It is true that not all the tests available test for everything.

We are constantly exposed to things, that could cause some
autoimmune reaction. (Vaccines and their contaminants come to MY mind).

This is illustrated by the Myasthenia gravis board here, where some of them test negative for the typical antibodies, but still they have the weakness anyway. Something not yet discovered is causing the problem for them.

Glenntaj posts about the skin biopsy quite a bit. If you search
"skin biopsy" his posts explain the rationale behind them in detail.

--that yes, a skin biopsy is the current "gold standard" for for determining if there is a small fiber neuropathy.

It's much easier to tolerate than a nerve biopsy, as well--a few shots of local anesthetic, a few 3mm wide by 1mm deep skin samples taken, a few band aids, and it's done--the samples are sent off for electron microscopy to determine the intraepidermal nerve fiber density and condition.

In my case, for example, the biopsy revealed a non-length dependent small fiber neuropathy. Nerve fiber density was significantly reduced as both ankle and thigh sites (many will also take a back-of-arm by the elbow sample), and the nerve fibers that were in evidence there were swollen and inflamed.

Unfortunately, skin biopsies aren't very good at determining the CAUSE of such a situation. Once in a while, more specialized testing of the samples might reveal something. (I had mine tested for amyloid--fortunately negative.)

There are a lot of people out there with skin-biopsy documented small-fiber neuropathy with severe symptoms still looking to determine a cause. Many have had a lot of the tests listed in the Liza Jane spreadsheets for neurologic symptoms (see: www.LizaJane.org--you can see what you've had to date in comparison) and they've all come back negative/normal. It's estimated that a good third or more of all small fiber syndromes are idiopathic.

Thank you for your comments.

I have done all the tests listed in Liza's, except for: 1. Tilt Table; 2. Sweat Test; 3. Quantitative Sensory Testing; 4. Fat Asipirate; 5. Sural Nerve Biopsy and 6. Bowel Studies.

My past tests are :

1. Thyroid Antibodies
2. Lyme Disease
3. Vit. B12 and Folate
4. Rheumatoid Arthritis Factor
5. Ana Direct
6. LDH
6. Sedimentation Rate
7. ANA Comprehensive Panel
8. Glucose
9. Anti-Hu Antibodies
10. Immunofixation Serum
11. RPR
12. Heavy Metal (Urine)
13. Hepatitis Profile
14. Thyroid Function - TSH : since the onset of my neuropathic symptoms last October 2011, this is the only test that is abnormal (I had total thyroidectomy in 2007). My primary care physician is trying to adjust my dosage of Synthroid. The neurologist(s) dont seem to be concerned about the hypothyroidism because they think that my numbers are not "far way-off" and besides I am taking medication for it so it must not be the cause. In the deepest of my heart, I am still hoping that its my abnormal TSH that is causing this horrible pain. I wanted to take R Lipoic Acid as it is highly recommended by most members here but when I asked my neurologist about it, she advised that I should wait until my TSH becomes normal.

Mrs.D mentioned about your posts on skin biopsy but I could not find it. Please direct me how I could search it.

I have the typical symptoms like prickly, stabbing "pins and needles", lancinating pain in my arms and legs and sometimes in my back. I have also the tight-band feeling, numbness and pain in both my feet. I could hardly walk nor stand now. I started on 100mg of Gabapentin (1200mg/day) but now the dosage has been increased to 600mg (1800mg/day).

I will really appreciate for your ideas/information.

Thank you.

Tactile Allodynia. It may follow the same pattern of other neuropathic pain, including being worse at night.

Lidocaine is a topical anesthetic, meaning it only numbs what it directly touches. So gluing a patch over unaffected skin in hopes it will have a deeper affect will only give you numb skin.

--is just to put "skin biopsy" in the pop up box that appears when you left click on "Search" along the top bar here; that way you'll not only get mine bout lots of others. I have often talked a lot about how the skin biopsy protocols were originally developed at Johns Hopkins and how the cut-off points for "abnormal" intrapidermal nerve fiber densities were determined.

I received the lidoderm patches today, so anxious to give them a try. I'll try different locations MrsD suggested over the next few days.

I had a skin biopsy almost 3 years ago at Hopkins. There were some mild changes in the fibers themselves, but nothing consistent enough with SFN. I wonder if I should consider repeating the test with increased pain in my feet, and now the new allodynia in both lower legs?

Glenn, isn't the allodynia consistent with SFN? If so, then the skin biopsy should pick it up this time, right?

--but it could be a symptom of a lot of other things as well.

Interesting that your first skin biopsy picked up some "mild changes" in the fibers; can you elucidate? (What did the report actually say?) Often, symptoms are not correlated with degree of damage; there've been many people with "mild" damage of small fibers who have considerable pain or numbness.

Sometimes, also, the damage is patchy and may not be completely picked up at a specific skin site.

One of the good things about the relatively non-invasive nature of skin biopsy is that it can be done over and over again and comparisons made from sample to sample.

The biopsy (done at JH) included samples from the distal thigh, proximal thigh, and distal leg (both legs).

Most locations reported nerve fiber density within normal limits (although 2 had distribution as patchy). However, all locations reported some occasional medium sized swellings, segmented fibers and/or tortuous fibers.

The summary said there were normal small fiber densities, and the morphological changes are mild and not definitive for a neuropathic process.

The pain in my feet has definitely increased (both severity & 24/7 now) since this was last done, as well as with the relatively new allodynia in both legs. Like I said it's been almost 3 years, so I'm wondering about a repeat biopsy. What do you think? I personally think a comparison would be interesting to see if its consistent with the clinical changes.

Yes that was what my pain doctor said that he has patients with mild dx and the pain is so bad and others with severe damage and pain reported less. I guess some is how ones brain reacts to it?
On a side not with hypersensitivity I know for me the more I stay away from touching or fabrics and the more protective I have become the more sensitive I have become. It is a vicious cycle cause when the pain is higher that happens. I try for ex if I can't tolerate socks on a day to make myself wear them even for a short time. Otherwise when days pass it becomes even harder.