A Spanish teen’s genome may hold the secret to lupus
freethink.com
freethink.com
She was on that drug for 10-odd years before going to a different hospital on a whim. The new doctor concluded that actually the Lupus wasn't even active. It was in remission and had been for years. Turns out, the previous doctor was skipping some routine tests because the results were always the same.
Mom got off the drug and her mind got better but her body didn't. Off the drug, she was basically in the same physical state as she was on the drug. Couldn't walk or even sit down for more than a couple hours without pain. So what's going on? She started getting her bones checked to see if there was some kind of alignment problem. There was some old film of her as a toddler that showed her walking funny, and she also once had a bad accident doing sports, which seemed like potential evidence for something skeletal.
Before she could figure anything else out, she found a lump and got diagnosed with cancer. It originally looked like regular breast cancer but the breast cancer chemo didn't work. Turns out it's this super-rare "meta-plastic" cancer that nobody at the hospital had ever seen before. She just went through palliative care and hospice then died only a year after finding the tumor.
Turns out there were some studies saying the drug she was on for longer than necessary is correlated with rare cancers. Unfortunately I don't have the name of the drug or the details of the cancer on hand right now. Anyway, it's cool to see some research that might eventually help Lupus patients avoid getting yelled at for popping pills (even when not actually popping pills).
What worked for us was finding a primary care doctor who was recommended by others, even if the wait for a new patient appointment was measured in months or years. From there, the PCP was used as a pivot point to get to specialists who knew what they were doing and as a contact point for basic medication management. Letting PCPs try to manage complex conditions is a mistake, IMO.
I should mention that this failure mode isn't unique to American medicine. The same dynamic plays out in many countries and indeed in many industries beyond medicine. Getting into the experts who know what they're doing is hard because they're in the highest demand. Getting into below-average providers of any profession is always easy because they're not buried under referrals and people knocking on their door.
What tests to get. What sort of doctors to see. What works and doesn’t work. Tips dealing with doctors.
There are even a few chronic conditions that attract a lot of incorrect self-diagnosed people who insist they have the condition despite every test suggesting they don’t. For example, many people self-diagnose as having various thyroid disorders based on vague symptoms (or WebMD, etc) but won’t let go of the diagnosis when all of their thyroid tests come back perfectly normal. This leads to weird social media bubbles where people insist the tests are wrong and start sourcing their own medications, with predictably bad results.
Low testosterone is the current big trap for men. You can find social media groups that claim that testosterone is basically a cure-all and that the current reference ranges are far too low. Again, they’re usually quite confused when they finally get a testosterone prescription and it doesn’t fix all of their problems like the Facebook groups or TikToks led them to believe.
Be careful out there.
My advice is read all you can to thoroughly understand what’s happening to you - The Lupus Book by Dr. Wallace, The Lupus Encyclopedia by Dr. Thomas are two great compendiums and candidates for Kindle. Then find support resources that look at the condition as something that can be and should be managed, eschewing the mesmerizing appeal of self-pity and one-upsmanship with symptoms.
The fact is that managing lupus puts a higher priority than normies have on diet, fitness, sleep, mental and physical stress management, and UV exposure. Ordering your own blood work - understanding the tests that are valuable and how to diagnose results is also a good practice for taking charge of your condition - i.e. what are the early warning signs that my kidneys may be “silently” failing; what are my baseline CBC numbers, specifically white blood cells, and can I provide those to a GP/PCP on the fly; etc.
Social media, I found, doesn’t really advance what is mostly a solo journey to preserve function through daily mental and physical discipline. However, another thing I’ve come to appreciate is that most (healthy) people don’t enjoy listening to stories about medical problems, and if you just need to tell your story and get some brief positivity and empathy, online groups can fill that need.
Many conditions can take dozens of doctor visits and years to get a correct diagnosis. Many doctors are not up to date or even aware of common conditions.
People that have a chronic condition are continuously called hypochondriacs. There are a lot of people that basically tell them to shut up and just pretend everything is okay
I also found that doctors are just awful, they don't have enough time to hear about 10+ symptoms that may be common with complex autoimmune or neurological issues. I never received proper referral. I have been to Mayo clinic, which was close to proper diagnosis but decided against blaming the drug.
As far as reddit and facebook being a huge source of misinformation, I have to disagree. Some groups are awful. However, the SFN subreddit has great document written by a frustrated physician. Many autoimmune groups link to research papers and non-profit organizations which provide databases of doctors interested in treating particular issues.
One just needs to understand that some commenters are just average people who may or may not be well informed on the subject. However, the wikis and documents on those support groups are generally fantastic.
Yes, many people on these subreddits are hypochondriacs, by definition, but you can find them coalescing there, buying placebos, going to chiropractors, functional medicine doctors, naturopaths and reading sketchy journals because they've been told they're fine by doctors. However, it's blatantly obvious they are not fine, because if they were fine, they wouldn't be experiencing those symptoms. They may not be ill in the way they think they are, but they are not well.
Doctors are too ready to write off patients as worried well, but sometimes it turns out those symptoms are due to a real physical issue, and it can take years of fighting the system to find a solution. We're increasingly seeing that autoimmune, neurological, gastrointestinal, hormonal and other types of issues can cause issues across the whole body as well as directly triggering psychological disorders. Often these disorders are not even known to GPs who haven't kept up to date since leaving medical school. A patient with no history of mental health issues presents with sudden health anxiety and panic disorder out of nowhere, is it a primary mental health disorder or is there another underlying issue (psychological or physical) that's brought it on? You can't know unless you take their complaint seriously and properly investigate, but doctors are under time pressure and keen to just write it off as anxiety disorder and stick the patient on the antidepressant treadmill.
Other times, it is purely psychological or somatic, but so what? Mind and body health are intimately tied together. When one starts to deteriorate, the other often follows. Take some Zoloft and go for a walk may be a quick and convenient answer, it may even work a lot of the time, but evidently there are many, many people who find it unhelpful. Rather than looking at alternatives, some doctors will just try and say the same things over and over until the patient gives up.
Then we wonder why people give up on modern, science-based healthcare and get roped into less scientific disciplines. Modern medicine is one of the greatest achievements of human civilization, but many doctors seem to have forgotten that you're treating the patient, not the disease.
I know it sounds like a massive conflict of interest to have one's physician working for one's insurance company, but, somehow, it really seems to work and work well, bypassing those failure modes you mentioned entirely. I've gotten in to see specialists within a matter of a couple of weeks whenever I've needed it.
Kaiser exists to maximize healthcare for reasonable costs across a wide range of people, and they do so by keeping general health high, but at the expense of specialty. In a city like SF, that means Kaiser will send you to UCSF for a transplant and pay a significant fraction. In Solano and Yolo/Sacramento there are far fewer specialists and even then I'd expect you to be referred to UCSF (when I worked there, there were constantly people visiting from all over the state for transplants).
That said, my experience and my family's is from Kaiser Permanente Southern California (San Diego).
(...)
The Doctor
She is a primary care doctor. Every day, patients come to her and says “My back hurts” or “My stomach feels weird”. She inspects, palpates, percusses and auscultates various body parts, does some tests, and says “It’s nothing, take two aspirin and call me in a week if it doesn’t improve”. It always improves; no one ever calls her.
Eventually, she gets sloppy. She inspects but does not palpate. She does not do the tests. She just says “It’s nothing, it’ll get better on its own”. And she is always right.
She will do this for her entire career. If she is very lucky, nothing bad will happen. More likely, two or three of her patients will have cancer or something else terrible, and she will miss it. But those people will die, and everyone else will remember that she was such a nice doctor, such a caring doctor. Always so reassuring, never poked and prodded them with needles like everyone else.
Her heuristic is right 99.9% of the time, but she provides literally no value. There is no point to her existence. She could be profitably replaced with a rock saying “IT’S NOTHING, TAKE TWO ASPIRIN AND WAIT FOR IT TO GO AWAY”.
(...)
https://astralcodexten.substack.com/p/heuristics-that-almost...
https://www.hopkinslupus.org/lupus-tests/lupus-blood-tests/
"In fact, only 2% of people with lupus will have a negative ANA. People with lupus who have a negative ANA test may have anti-Ro/SSA or antiphospholipid antibodies."
The current protocol is that if your ANA is negative they will not look any further. See figure 2: https://ard.bmj.com/content/78/9/1151
My sister is experiencing these symptoms too and puts it on MS, but doctor can't confirm and in the meantime basically medical system is zero help. Canada is a bad place to be debilitatingly ill but not visibly bleeding out.
It could be that, on average, doctors become accustomed to the idea that when a man visits them it must be very serious, and therefore when they are visited by women they generally display milder or less obvious signs and symptoms by comparison (again, on average). Hence, doctors may get the impression that women are more hypochondriac than men when the fact of the matter is actually the inverse.
I have lupus. I am on disability for it mostly because of the neuropsychiatric issues. It took 35 years for them to diagnose me and it was the doctors who figured it out, it was because of my own investigations. When I look at these drugs I asked them "can I do the same with diet and environmental changes", they said no. I proved them wrong. I still have flare ups and they are sometimes unpredictable. Just three days ago I had a psychotic episode from COVID, and stress can set me off as well, but the constant pain is not there and my WBC is up and my panels are usually negative.
The biggest problem my mother and I had was that we had neuropsychiatric lupus which meant they they only saw the mental illness and refused to look at other issues. I had constant low WBC, hyperkalemia, leukopenia, discoid lupus, and arthritis but all they ever saw was the metal illness.
So I mostly proved them wrong. For most people with Lupus, it can be overcome with diet and environmental changes.
So, back to the article. I hate articles like this. Lupus is a highly polygenic disease. I have my genetics, I have some SNPs in TLR7 gene at ~10% for europeans. But I feel my Lupus is mostly caused by several purine nucleoside phosphorylase (PNP) SNPs.
https://pubmed.ncbi.nlm.nih.gov/28859258/
But it does not end there, I see STAT4, IL10RB, TNFAIP3 and mutations that probably play a role.
But how is it my diet can negate all these SNPs? Why do some people with these SNPs not get Lupus.
For me, this is where diet and my FADS1 and FAD2 genes play a role. Ever since I started eating only fish and shellfish, and zero plant oils but for some olive oil I have been way more stable than any drug they gave me.
https://www.lupus.org/news/study-shows-omega3-fatty-acid-sup...
I thought being vegan would help when I was younger but it made me worse.
So while that kid is interesting it makes it seem like there is nothing the rest of us can do who do not have these rare point mutations. TLR7 mutations do not cause every case of Lupus.
It is frustrating to watch as those affected have to fight every day just to get the energy to live their lives, constantly changing diets and routines just to try to make sense of what triggers flare-ups in their condition.
https://en.wikipedia.org/wiki/Periodic_fever,_aphthous_stoma...
From my own research and observations I'm quite confident it is, as you elude to, an auto-immune related disease. The two major triggers for me are exercise; particularly anaerobic e.g weightlifting, and alcohol. Alcohol actually alleviates the symptoms for a day or more and then undoubtedly i'll struggle for a few days after that. Which points to alcohol's suppressive effects on the immune system.
I really really hope this, and similar research[1], turns into something tangible
[1] https://med.stanford.edu/news/all-news/2019/04/biomarker-for...
For me, the trigger is carbohydrates. Doesn't make having a good social life easy. I'm on a forced ketogenic diet because of it.
I quickly became manic when I only eat red meat.
How confident are you that this is the case? This is now the second story I've read of someone on a keto/carnivore diet having to get a triple bypass after eating too much red meat. Was his omega-3/omega-6 ratio really that much worse than that of the average person not on such a diet (not that that's a great standard to compare against, but the average person is also not getting triple bypass surgery)?
I know there's a lot of evidence against the notion that saturated fats cause CVD, and omega-6s and inflammation is a compelling case, but I'm worried we're missing something.
Intermittent fast and eat very low carb – no stomach problems. Eat too many carbs more than ~25-35 – stomach problems.
It's not one super rare disease, but a combination of lupus + something else
The condition is also one for which there is no test; it's one that is diagnosed via exclusion.
"Bioinformatics analysis revealed a de novo, TLR7 p.Tyr264His (Y264H) missense variant that was predicted to be damaging by SIFT and CADD (Fig. 1a–c (family A) and Supplementary Table 2). This variant was not present in the databases of normal human genome variation (gnomAD, ExAC, dbSNP). Examination of the BAM files together with paternity analysis confirmed that the mutation occurred de novo (Extended Data Fig. 1a, b, d)."
I read that and thought that was pretty neat. CADD is Combined Annotation Dependent Depletion, and is "a widely used measure of variant deleteriousness that can effectively prioritize causal variants in genetic analyses." SIFT stands for Sorting Intolerant From Tolerant, and is "an algorithm that predicts the potential impact of amino acid substitutions on protein function."
When we cleaned up our diets and got chemical based products out of our house, we switched to Hemp based cleaning and body products, her Lupus and RA symptoms went away and never returned.
Common Nightshades are:
Potatoes Tomatoes Eggplant Peppers (including bell, cayenne pepper, and paprika). Gojo berries are also Nightshades, they are not a 'superfood'.
The list is far longer than just those common ones.
We are what we absorb from all sources.
In this case, a better title would have been "a teen's genome may hold ...".
They are the ones that uses that teen’s genome, so every press release must mention “the Spanish teen”. It’s branding.
Some genetic disorders are predominantly found in certain populations. Cystic Fibrosis is predominantly Caucasian. Sickle Cell is predominantly (or perhaps exclusively) African (ancestry). Etc.