Case of the month

This woman was diagnosed several years ago with melasma. She has been using a topical over-the-counter hydroquinone (2%) cream product to fade the brown macules and patches of melasma for the past 11 months. She noted that at approximately six months after initiating the hydroquinone (2%) cream treatment, the areas actually started to worsen and become darker. She has been using the topical hydroquinone (2%) cream ever since with hopes of improvement, but without any success and the condition, by her husband's report, has gradually worsened over the past several months.

What is your diagnosis?

Diagnosis:

There are 2 types of ochronosis: Exogenous ochronosis and Endogenous ochronosis. Endogenous ochronosis is a rare genetic condition also know as alkaptonuria. Alkaptonuria is an autosomal recessive disease where a defect in the production of homogentistic acid oxidase causes a build up of homogentistic acid. Homogentistic acid binds to collagen fibers causing arthropathy in systemic (endogenous) disease and dark patches in the exogenous form.

Hydroquinone is used to treat melasma by inhibiting tyrosinase, which inhibits melanin production. Unfortunately, over time hydroquinone also blocks homogentistic acid oxidase resulting in a build up of homogentistic acid. This homogentistic acid polymerizes and binds to collagen fibers in the skin producing the dark brown (ochronotic) color.
Is also seen with the chronic use of other medications including certain antimalarials and products that contain resorcinol, phenol, mercury, or picric acid.
Dermatopathologically, exogenous ochronosis has a very characteristic look; often described as “brown banana shaped deposits/fibers in the dermis”.
There has been quite a bit of internet concern and discussion on the safety of hydroquinone products. Most of it has been perpetuated by non-physicians who don’t have any experience or ability to prescribe hydroquinone. I have had discussions with several senior dermatologists who have used it effectively and safely for many years. To a person, no dermatologist I have ever asked has ever seen any malignancy from the use of hydroquinone. In fact, the (poorly done?) studies showed renal malignancies in rats that were species specific. For a very nice review of this concern, please see:

Although reported to be rare, I do see exogenous ochronosis on a regular basis by patients using topical hydroquinone-containing products over a long period of time. I have not seen if the hydroquinone included exogenous ochronosis if hydroquinone is used for 4 months or less, and that is what I recommend to my patients. I limit the use of hydroquinone-containing products to 4 months. I don’t allow a re-start unless a 2 month “vacation” is taken from hydroquinone product.

As an aside, I have recently used platelet rich plasma injections combined with meticulous sun protection with good results in treating melasma.

References:

The safety of hydroquinone: A dermatologist's response to the 2006 Federal Register

US Library of Medicine Exogenous ochronosis After Prolonged Use of Topical Hydroquinone (2%) in a 50-Year-Old Indian Female

For more cases of the month

Dermatology Case of the Month Archive by Charles Crutchfield III, MD