Diseases and Conditions

Can small fiber neuropathy mimic fibromyalgia?

July 19, 2017
Small fiber neuropathy can feel like your legs and feet are on fire. Can small fiber neuropathy mimic fibromyalgia?

Can small fiber neuropathy (SFN) mimic fibromyalgia?  The simple answer is yes, but it’s more complicated… So why does a rheumatologist care about small fiber neuropathy?  The answer is very simple.  Many people get referred to a rheumatologist for fibromyalgia, which is a disease that causes widespread pain, brain fog, non-restorative sleep, and various other unexplained symptoms such as headaches.  While fibromyalgia IS NOT an autoimmune disease, small fiber neuropathy can present very similarly but CAN BE caused by autoimmune diseases.

There’s a lot of controversy in the medical community about fibromyalgia.  One group believes that it’s a separate entity, some do not believe in its existence, and some people are somewhere in the middle.  Personally, I believe that fibromyalgia likely represents many diseases that we haven’t identified yet.  Until we can categorize them into distinct entities, we’re going to have a hard time understanding them, let alone come up with effective treatments.

First, let’s review the clinical criteria that doctors use to make a diagnosis of fibromyalgia.

2010 ACR criteria for fibromyalgia

Criteria A patient satisfies diagnostic criteria for fibromyalgia if the following 3 conditions are met:

  1. Widespread pain index (WPI) ≥ 7 and symptom severity (SS) scale score ≥5 or WPI 3–6 and SS scale score ≥ 9.
  2. Symptoms have been present at a similar level for at least 3 months.
  3. The patient does not have a disorder that would otherwise explain the pain.

Number #1 are various validated pain scores.  These are rarely used in clinic but are often used for clinical trials.  It helps researchers objectively quantify pain levels at any given time.  As you can see, we don’t use trigger points to check for fibromyalgia anymore.

Small fiber neuropathy in people with fibromyalgia

So is small fiber neuropathy a feature of fibromyalgia, just like it is for diseases like Sjogren’s syndrome or are patient’s with small fiber neuropathy mistakenly diagnosed with fibromyalgia?

In one study, 46 patients with fibromyalgia and 34 normal controls were tested for small fiber neuropathy with a specialized skin biopsy.  I’ll talk more about this later on.  The researchers measured pain intensity with a survey called the Neuropathic Pain Symptom Inventory. They found that 32.6% of patients with fibromyalgia had reduced nerve fiber density on their biopsy, i.e, they had small fiber neuropathy.  Interestingly, they also didn’t find any correlation between pain scores and nerve density.

This implies three things.  First of all, the level of pain and symptoms experienced by people with fibromyalgia was the same as those with small fiber neuropathy.  So you can’t distinguish between fibromyalgia and small fiber neuropathy based on symptoms alone.  Second, about 1/3 of people diagnosed with fibromyalgia have small fiber neuropathy.  Finally, having worse nerve density doesn’t necessarily mean you’ll experience more pain.  Other studies have also found similar results.

Now this still doesn’t answer all our questions but I think it’s safe to say that testing for small fiber neuropathy should happen when there is a clinical diagnosis of fibromyalgia. Now let’s talk about small fiber neuropathy.

What is Small Fiber Neuropathy?

Small fiber neuropathy results from damage to the small, unmyelinated nerve fibers that send pain and temperature and control autonomic functions like sweating.  The following are some of the symptoms caused by SFN:

  • Burning pain
  • Numbness and tingling
  • Pain that is out of proportion
  • Cramping
  • Unexplained itching
  • Lack of sweating
  • Temperature dysregulation
  • Dryness

How to diagnose small fiber neuropathy?

The first step to diagnose small fiber neuropathy is taking a care history, reviewing risk factors, and performing a detailed physical examination.  On physical exam, deep tendon reflexes (e.g., knee jerk reflex) are normal and there’s no loss of strength.  If there is a suspicion for SFN your doctor may send you for electrodiagnostic tests (EMGs).  These are colloquially called nerve conduction tests.

Small fiber neuropathy affects small myelinated A-delta and unmyelinated C fibers, NOT large fibers.  This means that EMGs are typically negative because these are good for looking for problems affecting large fibers like carpal tunnel syndrome.

One way to diagnose small fiber neuropathy is with a skin biopsy, more specifically epidermal nerve fiber density testing (ENFD).  This technique allows direct visualization, quantification, and morphologic assessment of small sensory fibers innervating the skin.  This technique has a sensitivity of 88% and a specificity of 95 – 97%.  In layman’s terms, the test will miss 12% of cases of small fiber neuropathy, but if the test is positive, there’s a 3 – 5% chance that it’s a mistake (false positive).   These are actually pretty good values.    A report by the European Federation of Neurological Societies states that ENFD is a reliable and efficient tool to assess for SFN.

How is epidermal fiber density testing done?

Epidermal fiber density testing is done by taking 2-4 three mm punch biopsies.  This test happens in clinic.  It’s quick and safe.  Your doctor can only do these in areas that have been validated: near the ankle, upper thigh, the foot, near the wrist, and the upper arm.

The biopsy is then sent to a specialized pathologist and stained with anti-protein gene product 9.5 antibody (PGP 9.5), which stains all the axons.  The pathologist can then painstakingly count all the nerves and calculate the density.  The density is then compared to age and sex matched control values to decide whether it’s abnormal.

Common causes of small fiber neuropathy

Once your doctor makes a diagnosis of small fiber neuropathy, then the question is whether there is an underlying cause.  About 50% of small fiber neuropathy cases are idiopathic, meaning that doctors can’t find an underlying cause.  As a result that leaves us with the other 50%.  Of those cases, the most common cause is diabetes mellitus.  In fact, autoimmune diseases make a relatively small proportion of cases, so it’s important to look for other causes first.  There are MANY other causes but these are some of the more common conditions that can cause small fiber neuropathy.

Non-autoimmune causes

  • Diabetes mellitus
  • Lyme disease
  • Hepatitis C infection
  • HIV
  • Celiac disease
  • Chronic kidney disease
  • Hypo/hyperthyroidism
  • Alcohol abuse
  • Medications, especially chemotherapy
  • Vitamin B12, B6, B1 deficiency
  • Paraneoplastic syndromes
  • Amyloidosis
  • Exposure to heavy metals

Autoimmune causes

  • Sjögren’s syndrome
  • Systemic lupus erythematosus
  • Sarcoidosis
  • Rheumatoid arthritis
  • Scleroderma
  • Inflammatory bowel disease (Crohn’s disease and ulcerative colitis)
  • Vasculitis
  • Psoriasis and psoriatic arthritis

Some genetic conditions can also cause small fiber neuropathy, like Fabry’s, but these are very rare.


I won’t talk too much about treatment because it really depends on the underlying cause.  If you’re dealing with an autoimmune disease… treat it.  Sometimes symptomatic treatment is also necessarily. The following are some medications that are often used:

  • Tricyclic antidepressants
  • Serotonin norephinephrine re-uptake inhibitors (SNRIs)
  • Pregabalin
  • Gabapentin
  • Topical lidocaine
  • Topical capsaicin

Doctors sometimes use intravenous immunoglobulin (IVIG) in extreme situation, particularly in situations where an autoimmune disease is the culprit. The evidence supporting this type of treatment isn’t great.  Sometimes it works, sometimes it doesn’t.  Moreover, there are no large randomized controlled studies looking at IVIG treatment for small fiber neuropathy.

Ultimately, we’re going to need to understand why and how small fiber neuropathy happens to come up with effective treatments.


I hope this helps explain how small fiber neuropathy (SFN) mimics fibromyalgia and why it’s important to distinguish between both.  For those who want to learn more about small fiber neuropathy and how to live with it, I’ve included a link to a great YouTube video.

Please leave your comments below!


Lauria G, Devigili G. Skin biopsy as a diagnostic tool in peripheral neuropathy. Nature Clinical Practice Neurology. 2007 Oct 3;3(10):546-57.

Devigili G, Tugnoli V, Penza P, Camozzi F Lombordi R, Milli G, Broglio , Granieri E, Lauria G. The diagnostic criteria for small fibre neuropathy : from symptoms to neuropathology. Brain 2008; 131; 1912-19.

Lauria G, Hsieh ST, Johansson O, Kennedy WR, Leger JM, Mellgren SI, Nolano M, Merkies IS, Polydefkis M, Smith AG, Sommer C, Valls-Sole J. European Federation of Neurological Societies/Peripheral Nerve Society Guideline on he use of skin biopsy in the diagnosis of small fiber neuropathy. Report of a joint task force of the European Federation of Neurological Societies and the peripheral nerve society. J Peripher Nerv Syst. 2010 Jun;15(2):79-92.

Giannoccaro MP, DonadioV, Incensi A, Avoni P, Liguori R. Small nerve fiber involvement in patients referred for fibromyalgia. Muscle Nerve. 2014 May;49(5):757-9.

Kosmidis ML, Koutsogeorgopoulou L, Alexopoulos H, Mamali I, Vlachoyiannopoulos PG, Voulgarelis M, Moutsopoulos HM, Tzioufas AG, Dalakas MC. Reduction of intraepidermal nerve fiber density (IENFD) in the skin biopsies of patients with fibromyalgia: a controlled study. J Neurol Sci. 2014 Dec 15;347(1-2):143-7.

Chan AC, Wilder-Smith EP. Small fiber neuropathy: getting bigger! Muscle Nerve. 2016 Feb 13. [Epub ahead of print]

UpToDate 2017

Uceyler N, Zeller D, Kahn AK, Kewenig S, Kittel-Schneider A, Casanova-Molla J, Reiners K, Sommer C. Small fibre pathology in patients with fibromyalgia syndrome. Brain. 2013 Jun;136(Pt 6):1857-67.

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Can small fiber neuropathy mimic fibromyalgia?
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  • Reply Laurel Barclay McIsaac January 17, 2018 at 2:54 pm

    When I had testing and the neurologist was stumped as to why I would have peripheral neuropathy, not being diabetic and it being small nerve he said. I offered Post Herpetic Neuropathy PHN as a possibility. I had a severe case of untreated shingles that started on my cranial nerves and nearly drove me to suicide before they worked their way through me to break out in a horrible rash on my leg that took another 10 days to stop the spread of. My life will never be the same. I’m wondering if you’ve looked at anything like this because I’m not the only PHN sufferer with this complaint. I’m on a support site, you’d be amazed!

    • Reply jessica@rheumdoctor.com January 17, 2018 at 8:03 pm

      I personally have not followed the literature regarding postherpetic neuralgia, however, it is a well known cause of small fiber neuropathy, and yes can be quite debilitating. Many of the medications used in rheumatology can increase the risk of shingles, so I’m always on the lookout for this. I’m also really excited about the new shingles vaccine, which is a NON-LIVE vaccine as opposed to the old one which was a live vaccine. Hoping this prevents people from getting shingles and possibly PHN. http://www.cnn.com/2017/10/25/health/cdc-new-shingles-vaccine/index.html

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