Volume 10 Supplement 1
Proceedings of the Seventh Scientific Meeting of The TMJ Association
Small-fiber polyneuropathy (SFPN), a common underlying diagnosis in syndromes involving unexplained chronic pain and multi-system symptoms
© Oaklander et al; licensee BioMed Central Ltd. 2014
Published: 15 December 2014
Syndromes involving unexplained chronic widespread pain (CWP) and multi-system symptoms are common, with 1-5% prevalence for fibromyalgia alone. They more often affect females and cause disability and high costs [1–3]. Other common syndromes include chronic fatigue, seronegative Lyme, and Gulf War Illness. Fragmentary syndromes include TMJD, POTS, CRPS, irritable bowel). These syndromes are particularly devastating in children and young adults, where they interfere with education and development and disrupt entire families [4–6]. SFPN is known to cause CWP and multi-system complaints in older adults. Unlike the syndromes above, SFPN can be objectively diagnosed by measuring innervation in lower-leg skin biopsies, and autonomic functions testing (AFT) of heart rate, blood pressure and sweating . SFPN has several established causes including diabetes, infections, cancer, and toxins. Many causes are diagnosable, treatable, and sometimes curable . Our work suggests that unrecognized SFPN contributes to several syndromes involving CWP and multi-organ symptoms.
Materials and methods
With IRB permission, we retrospective analyzed the medical records of 41 patients with onset of unexplained CWP and multisymptoms before age 21; most had objective testing for SFPN . We also prospectively studied 27 adult patients with fibromyalgia and 30 healthy volunteers using history, examination, skin biopsies and AFT .
Retrospective chart review identified definite (in 59%) and probable SFPN (in 17%) among the young patients with onset before age 21 . We characterized the clinical features, diagnostic, and treatment options for this new early-onset SFPN. Studying children, who lacked the typical causes of late-onset SFPN, implicated autoimmune causality in most. Among patients treated with immunomodulatory therapies, pain and other symptoms improved in 2/3 . Among adults with fibromyalgia, 41% of skin biopsies from subjects with fibromyalgia vs. 3% of biopsies from controls were diagnostic for SFPN, and symptom and examination scores were higher in fibromyalgia subjects than in controls (all P ≤ 0.001) . All fibromyalgia patients diagnosed with SFPN then had blood tests for all known causes . None had diabetes but 62% had test-results consistent with dysimmunity, and some had genetic causes . Other laboratories have now also linked fibromyalgia to SFPN [11–15].
Some patients with unexplained widespread pain and multi-system syndromes such as fibromyalgia have objectively diagnosable SFPN. SFPN can affect children and young adults, not just older adults. Multiple lines of evidence suggest that early-onset SFPN has novel causes that can be treated. The prevalence of SFPN among TMJD patients is unstudied.
None of the authors have any conflicts of interest.
Supported in part by the NIH (NINDS K24NS059892, Department of Defense grant GW093049, and donations from the Bradley, Collman, and Cheever Powell family foundations.
- Lindell L, Bergman S, Petersson IF, Jacobsson LT, Herrstrom P: Prevalence of fibromyalgia and chronic widespread pain. Scand J Prim Health Care 2000, 18: 149–153. 10.1080/028134300453340PubMedView ArticleGoogle Scholar
- White KP, Speechley M, Harth M, Ostbye T: The London Fibromyalgia Epidemiology Study: the prevalence of fibromyalgia syndrome in London, Ontario. J Rheumatol 1999, 26: 1570–1576.PubMedGoogle Scholar
- White KP, Speechley M, Harth M, Ostbye T: The London Fibromyalgia Epidemiology Study: direct health care costs of fibromyalgia syndrome in London, Canada. J Rheumatol 1999, 26: 885–889.PubMedGoogle Scholar
- Buskila D: Pediatric fibromyalgia. Rheumatic Disease Clinics of North America 2009, 35: 253–261. 10.1016/j.rdc.2009.06.001PubMedView ArticleGoogle Scholar
- van Geelen SM, Bakker RJ, Kuis W, van de Putte EM: Adolescent chronic fatigue syndrome: A follow-up study. Arch Pediatr Adolesc Med 2010, 164: 810–814.PubMedView ArticleGoogle Scholar
- Mikkelsson M, El-Metwally A, Kautiainen H, Auvinen A, Macfarlane GJ, Salminen JJ: Onset, prognosis and risk factors for widespread pain in schoolchildren: A prospective 4-year follow-up study. Pain 2008, 138: 681–687. 10.1016/j.pain.2008.06.005PubMedView ArticleGoogle Scholar
- England JD, Gronseth GS, Franklin G, Carter GT, Kinsella LJ, Cohen JA, et al.: Practice Parameter: Evaluation of distal symmetric polyneuropathy: role of autonomic testing, nerve biopsy, and skin biopsy (an evidence-based review). Report of the American Academy of Neurology, American Association of Neuromuscular and Electrodiagnostic Medicine, and American Academy of Physical Medicine and Rehabilitation. Neurology 2009, 72: 177–184. 10.1212/01.wnl.0000336345.70511.0fPubMedView ArticleGoogle Scholar
- England JD, Gronseth GS, Franklin G, Carter GT, Kinsella LJ, Cohen JA, et al.: Practice Parameter: Evaluation of distal symmetric polyneuropathy: role of laboratory and genetic testing (an evidence-based review). Report of the AAN, AANEM, and AAPMR. Neurology 2009, 72: 185–192. 10.1212/01.wnl.0000336370.51010.a1PubMedView ArticleGoogle Scholar
- Oaklander AL, Klein MM: Evidence of small-fiber polyneuropathy in unexplained, juvenile-onset, widespread pain syndromes. Pediatrics 2013, 131: e1091-e1100. 10.1542/peds.2012-2597PubMed CentralPubMedView ArticleGoogle Scholar
- Oaklander AL, Herzog ZD, Downs HM, Klein MM: Objective evidence that small-fiber polyneuropathy underlies some illnesses currently labeled as fibromyalgia. Pain 2013.Google Scholar
- Üçeyler N, Zeller D, Kahn AK, Kewenig S, Kittel-Schneider S, Schmid A, et al.: Small fibre pathology in patients with fibromyalgia syndrome. Brain 2013.Google Scholar
- 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, 14: 895–915. 10.1111/pme.12139PubMedView ArticleGoogle Scholar
- Serra J, Collado A, Sola R, Antonelli F, Torres X, Salgueiro M, et al.: Hyperexcitable C nociceptors in fibromyalgia. Ann Neurol 2013.Google Scholar
- Giannoccaro MP, Donadio V, Incensi A, Avoni P, Liguori R: Small nerve fiber involvement in patients referred for fibromyalgia. Muscle Nerve 2013.Google Scholar
- Caro XJ, Winter EF: Evidence of abnormal epidermal nerve fiber density in fibromyalgia: Clinical and immunologic implications. Arthritis Rheumatol 2014.Google Scholar
This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.