Carotenosis
Encyclopedia
Carotenaemia is the presence in blood of the yellow pigment carotene from excessive intake of carrots or other vegetables containing the pigment resulting in increased serum carotenoids. It can lead to subsequent yellow-orange discoloration (xanthoderma or carotenoderma) and their subsequent deposition in the outermost layer of skin
. Carotenoid
s are lipid-soluble compounds that include alpha- and beta-carotene
, beta-cryptoxanthin, lycopene
, lutein
, and zeaxanthin
. The primary serum carotenoids are beta-carotene, lycopene, and lutein. Serum levels of carotenoids vary between region, ethnicity, and sex in the healthy population. All are absorbed by passive diffusion from the gastrointestinal tract
and are then partially metabolized in the intestinal mucosa and liver
to vitamin A
. From there they are transported in the plasma into the peripheral tissues. Carotenoids are eliminated via sweat
, sebum, urine
, and gastrointestinal secretions. Carotenoids contribute to normal-appearing human skin color and are a significant component of physiologic ultraviolet photoprotection.
Carotenemia is a benign condition most commonly occurring in vegetarians and young children. Carotenemia is more easily appreciated in light-complexioned people, and it may present chiefly as an orange discolouration of the palms and the soles in more darkly pigmented persons. Carotenemia does not cause selective orange discoloration of the sclerae of the eyes, and thus is usually easy to distinguish from the yellowing of the skin caused by bile pigments in states of jaundice
.
Carotenoderma is deliberately caused by beta-carotenoid treatment of certain photo-sensitive dermatitis diseases such as erythropoietic protoporphyria
, where beta carotene in quantities which discolor the skin is prescribed. These high doses of beta carotene have been found to be harmless in studies, though cosmetically displeasing to some. In a recent meta analysis of these treatments, however, the effectiveness of the treatment has been called into question.
is the characteristic sparing of the conjunctiva
e in carotenoderma, which would be involved in jaundice if the bilirubin
is at a level to cause skin findings. In contrast to jaundice, carotenoderma is reported to be paralytic under artificial light. It is of note that lycopenemia is specifically associated with discoloration of the soft palate and deposition in the liver parenchyma, which can be visualized on ultrasound
.
Carotenoderma can be divided into two major types, primary and secondary. Primary carotenoderma is that developing from increased oral ingestion of carotenoids, whereas secondary carotenoderma is caused from underlying disease states that increase serum carotenoids with normal oral intake of these compounds. Primary and secondary carotenoderma can coexist in the same patient.
Foods associated with high levels of carotenoids include:
, diabetes mellitus
, anorexia nervosa
, nephrotic syndrome, and liver disease. In hypothyroidism and diabetes mellitus, the underlying mechanism of hypercarotenemia is through both impaired conversion of beta-carotene into retinol and the associated increased serum lipids. Diabetes mellitus
has also been associated with carotenoderma through disease-specific diets that are rich in vegetables. In the nephrotic syndrome, the hypercarotenemia is related to the associated increased serum lipids, similar to the above entities. It is of note that kidney dysfunction in general is associated with hypercarotenemia as a result of decreased excretion of carotenoids. Liver dysfunction, regardless of origin, causes hypercarotenemia as a result of the impaired conversion of carotenoids to retinol. This is of particular interest because jaundice and carotenoderma can coexist in the same patient. Anorexia nervosa causes carotenoderma mainly through diets that are rich in carotenoids and the associated hypothyroidism. It tends to be more common in the restricting subtype of this disease, and is associated with numerous other dermatologic manifestations, such as brittle hair and nails, lanugo
-like body hair, and xerosis. Although Alzheimer's disease has been associated with carotenoderma in some reports, most studies on serum carotenoids in these patients show that their levels of carotenoids and retinol are depressed, and may be associated with the development of dementia. A true association between Alzheimer's disease and carotenoderma is unclear at this time. There have been case reports in the literature of increased serum carotenoids and carotenoderma that is unresponsive to dietary measures, with a genetic defect in carotenoid metabolic enzymes proposed. Canthaxanthin and astaxanthin are naturally occurring carotenoids that are used in the British and US food industry to add color to foods such as sausage and fish. Canthaxanthin has been used in over-the-counter “tanning pills” in the United States and Europe, but is not currently Food and Drug Administration
(FDA)-approved for this purpose in the United States
because of its adverse effects. These include hepatitis
, urticaria, aplastic anemia, and a retinopathy
characterized by yellow deposits and subsequent visual field defects.
Infants and small children are especially prone to carotenoderma because of the cooked, mashed, and pureed vegetables that they eat. Processing and homogenizing causes carotene
to become more available for absorption. A small 2.5 ounce jar of baby food sweet potatoes or carrots contains about 400-500% of an infant's recommended daily value of carotene. In addition to that source of carotene, infants are usually prescribed a liquid vitamin supplement, such as Tri-Vi-Sol, which contains vitamin A.
As to underlying disorders in secondary carotinemia and carotenoderma, treatment depends wholly on the cause.
, a plant pigment similar to carotene and present in tomato
es, can cause a deep orange discoloration of the skin. Like carotenodermia, lycopenodermia is harmless.
Excessive consumption of elemental silver
, silver dust or silver compounds can cause the skin to be colored blue or bluish-grey. This condition is called argyria
. Similarly, prolonged exposure to gold leads to chrysiasis
. Argyria and chrysiasis, however, are irreversible, unlike carotenosis.
Stratum corneum
The stratum corneum is the outermost layer of the epidermis, consisting of dead cells that lack nuclei and organelles. The purpose of the stratum corneum is to form a barrier to protect underlying tissue from infection, dehydration, chemicals and mechanical stress...
. Carotenoid
Carotenoid
Carotenoids are tetraterpenoid organic pigments that are naturally occurring in the chloroplasts and chromoplasts of plants and some other photosynthetic organisms like algae, some bacteria, and some types of fungus. Carotenoids can be synthesized fats and other basic organic metabolic building...
s are lipid-soluble compounds that include alpha- and beta-carotene
Beta-carotene
β-Carotene is a strongly-coloured red-orange pigment abundant in plants and fruits. It is an organic compound and chemically is classified as a hydrocarbon and specifically as a terpenoid , reflecting its derivation from isoprene units...
, beta-cryptoxanthin, lycopene
Lycopene
Lycopene is a bright red carotene and carotenoid pigment and phytochemical found in tomatoes and other red fruits and vegetables, such as red carrots, watermelons and papayas...
, lutein
Lutein
Lutein is a xanthophyll and one of 600 known naturally occurring carotenoids. Lutein is synthesized only by plants and like other xanthophylls is found in high quantities in green leafy vegetables such as spinach and kale...
, and zeaxanthin
Zeaxanthin
Zeaxanthin is one of the most common carotenoid alcohols found in nature. It is important in the xanthophyll cycle. Synthesized in plants & some micro-organisms, it is the pigment that gives paprika , corn, saffron, and many other plants & microbes their characteristic color.The name is derived...
. The primary serum carotenoids are beta-carotene, lycopene, and lutein. Serum levels of carotenoids vary between region, ethnicity, and sex in the healthy population. All are absorbed by passive diffusion from the gastrointestinal tract
Gastrointestinal tract
The human gastrointestinal tract refers to the stomach and intestine, and sometimes to all the structures from the mouth to the anus. ....
and are then partially metabolized in the intestinal mucosa and 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...
to vitamin A
Vitamin A
Vitamin A is a vitamin that is needed by the retina of the eye in the form of a specific metabolite, the light-absorbing molecule retinal, that is necessary for both low-light and color vision...
. From there they are transported in the plasma into the peripheral tissues. Carotenoids are eliminated via sweat
SWEAT
SWEAT is an OLN/TSN show hosted by Julie Zwillich that aired in 2003-2004.Each of the 13 half-hour episodes of SWEAT features a different outdoor sport: kayaking, mountain biking, ice hockey, beach volleyball, soccer, windsurfing, rowing, Ultimate, triathlon, wakeboarding, snowboarding, telemark...
, sebum, urine
Urine
Urine is a typically sterile liquid by-product of the body that is secreted by the kidneys through a process called urination and excreted through the urethra. Cellular metabolism generates numerous by-products, many rich in nitrogen, that require elimination from the bloodstream...
, and gastrointestinal secretions. Carotenoids contribute to normal-appearing human skin color and are a significant component of physiologic ultraviolet photoprotection.
Jaundice
Jaundice is a yellowish pigmentation of the skin, the conjunctival membranes over the sclerae , and other mucous membranes caused by hyperbilirubinemia . This hyperbilirubinemia subsequently causes increased levels of bilirubin in the extracellular fluid...
.
Carotenoderma is deliberately caused by beta-carotenoid treatment of certain photo-sensitive dermatitis diseases such as erythropoietic protoporphyria
Erythropoietic protoporphyria
Erythropoietic protoporphyria is a relatively mild form of porphyria, although very painful, which arises from a deficiency in the enzyme ferrochelatase, leading to abnormally high levels of protoporphyrin in the tissue...
, where beta carotene in quantities which discolor the skin is prescribed. These high doses of beta carotene have been found to be harmless in studies, though cosmetically displeasing to some. In a recent meta analysis of these treatments, however, the effectiveness of the treatment has been called into question.
Physiology
Carotenoids are deposited in the intercellular lipids of the stratum corneum, and the color change is most prominent in regions of increased sweating and thickness of this layer. This includes the palms, soles, knees, and nasolabial folds, although the discoloration can be generalized. The primary factor differentiating carotenoderma from jaundiceJaundice
Jaundice is a yellowish pigmentation of the skin, the conjunctival membranes over the sclerae , and other mucous membranes caused by hyperbilirubinemia . This hyperbilirubinemia subsequently causes increased levels of bilirubin in the extracellular fluid...
is the characteristic sparing of the conjunctiva
Conjunctiva
The conjunctiva covers the sclera and lines the inside of the eyelids. It is composed of rare stratified columnar epithelium.-Function:...
e in carotenoderma, which would be involved in jaundice if the bilirubin
Bilirubin
Bilirubin is the yellow breakdown product of normal heme catabolism. Heme is found in hemoglobin, a principal component of red blood cells. Bilirubin is excreted in bile and urine, and elevated levels may indicate certain diseases...
is at a level to cause skin findings. In contrast to jaundice, carotenoderma is reported to be paralytic under artificial light. It is of note that lycopenemia is specifically associated with discoloration of the soft palate and deposition in the liver parenchyma, which can be visualized on ultrasound
Ultrasound
Ultrasound is cyclic sound pressure with a frequency greater than the upper limit of human hearing. Ultrasound is thus not separated from "normal" sound based on differences in physical properties, only the fact that humans cannot hear it. Although this limit varies from person to person, it is...
.
Causes
There are three main mechanisms involved in hypercarotenemia: excessive dietary intake of carotenoids, increased serum lipids, and decreased metabolism of carotenoids. The most common reported cause of hypercarotenemia (and thus carotenoderma) is increased intake, either through increased dietary foods or nutritional supplements. This change takes approximately 4 to 7 weeks to be recognized clinically. Numerous ingested substances are rich in carotenoids. Increased serum lipids also cause hypercarotenemia because there are increased circulating lipoproteins that contain bound carotenoids. Finally, in certain disease states, the metabolism and conversion of carotenoids to retinol is slowed, which can lead to decreased clearance and increased plasma levels.Carotenoderma can be divided into two major types, primary and secondary. Primary carotenoderma is that developing from increased oral ingestion of carotenoids, whereas secondary carotenoderma is caused from underlying disease states that increase serum carotenoids with normal oral intake of these compounds. Primary and secondary carotenoderma can coexist in the same patient.
Foods associated with high levels of carotenoids include:
|
|
|
Secondary carotenoderma
Disease states associated with carotenoderma include hypothyroidismHypothyroidism
Hypothyroidism is a condition in which the thyroid gland does not make enough thyroid hormone.Iodine deficiency is the most common cause of hypothyroidism worldwide but it can be caused by other causes such as several conditions of the thyroid gland or, less commonly, the pituitary gland or...
, diabetes mellitus
Diabetes mellitus
Diabetes mellitus, often simply referred to as diabetes, is a group of metabolic diseases in which a person has high blood sugar, either because the body does not produce enough insulin, or because cells do not respond to the insulin that is produced...
, anorexia nervosa
Anorexia nervosa
Anorexia nervosa is an eating disorder characterized by refusal to maintain a healthy body weight and an obsessive fear of gaining weight. Although commonly called "anorexia", that term on its own denotes any symptomatic loss of appetite and is not strictly accurate...
, nephrotic syndrome, and liver disease. In hypothyroidism and diabetes mellitus, the underlying mechanism of hypercarotenemia is through both impaired conversion of beta-carotene into retinol and the associated increased serum lipids. Diabetes mellitus
Diabetes mellitus
Diabetes mellitus, often simply referred to as diabetes, is a group of metabolic diseases in which a person has high blood sugar, either because the body does not produce enough insulin, or because cells do not respond to the insulin that is produced...
has also been associated with carotenoderma through disease-specific diets that are rich in vegetables. In the nephrotic syndrome, the hypercarotenemia is related to the associated increased serum lipids, similar to the above entities. It is of note that kidney dysfunction in general is associated with hypercarotenemia as a result of decreased excretion of carotenoids. Liver dysfunction, regardless of origin, causes hypercarotenemia as a result of the impaired conversion of carotenoids to retinol. This is of particular interest because jaundice and carotenoderma can coexist in the same patient. Anorexia nervosa causes carotenoderma mainly through diets that are rich in carotenoids and the associated hypothyroidism. It tends to be more common in the restricting subtype of this disease, and is associated with numerous other dermatologic manifestations, such as brittle hair and nails, lanugo
Lanugo
Lanugo is fine, downy hair as a type of fur. It is often found in teratomas .-Fetal development:Lanugo grows on fetuses as a normal part of gestation, but is usually shed and replaced by vellus hair at about 33 to 36 weeks of gestational age...
-like body hair, and xerosis. Although Alzheimer's disease has been associated with carotenoderma in some reports, most studies on serum carotenoids in these patients show that their levels of carotenoids and retinol are depressed, and may be associated with the development of dementia. A true association between Alzheimer's disease and carotenoderma is unclear at this time. There have been case reports in the literature of increased serum carotenoids and carotenoderma that is unresponsive to dietary measures, with a genetic defect in carotenoid metabolic enzymes proposed. Canthaxanthin and astaxanthin are naturally occurring carotenoids that are used in the British and US food industry to add color to foods such as sausage and fish. Canthaxanthin has been used in over-the-counter “tanning pills” in the United States and Europe, but is not currently Food and Drug Administration
Food and Drug Administration
The Food and Drug Administration is an agency of the United States Department of Health and Human Services, one of the United States federal executive departments...
(FDA)-approved for this purpose in the United States
United States
The United States of America is a federal constitutional republic comprising fifty states and a federal district...
because of its adverse effects. These include hepatitis
Hepatitis
Hepatitis is a medical condition defined by the inflammation of the liver and characterized by the presence of inflammatory cells in the tissue of the organ. The name is from the Greek hepar , the root being hepat- , meaning liver, and suffix -itis, meaning "inflammation"...
, urticaria, aplastic anemia, and a retinopathy
Retinopathy
Retinopathy is a general term that refers to some form of non-inflammatory damage to the retina of the eye. Frequently, retinopathy is an ocular manifestation of systemic disease.-Pathophysiology:Causes of retinopathy are varied:...
characterized by yellow deposits and subsequent visual field defects.
Infants and small children are especially prone to carotenoderma because of the cooked, mashed, and pureed vegetables that they eat. Processing and homogenizing causes carotene
Carotene
The term carotene is used for several related unsaturated hydrocarbon substances having the formula C40Hx, which are synthesized by plants but cannot be made by animals. Carotene is an orange photosynthetic pigment important for photosynthesis. Carotenes are all coloured to the human eye...
to become more available for absorption. A small 2.5 ounce jar of baby food sweet potatoes or carrots contains about 400-500% of an infant's recommended daily value of carotene. In addition to that source of carotene, infants are usually prescribed a liquid vitamin supplement, such as Tri-Vi-Sol, which contains vitamin A.
Treatment
Carotenemia and carotenoderma is in itself harmless, and does not require treatment. In primary carotenoderma, when the use of high quantities of carotene is discontinued the skin color will return to normal. It may take up to several months, however, for this to happen. Infants with this condition should not be taken off prescribed vitamin supplements unless advised to do so by the child's pediatrician.As to underlying disorders in secondary carotinemia and carotenoderma, treatment depends wholly on the cause.
Similar conditions
Excessive consumption of lycopeneLycopene
Lycopene is a bright red carotene and carotenoid pigment and phytochemical found in tomatoes and other red fruits and vegetables, such as red carrots, watermelons and papayas...
, a plant pigment similar to carotene and present in tomato
Tomato
The word "tomato" may refer to the plant or the edible, typically red, fruit which it bears. Originating in South America, the tomato was spread around the world following the Spanish colonization of the Americas, and its many varieties are now widely grown, often in greenhouses in cooler...
es, can cause a deep orange discoloration of the skin. Like carotenodermia, lycopenodermia is harmless.
Excessive consumption of elemental silver
Silver
Silver is a metallic chemical element with the chemical symbol Ag and atomic number 47. A soft, white, lustrous transition metal, it has the highest electrical conductivity of any element and the highest thermal conductivity of any metal...
, silver dust or silver compounds can cause the skin to be colored blue or bluish-grey. This condition is called argyria
Argyria
Argyria is a condition caused by improper exposure to chemical forms of the element silver, silver dust, or silver compounds. The most dramatic symptom of argyria is that the skin becomes blue or bluish-grey colored. Argyria may be found as generalized argyria or local argyria...
. Similarly, prolonged exposure to gold leads to chrysiasis
Chrysiasis
Chrysiasis is a dermatological condition induced by the parenteral administration of gold salts, usually for the treatment of rheumatoid arthritis...
. Argyria and chrysiasis, however, are irreversible, unlike carotenosis.