Exogenous ochronosis associated with hydroquinone: a systematic review

Abstract Exogenous ochronosis is a potential side effect associated with hydroquinone, and treatment is often unsatisfactory. Our study objectives were to review data on hydroquinone‐associated ochronosis to determine risk factors for patients experiencing this adverse event. On September 27, 2020 (MEDLINE/PubMed), and October 30, 2020 (Scopus and Web of Science), databases were searched for “ochronosis + hydroquinone” by both authors to reduce risk basis. PRISMA reporting guidelines were used to select 56 articles with a total of 126 patients with hydroquinone‐associated ochronosis. Included articles described hydroquinone‐associated ochronosis. Articles were excluded if they had irrelevant content, were non‐English language text, and were non‐case studies. Full text articles were assessed and recorded. Cross‐tabulation analysis was performed on categorical data, and Fisher exact test was performed. Ochronosis was most often reported in middle‐aged women (53.2%), of African descent (45.2%), Black races (55.5%), and Fitzpatrick skin types V–VI (52.4%). It was most frequently reported with unknown and hydroquinone concentrations greater than 4% (32.5 and 35.7% cases, respectively). Median duration of use was 5 years, with only four cases reported with courses 3 months or shorter and eight cases reported with use 1 year or less. All patients presented with facial blue‐black or gray‐blue macules in a reticulate, lace‐like fashion. Histopathology consistently showed solar elastosis and brownish‐yellow, ‘banana‐shaped’ fibers between degenerated collagen fibers of the papillary dermis. Based on these findings, we conclude that hydroquinone in concentrations above 4% and in treatment courses longer than 3 months may be associated with new‐onset ochronosis.