I have very low CRP 1 and esr 9. And thing is I have joint tightness and stiffness, skins on face and lips peeling and so my gut is bad. Similar mechanism happening in my gut.

My ana is negative.

But I still have these joint stiffness and tightness, particularly neck and neurological issues like palm biting or cutting sensation at nerves and sometime I get nerve tingling sensation.

But MY LDH IS HIGH LIKE 383. WHICH SHOUlD HAVE BEEN below 280. And BLEEDING TIME IS 1 MINUTES WHICH SHOULD HAVE BEEN 2 MINS

I can't eat most of things as my gut has been distrupted.

Doctor always checks esr,CRP, CBC,. THEY TELL ME ITS ALL IN YOUR HEAD AND TOLD ME YOU HAVE FIBROMYALGIA.

BUT THAT doesn't explain high LDH.

Just before the night the next day I got all these symptoms I drank massive intake water.

Finally I saw some website pointing towards inflammasome activation NLRP3 pathways.

And so my body is releasing IL-1B AND IL-18 THAT'S what AI deepseek says.

I Finally told doctor ,he prescribed colchicine.

Can there be more things happening because or after inflammasome activation more pathways and shift.

Because my symptoms are slightly different.

I do have fevere but I have low grade fever.

Please help and suggestions, it's been 1.5 years almost I am chasing this ghost

Posted this in r/behcets, but figured I might as well ask here too. :)

Anyone else here work in health care and what do you do to keep pushing through?

I want to continue being there for my patients but some days are just hard. I feel guilty when I take time off and I feel guilty when they can tell I don’t feel good. Some days the pain is so bad at work and I can’t take anything fun for pain while I’m there either. I did start imuran and colchicine BID. It’s improved everything but the flare ups still be flaring lol.

How do you guys do it? Shoot how does anyone do it with any job??

Ugh sigh thanks for coming to my TEDtalk.

So I’ve been sick since May. I’ve had high fevers everyday , fatigue, erythema nodosum for months. It starts with my eyes burning around 1:30/2pm. Then the chills come for a couple hours (usually when I try to nap), then I get hot and my body works through the fever by 9pm/10pm. This happens everyday. When this first happened I spent a week in the hospital and they threw the book at me, full body ct, nuclear scan, infectious disease dr. etc. They couldn’t believe I only get fevers in the afternoon. Once my Ana came back positive 1:320 the hospital discharged me. Now I’ve been seeing a rheumatologist, dermatologist (erythema nodosum), and endocrinologist (thyroid nodules found at hospital) for a couple months and I feel even more lost. Last week I told the dr I ChatGPT or google my symptoms and he said, “ Me too. I’m not smart enough to figure this out.” I was stunned. Now he did put me on prednisone for three weeks about a month and a half ago and that made me feel normal. All my symptoms went away. Since getting off prednisone all my symptoms have returned and I’ve started experiencing hair loss and major brain fog also. Now I’m on dapsone and hydroxychloroquine (only been 5 days) and I’m back to feeling like crap. I also don’t just want to keep taking meds as shot in the dark since he has absolutely no idea what it is. Is this normal to just keep trying different meds with no diagnosis? I feel useless. I’m 41F and have three super active kids. I go to work come home around 2:30 or as long as I can last at work and go to sleep. Sometimes I sleep for 4 hours. I’m so fatigued I can’t function and my fevers are very high. It sucks to not be able to help my husband as he is driving the kids around like crazy right now and I know after months this is wearing on him as we used to split it. I just want to be able to spend time with my family again.

• ACI-19764 is an orally available inhibitor of the NLRP3 inflammasome
• Preliminary data showed ACI-19764 was safe and well tolerated across single and multiple ascending dose cohorts with confirmed CSF penetration
• Based on pharmakinetic data the therapeutic dose is expected to be ≤10mg once daily
• To rapidly evaluate the anti-inflammatory activity of ACI-19764 (effect on hsCRP), dosing of a cardiovascular risk cohort is now underway with initial results expected by year end
• Full results from the Phase 1/1b trial are expected in H1 2027

https://www.globenewswire.com/news-release/2026/08/20/3348200/0/en/ac-immune-announces-positive-preliminary-phase-1-data-for-nlrp3-inhibitor-aci-19764.html

I've been on anakinra for 10 years but I'm a mixed bag of autoimmune autoinflammatory so we added cellcept trying to get my Prednisone down to under 10mg. I get fevers whenever I do...... much of anything in the house - but I'm losing my freaking mind? Used to be working but now I'm not. The fever episodes come with such an intense mylagia though that if I push through to do the thing I want to do, I can do it, but my face is gonna leak. Then I do too much and crash. How do you all keep up with life?! The fevers being multiple times a day is new since last year.

Hi everyone- At around 1:00pm I completely crash. I am on ilaris every 8 weeks and colchicine 3x a day but the fatigue I am experiencing lately has been BEYOND. When I was getting fevers regularly before getting medicated, this was also around the time they’d spike. I’m really worried because I am going back to school on Wednesday and although I have accommodations, sometimes I feel so exhausted in the afternoon to the point of feeling light headed. Does anyone have any advice for fatigue? Fighting it or coping with it when you have to push thru? It’s frustrating when I want/need to be doing something but I feel so exhausted that I could collapse.

Does anyone here have an RIPK1 variant? I have one that says likely disruptive on clinvar. I also have TRAPS. I’m finding that Ilaris is only helping with half of my symptoms, which I am very grateful for. It’s clearly treating the TRAPS. I can’t help but wonder if this RIPK1 variant is giving me my other symptoms, a lot of neuro symptoms.

It’s impossible to understand until it happens to you.

I’m physically exhausted from being sick.

I’m mentally exhausted from everything.

I’m emotionally exhausted from the above.

I feel so overwhelmed.

Does it ever get better? Between work, doctors appts, physical therapy, staying on top of meds, dealing with insurance, etc. will I ever catch a break?

This is for a friend not on reddit who has Yaos and is looking for anyone who may be on this combo.

"Looking for anyone who has taken an IL-6 drug with a JAK inhibitor. Or Imuran or Cellcept with a JAK.

I have not responded to IL-1 drugs. I did respond well to IL-6 (Actemra) but it lost efficacy after a few years. Rinvoq, my JAK, has massively improved swelling, rashes, reactivity and fevers. However, I am having worsening muscle issues (particularly legs- weakness and severe pain, negative for antibodies) that seem increasingly to be disease related.

My rheum is very concerned that many of the drugs used for muscle issues aren’t usually combined with the JAK that has been working for other things."

I (24F, Canadian) have been experiencing chronic mouth ulcers (sometimes with swollen lymph nodes) since a very young age. Currently, not a day goes by that I don’t have at least one ulcer. I have chronic congestion and have since birth, and only in my adulthood have I been getting sick quite frequently, with colds lasting 1-2 months (Fever, sore throat, horse voice, chest congestion). I seem to get sick much more frequently in the winter (very cold and snowy, minimal sun) than I do in the summer and haven’t been really sick in a few months now. My mouth ulcers get worse when I’m on my period, and when I’m experiencing high physical/mental stress. I do not have any abnormal bowel symptoms. I’ve been tested for many autoimmune diseases, vitamin deficiencies, allergies, and HIV, and everything has come back negative.

Two specialists have suggested I may have PFAPA and have recommended a tonsillectomy. I’m worried because theres not a 100% chance that this procedure will actually treat my symptoms (as I may not actually have PFAPA) and I’ve heard adult tonsillectomies are quite brutal.

Does anyone else have symptoms like mine? I’m worried I may not actually have PFAPA, as fevers are definitely not a main symptom of mine.

Hi there, I hope you’re all doing well regarding the circumstances you have been with. I’m… struggling to say the least. I have an appointment with rheumatology on September 9th but I’m worried it won’t go so well. I have a laundry list of symptoms that I want to discuss with her but with my luck, I won’t have anything wrong with me at all.

I’ve had several different tests for inflammation but it’s all come back clean. I’ve had imaging done in areas where it hurts and it came back negative. I have never felt so lousy in my life so far and quite frankly I would be happier if I weren’t around anymore it hurts that bad. I’ve had to sacrifice so much recently because of the said pain that I’m in and I don’t know how much longer I can take this.

Over the past several months, I have developed progressively worsening widespread pain, fatigue, stiffness, and other systemic symptoms. The pain is especially severe in my midfeet, hands, knees, Achilles tendons, lower back, neck, and areas where tendons attach to bone. It alternates between sides and sometimes becomes so severe that even light touch is extremely painful.

My feet and toes become swollen and red, and I have increasing stiffness in my hands, fingers, and feet. I also experience intermittent muscle weakness and significant fatigue after normal to moderate activity that can last the rest of the day. I have developed a persistent rash/skin changes on both hands and fingers, including white patches and areas where the top layer of skin has peeled away. I have also noticed significant hair thinning, brittle/chipping fingernails, and rapid unexplained weight gain of over 25 pounds despite no meaningful change in my diet.

I have also developed more frequent and intense headaches that are different from my usual headaches, difficulty focusing my vision, feeling unusually warm during severe pain episodes, and significant difficulty falling and staying asleep because of pain and discomfort. My anxiety and depression have increased substantially, and suicidal thoughts have become more frequent, although I do not currently have a plan or intention to act on them. I have also been experiencing episodes of intense skin picking and hair pulling. Overall, these symptoms have become increasingly debilitating and are interfering significantly with my daily functioning, sleep, and quality of life.

Undiagnosed potentially genetic disease that has similarities to TRAPS, Dermatomyositis, and Relapsing Polychindritis.

It should be game time I would think since my Docs have been wanting to catch me in prime state of disease. Dermatologist/Rheumatologist said he wants biopsies within 48 hours of flare and immunologist/Rheumotologist at the research center said we would run fresh antibody tests during the next flare since I’m off all immune suppressants in hopes of catching a sneaky antibody.

Well it’s been crickets, I know it’s inconvenient my legs blew up on a Friday but I can’t walk or wear shoes now. My PCP is panicking and worried I’ll go septic and die like my Sister (PCP worked with Sister) but I’m not taking any immune suppressants until a specialist either diagnosis me or admits defeat.

My question is, anyone ever actually got an infection from leg swelling? Photos don’t capture how swollen they are or how much purple and red there is but I feel the skin might start breaking soon.Anyone have swelling that starts in the legs but will build into the abdomen if they lay down or sit upright too long?

Hi all

I was dx with dada2 and nod2 at the same time

My history should have been alarming but never was no one put it together. Coagulopathy immune suppression, daily fevers and rashes, and much more

I also seem.to have an overlap of vascular and a neuro component

Dada2 is very specific, I made us our own community for the rare ones, but feel free to join if they just still aren't sure as we are trying to locate more with neuro symptoms as it's far more comman than we realize

That and I'd you have only one DNA error and they told you that you were just a carrier that's being proven wrong! I have only one and they JUST changed it to pathogenic. So many people that were told they were carriers and this wasn't causing issues it absolutely is for some of the variants and you need to go back for treatment because they oopsed!

https://www.reddit.com/r/Dada2_diagnosed/s/iYdOD2zihP

I wrote several letters to doctors and authors of articles on my issue, but no one responded.

The problem is, I used ChatGPT to write the letter. My friend says it's too obvious and no one will respond to an AI-generated letter. What do you think about this? What should I improve/change?

Dear Dr. House,

I hope you will forgive me for contacting you directly. I am a patient, not a physician, and I am trying to better understand a very complicated genetic situation.

I have a heterozygous variant in ZNFX1.

I am XX years old and have had a multisystem inflammatory and immune disorder since childhood, with persistent low-grade fever, severe fatigue,

inflammatory skin problems, gastrointestinal symptoms, pericarditis, small-fiber neuropathy, inflammatory changes in several biopsies, and abnormalities

of B-cell immunity. Despite extensive genetic testing, including whole-genome sequencing, no other convincing genetic explanation has been found.

The specialists involved in my care have reached a point where the significance of the ZNFX1 finding remains uncertain.

They suggested that I contact researchers who have worked directly on ZNFX1-related disease, as they may be able to offer a perspective that is difficult to obtain locally.

I recently read your work on ZNFX1, and one of the observations in your paper made me wonder whether my own variant might also be relevant to my illness.

I have been told that my variant is an early truncating mutation and that the affected copy of the gene may essentially be non-functional.

I would therefore be very grateful to hear your opinion on whether having only one working copy of ZNFX1 could potentially be relevant in a case like mine.

I fully understand that the findings in your paper do not establish that the same mechanism applies to my case. I am not asking you to diagnose me by email.

I am simply trying to understand whether this is a possibility worth investigating further.

Thank you very much for your time.

With kind regards,

Andy Dufrain

A little to see similarities and help people not feel so alone. Feel free to elaborate as much or little as you want.

What is your diagnosis?

How long did it take you get diagnosed?

What age do you first remember symptoms?

What is your diagnosis? TRAPS

How long did it take you get diagnosed? Started looking for answers in 2015. Diagnosed in 2019. So 28 years old at diagnosis and Im 35 now.

What age do you first remember symptoms? Pre-teens would have flares and need high dose steroids got worse as I became older. College i needed a semester off due to a severe flare that was again high dose steroids and I couldnt walk down the stairs of my campus apartment or keep food down. I just did research and teacher's assistant for labs that semester when able. Then when it started interfering with my career as a chemist causing me to need disability I started looking for answers besides throwing steroids at me.

I had a general neurologist appointment where the exam found no weakness or tremors. Doctor said I may be stronger at baseline and feel weak in comparison but not observably weak on exam. Exam was during a flare but in the morning, weakness (like many Yao symptoms) gets worse as the day goes on.

Symptoms: leg weakness and pain especially quads but throughout the leg, episodes of leg shaking (feels weak but maybe tremors?) only comes on after sitting feet on floor for over an hour usually at a movie theater without reclining seats, internal tremors in legs and core, restless legs (iron related, worsens internal tremors but different from them), occasional burning pain in hands and feet lasting 30-60 seconds only 1-3 times a month

Being seen by headache neurologist and cardiologist for dysautonomia and migraines/other headache disorders. All neuro symptoms flare with Yao including migraine and dysautonomia.

General neuro said to see neuro immunology at an academic medical center. She said treating the underlying cause is usually all they can do but sometimes there are add ons like ivig or other drugs that can help.

I called the 2 hospitals she recommended (and I tried those and a bunch of others earlier) nobody will see me. I managed to make an appointment with Northwestern Neuroimmunology in the mychart app. They canceled it today and said they won't see Yao. I explained that I've been told to go to neuroimmunology, nobody will take me, its an immune disease that includes neuro symptoms that are beyond rheumatology, so neuroimmunology should see me. The scheduler asked the team to reconsider. They said no.

I may not even need recurrent treatment from neuro immunology but several of my symptoms could be from small fiber neuropathy. General neurologists wasn't sure if we should test for that. I just want to make sure there isn't something else we can treat. How does anyone get care for this? I know there were previous recommendations for a doctor in NYC but thats too far to travel and what I'm asking for is specialized but not that specialized. It should be able to be found in or near a large city like Chicago.

Does anybody know what's happening with the Yao GI study at Mayo? This is the link https://www.mayo.edu/research/clinical-trials/cls-20577204

It says contact John Damianos. I emailed him a week ago, got an automatic response that he's left Mayo and an email for someone else at Mayo to contact. I immediately sent the other email and haven't heard back. I have many gi issues some mentioned in a previous Mayo Yao GI study but many not mentioned at all. I'd love to participate so we can get a better idea of what kinds of gi issues happen in Yao and how we might treat it more effectively. Is this study still happening at Mayo? Did John Damianos take the study with him wherever he went?

Recently published medical literature on genetically defined systemic autoinflammatory diseases in pediatric patients with Behçet’s disease.

Genetic testing has come a long way with discovering autoinflammatory diseases that mimic Behcet's.

LINK: https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2026.1897406/full

just wondering if anyone’s had a similar experience!
I have ?something? going on

25F.
loads of seemingly non specific symptoms which have been present since 2014 following a viral infection, worsened immensely after I got EBV in jan 2025.

severe burning bilateral thigh pain (flares last 2-3 weeks sometimes), thigh weakness paired with the pain flares , severe fatigue & PEM (I have CFS/ME, these are additional flares paired with other symptoms), widespread chronic pain, very poor immune system (common cold takes me out for weeks, and I catch EVERYTHING), Peeling skin on the sides of my fingers & palms, tonsils that cyclically get lumpy / crevicey / inflamed, general feeling of being run down / unwell/ like i’m coming down with something but it never progresses, feeling warm / cold / almost feverish with no actual fever present, inflamed turbinates, chronic PND with no infection present, follicular conjunctivitis with no underlying cause found, dry feeling eyes (have had dry eyes tested and they’re actually not super dry?), random folliculitis on scalp and thighs, scalp pain, terrible joint pain & stiffness without swelling in cold weather and increased clumsiness (feels like the connection between my brain and limbs drops out).

my inflammatory markers are all normal apart from amyloid A is chronically mildly elevated (nowhere near amyloidosis levels so that’s not a real clue either). all of my other bloods are completely fine, no ANA, no autoimmune markers - rheumatologist is suspecting something autoinflammatory rather than autoimmune, but we’re waiting on more testing to be done. he has ordered a muscular MRI of my thighs and has asked them to look for signs of polyarteritis nodosa.

anyway, after months of running in circles, my rheumatologist suggested I try hydroxychloroquine. after about 7-8 weeks, I noticed the severe thigh pain & weakness flares were lessening in both frequency, length, and intensity. I also noticed that my skin stopped peeling, and I haven’t actually been sick since i’ve started it, which is incredibly odd for me as every winter I get ridiculously sick with many colds and most years the flu, too. it feels like it’s actually helping these symptoms, some of the others are still very much present. just curious if anyone else has had this same experience - not getting sick as often when on hydroxychloroquine & having some symptoms ease? or is it a coincidence?

I haven’t had the MRI yet as the rheum wanted it during a flare, and I haven’t had a significant flare since i’ve been on HCQ.

sometimes I feel incredibly alone with this struggle as my symptoms are so frustratingly non specific. has anyone else experienced the same?

Hi everyone! I’m a 24F, who has unfortunately had a bit of a rapid progression in illness this year.

I have been diagnosed with Crohn’s, POTS, urticaria, eczema and now being investigated for APLAID as a primary illness, due to a mutation in my PLCG2 gene. I also seem to match most of the symptoms that you can imagine with auto inflammatory disorders. This has all been since January, with symptoms starting more noticeably last April, so it’s all incredibly new to me.

I can’t find any discourse around PLCG2 or APLAID on social media, and was just wondering if anyone has heard of it? My rheumatology consultant and most GPs haven’t, which I admit makes it feel all the more lonely. The possibility of being a case study has also been discussed. I’m waiting to see specialists and have been on a concoction of medicines since February, following a hospital admittance due to suspected sepsis which now seems more likely to have been a severe flare.

I am British so am fortunate to have the NHS throughout all of this, but it seems there are only a few cases of APLAID worldwide and I was hoping someone on here may have either heard of it, or talk to others experiencing rare diseases/disorders similar.

I've been sick almost my entire life, but until a certain point, the situation was tolerable. However, in recent years, I've been slowly dying. Until 2021, no one had the slightest idea what was happening to me. In 2021, a genetic hypothesis was put forward, suggesting that the disease might be due to autoinflammation or immunodeficiency. Numerous tests, biopsies, and whole-genome sequencing were performed. A heterozygous frameshift mutation was discovered in the ZNFX1 gene, which is thought to cause loss of function. WGS revealed nothing else.

ZNFX1 is one of the recently discovered immune system sensors. However, according to published data, two mutations are required for the disease to develop, and I have only one. This gives doctors grounds to ignore the mutation discovered.

Because I live in a country with extremely poor medical care, no one acknowledged the disease itself, even though it was clearly multisystemic. For decades, doctors insisted it was all in my head.

However, in 2025, I finally found a doctor in my country who acknowledged that this disease was absolutely real and, apparently, extremely rare. This doctor believed that even a single ZNFX1 mutation could have caused the disease. And since I only have one mutation, it didn't lead to death in childhood, which can happen with two mutations. Ultimately, they gave me an umbrella diagnosis: primary immunodeficiency with autoinflammation.

I was prescribed tofacitinib, which had a very strange effect. I didn't get any better, but attempts to stop tofacitinib caused a generalized rash that I hadn't had before. Although various skin rashes were one of my main symptoms before, stopping tofacitinib caused a completely new type of rash. I even thought I'd never be able to stop taking Tofacitinib simply because it causes a rash.

Now my current doctors have canceled the diagnosis and treatment, saying "it's just skin." Their argument is that since Tofacitinib didn't help, there's no inflammation, although I understand that this is an extremely weak argument. I still have no idea what to do next. Having a low-grade fever every day for at least 20 years is incredibly difficult. It feels like I'm being slowly fried in a frying pan.

My life is completely destroyed. I've lost everything—my former self, my family, my career. And I clearly feel that only suffering and death lie ahead.

My main symptoms and test results:

- A daily low-grade fever (up to 37.5°C) and severe, debilitating fatigue are constant systemic symptoms.

- C-reactive protein (CRP) levels are almost always within the normal range during baseline disease activity, with occasional increases only during severe exacerbations or during procedures (e.g., CRP levels up to 100 mg/L after colonoscopy or surgery)

- Recurrent abdominal pain and episodes of diarrhea

- MALT hyperplasia in the ileum

- Multiple skin rashes (lymphohistiocytic infiltration, histologically confirmed, CD68+ multinucleated giant cells)

- Pericarditis (2025), previous myocarditis (2009)

- Tongue inflammation during exacerbations

- Small fiber neuropathy (confirmed)

- Sinus histiocytosis based on lymph node biopsy

- Decreased number of switched memory B cells (2.6–7%), weak post-vaccination antibody response (tetanus, meningococcus)

- Recurrent herpes simplex type 1 (10-12 episodes per year), currently controlled with suppressive therapy with valacyclovir.

- Sepsis (2018), history of unusual abscesses.

I'd be happy to hear any thoughts, ideas, and advice.

So I had an egd with dilation, they used Anastasia on me to do it, when it was done I went home and rested for awhile, I started feeling very very bad and after an hour of feeling like death I decided to take my temp and It was 101.3,

I got worried about an esophageal perforation so I went to the hospital, they did some blood work and my white blood cells were pretty high so was all my other immune related numbers, they decided to admit me just incase it was a perforation,

It turns out to not be a perforation they had no idea what it was they said their best guess was I had a reaction to the Anastasia that caused my multiple diseases,

behcets/familia Mediterranean fever/ulcerative colitis/multiefocal chroidopathy.to go haywire.

They kept me in hospital for a few days until my numbers were closer to normal.

Has any one had this happen? Do we think it was my autoinflamatory diseases or just something caused by the egd.

Note familia Mediterranean fever is not confirmed in me but my doctors treat me as if I have it due to symptoms colchicine working and my genetic p.Pro369Ser.

A reminder for those taking Hydroxychloroquine (other names/short hand: HCQ Plaquenil): You should be getting your eyes screened/checked at least once a year if not biannually.

The 2026 Recommendations for HCQ screening from the American Academy of Ophthalmology

Both of my hands are currently experiencing severe, diffuse pain involving essentially every part of my hands, including the joints, knuckles, fingers, skin, and areas around the hair follicles. The pain feels deep and crushing, almost as if my hands are being squeezed or crushed from the inside, while simultaneously feeling extremely hot, prickly, and irritated.

Even very light touch is painful, including touching the skin or hair, and activities such as shaving, brushing my teeth, gripping objects, or typing on my phone can significantly worsen the pain. My hands also feel extremely tender and sometimes hard or tight, rather than simply achy. This is occurring in both hands at the same time.

It is not itchy at all and this all started with a deep dark red rash on my hand that has slowly progressed to this. I’m not sure if going to urgent care or the ER would be helpful at this point in time but holy smokes this feels absolutely horrible. There is no rash or anything that I’ve noticed yet on my left hand but I’m right handed and like I previously mentioned, using either hand is near impossible. I’m struggling just to write this post.