Autoimmune type issues for years without clear diagnosis

Posted by yellowfleurs @yellowfleurs, Feb 17 9:42am

Hi All,

I have had evolving (auto?) immune type issues for years with normal labs and it is still unclear what is going on. I am wondering if anyone had a similar journey or has suggestions in general?

When I was 17 I developed sudden Achilles tendonitis pretty much overnight along with Raynaud's. I initially thought it was an injury but then it spread to other tendons in my feet and eventually other joints. I also became fatigued and had muscle aches and pains. When was 21 I was diagnosed with Lyme disease and treated for it, with some improvement in symptoms (but I know doxycycline is generally anti-inflammatory as well).

A few years after that I had a bout of gastroenteritis and a major flare up of tendon symptoms to the point I couldn't walk. I had some urinary symptoms as well and was told it seemed I had reactive arthritis. Things improved over time, but did not fully resolve.

Fast forward to my mid 30s and I became suddenly sick in summer of 2024. I had nerve symptoms (numbness, tingling, pain), muscle and joint pain, intense flu-like symptoms, rapid heart rate, weakness, sweating, shortness of breath, swollen lymph nodes. I ended up diagnosed with POTS and eventually the flare went away and I felt mostly better. This was not right after any obvious viral illness, but it was during a heat wave and after trying a new medication.

I had another similar flare in summer/fall of 2025 but this time I also had some subcutaneous pain and itching on one side and developed a puffy lipoma. I felt incredibly sick for months and ended up taking steroids followed by a course of doxycycline (both helped). This time I had more lingering tendon pain. Both recent flares were intense and I kept saying I felt like I was dying. Lost 10 pounds each time and could barely get out of bed.

I also pretty much had normal labs throughout all of this other than a few minor things like low electrolytes and high B12 and slightly high WBCs in 2024. I still have enlarged lymph nodes that are being monitored, and an MRI showed some arthritis in one my feet recently, but nothing severe. A rheumatologist said I might have seronegative spondyloarthropathy which makes sense to me, but some of these symptoms like nerve and subcutaneous stuff seem like they don't match this. He also mentioned post treatment Lyme but some of these evolving symptoms make me question if it is all that. I have also had hair loss, nail changes, livedo reticularis pop up in the last year and get dry eyes and mouth but am negative for Sjogren's labs. I have also become sensitive to sunlight and heat which I guess tracks with POTS.

Sorry this is so long, but does anyone have any feedback or recommendations? Thanks!

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lkirnbauer | @lkirnbauer | Feb 19 7:48am

Some of your symptoms sound like Long Covid, which I have. There’s no cure as of yet, at least that’s what I’ve been told. I wish you well on your health journey.

fairn | @fairn | Feb 19 8:01am

I'm sorry to hear about all the difficulties in finding answers! My situation has some similarities so passing this along- I had a positive result on the ANA test about 7 years ago. My PCP ran a few tests to see if they could identify anything and nothing came back. My blood work consistently showed a low white cell count. I was frequently sick, things like bronchitis, low-grade fevers, low vitamin d, etc. . My symptoms made me suspect some kind of autoimmune disease but my blood test didn't show that. Every year and a half to two years a test would be repeated including a visit during covid to rheumatologist. He mentioned osteoarthritis and possibly fibromyalgia which I didn't think quite fit. I did have an elevated CCP result, which showed inflammation. Finally this past year I saw a new rheumatologist who ran several tests. This time it included something called Early Sjogren's Profile Panel and it came back indicating I could be in early stages for Sjogren's. The most helpful thing with my current rheumatologist was he takes the approach that if there's obvious inflammation and other symptoms ( in my case dry eyes, dry mouth, arthritic hand, fatigue, MRI showing inflammation in the spine, flares with low-grade fever, and other things that had been looked at and treated separately), he was going to treat the symptoms regardless of all the tests coming back positive. The classic Sjogren's test as well as many other autoimmune tests unfortunately have a fairly high rate of false negatives. His explanation is that many tests will not show positive until considerable damage has been done and it's important in these diseases to intervene early. My encouragement is to listen to your symptoms and your gut and keep asking questions. I did go into the new rheumatologist armed with a printed out document of all my past illnesses and symptoms, no matter how inconsequential they might have seen. Looked at individually they don't seem significant, but once they are all put together often times you see a cluster or a pattern that points to a certain disease process. Hope this is helpful, wishing you the best!

artemis1886 | @artemis1886 | Feb 19 8:57am

Go see an ENT doctor and request a lip biopsy for Sjogrens . The neurologist had me do that. Labs were negative for Sjogrens but the biopsy of the glands showed positive.
They were enlarged and popped right out they were so big. There is more than one way to test for an autoimmune disease. Blood work is not the only way. It did not hurt. Took less than 5 minutes the doctor knew immediately buy looking at the glands and the size.
https://sjogrens.org/blog/2021/the-lip-biopsy-its-not-as-bad-as-it-sounds

yellowfleurs | @yellowfleurs | Feb 19 9:03am

In reply to @swalex "I would like to encourage you to watch: "COVID Isn't Just a Lung Disease—What the Microscope..." + (show)

@swalex thank you I will check it out!

yellowfleurs | @yellowfleurs | Feb 19 9:14am

In reply to @mviscomi "@yellowfleurs I had Covid in late September 2022 and this is my experience with long covid..." + (show)

@mviscomi thank you for the response. Sorry you've been dealing with all that and that it continues to cause new problems. It is hard to ignore the timing of my new symptoms and overlap with long covid that people describe. I'm wondering if maybe I had some immune dysregulation from the Lyme disease and reactive arthritis but then covid caused that immune dysregulation to evolve? Or maybe I have 2 overlapping issues. Do you recommend the mayo clinic?

yellowfleurs | @yellowfleurs | Feb 19 9:23am

In reply to @fairn "I'm sorry to hear about all the difficulties in finding answers! My situation has some similarities..." + (show)

@fairn

Jump to this post

@fairn thank you for the reply! Yes it's everything together that makes me think something is going on. Ever since developing tendonitis at 17 I just haven't felt right and new things keep popping up. I/my doctors have wondered about Sjogrens actually but then after my labs were normal no one considered it any more. I'm fortunate I finally found a rheumatologist who isn't just brushing me off despite the labs. But I worry he'll get burnt out trying to help me figure it out. Past rheumatologists have immediately said I'm fine when my labs came back normal.

Can I ask how you are being treated and if you're doing any better? Also what kind of eye symptoms do you have? I was told by an optometrist I have dry eyes with Meibomian gland dysfunction and mild cornea inflammation, but my understanding was Sjogrens more so affects tear production? I have rosacea which can cause the MGD as well. Thanks!

yellowfleurs | @yellowfleurs | Feb 19 9:27am

In reply to @artemis1886 "Go see an ENT doctor and request a lip biopsy for Sjogrens . The neurologist had..." + (show)

@artemis1886 you know I'm actually seeing an ENT due to the lymph node swelling I had (in my neck and in submandibular area). He's been following the lymph nodes with ultrasounds. He knows about all my symptoms but never suggested a biopsy. My submandibular glands themselves looked normal on US but I feel like they get puffy and painful during flares. Maybe same with my parotid glands last time. Perhaps I should ask him directly. Thanks!

yellowfleurs | @yellowfleurs | Feb 19 9:32am

In reply to @becsbuddy "@yellowfleurs Welcome to MayoClinicConnect! I’m glad you found this site and Im sure you are, too...." + (show)

@becsbuddy thanks so much! I'm seeing a POTS specialist at a university hospital but rheumatologist is local. Did you need a special referral to go? I wonder if anyone would even see me with my normal labs. The POTS specialist agrees there's a pattern with my immune system and dysautonomia based on the flares, but says research just isn't really there at the moment to explain. I'll take a look around at other posts too!

fairn | @fairn | Feb 19 9:42am

In reply to @yellowfleurs "@fairn thank you for the reply! Yes it's everything together that makes me think something is..." + (show)

@yellowfleurs I am taking Hydroxychloroquine which has helped with most symptoms. The dry eyes and mouth haven't stopped, but are better. I had issues with sprained ankles when I was a child, now have tendon issues in my hands and feet. I've found that Sjogren's is much more than the eyes and mouth! I recently had an endoscopy that showed chronic gastritis in my stomach and I started a deeper dive into all of the areas that having Sjogren's can impact and it's pretty much everything 😵‍💫. My sister had episcleritis, dry mouth and back pain for years and I encouraged her to see my doctor. She was diagnosed with sica syndrome (another term for Sjogren's) and ankylosing spondylosis. We've both tested positive for the gene HLA- B27 which is not related to Sjogren's but is an umbrella for several arthritis related diseases. He told her she should have seen him 20 years ago. I think the key is having a doctor who will do the testing while at the same time knows the weaknesses of those tests and listens well to the symptoms. If you are having cornea or other issues of the eye I would press for more tests.