Autoimmune Epithelitis

[inga]

Anita, I would asume that the epithelial tissue is part of the glandular structure. 

http://www.otohns.net/default.asp?id=14646

I would wonder if the structure of the salivary gland would deteriorate without innervation, regardless of a systemic inflammatory process.  The citing above indicates that autonomic nervous system involvement is crucial to the development of the gland, then would it not also be involved in the deterioration of the gland as well.

I am also wondering if diagnosis of SjS on the basis of labial gland biopsy, is not as accurate at purported? If the glands are deteriorating due to denervation the epithelium will also suffer, since it contains nerves, and as these nerves die, they would kill epithelium and interfere with labial gland structure as well, producing what appears to be SjS.  So I feel there is THIS kind of result.  Then there is the Epithelitis result.  Two distinct kinds of 'inflammation' of the gland, from different reasons, both deemed Sjogren's.

I would feel more comfortable with my diagnosis if I had SSA or SSB (I don't.)  I do have nerve degeneration in my intraepidermal biopsy, which is 'epithelial' tissue.

[anita]

Inga,

I think you've opened a new door.  I wonder if what you've found is a perfectly valid explanation for my lip biopsy showing almost complete destruction of the Acinar structure.  As you said and found, the autonomic nervous system plays a crucial role in the development of the gland.  Therefore, knowing my severe autonomic neuropathy (for almost every function), this could explain the findings on biopsy. 

This would also mean that the lip biopsy may NOT be as accurate, since other factors could be changing the structure of the glands. 

I believe you have some significant autonomic dysfunction as well, right?

Well, now if I could just find an explanation for the autonomic dysfunction.

I would be interested in those who are sero-negative, but positive lip biopsy...and that have autonomic dysfunction.   

You know, Birnbaum is a research nut...I may throw this his way to see what he thinks.  I should be seeing him after my brain MRI (which I'm more and more interested in now).

I do have one question for you.  Which came first, something destroying the epithelium (at gland level) which destroyed the nerves (and affected autonomic function) and subsequent gland structure...or something is destroying the autonomic system (widespread) and then affects the epithelium and gland structure?

Maybe Nathan and Bakvalas will pipe in also.

Very interesting find, Inga.

[inga]

I am not sure which came first, the epithelitis or the nerve damage.

I have the added issue of a +ANA, but -SSA/SSB.

Epithelial tissue is innervated but does not have blood vessels.

I have never been convinced that Sjogren's can stand alone as a disease without the SSA and SSB serum markers....if one doesn't have those, one has a Sicca Syndrome of unspecified origin OR UCTD in the presence of a +ANA, IMHO.

Now the neurological damage could be inflammatory, in essence, similar to CIDP, but, of the small fibers, not myelinated fibers.  Whether or not this precedes epithelial damage, or is cause and effect,  I don't know.  But looking at what this does to the salivary gland, it is not comforting to think about other organ damage.

[inga]

Anita, one more thing....

I have found I am running very low blood sugars, which could be reactive hypoglycemia, from food with a high glycemic index.  I believe hypogylcemia is just as damaging to nerves as hyperglycemia.  It could be that.

This does not explain the ANA being high for me.

Also, the acidemia, I am experiencing lately.....not ulkine what a diabetic gets, but slightly different.

This could be metabolic?

[anita]

In your case, the +ANA should definitely put you in the UCTD category.  Being that I'm sero-negative across the board (don't even have the +ANA), I don't think I fit yet.  Frankly, after absorbing what we've just discussed about the lip biopsy and what might also cause that kind of damage, I don't know where I fit...no-mans land??

About those low blood sugars:  If you are having low blood sugar frequent enough to cause nerve damage, then I think it might go way beyond food.  Have you had your liver function checked?

And no, it doesn't explain the +ANA.   I think the UCTD---and epithelitis (regardless of which came first--because they are both likely present)

Can't the epithelitis be a cause of the dRTA (and acidemia)?

[inga]

Yes, the epithelitis could be a cause of dRTA and therefore the acidemia.  I would think biopsy of other sites could yield evidence of inflammation, or 'itis' of the epithelium.  I would think some researcher would want to explore this.  Also, I would like to know why this is so unresponsive to most treatment.

[anita]

Could the answer to your last question (unresponsive to treatment) have anything to do with excessive B cell activation?

Do you think some get relief with depleting B cell treatments (rituxan, etc) because it stops the apoptosis (I think that's the right word, but not sure) so that tissues, glands, organs, and even epithelium can heal and/or rejuvenate?

[inga]

The jury is still out on the monoclonal antibody drugs for SjS neuropathy....I am not inclined to risk it.  Interestingly, my B cell count is normal.  It is just the CD4+ that is out of whack, if I am correct.  I don't know enough about this yet, to assume that the B cell proliferation is due to CD4+ cell elevation.  I am not sure that B follows T?

[anita]

I think I'll sit back and watch the new drugs/treatments for a while myself.   I must say I'm interested in learning more about it though. 

Isn't a high B cell count associated with leukemia? 

Are blood tests for the B cell count the same as the detecting B cell activation (associated with autoimmune dis.)?  If so, then why not use this test as a "marker"?  Can someone have a normal B cell count, yet the "activation" be greater than normal? 

Can cell "activation" or apoptosis be determined in a test? 

Please pardon my ignorance for some of this stuff...I'm brain storming.  LOL

[inga]

I am not up to snuff on all the T cell, B cell stuff.  I believe my B cell count is WNL (within normal limits).  It is just my CD4+ (which is helper cells) that are out of whack.  T or helper cells are associated with AI disease.

I don't think we (medicine) understand how this process works, and it seems that the B cells are targeted by current monoclonal antibodies.  I am just not confident that these are hitting the mark with the issue that you and I have.  I think more information will emerge as the humane genome is further studied.  Monoclonal antibodies are still relatively new and we just don't know long term side effects.

I can't remember if you ever tried IVIG, and I realize you have kidney issues, but I wonder if they are of the type that preclude IVIG?  IVIG has, in general, less dire consequences than the monoclonal antibody drugs.  I am far from convinced that IVIG is the solution for this either, but, for me it is probably the only option.

[CAT1962]

Interesting info! And, I DO love to google.  Thank you.

CAT

[anita]

I did IVIG for 11 years...and did quite well on it during that time period. 

In 2007, I (out of the blue) got a severe case of aspectic meningitis (CSF  white cell count over 700)...so no more IVIG.  The only change was that I had to stop for a while before that time due to insurance bitching.  My neuro got approval under CIDP and the meningitis occured on the second day of the loading dose.  I spent 5 days in the hospital and 30 days recovering afterward at home. 

There are numerous articles about B cells.  Not really just "B cells", but B cell hyperactivity (BAFF).  There seems to be a difference.  Much of it is way over my head.  Birnbaum was the first to tell me about B cell activation and his belief this was behind the trigger (so to speak) for sjogren's (including neruo problems) and why these new B cell depleting treatments were working (rituxan, etc).  Of course his explanation was very brief and I truly had no idea what he was talking about until about 2 years later while doing more research.

http://www.medscape.com/viewarticle/561880  (notice the mention of both epithelial cells and T cells)

Not being a medical professional, I can't access most articles (other than a few abstracts posted), but you can certainly check them out.  There are several listed to the right of this abstract that look interesting.

They have just barely touched on cell (all--B, T, Epithelial) involvement and rushing to cell depletion (monoclonal antibody drugs) might be reckless if they don't understand the mechanics 'completely'.

[inga]

I have had triamcinalone injections into hip bursae, and it must get systemic and I feel better, much better for a few days....however, I can't have steroids since I have such bone issues....I am not convinced I want to risk PML from a monoclonal antibody, so IVIG seems the only option right  now.  I understand they are on this B cell thing right now...but, I don't think they full understand the process.  For me, I am inclined to leave well enough alone, even tho, well enough isn't very good.

[anita]

I think my days of steroids are over as well...unless something becomes life-threatening.   I already have (and had for several years) osteoporosis at just 46.  Last week I had a my third (annual) IV of Relcast since bisphosphonates and gastroparesis don't go together very well.  I have not had any previous problems, but this one caused a significant reaction and left me watching the clock for another dose of percocet for several days severe joint & muscle pain.  Let's not forget that narcotics and gastroparesis are not much fun either and I avoid them at all cost...unless crying is the only alternative...LOL

Lesson learned:  Never do any infusion (regardless of history) the week of Christmas....NEVER.  LOL

I have not tried triamcinalsone.  Cortisone injections for joint pain work well for me (at least a couple months worth)...is this in the same class?  Does it work the same way?

I was real disappointed about the loss of IVIG...there was a change in symptoms and severity after I stopped.

Now I'm doing nothing but Plaquenil (and my assorted AN meds)...and have recently added neurontin for the nerve pain (and no luck as of yet but still working up to a higher dose)

[inga]

Triamcinalone is basically a steroid...a kind of cortisone.

I am at the point that I think the complexity of my condition exceeds the ability of medicine to manage it.  I am also, just flying by the seat of my pants.