Alexis Boneparth1, Shan Chen2, Daniel B Horton3, L Nandini Moorthy4, Ian Farquhar5, Heather M Downs5, Hang Lee6, Anne Louise Oaklander7. 1. A. Boneparth, MD, Department of Pediatrics, Columbia University Medical Center, New York, New York; ab4459@cumc.columbia.edu. 2. S. Chen, MD, PhD, Department of Neurology, Rutgers Robert Wood Johnson Medical School, New Brunswick, New Jersey. 3. D.B. Horton, MD, MSCE, Department of Pediatrics, Rutgers Robert Wood Johnson Medical School, New Brunswick, and Rutgers Center for Pharmacoepidemiology and Treatment Science, Institute for Health, Health Care Policy, and Aging Research, New Brunswick, and Department of Biostatistics and Epidemiology, Rutgers School of Public Health, Piscataway, New Jersey. 4. L.N. Moorthy, MD, MS, Department of Pediatrics, Division of Rheumatology, Rutgers Robert Wood Johnson Medical School, New Brunswick, New Jersey. 5. I. Farquhar, BA, H.M. Downs, BS, Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, Masschusetts. 6. H. Lee, PhD, Biostatistics Center, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts. 7. A.L. Oaklander, MD, PhD, Department of Neurology, Massachusetts General Hospital and Harvard Medical School, and Department of Pathology (Neuropathology), Massachusetts General Hospital, Boston, Massachusetts, USA.
Abstract
OBJECTIVE: Fibromyalgia (FM) is defined by idiopathic, chronic, widespread musculoskeletal pain. In adults with FM, a metaanalysis of lower-leg skin biopsy demonstrated 45% pooled prevalence of abnormally low epidermal neurite density (END). END < 5th centile of the normal distribution is the consensus diagnostic threshold for small-fiber neuropathy. However, the clinical significance of END findings in FM is unknown. Here, we examine the prevalence of small-fiber pathology in juvenile FM, which has not been studied previously. METHODS: We screened 21 patients aged 13-20 years with FM diagnosed by pediatric rheumatologists. Fifteen meeting the American College of Rheumatology criteria (modified for juvenile FM) underwent lower-leg measurements of END and completed validated questionnaires assessing pain, functional disability, and dysautonomia symptoms. The primary outcome was proportion of FM patients with END < 5th centile of age/sex/race-based laboratory norms. Cases were systematically matched by ethnicity, race, sex, and age to a group of previously biopsied healthy adolescents with selection blinded to biopsy results. All 23 controls matching demographic criteria were included. RESULTS: Among biopsied juvenile FM patients, 53% (8/15) had END < 5th centile vs 4% (1/23) of healthy controls (P < 0.001). Mean patient END was 273/mm2 skin surface (95% CI 198-389) vs 413/mm2 (95% CI 359-467, P < 0.001). As expected, patients with FM reported more functional disability, dysautonomia, and pain than healthy controls. CONCLUSION: Abnormal END reduction is common in adolescents with FM, with similar prevalence in adults with FM. More studies are needed to fully characterize the significance of low END in FM and to elucidate the clinical implications of these findings.
OBJECTIVE: Fibromyalgia (FM) is defined by idiopathic, chronic, widespread musculoskeletal pain. In adults with FM, a metaanalysis of lower-leg skin biopsy demonstrated 45% pooled prevalence of abnormally low epidermal neurite density (END). END < 5th centile of the normal distribution is the consensus diagnostic threshold for small-fiber neuropathy. However, the clinical significance of END findings in FM is unknown. Here, we examine the prevalence of small-fiber pathology in juvenile FM, which has not been studied previously. METHODS: We screened 21 patients aged 13-20 years with FM diagnosed by pediatric rheumatologists. Fifteen meeting the American College of Rheumatology criteria (modified for juvenile FM) underwent lower-leg measurements of END and completed validated questionnaires assessing pain, functional disability, and dysautonomia symptoms. The primary outcome was proportion of FM patients with END < 5th centile of age/sex/race-based laboratory norms. Cases were systematically matched by ethnicity, race, sex, and age to a group of previously biopsied healthy adolescents with selection blinded to biopsy results. All 23 controls matching demographic criteria were included. RESULTS: Among biopsied juvenile FM patients, 53% (8/15) had END < 5th centile vs 4% (1/23) of healthy controls (P < 0.001). Mean patient END was 273/mm2 skin surface (95% CI 198-389) vs 413/mm2 (95% CI 359-467, P < 0.001). As expected, patients with FM reported more functional disability, dysautonomia, and pain than healthy controls. CONCLUSION: Abnormal END reduction is common in adolescents with FM, with similar prevalence in adults with FM. More studies are needed to fully characterize the significance of low END in FM and to elucidate the clinical implications of these findings.
Authors: Susmita Kashikar-Zuck; Stacy R Flowers; Robyn Lewis Claar; Jessica W Guite; Deirdre E Logan; Anne M Lynch-Jordan; Tonya M Palermo; Anna C Wilson Journal: Pain Date: 2011-03-31 Impact factor: 6.961
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