Panagiotis Kokotis1, Nurcan Üçeyler2, Christian Werner3, Georgios Tsivgoulis4, Nektaria Papanikola5, Aristeidis H Katsanos6, Nikos Karandreas7, Claudia Sommer2. 1. First Department of Neurology, "Aeginition University Hospital", School of Medicine, National and Κapodistrian University of Athens, Athens, Greece; Department of Neurology, University of Würzburg, Würzburg, Germany. Electronic address: pkokotis@med.uoa.gr. 2. Department of Neurology, University of Würzburg, Würzburg, Germany; Fabry Center for Interdisciplinary Therapy (FAZIT) University of Würzburg, Germany. 3. Department of Neurology, University of Würzburg, Würzburg, Germany. 4. Second Department of Neurology, School of Medicine, National and Capodistrian University of Athens, Athens, Greece. 5. School of Medicine, National and Kapodistrian University of Athens, Athens, Greece. 6. Department of Neurology, University of Ioannina School of Medicine, Ioannina, Greece. 7. First Department of Neurology, "Aeginition University Hospital", School of Medicine, National and Κapodistrian University of Athens, Athens, Greece.
Abstract
INTRODUCTION: Hypohidrosis and heat intolerance, frequently reported by men and women with Fabry disease (FD), is thought to be related not only to the deposition of globotriaosylceramide (Gb3) in eccrine sweat glands, but also to reduced sweat gland sympathetic innervation. METHODS: We performed a case-control study to compare the density of sweat gland innervation between patients with FD and healthy controls by examining lower leg skin punch biopsies. We used a standardized grid of circles superimposed upon the immunofluorescent specimen to create a simple pattern of circles over the sweat gland. Nerve fibers that crossed within the circles were manually counted ("crossed circles"). Nerve fibers that touched the edge of the circle but did not enter were spared ("uncrossed circles"). The percentage of crossed circles from all circles was determined. RESULTS: Biopsy specimens were available of 37 FD patients (median age 44 years, 19-67; n = 18 men) and 16 controls (median age 48 years, 24-83, n = 7 men). Totally there were 153 sweat glands from FD patients and 63 from controls, in which innervation was quantified. While mean sweat gland innervation per biopsy did not differ between the entire FD cohort and controls, data stratification for the reported sweating phenotype revealed a stepwise lower innervation in women with FD and hypohidrosis (n.s.) and anhidrosis (p < .05) compared to women reporting normal sweating. CONCLUSION: Sweat gland innervation is reduced in women with FD and anhidrosis compared to female patients without sweating impairment. Loss of sweat gland innervation may play a role in FD associated anhidrosis, at least in women.
INTRODUCTION:Hypohidrosis and heat intolerance, frequently reported by men and women with Fabry disease (FD), is thought to be related not only to the deposition of globotriaosylceramide (Gb3) in eccrine sweat glands, but also to reduced sweat gland sympathetic innervation. METHODS: We performed a case-control study to compare the density of sweat gland innervation between patients with FD and healthy controls by examining lower leg skin punch biopsies. We used a standardized grid of circles superimposed upon the immunofluorescent specimen to create a simple pattern of circles over the sweat gland. Nerve fibers that crossed within the circles were manually counted ("crossed circles"). Nerve fibers that touched the edge of the circle but did not enter were spared ("uncrossed circles"). The percentage of crossed circles from all circles was determined. RESULTS: Biopsy specimens were available of 37 FDpatients (median age 44 years, 19-67; n = 18 men) and 16 controls (median age 48 years, 24-83, n = 7 men). Totally there were 153 sweat glands from FDpatients and 63 from controls, in which innervation was quantified. While mean sweat gland innervation per biopsy did not differ between the entire FD cohort and controls, data stratification for the reported sweating phenotype revealed a stepwise lower innervation in women with FD and hypohidrosis (n.s.) and anhidrosis (p < .05) compared to women reporting normal sweating. CONCLUSION: Sweat gland innervation is reduced in women with FD and anhidrosis compared to female patients without sweating impairment. Loss of sweat gland innervation may play a role in FD associated anhidrosis, at least in women.