The pathogenesis of melasma and implications for treatment.

Background: Melasma is a complex and poorly understood disorder, with high rates of treatment failure and recurrences.
Objectives: We aimed to review the current knowledge of the pathogenesis of melasma and apply this knowledge to clinical implications on relevant therapeutic interventions.
Methods: A systematic PubMed search was performed using the search term "((melasma[Text Word]) OR facial melanosis[Text Word]) AND (pathogenesis OR causality[MeSH Terms])" for articles published between 1990 and 2020. Included articles were then evaluated by two authors and assessed for relevant pathomechanistic pathways, after which they were divided into groups with minimal overlap. We then reviewed current treatment modalities for melasma and divided them according to the involved pathomechanistic pathway.
Results: A total of 309 search results were retrieved among which 76 relevant articles were identified and reviewed. Five main pathomechanisms observed in melasma were identified: (1) melanocyte inappropriate activation; (2) aggregation of melanin and melanosomes in dermis and epidermis; (3a) increased mast cell count and (3b) solar elastosis; (4) altered basement membrane; and (5) increased vascularization. Treatment modalities were then divided based on these five pathways and detailed in 6 relevant tables.
Conclusion: The pathophysiology of melasma is multifactorial, resulting in treatment resistance and high recurrence rates. This wide variety of pathomechanisms should ideally be addressed separately in the treatment regimen in order to maximize results.
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