Vitiligo, from Pathogenesis to Therapeutic Advances: State of the Art

Abstract

Vitiligo is an acquired hypopigmentation of the skin due to a progressive selective loss of melanocytes; it has a prevalence of 1-2% and appears as rounded, well-demarcated white macules. The etiopathology of the disease has not been well defined, but multiple factors contribute to melanocyte loss: metabolic abnormalities, oxidative stress, inflammation, and autoimmunity. Therefore, a convergence theory was proposed that combines all existing theories into a comprehensive one in which several mechanisms contribute to the reduction of melanocyte viability. In addition, increasingly in-depth knowledge about the disease's pathogenetic processes has enabled the development of increasingly targeted therapeutic strategies with high efficacy and fewer side effects. The aim of this paper is, by conducting a narrative review of the literature, to analyze the pathogenesis of vitiligo and the most recent treatments available for this condition.

Keywords: Janus kinase inhibitors; afamelanotide; pathogenesis; prostaglandin; treatments; vitiligo.

Figure 1

Summary of the main pathogenetic mechanisms involved in vitiligo. FOXD3 (Forkhead Box D3), NLRP1 (NLR family pyrin domain containing 1), PDGFRA (Platelet Derived Growth Factor Receptor Alpha), HLA (human leukocyte antigen), XBP1 (X-box binding protein 1) TYR (Tyrosinase), CTLA-4 (Cytotoxic T-Lymphocyte Antigen 4), ACE (Antigen converting enzyme), CAT (Catalase), PTPN22 (Protein Tyrosine Phosphatase Non-Receptor Type 22), IKZF4 (IKAROS Family Zinc Finger 4, VEGF (Vascular endothelial growth factor), MYG1 (MYG1 Exonuclease), MITF (Melanocyte Inducing Transcription Factor), KIT (KIT Proto-Oncogene, Receptor Tyrosine Kinase), ESR 1 (Estrogen Receptor 1), AIRE (Autoimmune Regulator), COMT (Catechol-O-methyltransferase), NALP1 (Nucleotide-binding oligomerization domain, Leucine-rich Repeat and Pyrin domain containing), FAS (Fas Cell Surface Death Receptor), EDN1 (Endothelin 1), COX2 (Cyclooxygenase 2), VIT1 (Vacuolar iron transporter 1), CXCL9-10-11 (C-X-C Motif Chemokine Ligand 9-10-11), DAMPs (Damage-associated molecular patterns), HSP70 (Heat Shock Protein 70 kilodaltons), CCL22 (C-C Motif Chemokine Ligand 22), IL-15 (Interleukin-15), CD8 (cluster of differentiation 8, IFN-γ (Interferon gamma), JAK1–2 (Janus Kinases 1 and 2), TREGS (regulatory T cells), TRM (Resident memory T cells), ROS (Reactive oxygen species), and NGF (Neural growth factor).