Small Fiber Neuropathy Skin Biopsy: What to Expect Before, During, and After

If your neurologist has suggested a skin biopsy for small fiber neuropathy, the word biopsy may sound bigger than the procedure is. This is a skin sample the size of a pencil tip, not surgery on a nerve. Here is what actually happens, from the appointment before to the day your result comes back.

What is a small fiber skin punch biopsy?

A skin biopsy for neuropathy removes two tiny round samples of skin, 3 mm across, from the leg. Each sample contains the endings of the small nerve fibers that carry pain and temperature. A specialized laboratory stains those fibers, counts them under a microscope, and compares the count to normal values for your age and sex. A low count confirms small fiber neuropathy.

The test exists because the small fibers are invisible to nerve conduction studies and EMG, which measure only the large fibers. If you have burning, stabbing, or tingling feet and a normal EMG, this is the test that can still give you an answer. It is called a punch biopsy because the tool is a small hollow cylinder that removes a round core of skin, like a very small cookie cutter.

It is sometimes confused with a nerve biopsy, which surgically removes a piece of a nerve. That is a different, more involved procedure that is rarely needed. The skin biopsy is what is used for small fiber neuropathy. How well it performs, and what a normal result can and cannot rule out, is covered in how accurate is a skin biopsy for small fiber neuropathy.

Anatomy at a glanceSmall nerve fibers

What a skin biopsy looks for

A small skin sample gives the laboratory a close look at fine nerve endings.

View larger illustration

1. 1

   Epidermis

   The outer skin layer. Small sensory nerve endings reach into this layer from the dermis below.

2. 2

   Small nerve fibers

   These fine endings help you sense pain and temperature.

3. 3

   Skin sample

   The laboratory stains the sample and counts nerve fibers, comparing their density with reference values.

A fiber count adds evidence. It does not identify the cause on its own.

Before your skin punch biopsy

The biopsy is scheduled after a neurological evaluation, where Dr. Ntranos examines you and decides whether the test will answer your question. Blood work for treatable causes of neuropathy is usually ordered at that visit, so the two results can be read together.

There is no preparation. Eat and drink as usual and keep taking your medications. If you take a blood thinner, tell us when you book so we can plan for it; in most cases nothing changes. Wear or bring shorts, or trousers that roll easily above the knee, since the samples come from the outer ankle and the upper outer thigh of one leg. You do not need anyone to drive you.

During the skin punch biopsy procedure

Dr. Ntranos performs the biopsy himself in our Beverly Hills office. You lie on the examination table with one leg exposed. Two sites are cleaned and marked: one just above the outer ankle and one on the upper outer thigh. Two sites are used so the fiber count near the foot can be compared with the count higher up, which tells us about the pattern of the neuropathy and not just whether it is present.

Each site gets a small injection of local anesthetic. This is the part that stings, for a few seconds, much like a dental injection. Within a minute or two the skin is numb. The 3 mm punch is then pressed and turned to take the sample, which takes seconds. You may feel pressure or a slight tug, but not sharp pain. Light pressure stops the small amount of bleeding, and a small adhesive bandage goes on. No stitches are needed for a wound this size.

The samples go into preservative and ship to the laboratory the same day. Most people say the whole thing was easier than they expected.

Visual guide

A small sample, a laboratory answer

• Local numbing: The skin is numbed before each small sample is taken.
• Two sites: Samples from near the ankle and upper thigh help show the pattern.
• Aftercare and results: Follow the written wound-care instructions while the laboratory processes the samples.

After your skin punch biopsy

You can drive yourself home and go back to work or your usual day. The sites feel like a small scrape for a day or two. You leave with written aftercare instructions covering bandage changes, showering, and when to avoid soaking the sites, and you can call us with any question in the meantime. Contact us sooner if a site becomes increasingly red, warm, swollen, or starts to leak, since that can mean a minor infection that is easy to treat.

How long does a punch biopsy take to heal?

A 3 mm punch site closes on its own in about a week to ten days. It scabs, the scab falls away, and what remains is a small pale dot that fades over the following months. Most people cannot find the sites a year later. Vigorous exercise and swimming wait until the sites have closed; the written instructions cover the specifics.

Getting your results

Your samples are analyzed at Therapath, a laboratory that specializes in nerve fiber counting. The report gives an epidermal nerve fiber density, meaning the number of small fibers per millimeter of skin, at each site, alongside the normal range for your age and sex.

Results usually take about two weeks, sometimes three when sweat gland density is included, and we tell you when yours is back. At the results visit Dr. Ntranos goes through the numbers with you. A reduced count at the ankle with a normal count at the thigh is the commonest pattern and indicates a length-dependent small fiber neuropathy. A reduced count at both sites suggests a different process, often an autoimmune one, which changes the search for a cause. A normal count does not exclude every form of small fiber neuropathy, and the accuracy article explains why.

The biopsy tells us the fibers are reduced, not why. What comes next, from finding and treating the cause to managing the pain, is covered on neuropathy in the feet and can peripheral neuropathy be reversed.

If you have burning or tingling feet and a normal EMG, or you have never been tested at all, you can request a visit in Beverly Hills or Los Angeles, or by video anywhere in California, to find out whether the biopsy is the right next step for you.

Visual guide

From laboratory result to the next step

• Laboratory analysis: The laboratory stains and counts the small nerve fibers.
• Clinical interpretation: The count is compared with reference information and your symptoms.
• Next steps: The result helps guide further evaluation and a treatment discussion.

References

1. Lauria G, et al. European Federation of Neurological Societies/Peripheral Nerve Society Guideline on the use of skin biopsy in the diagnosis of small fiber neuropathy. European Journal of Neurology, 2010.
2. National Institute of Neurological Disorders and Stroke. Peripheral Neuropathy.
3. Cleveland Clinic. Small Fiber Neuropathy.
4. Therapath Neuropathology. Epidermal Nerve Fiber Density.
5. Therapath Neuropathology. Skin Biopsy: specimen handling and turnaround.
6. Johns Hopkins Medicine. Cutaneous Nerve Laboratory.