Search

Vitiligo development in melanoma patients during immunotherapy is a favorable prognostic sign and indicates breakage of tolerance against melanocytic/melanoma antigens. We investigated a novel immunotherapeutic approach of the skin-depigmenting compound monobenzone synergizing with imiquimod in inducing antimelanoma immunity and melanoma regression. Stage III-IV melanoma patients with non-resectable cutaneous melanoma metastases were treated with monobenzone and imiquimod (MI) therapy applied locally to cutaneous metastases and adjacent skin during 12 weeks, or longer. Twenty-one of 25 enrolled patients were evaluable for clinical assessment at 12 weeks. MI therapy was well-tolerated. Partial regression of cutaneous metastases was observed in 8 patients and stable disease in 1 patient, reaching the statistical endpoint of treatment efficacy. Continued treatment induced clinical response in 11 patients, including complete responses in three patients. Seven patients developed vitiligo-like depigmentation on areas of skin that were not treated with MI therapy, indicating a systemic effect of MI therapy. Melanoma-specific antibody responses were induced in 7 of 17 patients tested and melanoma-specific CD8+T-cell responses in 11 of 15 patients tested. These systemic immune responses were significantly increased during therapy as compared to baseline in responding patients. This study shows that MI therapy induces local and systemic anti-melanoma immunity and local regression of cutaneous metastases in 38% of patients, or 52% during prolonged therapy. This study provides proof-of-concept of MI therapy, a low-cost, broadly applicable and well-tolerated treatment for cutaneous melanoma metastases, attractive for further clinical investigation.

Background  Ultraviolet radiation following punch grafting may stimulate the migration of melanocytes from the grafts into the vitiliginous skin, thereby increasing the rate of repigmentation. We compared the effects of the 308-nm xenon chloride excimer laser (EL) vs. narrow-band ultraviolet B (NB-UVB) after punch grafting in patients with vitiligo. Objectives  The aims of this study were to evaluate (i) repigmentation (%); (ii) treatment satisfaction; and (iii) patient preferences for EL vs. NB-UVB therapy after punch grafting in vitiligo. Methods  Fourteen patients were treated with the punch-grafting technique on two symmetrical vitiligo patches. Starting 1 week after the punch grafting, the vitiligo patches were treated twice a week during 3 months, with EL on one side and with NB-UVB on the other side. Repigmentation (%) was measured by a digital image analysis system. Patients' satisfaction and preference for treatment were also assessed. Results  Whereas both treatment modalities induced repigmentation, no statistically significant difference was found in grade of repigmentation after 3 months. With EL, 71.4% lower cumulative dose was reached. Patients were significantly more satisfied with NB-UVB and preferred it over EL. Conclusions  The choice between EL and NB-UVB cannot solely be based on repigmentation, but rather on other factors, such as patients' preferences. However, given the lower UV dose of EL, we recommend its use in vulnerable populations, such as in small children and patients with sun-damaged skin with a history of long-term UVB treatment., (© 2011 The Authors. Journal of the European Academy of Dermatology and Venereology © 2011 European Academy of Dermatology and Venereology.)

To study protection of melanocytes from stress-induced cell death by heme oxygenases during depigmentation and repigmentation in vitiligo, expression of isoforms 1 and 2 was studied in cultured control and patient melanocytes and normal skin explants exposed to UV or bleaching agent 4-TBP. Similarly, expression of heme oxygenases was followed in skin from vitiligo patients before and after PUVA treatment. Single and double immunostainings were used in combination with light and confocal microscopic analysis and Western blotting. Melanocyte expression of heme oxygenase 1 is upregulated, whereas heme oxygenase 2 is reduced in response to UV and 4-TBP. Upregulation of inducible heme oxygenase 1 was also observed in UV-treated explant cultures, in skin of successfully PUVA-treated patients and in melanocytes cultured from vitiligo non-lesional skin. Heme oxygenase encoding genes were subsequently cloned to study consequences of either gene product on cell viability, demonstrating that HO-1 but not HO-2 overexpression offers protection from stress-induced cell death in MTT assays. HO-1 expression by melanocytes may contribute to beneficial effects of UV treatment for vitiligo patients., (© 2011 John Wiley & Sons A/S.)

Objective: To compare the efficacy and safety of using a combination of fluticasone propionate (FP) and UV-A with that of either drug used alone in the long-term treatment of vitiligo., Design: Prospective, randomized, controlled, left-right comparison study. Repigmentation was judged by a single dermatologist (L.N.-K.) and skin thickness was scored by a pathologist (using biopsy samples), a dermatologist (L.N.-K.) (visually), and patients (using a standard questionnaire)., Setting: Netherlands Institute for Pigmentary Disorders, Amsterdam., Patients: Patients with lesions on arms, legs, and trunk were treated on 2 symmetrical lesions for 9 months with FP alone and a combination of FP and UV-A (FP group) or with UV-A alone and a combination of FP and UV-A (UV-A group). Fluticasone propionate cream was applied once daily at about bedtime, and UV-A (10 J/cm2) exposure was twice a week. Patients attended the clinic at 3-month intervals., Results: One hundred thirty-five patients were included, 96 of whom were evaluable after 9 months. Patients not reaching the end point withdrew because of insufficient repigmentation (n = 23), decreased motivation (n = 11), or protocol violations (n = 5). No patient (irrespective of whether they withdrew) experienced any adverse effects. The FP and UV-A groups were comparable with respect to sex, age, and location of lesions. On average, combination treatment was 3 times more effective than either UV-A or FP treatment alone. In the FP group, no atrophy was seen after 9 months with either treatment. In the UV-A group, a little atrophy was detected twice: as well during UV-A treatment alone as during combination treatment., Conclusions: Combination treatment with FP and UV-A is much more effective in reaching complete repigmentation than are FP and UV-A used alone, but large inter-individual differences occur. Fluticasone propionate, UV-A, and a combination of FP and UV-A seem to be safe for long-term treatment of vitiligo.

Objective: To compare the efficacy and safety of 2 treatment modalities, topical psoralen plus UV-A (PUVA) with unsubstituted psoralen and 311-nm UV-B radiation, in patients with vitiligo., Design: This intervention study was designed as a before-and-after trial with 2 arms, in which patients were consecutively included., Patients: Male (n = 99) and female (n = 182) patients, who predominantly had skin type III, with extensive, generalized vitiligo of more than 3 months' duration., Interventions: Two patient groups were investigated. The first group of patients was treated for 4 months with either topical PUVA (n = 28) or 311-nm UV-B radiation (n = 78). The second group of patients, treated twice weekly with 311-nm UV-B radiation, was followed up for 3 (n = 60), 6 (n = 27), 9 (n = 37), or 12 months (n = 51)., Results: Thirteen (46%) patients in the first group treated with topical PUVA showed repigmentation after 4 months. Fifty-two patients (67%) in the 311-nm UV-B treatment group showed repigmentation after 4 months. After 3 months, 5 patients (8%) in the second group showed more than 75% repigmentation of lesional skin compared with 32 patients (63%) after 12 months. As in other treatment modalities, the face showed good repigmentation, whereas hands and feet responded poorly. No adverse effects were encountered with treatment with narrowband UV-B radiation, contrary to those seen with topical PUVA treatment. The cumulative UV-B dose was very small compared with that of the topical PUVA treatment., Conclusions: According to our results, the treatment of patients with vitiligo with 311-nm UV-B radiation is as efficient as with topical PUVA and has fewer adverse effects.