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

Abstract

Ochronosis is a rare disease characterized by speckled and diffuse pigmentation symmetrically over the face, neck, and photo-exposed areas. It is characterized histologically by banana-shaped ochre-colored deposits in the dermis. It can present in exogenous or endogenous form. We report a case of exogenous ochronosis in a 50-year-old Indian woman after prolonged use of topical hydroquinone which is a rare complication with a commonly used drug which is available over the counter.

Introduction

Ochronosis is a rare disease characterized by speckled and diffuse pigmentation symmetrically over the face, neck, and photo-exposed areas. It is characterized histologically by banana-shaped ochre-colored deposits in the dermis. It can present in exogenous or endogenous form. We report a case of exogenous ochronosis in a 50-year-old Indian woman.

Case Report

A 50-year-old Indian woman presented with dark pigmentation symmetrically distributed over cheeks, forehead, chin, and neck. She had developed asymptomatic brown-colored pigmentation over the right cheek 25 years ago, which gradually involved the left cheek. The pigment gradually increased in extent while on topical treatment over last 7-8 years, to involve both cheeks, forehead, and chin, and the color became dark brown to black. She gave a history of prolonged topical use of 2-5% hydroquinone. There was no history of pigmentation at other sites and complaints pertaining to systemic involvement. On examination, there were multiple dark brown to black discrete pin-head-sized macules coalescing to form larger macules present in a reticulate and cribriform pattern over both malar and mandibular area, chin, and forehead [Figure 1a, b]. Atrophy and telangiectasias were present over some lesions. Rest of the skin examination was unremarkable. Histologic examination revealed ochre-colored fibers in the dermis, and homogenization of the collagen fibers in the dermis [Figure 2]. A diagnosis of exogenous ochronosis due to prolonged use of topical hydroquinone was made.

Figure 1.

(a, b) Dark brown to black descrete pin-head sized macules present in malar, mandibular, chin, and forehead

Figure 2.

Banana-shaped ochre-colored deposits in the dermis (H&E, 400×)

Discussion

Ochronosis is a rare disease characterized histologically by banana-shaped ochre-colored deposits in the dermis.[1] Ochronosis can present itself in either exogenous or endogenous form. Endogenous ochronosis or alkaptonuria is an autosomal recessive disease caused by a deficiency of homogentisic acid oxidase, which results in the accumulation of homogentisic acid, a hydroquinone metabolite of tyrosine. Homogentisic acid binds irreversibly to dermal fibrillar collagen which is said to be responsible for skin pigmentation and/or arthropathy.[2]

Exogenous ochronosis is a localized paradoxical hyperpigmentation of the skin due to prolonged use of bleaching agents containing hydroquinone and phenolic compounds. This entity was first described by Findlay et al.[3] The condition, unlike endogenous ochronosis, does not exhibit systemic involvement. The etiology of this hyperpigmentation remains unknown.[4] Topical hydroquinone may inhibit homogentisic acid oxidase in the dermis, with the result of a local accumulation of homogentisic acid that polymerizes to form ochronotic pigment.[5,6] The ochronotic coloration most commonly results from the prolonged use of certain topical agents like hydroquinones, but it also occurs with the use of antimalarials and products containing resorcinol, phenol, mercury, or picric acid.[7]

Histology of exogenous ochronosis characteristically reveals yellow- brown banana-shaped fibers in the papillary dermis. Homogenization and swelling of the collagen bundles are noted and a moderate histiocytic infiltrate may be present.[7]

Although it was originally believed that high concentrations of hydroquinone were causal, yet there have been reports of ochronosis after the use of 2% hydroquinone preparations.[8,9] Our patient applied 2% hydroquinone for a prolonged period of time, which suggests that it is not the high concentration of hydroquinone, but rather extended use of this substance, which causes the disease. Volatile excipients, occlusive vehicles, and keratolytic agents enhance penetration of hydroquinone. Treatment of this condition is very difficult. The causal agent must be avoided and improvement occurs slowly. Q-switched 755 nm alexandrite laser, Q-switched ruby laser, CO₂ laser, cryotherapy, trichloroacetic acid, tretinoin gel, dermabrasion have all been used for treatment.[4] So far we are aware of a single case report of exogenous ochronosis from India[1] and it has sparingly been reported from Asia.[10]

Conclusion

Exogenous ochronosis is a frequently missed and/or under-reported entity, which needs to be taken cognizance of, in order to prevent the cosmetically abrading, difficult to treat side effect, as a consequence of the relentless use of hydroquinone and its products.