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.

Apoptosis in follicles of individuals with female pattern hair loss is associated with perifollicular microinflammation.

OBJECTIVE: The objective of this study is to evaluate apoptosis in hair follicles of patients with female pattern hair loss (FPHL) and its association with follicular microinflammation. METHOD: Cross-sectional study involving 17 women with FPHL and five controls. Scalp skin samples were processed for HE and TUNEL assays. The variables were compared according to the categories of follicles (terminal versus miniaturized) and groups of patients (FPHL vs. controls). RESULTS: There was a higher apoptosis index among miniaturized follicles and among the test cases (P < 0.01). Microinflammation was prominent among miniaturized follicles, especially from FPHL (P = 0.02). In addition, a positive correlation between inflammatory infiltrate and apoptosis in miniaturized follicles (rS = 0.68; P < 0.01) was found. CONCLUSIONS: Apoptosis was prominent in hair follicles from the FPHL group, as well as in miniaturized ones. Moreover, it was also correlated with the inflammatory infiltrate, which suggests that inflammation can lead to apoptosis and play a role in the pathogenesis of follicle miniaturization.

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.