Last updated:
June 08, 2021
Years published: 1988, 1989, 1991, 1992, 1993, 1997, 2006, 2021
NORD gratefully acknowledges Thalia Nguyen, MDCM Candidate, McGill University School of Medicine, and Peter R. Hull, MB.BCh. FFDerm(SA) FRCPC PhD, Professor of Medicine, Division of Clinical Dermatology and Cutaneous Science, Department of Medicine, Dalhousie University and NSHealth, Halifax, Nova Scotia for assistance in the preparation of this report.
Summary
Keratolytic winter erythema (KWE) is an extremely rare form of skin shedding that was first described in South Africa but has subsequently been identified in other countries. In such cases, a link to South Africa has NOT been determined. The disorder is characterized by periodic episodes of palmoplantar skin shedding preceded by redness and the appearance of dry superficial blisters. The peel is substantial and may be easily gripped. The peeling is enhanced by exposure to water. Symptoms may improve during pregnancy and with age. The disorder may worsen with cold weather and improve in the summer.
Introduction
KWE was first described in 1977 by Findlay et al. Many of the Afrikaner families seen could trace their family back to a town in the Western Cape Province of South Africa, called Oudtshoorn, hence the name Oudtshoorn skin or Oudtshoorn disease. In a genealogical study, the condition was traced to Francois Renier Duminy (born 1747 in Lorient, France), a ship captain who settled in South Africa in the late 1700s.
KWE is characterized by the cyclical patchy redness and thickening of the skin of the palms and soles, followed by the appearance dry blisters which subsequently peel in an expanding pattern. The shedding skin has a thickish peel. The revealed surface skin appears glazed. These signs first appear during infancy or childhood and the disorder usually improves with age. The condition may be worsened by cold weather or episodes of fever. Secondary infection may complicate the condition. In some patients, slowly enlarging circular red patches may develop, usually on the extremities. These slowly expand and have a trailing edge of peeling. Other frequently encountered associated symptoms include itching, excessive sweating (hyperhidrosis or palmoplantar sweating) and a strong unpleasant odor.
KWE is inherited and follows an autosomal mode of inheritance with males and females equally affected. It has been found to be associated with a duplication of an area of a chromosome that included an element known as an enhancer. This ‘switches on’ a nearby gene or genes. One of these appears to be the gene CTSB which is has been shown to be overexpressed. The protein produced by this gene is cathepsin B. This is an enzyme that plays an important role in proteolysis (breakdown of proteins) causing a major disruption to the epidermal cell’s normal growth and development. These damaged cells fail to mature properly and are pushed outwards, still retaining their nuclei and this forms the peel.
Furthermore, two different duplications have been discovered. The duplication found in the South African families is 7.67-kb in length while the duplication in Norwegian families is 15.93-kb. Both duplications overlap in the region of the enhancer. The genetic variation has not been determined for the families with KWE reported from Germany, Denmark or the USA.
In South Africa, families with KWE are scattered throughout the country and some families have emigrated to the UK and to other countries. The condition is much more common in South Africa owing to the founder effect. It affects families of both the white population and those of mixed racial descent. The patients in Germany, Denmark, Norway and the USA do not share the same ancestry.
The diagnosis of KWE is based on the clinical findings of cyclical peeling of skin on the palms and soles and a family history of this condition. In most patients, skin biopsies are not required for the diagnosis. Genetic testing is limited to research laboratories.
Treatment
There is currently no effective treatment for KWE. Topical steroids (anti-inflammatory preparation used to control many skin conditions) and retinoids (chemical compounds that are analogs of vitamin A) might help a little, but they can also aggravate it. Topical calciprotriol (a form of vitamin D) might also have minimal effect. Systemic steroids (anti-inflammatory derivatives of cortisol) have temporally resolved the circular lesions in a single patient. Measures to control sweating may be helpful. Photodynamic therapy has been used successfully in one patient.
Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site. There are currently no listed clinical trials for KWE.
For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:
Toll-free: (800) 411-1222
TTY: (866) 411-1010
Email: [email protected]
Some current clinical trials also are posted on the following page on the NORD website:
https://rarediseases.org/living-with-a-rare-disease/find-clinical-trials/
For information about clinical trials sponsored by private sources, contact:
https://www.centerwatch.com/
For more information about clinical trials conducted in Europe, contact:
https://www.clinicaltrialsregister.eu/
Textbooks
Champion RH, Burton JL, Ebling FJG., eds. Textbook of Dermatology. 5th ed. Blackwell Scientific Publications. London, UK; 1992:1352.
Reynolds CR, Vannest KJ, Fletcher-Janzen E. Encyclopedia of Special Education, Volume 2: A Reference for the Education of Children, Adolescents, and Adults Disabilities and Other Exceptional Individuals. John Wiley & Sons; 2018.
Journal Articles
Ajebo E, Wall WB, Davis LS. Chronic symmetrically distributed hyperpigmented plaques in a middle-age woman. JAAD Case Rep. 2019;5(3):249-251.
Ramsay M, Ngcungcu T, Grayson W. Keratolytic Winter Erythema: An Update. Dermatopathology (Basel). 2019;6(2):126-132.
Ngcungcu T, Oti M, Sitek JC, et al. Duplicated Enhancer Region Increases Expression of CTSB and Segregates with Keratolytic Winter Erythema in South African and Norwegian Families. Am J Hum Genet. 2017;100(5):737-750.
Pigors M, Sarig O, Heinz L, Plagnol V, Fischer J, Mohamad J, et al. Loss-of-function mutations in SERPINB8 linked to exfoliative ichthyosis with impaired mechanical stability of intercellular adhesions. Am J Hum Genet. 2016 Aug;99(2);430-6. Available from doi: 10.1016/j.ajhg.2016.06.004
Hull PR, Hobbs A, Aron S, Ramsay M. The elusive gene for keratolytic winter erythema. S Afr Med J. 2013;103(12 Suppl 1):961-965.
Pavlovic S, Krunic AL, Bulj TK, Medenica MM, Fong K, et al. Acral peeling skin syndrome: a clinically and genetically heterogenous disorder. Pediat Derm. 2012 May-Jun;29(3);258-63. Available form doi: 10.1111/j.1525-1470.2011.01563.x
Amin AN, DeGiovanni CV, Farrant PB, Hull PR, Woollons A. Photodynamic therapy for the treatment of keratolytic winter erythema. Clin Exp Dermatol. 2011 Aug;36(6):668-9
Kiritsi D, Cosgarea I, Franzke CW, Schumann H, Oji V, Kohlhase J, et al. Acral peeling skin syndrome with TGM5 gene mutations may resemble epidermolysis bullosa simplex in young individuals. J Invest Derm. 2010 Feb; 130(6);1741-6. Available from: doi: 10.1038/jid.2010.23
Degiovanni CV, Farrant PB, Howell S, Hull PR, Woollons A. Keratolytic winter erythema with facial involvement: a novel presentation. Clin Exp Dermatol. 2009;34(2):206-208
Kharfi M, El Fekih N, Ammar D, Jaafoura H, Schwonbeck S, van Steensel, MA, et al. A missense mutation in TGM5 causes acral peeling skin syndrome in a Tunisian family. J Invest Derm. 2009 Oct;129(10);2512-5.
Cassidy AJ, van Steensel MA, Steijlen PM, van Geel M, van der Velden J, Morley SM, et al. A homozygous missense mutation in TGM5 abolishes epidermal transglutaminase 5 activity and causes acral peeling skin syndrome. Am J Hum Genet. 2005 Dec 77(6);909-17. Available from: doi: 10.1086/497707
Appel S, Filter M, Reis A, et al. Physical and transcriptional map of the critical region for keratolytic winter erythema (KWE) on chromosome 8p22-p23 between D8S550 and D8S1759. Eur J Hum Genet. 2002;10:17-25.
Hashimoto K, Hamzavi I, Tanaka K, Shwayder T. Acral peeling skin syndrome. J Am Acad Derm. 2000 Dec 43(6);1112-9. Available from: https://doi.org/10.1067/mjd.2000.103645
Danielsen AG, Weismann K, Thomsen HK. Keratolytic winter erythema (keratolytic winter erythema): a case report from Denmark. J Eur Acad Dermatol Venereol. 2001;15:255.
Brusasco A, Veraldi S, Tadini G, et al. Localized peeling skin syndrome: case report with ultrastructural study. Br J Dermatol. 1998;139:492-95.
Shwayder T, Conn S, Lowe L. Acral peeling skin syndrome. Arch Derm [Internet]. 1997 Apr ;133(4);535-6. Available from: doi:10.1001/archderm.1997.03890400141031
Findlay GH, Nurse GT, Heyl T, et al. Keratolytic winter erythema or ‘Oudtshoorn skin’: a newly recognized inherited dermatosis prevalent in South Africa. S Afr Med J. 1977;52(22):871-874.
INTERNET
McKusick VA, ed. Keratolytic Winter Erythema. Online Mendelian Inheritance In Man (OMIM). The Johns Hopkins University. Entry Number 148370: Updated 08/29/2018. https://www.omim.org/entry/148370. Accessed June 7, 2021.
McKusick VA, ed. Peeling Skin Syndrome 5. Online Mendelian Inheritance in Man (OMIM). The Johns Hopkins University. Entry Number 617115 :Updated 09/13/2016. https://omim.org/entry/617115 Accessed June 7, 2021.
Ramsay M, Ngcungcu T. How a rare skin disease links South Africa to an 18th Century French seaman. The Conversation. June 4, 2017. https://theconversation.com/how-a-rare-skin-disease-links-south-africa-to-an-18th-century-french-seaman-77256. Accessed June 7, 2021.
Living with Keratolytic winter erythema / Oudtshoorn disease. Geni Family Tree. https://www.geni.com/projects/Living-with-Keratolytic-winter-erythema-Oudtshoorn-disease/43323. Accessed June 7, 2021.
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The Genetic and Rare Diseases Information Center (GARD) has information and resources for patients, caregivers, and families that may be helpful before and after diagnosis of this condition. GARD is a program of the National Center for Advancing Translational Sciences (NCATS), part of the National Institutes of Health (NIH).
View reportOrphanet has a summary about this condition that may include information on the diagnosis, care, and treatment as well as other resources. Some of the information and resources are available in languages other than English. The summary may include medical terms, so we encourage you to share and discuss this information with your doctor. Orphanet is the French National Institute for Health and Medical Research and the Health Programme of the European Union.
View reportOnline Mendelian Inheritance In Man (OMIM) has a summary of published research about this condition and includes references from the medical literature. The summary contains medical and scientific terms, so we encourage you to share and discuss this information with your doctor. OMIM is authored and edited at the McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine.
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