This reminds me of my struggles for patients with Chronic Fatigue Syndrome, Gulf War Syndrome, “Chronic Lyme Disease” and Delusional Parasitosis
The CFS patient I had was in the early 90’s, the daughter of a patient I was trying to treat for recurrent CDI. She’d moved back in with her parents after losing her jog to fatigue and lassitude.…
This reminds me of my struggles for patients with Chronic Fatigue Syndrome, Gulf War Syndrome, “Chronic Lyme Disease” and Delusional Parasitosis
The CFS patient I had was in the early 90’s, the daughter of a patient I was trying to treat for recurrent CDI. She’d moved back in with her parents after losing her jog to fatigue and lassitude. I did everything I could, sent off every test, obtained the fever logs but, in the end all I could was sympathize. Eventually I suggested a Psychiatrist to help her deal with tghe disease. She went on to start a Group and write a newsletter. I don’t know what happened to her. At the time I was told it was psychosomatic.
The GWS was a guy who was having unremitting anxiety after serving on the ground in Desert Storm. He also had fatigue, memory loss, inability to concentrate, arthralgia and sleep disturbance. He’d been to the VA. Where they blew him off. I sent all the testing his symptoms and exam (negative) led me to, including a brain MRI which was challenged by the Chief of Imaging. After coming back with negative results all I could do was empathize. Eventually I suggested a Psychiatrist. He denounced me in the most forceful of ways and I never saw him again.
The Chronic Lyme Disease patient was my associates but I was asked to render a second opinion. His chronic fatigue, inability to focus and diffuse joint aches were diagnosed by a positive urine test from a lab I’d never heard of using an assay I’d never heard of. He’s been hustled by a physician to whom he was paying cash for 4 grams of Ceftriaxone, had experienced upper extremity DVT from the innumerable PICCs, and was now demanding we cover all that care. Hs symptoms were no better after almost two years of this nonsense and I told him my colleague’s assessment was accurate and we were no longer going to administer the treatments he’d been described. I suggested he see a Psychiatrist. he denounced me in the most forceful of ways. However, a year later he wrote a letter to my colleague informing him he realized our assessments of his Lyme disease were correct.
The DP patient was convinced worms were emerging from his umbilicus and showed me the lint he’d collected in sample jar as proof. He told me one was emerging at that moment. I’ll never forget he, I and my assistant standing and staring, transfixed at his posed navel and expecting…what? A Xenomorph? I told him he didn’t have parasites, he denounced me…you know the story
This is the other side of the many many complaints about "gaslighting" from autoimmune, ME/CFS & Long covid patients, usually women.
Have no Dx, send to psych seems to be a response of first ("get this crazy woman out of my hair") or last ("no idea what she has, maybe psych can help") resort.
My husband has a chronic debilitating condition: myalgia, POTS, dysautonomia. His rheumatologist (now dead) years ago told him., "Mr Z, no matter how I try I can't believe you're crazy."
Z used to chat up the women in the waiting area for his long-standing PT practice in Berkeley. His comment that applied to nearly all of them, "Just because they are crazy doesn't mean they aren't sick."
I'd add to that that many chronic conditions produce perfectly understandable depression & anxiety. I've met many such women myself and they do read crazy. While that doesn't mean they aren't physically sick, too, I can understand the impulse to just not deal with them.
It's sad that you DID try everything, including listening, and that wasn't appreciated. I've found in my 80 years that you can tactfully disagree and not burn a bridge.
Just out of curiosity, what was the extent of "every test" for the first two? Part of the reason for asking is that one aspect of diagnosis that I feel is under-appreciated is that it's a variation of the "halting problem":
I don't have a dog in the hunt for any of those things you listed, but there are studies coming out re: measurable biological abnormalities for ME-CFS-related cases and then there's the Gulf War problems with measurable brain changes reflected, say, in the relevant episode of Dr. Sander's Netflix "Diagnosis" show. Psychology alone - especially if not itself accompanied by a measurable biological abnormality - has proven to be a risky branch to rely on. (Say vs. h. pylori in ulcers or it's replication crisis as a field).
Now you are putting me through my paces it was so long ago. If memory serves “every test” was directed at autoimmune disorders such as what was available at the time: CBC, ANA, RF, wESR, SPIEP plus LFTs, CPK, Aldolase , HLA B27. Sometimes CT scan of chest and abdomen. Mostly a fishing expedition because, like “Long COVID” now, the symptoms were non specific and the physical findings absent.
Regarding CFS and Gulf War Syndrome of course I’m now aware that a lot of blood has passed under those bridges and treatments are available to, at least, try. For CFS back then Imipramine or Desipramine were suggested, SSRIs were too new. I think I tried Elavil on one patient with horrible side effects. Soon after the ID docs decided CFS was not an Infectious Disease and the referrals stopped.
I was not satisfied with any of these cases and Rheumatology took over.
As far as the halting syndrome that is incomprehensible to me
First, thanks for sharing! Part of the challenge in discussing these things is that just like there’s wide variations in doctor skills - like anything else - there are widely varying views re how much testing is enough vs too much.
The halting problem is easiest to describe in computers. If a computer ends up being asked to solve an unsolvable equation, it freezes up. To avoid that, you can limit how deep into the solving process the computer will run. This prevents freezing but there will be some number of solvable problems that won’t be solved because the number of steps (or time) to solve it exceeds the cut-off.
In theory, it’d be ideal to figure out ahead of time which problems can’t be solved vs. those that can. Or those that can be diagnosed vs. those that can’t. But it turns out it’s impossible to really do that.
So there are big trade-offs involved in limiting vs. going on. If someone’s body seems to be kicking their butt, that trade-off looks very different for them than it would sitting on the other side of a desk.
Take VEXAS syndrome. It has to have been around far longer than its recent discovery. But how many sufferers must have been put on the back-burner or disbelieved before a biological cause was found? I’d submit that the objective evidence of high diagnostic error rates like 25% in repeated contexts (autopsies, etc.) is enough to warrant great caution in latching on to conclusions that effectively foreclose finding a potentially mundane or treatable non-psych cause.
With dependable commercial WGS running for as little as a couple hundred bucks, there’s really no reason not to find a way to use it to flush (and flesh) out a hard to diagnose person’s genetic playing field. Don’t use it for initial clinical reliance but rather as a tool for generating testable clinical hypothesis. Even if self-ordered commercially. It’s actually not hard to push things like CADD scores (rough predicted pathogenicity) and alt allele frequencies to every single variant in a person’s most likely relevant genes to then ID a relatively small set of potential problem areas.
This. My husband has an undiagnosable chronic condition, likely autoimmune adjacent, judging by his family history (mother with MS) & DNA tests. But he's negative on all labs, despite debilitating symptoms.
When these cases were referred to me they were problems which hadn’t been solved. Each patient, again, if memory serves, was frustrated and pessimistic but given high expectations by the referring physicians that their problem would be solved.
VEXAS reminds me of when I began my private practice at the very beginning of the HIV Pandemic - back when it the acronym was GRIDS, so I had to be good at relating to patients for whom there was little, if anything to be done. I could write a Substack about what that was like but to your point the measure of a good physician may be how they are able to deal with what can’t be solved. Put another way, solving the solvable is easy.
I can only imagine what that was like at the time. It's hard enough to see so much suffering today and it was so concentrated and intense in the US. Plus the toll in Africa itself - even with PEPFAR.
I'm with you on "solving the solvable is easy" but would add one word: "solving the easily solvable ..."
The difference is slight but important.
As I like to put it, "there must be a reason why hard cases are hard." Some may be unsolvable and undetectable -- even with modern technology. But as the tools available have grown in extent, power and economic availability, it's demonstrable that the scope of the unsolvable has shrunken considerably.
As patients it's important to realize that having a hard case is going to be different than walking in with a running nose. It's a marathon rather than a sprint. And a key thing to be on the lookout for is objectively observable abnormalities - like blood tests - that can potentially bridge to and even explain the subjectively experienced problems.
But doctors almost universally could -- and really need to -- recognize the same thing: there's a reason hard cases are hard. And just on odds alone, having a rare disease or atypical presentation should usually be at or near the top of heap. So there's always good reason to keep an eye open for the possibility of a measurable problem as well as a diagnosable or treatable cause.
One reason I keep coming back to the rare disease example is because it's so well-studied as an area but also counter-intuitive. Yes, individually, each disease has to have 200,000 or less in the US, and for many it may be as few as 10-20.
But with an est. of, what, 7,000 to 10,000 of them, they collectively involve tens of millions of Americans. Look for horses first, but the equine world isn't exactly lacking for zebras. Especially in Africa.
It's unreasonable to expect any doctor to just light on the right one, especially on a single visit to an over-worked PCP. But there's plenty of room to more methodically approach each problem. And for both patients and doctors to strive for a better -- or even real -- partnership to try and advance the ball. Even when some hard challenges exist on both sides.
Even if it takes a year or three (or more) to do it right, that's a huge improvement on what's often decades with multiple rounds of diagnostic error and harmful treatments for those with problems. Especially when there's diagnostic disagreement between doctors, which I've never seen or heard of being handled well but have seen leaving too many patients left holding the bag. And then resented for it.
Lifestyle is important too, but it's often treated as an exclusive reason when it shouldn't be. As I tell some of the people I chat with, doing heroin isn't going to help move the diagnostic ball forward. (A little dark humor helps to get through...)
But the flip side parallels a line I heard from a hematologist: for polycythemia vera patients, they can try to eat their way out of their functional iron deficiency, but as long as the flip is switched on to always making too much blood, they can't do it. And so they'll suffer as long as it is untreated. Or until they go on Jakafi. (grin)
If a problem is recognized as life-threatening or devastating enough, the medical system often performs some amazing miracles (esp. with the best doctors). But it just as often struggles with the progressive medical problems -- whatever the reason for them existing in the first place -- until a person has lost key abilities to help themselves.
Ironically, I suspect part of the "problem" is that we've gotten so good at keeping people alive who had episodes earlier in life in which they would have died in decades or centuries past. I have personal reasons to appreciate that! But we should also probably be less surprised that many of those same people have unusual health problems later. (I get that the treating doctors are almost always different...)
A parting thought is that I'm not sure that it's appreciated just how wide the range of doctoring skills is out there. Just as with lawyers, a shocking number really suck. And even in specialty areas, the difference (persisting over decades) between say the best-performing and the average-performing cystic fibrosis center is shockingly large.
Plus, we're all human. Even the very best will make mistakes. The best way to minimize those risks is to be aware of them and to maintain epistemic humility even in the face of a patient whose every visit might be dreaded or a source of annoyance. Unfortunately, scars can run deep on both sides of the relationship.
The one sure way to make sure a problem is both unsolvable and untreatable is for both the patient and treating doctors to give up. But even if only one side or the other does, the result almost surely will the same. I just think there's both hope and good reason to think we can all do better. (grin)
"Ironically, I suspect part of the "problem" is that we've gotten so good at keeping people alive who had episodes earlier in life in which they would have died in decades or centuries past. I have personal reasons to appreciate that! But we should also probably be less surprised that many of those same people have unusual health problems later. (I get that the treating doctors are almost always different...)"
Indeed, antibiotics & vaccines have produced big evolutionary changes in the human genome in a remarkably short period of time, mostly because survivors now reproduce who never would have in the pre-antibiotic era.
This reminds me of my struggles for patients with Chronic Fatigue Syndrome, Gulf War Syndrome, “Chronic Lyme Disease” and Delusional Parasitosis
The CFS patient I had was in the early 90’s, the daughter of a patient I was trying to treat for recurrent CDI. She’d moved back in with her parents after losing her jog to fatigue and lassitude. I did everything I could, sent off every test, obtained the fever logs but, in the end all I could was sympathize. Eventually I suggested a Psychiatrist to help her deal with tghe disease. She went on to start a Group and write a newsletter. I don’t know what happened to her. At the time I was told it was psychosomatic.
The GWS was a guy who was having unremitting anxiety after serving on the ground in Desert Storm. He also had fatigue, memory loss, inability to concentrate, arthralgia and sleep disturbance. He’d been to the VA. Where they blew him off. I sent all the testing his symptoms and exam (negative) led me to, including a brain MRI which was challenged by the Chief of Imaging. After coming back with negative results all I could do was empathize. Eventually I suggested a Psychiatrist. He denounced me in the most forceful of ways and I never saw him again.
The Chronic Lyme Disease patient was my associates but I was asked to render a second opinion. His chronic fatigue, inability to focus and diffuse joint aches were diagnosed by a positive urine test from a lab I’d never heard of using an assay I’d never heard of. He’s been hustled by a physician to whom he was paying cash for 4 grams of Ceftriaxone, had experienced upper extremity DVT from the innumerable PICCs, and was now demanding we cover all that care. Hs symptoms were no better after almost two years of this nonsense and I told him my colleague’s assessment was accurate and we were no longer going to administer the treatments he’d been described. I suggested he see a Psychiatrist. he denounced me in the most forceful of ways. However, a year later he wrote a letter to my colleague informing him he realized our assessments of his Lyme disease were correct.
The DP patient was convinced worms were emerging from his umbilicus and showed me the lint he’d collected in sample jar as proof. He told me one was emerging at that moment. I’ll never forget he, I and my assistant standing and staring, transfixed at his posed navel and expecting…what? A Xenomorph? I told him he didn’t have parasites, he denounced me…you know the story
This is the other side of the many many complaints about "gaslighting" from autoimmune, ME/CFS & Long covid patients, usually women.
Have no Dx, send to psych seems to be a response of first ("get this crazy woman out of my hair") or last ("no idea what she has, maybe psych can help") resort.
My husband has a chronic debilitating condition: myalgia, POTS, dysautonomia. His rheumatologist (now dead) years ago told him., "Mr Z, no matter how I try I can't believe you're crazy."
Z used to chat up the women in the waiting area for his long-standing PT practice in Berkeley. His comment that applied to nearly all of them, "Just because they are crazy doesn't mean they aren't sick."
I'd add to that that many chronic conditions produce perfectly understandable depression & anxiety. I've met many such women myself and they do read crazy. While that doesn't mean they aren't physically sick, too, I can understand the impulse to just not deal with them.
Being sick changes everything about a person’s life. Stating the obvious, humans are very complex organisms and sick people are even more complex.
I tried to see it that way.
It's sad that you DID try everything, including listening, and that wasn't appreciated. I've found in my 80 years that you can tactfully disagree and not burn a bridge.
Just out of curiosity, what was the extent of "every test" for the first two? Part of the reason for asking is that one aspect of diagnosis that I feel is under-appreciated is that it's a variation of the "halting problem":
https://en.wikipedia.org/wiki/Halting_problem
I don't have a dog in the hunt for any of those things you listed, but there are studies coming out re: measurable biological abnormalities for ME-CFS-related cases and then there's the Gulf War problems with measurable brain changes reflected, say, in the relevant episode of Dr. Sander's Netflix "Diagnosis" show. Psychology alone - especially if not itself accompanied by a measurable biological abnormality - has proven to be a risky branch to rely on. (Say vs. h. pylori in ulcers or it's replication crisis as a field).
Now you are putting me through my paces it was so long ago. If memory serves “every test” was directed at autoimmune disorders such as what was available at the time: CBC, ANA, RF, wESR, SPIEP plus LFTs, CPK, Aldolase , HLA B27. Sometimes CT scan of chest and abdomen. Mostly a fishing expedition because, like “Long COVID” now, the symptoms were non specific and the physical findings absent.
Regarding CFS and Gulf War Syndrome of course I’m now aware that a lot of blood has passed under those bridges and treatments are available to, at least, try. For CFS back then Imipramine or Desipramine were suggested, SSRIs were too new. I think I tried Elavil on one patient with horrible side effects. Soon after the ID docs decided CFS was not an Infectious Disease and the referrals stopped.
I was not satisfied with any of these cases and Rheumatology took over.
As far as the halting syndrome that is incomprehensible to me
First, thanks for sharing! Part of the challenge in discussing these things is that just like there’s wide variations in doctor skills - like anything else - there are widely varying views re how much testing is enough vs too much.
The halting problem is easiest to describe in computers. If a computer ends up being asked to solve an unsolvable equation, it freezes up. To avoid that, you can limit how deep into the solving process the computer will run. This prevents freezing but there will be some number of solvable problems that won’t be solved because the number of steps (or time) to solve it exceeds the cut-off.
In theory, it’d be ideal to figure out ahead of time which problems can’t be solved vs. those that can. Or those that can be diagnosed vs. those that can’t. But it turns out it’s impossible to really do that.
So there are big trade-offs involved in limiting vs. going on. If someone’s body seems to be kicking their butt, that trade-off looks very different for them than it would sitting on the other side of a desk.
Take VEXAS syndrome. It has to have been around far longer than its recent discovery. But how many sufferers must have been put on the back-burner or disbelieved before a biological cause was found? I’d submit that the objective evidence of high diagnostic error rates like 25% in repeated contexts (autopsies, etc.) is enough to warrant great caution in latching on to conclusions that effectively foreclose finding a potentially mundane or treatable non-psych cause.
With dependable commercial WGS running for as little as a couple hundred bucks, there’s really no reason not to find a way to use it to flush (and flesh) out a hard to diagnose person’s genetic playing field. Don’t use it for initial clinical reliance but rather as a tool for generating testable clinical hypothesis. Even if self-ordered commercially. It’s actually not hard to push things like CADD scores (rough predicted pathogenicity) and alt allele frequencies to every single variant in a person’s most likely relevant genes to then ID a relatively small set of potential problem areas.
Hope that makes some sense.
This. My husband has an undiagnosable chronic condition, likely autoimmune adjacent, judging by his family history (mother with MS) & DNA tests. But he's negative on all labs, despite debilitating symptoms.
When these cases were referred to me they were problems which hadn’t been solved. Each patient, again, if memory serves, was frustrated and pessimistic but given high expectations by the referring physicians that their problem would be solved.
VEXAS reminds me of when I began my private practice at the very beginning of the HIV Pandemic - back when it the acronym was GRIDS, so I had to be good at relating to patients for whom there was little, if anything to be done. I could write a Substack about what that was like but to your point the measure of a good physician may be how they are able to deal with what can’t be solved. Put another way, solving the solvable is easy.
I can only imagine what that was like at the time. It's hard enough to see so much suffering today and it was so concentrated and intense in the US. Plus the toll in Africa itself - even with PEPFAR.
I'm with you on "solving the solvable is easy" but would add one word: "solving the easily solvable ..."
The difference is slight but important.
As I like to put it, "there must be a reason why hard cases are hard." Some may be unsolvable and undetectable -- even with modern technology. But as the tools available have grown in extent, power and economic availability, it's demonstrable that the scope of the unsolvable has shrunken considerably.
As patients it's important to realize that having a hard case is going to be different than walking in with a running nose. It's a marathon rather than a sprint. And a key thing to be on the lookout for is objectively observable abnormalities - like blood tests - that can potentially bridge to and even explain the subjectively experienced problems.
But doctors almost universally could -- and really need to -- recognize the same thing: there's a reason hard cases are hard. And just on odds alone, having a rare disease or atypical presentation should usually be at or near the top of heap. So there's always good reason to keep an eye open for the possibility of a measurable problem as well as a diagnosable or treatable cause.
One reason I keep coming back to the rare disease example is because it's so well-studied as an area but also counter-intuitive. Yes, individually, each disease has to have 200,000 or less in the US, and for many it may be as few as 10-20.
But with an est. of, what, 7,000 to 10,000 of them, they collectively involve tens of millions of Americans. Look for horses first, but the equine world isn't exactly lacking for zebras. Especially in Africa.
It's unreasonable to expect any doctor to just light on the right one, especially on a single visit to an over-worked PCP. But there's plenty of room to more methodically approach each problem. And for both patients and doctors to strive for a better -- or even real -- partnership to try and advance the ball. Even when some hard challenges exist on both sides.
Even if it takes a year or three (or more) to do it right, that's a huge improvement on what's often decades with multiple rounds of diagnostic error and harmful treatments for those with problems. Especially when there's diagnostic disagreement between doctors, which I've never seen or heard of being handled well but have seen leaving too many patients left holding the bag. And then resented for it.
Lifestyle is important too, but it's often treated as an exclusive reason when it shouldn't be. As I tell some of the people I chat with, doing heroin isn't going to help move the diagnostic ball forward. (A little dark humor helps to get through...)
But the flip side parallels a line I heard from a hematologist: for polycythemia vera patients, they can try to eat their way out of their functional iron deficiency, but as long as the flip is switched on to always making too much blood, they can't do it. And so they'll suffer as long as it is untreated. Or until they go on Jakafi. (grin)
If a problem is recognized as life-threatening or devastating enough, the medical system often performs some amazing miracles (esp. with the best doctors). But it just as often struggles with the progressive medical problems -- whatever the reason for them existing in the first place -- until a person has lost key abilities to help themselves.
Ironically, I suspect part of the "problem" is that we've gotten so good at keeping people alive who had episodes earlier in life in which they would have died in decades or centuries past. I have personal reasons to appreciate that! But we should also probably be less surprised that many of those same people have unusual health problems later. (I get that the treating doctors are almost always different...)
A parting thought is that I'm not sure that it's appreciated just how wide the range of doctoring skills is out there. Just as with lawyers, a shocking number really suck. And even in specialty areas, the difference (persisting over decades) between say the best-performing and the average-performing cystic fibrosis center is shockingly large.
Plus, we're all human. Even the very best will make mistakes. The best way to minimize those risks is to be aware of them and to maintain epistemic humility even in the face of a patient whose every visit might be dreaded or a source of annoyance. Unfortunately, scars can run deep on both sides of the relationship.
The one sure way to make sure a problem is both unsolvable and untreatable is for both the patient and treating doctors to give up. But even if only one side or the other does, the result almost surely will the same. I just think there's both hope and good reason to think we can all do better. (grin)
"Ironically, I suspect part of the "problem" is that we've gotten so good at keeping people alive who had episodes earlier in life in which they would have died in decades or centuries past. I have personal reasons to appreciate that! But we should also probably be less surprised that many of those same people have unusual health problems later. (I get that the treating doctors are almost always different...)"
Indeed, antibiotics & vaccines have produced big evolutionary changes in the human genome in a remarkably short period of time, mostly because survivors now reproduce who never would have in the pre-antibiotic era.