A Case Study in Treating Carotenoderma

Carotenoderma is characterized by orange-yellow skin pigmentation due to carotene deposition in the stratum corneum and is linked to high blood β-carotene levels. Although primarily benign, it can result from excessive dietary β-carotene intake or metabolic conditions like hypothyroidism, diabetes, pregnancy, and anorexia nervosa.¹ First described by Von Noorden in 1907, carotenoderma has been documented in various contexts, such as during World War II due to dietary changes and in populations consuming carotenoid-rich foods like red palm oil in West Africa.¹ 

In enterocytes, most β-carotene is converted into retinal by the enzyme 15-15’-dioxygenase. Retinal is then converted into retinol (vitamin A) and transported to the liver as chylomicrons after being complexed with long-chain fatty acids.¹ Absorption of intact β-carotene varies between 10% and 80%, influenced by dietary intake and vitamin A levels, and can be enhanced by small amounts of dietary fat, pancreatic lipase, bile acids, and thyroid hormone. Factors like high gastric pH, certain food constituents, and pectin can hinder absorption, while lutein and canthaxanthin inhibit its conversion to retinal.¹

β-carotene is stored in the liver and adipose tissues, with high concentrations in the testes and adrenal glands. There is a linear relationship between serum β-lipoprotein and β-carotene levels in normal individuals. β-carotene is absorbed in the small intestine and is excreted through the colon and epidermis via sebaceous glands, with a small amount excreted in urine.¹ In the epidermis, carotene accumulates in the lipid-rich stratum corneum.

Clinically, carotenoderma manifests when serum β-carotene levels exceed 250 µg/dL, causing pigmentation primarily in sweat-prone areas, which can be differentiated from jaundice by the lack of scleral involvement.² A skin biopsy could reveal autofluorescence in the superficial layer and a pemphigus-like pattern of intracellular autofluorescence.³ Though generally harmless, long-term high β-carotene levels may have potential complications, including weakness and hepatomegaly, although this is debated.¹ Treatment involves dietary changes, resolving the condition within weeks to months.¹ Recognizing carotenoderma is crucial to avoid unnecessary medical tests and to reassure patients, with further research needed to understand its long-term health implications.¹

Case Presentation

A 28-year-old female, with no significant past medical history, presented to a university dermatology clinic for evaluation of yellow-orange discoloration of the face and bilateral hands and feet. She reported that the discoloration had been present for 6 years and was asymptomatic. Family history was significant for similar discoloration of the skin in her mother and sister. The patient stated her current diet consisted predominantly of vegetables and lean meats, avoiding wheat and dairy. Among a multitude of vegetables, she reported consuming large quantities of carrots in her diet. She self-discontinued consumption of carrots for about a year, but she did not notice any improvement in the discoloration. She also previously took a multivitamin containing vitamin A, which she has since discontinued.

Her exam was significant for diffuse yellow-orange discoloration of the face (Figure 1), bilateral palms of the hands (Figure 2), and soles of the feet (Figure 3). The discoloration was greatest on the palms and soles and notably spared the sclera and mucous membranes. Laboratory findings revealed abnormally high serum carotene levels at 532 µg/dL (normal range 60 - 200 ug/dL), while her thyroid function tests, including TSH and Free T4, were within normal limits. Additional workups, including copper levels, a comprehensive metabolic panel, and tests for Gilbert syndrome and Addison’s disease performed in the past, had been within normal limits. The patient maintained a healthy BMI. 

Figure 1.  A 28-year-old female with diffuse yellow-orange discoloration of the face.

FIgure 2. Diffuse yellow-orange discoloration of bilateral palms of the hands in the same patient.

Figure 3. Diffuse yellow-orange discoloration of bilateral soles of the feet in same patient.

Discussion

This case underscores the importance of recognizing the potential genetic component in carotenoderma, especially when dietary intake alone does not explain the elevated serum β-carotene levels and persistent skin discoloration. While our patient’s history of high carrot consumption might initially suggest a dietary cause, the persistence of symptoms despite dietary changes and the presence of similar discoloration in her mother suggest a possible inherited metabolic predisposition. 

Carotenemia describes yellow pigmentation of the skin secondary to increased blood-carotene levels.4 This condition most commonly presents in infants and toddlers who consume large amounts of carrots in commercial infant food combinations.⁵ Cooking, pureeing, or mashing vegetables breaks down their cell wall and increases carotene availability for absorption, further making infants more susceptible to this condition.⁶ However, carotenemia can also be seen in older children and adults, particularly those who follow a vegetarian diet and eat large quantities of carotene-rich fruits and vegetables.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.6 While some carotene gets converted to vitamin A in the duodenum during digestion, the process of conversion is very slow, and massive quantities of carotene consumption cannot cause vitamin A toxicity.⁶

Carotene is a yellowish lipochrome that is normally present in keratin.⁶ The stratum corneum of the skin has a high lipid content and affinity for carotene; therefore, the yellow discoloration is usually most prominent on the palms and soles due to the thickness of the stratum corneum in those areas.6 Notably carotenemia spares the sclera of the eyes and mucous membranes.⁶ This is an important distinction to make to differentiate carotenemia from jaundice due to elevated bilirubin levels. Accurately differentiating between these conditions can avoid unnecessary workups and referrals. A similar condition to carotenemia, lycopenemia, has also been described.6 Lycopene is an isomer of beta-carotene found in tomatoes and other fruits.8 Elevated levels of blood lycopene from ingesting high quantities of tomatoes or tomato juice can cause a deep orange pigmentation of the skin similar to carotenemia.6 

Carotenemia is a benign condition, and the diagnosis can be made clinically. It can be seen with excessive ingestion of carotene (greater than 30mg a day) for a prolonged period.9 This is roughly equivalent to eight medium-sized raw carrots, 16 ounces of carrot juice, or one and a half cups of cooked sweet potato per day.^10-12 Carotene levels can be checked and typically exceed 250 μg/dl in affected patients.⁶ With dietary modification, skin pigmentation should return to normal in two to six weeks.6 Although it may be delayed several months after carotene levels return to normal due to the lipophilic nature of carotenoids.⁶ Carotenemia has also been associated with hypothyroidism and diabetes mellitus in the literature.^6,13,14 This is likely due to an increase in beta-lipoproteins seen in these conditions, with subsequent decrease in the conversion of carotene into vitamin A.⁶ The condition has also been associated with anorexia nervosa in patients who consume a pure or predominantly vegetarian diet.⁷ Therefore, if clinical suspicion is present, it may be reasonable to check for these comorbid conditions in a patient presenting with carotenemia. Metabolic carotenemia due to a deficiency of the beta-carotene 15-15’ dioxygenase enzyme, which converts carotene into vitamin A, has also been described in familial cases.¹⁵ The mode of inheritance is unknown and has been described in individuals exhibiting carotenemia in the absence of excessive carotene intake.^16,17 A referral to genetic counseling may be considered in such cases. 

Genetic abnormalities may involve mutations in the BCMO1 gene, which encodes the enzyme β-carotene-15,15’-monooxygenase, critical for converting carotenoids to vitamin A.¹⁶ This mutation, a T170M missense mutation, leads to a 90% reduction in enzyme activity, suggesting that haploinsufficiency of BCMO1 may contribute to these conditions, particularly in individuals consuming a diet high in carotenoids but low in preformed vitamin A.¹⁸ Cases in the literature have documented individuals with hypercarotenaemia and normal vitamin A levels, suggesting enzymatic deficiencies or blockages in this metabolic pathway. Although specific genetic mutations, such as those in the BCMO1 gene, have been implicated, not all cases present with these known mutations, indicating potential variability in genetic factors contributing to the disorder.¹⁶ This underscores the need for further genetic investigation to better understand the underlying mechanisms and heritability of this metabolic condition. 

Disclosures: The authors report no financial disclosures. 

1. Maharshak N, Shapiro J, Trau H. Carotenoderma—a review of the current literature. Int J Dermatol. 2003;42(3):178-181. https://doi.org/10.1046/j.1365-4362.2003.01657.x

2. Tung EE, Drage LA, Ghosh AK. Carotenoderma and hypercarotenemia: markers for disordered eating habits. J Eur Acad Dermatol Venereol. 2006;20(9):1147-1148. https://doi.org/10.1111/j.1468-3083.2006.01643.x

3. Al Nasser Y, Jamal Z, Albugeaey M. Carotenemia. In: StatPearls. StatPearls Publishing; 2024. Accessed August 24, 2024. https://www.ncbi.nlm.nih.gov/books/NBK534878/

4. Leung AK. Benign carotenemia in children. Can Fam Physician. 1989;35:81-83.

5. Karthik SV, Campbell-Davidson D, Isherwood D. Carotenemia in infancy and its association with prevalent feeding practices. Pediatr Dermatol. 2006;23(6):571-573. https://doi.org/10.1111/j.1525-1470.2006.00312.x

6. Lascari AD. Carotenemia: a review. Clin Pediatr (Phila). 1981;20(1):25-29. https://doi.org/10.1177/000992288102000103

7. Kemmann E, Pasquale SA, Skaf R. Amenorrhea associated with carotenemia. JAMA. 1983;249(7):926-929.

8. Agarwal S, Rao AV. Tomato lycopene and its role in human health and chronic diseases. CMAJ. 2000;163(6):739-744. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC80172/

9. Rock CL. Carotenoids: biology and treatment. Pharmacol Ther. 1997;75(3):185-197. https://doi.org/10.1016/S0163-7258(97)00054-5

10. FoodData Central. U.S. Department of Agriculture. Accessed August 26, 2024. https://fdc.nal.usda.gov/fdc-app.html#/food-details/168483/nutrients

11. Zelman KM. Carrot juice: what are the health benefits? WebMD. Accessed August 26, 2024. https://www.webmd.com/diet/health-benefits-carrot-juice

12. Can eating too many carrots turn your skin orange? Cleveland Clinic. Accessed August 26, 2024. https://health.clevelandclinic.org/can-eating-too-many-carrots-turn-your-skin-orange

13. Christopher R, Rangaswamy GR, Santhoshkumar N, Shetty KT. Carotenoderma in metabolic carotenemia. Indian Pediatr. 1997;34(11):1032-1034.

14. Aktuna D, Buchinger W, Langsteger W, et al. Beta-carotene, vitamin A and carrier proteins in thyroid diseases. Acta Med Austriaca. 1993;20(1-2):17-20.

15. Vaughan Jones SA, Black MM. Metabolic carotenaemia. Br J Dermatol. 1994;131(1):145. https://doi.org/10.1111/j.1365-2133.1994.tb08480.x

16. Chattopadhyay M, Pramanik R, McGrath JA, Burrows NP. Familial carotenaemia and carotenoderma. Clin Exp Dermatol. 2014;39(6):771-772. https://doi.org/10.1111/ced.12317

17. Svensson A, Vahlquist A. Metabolic carotenemia and carotenoderma in a child. Acta Derm Venereol. 1995;75(1):70-71. https://doi.org/10.2340/00015555757071

18. Lindqvist A, Andersson S, Biörklund A, et al. Loss-of-function mutation in carotenoid 15,15′-monooxygenase identified in a patient with hypercarotenemia and hypovitaminosis A. J Nutr. 2007;137(11):2346-2350. https://doi.org/10.1093/jn/137.11.2346

Marcus Rossi, MD

Resurrection Medical CenterUniversity of Illinois Chicago College of Medicine
Chicago

Ryan Bunney, MD

University of Illinois Chicago College of Medicine
Chicago

Melissa Nickles, MD

University of Illinois Chicago College of Medicine
Chicago

Roger Haber, MD

University of Illinois Chicago College of Medicine
Chicago

Key Takeaways

• Carotenoderma is a benign condition characterized by yellow-orange skin pigmentation due to elevated serum β-carotene levels, most prominently affecting the palms and soles while sparing the sclera and mucous membranes.
• Excessive dietary intake of carotene (>30 mg/day) is the most common cause, although metabolic conditions such as hypothyroidism, diabetes mellitus, anorexia nervosa, and rare enzymatic deficiencies should be considered.
• Persistent hypercarotenemia despite dietary modification and a positive family history may indicate a genetic predisposition.
• Accurate clinical recognition is essential to differentiate carotenoderma from jaundice and avoid unnecessary laboratory workups, imaging, and referrals.