Advances in the biology of pigmentation have practical applications for dermatologic practice, according to Dr. Thierry Passeron, professor and chair of the dermatology department at the Université Côte d’Azur in Nice, France. Next Steps in Derm, in partnership with Pigmentary Disorders Exchange Symposium, interviewed Dr. Passeron about what clinicians should know about the biology of pigmentation. Learn about the impact of visible light and why there’s more at play in pigmentation than keratinocytes and melanocytes. Plus hear Dr. Passeron’s vision for a potential cure for melasma.
Further Reading
If you want to read more about pigmentary disorders, check out the following articles published in the Journal of Drugs in Dermatology:
Advances in Pigmentation Management: A Multipronged Approach
ABSTRACT
Background: Key cellular players regulating human skin pigmentation include melanocytes in the epidermis that synthesize melanin, neighboring keratinocytes that receive and distribute melanin in the upper layers, and fibroblasts in the dermis that affect overlying melanocytes and keratinocytes. In addition, endocrine factors from the blood supply (endothelial cells) and inflammation-related factors play a role. Thus, new strategies for affecting pigmentation need to consider these multiple cell lines to adequately cover various causes and disease processes associated with hyperpigmentation.
Methods: Pathophysiologic mechanisms and cellular pathways involved in melanogenesis were thoroughly reviewed with particular emphasis on the cellular interplay involved in the process. A complex system of interlinking and independent pathways was defined and described demonstrating differing pathways for altered pigmentary disorders – melasma associated with endothelial cell interactions; post inflammatory hyperpigmentation associated with keratinocyte inflammatory mediators (PGE2 in particular); and photodamage involving all 4 cell types. In vitro validation studies were then undertaken to define differing cell group gene expression profiles with selected peptides and other active agents. Melanocytic production of pigment was then tested with these agents to identify key potential players capable of limiting pigmentation.
Results: Hexapeptide-12 and lactoferrin (melanocytes), Hexapeptide-11 (in keratinocytes), and phosphatidylserine (endothelial cells) were identified as major inhibitors of melanogenesis based on their gene expression profiles. This was confirmed by secondary melanin production tests performed on melanocytic lines. Additional active agents were also identified as inhibitors of melanocytic production of melanin, and together, these constituents formed the basis for a novel formulation for use in pigmentary disorders.
Conclusion: A comprehensive scientific narrative of the various facets relating to pigmentation has been presented including differing pathways affecting varied cell lines that effect pigment production. Based on this concept, actives were tested using gene expression studies as well as in vitro melanogenic model testing in different cell lines. Using this novel multi-faceted approach, we have selected and validated a series of active agents to be used in a formulation targeting the complex problem of hyperpigmentation.
Topical Treatments for Melasma and Post-inflammatory Hyperpigmentation
ABSTRACT
Background: Dyschromia is one of the most common reasons for patients to seek dermatological care, especially among individuals with skin of color. Most cases present as melasma or post-inflammatory hyperpigmentation (PIH); both are chronic issues requiring long-term treatment. While many pharmaceutical (topical or systemic) or procedural (lasers/chemical peels) options are available, some treatments are not safe/tolerable for long-term use or can induce/exacerbate PIH.
Methods: This qualitative review provides an overview of topical treatments for melasma and PIH, including recent data from an investigator-initiated trial of the retinoid tazarotene.
Results: Topical hydroquinone (HQ) in the form of triple combination HQ 4%/tretinoin 0.05%/fluocinolone acetonide 0.01% cream is the gold-standard treatment for melasma and PIH but should not be used long-term due to safety concerns. Efficacy data for OTC/cosmeceutical products are limited or lacking. Topical retinoids are efficacious and safe, though dose and formulation differences may affect tolerability. Tazarotene 0.045% polymeric emulsion lotion demonstrated good efficacy, safety, and tolerability over 24 weeks in adult female patients with moderate-to-severe melasma and/or PIH.
Conclusions: There are multiple topical treatments available for dyspigmentation. However, many are lacking efficacy data and others are limited by tolerability or safety concerns. Retinoids, such as tazarotene, may be an efficacious and safe treatment for melasma or PIH.
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