Vitiligo is a pigmentary disorder characterized by the loss of functional melanocytes, leading to depigmented skin patches and significant psychological burden. Platelet-rich plasma (PRP) and its derived exosomes have recently gained attention as potential regenerative therapies due to their immunomodulatory and antioxidant effects.To evaluate the therapeutic effects of platelet-rich plasma (PRP) versus its derived exosomes in a hydrogen peroxide-induced depigmentation model in guinea pigs.Forty-two adult male guinea pigs were divided into control, depigmentation, PRP-treated, and PRP-exosome-treated groups. Depigmentation was induced using topical H2O2. A recovery group was included to assess spontaneous repigmentation after discontinuation of H2O2. Histological, immunohistochemical, histomorphometric, and biochemical analyses were performed.The depigmentation group showed progressive spongiosis in the epidermis with significant increase in the epidermal thickness. Significant decrease in melanin pigment and significant decrease in the number of melanocytes were noticed in the epidermis and hair follicles. Administration of PRP and PRP-Exosomes reversed these histological alterations with significant reduction in epidermal thickness and negative CD3 reaction in the dermis. More improvement was observed in PRP-exosome group compared to PRP group, as evidenced by significant increased amount of melanin granules and number of melanocytes in exosome group.Within the limitations of this oxidative stress-induced depigmentation model, both PRP and its derived exosomes were associated with histological improvement, with greater changes observed in the exosome-treated group. However, further studies are needed to confirm these findings in models more representative of human vitiligo.

Segmental vitiligo (SV) is a distinct clinical subtype of vitiligo characterized by unilateral, sharply demarcated depigmentation, rapid progression and early stabilization, and frequent leukotrichia. Compared with non-segmental vitiligo (NSV), SV is generally less strongly associated with systemic autoimmunity, suggesting potential differences in pathogenic mechanisms, although overlap phenotypes and mixed presentations have been reported. Accumulating clinical, epidemiological, and mechanistic evidence supports the concept that SV arises from somatic mosaicism, in which post-zygotic genetic or epigenetic alterations occur during embryogenesis and give rise to a clonally distinct melanocyte population distributed along developmental territories. Embryologic studies indicate that melanoblast migration from the neural crest, coupled with high proliferative activity during early development, creates a permissive context for mosaic mutation accumulation. The resulting melanocyte clones align with Blaschko's lines or other embryonic patterning units, accounting for the segmental distribution of SV. Beyond melanocytes, segment-restricted abnormalities in neural and vascular structures have also been reported, raising the possibility of broader neurocutaneous mosaicism, although whether these changes are primary or secondary to localized immune injury remains unresolved. Recognizing SV as a mosaic disorder has important clinical implications, particularly for early intervention, recurrence risk assessment, and the prominent role of autologous surgical therapies. Future advances will depend on multi-omics approaches to identify causal mosaic mutations, refined disease models, and long-term registries to translate developmental insights into precision management strategies.

Atopic dermatitis (AD) is the most common inflammatory skin disease and carries the highest disability-adjusted life-years burden, ranking 15th among all non-fatal diseases globally. It is characterized by intensely itchy skin and is associated with multiple comorbidities, such as food allergy, asthma, allergic rhinitis and eosinophilic oesophagitis, which are mainly driven by type 2 immune responses. Other comorbidities include mental health disorders, disordered bone health, and cutaneous and extracutaneous infections. AD is also associated with other immune-mediated inflammatory diseases, including alopecia areata, vitiligo and inflammatory bowel disease. AD most often starts in the first 2 years of life but can occur at any life stage and onset at >60 years of age is increasingly common. The twenty-first century has brought greater insights into disease pathology, with an understanding of the complex interplay between the skin barrier, cutaneous and systemic immune pathways, cutaneous microbiome and neural networks. This improved mechanistic understanding has enabled rational drug design and a shift from non-specific broad immunomodulation to targeted biologic therapies and small molecules for severe disease and from topical corticosteroids to next-generation therapies for mild and moderate disease. Yet, considerable global inequity remains in access to these novel therapeutics.

Vitiligo is an autoimmune disease characterized by depigmented skin lesions, caused by autoreactive-CD8-T-cells inducing melanocyte apoptosis. Effective treatment is challenging due to limited understanding of the processes underlying skin repigmentation. This study aimed to identify these processes using proteomics. Plasma and skin blister-fluid samples from 30 vitiligo patients starting standard-of-care treatment were analyzed. A large proteomic screen of 5080 proteins was measured with Somascan on samples collected at baseline and at 3-months of treatment. Analyses of proteins that changed and not changed under treatment, revealed 5 proteins associated with repigmentation. Higher baseline levels of TIM-1, TFF3 and NLRP1 in blister-fluid and an increase of KRT5 in plasma under treatment, were associated with repigmentation. TIM-1 and TFF3 have immunosuppressive effects, while NLRP1 and KRT5 can stimulate melanogenesis. The NLRP1-inflammasome pathway was enriched in these proteins. These proteins and pathways were distinct from the previously identified differences between lesional and non-lesional skin, indicating differential expression of melanocyte-specific pathways. This suggests that treatment-induced repigmentation in vitiligo involves processes other than simply reversing lesional skin to a non-lesional state. These findings enhance understanding of repigmentation in vitiligo and could guide future therapeutic strategies.