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

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

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 Jaundice, also known as icterus, is a yellowish or, less frequently, greenish pigmentation of the skin and sclera due to high bilirubin levels. Jaundice in adults is typically a sign indicating the presence of underlying diseases involving ...

Carotenoid Carotenoids () are yellow, orange, and red organic pigments that are produced by plants and algae, as well as several bacteria, archaea, and fungi. Carotenoids give the characteristic color to pumpkins, carrots, parsnips, corn, tomatoes, cana ...

s 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 '' Lycopersicon'', the name of a former tomato genus) is a bright red carotenoid hydrocarbon found in tomatoes and other red fruits and ve ...

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 The gastrointestinal tract (GI tract, digestive tract, alimentary canal) is the tract or passageway of the Digestion, digestive system that leads from the mouth to the anus. The tract is the largest of the body's systems, after the cardiovascula ...

and are then partially metabolized in the intestinal mucosa and

liver The liver is a major metabolic organ (anatomy), organ exclusively found in vertebrates, which performs many essential biological Function (biology), functions such as detoxification of the organism, and the Protein biosynthesis, synthesis of var ...

vitamin A Vitamin A is a fat-soluble vitamin that is an essential nutrient. The term "vitamin A" encompasses a group of chemically related organic compounds that includes retinol, retinyl esters, and several provitamin (precursor) carotenoids, most not ...

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

sweat Perspiration, also known as sweat, is the fluid secreted by sweat glands in the skin of mammals. Two types of sweat glands can be found in humans: eccrine glands and Apocrine sweat gland, apocrine glands. The eccrine sweat glands are distribu ...

sebum A sebaceous gland or oil 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 ...

urine Urine is a liquid by-product of metabolism in humans and many other animals. In placental mammals, urine flows from the Kidney (vertebrates), kidneys through the ureters to the urinary bladder and exits the urethra through the penile meatus (mal ...

, and gastrointestinal secretions. Carotenoids contribute to normal-appearing

human skin color Human skin color ranges from the Dark skin, darkest brown to the Light skin, lightest hues. Differences in Human skin, skin color among individuals is caused by variation in pigmentation, which is largely the result of genetics (inherited from o ...

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

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

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 In the anatomy of the eye, the conjunctiva (: conjunctivae) 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 gobl ...

l membranes over the

sclera The sclera, also known as the white of the eye or, in older literature, as the tunica albuginea oculi, is the opaque, fibrous, protective outer layer of the eye containing mainly collagen and some crucial elastic fiber. In the development of t ...

e (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

. Carotenoderma is deliberately caused by beta-carotenoid treatment of certain photo-sensitive dermatitis diseases such as erythropoietic protoporphyria, 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 The stratum corneum (Latin language, Latin for 'horny layer') is the outermost layer of the epidermis (skin), epidermis. Consisting of dead tissue, it protects underlying tissue from infection, dehydration, chemicals and mechanical stress. It is ...

, 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

is the characteristic sparing of the

e in carotenoderma, which would be involved in jaundice if the

bilirubin Bilirubin (BR) (adopted from German, originally bili—bile—plus ruber—red—from Latin) is a red-orange compound that occurs in the normcomponent of the straw-yellow color in urine. Another breakdown product, stercobilin, causes the brown ...

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 Hypothyroidism is an endocrine disease in which the thyroid gland does not produce enough thyroid hormones. It can cause a number of symptoms, such as cold intolerance, poor ability to tolerate cold, fatigue, extreme fatigue, muscle aches, co ...

diabetes mellitus Diabetes mellitus, commonly known as diabetes, is a group of common endocrine diseases characterized by sustained hyperglycemia, high blood sugar levels. Diabetes is due to either the pancreas not producing enough of the hormone insulin, or th ...

anorexia nervosa Anorexia nervosa (AN), often referred to simply as anorexia, is an eating disorder characterized by Calorie restriction, food restriction, body image disturbance, fear of gaining weight, and an overpowering desire to be thin. Individuals wit ...

, 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 mellitus, commonly known as diabetes, is a group of common endocrine diseases characterized by sustained hyperglycemia, high blood sugar levels. Diabetes is due to either the pancreas not producing enough of the hormone insulin, or th ...

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 is very thin, soft, usually unpigmented hair that is sometimes found on the body of a fetus or newborn. It is the first hair to be produced by the fetal hair follicles, and it usually appears around sixteen weeks of gestation and is abunda ...

-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 respo ...

(FDA)-approved for this purpose in the

United States The United States of America (USA), also known as the United States (U.S.) or America, is a country primarily located in North America. It is a federal republic of 50 U.S. state, states and a federal capital district, Washington, D.C. The 48 ...

because of its adverse effects. These include

hepatitis Hepatitis is inflammation of the liver parenchyma, 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), Anorexia (symptom), poor appetite ...

, 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 in ...

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 The term carotene (also carotin, from the Latin ''carota'', "carrot") is used for many related unsaturated hydrocarbon substances having the formula C40Hx, which are synthesized by plants but in general cannot be made by animals (with the ex ...

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 in the morning glory family, Convolvulaceae. Its sizeable, starchy, sweet-tasting tuberous roots are used as a root vegetable, which is a staple food in parts of the ...

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 (, ), ''Solanum lycopersicum'', is a plant whose fruit is an edible Berry (botany), berry that is eaten as a vegetable. The tomato is a member of the nightshade family that includes tobacco, potato, and chili peppers. It originate ...

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; it has Symbol (chemistry), symbol Ag () and atomic number 47. A soft, whitish-gray, lustrous transition metal, it exhibits the highest electrical conductivity, thermal conductivity, and reflectivity 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 or argyrosis is a condition caused by excessive exposure to chemical compounds of the element silver, or silver dust. The most dramatic symptom of argyria is that the skin turns blue or blue-gray, and is usually most prominent in sun-ex ...

. 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