Small Fiber Neuropathy in Fibromyalgia and CFS

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Can small fiber neuropathy (SFN) 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.

SFPN may actually be the cause of fibromyalgia in some patients.

We’ve all been told fibromyalgia is a diagnosis of exclusion, but how thorough was your doctor in ruling out other conditions that mimic fibromyalgia? I’m sure we were all tested for rheumatoid arthritis, lupus, hypothyroidism, anemia and maybe Lyme disease, if we were lucky. But I bet there’s one test most of our doctors skipped: a skin biopsy for small-fiber polyneuropathy (SFPN).

SFPN is a neurological condition that causes chronic widespread pain and affects autonomic functions in the body, such as heart rate, blood pressure and sweating. Multiple studies have confirmed SFPN is extremely common in fibromyalgia patients. But Anne Louise Oaklander, associate professor of neurology at Harvard Medical School and director of Massachusetts General Hospital’s Nerve Unit, doesn’t think SFPN is just a co morbidity of fibromyalgia; her research suggests SFPN may actually be the cause of fibromyalgia in some patients.

Clinical triad

In 2013, Oaklander published a study that found 41 percent of fibromyalgia patients tested positive for SFPN using a skin biopsy versus only 3 percent of healthy controls. Fibromyalgia patients with SFPN were then tested for various causes of the neurological condition, and Oaklander found an interesting trend: The most common cause of SFPN found among patients with fibromyalgia was immune system dysfunction.

These findings could be a game changer for some fibromyalgia patients since SFPN can be treated, and in some cases, cured. “This provides some of the first objective evidence of a mechanism behind some cases of fibromyalgia,” Oaklander said in a press release. “Identifying an underlying cause is the first step towards finding better treatments.”

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


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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.

Skin biopsy

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.

SFPN can cause a range of symptoms reported by fibromyalgia patients

SFPN can cause a range of symptoms reported by fibromyalgia patients, including various manifestations of pain, chronic fatigue, digestive issues, brain fog, headaches and many others. A lot of these fibro patients I’ve seen may have gone to see dozens of different doctors over the years,” Oaklander said during an interview.

“What happens is [medical providers] haven’t focused on finding what’s called a unifying diagnosis. Instead, they tell the patient, ‘Oh, you have irritable bowel. Oh, you have interstitial cystitis. Oh, you have fibro. Oh, you have chronic fatigue.’ They don’t say, ‘Wait a minute, how likely is it that one person would have six different problems that are not related in some way?

Because these [small-fiber] nerves go everywhere in the body, one disease can cause many, many different symptoms. [Medical providers] have been looking at this from their own perspective of their medical specialty and not seeing the big picture. Small-fiber polyneuropathy brings the big picture in that it can explain a lot of different symptoms.”

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.


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  • Gupta D, Harney J. Small fiber neuropathy demonstrated in pain syndromes. Poster session presented at Annual Meeting of the American Academy of Neurology; 2010 Apr 10-17; Toronto, Ontario.
  • Small Fiber Neuropathy in Fibromyalgia and CFS by Adriene Dellwo via Verywell Health

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