What is Small Fiber Neuropathy?

Small fiber neuropathy is a fairly rare condition that affects the nerves. Although it is considered a peripheral neuropathy (affects the limbs), it can also cause symptoms in other parts of the body. It is poorly understood, and the exact incidence and prevalence are not well-known.

In this article, we will go into more detail about the following areas regarding small fiber neuropathy.
  1. What are the symptoms of small fiber neuropathy?
  2. How is small fiber neuropathy diagnosed?
  3. What causes small fiber neuropathy?
  4. How is small fiber neuropathy treated?
  5. What makes small fiber neuropathy different from other types of neuropathy?
  6. Can small fiber neuropathy be reversed?
  7. Is there a cure for small fiber neuropathy?
  8. Some common misconceptions about small fiber neuropathy
  9. What it feels like to have small fiber neuropathy
  10. Where can I get more information and support if I have small fiber neuropathy? 

What are the symptoms of small fiber neuropathy?

The word neuropathy means "nerve disease." This condition affects the nerves related to pain and the sense of touch. People with small fiber neuropathy experience pain, and also can have increased or decreased sense of touch. That means that they may experience numbness or tingling in their extremities, or be hypersensitive to touch. Even the brush of clothing on the skin may sometimes be painful.

Other symptoms are abnormal reactions to hot or cold, itchiness without a rash, and problems with the autonomic nervous system. For more information about autonomic dysfunction, read my article entitled What is Dysautonomia?

How is small fiber neuropathy diagnosed?

First, a patient would need to discuss their symptoms with their physician. A neurological examination may be performed along with a detailed medical history.

If your doctor suspects this condition, the gold standard for diagnosing small fiber neuropathy is through punch biopsies. This is an outpatient procedure that can be done in your doctor's office if they have experience doing it. Three small core biopsies are taken from the patient's leg at three different locations. First, the physician will numb each area with a local anesthetic, usually lidocaine. Then the samples are placed in a fixative and tested by a lab. The wounds made by the biopsies are very small but may require a few stitches depending on your doctor's preference. They are covered with light bandages and there may be some mild pain or bruising. When they heal, small scars may remain at the biopsy sites.

The advantage of this type of test is its availability. Most, if not all, hospitals and many doctor's offices or procedure centers should be able to perform this type of biopsy. Not every lab can test the samples, but most major hospitals should have the capability.

Unfortunately, patients with slow wound healing or compromised immunity may have a more difficult time with this test. It is not without risk of infection, and these risks are increased in certain populations. If you typically have a high tolerance to anesthesia, discuss this with your doctor in advance, because they should have extra lidocaine on hand in case the standard dose doesn't numb you.

Other methods are also sometimes used to diagnose small fiber neuropathy. One is called Sudoscan. During this test, a patient places their hands and bare feet on sensors for three minutes. The test evaluates the functionality of the patient's sweat glands by sending a low-voltage electrical current into the body to activate them. Because small nerve fibers control the sweat glands, if the nerves are not working properly, then the sweat glands will not respond properly. This test may cause the patient to feel a tingling sensation during the test. There should be no after-effects and no recovery time.

The disadvantage of this testing is that it is fairly new and not widely available. The Sudoscan device was only FDA-approved in 2013, and not many major medical centers have purchased them at the time of this writing. The good news is that if you can find a place to do the testing, it appears that most major insurances will cover it.

Another way to test for small fiber neuropathy is called QSART (Quantitative Sudomotor Axon Reflex Test). Like Sudoscan, this method stimulates the sweat glands. A medication is placed on an arm and leg at certain intervals and then sensors are placed over the medication. A small current is sent into the nerves and sweat gland response is evaluated by the sensors.

As with Sudoscan, this test is minimally invasive and potentially less painful than a punch biopsy. It also may be more readily available that Sudoscan, because the method has been around since the early 1980s. However, it can garner mixed results. My personal physician reported that several people who were tested this way (including me) had signs of nerve dysfunction at some sites but not others. Therefore, the test was inconclusive and the punch biopsy had to be done anyway to confirm the diagnosis. It's unclear at this time what causes these inconclusive results. Perhaps it was operator error, and the technician did not properly apply the medication or sensors. Or maybe this is a normal variation of small fiber neuropathy that we don't understand at this time.

Nonetheless, QSART can be a good place to start if this testing method is available. If you don't care about a 100% confirmed diagnosis, a patient and doctor who are both comfortable with it can start treatment right away after testing. Meanwhile, with punch biopsies, a pathology lab can take several weeks to give results.

Most medical centers that perform autonomic testing will have the equipment to do QSART. It is covered by most insurances and depending on how busy the hospital is, a neurologist can read and interpret the results immediately. There is typically no recovery time needed and no lasting side effects of testing.

When deciding which method to use to confirm a diagnosis of small fiber neuropathy, I recommend checking with your insurance to ensure that they consider the testing method valid. They are more likely to cover any subsequent treatment if they also support the validity of the diagnosis.

What causes small fiber neuropathy?

Small fiber neuropathy can be caused by mutations to certain genes.1 Other conditions can also cause small fiber neuropathy. Some of the most likely culprits are diabetes, Fabry disease,2 celiac disease, Sjogren syndrome, sarcoidosis, and HIV. Ehlers-Danlos Syndrome and joint hypermobility spectrum disorders also have a high occurrence of small fiber neuropathy. One article I read stated that 63% of people with EDS also have small fiber neuropathy. Another study with a relatively small cohort showed that 100% of participants tested positive for small fiber neuropathy.3

It is generally believed that the symptoms of small fiber neuropathy are caused by damage to the nerves. But as mentioned previously, this condition is poorly understood, so there may be other correlations that exist that we don't know about at this time.

If a physician suspects that there is a genetic component to a patient's neuropathy, they may order genetic testing to confirm.

How is small fiber neuropathy treated?

When someone is diagnosed, the first thing many doctors do is rule out another condition as the cause of small fiber neuropathy. For example, if the patient has untreated or poorly-controlled diabetes, then it is likely affecting the neuropathy symptoms. Getting diabetes under control would then help manage the neuropathy.

If there is no underlying cause or a condition that is difficult to control (such as Ehlers-Danlos Syndrome), then doctors will often go directly to treating neuropathy symptoms. The most common symptoms are neuropathic pain, numbness, and tingling, and the standard treatment is the use of medication. A 2012 study4 provides a table of recommended treatment modalities. Effectiveness varies based on the individual, so a patient and their care team may go through several drugs before finding one that works.

At times, small fiber neuropathy has a cause that does not respond well to typical treatments. For example, the neuropathic pain that stems from HIV or chemotherapy does not respond well to typical neuropathy treatment. This can be very frustrating for both the care provider and the patient, but if the symptoms are disruptive to normal activity, the patient should insist upon continued investigation and referral to other physicians as necessary.

Some non-pharmaceutical treatments have been used, such as acupuncture, physical therapy, and TENS machines.4 But there hasn't been much in the way of clinical trials for these modalities, so it's difficult to say how effective they are.

What makes small fiber neuropathy different from other types of neuropathy?

As the name suggests, small fiber neuropathy affects the small nerve fibers. 

Nerve fibers vary in size; large fiber neuropathy affects nerves that are at least five micrometers in diameter, and the axons (a projection of the nerve cell that conducts electrical impulses away from the nerve body or neuron) are covered in myelin (a sheath that insulates the axon and improves conductivity of the electrical impulses).

Large fiber neuropathy typically occurs when a joint, such as a vertebra from the spine, compresses the nerve. This reduces its conductivity and irritates the nerve, causing pain. The nerves start centrally and work their away out to the limbs, which is why pain from a pinched nerve in the spine can refer to an arm or leg.

Small nerve fibers are less than five micrometers in diameter. They have very thin myelin sheaths (C fibers) or no myelin at all. They are considered peripheral nerves. They are found in the arms, legs, and internal organs. Because nobody fully understands how small fiber dysfunction occurs, it's difficult to say how it differs from other neuropathies. However, it does appear to happen without compression from joints.

Can small fiber neuropathy be reversed?

In some cases, yes. It depends on the source of the neuropathy and how quickly it is addressed. If small fiber neuropathy is treated early enough, under certain circumstances, it's possible to reduce the symptoms. Nerves have the ability to heal themselves, assuming that they are no longer being affected by the underlying condition.

Is there a cure for small fiber neuropathy?

Unfortunately, there is little to no evidence of a cure at this time for small fiber neuropathy. There isn't much research yet into this condition, and with so little information, it's hard to treat, let alone cure.

Some common misconceptions about small fiber neuropathy

If someone has signs of nerve dysfunction, due to small fiber neuropathy being a rare disease, doctors are less likely to suspect it. Doctors testing for large fiber neurological dysfunction will not be likely to find any evidence of disease. They may then assume that there is no neuropathy because they don't know about small fiber neuropathy or how to test for it.

A person with small fiber neuropathy may have a normal neurological exam. A physical neurological exam evaluates motor function, which is primarily directed by large nerve fibers. 

A person who says they have numbness, tingling, or pain in their hands or feet may think they have a pinched nerve due to problems in their spine. If a doctor does not find problems in the spine, this does not exclude the diagnosis of small fiber neuropathy. The small fibers are found mostly in the periphery of the body, while the nerves in the spine are considered central nerves.

A normal MRI, X-Ray, or CT scan of the spine or other joints does not mean that you don't have small fiber neuropathy. These types of imaging are not sensitive enough to detect small nerve fibers.

A nerve conduction study or EMG cannot detect small fiber neuropathy. This test is designed to evaluate large nerve fibers; the chances that they will find abnormalities with the smaller nerve fibers is very low.

As mentioned in the section about how small fiber neuropathy is diagnosed, there are only a few reliable tests to confirm that someone has the condition. Having normal results from tests other than the ones listed above does not rule out the possibility of small fiber neuropathy.

That being said, doctors should also test for large fiber neuropathy to ensure that it is not also causing symptoms. It is possible to have both large and small-fiber nerve dysfunction. But if tests for large nerve fibers are negative, patients should ask for testing for small fiber neuropathy.

Small fiber neuropathy can be dangerous because it can progress if it goes untreated. Symptoms can become permanent and even sometimes start to affect larger nerve fibers.5

So if you have symptoms that indicate nerve dysfunction, please check with your doctor.

What it feels like to have small fiber neuropathy

The first thing I have to say about having small fiber neuropathy is how frustrating it is to get diagnosed. I have had a lot of imaging over the years, and while it was abnormal, none of it showed signs of a pinched nerve.

I complained for over 15 years of neuropathy. Doctors ordered nerve conduction studies, with needles, at least three times with normal results. They didn't know what else to do for me, so they gave up. During this time my symptoms persisted and progressed until the point where I started to have daily symptoms that interfered with my ability to live a normal life. Now, it may be too late to reverse any of my symptoms.

I have sharp, burning pain in my hands and feet. I also sometimes have shooting pain down my arms and legs or stabs of pain on my sides along my rib cage. Sometimes my torso feels itchy and burning, like when I had Shingles, but without the rash. 

There is also patchy tingling and numbness in my limbs, and sometimes at my hips. I explained to someone that it feels like ants are stomping all over my skin. My circulation is very poor so my extremities are often much colder than the rest of me.

I react poorly to extremes of heat or cold. Exposures to either can cause extreme pain and fatigue, to the point where I'm unable to stay awake. I've also been diagnosed with POTS, a type of dysautonomia, and the symptoms can sometimes overlap. That includes abnormal pulse, lightheadedness, and syncope (fainting) or near-syncope.

Sometimes, my skin is too painful to touch. Yet other things, I can't feel at all. For example, I can't sense a pinprick (like when I used to get acupuncture). Sometimes when touching something too hot, I can't feel it until it's already burned me.

Even though small fibers are not in charge of motor function, my neuropathy still affects my motor skills. Things drop from my hands because of numbness because I can't tell whether I'm gripping them properly or not. This can be dangerous when I'm trying to move hot food and it falls out of my hands and splatters on my skin. I no longer drive, at least in part because both my hands and feet go numb. Sharp pains and numbness in my feet make it difficult to walk.

Nighttime is particularly uncomfortable for me. The more activities I do (sitting in a car, walking or standing for even short amounts of time), the worse my symptoms are at night. The numbness and tingling in my legs and feet make it hard to find a good position to sleep.

Objectively, I have an abnormal QSART test and punch biopsies confirmed small fiber nerve dysfunction. An evaluation with a hand therapist showed that my grip strength is very poor.

My digestion and urinary function are also abnormal. These are said to be symptoms of small fiber neuropathy, but could also be from the other conditions I have.

Where can I get more information and support if I have small fiber neuropathy?

**Please note: the URLs listed are not clickable links. You can copy and paste them into your web browser if you wish to visit the site.**

The U.S. National Library of Medicine has a page about small fiber neuropathy: https://ghr.nlm.nih.gov/condition/small-fiber-neuropathy#definition.

The website Neuropathy Commons has a Neuropathy Overview page where both small and large fiber neuropathy are discussed: https://neuropathycommons.org/neuropathy/neuropathy-overview?fbclid=IwAR0DzAKfD24-P9MKciKFKIaoRj2lHPej2C1Lid9UbXX0CBTpP8HI0SkHYto

Dr. Anne Oaklander, a neuropathologist from Massachusetts General Hospital/Harvard Medical School, did an hour-long presentation about small fiber neuropathy and its relationship with fibromyalgia: https://youtu.be/s66LvWQ5Qso

If you go to places like Facebook, Inspire, and The Mighty, they will all probably have support groups you can join for free. These are great places to talk to other people who understand what you're going through. They can also be great resources for recommendations on experts in diagnosing and treating small fiber neuropathy, especially if the support group has a local chapter.

Lastly, if you want to help the cause to find better treatment for small fiber neuropathy for yourself and others, consider going to www.clinicaltrials.gov to look for research studies you might qualify for.

1. https://ghr.nlm.nih.gov/condition/small-fiber-neuropathy#genes
2. https://ghr.nlm.nih.gov/condition/fabry-disease
3. https://n.neurology.org/content/87/2/155
4. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3086960/
5. https://www.health.harvard.edu/diseases-and-conditions/new-thinking-on-peripheral-neuropathy