Efficacy and safety of topical isobutylamido thiazolyl resorcinol (Thiamidol) vs. 4% hydroquinone cream for facial melasma: an evaluator-blinded, randomized controlled trial.

BACKGROUND: Melasma can be refractory to treatment, and relapses are frequent. Thiamidol is a new potent tyrosinase inhibitor that has been found effective as a cosmeceutical for the depigmenting of melasma. OBJECTIVE: This study compared the efficacy and tolerability of topical 0.2% Thiamidol vs. 4% hydroquinone for facial melasma. METHODS: Fifty women with facial melasma participated in a randomized, evaluator-blinded, controlled study from September through November 2020. Patients were randomly assigned to apply a double layer of 0.2% Thiamidol twice a day or 4% hydroquinone cream at bedtime, for 90 days. Both groups received tinted sunscreen (sun protection factor 60, PPD 20). The primary outcome was the change from the baseline Modified Melasma Area Seve:rity Index (mMASI) score. Secondary outcomes were improvements in the patients' quality of life [Melasma Quality of Life Index (MELASQoL)], colourimetry, and Global Aesthetic Improvement Scale (GAIS) evaluation. RESULTS: One participant, from the hydroquinone group, did not complete the study (unrelated to adverse effects). The mean (SD) age of the participants was 43 (6) years, and 86% were phototypes III-IV. Both groups exhibited a reduction in mMASI, MELASQoL, and colour contrast scores (P < 0.01). The mean [95% confidence interval (CI 95%)] reductions of the mMASI scores were 43% (35-50%) for Thiamidol and 33% (23-42%) for hydroquinone. There was no difference between the groups in the reductions in mMASI, MELASQoL, colourimetric contrast and GAIS scores (P ≥ 0.09). The GAIS analysis resulted in an improvement of 84% (CI: 95% 67-97%) for participants in the Thiamidol group and 74% (CI: 95% 61-93%) for those in the hydroquinone group. There were only mild adverse effects in the Thiamidol group, but allergic contact dermatitis was evidenced in two (8%) participants. CONCLUSION: The melasma improvement achieved using 0.2% Thiamidol did not differ from that of 4% hydroquinone cream. Thiamidol can be considered a suitable option for melasma patients with poor tolerability or treatment failure with hydroquinone.

French maritime pine bark extract (pycnogenol) in association with triple combination cream for the treatment of facial melasma in women: a double-blind, randomized, placebo-controlled trial.

BACKGROUND: Melasma can be recalcitrant to treatment, and relapses are common. Pycnogenol has been reported to be effective in treating melasma. OBJECTIVE: To compare the efficacy, safety and tolerability of 75 mg pycnogenol taken orally twice a day vs. a placebo, in association with the triple combination and broad-spectrum sunscreen for the treatment of facial melasma. METHODS: A randomized, double-blind, parallel, placebo-controlled study was conducted on 44 women with facial melasma in a single centre from May 2019 through November 2019. Patients with melasma were randomly assigned to orally take 75 mg pycnogenol (PYC) or a placebo (PLAC) twice a day for 60 days. Both groups also received tinted sunscreen [Sun Protection Factor (SPF) 50; Persistent Pigment Darkening (PPD) 17] for daytime use and a topical triple combination at bedtime. The primary outcome was a change from the baseline Modified Melasma Area Severity Index (mMASI) score. Secondary outcomes were improvements in the patients' quality of life (MELASQoL), colorimetric indices and Global Aesthetic Improvement Scale (GAIS). RESULTS: All participants completed the trial. The mean (SD) age of the participants was 39 (7) years, and 91% were phototypes III-IV. Both groups exhibited a reduction in mMASI scores, MELASQoL scores and colour contrast (P < 0.01). The mean (CI 95%) reductions of the mMASI scores were 49% (36-61%) for PYC and 34% (16-47%) for PLAC. The reductions in mMASI scores and colorimetric contrast were superior for the PYC group (P < 0.05). The analysis of GAIS resulted in an improvement of 86% (CI 95%: 68-96%) for the participants in the PYC group and 55% (CI 95%: 32-73%) for those in the PLAC group. There were no adverse effects related to oral treatment. CONCLUSION: Pycnogenol is well-tolerated and increases the effectiveness of broad-spectrum sunscreen and the triple combination in the treatment of facial melasma in women.

Factors associated with quality of life in facial melasma: a cross-sectional study.

BACKGROUND: Melasma is a common chronic focal hypermelanosis that affects photexposed areas as face, mainly in women at fertile age. It inflicts a significant impact in quality of life; nevertheless, quality of life scores (e.g. MELASQoL) are not strongly correlated with clinical severity (e.g. MASI) in facial melasma, suggesting that different factors can influence the perception of disease beyond the clinical extension or the intensity of pigmentation. OBJECTIVES: To explore clinical and socio-demographic aspects that influences MELASQoL scores. METHODS: Cross-sectional study enrolling 155 adults (>18 y.o.) with facial melasma. MELASQoL, MASI, clinical and demographic information were assessed. The associations among factors were explored by multivariable methods. RESULTS: The mean (SD) age of the participants was 39 (8) years, and 134 (86%) were females. The correlation (Spearman's rho) between MELASQoL and MASI was 0.35 (P < 0.05). In a multivariate regression, MELASQoL score was associated (P ≤ 0.05) to MASI score (ß = 0.6), lower income (ß = 6.8), be single (ß = 4.2) and low education level (ß = 5.0). At multiple correspondence analysis, MASI, sex, marriage, education and income were associated with MELASQoL, as well as MASI was associated to skin phototypes, income and education level. CONCLUSION: The perception of life quality impairment in melasma is influenced by low scholarly, low family income, single marital status and greater clinical severity.

Exploring pathways for sustained melanogenesis in facial melasma: an immunofluorescence study.

BACKGROUND: The physiopathology of epidermal hypermelanization in melasma is not completely understood. Several cytokines and growth factors are increased in skin with melasma, nevertheless, nor the pathways involved in the increased αMSH expression have been adequately evaluated, nor a model for sustained focal melanogenesis is available. OBJECTIVE: To explore stimulatory pathways for epidermal pigmentation in facial melasma related to αMSH: those linked to ultraviolet radiation, oxidative stress, inflammation, neural crest pigmentation cell differentiation and antagonism of αMSH. METHODS: Paired skin biopsies (3 mm) from 26 women with facial melasma and from normal adjacent skin (<2 cm far) were processed for immunofluorescence with markers for p53, p38, αMSH, MC1R, Melan-A, IL-1α, COX2, Wnt1, WIF-1 and ASIP. RESULTS: The fluorescence intensity in the skin from melasma was higher for MC1R, αMSH at epidermis as at melanocytes (P < 0.05). There were no differences between the sites in epidermal protein expression of COX2, IL-1α, p53, WIF-1 and ASIP (P > 0.1). P53 was expressed only in epidermis, without difference between sites (P = 0.92). WNT1 was remarkable in the epidermis of melasma (P < 0.01), but not in dermis. Positive p38 cells were prominent in the upper dermis of melasma (P < 0.01), despite no marking in epidermis. CONCLUSION: Melanogenesis in melasma involves epithelial secretion of αMSH and activation of the Wnt pathway; nevertheless, it seems to be independent of the stimulation by ultraviolet radiation/p53, IL-1α, COX2/PgE2 , WIF-1 and ASIP. Damaged cells at upper dermis suggest the role of senescence/autophagy in sustained pigmentation in melasma.

Gene and protein expression of oestrogen-ß and progesterone receptors in facial melasma and adjacent healthy skin in women.

OBJECTIVE: Compare gene and protein expression for oestrogen receptor-ß (ER-ß) and progesterone receptor (PR) in facial melasma and adjacent healthy skin. METHODS: A cross-sectional study including 42 women with facial melasma, conducted at the Dermatology Service of Botucatu Medical School of São Paulo State University, Brazil. Biopsies of the melasma skin were performed, together with healthy surrounding skin. The gene expression (real-time PCR) of the hormone receptors in the tissue was evaluated. Subsequently, skin fragments were immunostained for nuclear ER-ß and PR, evaluated according to their HSCORE (epidermis) and percentage of staining per microscopic field (dermis). RESULTS: Messenger RNA tissue expression for ER-ß and PR showed no difference between melasma-affected skin fragments and the healthy perilesional areas (P > 0.2). Median nuclear epithelial expression for ER-ß and PR was higher in lesioned skin (HSCORE 157 and 58) than in the healthy perilesional skin (HSCORE 97 and 19; P < 0.01), with no difference in dermal immunostaining. Nuclear histological expression for ER-ß was associated to sun-induced melasma and negative familiar background; PR expression was associated to sun-induced melasma and darker phototypes. CONCLUSION: No difference was observed in gene expression for oestrogen-ß and progesterone receptors in melasma-affected skin compared with adjacent healthy skin. However, the higher protein expression of these receptors in melasma-affected epithelia suggests hormonal participation in the pathogenesis of this disease.

Changes in nuclear morphology and chromatin texture of basal keratinocytes in melasma.

BACKGROUND: The pathogenesis of melasma and the role of keratinocytes in disease development and maintenance are not completely understood. Dermal abnormalities, the expression of inflammatory mediators, growth factors, epithelial expression of melanocortin and sexual hormones receptors suggest that not only melanocytes, but entire epidermal melanin unit is involved in melasma physiopathology. OBJECTIVES: To compare nuclear morphological features and chromatin texture between basal keratinocytes in facial melasma and adjacent normal skin. METHODS: We took facial skin biopsies (2 mm melasma and adjacent normal skin) from women processed for haematoxylin and eosin. Thirty non-overlapping basal keratinocyte nuclei were segmented and descriptors of area, highest diameter, perimeter, circularity, pixel intensity, profilometric index (Ra) and fractal dimension were extracted using ImageJ software. RESULTS: Basal keratinocyte nuclei from facial melasma epidermis displayed larger size, irregular shape, hyperpigmentation and chromatin heterogeneity by fractal dimension than perilesional skin. CONCLUSION: Basal keratinocytes from facial melasma display changes in nuclear form and chromatin texture, suggesting that the phenotype differences between melasma and adjacent facial skin can result from complete epidermal melanin unit alterations, not just hypertrophic melanocytes.

Risk factors for facial melasma in women: a case-control study.

BACKGROUND: Melasma is a localized chronic acquired hypermelanosis, common in adult women and which has an important impact on their life quality. Its pathology is unknown, despite some recognized triggering factors. OBJECTIVE: To evaluate risk factors for developing facial melasma in women. METHODS: This was a case-control study involving adult women with or without facial melasma, paired by age. Variables were grouped into hierarchical levels: personal characteristic data, exposure variables, links to hormonal stimuli and the State-Trait Anxiety Inventory questionnaire, Brazilian version. The data were analysed using conditional multiple logistic regression. RESULTS: We evaluated 207 patients and 207 controls. The mean age was 38 years. Cases differed from controls for phototype, Amerindian ancestry [odds ratio (OR) 2·59], years of beach or rural residence (OR 1·06), time exposed to sun at work (OR 1·65), time exposed to sun in leisure activities (OR 1·04), antidepressant/anxiolytic use (OR 4·96), menstrual irregularity (OR 3·83), pregnancy history (OR 3·59), years of oral contraceptive use (OR 1·23) and anxiety scores (OR 1·08). A family history of melasma was reported in 61% of cases and 13% of controls (OR 10·40). CONCLUSIONS: Facial melasma is independently associated with elements linked to pigmentation capacity, family ancestry, chronic sun exposure, sexual hormone stimuli, psychotropics and anxiety traits.

Clinical patterns and epidemiological characteristics of facial melasma in Brazilian women.

UNLABELLED: BACKGROUND; Melasma is a common acquired chronic hypermelanosis of sun-exposed areas which significantly impacts quality of life. There are few epidemiological studies in medical literature concerning these patients. OBJECTIVE: Characterize clinical and epidemiological data on Brazilian female patients with melasma. METHODS: A semi-structured questionnaire was administered to melasma patients treated at a dermatology clinic between 2005 and 2010. Association between variables was performed by multivariate regression models. RESULTS: We assessed 302 patients; intermediate skin phototypes III (34.4%) and IV (38.4%) were prevalent. Mean disease onset age was 27.5 ± 7.8 years and familiar occurrence of melasma was identified in 56.3%. The most commonly reported trigger factors were pregnancy (36.4%), contraceptive pills (16.2%) and intense sun exposure (27.2%). Preferred facial topographies were zygomatic (83.8%), labial superior (51.3%) and frontal (49.7%). Pregnancy induced melasma has been associated to early disease (OR = 0.86) and number of pregnancies (OR = 1.39). Childbearing was correlated to melasma extension. Older disease onset age was associated to darker skin phototypes. Co-occurrence of facial topographies supported clinical classification as centrofacial and peripheral melasma. CONCLUSION: This population was characterized by: a high prevalence in adult females, intermediate skin phototypes, disease precipitation by hormonal stimulus and familiar genetic influence.

Association between palmoplantar pustulosis and cigarette smoking in Brazil: a case-control study.

BACKGROUND: Palmoplantar pustulosis (PPP) discloses some differences compared to vulgar psoriasis (PV) in terms of age of onset, female predominance and low occurrence of psoriasis lesions elsewhere. Cigarette smoking has been associated to PPP in international studies; nevertheless, these studies were never performed among Brazilian. OBJECTIVES: To compare prevalence of smoking among PPP, PV and other dermatologic patients (NPD). METHODS: Case-control study involving 25 PPP patients from a reference psoriasis centre. Two control groups were matched according to gender and age: 50 patients with PV and 50 NPD. Confounders were adjusted by conditional multiple logistic regression. RESULTS: Among cases, 84.0% were female and PPP age of disease onset (41.4 years) was greater than PV (34.5 years). Prevalence of ever smoking was higher among cases (92.0%) than PV (52.0%) and NPD (30.0%). Adjusted odds ratio of PPP ever smoking compared to PV and NPD was 9.5 and 36.2, respectively. All smokers reported the onset of their habit before the development of PPP. CONCLUSIONS: There was significant association between PPP and smoking. However, the impact of giving it up in the clinical course of the disease remains to be established.