Evaluation of small-fiber polyneuropathy as a cause of chronic widespread pain in youth

小纤维多发性神经病作为青少年慢性广泛性疼痛病因的评估

• 批准号: 9126626
• 负责人: Anne Louise Oaklander
• 金额: $ 79.38万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-08-15 至 2020-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9126626
• 关键词: 1 year old; 21 year old; Address; Adrenal Cortex Hormones; Adult; Affect; Age; Analgesics; Autoimmune Process; Axon; Biopsy; Blood Tests; Child; Childhood; Clinical; Clinical Trials; Communities; Confocal Microscopy; Cornea; Data; Degenerative polyarthritis; Devices; Diagnosis; Diagnostic; Diagnostic tests; Disabled Persons; Disease; Distal; Epidemiology; Evaluation; Family; Feasibility Studies; Fiber; Fibromyalgia; Foundations; Future; Goals; Health; Hypersensitivity skin testing; Immune; Immunity; Inflammation; Investigation; Iodine; Laboratories; Language; Left; Life; Measurement; Measures; Medical; Methods; Minor; Modeling; Monitor; Morphine; Names; Natural History; Nerve Endings; Neuropathy; Pain; Pain Measurement; Pain Research; Pain management; Patient Monitoring; Patients; Pharmaceutical Preparations; Polyneuropathy; Population; Predictive Value; Prevalence; Publishing; Questionnaires; Recruitment Activity; Recurrence; Reporting; Research; Resources; Retrospective Studies; Sampling; Schools; Sensitivity and Specificity; Signs and Symptoms; Skin; Specificity; Starch; Sweat; Sweat test; Sweating; Symptoms; Syndrome; Teenagers; Testing; Time; Weaning; Work; Youth; base; chronic pain; chronic widespread pain; cohort; common symptom; cost; cost effective; density; diagnostic biomarker; disabling symptom; early onset; evidence base; evidence based guidelines; handicapping condition; improved; in vivo; prospective test; tool; treatment trial; university student; young adult

 DESCRIPTION (provided by applicant): Medically unexplained chronic widespread pain (uCWP) is a common and disabling symptom that can even affect children and young adults, leaving some disabled from school or work. UCWP in the young can disrupt entire families and cause life-long handicap. UCWP syndromes go by various names including fibromyalgia. In 2013 we published a retrospective study of 41 of our patients with uCWP that began before age 21. We reported that most had objective evidence of small-fiber polyneuropathy (SFPN), a biologically plausible cause of their symptoms. The most useful test was PGP9.5 immunolabeled skin biopsies, which permit quantitation of small-fiber nerve ending density. Some patients appeared to have dysimmune causes of their SFPN, but this was far from certain. The goal of the proposed research is to rigorously test our hypothesis that SFPN is a common cause of CWP in children and young adults and that many have evidence of dysimmune causes. Our observations need prospective testing in a larger community-based sample with determination of best methods for diagnosis of early-onset small-fiber polyneuropathy (SFPN) and assessment of how to monitor patients over time. The tests used to diagnose SFPN are not widely available, and have not been normed for young patients. We provide evidence that more than half of SFPN patients under age 35 receive false-negative diagnoses when they are based on data from older normal adults with far fewer axons. This project addresses the clinical need for better evidence-based methods for diagnosing SFPN in young people with uCWP who currently have few options. It should have immediate, widespread clinical impact. It will also lay foundations for research including treatment trials an basic investigation of mechanisms. Both require rigorously diagnosed and longitudinally well-characterized patients, which this project should provide. Aim 1 proposes to identify the best objective tests for early onset SFPN in young patients with CWP and in positive and negative controls recruited from the community. We will focus on the recommended tests, autonomic function testing and skin biopsy, but will also investigate less invasive or cheaper tests such as in vivo corneal confocal microscopy, the Minor starch-iodine sweat test, a new questionnaire, and Sudoscan, a new sweat-measuring device. The goal is to develop the best tests that can be applied in diverse circumstances, including low-resource settings. Aim 2 will more rigorously define the medical causes of SFPN using laboratory blood tests and dermatopathologic study of skin biopsies in community-based cohorts. We will also see if these tests support our prior finding that half of people with early-onset uCWP have evidence of SFPN. Aim 3 will apply the questionnaire and best tests developed above at defined intervals to prospectively track SFPN patients with various causes being treated in different ways, and will also follow untreated SFPN patients to gather the first natural history data about early-onset SFPN. This should provide the information needed to plan for future clinical trials of promising treatments.

 医学上无法解释的慢性广泛性疼痛（uCWP）是一种常见的致残症状，甚至可以影响儿童和年轻人，使一些残疾人无法上学或工作。年轻人的UCWP可能会破坏整个家庭并导致终身残疾。UCWP综合征有各种名称，包括纤维肌痛。2013年，我们发表了一项回顾性研究，研究对象是41例21岁之前开始的uCWP患者。我们报告了大多数患者有小纤维多发性神经病（SVPN）的客观证据，这是其症状的生物学合理原因。最有用的测试是PGP9.5免疫标记的皮肤活检，它允许定量的小纤维神经末梢密度。一些患者似乎有免疫障碍的原因，他们的SFPN，但这是远远不能肯定的。这项研究的目的是严格检验我们的假设，即SFPN是儿童和年轻人CWP的常见原因，并且许多人有免疫障碍原因的证据。我们的观察需要在更大的社区样本中进行前瞻性测试，确定诊断早发性小纤维多发性神经病（SVPN）的最佳方法，并评估如何随时间推移监测患者。用于诊断SFPN的测试尚未广泛使用，并且尚未针对年轻患者进行规范。我们提供的证据表明，超过一半的35岁以下的SFPN患者接受假阴性诊断时，他们的数据是基于年龄较大的正常成人少得多的轴突。 该项目解决了临床需要更好的循证方法来诊断患有uCWP的年轻人的SFPN，他们目前几乎没有选择。它应该有立即的，广泛的临床影响。它还将为研究奠定基础，包括治疗试验和机制的基本调查。两者都需要严格的诊断和纵向特征良好的患者，这一项目应该提供。 目的1提出了确定最佳的客观测试早发性SFPN在年轻患者CWP和阳性和阴性对照组从社区招募。我们将重点关注推荐的测试，自主神经功能测试和皮肤活检，但也将研究侵入性较小或更便宜的测试，如体内角膜共聚焦显微镜，小淀粉碘汗液测试，一个新的问卷，和Sudoscan，一个新的汗液测量设备。其目标是开发可在不同情况下应用的最佳测试，包括低资源环境。目标2将更严格地定义SFPN的医学原因，使用实验室血液检查和皮肤活检的皮肤病理学研究，以社区为基础的队列。我们还将看看这些测试是否支持我们先前的发现，即早发性uCWP患者中有一半有SFPN的证据。目标3将在规定的时间间隔内应用上述问卷和最佳测试，以前瞻性地跟踪以不同方式治疗的各种原因的SFPN患者，并且还将跟踪未经治疗的SFPN患者，以收集关于早发性SFPN的第一自然史数据。这将为计划未来有希望的治疗方法的临床试验提供所需的信息。