Arsenical keratosis
Encyclopedia
An arsenical keratosis is a growth of keratin
on the skin
caused by arsenic
, which occurs naturally in the earth's crust
and is widely distributed in the environment, 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. Arsenic may also causes other conditions including: Bowen's disease
, cardiovascular diseases, developmental abnormalities, neurologic and neurobehavioral disorders
, diabetes, hearing loss, hematologic disorders, and various types of cancer
. 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.
excision repair
,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 keratinocyte
s) a sensitive target for arsenic-induced toxicity. Arsenic has been shown to alter epidermal keratinocyte differentiation processes,induce overexpression of growth factors, and enhance proliferation of human keratinocytes.
Keratin
Keratin refers to a family of fibrous structural proteins. Keratin is the key of structural material making up the outer layer of human skin. It is also the key structural component of hair and nails...
on the skin
Skin
-Dermis:The dermis is the layer of skin beneath the epidermis that consists of connective tissue and cushions the body from stress and strain. The dermis is tightly connected to the epidermis by a basement membrane. It also harbors many Mechanoreceptors that provide the sense of touch and heat...
caused by arsenic
Arsenic
Arsenic is a chemical element with the symbol As, atomic number 33 and relative atomic mass 74.92. Arsenic occurs in many minerals, usually in conjunction with sulfur and metals, and also as a pure elemental crystal. It was first documented by Albertus Magnus in 1250.Arsenic is a metalloid...
, which occurs naturally in the earth's crust
Crust (geology)
In geology, the crust is the outermost solid shell of a rocky planet or natural satellite, which is chemically distinct from the underlying mantle...
and is widely distributed in the environment, Arsenical compounds are used in industrial
Industry
Industry refers to the production of an economic good or service within an economy.-Industrial sectors:There are four key industrial economic sectors: the primary sector, largely raw material extraction industries such as mining and farming; the secondary sector, involving refining, construction,...
, agricultural, and medicinal substances. Arsenic is also found to be an environmental contaminant in drinking water (well
Water well
A water well is an excavation or structure created in the ground by digging, driving, boring or drilling to access groundwater in underground aquifers. The well water is drawn by an electric submersible pump, a trash pump, a vertical turbine pump, a handpump or a mechanical pump...
water) and an occupational hazard for miners and glass
Glass
Glass is an amorphous solid material. Glasses are typically brittle and optically transparent.The most familiar type of glass, used for centuries in windows and drinking vessels, is soda-lime glass, composed of about 75% silica plus Na2O, CaO, and several minor additives...
workers. Arsenic may also causes other conditions including: Bowen's disease
Bowen's disease
Bowen's disease is a neoplastic skin disease, it can be considered as an early stage or intraepidermal form of squamous cell carcinoma. It was named after Mark Bowen...
, cardiovascular diseases, developmental abnormalities, neurologic and neurobehavioral disorders
Emotional and behavioral disorders
Emotional and behavioral disorders is a broad category which is used commonly in educational settings, to group a range of more specific perceived difficulties of children and adolescents...
, diabetes, hearing loss, hematologic disorders, and various types of cancer
Cancer
Cancer , known medically as a malignant neoplasm, is a large group of different diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the...
. Arsenical keratoses may persist indefinitely, and some may develop into invasive squamous cell carcinoma
Squamous cell carcinoma
Squamous cell carcinoma , occasionally rendered as "squamous-cell carcinoma", is a histologically distinct form of cancer. It arises from the uncontrolled multiplication of malignant cells deriving from epithelium, or showing particular cytological or tissue architectural characteristics of...
. Metastatic arsenic squamous cell carcinoma and arsenic-induced malignancies in internal organs such as the bladder
Bladder
Bladder usually refers to an anatomical hollow organBladder may also refer to:-Biology:* Urinary bladder in humans** Urinary bladder ** Bladder control; see Urinary incontinence** Artificial urinary bladder, in humans...
, kidney
Kidney
The kidneys, organs with several functions, serve essential regulatory roles in most animals, including vertebrates and some invertebrates. They are essential in the urinary system and also serve homeostatic functions such as the regulation of electrolytes, maintenance of acid–base balance, and...
, skin
Skin
-Dermis:The dermis is the layer of skin beneath the epidermis that consists of connective tissue and cushions the body from stress and strain. The dermis is tightly connected to the epidermis by a basement membrane. It also harbors many Mechanoreceptors that provide the sense of touch and heat...
, liver
Liver
The liver is a vital organ present in vertebrates and some other animals. It has a wide range of functions, including detoxification, protein synthesis, and production of biochemicals necessary for digestion...
, and colon
Colon (anatomy)
The colon is the last part of the digestive system in most vertebrates; it extracts water and salt from solid wastes before they are eliminated from the body, and is the site in which flora-aided fermentation of unabsorbed material occurs. Unlike the small intestine, the colon does not play a...
, may result in death.
Pathophysiology
Arsenite impairs nucleotideNucleotide
Nucleotides are molecules that, when joined together, make up the structural units of RNA and DNA. In addition, nucleotides participate in cellular signaling , and are incorporated into important cofactors of enzymatic reactions...
excision repair
Excision repair
Excision repair is a term applied to several DNA repair mechanisms. They remove the damaged nucleotides and are able to determine the correct sequence from the complementary strand of DNA.Specific mechanisms include:...
,and it may also affect gene expression
Gene expression
Gene expression is the process by which information from a gene is used in the synthesis of a functional gene product. These products are often proteins, but in non-protein coding genes such as ribosomal RNA , transfer RNA or small nuclear RNA genes, the product is a functional RNA...
by increasing or decreasing DNA methylation
DNA methylation
DNA methylation is a biochemical process that is important for normal development in higher organisms. It involves the addition of a methyl group to the 5 position of the cytosine pyrimidine ring or the number 6 nitrogen of the adenine purine ring...
. The high affinity of arsenic for sulfhydryl groups makes keratin-rich cells (e.g., epidermal keratinocyte
Keratinocyte
Keratinocytes are the predominant cell type in the epidermis, the outermost layer of the human skin, constituting 95% of the cells found there. Those keratinocytes found in the basal layer of the skin are sometimes referred to as "basal cells" or "basal keratinocytes"...
s) a sensitive target for arsenic-induced toxicity. Arsenic has been shown to alter epidermal keratinocyte differentiation processes,induce overexpression of growth factors, and enhance proliferation of human keratinocytes.
Treatment
- A chelating agent (e.g., dimercaprolDimercaprolDimercaprol or British anti-Lewisite , is a compound developed by British biochemists at Oxford University during World War II. It was developed secretly as an antidote for lewisite, the now-obsolete arsenic-based chemical warfare agent. Today, it is used medically in treatment of arsenic,...
) 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., acitretinAcitretinAcitretin is a second generation retinoid. It is taken orally, and is typically used for psoriasis....
, etretinateEtretinateEtretinate is a medication developed by Hoffmann–La Roche that was approved by the FDA in 1986 to treat severe psoriasis...
) 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% imiquimodImiquimodImiquimod is a prescription medication that acts as an immune response modifier. It is marketed by Meda AB, Graceway Pharmaceuticals and iNova Pharmaceuticals under the trade names Aldara and Zyclara, and by Mochida as Beselna. It is also referred to as R-837.- History :The original FDA approval...
cream may be useful in treating arsenical keratoses and Bowen's disease.