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Hydroquinone is the first choice of topical bleaching agents used in treatment of melasma. In Brazil, hydroquinone is widely prescribed by physicians and often used by patients without a prescription. The principal adverse effects of its chronic use are confetti-like depigmentation and exogenous ochronosis. The latter manifests clinically with gray-brown or blue-black hyperpigmentation, as well as pinpoint hyperchromic papules that look like caviar, and therefore called caviar-like. On histopathology, curved ochre-colored structures, 'banana-shaped' fibers, appear in the papillary dermis. No description of dermoscopy in ochronosis is found in the literature. We report four cases of hydroquinone-induced exogenous ochronosis. Dermoscopy was performed in two patients on the areas with ochronosis, and in addition to the melasma findings, amorphous densely pigmented structures obliterating some follicular openings were observed. Exogenous ochronosis is an avoidable dermatosis that is difficult to treat. Dermatologists should be able to differentiate it from melasma and immediately discontinue hydroquinone. Dermoscopy might become a valuable resource in approaching exogenous ochronosis.

Background: Melasma is a common hypermelanosis characterized by symmetrical brownish macules, especially on the face. Histologic analysis demonstrates increased epidermal and dermal melanin. Dermoscopy is useful to estimate the depth of the melanin and may help in the diagnosis and classification of melasma, with therapeutic importance., Objectives: To evaluate the diagnostic concordance of dermoscopic classification of epidermal or mixed subtypes of melasma and the correlation between dermoscopic and histopathological findings., Methods: Twenty-eight women with facial melasma, phototypes III to V, ages between 30 and 61 years were selected. Based on the evaluation of clinical and dermoscopic images, two independent observers classified melasma into epidermal or mixed subtypes. The intra and interobserver concordances were calculated. Histopathological analysis of epidermal melanin extension and maximum number of melanophages per high-power field (400×; HPF) have been assessed. Association between the melanophages count and the dermoscopic classification was evaluated., Results: Intraobserver agreement was 82.1%, and between observers, from 78.6% to 89.3%, according to the Kappa index. Histopathology revealed increased intraepidermal melanin and the presence of dermal melanophages in all the samples. Ten or more melanophages/HPF was significantly associated with mixed melasma., Conclusions: Moderate to substantial concordance in the dermoscopic classification of melasma was found, and the correlation between this classification and the dermal melanophages count have been suggested. Intradermal component of every case of melasma should be considered for therapeutic and prognostic purposes., (© 2022 Wiley Periodicals LLC.)

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., (© 2021 the International Society of Dermatology.)

Background: Melasma has a complex pathogenesis, and various aggravating factors contribute to its recalcitrance to treatments. A combination of isobutylamido thiazolyl resorcinol (ITR) and hyaluronic acid (HA) could increase melasma treatment efficacy., Aims: To compare the efficacy and safety of 0.15% ITR plus HA vs 0.15% ITR or HA alone in melasma treatment., Methods: Ninety-two patients received ITR 0.15% plus HA (n = 30), 0.15% ITR (n = 31), or HA (n = 31) along with broad-spectrum sunscreen application for 12 weeks. Treatment efficacy was determined using modified Melasma Area Severity Index (mMASI), average melanin and melanin variation with Antera3D ® , and safety based on transepidermal water loss., Results: Compared with the HA group, the ITR+HA group showed significantly reduced mMASI at weeks 4, 8, and 12 (p = 0.026, 0.015, and 0.001, respectively), whereas the ITR group showed a significant reduction at week 12 (p = 0.027). There was no significant difference in the mMASI or average melanin level between the ITR+HA and ITR groups. Melanin variation was significantly lower in the ITR+HA group than in the ITR group at weeks 4, 8, and 12 (p = 0.027, 0.019, and 0.023, respectively)., Conclusions: The combination of 0.15% ITR and 0.15% ITR+HA effectively reduced melasma severity. HA could synergistically improve melasma homogeneity., (© 2021 Wiley Periodicals LLC.)