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Small-fiber polyneuropathy and Fibromyalgia

There was an intriguing study done in the University of Würzburg and published in Brain march 9, 2013indicateing fibromyalgia pain is due to small fiber neuropathy. One did wonder at the time if this was a feature of fibromyalgia and if so what was the cause of the neuropathy. However what if it is the case that many people diagnosed with fibromyalgia actually in fact have small-fiber polyneuropahy? This can not only affect treatment dramatically but this is due to the fact small-fiber polyneuropahies are often caused by underlying conditions. If the recent studies on this are accurate then this is a common cause of misdiagnosis with fibromyalgia.

Study: Pain Journal: Objective evidence that small-fiber polyneuropathy underlies some illnesses currently labeled as fibromyalgia Painu June 5, 2013. By Anne Louise Oaklander, Zeva Daniela Herzog, Heather Downs and Max M. Klein. Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, 02114; Department of Pathology (Neuropathology), Massachusetts General Hospital, Boston, Massachusetts, 02114.
The study aimed to evaluate whether some people with fibromyalgia might in fact have small-fiber polyneuropathy (SFPN) as an actual cause to the illness. They reviewed 27 people with fibromyalgia and 30 controls for SFPN symptoms and markers. The study made use of Michigan Neuropathy Screening Instrument (MNSI), the Utah Early Neuropathy Scale (UENS),autonomic-function testing (AFT) and distal-leg neurodiagnostic skin biopsies.

Objective: Fibromyalgia is “a common, disabling, syndrome that includes chronic widespread pain plus other diverse symptoms. No specific objective abnormalities have been identified, precluding definitive testing, disease-modifying treatments, and identification of causes. In contrast, small-fiber polyneuropathy (SFPN), despite causing similar symptoms, is definitionally a disease caused by dysfunction and degeneration of peripheral small-fiber neurons. SFPN has established etiologies, some diagnosable and definitively treatable, e.g., diabetes.” (Pain Journal June, 5, 2013)
  • -41% of the skin biopsies from the FM subjects compared to only 3% from the control subjects were diagnostic for SFPN
  • -Michigan Neuropathy Screening Instrument (MNSI) and Utah Early Neuropathy Scale (UENS) scores were higher with fibromyalgia subjects than with control sets. (all P ≤ 0.001)
  • -autonomic-function testing (AFT) were of equally prevalent indicating FM related SFPN is primarily somatic.
  • -Blood tests from 13 FM subjects with the SFPN diagnostic skin biopsies revealed some insights into possible etiologies. All of the glucose tests were normal. Eight of the subjects had dysimmune markers. Two had hepatitis C serologies. One had a family genetic causality for the condition.
The diagnostic test results and markers were analyzed in a blinded fashion. Intraepidermal nerve fiber (IENF) densities were normalized to control values expected for age and sex."The diagnostic criterion, universally accepted around the world, is that someone whose nerve fiber density in their biopsy is below the fifth centile of predicted value is considered to have definite small-fiber polyneuropathy," Dr. Oaklander said. "The major finding of our study is that half of the cohort of fibromyalgia patients but none of an age-matched control group had evidence of nerve loss. And so to neurologists this meets the diagnostic criteria for small-fiber polyneuropathy."For the various tests overall, 46% of the patients with fibromyalgia and 17% of controls (P < .001) met the rigorous criteria for SFPN.More specifically, 40% of the patients with fibromyalgia met the SFPN diagnostic criteria upon IENF staining. Their IENF densities averaged 28% ± 6% of the predicted norm vs 47% ± 6% for controls (P < .02).Interestingly, there was no overall difference between patients with fibromyalgia and controls on autonomic function testing. Among the fibromyalgia cohort, 17% met diagnostic criteria for SFPN on autonomic testing vs 15% of controls (P = .67).” (Medscape News)
The study concluded that “These findings suggest that some pain patients labeled with "fibromyalgia" have unrecognized small-fiber polyneuropathy, a distinct disease that can be objectively tested for and sometimes definitively treated.” Indeed while it is a small study 41% is a significant number for people to not have this properly looked into as a cause for their symptoms.

Causes of small-fiber polyneuropathy
Since SFPN is often caused by an underlying condition if you know what that is it can treat that condition. In most cases that is diabetes or pre-diabetes. Other than diabetes there can be many conditions that can be the cause such as autoimmune conditions, neurotoxins, genetic mutations, tumors and it can also be unknown or idiopathic. It can have sensory loss or autonomic symptoms associated with the disease, such as gastrointestinal problems and abnormal blood pressure. People with fibromyalgia can often have many symptoms associated with the syndrome such as dizziness, vertigo, digestion complaints, cognitive dysfunction, weakness, numbness, fatigue, paraesthesia in the limbs and stress that lead to a diagnosis of the syndrome but in fact can be associated with SFPN. The treatment of fibromyalgia is vastly different than the treatment required for what may be the cause for the underlying condition for SFPN in a patient so proper diagnosis of the condition is vital.

We saw one study that see small fiber neurpathy with fibromyalgia patients. At the time it was fascinating research that it would have been absolutely interesting to see more of. This study is exactly that, another study showing again patients with FM showing not just small fiber neuropathy in a context of fibromyalgia but have instead of FM having SFPN. The fact that it was almost half of the subjects is astonishing. It makes one wonder if it was a larger study would we continue to see this percentage? If so, we are looking at a great deal of people with a misdiagnosis. How could this happen one wonders? Pretty easily when you consider every patient either gets diagnosed by a general practitioner or a rheumatologist who are ruling out different conditions such rheumatologic condition and other conditions that have been traditionally thought to be similar to FM. Patients do not get sent to neurologists despite evidence that fibromyalgia is a neurological condition and a neurologist would be the one to rule out other neurological conditions such as SFPN. It is therefore has never been something considered or ruled out. It would be hoped that it will be in the future however we must remember fibromyalgia treatment is no longer being passed to any specialist so it will have to be the patient demanded to be tested for this to rule it out. Certainly it seems logical to ask that doctors consider ruling this out because the test is simple enough, and objective, and if you have SFPN instead then your physician or neurologist must seek the cause of it and proper treatment of that cause.

Second Study 

Now a new study has come out to back this one up. In October issue of Seminars in Arthritis and Rheumatism looking at small fiber polyneuropathy (SFPN) in FM patients, or as they say, they may have been misdiagnosed. It involved 17 women and 17 control women.

Compared with healthy controls, patients with fibromyalgia had significantly thinner corneal stromal nerves (mean, 5.0 ± 1.0 µm vs 6.1 ± 1.3 µm, P = .01), as well as diminished sub-basal plexus nerve density per square millimeter (85 ± 29 vs 107 ± 26, P = .02).3
All but 1 patient in the fibromyalgia group had a Leeds assessment of neuropathic symptoms and signs (LANSS) score above the 12 cutoff point, suggesting a neuropathic component to their pain. Patients also had high Composite Autonomic Symptoms and Signs (COMPASS) tallies (54.6 ± 16.9), reflecting prominent autonomic nervous system dysfunction.
Further analysis revealed a link between nerve slenderness and LANSS neuropathic pain symptoms questionnaire scores (Fisher׳s exact test P = .007); similarly, an association was found between sub-basal nerve scarcity and LANSS score (Fisher׳s exact test P = .008).
“Our group suspects that fibromyalgia is a neuropathic pain syndrome. We believe it is primarily a peripheral nerve disorder that causes central nervous system sensitization. We think that fibromyalgia is sympathetically maintained based on stress as a triggering event; heart rate studies suggest ongoing sympathetic hyperactivity,” Dr. Martinez-Lavin stated Clinical Pain Advisor

They suggest up to 50% of FM patients have SFPN instead

1.           Bottom Line/Health, Fibromyalgia: New Research Helps Unravel the Mystery,
2.           Pain Research Forum, Multiple Studies, One Conclusion: Some Fibromyalgia Patients Show Peripheral Nerve Pathologies,
3.           Ramirez M, Martinez-Martinez LA, Hernandez-Quintela E, et al. Seminars in Arthritis and Rheumatism, Small fiber neuropathy in women with fibromyalgia. An in vivo assessment using corneal confocal bio-microscopy. Semin Arthritis Rheum. 2015 Oct;45(2):214-9. doi: 10.1016/j.semarthrit.2015.03.003. Epub 2015 Mar 19.
4.           Albrecht PJ, Hou Q, Argoff CE, Storey JR, Wymer JP, Rice FL. Excessive peptidergic sensory innervation of cutaneous arteriole-venule shunts (AVS) in the palmar glabrous skin of fibromyalgia patients: implications for widespread deep tissue pain and fatigue. Pain Med. 2013 Jun;14(6):895-915. doi: 10.1111/pme.12139.
5.           Oaklander AL, Herzog ZD, Downs HM, Klein MM. Objective evidence that small-fiber polyneuropathy underlies some illnesses currently labeled as fibromyalgia. Pain. 2013 Nov;154(11):2310-6. doi: 10.1016/j.pain.2013.06.001.

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