Arsenical keratosis
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Arsenical keratosis (AK) is growth of keratin on the skin caused by arsenic,Freedberg, et al. (2003). Fitzpatrick's Dermatology in General Medicine. (6th ed.). McGraw-Hill. {{ISBN|0-07-138076-0}}.{{rp|725}} which occurs naturally in the Earth's crust and is widely distributed in the environment,{{cite journal |vauthors=Duker AA, Carranza EJ, Hale M |title=Arsenic geochemistry and health |journal=Environ Int |volume=31 |issue=5 |pages=631–41 |date=July 2005 |pmid=15910959 |doi=10.1016/j.envint.2004.10.020 }} Arsenical compounds are used in industrial, agricultural, and medicinal substances. Arsenic is also found to be an environmental contaminant in drinking water (well water) and an occupational hazard for miners and glass workers.{{cite book |author=James, William D. |author2=Berger, Timothy G. |title=Andrews' Diseases of the Skin: clinical Dermatology |publisher=Saunders Elsevier |year=2006 |isbn=0-7216-2921-0 |display-authors=etal}}{{rp|640}} Arsenic may also causes other conditions including: Bowen's disease,{{cite journal |vauthors=Yerebakan O, Ermis O, Yilmaz E, Basaran E |title=Treatment of arsenical keratosis and Bowen's disease with acitretin |journal=Int. J. Dermatol. |volume=41 |issue=2 |pages=84–7 |date=February 2002 |pmid=11982642 |doi= 10.1046/j.1365-4362.2002.01372.x|doi-access=free }} cardiovascular diseases, developmental abnormalities, neurologic and neurobehavioral disorders, diabetes, hearing loss, hematologic disorders, and various types of cancer.{{cite journal |vauthors=Tchounwou PB, Centeno JA, Patlolla AK |title=Arsenic toxicity, mutagenesis, and carcinogenesis--a health risk assessment and management approach |journal=Mol. Cell. Biochem. |volume=255 |issue=1–2 |pages=47–55 |date=January 2004 |pmid=14971645 |doi= 10.1023/B:MCBI.0000007260.32981.b9|url=http://www.kluweronline.com/art.pdf?issn=0300-8177&volume=255&page=47 }} Arsenical keratoses may persist indefinitely, and some may develop into invasive squamous cell carcinoma. Metastatic arsenic squamous cell carcinoma and arsenic-induced malignancies in internal organs such as the bladder, kidney, skin, liver, and colon, may result in death.
Definition
AK is a pre-cancerous skin condition caused by longterm poisoning with arsenic.{{cite journal |last1=Shajil |first1=Chandana |last2=Mahabal |first2=Gauri D. |title=Arsenical Keratosis |journal=StatPearls |date=2024 |url=https://www.ncbi.nlm.nih.gov/books/NBK560570/#:~:text=Arsenical%20keratosis%20is%20a%20precancerous,affecting%20the%20palms%20and%20soles. |publisher=StatPearls Publishing}}
Signs and symptoms
AK typically presents with small yellow corn-like warty bumps in the skin preceded by dark marks.{{cite book |last1=DE |first1=Elder |last2=D |first2=Massi |last3=RA |first3=Scolyer |last4=R |first4=Willemze |title=WHO Classification of Skin Tumours |date=2018 |publisher=World Health Organization |location=Lyon (France) |isbn=978-92-832-2440-2 |edition=4th |volume=11 |url=https://publications.iarc.fr/Book-And-Report-Series/Who-Classification-Of-Tumours/WHO-Classification-Of-Skin-Tumours-2018 |language=en |chapter=Premalignant keratoses: Arsenical keratosis |pages=52-53 }} It is frequently seen on the sides of the palms of hands, and base and sides of fingers and feet. The dark marks may look like 'raindrops' and these may be associated with Mees' lines across the nails. The bumps typically appear 20 to 30 years after exposure to arsenic from usually a herbal medicine or contaminated water from wells.
AK may precede the development of squamous cell carcinoma or basal cell carcinoma.{{cite book |last1=James |first1=William D. |last2=Elston |first2=Dirk |last3=Treat |first3=James R. |last4=Rosenbach |first4=Misha A. |last5=Neuhaus |first5=Isaac |title=Andrews' Diseases of the Skin: Clinical Dermatology |date=2020 |publisher=Elsevier |location=Edinburgh |isbn=978-0-323-54753-6 |pages=643 |edition=13th |chapter-url=https://books.google.com/books?id=UEaEDwAAQBAJ&pg=PA643 |language=en |chapter=29. Epidermal nevi, neoplasms, and cysts: Arsenical keratosis }}
Pathophysiology
Arsenite impairs nucleotide excision repair,{{cite journal |vauthors=Hartwig A, Groblinghoff UD, Beyersmann D, Natarajan AT, Filon R, Mullenders LH |title=Interaction of arsenic(III) with nucleotide excision repair in UV-irradiated human fibroblasts |journal=Carcinogenesis |volume=18 |issue=2 |pages=399–405 |date=February 1997 |pmid=9054635 |doi= 10.1093/carcin/18.2.399|doi-access=free }} and it may also affect gene expression by increasing or decreasing DNA methylation. The high affinity of arsenic for sulfhydryl groups makes keratin-rich cells (e.g., epidermal keratinocytes) a sensitive target for arsenic-induced toxicity. Arsenic has been shown to alter epidermal keratinocyte differentiation processes,{{cite journal |vauthors=Kachinskas DJ, Phillips MA, Qin Q, Stokes JD, Rice RH |title=Arsenate perturbation of human keratinocyte differentiation |journal=Cell Growth Differ. |volume=5 |issue=11 |pages=1235–41 |date=November 1994 |pmid=7848924 |url=http://cgd.aacrjournals.org/cgi/pmidlookup?view=long&pmid=7848924 |access-date=2009-02-09 |archive-date=2013-02-23 |archive-url=https://archive.today/20130223104217/http://cgd.aacrjournals.org/cgi/pmidlookup?view=long&pmid=7848924 |url-status=dead }} induce overexpression of growth factors,{{cite journal |vauthors=Germolec DR, Yoshida T, Gaido K |title=Arsenic induces overexpression of growth factors in human keratinocytes |journal=Toxicol. Appl. Pharmacol. |volume=141 |issue=1 |pages=308–18 |date=November 1996 |pmid=8917704 |doi=10.1006/taap.1996.0288 |display-authors=etal}} and enhance proliferation of human keratinocytes.
Differential diagnosis
Actinic keratosis, seborrhoic keratosis, and squamous cell carcinoma in situ may appear similar.
Treatment
- A chelating agent (e.g., dimercaprol) may be helpful to correct acute arsenic exposure, but it has minimal or no effect for patients who had arsenic exposure a long time ago.
- Oral retinoids (e.g., acitretin,{{cite journal |vauthors=Son SB, Song HJ, Son SW |title=Successful treatment of palmoplantar arsenical keratosis with a combination of keratolytics and low-dose acitretin |journal=Clin. Exp. Dermatol. |volume=33 |issue=2 |pages=202–4 |date=March 2008 |pmid=18039342 |doi=10.1111/j.1365-2230.2007.02596.x |url=http://www3.interscience.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=0307-6938&date=2008&volume=33&issue=2&spage=202 |archive-url=https://archive.today/20130105085335/http://www3.interscience.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=0307-6938&date=2008&volume=33&issue=2&spage=202 |url-status=dead |archive-date=2013-01-05 |url-access=subscription }}{{cite journal|vauthors=Khandpur S, Sharma VK |title=Successful treatment of multiple premalignant and malignant lesions in arsenical keratosis with a combination of acitretin and intralesional 5-fluorouracil |journal=J. Dermatol. |volume=30 |issue=10 |pages=730–4 |date=October 2003 |pmid=14684956 |doi=10.1111/j.1346-8138.2003.tb00468.x |url=http://www.dermatol.or.jp/Journal/JD/2003/030100730.html |archive-url=https://web.archive.org/web/20110722120942/http://www.dermatol.or.jp/Journal/JD/2003/030100730.html |url-status=dead |archive-date=2011-07-22 |url-access=subscription }} etretinate{{cite journal |vauthors=Sharma SC, Simpson NB |title=Treatment of arsenical keratosis with etretinate |journal=Acta Derm. Venereol. |volume=63 |issue=5 |pages=449–52 |year=1983 |pmid=6197851 }}) may be helpful in treating arsenic-induced cutaneous lesions and in reducing the risk of cutaneous and internal malignancy formation, especially in Bowman's disease.
- Topical 5-fluorouracil cream or 5% imiquimod cream{{cite journal|author=Boonchai W |title=Treatment of precancerous and cancerous lesions of chronic arsenicism with 5% imiquimod cream |journal=Arch Dermatol |volume=142 |issue=4 |pages=531–2 |date=April 2006 |pmid=16618886 |doi=10.1001/archderm.142.4.531}} may be useful in treating arsenical keratoses and Bowen's disease.