Exploratory Study of Epidermis, Basement Membrane Zone, Upper Dermis Alterations and Wnt Pathway Activation in Melasma Compared to Adjacent and Retroauricular Skin

Abstract

Background: Melasma is a chronic acquired focal hypermelanosis which pathogenesis has not been fully elucidated. Classical pathophysiologic studies have analysed the affected and perilesional areas, but little is known about the status of sun-protected skin, which is subjected to the same endogenous and genetic factors. Objective: To assess the histological characteristics of melasma compared to adjacent and retroauricular skin. Methods: Skin samples were collected from 10 female from: melasma, perilesional area and retroauricular. The samples were stained (haematoxylin-eosin, periodic acid-Schiff, Fontana-Masson, picrosirius red, toluidine blue and Verhoeff), immunolabelled for CD34 and Wnt1. The data from the skin sites were analysed simultaneously by a multivariate model. Results: Melasma skin exhibited noteworthy stratum corneum compaction, greater collagen heterogeneity, solar elastosis, higher number of mast cells, basement membrane zone (BMZ) damage, Wnt1 expression, pendulum melanocytes, higher cellularity and vascular proliferation at the superficial dermis. Stratum cor-neum compaction, collagen heterogeneity and BMZ abnormalities were variables associated to melasma that not follow a continuum through retroauricular to adjacent skin. Mast cell count was the variable that disclosed correlation with the most other abnormalities as well as had the greater contribution in the multivariate model. Conclusion: In addition to melanocyte hyperactivity, melasma skin exhibits alterations in the epidermal barrier, upper dermis and BMZ, which differ from the adjacent sun-exposed skin and retroauricular skin, indicating a distinct phenotype, rather than a mere extension of photoageing or intrinsic ageing. Mast cells appear to play a central role in the physiopathology of melasma.

Evaluation of ex vivo melanogenic response to UVB, UVA, and visible light in facial melasma and unaffected adjacent skin

“…The role of dermal melanin remains unclear in melasma; one of the hypotheses is that the architectural dysfunction of the basement membrane and the autophagy of the melanocytes of the dermis may cause the presence of dermal melanophages, similar to what occurs in photoaging. 24 , 25 In the present study, UVA and UVB promoted a higher rate of melanin in the upper dermis; however, this density was approximately 100 times smaller than that of the epidermis in both anatomical sites, which likely little contributes to the clinical phenotype, but may signal underlying alterations in the upper dermis, basement membrane, and basal layer.…”

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

“…epidermis, basement membrane and upper dermis), and Thiamidol should be further explored in combination with other treatments, such as oral tranexamic acid, antioxidants, lasers and microneedling, to maximize its benefits. [30][31][32][33][34] In conclusion, the melasma improvement achieved using 0.2% Thiamidol did not differ from that of 4% hydroquinone cream; Thiamidol has a safe profile with well-tolerated adverse effects. Thiamidol can be considered a suitable option for melasma patients with poor tolerability or treatment failure with 4% hydroquinone cream.…”

A comparative study of topical 5% cysteamine versus 4% hydroquinone in the treatment of facial melasma in women

“…Melasma has a complex pathogenesis that surpasses melanocyte hypertrophy, and a combination of strategies can lead to more effective results. [24][25][26][27] Specific designs for assessing the long-term efficacy of cysteamine as well as its use as a maintenance treatment after other potent depigmenting agents (e.g., triple combination), laser or oral tranexamic acid are needed in order to position it among the existing strategies for the management of melasma. 15,28…”