Carotenemia

Article Author:
Yasser Al Nasser
Article Editor:
Mohammed Albugeaey
Updated:
11/23/2018 10:35:12 AM
PubMed Link:
Carotenemia

Introduction

First described in 1919 by Hess and Meyers, carotenemia is the medical terminology describing yellow-orange skin pigmentation due to high levels of carotene in blood.[1] Excessive consumption of fruits and vegetables high in carotene content is often the culprit.[2] Historically, carotenemia is relatively an old condition that was mentioned in a few old medical case reports. This condition was also reported during World War I and World War II when people mostly consumed 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 most 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.

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.[5] 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.[6] 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 beta-carotene-15-15'-dioxygenase enzyme.[7][3]

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 who were on a high carotenoid-containing diet.[8] Age of presentation varies, but it mainly presents in children. A study from Glasgow found that 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.[9] Another study reported a much higher prevalence (approximately 22%) of carotenemia among children with mental disability. The authors commented it might be due to the different mode and type of feeding they received compared to healthy children.[10]

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.[8] Beta-carotene is converted into vitamin A through 2 key enzymes, 15-15`-carotenoid dioxygenase and beta-carotene-15-15'-dioxygenase.[11] Carotene serves as the primary precursor of vitamin A in human. 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.[9] Fortunately, hypervitaminosis A does not occur with excess carotene ingestion as the body converts a limited quantity of carotene to vitamin A daily.[12] Carotene has a high affinity to fat and get deposited in the corneum contributing to yellow skin discoloration sparing mucus membranes if blood levels are excessively high.[6]

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. Screening should be made for other conditions that could present with carotenemia such as diabetes, anorexia, hypothyroidism, and liver and kidney diseases.

Physical Exam: 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, the tip of the nose, and nasolabial folds.[1] Examiner should also seek signs of diabetes, anorexia, and liver and kidney diseases.

Evaluation

A good history and physical exam help narrow down the laboratory investigation necessary. Laboratory investigation reveals elevated serum carotene level, often in the range of 250 to 500 microgram/dl, with normal or slightly elevated liver enzymes. Vitamin-A level is normal[13] except in the rare case of inherited enzyme deficiency where the level will be low.[14] The evaluation must also include liver enzymes with bilirubin, thyroid function test and screening for diabetes. Extensive investigations are seldom needed.

Treatment / Management

Reassurance should be provided to the patients and their families as this is a benign condition and unlikely to lead to any 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.[15] Consultation with a dietitian may be useful in some cases.[9]

Differential Diagnosis

Yellow skin discoloration has been reported in uncontrolled diabetes with no history of excess carotene ingestion. Often, the yellow pigmentation resolves with regulating blood sugar.[16] Hypercarotenemia may also be seen in anorexia nervosa.[17][18][19] Lycopenemia, a variant of carotenemia, is a yellow skin pigmentation caused by excessive tomato ingestion.[20][21] Carotenemia has also been associated with a variety of other conditions such as hypothyroidism, hypopituitarism, hypothalamic amenorrhea, liver disease, inborn errors of metabolism, nephritic and nephrotic syndromes.[6] In most of the above condition, Hypercarotenemia is probably associated with hyperlipidemia or impaired conversion of carotene to vitamin A.[9] Ingestion of some other chemicals besides carotene could lead to yellow skin staining. Examples include saffron, quinacrine, tetryl, picric acid, and dinitrophenol.[6] Carotenemia was also reported as a presentation for systemic lambda-type AL amyloidosis.[22] Neurological degenerative diseases and brain tumor seem (through unclear mechanisms) to affect carotene metabolism and could lead to carotenemia in the context of normal dietary carotene intake.[23] Some studies also suggested a correlation between biliary dyskinesia, celiac disease, and high carotene levels.[24][25]

Complications

The condition is fairly benign and seldom lead to any serious complications. Toxic retinopathy has reported due to excess canthaxanthin, which is a toxic carotenoid metabolite, however, changes are reversible and no long-term sequelae have been reported [26].

Enhancing Healthcare Team Outcomes

Patient education in collaboration with a dietitian improves the outcome of the condition and prevent further unnecessary investigations. Physicians and nurse practitioners should provide a simple explanation of the problem and how it is linked to the diet. This will help with treatment compliance. Assurance and education should also be provided to the referring primary care physicians and pharmacist.