Carotenemia

Practice Essentials

Carotenemia is a clinical condition characterized by yellow pigmentation of the skin (xanthoderma) and increased beta-carotene levels in the blood. In most cases, the condition follows prolonged and excessive consumption of carotene-rich foods, such as carrots, squash, and sweet potatoes. Carotenemia is a common finding in children. The condition of carotenemia is harmless, but it can lead to a mistaken diagnosis of jaundice. Orangeness also may possess a significant symbolic significance.^[1]

 See the image below.

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Carotenoderma visible on nasolabial folds of young child.

Carotene is a lipochrome that normally adds yellow color to the skin. With elevated blood levels of carotene, the prominence of this yellowing is increased. Carotenemia may be particularly evident when the stratum corneum is thickened or when the subcutaneous fat is strongly represented. The condition is more easily appreciated in light-complexioned people, and may present chiefly as yellowing of the palms and the soles in more darkly pigmented individuals.

Signs and symptoms

Also see History.

Carotenemia is characterized by a yellow pigmentation of the skin that is more pronounced under artificial light.

Because carotene is excreted by sebaceous glands and is present in sweat, the yellow pigmentation is particularly noticeable in areas where sweating is marked.

Yellow pigmentation often appears first on the tip of the nose, palms, soles, and nasolabial folds, extending gradually over the entire body.^[2]  However, the yellow pigmentation is most prominently displayed on the palms, soles, and nasolabial folds. The pigmentary change results from deposition of carotene in the fat-soluble stratum corneum.

The sclerae are always spared, which readily distinguishes carotenemia from jaundice; however, carotenemia occasionally may present with coloration of the palate. Note that the conjunctivae and oral mucosa are areas lacking stratum corneum.

Children who present with rare causes of carotenemia that are not related to diet may have physical signs specific to that disease process. Trichrome vitiligo with an orange coloration may be due to carotenemia.^[3]

Diagnostics

Laboratory studies are not generally indicated in the evaluation of diet-induced carotenemia. If studies are made, carotenemia can be verified by a high serum beta-carotene level, normal liver function test results, and a normal or slightly elevated vitamin A level. (The serum beta-carotene level can be increased 3-4 times the normal value and still be associated with a normal or only slightly elevated vitamin A level.) Accumulation of beta-carotene in the skin is delayed by up to 2 weeks, in contrast to the serum.

Elevated serum carotene levels range between 250-500 µg/dL. Multiple authors have reported wide variations in reference range values of serum carotene, making the interpretation of such values difficult.

Measuring carotene levels in skin may be facilitated by use of Resonance Raman spectroscopy and reflection spectroscopy, both noninvasive optical quantitative methods for the measurement of carotenoid antioxidant levels in human skin in vivo. Skin carotenoid status may be a good way to predict plasma carotenoid status.^{[4, 5]}

β-Carotenemia was misdiagnosed as jaundice using the Bilirubin Oxidase Method.^[6]

A skin biopsy specimen may show autofluorescence in the superficial horny layer and a pemphiguslike pattern of intracellular autofluorescence.

Management

Reassure parents of pediatric patients that diet-induced carotenemia is a benign condition that requires no treatment. If extreme parental anxiety is present, physicians can inform parents which foods are rich in carotene, and the child can be placed on a carotene-deficient diet.

With elimination of the intake of carotene-rich foods, serum carotene levels drop sharply within a week and the yellow discoloration of the skin gradually disappears over several weeks to months. Medications are not indicated for the treatment of diet-induced carotenemia.

Inform parents that many green vegetables, such as spinach and green beans, are rich in carotene.^[7]

Other causes of carotenemia are extremely rare in children. When suspected, direct appropriate investigation and treatment toward the underlying etiology.

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Background

Carotinemia was originally noted as xanthosis diabetica in 1904 by von Noorden, who observed it to be prominent in the nasolabial folds and on the palms and soles.^[8]

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Pathophysiology

Carotenoids are pigments of plant origin and are responsible for the yellow and orange color of fruits and vegetables. Carotenoids act as antioxidants, affect cell growth regulation, and modulate gene expression and immune response. Animals are incapable of synthesizing carotenoids. Carotenoids are among the nutrients most commonly linked with prenatal and neonatal health; avocados are high in carotenoids.^[9]

Carotenes are the hydrocarbon component of carotenoids. Carotene derived from plant foods is the primary source of dietary vitamin A (retinol). Ingested carotenes, enclosed as crystals or amorphous solids within vegetable cells, are converted to vitamin A in the mucosal cells of the small intestine.

Approximately 10% of ingested carotene is absorbed unchanged and is carried directly to the liver by portal circulation. Factors influencing the absorption of carotene include the fiber content of the plant and the particulate size of the food. Pancreatic lipase, bile acids, fat, and, possibly, thyroid hormone aid in the absorption of carotene.

Cooking, pureeing, or mashing fruits and vegetables ruptures cell membranes, thereby increasing the bioavailability of carotene for absorption. Consumption of mashed or pureed food, which is common in infants, may account for an increased incidence of diet-induced carotenemia.

Carotene is excreted through the colon and epidermis. In the latter area, the horny layer of skin reabsorbs carotene if excretion is unusually heavy. In fact, carotenoids accumulate in the epidermis about 2 weeks after serum levels achieve equilibrium, and maximum accumulation occurs in areas with an abundance of sweat glands, such as the nasolabial folds, palms, and soles.

Carotene does not readily cross the placenta but is found in high concentrations in human milk. Consequently, infants who are breastfeeding have higher serum levels of carotene than do infants fed with formula.

Excessive ingestion of carotenoids is nontoxic. Although in dietary carotenemia, elevated serum carotene often is accompanied by a corresponding elevation in serum vitamin A levels, hypervitaminosis A is not observed, presumably because the conversion of carotenoids to vitamin A is regulated. In other causes of carotenemia, serum vitamin A levels are within reference ranges or low.

Intestinal disease and infections may impair the absorption of carotene. Ingestion of mineral oil also decreases absorption, whereas water dispersion agents enhance absorption. The conversion of beta-carotene (provitamin A) to vitamin A is accelerated by thyroxine and hyperthyroidism.

• References

Etiology

Dietary sources

Diet-induced carotenemia is observed most frequently in infants and young children.^[10] Mothers may induce the condition by giving their infants large amounts of carrots in commercial infant food preparations.^[11]

In addition, vegetarians are more likely to develop carotenemia than nonvegetarians. The condition may also be associated with the ingestion of carotene-rich nutritional supplements.^[12]

The health benefits of foods that contain retinoids may encourage their excessive intake, whether for the foods’ antioxidant vitamins^[13] or to stimulate T cells.^{[14, 15]} The consumption of fresh fruits and vegetables, such as carrots, may be beneficial to patients with psoriasis and porphyria because of their high content of carotenoids.^{[16, 17]}

Carotenes occur in all pigmented fruits and vegetables, being synthesized as they ripen. In green vegetables, the color of carotene is often masked by the green color of chlorophyll. As a rule of thumb, the deeper the green or yellow of a fruit or vegetable, the more carotene it contains. Although often overlooked by parents, most strained baby foods on the market contain carrots. Ingestion of nutrient supplements is another source of carotenemia. A strict vegetarian who consumed more than six carrots daily for several years developed phytobezoars, first evident with severe epigastric pain and the yellow-orange pigmentation of hands, reflecting carotenemia.^[18]

Human and cow milk also contain carotene. The occasional yellow color of milk is due to carotene content, and human milk provides a rich source of carotene, especially if maternal serum carotene levels are high. (The yellow color of colostrum is caused by carotene content.)

Diseases-related sources

Diseases, including hypothyroidism,^[19]  diabetes mellitus,^[20]  hepatic disorders, anorexia nervosa, and renal diseases, may also give rise to carotenemia.^[7]

Diabetes mellitus

Many individuals with diabetes have elevated serum carotene levels, but only 10% of these individuals exhibit yellowing of the skin. Carotenemia may be related to restricted dietary habits, hyperlipidemia, or a deficiency in the conversion of carotene into vitamin A by the liver.

Hypothyroidism

The commonly accepted cause of carotenemia in hypothyroidism is a decrease in the conversion of carotene into vitamin A, as well as associated hyperlipidemia and hypercholesterolemia.

Thyroid hormone is antagonistic to vitamin A and controls its rate of consumption. In hypothyroidism, the consumption of vitamin A is decelerated, and the rate of conversion from carotene to vitamin A is reduced.

Anorexia nervosa

The association between carotenemia and anorexia nervosa is well documented. Carotenemia in patients with this disease is not thought to be associated with a high-carotene diet. It may instead be related to hypercholesterolemia, which is an occasional, albeit reversible, defect in the conversion of carotene to vitamin A, or it may result from a normal intake of dietary carotene in the presence of a decreased requirement.

Systemic amyloidosis

Systemic lambda-type AL amyloidosis may be associated with hyper–β-carotenemia with a prominent carotenoderma facilitating recognition of the diagnosis.^[21]

Other

Disorders associated with the development of carotenemia also include the following:

• Liver disease - Primary hepatic injury may prevent the conversion of carotene to vitamin A
• Kidney disease - Serum carotene levels may be markedly elevated in patients with chronic glomerulonephritis and nephrotic syndrome
• Inborn errors of metabolism - Carotenemia may result from a failure to convert carotene into vitamin A due to an inborn error of metabolism
• Familial conditions

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Prognosis

A low-carotene diet leads to progressive disappearance of the yellow skin discoloration. Because of the lipophilic nature of carotenoids, however, sufficient amounts can remain in tissue for several months, causing yellow skin even after serum carotene levels return to normal.

Carotenemia is a benign condition. Complications are rare with diet-induced carotenemia; Vitamin A poisoning does not occur even with massive doses of carotene, because the conversion of carotene to vitamin A takes place slowly. (However, a man who had allegedly ingested 6-7 pounds of carrots per week was observed with constipation, hypercarotenemia, elevated liver enzyme levels, and possible vitamin A toxicity.)^[22] )

A correlation between metabolic carotenemia and biliary dyskinesia has been suggested. In patients with metabolic carotenemia, significant relationships were identified between the gallbladder contraction rate and the levels of serum carotene, vitamin A, and lipids.

Amenorrhea may be associated with carotenemia. This occurs in patients who consume a pure or predominantly vegetarian diet without red meat. Dietary modifications can reduce carotene levels, which, in turn, normalize the menstrual cycle.

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History

A history of excessive carotene intake consistent with the diagnosis of hypercarotenemia is usually present.

Metabolic carotenemia without a history of excessive carotene intake may be due to a genetic defect in the metabolism of carotenoids.

As previously mentioned, amenorrhea may be associated with carotenemia. This occurs in patients who consume a pure or predominantly vegetarian diet without red meat. Dietary modifications can reduce carotene levels, which, in turn, normalize the menstrual cycle.

Patients may present with symptoms—such as pruritus, fatigue, abdominal pain, and weight loss—specific to one of the rare causes of carotenemia.^[23]

Pica, common in people with iron deficiency, may produce a compulsion to eat excessive amounts of carrots, which may possibly lead to carotenemia.^[24]

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