The Impact of Morphometric Skin Punch Biopsy Analysis for a Small Nerve Fiber Involvement in Children with Pain Syndrome

Background: Pain syndromes in children are often unexplained and therefore difficult to treat. A small fiber neuropathy (SFN) is associated with pain and an involvement of small nerve fibers might be contributing to the symptoms in some of these patients. The diagnosis of SFN by conventional neurophysiological techniques is difficult. In adults, intraepidermal nerve fiber density (IENFD) analysis in small punch skin biopsies is the gold standard for diagnosing SFN. The aim of the study is to investigate whether this method is also suitable in children with otherwise-unexplained pain.

Methods: Small skin punch biopsies were taken at the distal leg in eight patients with chronic pain ranging from 7 to 17 years. Five of eight patients complained about generalized pain and three of eight complained about pain in the legs and hands only. Four of eight patients had restless leg syndrome. The samples were fixed in Zamboni’s solution and immunofluorescence staining with antibodies against PGP 9.5 and myelin basic protein was performed. IENFD, myelinated and unmyelinated dermal nerve fibers as well as sweat gland nerve fiber density (SGNFD) were analyzed using quantitative morphometric methods.

Results: IENFD was reduced severely in six of eight and moderately in two of eight patients compared with normal values. Additionally, SGNFD was reduced in all the eight patients and the number of dermal myelinated nerve bundles in seven of the eight biopsies.

Conclusion: Morphometric analysis of skin punch biopsies can be helpful in disclosing the involvement of small nerve fibers in children with otherwise unexplained pain syndrome and may help with a disease modifying treatment.