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.

 描述（由适用提供）：医学上无法解释的慢性宽度疼痛（UCWP）是一种常见且残疾的症状，甚至会影响儿童和年轻人，使一些人在学校或工作中残疾。年轻的UCWP可能会破坏整个家庭，并造成终身障碍。 UCWP综合征通过包括纤维肌痛在内的各种名称。 2013年，我们发表了一项回顾性研究，对21岁之前开始的41例UCWP患者。我们报告说，大多数人都有小纤维多神经病（SFPN）的客观证据，这是其症状的生物学上合理的原因。最有用的测试是PGP9.5免疫标记的皮肤活检，可定量小纤维神经终结密度。一些患者似乎患有SFPN的dysimmune原因，但这远非确定。拟议的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，许多人都有舒张障碍原因的证据。我们的观察结果需要在较大的基于社区的样本中进行前瞻性测试，并确定诊断早期发作的小纤维多神经病（SFPN）的最佳方法，并评估如何随着时间的推移监测患者。用于诊断SFPN的测试并不广泛，尚未针对年轻患者进行规范。我们提供的证据表明，一半以上的SFPN患者在35岁以下的患者基于轴突少少年的正常成年人的数据时接受假阴性诊断。该项目解决了对UCWP年轻人目前几乎没有选择的年轻人的诊断SFPN的临床需求。它应该立即具有宽度临床影响。它还将为研究（包括治疗试验）的基础研究基础。这两者都需要严格诊断和纵向良好的患者，该项目应提供。目标1提案，以确定CWP年轻患者以及从社区招募的阳性和阴性对照中的早期发作SFPN的最佳客观测试。我们将重点关注推荐的测试，自主功能测试和皮肤活检，但还将研究较少的侵入性或更便宜的测试，例如体内角膜共聚焦显微镜，次要淀粉 - 碘汗水测试，新的问卷，新的问卷，以及Sudoscan，一种新的汗水，新的汗水。目的是制定最佳的测试，这些测试可以在多样性的环境中（包括低资源设置）应用。 AIM 2将使用实验室血液测试和对基于社区的同类的皮肤活检的皮肤病理学研究更严格地定义SFPN的医学原因。我们还将看看这些测试是否支持我们先前的发现，一半患有早期UCWP的人有SFPN的证据。 AIM 3将在上面定义的时间间隔内应用问卷和最佳测试，以前瞻性跟踪以不同方式进行治疗的SFPN患者，还将跟随未经治疗的SFPN患者收集有关早期发作SFPN的第一个自然史数据。这应该提供为未来的承诺治疗临床试验计划所需的信息。