Keratolytic Winter Erythema: Make this Cold Case Warm Again
Dr. Ngcungcu first became interested in Keratolytic Winter Erythema disease (KWE) during her graduate studies at Sydney Brenner Institute for Molecular Bioscience in South Africa. She expended her research on finding the specific genetic mutation responsible for this rare skin disease at the Next Generation Scientist program at Novartis, Switzerland and continued to focus on this scientific mystery during her PhD at Sydney Brenner Institute 2. The discovery of a genetic mutation responsible for KWE by Dr. Ngcungcu, in collaboration with researchers from Europe and North America, was published in 2017 in the American Journal of Human Genetics 1.
Keratolytic winter erythema (KWE) is a rare disease of the skin that predominantly affects the Afrikaner population in South Africa. Affected patients experience recurrent episodes of erythema (skin redness) and epidermal peeling of large sections of thick skin on the palms and soles 3. These episodes are often preceded by severe itching, discomfort and hyperhidrosis (excessive sweating) with increased prominence and severity during winter months. KWE was brought by a small group of Dutch, German, and French settlers who arrived in South Africa in the 17th and 18th century and spread throughout the country 3. KWE was first described in 1977 but it took another 20 years to establish that KWE in South African families follows an autosomal dominant mode of transmission due to a defective gene on chromosome 8. Although doctors knew that KWE was an inherited genetic condition, the specific mutation that causes this rare skin condition was unknown 3.
“During her work in Switzerland she performed genetic sequencing on a number of patients with the disorder and their family members.”
Dr. Ngcungcu’s graduate studies led to the finding of the mutation responsible for KWE and included large-scale DNA sequencing, ancestry mapping, genomic comparison analysis, and global peer collaboration. During her work in Switzerland she performed genetic sequencing on a number of patients with the disorder and their family members. Her work was supported by other scientists that conducted research in this field, further strengthening her findings. A team of scientists working on KWE patients from two Norwegian families identified a genetic mutation that closely corresponded to that identified in the South African population. This combined evidence from South Africa and Norway enabled characterization of the genetic cause of KWE: a gene duplication. The duplications of the genetic material associated with the disease was linked with a gene encoding cathepsin B, an enzyme cysteine protease involved in keratinocyte homeostasis, which is the predominant cell type in the outermost layer of the skin 4.
“The significance Dr. Ngcungcu’s finding is that it enables dermatologists to make a definitive diagnosis of KWE in suspected patients using genetic testing.”
As with many genetic diseases, there is currently no cure for KWE. The significance Dr. Ngcungcu’s finding is that it enables dermatologists to make a definitive diagnosis of KWE in suspected patients using genetic testing. This is of great importance for both patients and scientists. A timely and accurate diagnosis will help patients to avoid unnecessary and inadequate treatments. Further, it will also enable scientists to better understand the maintenance of normal skin and recognition of similar skin diseases. Of equal importance is that this discovery is a starting point for developing possible treatments.
“Without the genetic knowledge discovered by Dr. Ngcungcu, in conjunction with a comprehensive understanding of the clinical presentation, these advancements would not be possible.
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As of recent, researchers are investigating the development of treatments focused on down regulating, or even suppressing, cathepsin B in individuals who suffer from KWE with the aim of reducing their symptoms and discomfort
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. Without the genetic knowledge discovered by Dr. Ngcungcu, in conjunction with a comprehensive understanding of the clinical presentation, these advancements would not be possible.
Mila Pastrak
Works Cited:
1. Ngcungcu, T., Oti, M., Sitek, J. C., Haukanes, B. I., & Linghu, B. (2017, April 27). Duplicated Enhancer Region Increases Expression of CTSB and Segregates with Keratolytic Winter Erythema in South African and Norwegian Families. Retrieved from https://www.sciencedirect.com/science/article/pii/S0002929717301441
2. University of the Witwatersrand. (2017, May 5). Scientists find genetic mutation responsible for rare skin disease in Afrikaners: Scientists have discovered the genetic mutation that causes the rare skin disease, keratolytic winter erythema (KWE), or 'Oudtshoorn skin', in Afrikaners. ScienceDaily. Retrieved February 22, 2019 from www.sciencedaily.com/releases/2017/05/170505103652.htm
3. Findlay, G. H., Nurse, G. T., Heyl, T., Hull, P. R., Jenkins, T., Klevansky, H., Morrison, J. G. L., Sher, J., Schultz, E. J., Swart, E., Venter, I. J., Whiting, D. A. Keratolytic winter erythema of 'Oudtshoorn skin': a newly recognized inherited dermatosis prevalent in South Africa. S. Afr. Med. J. 52: 871-874, 1977. [PubMed: 607500, related citations]
4. Huntington, M. K., Jassim, A. D. Genetic heterogeneity in keratolytic winter erythema (Oudtshoorn skin disease). Arch Derm. 142: 1073-1074, 2006. [PubMed: 16924068, related citations] [Full Text]
5. Ramsay M, Ngcungcu T, Grayson W. Keratolytic Winter Erythema: An Update. Dermatopathology. 2019;6(2):126-132. doi:10.1159/000496338
Cite this article:
Pastrak M. Keratolytic Winter Erythema: Make this Cold Case Warm Again. Illustrated by C. Qian. Rare Disease Review. October 2020. DOI: 10.13140/RG.2.2.23239.32165
