Skin punch biopsy in fibromyalgia patients

Routine use of punch biopsy to diagnose small fiber neuropathy in fibromyalgia patients – Clin Rheumatol  2014 Dec – free full-text /PMC4348533/

Recent work has demonstrated that approximately 50 % of patients diagnosed with fibromyalgia have damage to their small unmyelinated nerve fibers

A skin punch biopsy is a sensitive and specific diagnostic test for this damage as a reduction in nerve fiber density allows for the diagnosis of small fiber neuropathy.

Small fiber neuropathy is a disease with symptoms similar to fibromyalgia, but it often has a definable etiology

Identifying small fiber neuropathy and its underlying cause in fibromyalgia patients provides them with a succinct diagnosis, increases treatment options, and facilitates more specific studies for future therapeutics.


Fibromyalgia (FM) is the second most commonly diagnosed rheumatic disorder and is prevalent in 2 to 8 % of the population.

FM has been described as a clinical syndrome without any specific pathological findings to confirm a diagnosis.

The diagnosis of FM is particularly challenging as it commonly presents as a constellation of ill-defined symptoms producing a heterogeneous group of diseases with similar complaints.

For many patients, FM is a lifelong disorder, which many sufferers describe as being in a state of chronic pain.

Although the centralized nature of the pain implies that it originates in, or is amplified by, the central nervous system, it does not rule out peripheral nociceptor input as a contributing factor to the pain.

In fact, FM patients may experience more pain than typically expected from the contributing nociceptive input.

While FM is a syndrome with unidentifiable causes and pathophysiology, small fiber neuropathy (SFN) is a well-defined disorder with an identifiable pathogenesis and distinct underlying causes.

Symptoms of SFN usually present distally, manifesting as foot or leg pain. As SFN advances, the symptoms can spread proximally and involve the torso as well.

Typical symptoms of SFN include

  • paresthesia,
  • allodynia,
  • hyperesthesia, and
  • numbness.

Patients usually describe these sensations as painful, using terms such as burning or shooting. SFN patients often exhibit decreased pinprick sensation, hyperalgesia, or reduced thermal sensation in affected areas. However, sensory examination can be entirely normal in patients with SFN.

Additionally, skin changes of the affected area such as shiny skin or decreased moisture of the skin surface that leads to cracking may also be observed

Nerve fibers vary in size and function, with large myelinated A-alpha and A-beta fibers transmitting signals for proprioception and touch, while small myelinated A-delta fibers and unmyelinated C fibers transmit signals for pain and temperature.

SFN is caused by dysfunction and degeneration of the small unmyelinated C fibers and the thinly myelinated A-delta fibers.

The most frequent underlying cause of SFN is diabetes mellitus, with other causes including

  • impaired glucose tolerance,
  • vitamin deficiency (especially B12),
  • hepatitis C virus,
  • human immunodeficiency virus,
  • vasculitis,
  • celiac disease,
  • Sjorgen’s syndrome and
  • other autoimmune conditions,
  • hematological malignancies,
  • infections,
  • toxins (alcohol, medications), and
  • genetic mutations

These various conditions cause deterioration of the small nerves under the skin, leaving them damaged or dead, which then results in transmission of abnormal signals, and ultimately produces the burning or shooting pain associated with SFN.

Some of the available tools for testing have included the neuropathic pain inventory, quantitative sensory testing (QST), quantitative sudomotor axon reflex testing (QSART), electromyography, and nerve conduction studies.

Additionally, another diagnostic technique that has recently become widely and commercially available is the skin punch biopsy, which is used to measure epidermal nerve fiber density (ENFD)

FM/SFN diagnosis

In 2010, the ACR updated the FM criteria based on the Widespread Pain Index (WPI) and Symptoms Severity Scale. However, neither of these diagnostic criteria included any objective testing, forcing most clinicians to rely on subjective clinical complaints to diagnose their FM patients.

Due to the subjective diagnostic criteria, unknown causes, and non-specific symptoms, many clinicians consider FM to be a collection of ill-defined illnesses.

SFN is one such condition that, in the absence of an established objective diagnostic test, had been placed under the generic diagnosis of FM.

Patients with SFN have complaints of tingling, burning, and pain, which often is not recognized as a distinct condition and continues to be misinterpreted as FM.

With the most prominent symptom of SFN being only the “burning” pain, many patients describe no unique feature to distinguish SFN from other disorders.

To fill in the void of objective diagnostics for SFN, the skin punch biopsy technique was developed at the Karolinska Institute and later standardized at the University of Minnesota and at Johns Hopkins University.

These punch biopsies began to be included in the diagnostic workup of patients with suspected SFN.

This skin biopsy test was so specialized, however, that it remained solely in research hands for many years. It requires skilled and highly trained pathologists to process the sample and perform the very detailed task of manually counting the nerve fibers

It has, however, recently become commercially available at many academic centers and a few specialized labs in the USA.

Each lab has its own established cutoff values for ENFD (lab norms), which allow the practitioners to make a diagnosis of SFN with greater certainty. The convenience and ease of modern day shipping methods have made this test readily available to clinicians all over the country.

Over the past few years, skin punch biopsy testing has emerged as a diagnostic standard for SFN.

based on the vast experience of skin punch biopsies in 10 established laboratories worldwide, the 3-mm skin punch biopsy technique is a safe and minimally invasive procedure.

Specificity and sensitivity reported for the skin punch biopsy vary from 88 to 92 %.

an accurate diagnosis of SFN can prompt an in-depth assessment to uncover any underlying diseases as a possible root cause of the patient’s symptoms.

Incorporating the skin biopsy test as a routine evaluation for all FM patients may be beneficial in diagnosing SFN in approximately 50 % of patients.

Because the skin biopsy test can reliably demonstrate the loss of epidermal nerve fibers, it can not only confirm the diagnosis of SFN when clinical and neurophysiologic examinations are not adequately informative but also indicate progression of the disease by observing the reduction of ENFD over time with repeated skin biopsies


The skin punch biopsy is a simple, reliable, and definitive diagnostic test that is currently available for the measurement of ENFD for these patients

The biopsy can be performed in any physician’s office and shipped at room temperature to one of the few specialized labs that performs this type of testing.

The results give physicians an objective diagnostic tool to fulfill the diagnostic criteria for FM by excluding SFN as a cause of their patients’ pain and may allow for the detection of any underlying etiology and ultimately provide appropriate treatment and a possible cure for some of these SFN patients

The skin punch biopsy procedure is no longer an experimental test, it is endorsed by the major neurology and neuropathy associations nationally and internationally, making it reimbursable by most insurance carriers.

It is also easily performed in the clinic with minimal discomfort to the patient. The benefits of accurate diagnosis and the ease of testing make the skin punch biopsy an integral part of diagnostic testing for SFN among FM patients.

3 thoughts on “Skin punch biopsy in fibromyalgia patients

  1. Laura P. Schulman, MD, MA

    Many thoughts in response to this:
    1. Finally! This will be a beginning, to parse out the jumble of separate conditions currently lumped under “fm”
    2. Maybe this will lead to better treatments? Always good to know what we’re trying to treat…rather than simply throwing shit at a wall in hopes that some will stick.
    3. What about those who have total body pain but no sfn? Do they get tossed aside?
    4. What’s causing all this pain? Surely not the sea of toxic chemicals we live in…or the toxic lifestyle most humans live….
    The veterinarians, all the way from the CSU academics to the local vets, are always asking about possible toxic exposures. Why are the vets so concerned, but the human docs never even mention it? Why is it that in our training for human medicine, environmental medicine takes a back seat and many never get any training at all? Maybe it has to do with Big Donors and the owning of the government by Big Industry. 😯

    Liked by 1 person

    1. Zyp Czyk Post author

      Sadly, even science is now being corrupted by financial interests. We are living in an era where corporations are people and can throw their billions behind any scheme that increases their profit.

      We’ve become a third world country :-(

      Liked by 1 person


Other thoughts?

Fill in your details below or click an icon to log in: Logo

You are commenting using your account. Log Out /  Change )

Google photo

You are commenting using your Google account. Log Out /  Change )

Twitter picture

You are commenting using your Twitter account. Log Out /  Change )

Facebook photo

You are commenting using your Facebook account. Log Out /  Change )

Connecting to %s

This site uses Akismet to reduce spam. Learn how your comment data is processed.