5 ms·

$100K 30 doctor visits, no answers, sounds like my experience with Ehlers Danlos Syndrome (hEDS), perhaps I missed it but did not see what the final diagnosis w

$100K 30 doctor visits, no answers, sounds like my experience with Ehlers Danlos Syndrome (hEDS), perhaps I missed it but did not see what the final diagnosis was. Autoimmune could be a lot of things. If I feed in my symptoms today into AI, the same list I gave to doctors, I do get hEDS and specifically I get TNXB as a candidate gene. I don't include my WGS DNA data which came after I stoped bothering with doctors. AFAIK only specialists will diagnose hEDS and AFAIK absolutely none would predict TNXB. They call it clEDS instead and consider it 1 in a million, only if you have a specific TNXB SNP and it’s homozygous. Where I think most of hEDS is caused by presumed benign TNXB SNPs. Even the studies that specifically search for DNA candidates for hEDS skip over TNXB due to the belief that hEDS is rare and TNXB SNPs are common. So I don’t know where AI it’s getting its info from but the TNXB theory is mostly a patient led theory held by some of us who have it. There are some fringe giftedness researchers who focus on the RCCX gene cluster - which incidentally cause a ton of autoimmune conditions. So it’s definitely a situation where I think the answers from AI are far better than from doctors - I would have found out decades sooner. hEDS is such a perfect match for my symptoms that it becomes obviously true once I researched it so even if the AI guessed wrong it wouldn’t be worse than all of the doctors who guessed wrong. One even told me I should have thyroid surgery, thankfully I had already lost faith in them by that stage.

itchyouch 2y ago
Whenever I come across folk with hEDS-like symptoms, I always like to bring up fluoroquinolone (FQ) antibiotics, as a "btw do you know about this?" I have a suspicion that some non-trivial amount of the non-genetic EDS folks may suffer from fluoroquinolone antibiotic toxicity. Among the many effects of FQs is how it can cause a net-loss of collagen in the body. It increases MMPs that breakdown collagen in the body. Part of the reason FQ antibiotics have a black box warning for tendon tearing. I have a family member that was sure they had hEDS, but it turned out to be FQ toxicity. 20-30 courses over years that would degrade their health, one small bit at a time, unbeknownst to them. While safe for many, for some amount of the population, it can cause what feels like every bodily system slowly failing. The frustrating bit of it all is how resilient the body is, and most common blood work shows up "normal."
- monkburger 2y ago
  FQ toxicity is likey caused by SNP in a specific gene related to pharmaceutical metabolism (one of the CYP450s). I believe this was published in the literature. Another possibility is that FQ toxicity is caused by certain genes relating to detoxifying (GSH, COMT, etc) - where the body incorrectly metabolises it, leading to toxicity against cells.
  - itchyouch 2y ago
    That's great to know. It's unfortunate that there's an insanely high number of folks in the population that are taking FQs and running into toxicity without any hope of figuring out what is going on with their bodies. It seems that it would behoove folks to be able to take the test and know whether they are safe candidates to take FQ antibiotics.
monkburger 2y ago
Similarly rare is the "traditional" EDS phenotype with stretchy skin and hypermobile joints. Usually seeing them for shoulder dislocations or other orthopedic injuries. By far the most common (and massively increased over the past few years) is the crowd that attracts all the eye rolls. These are almost exclusively women, usually white, age 16-35, presenting with a constellation of nonspecific chronic complaints including myalgias/arthralgias, fatigue, GI symptoms, etc. None of them have stretchy skin or abnormally hypermobile joints. Very high rate of fibromyalgia/POTS/CFS in this group. They're usually coming to the ED for diffuse pains, dizziness, or something else I really can't fix. Maybe there is some underlying organic disorder we haven't sorted out yet, maybe these are somatic manifestations of untreated anxiety/depression. One thing about the hEDS diagnosis is the explosion of self-dx from social media (TikTok) which makes physicians cringe. There's no good genetic test, and even if there was there is not much to be done other than supportive measures.
- cjbgkagh 2y ago
  I believe that you're a doctor because your response is exactly typical for a doctor. Have you considered for a second that all these people are right and that you might be wrong? I am similarly self diagnosed. 30 years of not being able to get a diagnosis despite having hypermobility so severe I can subluxate either shoulder on demand, I also had all of those other issues you mention - it's a cluster for a reason. Hear me out, what if hEDS was 1/50 and not 1/50K or 1/15K or 1/5K or 1/500 or whatever the current literature has it at - which as a data science person is some rather large order of magnitude error bars for a figure. The 1/50 would include those diagnosed with generalized joint hypermobility, this would allow for the more common TNXB SNPs to be causal for hEDS. And yeah, I've been told by many doctors that it's not worth even testing for because there is no treatment. Also consider the second order effects of not testing - how would you validate the original % numbers if people keep being talked out of getting tested, would subsequent surveys of population include those being talked out of the test? It's a good thing I don't rely on people who can't detect a condition to treat the condition. It is indeed very treatable - the dysautonomia aspect especially so.
  - LeafItAlone 2y ago

itchyouch 2y ago

Whenever I come across folk with hEDS-like symptoms, I always like to bring up fluoroquinolone (FQ) antibiotics, as a "btw do you know about this?" I have a suspicion that some non-trivial amount of the non-genetic EDS folks may suffer from fluoroquinolone antibiotic toxicity. Among the many effects of FQs is how it can cause a net-loss of collagen in the body. It increases MMPs that breakdown collagen in the body. Part of the reason FQ antibiotics have a black box warning for tendon tearing. I have a family member that was sure they had hEDS, but it turned out to be FQ toxicity. 20-30 courses over years that would degrade their health, one small bit at a time, unbeknownst to them. While safe for many, for some amount of the population, it can cause what feels like every bodily system slowly failing. The frustrating bit of it all is how resilient the body is, and most common blood work shows up "normal."

monkburger 2y ago
FQ toxicity is likey caused by SNP in a specific gene related to pharmaceutical metabolism (one of the CYP450s). I believe this was published in the literature. Another possibility is that FQ toxicity is caused by certain genes relating to detoxifying (GSH, COMT, etc) - where the body incorrectly metabolises it, leading to toxicity against cells.
- itchyouch 2y ago
  That's great to know. It's unfortunate that there's an insanely high number of folks in the population that are taking FQs and running into toxicity without any hope of figuring out what is going on with their bodies. It seems that it would behoove folks to be able to take the test and know whether they are safe candidates to take FQ antibiotics.

monkburger 2y ago

Similarly rare is the "traditional" EDS phenotype with stretchy skin and hypermobile joints. Usually seeing them for shoulder dislocations or other orthopedic injuries. By far the most common (and massively increased over the past few years) is the crowd that attracts all the eye rolls. These are almost exclusively women, usually white, age 16-35, presenting with a constellation of nonspecific chronic complaints including myalgias/arthralgias, fatigue, GI symptoms, etc. None of them have stretchy skin or abnormally hypermobile joints. Very high rate of fibromyalgia/POTS/CFS in this group. They're usually coming to the ED for diffuse pains, dizziness, or something else I really can't fix. Maybe there is some underlying organic disorder we haven't sorted out yet, maybe these are somatic manifestations of untreated anxiety/depression. One thing about the hEDS diagnosis is the explosion of self-dx from social media (TikTok) which makes physicians cringe. There's no good genetic test, and even if there was there is not much to be done other than supportive measures.

cjbgkagh 2y ago
I believe that you're a doctor because your response is exactly typical for a doctor. Have you considered for a second that all these people are right and that you might be wrong? I am similarly self diagnosed. 30 years of not being able to get a diagnosis despite having hypermobility so severe I can subluxate either shoulder on demand, I also had all of those other issues you mention - it's a cluster for a reason. Hear me out, what if hEDS was 1/50 and not 1/50K or 1/15K or 1/5K or 1/500 or whatever the current literature has it at - which as a data science person is some rather large order of magnitude error bars for a figure. The 1/50 would include those diagnosed with generalized joint hypermobility, this would allow for the more common TNXB SNPs to be causal for hEDS. And yeah, I've been told by many doctors that it's not worth even testing for because there is no treatment. Also consider the second order effects of not testing - how would you validate the original % numbers if people keep being talked out of getting tested, would subsequent surveys of population include those being talked out of the test? It's a good thing I don't rely on people who can't detect a condition to treat the condition. It is indeed very treatable - the dysautonomia aspect especially so.
- LeafItAlone 2y ago