more uncommon. For a bad stubborn infection it’s more like a level of tablets for six months to get anywhere just on the infection itself , not something easy to get hold of or try without tests to show something very wrong vs one dose might be over the counter or a doctor visit just noting symptoms for something else bht mightnt get anywhere to a ‘feeling cured’ level if it were something more significant going on (which is why packets say if 1-2 don’t work then you have to see a dr)?

 

[Robert 1973]

I think we are extremely fortunate that it was Fluge and Mella to whom this was reported. My guess is that most physicians wouldn’t have taken it any further.

Not really. If fungi were responsible they would have shown themselves in at one of tens of thousands of people with ME/CFS who has had medical attention. Just now and again at least they would have got out of hand enough to show.

I’ve been thinking more about this. Is it not likely that among all the ME/CFS patients in the world, a significant number will have been given daratumumab for other reasons (eg myeloma)? If it was found to be an effective treatment for some people with ME/CFS, could it not therefore be inferred that some people with ME/CFS will have either recovered or experienced a significant improvement in ME/CFS symptoms due to taking daratumumab?

And yet, as far as I’m aware, there is nothing in the scientific literature about such effects.

That could be because daratumumab isn’t an effective treatment for ME/CFS. But presumably Fluge and Mella (and others studying B cell depletion therapies for ME/CFS) have inferred that it is likely that if cases exist, they would not have been brought to the attention of scientists studying ME/CFS.

With that in mind, I’m wondering whether any ME/CFS researchers would know about it if there were a small number of cases where a local fungal infection in the sinuses which had been causing ME/CFS symptoms had got out of control. My guess is possibly not.

I’m also mindful of my episode of unexplained extremely high CRP in 2019. I tried to persuade various people to publish it as a case study but nobody showed any interest, despite the fact that it was the highest level of CRP that any of the doctors in the hospital had seen, and my symptoms didn’t fit with any known causes of extreme CRP.

It seems quite plausible to me that there may be other people with severe ME/CFS who have had similar episodes of unexplained extremely high CRP with associated symptoms that no ME/CFS researchers know about.

 

[Robert 1973]

I’m also mindful of my episode of unexplained extremely high CRP in 2019. I tried to persuade various people to publish it as a case study but nobody showed any interest, despite the fact that it was the highest level of CRP that any of the doctors in the hospital had seen, and my symptoms didn’t fit with any known causes of extreme CRP.

Today I entered my medical history and all the data from my admission to hospital in 2019 into Claude AI today.

I asked it to speculate about the cause and whether or not it could have been connected to my ME/CFS. Within a couple of seconds it suggested an autoinflammatory disorder as a possible cause – which took the hospital 4 weeks to consider. That remains a possibility but genetic analysis did not reveal any matches with rare variants which are currently known to cause autoinflammatory disorders, and my symptoms were highly unusual so the possibility still exists that it was connected to my ME/CFS in some way.

Interestingly, without me suggesting it, the AI suggested that if there was a connection to my ME/CFS it could represent (among several other suggestions) “A glimpse of the underlying ME/CFS pathology made visible — the possibility that what normally produces fatigue, post-exertional malaise and cognitive dysfunction at subclinical inflammatory levels occasionally, in some patients, tips into something measurably dramatic.”

It also said: “The most useful thing may be to ensure this case is known to ME/CFS researchers — particularly those working on immune dysregulation, neuroinflammation, and muscle pathophysiology. It’s an unusually well-documented case of what appears to be a dramatic acute escalation of ME/CFS-related biology, with serial bloods, hospitalisation records, and a thoughtful patient who has tracked the details carefully.”

Yes, I know AI flatters everyone but I thought it was interesting given the conversation we’ve had in this thread. Could this have been an example of some part of the mechanism of ME/CFS getting out of control before returning to a stable but still dysfunctional state?

I am in the process of correcting all the mistakes in the AI summary. When that is complete I would like to share it on the forum for others to consider. @Hutan Please can you or any other moderators advise me whether that would be within forum rules and if so whether I should start it as a new thread?

 

[Trish]

I am in the process of correcting all the mistakes in the AI summary. When that is complete I would like to share it on the forum for others to consider. @Hutan Please can you or any other moderators advise me whether that would be within forum rules and if so whether I should start it as a new thread?

Mods will discuss this and contact you.