- Introduction to Clinical Research Training
- Medical Education
- United Kingdom Clinical Scholars Research Training
- Vanderbilt Hall
- Financial Aid
- Office of the Registrar
- Campus Planning and Facilities
- Ombuds Office
- Committee on Microbiological Safety
- Human Resources
- HMS Foundation Funds
- Office for Academic and Clinical Affairs
- Joint Committee on the Status of Women
- The Academy
- Global Health Research Core
- Global Clinical Scholars Research Training Program
- HMA Standing Committee on Animals
- Office of Research Compliance
- Global & Community Health
- Harvard Medical School Event Calendar
- Contact @HMS
- Office of Diversity RIA Program
- Q&A Archive
- The Dean's Perspective
- Department of Pathology
- HMS NEXT
- Harvard Mahoney Neuroscience Institute
- OHRA Home
- Office of Research Subject Protection
- Tools and Technology
- Alumni Association
- HMS Information Technology
- HMS TransMed Program
- Office of Communications & External Relations
- test page
- Human Resources
- Jobs @ HMS
- Contact us
- Dental Medicine
- Harvard University
Explaining children's chronic pain
March 11, 2013
Harvard Medical School and Massachusetts General Hospital investigators have described what may be a newly identified disease that appears to explain some cases of widespread chronic pain and other symptoms in children and young adults. Their report, published online March 11 in the journal Pediatrics finds that most of a group of young patients seen at Mass General for chronic unexplained pain had test results indicating small-fiber polyneuropathy, a condition not previously reported in children. The investigators call this new syndrome juvenile-onset small-fiber polyneuropathy or JOSeFINE.
“We’ve found the beginnings of a way to better evaluate young patients with otherwise unexplained widespread body pain,” said Anne Louise Oaklander, HMS associate professor of neurology at Mass General and director of the hospital’s Nerve Injury Unit. She is corresponding author of the Pediatrics paper. “By identifying the tests that are useful for diagnosing this condition, we hope to reduce the use of unnecessary, expensive, sometimes painful and potentially harmful testing that many of these children have undergone.”
Small-fiber polyneuropathy (SFPN) involves widespread damage to the type of nerve fibers that carry pain signals from the skin and also control autonomic functions such as heart rate, blood pressure and sweating. Most commonly associated with diabetes, SFPN can be caused by other disorders in older adults or by exposure to toxic substances. Typical symptoms include chronic pain in several parts of the body, often beginning in the feet or lower legs, along with symptoms of autonomic dysfunction such as gastrointestinal problems, dizziness or fainting when standing, rapid heart rate, and changes in the appearance of skin. Specific diagnostic criteria have been established for SFPN, and accurate diagnosis can guide appropriate treatment choice.
Although polyneuropathy has been considered rare in children, occasional cases have been described. To get a better sense of the possible contribution of SFPN to chronic pain in children, Oaklander and her co-author Max Klein, HMS instructor in neurology at Mass General, reviewed the records of 41 patients treated by Oaklander between 2007 and 2011 for persistent widespread pain in several parts of the body that began before age 21. In a search for the cause of their symptoms, all of the patients had undergone a range of diagnostic tests at Mass General and other institutions.
Recommended diagnostic tests for SFPN include a type of skin biopsy that characterizes the number and condition of nerve fibers in the lower leg and autonomic function testing, including monitoring the heart rate and blood pressure when an individual breathes deeply, blows out when the airway is blocked or is placed on a tilt table. A control group of 38 age- and gender-matched volunteer children underwent the same autonomic function tests that the patients had received, and control values for neurodiagnostic skin biopsies were based on samples from healthy age- and gender-matched volunteers collected at Mass General.
The analysis revealed that 24 of the 41 patients met criteria for a diagnosis of SFPN, meaning that results of at least one test clearly indicated the presence of the disease. Of the remaining 17 patients, 16 were determined to possibly or probably have SFPN, based on test results that were less seriously abnormal. Among the autonomic function tests, sweat production—a sensitive diagnostic test for SFPN—was reduced in 82 percent of patients, compared with 34 percent of controls. In contrast, results of other tests that the patients had undergone—including magnetic resonance imaging, spinal taps and gastrointestinal endoscopy—provided no useful diagnostic information.
Many of the patients participating in the study had reported that their symptoms began after an earlier illness or injury. A third had some history of autoimmune illnesses, and around half had family histories of autoimmunity. Tests of blood and other bodily fluids revealed hints of disordered immunity—particularly low levels of complement, a protein involved in the innate immune system. Oaklander noted that these observations are preliminary and require further investigation.
“The importance that families placed on finding an accurate diagnosis and effective treatment for their sick children is illustrated by how many of them traveled thousands of miles, including some from other countries, in a desperate search for answers,” Oaklander said. “Because everyone wanted to help these children, they had undergone myriad tests, two-thirds had been hospitalized and some had tried many medications, usually without benefit.
“Based on our findings we now take a two-part approach to evaluating such patients: first, evaluation by a neurologist for the possibility of small-fiber neuropathy, and if that is confirmed, specific blood tests to pinpoint the cause. It’s important to consider this diagnosis, since there are treatments for many symptoms of neuropathy—including medications that increase blood pressure and improve gastrointestinal function—and for some of the underlying causes.”
The study was supported by U.S. Public Health Service grant K24NS059892, Department of Defense grant GW093049, and the Bradley and Curvey Family Foundations.
Adapted from a Mass General news release.