Carotenosis is a benign and reversible medical condition where an excess of dietary

carotenoids Carotenoids (), also called tetraterpenoids, are yellow, orange, and red organic pigments that are produced by plants and algae, as well as several bacteria, and fungi. Carotenoids give the characteristic color to pumpkins, carrots, parsnips, co ...

results in orange discoloration of the outermost skin layer. The discoloration is most easily observed in light-skinned people and may be mistaken for jaundice. Carotenoids are lipid-soluble compounds that include alpha- and beta-carotene, beta- cryptoxanthin,

lycopene Lycopene is an organic compound classified as a tetraterpene and a carotene. Lycopene (from the neo-Latin '' Lycopersicum'', the tomato species) is a bright red carotenoid hydrocarbon found in tomatoes and other red fruits and vegetables. Occu ...

lutein Lutein (;"Lutein"

zeaxanthin Zeaxanthin is one of the most common carotenoids in nature, and is used in the xanthophyll cycle. Synthesized in plants and some micro-organisms, it is the pigment that gives paprika (made from bell peppers), corn, saffron, goji ( wolfberries ...

. 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 The liver is a major organ only found in vertebrates which performs many essential biological functions such as detoxification of the organism, and the synthesis of proteins and biochemicals necessary for digestion and growth. In humans, it ...

vitamin A Vitamin A is a fat-soluble vitamin and an essential nutrient for humans. It is a group of organic compounds that includes retinol, retinal (also known as retinaldehyde), retinoic acid, and several provitamin A carotenoids (most notably ...

. From there they are transported in the plasma into the peripheral tissues. Carotenoids are eliminated via

sweat Perspiration, also known as sweating, is the production of fluids secreted by the sweat glands in the skin of mammals. Two types of sweat glands can be found in humans: eccrine glands and apocrine glands. The eccrine sweat glands are distrib ...

sebum A sebaceous gland is a microscopic exocrine gland in the skin that opens into a hair follicle to secrete an oily or waxy matter, called sebum, which lubricates the hair and skin of mammals. In humans, sebaceous glands occur in the greatest nu ...

urine Urine is a liquid by-product of metabolism in humans and in many other animals. Urine flows from the kidneys through the ureters to the urinary bladder. Urination results in urine being excreted from the body through the urethra. Cellular ...

, and gastrointestinal secretions. Carotenoids contribute to normal-appearing

human skin color Human skin color ranges from the darkest brown to the lightest hues. Differences in skin color among individuals is caused by variation in pigmentation, which is the result of genetics (inherited from one's biological parents and or indivi ...

, and are a significant component of physiologic ultraviolet photoprotection. Carotenemia most commonly occurs in

vegetarian Vegetarianism is the practice of abstaining from the consumption of meat (red meat, poultry, seafood, insects, and the flesh of any other animal). It may also include abstaining from eating all by-products of animal slaughter. Vegetariani ...

s and young children with light skin. 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

conjunctiva The conjunctiva is a thin mucous membrane that lines the inside of the eyelids and covers the sclera (the white of the eye). It is composed of non-keratinized, stratified squamous epithelium with goblet cells, stratified columnar epithelium ...

l membranes over the sclerae (whites of the eyes), and thus is usually easy to distinguish from the yellowing of the skin and conjunctiva 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 Erythropoietic protoporphyria (or commonly called EPP) is a form of porphyria, which varies in severity and can be very painful. It arises from a deficiency in the enzyme ferrochelatase, leading to abnormally high levels of protoporphyrin in the ...

, where beta carotene is prescribed in quantities which discolor the skin. 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.

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. Elevated serum beta-carotene does not necessarily result in carotenosis, but the latter is likely to show up when intake is more than 20 mg/day. Average adult intake in the U.S. around 2.3 mg/day. One medium-sized carrot has about 4.0 mg. Carotenoderma can be divided into two major types, primary and secondary. Primary carotenoderma is 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:

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 jaundice is the characteristic sparing of the sclerae 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 better observed under artificial light. It is of note that lycopenemia is specifically associated with discoloration of the soft palate and deposition in the liver parenchyma.

Secondary carotenoderma

Disease states associated with carotenoderma include hypothyroidism,

diabetes mellitus Diabetes, also known as diabetes mellitus, is a group of metabolic disorders characterized by a high blood sugar level ( hyperglycemia) over a prolonged period of time. Symptoms often include frequent urination, increased thirst and increased ...

anorexia nervosa Anorexia nervosa, often referred to simply as anorexia, is an eating disorder characterized by low weight, food restriction, body image disturbance, fear of gaining weight, and an overpowering desire to be thin. ''Anorexia'' is a term of Gr ...

, nephrotic syndrome, and liver disease. In hypothyroidism and diabetes mellitus, the underlying mechanism of hypercarotenemia is thought to be both impaired conversion of beta-carotene into retinol and the associated increased serum lipids.

Diabetes mellitus Diabetes, also known as diabetes mellitus, is a group of metabolic disorders characterized by a high blood sugar level ( hyperglycemia) over a prolonged period of time. Symptoms often include frequent urination, increased thirst and increased ...

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 The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respon ...

(FDA)-approved for this purpose in the

United States The United States of America (U.S.A. or USA), commonly known as the United States (U.S. or US) or America, is a country primarily located in North America. It consists of 50 states, a federal district, five major unincorporated territori ...

because of its adverse effects. These include

hepatitis Hepatitis is inflammation of the liver tissue. Some people or animals with hepatitis have no symptoms, whereas others develop yellow discoloration of the skin and whites of the eyes ( jaundice), poor appetite, vomiting, tiredness, abdominal ...

, urticaria, aplastic anemia, and a

retinopathy Retinopathy is any damage to the retina of the eyes, which may cause vision impairment. Retinopathy often refers to retinal vascular disease, or damage to the retina caused by abnormal blood flow. Age-related macular degeneration is technically inc ...

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 Homogeneity and heterogeneity are concepts often used in the sciences and statistics relating to the uniformity of a substance or organism. A material or image that is homogeneous is uniform in composition or character (i.e. color, shape, s ...

causes carotene to become more available for absorption. A small 2.5 ounce jar of baby food

sweet potatoes The sweet potato or sweetpotato ('' Ipomoea batatas'') is a dicotyledonous plant that belongs to the bindweed or morning glory family, Convolvulaceae. Its large, starchy, sweet-tasting tuberous roots are used as a root vegetable. The young sho ...

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.

Diagnosis

Differential diagnoses

Hyperbilirubinemia is the main differential diagnosis to be considered in evaluating jaundice suspected to be carotenemia.Patrick Yao, M.D. Carotenemia (clinical vignette) Excessive consumption of

, a plant pigment similar to carotene and present in

tomato The tomato is the edible berry of the plant ''Solanum lycopersicum'', commonly known as the tomato plant. The species originated in western South America, Mexico, and Central America. The Mexican Nahuatl word gave rise to the Spanish word ...

es, can cause a deep orange discoloration of the skin. Like carotenodermia, lycopenemia is harmless. Excessive consumption of elemental

silver Silver is a chemical element with the symbol Ag (from the Latin ', derived from the Proto-Indo-European ''h₂erǵ'': "shiny" or "white") and atomic number 47. A soft, white, lustrous transition metal, it exhibits the highest electrical ...

, silver dust or silver compounds can cause the skin to be colored blue or bluish-grey. This condition is called

argyria Argyria or argyrosis is a condition caused by excessive exposure to chemical compounds of the element silver, or to silver dust. The most dramatic symptom of argyria is that the skin turns blue or blue-grey. It may take the form of ''generalize ...

. A similar skin color can result from prolonged exposure to gold, typically as a little-used medical treatment. The gold-induced greyish skin color is called

chrysiasis Chrysiasis is a dermatological condition induced by the parenteral administration of gold salts, usually for the treatment of rheumatoid arthritis.James, William; Berger, Timothy; Elston, Dirk (2005). ''Andrews' Diseases of the Skin: Clinical Derma ...

. Argyria and chrysiasis, however, are irreversible, unlike carotenosis.

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.

References

External links

* {{Pigmentation disorders Skin conditions resulting from errors in metabolism Disturbances of human pigmentation