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Carotenemia

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Last Update: June 12, 2023.

Continuing Education Activity

First described in 1919 by Hess and Meyers, carotenemia is the medical terminology describing yellow-orange skin pigmentation due to high carotene levels in the blood. Excessive consumption of fruits and vegetables high in carotene content is often the culprit. Historically, carotenemia is a relatively old condition mentioned in a few old medical case reports. This condition was also reported during World War 1 and World War 2, when people mostly consumed a plant-based diet due to food shortages and famine. This activity describes the presentation of carotenemia and stresses the importance of the interprofessional team in its management.

Objectives:

  • Review the causes of carotenemia.
  • Describe the presentation of a patient with carotenemia.
  • Explain the differential diagnosis of carotenemia.
  • Summarize the importance of improving care coordination among interprofessional team members to improve outcomes for patients affected by carotenemia.
Access free multiple choice questions on this topic.

Introduction

First described in 1919 by Hess and Meyers, carotenemia is the medical terminology describing yellow-orange skin pigmentation due to high carotene levels in the blood.[1] Excessive consumption of fruits and vegetables high in carotene content is often the culprit.[2] Historically, carotenemia is a relatively old condition mentioned in a few old medical case reports. This condition was also reported during World War 1 and World War 2, when people mostly consumed a plant-based diet due to food shortages and famine.[3] Carotenoids are organic compounds found in various plants and food items. Beta-Carotene is the main carotenoid found in plants and is more often responsible for this condition.[4] Carotenemia is often first encountered by primary care providers. Although benign, this condition is often confused with jaundice, leading to unnecessary investigations. 

The condition of carotenemia is benign; however, it can lead to a wrong diagnosis of jaundice. Orangeness may also bear a significant symbolic significance.[5] Carotinemia was originally observed as xanthosis diabetica by von Noorden in 1904, who noted it to be more prominent on the palms and soles and in the nasolabial folds.[6]

Etiology

Ingestion is the main source of carotenoids in the human body. Excessive ingestion (greater than 30 mg a day) for a prolonged period could lead to carotenemia.[7] A high level of carotene is found in certain fruits and vegetables. Fruits include apricot, cantaloupe, mango, orange, papaya, peaches, and prunes. Vegetables include carrots, green beans, asparagus, broccoli, cucumber, lettuce, parsley, spinach, squash, mustard, pumpkins, kale, and sweet potatoes. Other food items with high carotene include butter, eggs, milk, and palm oil.[8] Although diet is often the culprit, cases of carotenemia have been reported in inherited disorders with the inability to convert carotene to vitamin A due to a deficiency in the beta-carotene-15-15'-dioxygenase enzyme.[9][3]

Diet-associated carotenemia is observed most commonly in infants and young children.[10] Mothers could also unknowingly induce carotenemia by feeding their infants excessive amounts of carrots in commercial food preparations.[2] Additionally, vegetarians are more prone to develop carotenemia than nonvegetarians. Consumption of carotene-rich nutritional supplements could also lead to this condition.[11]

Diseases, including hypothyroidism, hepatic disorders, diabetes mellitus, anorexia nervosa, and renal diseases, could also lead to carotenemia.[12]

Epidemiology

Although prevalence data is scarce, carotenemia is not an uncommon presentation to pediatricians and family physicians. A Sri Lankan study found a prevalence of carotenemia of 2% among 615 children on a high carotenoid-containing diet.[13] The age of presentation varies, but it primarily presents in children. A study from Glasgow found that the median age at presentation was 13 months, with a range of 7 months to 11 years. However, it may also be encountered in other age groups.[14] 

Another study reported a much higher prevalence (approximately 22%) of carotenemia among children with mental disabilities. The authors commented it might be due to the different modes and types of feeding they received compared to healthy children.[15]

Pathophysiology

Carotenoids are organic hydrocarbons mainly found in plant sources. Beta-carotene is the main carotenoid found in plants. Other carotenoids include alpha-carotene, beta-cryptoxanthin, lutein, and lycopene.[13] Beta-carotene is converted into vitamin A through 2 key enzymes, 15-15`-carotenoid dioxygenase, and beta-carotene-15-15'-dioxygenase.[16] Carotene serves as the main precursor of vitamin A in humans. It is mainly absorbed in the proximal small intestine into the portal circulation. Around 10% of ingested carotene is absorbed without conversion and is carried into the portal circulation to the liver.[14] Fortunately, hypervitaminosis A does not occur with excess carotene ingestion, as the body converts a limited quantity of carotene to vitamin A daily.[17] Carotene has a high affinity to fat and gets deposited in the corneum contributing to yellow skin discoloration and sparing mucus membranes if blood levels are excessively high.[8]

Many individuals with diabetes mellitus have increased serum carotene levels; however, only 10% of these patients have yellowing of the skin. Carotenemia could be associated with hyperlipidemia, restricted dietary habits, or a deficient hepatic conversion of carotene into vitamin A.

The commonly accepted pathophysiological mechanism underlying carotenemia in hypothyroidism is a deficient conversion of carotene into vitamin A, as well as hypercholesterolemia. The thyroid hormone is an antagonist to vitamin A and mediates its rate of catabolism. The consumption of vitamin A is reduced in hypothyroidism, and the conversion rate from carotene to vitamin A is decelerated.

Anorexia nervosa is also associated with carotenemia.[18] Carotenemia in patients with anorexia nervosa is associated with hypercholesterolemia, a reversible defect in carotene to vitamin A conversion. Furthermore, it could also be due to a normal carotene intake in the presence of a reduced requirement.

History and Physical

A good history and physical exam are key and often lead to the diagnosis. The following are the main items that should be addressed in the patient interview and physical examination.

History

A detailed history should be taken, including dietary history. The focus should be on the history of food consumption with high carotene with the estimation of the amount taken and duration. In addition, screening should be done for other conditions that could present with carotenemia, such as diabetes, anorexia, hypothyroidism, and liver and kidney diseases.

Metabolic carotenemia with no history of surplus carotene intake could be because of a genetic abnormality in the metabolism of carotenoids. Amenorrhea is also found to be associated with carotenemia. This is seen in vegetarians mainly. Patients may present with pruritus, abdominal pain, fatigue, and weight loss due to one of the rarer causes of carotenemia.[19] Pica, commonly seen in people with iron deficiency, could cause a compulsion to eat huge amounts of carrots, possibly leading to carotenemia.[20]

Physical Examination

Yellow-orange skin pigmentation is the hallmark of the condition. Pigmentation spares the sclera and mucous membranes (unlike jaundice) and concentrates in the palms, soles, forehead, tip of the nose, and nasolabial folds.[1] Yellow pigmentation often appears first in these areas, progressing gradually over the entire body.[21] Occasionally, carotenemia may also present with the coloration of the palate. It should be noted that the conjunctivae and oral mucosa lack stratum corneum. The pigmentary changes result from the accumulation of carotene in the stratum corneum. Examiners should also seek signs of diabetes, anorexia, and liver and kidney diseases. Children presenting with rarer causes of carotenemia unrelated to the diet may have physical signs suggestive of that specific disease process. Orange coloration in trichrome vitiligo may be due to carotenemia.[22]

Evaluation

Lab investigations are generally not required in establishing the diagnosis of diet-associated carotenemia. A good history and physical exam help narrow the differentials to tailor investigations. Laboratory investigation reveals elevated serum carotene levels, often in the range of 250 to 500 microgram/dl, with normal or slightly elevated liver enzymes. Measuring carotene levels in the skin could be facilitated by using reflection spectroscopy and Resonance Raman spectroscopy, both being noninvasive optical quantitative techniques for measuring carotenoid antioxidants in human skin in vivo. Plasma carotenoid status may be predicted by skin carotenoid status.[23][24] The bilirubin oxidase method has been reported to have misdiagnosed β-carotenemia as jaundice.[25]

A skin biopsy specimen could reveal autofluorescence in the superficial layer and a pemphigus-like pattern of intracellular autofluorescence.

Vitamin-A level is normal except in the rare case of inherited enzyme deficiency where the level will be low.[12][26] The evaluation must also include liver enzymes with bilirubin, thyroid function test, and screening for diabetes. Extensive investigations are seldom needed.

Treatment / Management

Clinicians should reassure the patients and their families as this is a benign condition unlikely to lead to serious consequences. The mainstay of treatment is reducing the amount of carotene in the diet, which will eventually lead to the resolution of skin pigmentation.[27] Parents should be informed that various green vegetables, such as green beans and spinach, are rich in carotene. Consultation with a dietitian may be helpful in some cases.[14]

Differential Diagnosis

Yellow skin discoloration has been reported in uncontrolled diabetes with no history of excess carotene ingestion. Often, yellow pigmentation resolves by regulating blood sugar.[6] Hypercarotenemia may also be seen in anorexia nervosa.[28][29][30]

Lycopenemia, a variant of carotenemia, is a yellow skin pigmentation caused by excessive tomato ingestion.[31][32]

Carotenemia has also been associated with a variety of other conditions, such as hypothyroidism, hypopituitarism, hypothalamic amenorrhea, liver disease, inborn errors of metabolism, and nephritic and nephrotic syndromes.[8]

In most of the above conditions, hypercarotenemia is probably associated with hyperlipidemia or impaired conversion of carotene to vitamin A.[14] Ingestion of some other chemicals besides carotene could lead to yellow skin staining. Examples include saffron, quinacrine, tetryl, picric acid, and dinitrophenol.[8] Carotenemia was also reported as a presentation for systemic lambda-type AL amyloidosis.[33] Neurological degenerative diseases and brain tumors seem (through unclear mechanisms) to affect carotene metabolism and could lead to carotenemia in the context of normal dietary carotene intake.[34] Some studies also suggested a correlation between biliary dyskinesia, celiac disease, and high carotene levels.[35][36]

Prognosis

A low-carotene diet leads to the progressive disappearance of yellow skin coloration. Yellow skin could persist for several months, even after carotene levels return to normal due to the lipophilic nature of carotenoids. Carotenemia is a benign condition.[37]

Complications

The condition is relatively benign and seldom leads to any severe complications. Toxic retinopathy has been reported due to excess canthaxanthin, a toxic carotenoid metabolite; however, changes are reversible, and no long-term sequelae have been reported.[38] Vitamin A poisoning does not usually occur even with very high doses of carotene, as the conversion of carotene to vitamin A occurs slowly. However, a man who allegedly ate 6-7 pounds of carrots weekly was found to have constipation, hypercarotenemia, increased liver enzymes, and possible vitamin A toxicity.[39]

Deterrence and Patient Education

Reassurance should be given to parents of the pediatric population that diet-induced carotenemia is a reasonably benign condition requiring no treatment. However, if there is extreme parental anxiety, providers may inform parents about diets rich in carotene, and the child could be started on a carotene-deficient diet.

Enhancing Healthcare Team Outcomes

Carotenemia is best managed by an interprofessional healthcare team. Clinicians (MDs, DOs, NPs, and PAs) will be primarily responsible for making an accurate diagnosis, although the issue may first be noticed by patients, parents, or nursing staff. Once diagnosed, the clinician and nurse will continue to follow and counsel the patient and their family if necessary and monitor the patient's progress and response to corrective actions. Patient education in collaboration with a dietitian improves the outcome of the condition and prevents further unnecessary investigations. Clinicians should provide a simple explanation of the problem and how it is linked to the diet. This will help with treatment compliance and appropriate food choices. Any interprofessional team member who notes a significant change in the patient's condition or a failure to respond to interventions should document their observations in the patient's health record and reach out to other team members as appropriate to enact corrective measures. This interprofessional approach will drive the best outcomes. [Level 5]

Review Questions

References

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Disclosure: Yasser Al Nasser declares no relevant financial relationships with ineligible companies.

Disclosure: Zohaib Jamal declares no relevant financial relationships with ineligible companies.

Disclosure: Mohammed Albugeaey declares no relevant financial relationships with ineligible companies.

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