Future Rheumatology
April 2008, Vol. 3, No. 2, Pages 127-131 , DOI 10.2217/17460816.3.2.127
(doi:10.2217/17460816.3.2.127)



Priority Paper Evaluation
Preliminary evidence for small-fiber neuropathy in fibromyalgia patients
Roland Staud*
University of Florida, McKnight Brain Institute, Department of Medicine, Gainesville, FL 32610–0221, USA. staudr@ufl.edu




Kim SH, Kim DH, Oh DH, Clauw DJ: Characteristic electron microscopic findings in the skin of patients with fibromyalgia – preliminary study. Clin. Rheumatol. 27(3), 407–411 (2008). Peripheral tissue abnormalities may contribute to the increased pain sensitivity of fibromyalgia (FM) patients. To address this issue, the authors obtained skin biopsies from the deltoid region of 13 FM patients and five healthy, pain-free control subjects. After fixation, all tissues were examined using electron-microscopy (EM) by an investigator who was blinded to the participants’ diagnosis. In contrast to healthy controls, the skin biopsies from nine out of 13 FM patients showed axons that were localized to the periphery of unmyelinated Schwann cell sheaths. These findings were associated with ballooning of Schwann cells, diminished folding of Schwann cell sheaths and smaller axonal size. Myelinated nerve fibers were unremarkable. The EM findings of this study show that the cutaneous nerve endings of FM patients possess unusual architecture, as well as ballooning of their associated Schwann cells. Similar changes were not detectable in skin biopsies of healthy pain-free controls.

That is very interesting! I wonder how that compares to SFN type explanations? I wonder if they could compare to PNers?

I don't know anything about the biopsy details. I hope Glenn sees this soon!

Wow, that is significant! I do feel that fibro is a neuropathy....it has so many components of autonomic dysfunction...and of course, pain. Great work Amit!

This is so interesting, since deltoid fibers are not tested in the SNF biopsy. I have always wanted them to test fibers that are more proximal on me. Maybe I should ask for one of these.....hmmm.

I wonder.... could these Fibro people have been misdiagnosed, with Fibro, and really be PNers? Rather than SNF being Fibro?

This paper discusses nerve root involvement in patients diagnosed with Fibro. It also discusses "triggers", and toxic neuropathies are listed.

http://docs.google.com/viewer?a=v&q=...F3dXWhP5RmYosA

Check the last sentence in the study (I can't seem to copy/paste it)!
"The tests support our theory that the cause of Fibromyalgia is pathology in the peripheral nerve roots."

And this is interesting...the discovery of "hidden" or undiscovered nerve endings in the skin that were not previously known:
http://www.sciencedaily.com/releases...1208083524.htm

And this is a list of discoveries linking several physiological states to Fibro:
http://www.myalgia.com/Pain_amplific...ic_studies.htm
Including elevated levels of substance P in the CNS and elevated activity of NMDA receptors. (perhaps this is why magnesium works for Fibro patients? )

And this link-- Fibro and the eyes... dry eyes, pain, and light intolerance!
http://www.ehow.com/about_5040994_fi...-problems.html

--that many people over the years who have been diagnosed with "fibromyalgia" actually have as yet undetected small-fiber neuropathies, since skin biopsy is still not a test that is widely available (or ven known about by a good number of physicians).

Fibro did become a sort of "catch all" diagnosis for patients who came in and reported severe pain that seemed to have no direct physcial basis. But I had always thought there was some confusion with those who mayhave acutally had neuropathies but were not skilled in describing the exact nature of the pain they were experiencing--neurologicla pain IS difficult to describe, especially for those who have not experienced it before--AND there are many doctors not skilled in listening to what their patients were trying to describe and/or solciting more information from them.

I'm most interested now in the nerve root theory of fibro--there is a category of nerve dysfunction, neuronopathy, that describes problems that stem from damage to the dorsal sensory ganglia (and is common in Sjogren's, by the way) and in which symptoms may be indistiguishable from that caused by damage to nerve fibers farther down the periphery:

http://neuromuscular.wustl.edu/antib...uron.html#sfsn

In neuronopathies, there seems to be an attack directly on the cell bodies of sensory neurons. This can, of course, cause degeneration of the axonal endings as well, which often shows up on skin biopsy as reduced fiber density. The catch, as Hopkins' Dr. Abhey Moghekar once described to me, is that while nerve fibers can regenerate under the right conditions if the cell body is intact, if the cell body dies that nerve is gone forever (though sometimes other intact nerve cells can frow fibers and take over the functions).

Could fibro involve a neurotransmitter imbalance at the dorsal nerve root/ganglia that oversensitizes to pain? That is an interesting question.

I am wondering if it is viral... like shingles! Maybe a virus infection triggers the genetically flawed cells?

Also, recall the genetic testing, of dorsal root damage?
Could be genetic too.

Anyway, it just expands the possibilities and justifies all the complex types and situations people find themselves in, and end up on this board...all with different stories of triggers, trauma, infection, etc.

There are so many things that could cause a widespread neuropathy or neuronopathy the list would be exhuastive. The chemicals we are exposed to in our food, fabrics and medically are just the beginning.

The system could save a great deal of money on Fibro cases by simply doing a skin biopsy. I do think that the skin biopsies could be done in more proximal sites to see if this trends more towards the Fibro like symptoms instead of the typical hands and feet involvement we see with SNF.

I can't believe that more doctors and researchers are not linking Fibro to SNF...especially given the dysautonomia of Fibro.

The issue with Sjogren's is the lack of good criteria. People are diagnosed with NO inflammatory blood markers. I don't have the +SSA and SSB and feel that I dont really meet the criteria for Sjogrens. I am not looking for a label, any label, but if people want a label, Sjogren's is easily proclaimed. Lip biopsy becoming disregarded lately which is good. Sicca is not Sjogren's. Because the criteria are so loose, it is hard to say if Neuropathy is common in SjS or if the 'SjS' the person has is really neuropathy! Without serum markers, likely the seroneg. SjS is Neuropathy.

Sicca is present in many conditions including SNF.

I think in the presence of a +ANA, and -ENA, the diagnosis of UCTD needs to be used. In the absence of both, SNF needs to be explored and SjS should not be bestowed so quickly.

SjS and Fibro are both catch all diagnosis. SjS should not be if they used serum diagnosis.

Attaching Fibro as an additional diagnosis to SNF, SJS or any other diagnosis is a moot point until they figure out what Fibro is, and I have a feeling it is already encompassed in other conditions.

Great conversation!

Why does it take them so long to even check a few skin biopsies?
In my case, I had multiple diagnoses by two researchers, each specializing in his own field. This was in the early 1980's!
This was a collaborative effort, to determine if CFS and FMS were the same or were separate conditions. I had agreed to participate with them and they had diagnosed me with both conditions (according to the definitions at that time).
These were extensive tests for each and they were listening carefully and asking lots of questions. They were in the room together at the time. (I also saw each of them individually for further follow-up.)

These gentlemen were very attentive to the person and to their research and have excellent reputations. They each had kept telling me he knew I had some severe neurological disease they could not yet recognize. (While also tagging me with CFS and FMS at the time. They also had me see some topnotch neurologists for consults then... due to their strong beliefs I truly had a severe neuro. condition underlying it all.)

It was another maybe 12-15 years before I had a skin punch biopsy and they all went wonky when they saw the results. Yet, with even what little they were saying to me about a neuro illness, why did it all take so long?
It is taking even longer for those not in research studies!

Is it true that not all neurology clinics (even at teaching hospitals) actually do the skin punch biopsies as a part of any work-up? Or is it more true they can obtain the biopsy, yet must send it out to a qualified pathologist?

(Our teaching hospital was doing sural nerve biopsies long before doing the skin punch biopsies... even when the skin punch biopsies were the thing to do at other centers. I'll never agree to a sural nerve biopsy again. Over 20 years later, I still have many diagnoses and things keep becoming increasingly overtly neurological... and a mix of all kinds of AI and neuro. "stuff." They just tell me they can't help me, except to try to help me with pain. The truth is, most of the time they try to prescribe, most of the meds make me even worse.)

It is so hard to believe it took so long to do a few biopsies to see what the trend might be with FMS groups!

I hope they do start offering skin punch biopsies to people with FMS diagnoses.
Everyone deserves to know what is going on in his/her own body, if there is any way to discern this for each individual.

~DejaVu

It would save a fortune to avoid all the wasted testing done for Fibro is they would just do the skin biopsy.

I was undiagnosed for 15 years....told I had fibro even tho I had a clear cut case of Lyme....told I had all kinds of things....not until I had an autonomic episode that resembled a TIA, did I get adequate care and an autonomic test. I had a good cardiologist who suspected dysautonomia and got me to a good neuro who found the small fiber. The autoimmune stuff developed later.

I wonder if there is a lack of availability of TEMs (transmission electron microscopes)? And that is why there are not as many sites for skin biopsies? They are not just found everywhere and need particular support lab equipment and technicians. But I think I have heard of results being done by other microscopes, however the details with TEM are more "detailed".

I'm a retired EMer so am prejudiced and a new member here who also had a skin-punch done but didn't know about the EM connection at the time...it has been good having those results to back me up several times and just for peace of mind. My own EM work was for 17 years but on viruses...we did have some chronic fatique work to do but nothing on FM when I was doing it. But I left that work 14 years ago. (I don't recall seeing anything in the CFS samples we had.)