title: Peripheral neuropathic changes in pachyonychia congenita.
abstract: We compared patterns of intraepidermal nerve fibers and mechanoreceptors from affected and unaffected plantar skin from patients with pachyonychia congenita (PC) and control subjects. Plantar biopsies from 10 genetically confirmed patients with PC (with a mutation in KRT6A) were performed at the ball of the foot (affected skin) and the arch (unaffected) and were compared to biopsies from corresponding locations in 10 control subjects. Tissue was processed to visualize intraepidermal nerve fibers (IENF) (PGP9.5), subsets of IENF (CGRP, substance P, tyrosine hydroxylase), myelinated nerve fiber (neurofilament H, NFH), blood vessels (CD31), Meissner corpuscles, and Merkel cells (MCs). Structures were quantified using stereology or validated quantification methods. We observed that PC-affected plantar skin had significantly lower sweat gland innervation (sweat gland nerve fiber density) and reduced numbers of Meissner corpuscles compared to PC-unaffected or anatomically matched control skin. In contrast, Merkel cell densities and blood vessel counts were higher in PC-affected skin compared to either control or PC-unaffected skin. There were no differences in myelinated nerve fiber densities, SP, or CGRP between the groups. Pressure pain thresholds in PC-affected skin were lower compared to PC-unaffected and anatomically matched control skin. Additionally, MC densities in callused plantar skin from healthy runners with callus and one subject with a nonpainful palmoplantar keratoderma (AQP5 mutation) were similar to PC-unaffected and control skin consistent with callus alone not being sufficient to increase MC number. These findings suggest that alterations in PC extend beyond keratinocytes and may provide strategies to study neuropathic pain in PC.
authors: Department of Neurology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors: Baohan
authors: B
authors: Pan
authors: Department of Neurology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors: Kelly
authors: K
authors: Byrnes
authors: Pachyonychia Congenita Project, Salt Lake City, UT, USA.
authors: Mary
authors: M
authors: Schwartz
authors: Department of Dermatology, University of Utah Health Sciences Center, Salt Lake City, UT, USA.
authors: C David
authors: CD
authors: Hansen
authors: Department of Psychiatry, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors: Claudia M
authors: CM
authors: Campbell
authors: Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom.
authors: Malvina
authors: M
authors: Krupiczojc
authors: Departments of Neurosurgery, Biological Chemistry, Neuroscience, and the Neurosurgery Pain Research Institute, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors: Michael J
authors: MJ
authors: Caterina
authors: Department of Neurology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors: Michael
authors: M
authors: Polydefkis
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D051402:Aquaporin 5 / Q000235:genetics; D001706:Biopsy; D005260:Female; D006801:Humans; D053554:Keratin-20 / Q000378:metabolism; D053553:Keratin-6 / Q000235:genetics; D008297:Male; D018862:Merkel Cells / Q000473:pathology; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D009413:Nerve Fibers, Myelinated / Q000378:metabolism / Q000473:pathology*; D016900:Neurofilament Proteins / Q000378:metabolism; D053549:Pachyonychia Congenita / Q000150:complications* / Q000235:genetics; D017288:Pain Threshold / Q000502:physiology; D010523:Peripheral Nervous System Diseases / Q000209:etiology* / Q000473:pathology*; D012867:Skin / Q000294:innervation / Q000378:metabolism; D043222:Ubiquitin Thiolesterase / Q000378:metabolism
chemical_list: C496036:AQP5 protein, human; D051402:Aquaporin 5; C507499:KRT20 protein, human; C507569:KRT6A protein, human; D053554:Keratin-20; D053553:Keratin-6; D016900:Neurofilament Proteins; C482860:UCHL1 protein, human; C051774:neurofilament protein H; D043222:Ubiquitin Thiolesterase