
Case of the Month

A 47 year old woman presents for the evaluation and treatment of dark patches on both of her cheeks. The bilateral dark cheek patches have been present for approximately one year. She is otherwise healthy. I asked her if she was applying any medicines to the area and she said “No.” Immediately her husband said “what about that cream you get at the Somali store that you rub on your cheeks to brighten them?” She asked me if I considered that a medicine and I said possibly, do you have it with you? She reached into her purse and pulled out a cream that said hydroquinone 4%. I asked how long she had been using it and she said almost 2 years. Below are photomicrographs of a biopsy we performed (photographed by Erick Jacobson, M. D.):


Exogenous Ochronosis
The pathology report from Erick Jacobson, M. D., board certified dermatopathologist said: Consistent with Ochronosis. There is flattening of the rete pattern with solar elastosis, consistent with sun-damaged skin. In the dermis are yellow/brown hyalin bodies, many of which are fractured, and some of which are surrounded by a granulomatous infiltrate. These findings are consistent with ochronosis.
Exogenous Ochronosis
Ochronosis is a relative rare condition represented histologically by banana/oval-shaped ochre (yellow-brown)-colored deposits in the dermis.
There are 2 forms ochronosis:
Endogenous Ochronosis and Exogenous Ochronosis. Endogenous Ochronosis is also known as Alkaptonuria. Alkaptonuria (autosomal recessive) is caused by a deficiency of an enzyme called homogentisic acid oxidase. Without this enzyme (homogentisic acid oxidase), homogentisic acid ,a hydroquinone metabolite of tyrosine, builds up and irreversibly binds to dermal collagen. The presence of the collagen-bound homogentisic acid produces the banana-shaped ochre bodies in the dermis and associated skin discoloration. In Alkaptonuria, there is also significant systemic involvement and complications including, but not limited to: dark urine, osteoarthritis, discolored ears and eyes, damaged heart valves and kidney stones.
Exogenous ochronosis is a related manifestation of the same process, but it is not caused by a lack of homogentisic acid oxidase, but rather a gradual and localized inhibition of the enzyme. Homogentisic acid oxidase is blocked (locally) by the topical application of agents known as “phenolic intermediates”. These include hydroquinone, phenol, picric acid, mercury and resorcinol. Antimalarial medicines and other systemic agents containing the “phenolic intermediates”, just listed, may also produce a similar clinical picture of skin discoloration.
Clinically, exogenous ochronosis presents as grey-brown-dark blue-black macules and patches, often associated with melasma on the cheeks, it that was what the hydroquinone was being used to treat. There may be associated confetti-like hypopigmented macules in the area as a result of partially treated melasma, and some reports indicate that there may be hyperpigmented macules and papules around follicular openings seen with dermatoscopy. Erythema, as seen in this case, is often present.
The skin findings of Alkaptonuria (endogenous ochronosis) and exogenous ochronosis are identical under the microscope (banana and oval shaped ochre-colored deposits) as clearly seen in our case’s dermatopathology micrographs, above.
Treatment of exogenous ochronosis is challenging, at best. Discontinuing the hydroquinone containing product may provide some improvement. Various lasers have shown potential but inconsistent results.
For additional information on Alkaptonuria, please see: https://en.wikipedia.org/wiki/Alkaptonuria

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