Exogenous ochronosis is the brown-black skin discoloration that occurs as a result of dermal accumulation of homogentisic acid. The most common cause of exogenous ochronosis is application of topical hydroquinone as part of the formulation in a variety of skin bleaching creams. It has also been reported to occur secondary to systemic antimalarials (ie, quinine, hydroxychloroquine) and the topical application of phenol derivatives, resorcinol, picric acid, and mercury. Resorcinol and mercury were historically added to hydroquinone-containing bleaching creams in unregulated preparations in some countries.

The pigmentation usually presents as dark brown, black, or blue-black macules, particularly over the zygoma and orbital ridges, but any other facial surface or skin coming into chronic contact with causative agents may be affected. It may be preceded by erythema, and, in advanced cases, papules and nodules may ensue.

Exogenous ochronosis from topical hydroquinone has been reported most frequently in individuals with darker skin, but individuals with lighter skin may be affected as well. This difference may represent the differential use of hydroquinone in different populations. Onset has been reported as soon as 3 months of use. While the condition is usually associated with the prolonged use of skin lightening creams containing higher concentrations of hydroquinone, it has also been reported with the use of lower concentrations for shorter periods. In a 2022 systematic review, the majority of cases occurred in individuals who had used hydroquinone for more than a year, but ochronosis developed before a year as well. The high incidence in South Africa has been postulated to occur secondary to the use of unregulated products with higher hydroquinone concentrations and resorcinol and mercury additives.

The pathogenic mechanism is unclear, but the leading hypothesis suggests that hydroquinone and other known causative agents cause local inhibition of homogentisic acid (HGA) oxidase, an enzyme in the tyrosine metabolic pathway required to break down HGA, thereby leading to an accumulation of HGA in the skin. HGA then polymerizes and forms ochronotic pigments in the dermis.

Related topic: Alkaptonuria