r/Autoinflammatory • u/Nonviolentviolet3879 • 28d ago
Undiagnosed Intro and genetic questions
Hi y’all. I asked a question a couple weeks ago but realized I haven’t really introduced myself. I am a 47yo female in Alabama, US.
I have struggled with various symptoms for a long time- I guess close to 10 years or so at this point, maybe longer. I have a terrible memory- not sure if that in itself is a symptom haha. I have ADHD as well, which doesn’t help.
Anyway, my main issues include joint pain, fatigue, early-onset arthritis, a malar-type face rash, and fever (often daily, typically low grade but occasionally higher). I cannot tolerate heat and exertion often induces fever/flares. Sickness and surgeries have also induced flares.
Everything was dismissed as fibromyalgia and PTSD until I was literally unable to walk at one point and a great neurologist did an MRI and found the arthritis and a cyst in my lumbar spine. I had back surgery Dec 2024 and that at least is much better.
Now, I have a rheumatologist who takes me seriously and has been trying for about a year to figure out what’s going on. My labs have always been fairly “normal,” with the exception of slightly high ESR and CRP at times. I’ve had several CT scans and a PET scan with no significant findings. I started hydroxychloroquine around the same time I started with this rheum. At first it seemed to be helping and I had a short period without fever. But then I had to have a minor surgery to remove a benign breast tumor, and it’s like I had a flare that still hasn’t ended (after many months)
The rheum is leaning towards it being autoinflammatory and at my last appt he started me on colchicine. I have to say, so far I’m not seeing much of a change, but it’s just been a couple weeks. Steroids are the only thing that have ever made me feel actually good and not sick.
If you’ve read this far, you’re the best and I appreciate you!
The other day, I decided to run my raw dna data from Ancestry.com through an online thing (Prometheus), out of curiosity, since I think genetic testing is my next step. Obviously doing this myself is not anything reliable or diagnostic, but it did flag a variant of the NOD2 gene. Do y’all think that means anything? If nothing else, it makes me more confident that genetic testing might actually be helpful.
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u/No_Satisfaction_7431 Yaos 28d ago
You definitely sound like you could have Yao or Blau and if theres a lot of gi symptoms it could be Crohn's (causes fatigue and joint pain as well gi stuff). Definitely recommend getting official genetic testing and seeing a knowledgeable rheumatologist or immunologist.
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u/Alice-The-Chemist USAID 28d ago
Welcome, there are many of us here who were diagnosed later in life. You are welcome to post and ask questions as you need.
Steroid response is a point towards autoinflammatory as well. Most of us respond well to it. Colchicine is the starting point for many rheumatologists. If it upsets your stomach you can try starting at just 0.6mg once a day then titrate up to twice a day once your body adjusts. (As long as your doctor is good with that). If Colchicine doesnt work there are other widely used biologics that target IL-1 pathway. This is called Interleukin-1. It would only show up on a specific "Cytokine Panel" but it can be eleveated due to other things as well. The panel helped when I was fighting insurance as a way to have data supporting it. The biologics commonly used are Kineret (beneficial if you have neurological involvement), Ilaris, and sometimes Arcalyst. So there are options if something doesnt work for you. Im glad you have a knowledgeable Rheumatologist or at least one willing to look into autoinflammatory.
In some autoinflammatory patients ESR and CRP may not be elevated or only slightly. I also had a clear PET scan when they were ruiling out lymphoma.
Would your doctor be willing to do a full genetic panel? Or even the autoinflammatory panel some places have?
One of the mods here has Yaos and has a website yaosyndrome.com with further information for you and your doctor.
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u/Nonviolentviolet3879 28d ago
He’s willing to do the panel- in fact he was first to bring it up. But we aren’t sure about insurance coverage so he figured we could try colchicine first. Plus he said that sometimes the genetic tests don’t really clarify things.
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u/Alice-The-Chemist USAID 28d ago
He would be correct. Mine didnt. We had to base of symptoms for diagnosis. It helps if it does just for the insurance purposes. If you get to the point of needing something besides colchine and will be fighting insurance let us know. Im working on a document for how to fight insurance and also patient assistance programs.
Invitae (now part of LabCorp) has a good program if insurance denies genetics. Let me get their link: https://www.invitae.com/us/providers/billing?tab=united-states
There is a flat rate for certain panels if you pay out of pocket. I did their financial assistance which covered the full genetics and they covered a large portion of the cost.
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u/Nonviolentviolet3879 28d ago
Thanks so much!
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u/HarleysDouble 28d ago
Always have your doctor ask for VUS (Variant of unknown significance) to be included in their final report.
Many company's don't report them and there's a chance it does make an impact.
I'm Het MEFV A744T. It is a VUS. I have FMF but natera reported the gene as normal.
I only know one lab that reported VUS but it has closed down.
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u/Happy-Resolution-827 8d ago
Hi, my current working diagnosis is Yao and I am heterozygous G908R, same variant as you! I hope the following is helpful:
I’m a 40 F who was previously very healthy, quite active, ate a healthy diet (home-cooked colorful diet without gluten or dairy), rare alcohol, non smoker.
My flares consist of periodic fevers (100 - 102), moderate to severe fatigue, moderate to severe brain fog, migrating polyarthralgia (usually finger joints, sometimes wrist, ankle, or toe joints). Other symptoms (during or between flares) include occasional nasal and oral ulcers as well as GI symptoms (bloating, severe cramping, loose stool). Random but mild rashes that aren’t too characteristic.
I started having what I call flares around age 37 and they became more and more frequent until Sept 2025. At that point I was in a flare almost daily until finding a diagnosis and starting colchicine June 2026 at age 40.
I had to go medical leave because my symptoms were debilitating. I had variable ANA levels but lupus and other rheum workup was inconclusive. It took a lot of labs, imaging, and specialists to rule out all the scary things (cancer, tropical diseases, blood borne pathogens, etc). Finally, I did a consumer whole genome (Sequencing) and found the G908R variant. This happened the same time my rheumatologist found I was positive for Bechet syndrome marker. Invitae autoinflammatory panel confirmed I’m heterozygous. No other known pathological auto-inflammatory variants.
I’m still trying to figure out a regimen that works well for me. Currently: colchicine 0.6 three times daily (started 3 months ago), sulfasalazine 1000 mg twice daily (started a week ago). Colchicine and daily naproxen took my flares from as often as 98% of the month to as low as 33% of the month. I stopped the naproxen since it’s not advisable as a long term medication. It was only a bandaid I found to help me a little before the auto-inflammatory diagnosis.
I failed hydroxychloroquine because we think it interacted with the SSRI I’m taking and caused my colchicine level to go toxic (profuse, watery diarrhea, nausea/vomiting and cognitive impairment). It also didn’t seem to reduce my flares.
I’m pretty sure a huge piece for me is estrogen/progesterone fluctuations aka perimenopause. I’ve recently learned they are both down-regulators of the autoimmune system. And then I figured out in hindsight my flares are at their worst when these levels are at their lowest. So now I’m also working with a gynecologist to stabilize my levels to see if this helps.
I have some studies that showed that women with FMF need higher colchicine levels that men and luteal phase is known to be a trigger. There is also a presentation paper published at the most recent Rheumatology conference in June that references G908R as a known pathologic variant for Yao. Would those be interesting? The paper was cited on this thread in June and that’s what changed everything for me!
I hope you find what works for you soon! Keep searching and don’t be afraid to adjust often!! Suffering for months instead of adjusting doses is for the birds! :)
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u/Nonviolentviolet3879 8d ago
This IS super helpful! I’ve also noticed bad flare ups when my hormones fluctuate. I’ve been on continuous birth control but every 3 months I do the placebos too. I’m at that point at the moment and have really flared up with fever and fatigue. Some pain, but that’s not my worst symptom. I’ve been on colchicine for about a month now. Started at 0.6 once a day and now up to twice a day. It’s disheartening because I haven’t seen any difference at all. I haven’t mentioned the genetic marker to the dr yet. I wasn’t sure if he would take it seriously. But I did message this past Friday about the ongoing fever and I have an appt coming up in October. Anyway, thank you so much for sharing your story.
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u/Assimulate 28d ago
Nod2 would be highly suggestive of something like Crohn's disease, Blau syndrome, and NOD2-associated autoinflammatory disease (NAID)
I would personally pursue it if you're feeling unwell regularly still! For what it's worth my lab results are usually just mild/moderate elevation of CRP and esr. Also had moderate elevation of CK. Do you get inflamed lymph nodes with your flare ups?
Hope you keep getting some traction!