History

Arsenical keratoses, skin hyperpigmentation, and several types of skin cancers, including basal cell carcinoma, squamous cell carcinoma, and Merkel cell carcinoma,^[42]are skin lesions characteristic of long-term arsenic exposure. A long latency period (years to decades) occurs before the development of these cutaneous lesions. A study in West Bengal, India, has shown an average latency for skin lesions was 23 years from first exposure to arsenic.^{[37, 21]}Chronic arsenic exposure usually does not cause symptoms, and the skin lesions are usually the first sign to manifest clinically.

Complications

Arsenical keratosis occasionally evolves into carcinoma after a number of years. Bowen disease is the most common form of skin cancer induced by arsenic exposure. Arsenical squamous cell carcinoma occurs less frequently than Bowen disease, but it appears to be more aggressive than sun-induced squamous cell carcinoma. Previous reports have shown a much higher incidence of fatal metastases among patients with arsenical squamous cell carcinoma. Basal cell carcinoma is also associated with chronic arsenicalism. Skin cancers may develop in areas not exposed to sun light.

A variety of internal cancers due to arsenic ingestion have been reported. The presence of arsenic-induced cutaneous Bowen disease has been viewed as a cutaneous marker of possible internal malignancy, but this issue is still controversial.

Differential Diagnoses

Shajil C, Mahabal GD. Arsenical Keratosis. 2022 Jan. [QxMD MEDLINE Link]. [Full Text].
Yoshida T, Yamauchi H, Fan Sun G. Chronic health effects in people exposed to arsenic via the drinking water: dose-response relationships in review. Toxicol Appl Pharmacol. 2004 Aug 1. 198(3):243-52. [QxMD MEDLINE Link].
Islam R, Khan I, Hassan SN, McEvoy M, D'Este C, Attia J, et al. Association between type 2 diabetes and chronic arsenic exposure in drinking water: a cross sectional study in Bangladesh. Environ Health. 2012 Jun 7. 11:38. [QxMD MEDLINE Link].
Khatun M, Siddique AE, Wahed AS, et al. Association between serum periostin levels and the severity of arsenic-induced skin lesions. PLoS One. 2023. 18 (1):e0279893. [QxMD MEDLINE Link]. [Full Text].
Ahmed TS, Misbahuddin M. Role of linoleic acid in arsenical palmar keratosis. Int J Dermatol. 2016 Mar. 55 (3):289-95. [QxMD MEDLINE Link].
WashingtonDeceit. Dermatopathology of arsenical keratosis. YouTube. Available at http://www.youtube.com/watch?v=xBreXMMHmLU. Accessed: February 26, 2008.
Kjerkegaard UK, Heje JM, Vestergaard C, Stausbøl-Grøn B, Stolle LB. [Arsenical keratosis treated by dermatome shaving.]. Ugeskr Laeger. 2014 May 5. 176(19):[QxMD MEDLINE Link].
Son SB, Song HJ, Son SW. Successful treatment of palmoplantar arsenical keratosis with a combination of keratolytics and low-dose acitretin. Clin Exp Dermatol. 2008 Mar. 33(2):202-4. [QxMD MEDLINE Link].
Yerebakan O, Ermis O, Yilmaz E, Basaran E. Treatment of arsenical keratosis and Bowen's disease with acitretin. Int J Dermatol. 2002 Feb. 41(2):84-7. [QxMD MEDLINE Link].
Boonchai W. Treatment of precancerous and cancerous lesions of chronic arsenicism with 5% imiquimod cream. Arch Dermatol. 2006 Apr. 142(4):531-2. [QxMD MEDLINE Link].
Tapio S, Grosche B. Arsenic in the aetiology of cancer. Mutat Res. 2006 Jun. 612(3):215-46. [QxMD MEDLINE Link].
Hartwig A, Groblinghoff UD, Beyersmann D, Natarajan AT, Filon R, Mullenders LH. Interaction of arsenic(III) with nucleotide excision repair in UV-irradiated human fibroblasts. Carcinogenesis. 1997 Feb. 18(2):399-405. [QxMD MEDLINE Link].
Jha AN, Noditi M, Nilsson R, Natarajan AT. Genotoxic effects of sodium arsenite on human cells. Mutat Res. 1992 Dec 16. 284(2):215-21. [QxMD MEDLINE Link].
Zhao CQ, Young MR, Diwan BA, Coogan TP, Waalkes MP. Association of arsenic-induced malignant transformation with DNA hypomethylation and aberrant gene expression. Proc Natl Acad Sci U S A. 1997 Sep 30. 94(20):10907-12. [QxMD MEDLINE Link].
Kachinskas DJ, Phillips MA, Qin Q, Stokes JD, Rice RH. Arsenate perturbation of human keratinocyte differentiation. Cell Growth Differ. 1994 Nov. 5(11):1235-41. [QxMD MEDLINE Link].
Germolec DR, Yoshida T, Gaido K, et al. Arsenic induces overexpression of growth factors in human keratinocytes. Toxicol Appl Pharmacol. 1996 Nov. 141(1):308-18. [QxMD MEDLINE Link].
Chen Y, Parvez F, Gamble M, Islam T, Ahmed A, Argos M. Arsenic exposure at low-to-moderate levels and skin lesions, arsenic metabolism, neurological functions, and biomarkers for respiratory and cardiovascular diseases: review of recent findings from the Health Effects of Arsenic Longitudinal Study (HEALS) in Bangladesh. Toxicol Appl Pharmacol. 2009 Sep 1. 239(2):184-92. [QxMD MEDLINE Link].
Ghosh P, Banerjee M, Giri AK, Ray K. Toxicogenomics of arsenic: classical ideas and recent advances. Mutat Res. 2008 Sep-Oct. 659(3):293-301. [QxMD MEDLINE Link].
Madhyastha H, Madhyastha R, Nakajima Y, Maruyama M. Deciphering the molecular events during arsenic induced transcription signal cascade activation in cellular milieu. Biometals. 2018 Feb. 31 (1):7-15. [QxMD MEDLINE Link].
Banerjee M, Sarma N, Biswas R, Roy J, Mukherjee A, Giri AK. DNA repair deficiency leads to susceptibility to develop arsenic-induced premalignant skin lesions. Int J Cancer. 2008 Jul 15. 123(2):283-7. [QxMD MEDLINE Link].
Smith AH, Steinmaus CM. Health effects of arsenic and chromium in drinking water: recent human findings. Annu Rev Public Health. 2009 Apr 29. 30:107-22. [QxMD MEDLINE Link].
Merck Pharmaceuticals. Merck's Manual of the Materia Medica. 1st ed. Whitehouse Station, NJ: 1899.
Tay CH. Cutaneous manifestations of arsenic poisoning due to certain Chinese herbal medicine. Australas J Dermatol. 1974 Dec. 15(3):121-31. [QxMD MEDLINE Link].
Tay CH, Seah CS. Arsenic poisoning from anti-asthmatic herbal preparations. Med J Aust. 1975 Sep 13. 2(11):424-8. [QxMD MEDLINE Link].
Chi YW, Chen SL, Yang MH, et al. [Heavy metals in traditional Chinese medicine: ba-pao-neu-hwang-san]. Zhonghua Min Guo Xiao Er Ke Yi Xue Hui Za Zhi. 1993 May-Jun. 34(3):181-90. [QxMD MEDLINE Link].
Guha Mazumder DN. Chronic arsenic toxicity: clinical features, epidemiology, and treatment: experience in West Bengal. J Environ Sci Health A Tox Hazard Subst Environ Eng. 2003 Jan. 38(1):141-63. [QxMD MEDLINE Link].
Morales KH, Ryan L, Kuo TL, Wu MM, Chen CJ. Risk of internal cancers from arsenic in drinking water. Environ Health Perspect. 2000 Jul. 108(7):655-61. [QxMD MEDLINE Link].
Mandal BK, Suzuki KT. Arsenic round the world: a review. Talanta. 2002 Aug 16. 58(1):201-35. [QxMD MEDLINE Link].
Tollestrup K, Frost FJ, Cristiani M, McMillan GP, Calderon RL, Padilla RS. Arsenic-induced skin conditions identified in southwest dermatology practices: an epidemiologic tool?. Environ Geochem Health. 2005 Feb. 27(1):47-53. [QxMD MEDLINE Link].
Barati AH, Maleki A, Alasvand M. Multi-trace elements level in drinking water and the prevalence of multi-chronic arsenical poisoning in residents in the west area of Iran. Sci Total Environ. 2010 Mar 1. 408(7):1523-9. [QxMD MEDLINE Link].
Yeh S, How SW, Lin CS. Arsenical cancer of skin. Histologic study with special reference to Bowen's disease. Cancer. 1968 Feb. 21(2):312-39. [QxMD MEDLINE Link].
Tseng WP, Chu HM, How SW, Fong JM, Lin CS, Yeh S. Prevalence of skin cancer in an endemic area of chronic arsenicism in Taiwan. J Natl Cancer Inst. 1968 Mar. 40(3):453-63. [QxMD MEDLINE Link].
Fierz U. [Follow-up studies of the side-effects of the treatment of skin diseases with inorganic arsenic]. Dermatologica. 1965. 131(1):41-58. [QxMD MEDLINE Link].
Rahman MM, Chowdhury UK, Mukherjee SC, et al. Chronic arsenic toxicity in Bangladesh and West Bengal, India--a review and commentary. J Toxicol Clin Toxicol. 2001. 39(7):683-700. [QxMD MEDLINE Link].
Ramos W, Ortega-Loayza AG, Díaz J, et al. Arsenicism by Chronic Exposure to Mine Tailings in Peru: An Analysis of 17 Cases with Lesions on Skin and/or Annexes. Clin Cosmet Investig Dermatol. 2022. 15:2407-2414. [QxMD MEDLINE Link]. [Full Text].
Tondel M, Rahman M, Magnuson A, Chowdhury IA, Faruquee MH, Ahmad SA. The relationship of arsenic levels in drinking water and the prevalence rate of skin lesions in Bangladesh. Environ Health Perspect. 1999 Sep. 107(9):727-9. [QxMD MEDLINE Link].
Haque R, Mazumder DN, Samanta S, et al. Arsenic in drinking water and skin lesions: dose-response data from West Bengal, India. Epidemiology. 2003 Mar. 14(2):174-82. [QxMD MEDLINE Link].
Miki Y, Kawatsu T, Matsuda K, Machino H, Kubo K. Cutaneous and pulmonary cancers associated with Bowen's disease. J Am Acad Dermatol. 1982 Jan. 6(1):26-31. [QxMD MEDLINE Link].
Ahsan H, Steinmaus C. Invited commentary: use of arsenical skin lesions to predict risk of internal cancer: implications for prevention and future research. Am J Epidemiol. 2013 Feb 1. 177(3):213-6. [QxMD MEDLINE Link]. [Full Text].
Sánchez G, Nova J. Risk factors for squamous cell carcinoma, a study by the National Dermatology Centre of Colombia. Actas Dermosifiliogr. 2013 Oct. 104(8):672-8. [QxMD MEDLINE Link].
Shannon RL, Strayer DS. Arsenic-induced skin toxicity. Hum Toxicol. 1989 Mar. 8(2):99-104. [QxMD MEDLINE Link].
Lien HC, Tsai TF, Lee YY, Hsiao CH. Merkel cell carcinoma and chronic arsenicism. J Am Acad Dermatol. 1999 Oct. 41(4):641-3. [QxMD MEDLINE Link].
Hsueh YM, Cheng GS, Wu MM, Yu HS, Kuo TL, Chen CJ. Multiple risk factors associated with arsenic-induced skin cancer: effects of chronic liver disease and malnutritional status. Br J Cancer. 1995 Jan. 71(1):109-14. [QxMD MEDLINE Link].

Media Gallery

Arsenical keratosis on the sole of a carpenter.

of 1

Author

Chih-Shan Jason Chen, MD, PhD Attending Physician, Dermatology Service, Memorial Sloan-Kettering Cancer Center; Director, Dermatologic Surgery and Mohs Micrographic Surgery Unit, MSK Skin Cancer Center; Chief, Dermatologic Surgery, Northport Veterans Affairs Medical Center; Associate Professor of Clinical Dermatology, Stony Brook University School of Medicine

Chih-Shan Jason Chen, MD, PhD is a member of the following medical societies: American Academy of Dermatology, American College of Mohs Surgery, American Society for Dermatologic Surgery, Association of Professors of Dermatology, Society for Investigative Dermatology

Disclosure: Nothing to disclose.

Coauthor(s)

Daniel Mark Siegel, MD, MS Clinical Professor of Dermatology, Department of Dermatology, State University of New York Downstate Medical Center

Daniel Mark Siegel, MD, MS is a member of the following medical societies: American Academy of Dermatology, American College of Mohs Surgery, American Association for Physician Leadership, American Society for Dermatologic Surgery, American Society for MOHS Surgery, International Society for Dermatologic Surgery

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Steven R Feldman, MD, PhD Professor, Departments of Dermatology, Pathology and Public Health Sciences, and Molecular Medicine and Translational Science, Wake Forest Baptist Health; Director, Center for Dermatology Research, Director of Industry Relations, Department of Dermatology, Wake Forest University School of Medicine

Steven R Feldman, MD, PhD is a member of the following medical societies: American Academy of Dermatology, American Society of Dermatopathology, North Carolina Medical Society, Society for Investigative Dermatology

Disclosure: Received honoraria from Amgen for consulting; Received honoraria from Abbvie for consulting; Received honoraria from Galderma for speaking and teaching; Received consulting fee from Lilly for consulting; Received ownership interest from www.DrScore.com for management position; Received ownership interest from Causa Reseasrch for management position; Received grant/research funds from Janssen for consulting; Received honoraria from Pfizer for speaking and teaching; Received consulting fee from No.

Chief Editor

Dirk M Elston, MD Professor and Chairman, Department of Dermatology and Dermatologic Surgery, Medical University of South Carolina College of Medicine

Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology

Disclosure: Nothing to disclose.

Additional Contributors

Arash Taheri, MD Research Fellow, Center for Dermatology Research, Department of Dermatology, Wake Forest University School of Medicine

Disclosure: Nothing to disclose.

Arsenical Keratosis Clinical Presentation

History

Complications

References

Tables

Contributor Information and Disclosures

What would you like to print?