Effective Melanoma Immunotherapy in Mice by the Skin-Depigmenting Agent Monobenzone and the Adjuvants Imiquimod and CpG

Background: Presently melanoma still lacks adequate treatment options for metastatic disease. While melanoma is exceptionally challenging to standard regimens, it is suited for treatment with immunotherapy based on its immunogenicity. Since treatment-related skin depigmentation is considered a favourable prognostic sign during melanoma intervention, we here aimed at the reverse approach of directly inducing vitiligo as a shortcut to effective anti-melanoma immunity. Methodology and Principal Findings: We developed an effective and simple to use form of immunotherapy by combining the topical skin-bleaching agent monobenzone with immune-stimulatory imiquimod cream and cytosine-guanine oligodeoxynucleotides (CpG) injections (MIC therapy). This powerful new approach promptly induced a melanoma antigen-specific immune response, which abolished subcutaneous B16. F10 melanoma growth in up to 85% of C57BL/6 mice. Importantly, this regimen induced over 100 days of tumor-free survival in up to 60% of the mice, and forcefully suppressed tumor growth upon re-challenge either 65- or 165 days after MIC treatment cessation. Conclusions: MIC therapy is effective in eradicating melanoma, by vigilantly incorporating NK-, B-and T cells in its therapeutic effect. Based on these results, the MIC regimen presents a high-yield, low-cost and simple therapy, readily applicable in the clini

Genome-wide association studies of autoimmune vitiligo identify 23 new risk loci and highlight key pathways and regulatory variants

Vitiligo is an autoimmune disease in which depigmented skin results from the destruction of melanocytes1, with epidemiological association with other autoimmune diseases2. In previous linkage and genome-wide association studies (GWAS1 and GWAS2), we identified 27 vitiligo susceptibility loci in patients of European ancestry. We carried out a third GWAS (GWAS3) in European-ancestry subjects, with augmented GWAS1 and GWAS2 controls, genome-wide imputation, and meta-analysis of all three GWAS, followed by an independent replication. The combined analyses, with 4,680 cases and 39,586 controls, identified 23 new significantly associated loci and 7 suggestive loci. Most encode immune and apoptotic regulators, with some also associated with other autoimmune diseases, as well as several melanocyte regulators. Bioinformatic analyses indicate a predominance of causal regulatory variation, some of which corresponds to expression quantitative trait loci (eQTLs) at these loci. Together, the identified genes provide a framework for the genetic architecture and pathobiology of vitiligo, highlight relationships with other autoimmune diseases and melanoma, and offer potential targets for treatment

Pigmentary disorders in Western countries

Countries in the so-called "Western" world, especially in Europe, witnessed a dramatic change in ethnic backgrounds of their populations starting in the last decennia of the last century. This had repercussions on various aspects of our society, including medical practice. In dermatology for instance, pigmentary disorders are seen more often, and the clinical pictures and their impact on patients are different from what doctors and researchers are used to and trained for. In this article, the experience from the Netherlands Institute for Pigment Disorders and the multicenter designed Netherlands guideline on vitiligo are described and the importance of the patient's point of view, as can be measured by patient reported outcomes like quality of life, is emphasize

Long-term remission of folliculitis decalvans after treatment with the long-pulsed Nd:YAG laser

Folliculitis decalvans (FD) is a rare inflammatory scalp disorder presenting with tufted folliculitis, follicular papules and pustules, progressing to cicatricial alopecia. Current treatments mainly consist of antibiotic and immunomodulatory therapies and are often disappointing. FD has previously shown to respond to treatment with neodymium:yttrium aluminium garnet (Nd:YAG) laser in one case. We present a case of recalcitrant FD, successfully treated with a long-pulsed Nd:YAG lase

Hypertrophy in port-wine stains: Prevalence and patient characteristics in a large patient cohort

Background: Port-wine stains (PWS) may thicken and darken with age. Little is known about the pathogenesis and epidemiology of PWS hypertrophy because of the lack of large studies. Objective: We sought to assess the prevalence and characteristics of patients with hypertrophic PWS. Methods: Medical records and clinical photographs of all patients with PWS visiting our clinic between 2005 and 2009 were examined to identify hypertrophy. Patients were sent questionnaires regarding their hypertrophic PWS. Results: In all, 335 patients (age 0-81 years; 69% female) with PWS were included. Hypertrophy was found in 68 patients (20%; 32 male, 36 female) and classified as thickened (5%), nodular (8%), or both (7%). Color of hypertrophic PWS was mainly red (50%) or purple (44%). Patients with hypertrophy in their PWS were mostly (68%) older than 40 years, and rarely (7%) younger than 20 years. When older than 50 years, 71% of all patients had hypertrophy in their PWS. Median age of onset of PWS hypertrophy was 31 years (12 years for thickened, 39 years for nodular). Limitations: This was a retrospective study in a selected population. Conclusion: Hypertrophy is an important feature in the development of PWS and affects a majority of patients older than 50 years. Depth of color of the PWS is associated with hypertrophy, whereas location and size appear not to be related. More attention should be drawn to therapy and prevention of hypertrophic PWS. Diffuse thickening and nodules should be distinguished, as a different age of onset may indicate different pathomechanisms. (J Am Acad Dermatol 2012; 67:1214-9.

The burden of vitiligo: patient characteristics associated with quality of life

BACKGROUND: Vitiligo is commonly regarded as a harmless cosmetic skin problem in Western societies, and the importance of treating patients with vitiligo is often underestimated. OBJECTIVE: We sought to determine the clinical and sociodemographic variables that adversely affect the quality of life in adult patients with generalized vitiligo so that these variables can be considered in the treatment and care. METHODS: A total of 245 adult patients with generalized vitiligo completed two quality-of-life questionnaires (the Medical Outcomes Study 36-Item Short-form General Health Survey and the Skindex-29). Physicians assessed sociodemographic and clinical characteristics of these patients. RESULTS: Dark skin type, vitiligo located on the chest, and treatment in the past appeared to have an adverse impact on the psychosocial domains of quality of life. Moreover, itch was reported by 20% of the patients in this study. LIMITATIONS: Psychiatric comorbidity was not evaluated in the analyses. CONCLUSION: Generalized vitiligo is a serious skin disorder with an adverse impact on the emotional state, comparable with that of other major skin disease

Non-ablative 1550 nm fractional laser therapy not effective for erythema dyschromicum perstans and postinflammatory hyperpigmentation: a pilot study

Background: Erythema dyschromicum perstans and postinflammatory hyperpigmentation (PIH) are characterized by papillary dermal pigmentation or pigment incontinence. To date, no standard treatment is available. Fractional laser therapy (FLT) was recently reported to improve different pigment disorders. Objectives: To assess the efficacy and safety of non-ablative FLT in the treatment of erythema dyschromicum perstans and PIH. Methods: Eight patients with erythema dyschromicum perstans and six patients with PIH were included. In each patient, two similar test regions were randomized to receive either five fractional laser treatments in combination with intermittent daily topical bleaching or the same intermittent regimen of topical bleaching alone. Three months after the last treatment, improvement of hyperpigmentation was assessed by melanin index, reflectance spectroscopy, physician's assessment, patient's assessment and patient's satisfaction. In addition, a biopsy of both laser treated and control site was evaluated by an independent blinded pathologist. Results: No clinical improvement of hyperpigmentation was observed. Reflectance spectroscopy, melanin index, number of melanocytes and amount of dermal melanin did not significantly differ. Patients considered FLT unsatisfactory. Moreover, three patients developed laser-induced PIH. Conclusions: With these specific laser settings, non-ablative FLT was not effective for the treatment of erythema dyschromicum perstans and PI