A 53-year-old woman without significant medical history presented with darkening of the skin on her face. She has a history of melasma and has been used a variety of skin lightening products from Mexico and Central America. Examination reveals bluish-black macules on the zygomatic regions of her face. A skin biopsy demonstrates a glassy yellow-brown substance deposited in the dermis.
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Exogenous ochronosis is characterized by gray-brown or bluish-black discoloration of the face, neck, back and extensor surfaces of the extremities. Other findings include caviar-like pinpoint papules and confetti-like hypopigmentation mixed with hyperpigmentation.
Ochronosis is a rare complication of certain topical medications, particularly when applied over long periods of time. Hydroquinone, a medication commonly found in both prescription and OTC skin-lightening agents, is most frequently implicated. Other medications (resorcinol, phenol, mercury, picric acid and antimalarials) have also been described.
The incidence of exogenous ochronosis is exceedingly rare. In the United States, only 22 cases of exogenous ochronosis associated with hydroquinone use have been reported. This represents about one reported case every year during the time period studied (1983-2006).
It is estimated that 10 to 15 million tubes of skin-lightening products containing hydroquinone are sold each year; hence, the risk of hydroquinone-induced ochronosis roughly equates to one patient per 10 to 15 million tubes sold. Overall, the use of topical hydroquinone is considered extremely safe and effective.
The exact cause of exogenous ochronosis remains unknown. However, several theories have been proposed. The use of hydroquinone may inhibit the activity of homogentisic acid oxidase, resulting in deposition of ochronotic pigment. Others suggest that hydroquinone stimulates melanin synthesis, either directly or via active metabolites. Sun exposure may also play a role in the pathogenesis.
Diagnosis & Treatment
Exogenous ochronosis diagnoses are made clinically and confirmed by biopsy. Histological examination of the dermis reveals yellow-brown (ochronotic) banana-shaped fibers, referred to as ochre bodies.
The first step in treatment is discontinuation of all possible offending medications. In some individuals the hyperpigmentation will gradually fade; although, it may take years before improvement is noted. Treatment of persistent ochronosis is difficult, and a number of modalities have been described: sunscreen, oral tetracycline, CO2 laser, dermabrasion and Q-switched laser. Referral to a dermatologist is recommended.
Brian S. Hoyt, BS, is a senior medical student at the University of Texas Medical School at Houston.
Adam Rees, MD, is a graduate of the University of California Los Angeles School of Medicine and a resident in the Department of Dermatology at Baylor College of Medicine in Houston.
- Bolognia J, Jorizzo JL, Schaffer JV. “Chapter 67: Disorders of Hyperpigmentation.” Dermatology. St. Louis: Mosby/Elsevier, 2012.
- James WD, Berger TD, Elston DM et al. “Chapter 26: Errors in Metabolism.” Andrews’ Diseases of the Skin: Clinical Dermatology. Philadelphia: Saunders Elsevier, 2011.
- Levin CY, Maibach H. “Exogenous ochronosis. An update on clinical features, causative agents and treatment options.” Am J Clin Dermatol. 2001; 2(4):213-7.
- Levitt J. “The safety of hydroquinone: a dermatologist’s response to the 2006 Federal Register.” J Am Acad Dermatol. 2007; 57(5):854-72.