Perspectives of topical formulations for melasma.

Melasma is acquired hyperpigmentation that mainly affects the face, can cause negative changes in self-esteem, and mostly affects women. Treatment is difficult, and different drugs can be used in mono or combination therapy. In this article, we present a brief overview of melasma, how to evaluate it, and a synthesis of the most commonly used topical therapies and their indications, including sunscreens, pharmacological agents, and plant extracts. Hydroquinone (4%) in monotherapy or combined with corticosteroids (dexamethasone and fluocinolone acetonide) and retinoids (tretinoin); arbutin (1%); methimazole (5%); kojic (2%), azelaic (20%), and tranexamic (5%) acids are the pharmacological agents that stand out. Correct application of these substances determines a variable improvement in melasma but often causes adverse reactions such as erythema, itching, and burning at the application site. Vitamin C can contribute to the reduction of melasma and have little or no adverse effects while sunscreens are normally used as coadjuvant therapies. In conclusion, we have compiled specific topical therapies for treating melasma and discussed those that are the most used currently. We consider it important that prescribers and researchers evaluate the best cost-benefit ratio of topical therapeutic options and develop new formulations, enabling efficacy in the treatment with safety and comfort during application, through the reduction of adverse effects.

Melasma en el 2021: actualización en la patogénesis y en el enfrentamiento terapéutico / Melasma in 2021: update on the pathogenesis and therapeutic coping

El Melasma es una patología con alta prevalencia a nivel mundial presente en alrededor de un 10% de la población Latinoamericana. Se caracteriza por ser una hipermelanosis cutánea adquirida que ocurre con más frecuencia en cara y cuello de mujeres con fototipos de piel III-VI de Fitzpatrick. Su patogenia aún no ha sido completamente dilucidada; sin embargo, existe evidencia que respalda la asociación del melasma con la radiación ultravioleta, la luz visible, la estimulación hormonal, factores genéticos y procesos inflamatorios. Su diagnóstico es fundamentalmente clínico, y es apoyado por instrumentos de medición que nos permiten objetivar la severidad e impacto en la calidad de vida de los pacientes afectados. El tratamiento continúa siendo un desafío ya que, si bien existen múltiples terapias que han demostrado efectividad, aún no han logrado una remisión completa, presentando una alta tasa de recurrencia. Dentro de las opciones terapéuticas destacan los tratamientos tópicos combinados, los peelings químicos y las terapias basadas en láser, sin embargo, lo más importante es hacer énfasis en la fotoprotección como medida preventiva. En esta revisión pretendemos actualizar sobre los últimos avances tanto de la fisiopatología como del tratamiento del melasma

Melasma is a pathology with a high prevalence worldwide, present in approximately 10% of the Latin American population. It is a cutaneous hypermelanosis that presents itself more frequently on the face and neck of women with Fitzpatrick skin phototypes III-VI. Its pathogenesis has not yet been fully elucidated, however, there is evidence that supports its association with ultraviolet radiation, hormonal stimulation, genetic factors, and inflammatory processes. Its diagnosis is fundamentally clinical, and is supported by clinical scores that allow us to objectify the severity and impact on the quality of life of patients who suffer from it. Treatment continues to be a challenge since, although there are multiple therapies that have demonstrated effectiveness, they have not yet achieved a complete and / or definitive remission of the disease, presenting a high recurrence rate. Treatment options include combined topical therapy, chemical peels and laser-based treatments. Much emphasis has been placed lately on photoprotection of the skin as a preventive measure. In this review we intend to update the latest advances in both the pathophysiology and treatment of melasma

Diffuse cutaneous melanosis: rare complication of metastatic melanoma.

Diffuse cutaneous melanosis is a rare complication of metastatic melanoma related to a worse prognosis. There are few cases reported in the literature. Its pathogenesis has not been completely elucidated, although studies have suggested certain mechanisms for its occurrence. It is clinically manifested as a blue-gray discoloration of the skin and mucous membranes in a cephalo caudal progression and usually associated with melanuria. Skin and mucosa histopathology reveals only the presence of melanophages in the dermis, mainly perivascular, and free interstitial melanin. We report the case of a 68-year-old male with metastatic melanoma, diffuse hyperpigmentation of the skin and melanuria.

African ancestry is associated with facial melasma in women: a cross-sectional study.

BACKGROUND: Melasma is a chronic acquired focal hypermelanosis affecting photoexposed areas, especially for women during fertile age. Several factors contribute to its development: sun exposure, sex steroids, medicines, and family history. Melanic pigmentation pathway discloses several SNPs in different populations. Here, we evaluated the association between genetic ancestry and facial melasma. METHODS: A cross-sectional study involving women with melasma and an age-matched control group from outpatients at FMB-Unesp, Botucatu-SP, Brazil was performed. DNA was extracted from oral mucosa swabs and ancestry determined by studying 61 INDELs. The genetic ancestry components were adjusted by other known risk factors by multiple logistic regression. RESULTS: We evaluated 119 women with facial melasma and 119 controls. Mean age was 39 ± 9 years. Mean age at beginning of disease was 27 ± 8 years. Pregnancy (40%), sun exposure (37%), and hormonal oral contraception (22%) were the most frequently reported melasma triggers. All subjects presented admixed ancestry, African and European genetic contributions were significantly different between cases and controls (respectively 10% vs 6%; 77% vs 82%; p < 0.05). African ancestry (OR = 1.04; 95% CI 1.01 to 1.07), first generation family history (OR = 3.04; 95% CI 1.56 to 5.94), low education level (OR = 4.04; 95% CI 1.56 to 5.94), and use of antidepressants by individuals with affected family members (OR = 6.15; 95% CI 1.13 to 33.37) were associated with melasma, independently of other known risk factors. CONCLUSIONS: Facial melasma was independently associated with African ancestry in a highly admixed population.

Diffuse cutaneous melanosis: rare complication of metastatic melanoma

Abstract Diffuse cutaneous melanosis is a rare complication of metastatic melanoma related to a worse prognosis. There are few cases reported in the literature. Its pathogenesis has not been completely elucidated, although studies have suggested certain mechanisms for its occurrence. It is clinically manifested as a blue-gray discoloration of the skin and mucous membranes in a cephalo caudal progression and usually associated with melanuria. Skin and mucosa histopathology reveals only the presence of melanophages in the dermis, mainly perivascular, and free interstitial melanin. We report the case of a 68-year-old male with metastatic melanoma, diffuse hyperpigmentation of the skin and melanuria.

Corneal melanosis successfully treated using topical mitomycin-C and alcohol corneal epitheliectomy: a 3-year follow-up case report.

We report a case of primary acquired corneal melanosis without atypia associated with corneal haze in a patient with a history of limbal malignant melanoma and the effect of mitomycin-C. A 75-year-old woman with a history of limbal malignant melanoma presented with loss of vision in right eye. Corneal examination showed a patchy melanotic pigmentation with a central haze. Topical mitomycin-C improved visual acuity and corneal haze. However, the pigmented lesions persisted, and they were removed with alcohol corneal epitheliectomy. Histopathological examination demonstrated primary acquired melanosis without atypia. The lesions were successfully removed, and there were no recurrences during the follow-up period of 36 months. The association of conjunctival and corneal melanosis without atypia is a rare condition. In addition, co-existence of central corneal haze and melanosis may decrease visual acuity. Topical mitomycin-C and alcohol corneal epitheliectomy can be useful treatments in this condition.

Corneal melanosis successfully treated using topical mitomycin-C and alcohol corneal epitheliectomy: a 3-year follow-up case report / Tratamento com êxito da melanose de córnea utilizando mitomicina-C tópica e epiteliectomia auxiliada por álcool: relato de caso com três anos de seguimento

ABSTRACTWe report a case of primary acquired corneal melanosis without atypia associated with corneal haze in a patient with a history of limbal malignant melanoma and the effect of mitomycin-C. A 75-year-old woman with a history of limbal malignant melanoma presented with loss of vision in right eye. Corneal examination showed a patchy melanotic pigmentation with a central haze. Topical mitomycin-C improved visual acuity and corneal haze. However, the pigmented lesions persisted, and they were removed with alcohol corneal epitheliectomy. Histopathological examination demonstrated primary acquired melanosis without atypia. The lesions were successfully removed, and there were no recurrences during the follow-up period of 36 months. The association of conjunctival and corneal melanosis without atypia is a rare condition. In addition, co-existence of central corneal haze and melanosis may decrease visual acuity. Topical mitomycin-C and alcohol corneal epitheliectomy can be useful treatments in this condition.

RESUMORelatar um caso de melanose adquirida primária de córnea sem atipia, associado a haze corneano em um paciente com história de melanoma maligno de limbo e o efeito da mitomicina-C. Uma mulher de 75 anos de idade, com história de melanoma maligno do limbo apresentado com diminuição de visão no olho direito. O exame de córnea mostrou uma pigmentação melânica irregular com um haze central. O uso de mitomicina-C tópica levou à melhora da acuidade visual e da opacidade corneana. No entanto, as lesões pigmentadas persistiram e foram removidas com epiteliectomia associada ao álcool. O exame histopatológico demonstrou melanose adquirida primária sem atipia. As lesões foram removidas com êxito, e não houve recidiva durante o período de acompanhamento de 36 meses. A associação melanose sem atipia da conjuntiva e da córnea é uma condição rara. Além disso, a coexistência de haze corneano central e melanose pode diminuir a acuidade visual. O uso de mitomicina-C tópica e epiteliectomia corneana auxiliada pelo álcool podem ser tratamentos úteis nessa situação.

Exposure to cigarette smoke causes DNA damage in oropharyngeal tissue in dogs.

More than 40 mutagenic and carcinogenic agents present in cigarette smoke have been identified as causative factors of human cancer, but no relation has been clearly documented in companion animals. In dogs, in addition to smoke inhalation and transdermic absorption, exposure to smoke includes oral ingestion of particles adhered to the animal's fur. This study evaluates the presence and type of histological alterations and DNA integrity in oropharyngeal tissue in dogs exposed and non-exposed to household cigarette smoke by means of histopathology and comet assay studies on biopsy and swab samples. A non-probabilistic convenience sample of 12 dogs were selected and classified in two groups: exposed and non-exposed to cigarette smoke. Non-parametric Kruskal-Wallis test was carried out on biopsy and swab data and a Chi(2) test was performed on the information obtained by histopathology. A significance level was set at P<0.05. Statistically significant differences were found between groups in comet assays carried out on biopsy samples. No differences (P>0.05) were found between groups based on comet assays swab samples and histopathology assessment. In conclusion, exposure to cigarette smoke causes DNA damage in dog oropharyngeal tissue. The use of dogs as sentinels for early DNA damage caused by exposure to environmental genotoxic agents like cigarette smoke is reported for the first time.

Melasma: a clinical and epidemiological review.

Melasma is a chronic acquired hypermelanosis of the skin, characterized by irregular brown macules symmetrically distributed on sun-exposed areas of the body, particularly on the face. It is a common cause of demand for dermatological care that affects mainly women (especially during the menacme), and more pigmented phenotypes (Fitzpatrick skin types III-V). Due to its frequent facial involvement, the disease has an impact on the quality of life of patients. Its pathogeny is not yet completely understood, although there are some known triggering factors such as sun exposure, pregnancy, sexual hormones, inflammatory processes of the skin, use of cosmetics, steroids, and photosensitizing drugs. There is also a clear genetic predisposition, since over 40% of patients reported having relatives affected with the disease. In this manuscript, the authors discuss the main clinical and epidemiological aspects of melasma.

Melasma: a clinical and epidemiological review

Melasma is a chronic acquired hypermelanosis of the skin, characterized by irregular brown macules symmetrically distributed on sun-exposed areas of the body, particularly on the face. It is a common cause of demand for dermatological care that affects mainly women (especially during the menacme), and more pigmented phenotypes (Fitzpatrick skin types III-V). Due to its frequent facial involvement, the disease has an impact on the quality of life of patients. Its pathogeny is not yet completely understood, although there are some known triggering factors such as sun exposure, pregnancy, sexual hormones, inflammatory processes of the skin, use of cosmetics, steroids, and photosensitizing drugs. There is also a clear genetic predisposition, since over 40% of patients reported having relatives affected with the disease. In this manuscript, the authors discuss the main clinical and epidemiological aspects of melasma.

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.

Epidemiology of melasma in Brazilian patients: a multicenter study.

BACKGROUND: Melasma is an acquired, irregularly patterned, light to dark-brown hypermelanosis, with symmetric distribution mostly over the face. The aim of this study was to evaluate clinical characteristics and factors related to melasma in Brazilian patients. METHODS: This was a cross-sectional, multicenter study performed in Brazil. Investigators examined and questioned 953 patients over 18 years of age on clinical characteristics and other factors related to their melasma. RESULTS: Melasma was more prevalent in women (97.5%) and in Fitzpatrick skin phototypes II (12.8%), III (36.3%), and IV (39.7%). Skin phototypes II and III and family history of melasma had early onset of the disorder when compared with skin phototypes IV, V, and VI (P<0.0001). Similar results were also observed when these same groups were compared with the absence of family history (P<0.0001). Extra-facial melasma was more frequent in postmenopausal women compared with those who were not experiencing menopause (14.2% vs. 3.5%, P<0.0001). CONCLUSIONS: Data suggested that the age of melasma onset are related to skin phototypes and family history. Additionally, extra-facial melasma was more common in menopausal women. This is the first study on the epidemiology of melasma in Brazil involving a large sample of the population. These data can be a source of new relevant research on the cause and development of melasma.

Prevalence of lip and perioral Ephelides in beach workers.

BACKGROUND: Ephelides are small hyperpigmented macules common in the skin, presenting as areas with increased melanin production. Ephelides are observed in genetically predisposed individuals, particularly fair-skinned people highly susceptible to sunburn. OBJECTIVES: This study aimed to determine the prevalence of lip and perioral ephelides in 362 beach workers in the city of Natal (Rio Grande do Norte) and to investigate potential associations with sociodemographic, occupational and general health. METHODS: For this purpose clinical tests were performed by calibrated examiners in the epidemiological area around the lips and the area bounded laterally by the nasolabial groove and at the bottom by the chin. A questionnaire was completed and assessed. The possible associations between sociodemographic variables, occupational and general health with the presence of lip and perioral ephelides were evaluated by chi-square test for a significance level of 5%. RESULTS: Approximately one third of the workers were affected by perioral ephelides (33.7%) and around a quarter of them by lip ephelides (24.0%). Gender was the only variable significantly associated with the presence of perioral ephelides (p = 0.002), unlike lip ephelides which proved to be significantly associated with habits (p = 0.036) and alcoholism (0.030). CONCLUSIONS: The prevalence of ephelides in lip and perioral region was high in the study population, with gender and certain habits associated with its occurrence.

Prevalence of lip and perioral Ephelides in beach workers / Prevalência de Éfelides labiais e periorais em trabalhadores de praias

Ephelides are small hyperpigmented macules common in the skin, presenting as areas with increased melanin production. Ephelides are observed in genetically predisposed individuals, particularly fair-skinned people highly susceptible to sunburn. This study aimed to determine the prevalence of lip and perioral ephelides in 362 beach workers in the city of Natal (Rio Grande do Norte) and to investigate potential associations with sociodemographic, occupational and general health. For this purpose clinical tests were performed by calibrated examiners in the epidemiological area around the lips and the area bounded laterally by the nasolabial groove and at the bottom by the chin. A questionnaire was completed and assessed. The possible associations between sociodemographic variables, occupational and general health with the presence of lip and perioral ephelides were evaluated by chi-square test for a significance level of 5%. Approximately one third of the workers were affected by perioral ephelides (33.7%) and around a quarter of them by lip ephelides (24.0%). Gender was the only variable significantly associated with the presence of perioral ephelides (p = 0.002), unlike lip ephelides which proved to be significantly associated with habits (p = 0.036) and alcoholism (0.030). The prevalence of ephelides in lip and perioral region was high in the study population, with gender and certain habits associated with its occurrence. .

Efélides são máculas hiperpigmentadas pequenas, comuns na pele, que constituem uma área com maior aumento da produção de melanina. São observadas em indivíduos geneticamente predispostos, de pele clara, com grande suscetibilidade a queimaduras solares. Esse estudo teve o propósito de verificar a prevalência de efélides labiais e periorais em 362 trabalhadores de praias do município de Natal/RN e investigar potenciais associações com variáveis sociodemográficas, ocupacionais e de saúde geral. Para tanto, foram realizados exames clínicos por examinadores calibrados, na área correspondente aos lábios e na área delimitada lateralmente pelo sulco nasolabial e inferiormente pelo mento, além de preenchimento de questionário validado. As possíveis associações das variáveis sociodemográficas, ocupacionais e de saúde geral com a presença de efélides labiais e periorais foram avaliadas pelo teste do qui-quadrado para um nível de significância de 5%. Aproximadamente um terço dos trabalhadores foi acometido por efélides perioral (33,7%) e um quarto por efélides labial (24,0%). O gênero foi a única variável que se mostrou associada significativamente com a presença de efélides periorais (p=0,002), ao contrário das efélides labiais que mostrou-se associada significativamente com hábito (p=0,036) e etilismo (0,030). Conclui-se que a prevalência de efélides em região perioral e labial foi elevada na população estudada e o gênero e hábitos ...

Fatores de risco para melasma facial em mulheres: um estudo caso-controle / Risk factors for facial melasma in women: a case-control

Melasma é hipermelanose crônica, localizada, simétrica adquirida, que acomete áreas fotoexpostas, preferencialmente a face, o que causa estresse emocional. Ocorre de forma mais frequente entre mulheres adultas. Sua patogênese não é totalmente compreendida apesar de alguns fatores de risco serem conhecidos, como história familiar, exposição solar, gravidez, hormônios sexuais, cosméticos e medicamentos fotossensibilizantes. Há evidente predisposição genética, já que mais de 40% dos pacientes referem familiares acometidos. O principal objetivo deste estudo foi avaliar os fatores de risco para o desenvolvimento de melasma facial em mulheres. Realizou-se estudo caso-controle envolvendo mulheres adultas, portadoras ou não de melasma facial, pareadas por idade. As variáveis foram agrupadas em níveis hierárquicos: dados constitucionais, variáveis de exposição, variáveis ligadas à estímulos hormonais e traços de ansiedade, avaliados pelo questionário IDATE-T; e analisados por regressão logística múltipla condicional. Pacientes com melasma apresentaram, preferencialmente, fototipos III a V, iniciaram sua doença entre a terceira e quarta décadas de vida, referiram frequente acometimento familiar e ascendência europeia e indígena. Do ponto de vista clínico, houve maior acometimento de topografias centrais da face e os principais fatores desencadeantes foram a gestação, insolação e contraceptivo oral combinado. Quando comparados aos controles, mulheres com melasma diferiram de seus controles quanto aos fototipos, ascendência indígena (OR=2,25), anos de moradia rural/praia (OR=1,07), tempo de trabalho exposto ao sol (OR=1,05), tempo de atividades de lazer exposto ao sol (OR=1,03), uso de antidepressivo/ansiolítico (OR=5,11), irregularidade menstrual (OR=3,99), histórico de gestação (OR=3,58), anos de uso de contraceptivo oral (OR=1,24) e escores de ansiedade (OR=1,07)...

Melanosis of the vagina and human papillomavirus infection, an uncommon pathology: case report.

Benign melanotic lesions of the vagina are uncommon and only a few cases have been reported in the literature. A 34-year-old woman was referred because of a Vaginal Intraepithelial Neoplasia 1 biopsy result. On the gynecological examination, two different hyperpigmented areas were noted in the vagina. The colposcopic visualization of the cervix and vagina found an aceto-white lesion at the right lateral wall of the upper third of the vagina. Biopsies from three areas were taken. Histological study reported a melanosis of the vagina and HPV infection. An immunohistochemical panel of epithelial markers was performed in vaginal samples, such as Cytokeratin AE1/AE3 and epithelial membrane antigen, mesenchymal marker: vimentin; melanocytic makers: protein S-100 and HMB45 (Human Melanoma Black); proliferating cell marker: proliferating cell nuclear antigen (PCNA), and P-53 oncoprotein. High Risk (16, 18, 31, 45) and Low Risk (6, 11) HPV types were studied by In Situ Hybridization using the same vaginal samples. CK, EMA and Vimentin were 2+. Melanocytic markers, HMB45 and S100, and PCNA were 1+ in basal cell layer. P-53 was negative. The melanotic tissue and acetowhite lesion were positives to HPV Types 6,11. In conclusion, melanosis of the vagina is a uncommon benign pathology. Usually, melanosis is present in women over 40 years old. We present a case of melanosis of the vagina in a young woman infected with low-risk HPV types and review the literature.