Perception of skin cancer risk and sun protective practices in individuals with vitiligo: a prospective international cross-sectional survey.

Many individuals with vitiligo are uncertain about their skin cancer risk, phototherapy risks, and recommended sun protective practices. This study examined the perceived skin cancer risk and sun protective practices among individuals living with vitiligo. A secondary objective was to understand where participants obtain this information. This was a prospective cross-sectional study. An online survey was distributed to vitiligo support group leaders globally who shared the survey with their members. Individuals over the age of 18 and with vitiligo were included. There were 209 survey respondents, the majority were between the ages 35-54 (45.5%, n = 95), female (70.8%, n = 148), White (66.0%, n = 138). Nearly half of respondents believed they were at increased risk of skin cancer because of their vitiligo (45.5%, n = 95) and nearly a quarter (22.5%, n = 47) believed that phototherapy increased their risk of skin cancer. Having vitiligo affected sun protective practices with less than a quarter (24.4%, n = 51) of respondents using sunscreen daily or often prior to their vitiligo diagnosis in comparison to the majority of respondents (60.3%, n = 126) using it after their vitiligo diagnosis. The three most common sources where patients obtained information were the internet and social media (46.4%, n = 97), vitiligo support groups (23.4%, n = 49), and dermatologists (20.6%, n = 43). Despite evidence indicating a decreased risk of skin cancer in individuals with vitiligo and supporting the safety of narrowband ultraviolet B phototherapy, many participants believed they were at an increased risk of skin cancer. Findings were sub-stratified and showed differences in sunscreen usage based on gender, skin color, and percent depigmentation. This study also found nearly half of respondents obtained information related to vitiligo from the internet and social media. The number of participants may limit the generalizability of the findings. Survey questionnaires are also subject to response bias. The findings from this study highlight demographic variations in sunscreen usage which may help guide the development of targeted interventions to improve sun protective behaviors among diverse populations with vitiligo. In addition, this study suggests certain sun protective practices and skin cancer risk perceptions may vary based on extent of depigmentation. Lastly, this study also demonstrates the internet and social media as a popular source for obtaining information, emphasizing the need for dermatologists to leverage various online communication channels to help disseminate accurate information.

Mechanisms of action of Lycium barbarum polysaccharide in protecting against vitiligo mice through modulation of the STAT3-Hsp70-CXCL9/CXCL10 pathway.

CONTEXT: Vitiligo is a common skin disease with a complex pathogenesis, and so far, no effective treatment is available. Lycium barbarum L. (Solanaceae) polysaccharide (LBP), the main active ingredient of goji berries, has been demonstrated to protect keratinocytes and fibroblasts against oxidative stress. OBJECTIVE: This study explored the effects and mechanism of LBP on monobenzone-induced vitiligo in mice. MATERIALS AND METHODS: C57BL/6 mice were randomly divided into five groups (n = 6): negative control that received vaseline, vitiligo model group induced by monobenzone that treated with vaseline, positive control that received tacrolimus (TAC), LBP groups that received 0.3 and 0.6 g/kg LBP, respectively. We quantified the depigmentation by visual examination and scores, detected the expression of CD8+ T cells, pro-inflammatory cytokines and analysed the STAT3-Hsp70-CXCL9/CXCL10 pathway. RESULTS: LBP 0.3 and 0.6 g/kg groups can significantly reduce depigmentation scores and the infiltration of local inflammatory cells in the skin lesions. Moreover, the expression of CXCL9, CXCL3, CXCL10 and HSP70 decreased by 54.3, 20.3, 48.5 and 27.2% in 0.3 g/kg LBP group, which decreased by 62.1, 26.6, 58.2 and 34.5% in 0.6 g/kg LBP group. In addition, 0.3 and 0.6 g/kg LBP decreased the release of IL-8 (9.7%, 22.8%), IL-6 (40.8%, 42.5%), TNF-α (25.7%, 35%), IFN-γ (25.1%, 27.6%) and IL-1ß (23.7%, 33.7%) and inhibited the phosphorylation expression of STAT3 by 63.2 and 67.9%, respectively. CONCLUSION: These findings indicated LBP might be recommended as a new approach for vitiligo which provide a theoretical basis for the clinical application of LBP in treating vitiligo patients.

Involvement of adenylate cyclase/cAMP/CREB and SOX9/MITF in melanogenesis to prevent vitiligo.

Vitiligo is autoimmune, acquired, idiopathic, chronic, and progressive de/hypopigmentary cutaneous condition that targets the cell-producing pigment called melanin. It binds to a thread of great disappointment and emotional stress in societies. Combining multiple stress-related theories like toxic compound accumulation, autoimmunity, mutations, altered cellular environment, infection, impaired migration/proliferation, and immunological mismatch of anti-melanocyte and self-reactive T-cells that cause melanocytes damage is formulated resulting in vitiligo. Vitiligo has an orphan status for drug synthesis. Still, different therapies are available, with topical steroids and narrow-band ultraviolet-B monotherapy being the most common treatments, others including medical, physical, or surgical, but not effective. Each modality has its baggage of disadvantages and side effects. Stimulation of the transcriptional process for melanogenesis is mainly achieved by the cAMP-dependent activation of several melanogenic genes by MITF. In this review, we summarized that cAMP encourages the expression of the enzyme tyrosinase, TYRP1, TYRP2, and most other biological effects of cAMP are mediated through the cAMP-dependent PKA pathway resulting in CREB phosphorylation. It has been shown that TYRP1 and 2 do not have cAMP response elements (CREs) in promoting regions; the regulation of these genes by cAMP occurs through the direct participation of MITF during melanogenesis. The available medicines, therefore, only provide symptomatic relief, but do not stop the disease progression. In addition, the treatment process needs to be changed; existing approaches need to be overlooked for patients who are suffering and therefore analyze its efficacy and safety to achieve a favorable risk-benefit ratio.

Future research into the treatment of vitiligo: where should our priorities lie? Results of the vitiligo priority setting partnership.

BACKGROUND: Vitiligo is the most frequent depigmentation disorder of the skin and is cosmetically and psychologically devastating. A recently updated Cochrane systematic review 'Interventions for vitiligo' showed that the research evidence for treatment of vitiligo is poor, making it difficult to make firm recommendations for clinical practice. OBJECTIVES: To stimulate and steer future research in the field of vitiligo treatment, by identifying the 10 most important research areas for patients and clinicians. METHODS: A vitiligo priority setting partnership was established including patients, healthcare professionals and researchers with an interest in vitiligo. Vitiligo treatment uncertainties were gathered from patients and clinicians, and then prioritized in a transparent process, using a methodology advocated by the James Lind Alliance. RESULTS: In total, 660 treatment uncertainties were submitted by 461 participants. These were reduced to a list of the 23 most popular topics through an online/paper voting process. The 23 were then prioritized at a face-to-face workshop in London. The final list of the top 10 treatment uncertainties included interventions such as systemic immunosuppressants, topical treatments, light therapy, melanocyte-stimulating hormone analogues, gene therapy, and the impact of psychological interventions on the quality of life of patients with vitiligo. CONCLUSIONS: The top 10 research areas for the treatment of vitiligo provide guidance for researchers and funding bodies, to ensure that future research answers questions that are important both to clinicians and to patients.

Recent onset vitiligo on acral areas treated with phototherapy: need of early treatment.

In vitiligo, the effect of phototherapy depends on lesional location. While face and neck lesions generally show good responses, acral areas are resistant to phototherapy. We describe two cases of recent onset vitiligo on acral areas that showed an excellent response with phototherapy. These results suggest that even acral areas in vitiligo can be markedly improved by phototherapy if it has a recent onset.

Immunotherapy can reject intracranial tumor cells without damaging the brain despite sharing the target antigen.

Although vaccines targeting tissue differentiation Ags represent a promising strategy for cancer immunotherapy, the risk of triggering autoimmune damage to normal tissues remains to be determined. Immunizing against a melanoma-associated Ag, dopachrome tautomerase (DCT), which normal melanocytes and glial cells also express, allowed concurrent analysis of autoimmune consequences in multiple tissues. We show that vaccination with recombinant adenovirus expressing DCT elicited a strong CTL response in C57BL/6 mice, leading to protection against intracranial challenge with B16-F10 melanoma cells. Both histological analysis and behavioral testing indicated that there was no evidence of neuropathology in vaccinated animals and long-term survivors. Although vitiligo or demyelination could be induced by additional stimuli (i.e., surgery or inflammation) in DCT-vaccinated mice, it did not extend beyond the inflammatory area, suggesting that there is self-regulatory negative feedback in normal tissues. These results demonstrate that it is possible to vaccinate against a tumor embedded in a vital organ that shares the target Ag.

Aberrant Notch signaling: a potential pathomechanism of vitiligo.

Vitiligo is characterized by a localized and progressive loss of melanocytes which are pigment cells responsible for the pigmentation of human. The etiopathogenetic mechanisms leading to melanocytes loss in vitiligo lesions are not yet fully understood and no effective treatment or cure exists. Notch signaling has been shown to control many cellular functions of melanocytes. Activation of Notch signaling occurs during the formation of melanocytic tumors and inactivation of Notch signaling causes a dramatic elimination of melanocytes precursors. So we postulate that inactivation of Notch signaling in the melanocytes may be a potential pathomechanism of vitiligo. If the hypothesis was proved to be practical, we could provide new understanding of the etiology of vitiligo and produce new therapeutic avenues.

The Arg160Trp allele of melanocortin-1 receptor gene might protect against vitiligo.

Melanocortin-1 receptor (MC1R) and agouti signaling protein (ASIP) play pivotal roles in the regulation of human pigmentation. We aimed to study whether single nucleotide polymorphisms (SNPs) of the MC1R and ASIP genes contribute to the pathogenesis of the polygenic pigment skin disorder, vitiligo. The PCR-amplified, full-length MC1R gene was studied with sequence analysis, and the 3' untranslated region (3' UTR) SNP of ASIP was detected using restriction fragment length polymorphism. The allele frequency of the ASIP SNP did not show any difference between the skin type, hair color and eye color-matched 97 vitiligo patients and the 59 healthy control individuals. As one of the MC1R polymorphisms showed significantly higher incidence among fair-skinned individuals (Fitzpatrick I+II, n=140) than among dark-skinned individuals (Fitzpatrick III+IV, n=90), both vitiligo patients and controls were divided into two groups and the frequency of the MC1R alleles was studied separately in fair-skinned and dark-skinned subgroups of diseased and healthy groups. C478T, one of the MC1R SNPs studied in 108 fair-skinned vitiligo patients and in 70 fair-skinned healthy control individuals, showed a significant difference (P=0.0262, odds ratio [95% confidence interval]=3.6 [0.0046-0.1003]) in allele frequency between the two groups: the allele frequency was higher in the control group, suggesting protection against vitiligo. Computer prediction of antigenicity has revealed that the Arg160Trp amino acid change caused by this SNP results in a decrease in antigenicity of the affected peptide epitope.

Hydrogen peroxide regulates the cholinergic signal in a concentration dependent manner.

The human epidermis holds the full capacity for autocrine synthesis, transport and degradation of acetylcholine as well as the muscarinic (m1-m5) and nicotinic signal transduction in keratinocytes and melanocytes. This cholinergic cascade is severely affected in patients with the depigmentation disorder vitiligo due to accumulation of hydrogen peroxide (H(2)O(2)) in the mM range as shown by in vivo FT-Raman spectroscopy. These high levels can oxidise susceptible amino acid residues such as methionine, tryptophan, cysteine and selenocysteine in the structure of proteins and peptides which in turn can severely affect the function. Here the effect of this reactive oxygen species was followed on the production and degradation of acetylcholine using immunofluorescence, enzyme kinetics, in vivo and in vitro FT-Raman and fluorescence spectroscopy as well as computer modelling. The results showed that both epidermal acetylcholinesterase (AchE) and butyrylcholinesterase (BchE) are target to H(2)O(2)-mediated oxidation of methionine and tryptophan residues close to the catalytic triad, while cholineacetyltransferase (chAT) is not affected. Enzyme kinetics revealed concentration dependent activation/deactivation of both degrading enzymes by H(2)O(2). Oxidation of methionine to methionine sulfoxide was confirmed by FT-Raman spectroscopy while oxidation of tryptophan to 5OH-tryptophan was identified by fluorescence spectroscopy. H(2)O(2)-mediated oxidation of both enzymes takes place in acute vitiligo yielding accumulation of acetylcholine in the epidermis of these patients. This process is reversible with a narrowband UVB activated pseudocatalase PC-KUS leading to recovery of epidermal and systemic enzyme activities as well as restoration of the lost skin colour.