Anti-Melanoma immunity and local regression of cutaneous metastases in melanoma patients treated with monobenzone and imiquimod; a phase 2 a trial.

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.

Ablative fractional laser therapy as treatment for Becker nevus: a randomized controlled pilot study.

BACKGROUND: Becker nevus (BN) is an uncommon pigment disorder characterized by hyperpigmentation and sometimes hypertrichosis. To date, no effective treatment has been available. OBJECTIVES: We sought to assess efficacy and safety of ablative 10,600-nm fractional laser therapy (FLT) in the treatment of BN. METHODS: Eleven patients with BN, older than 18 years, were included in a prospective randomized controlled, observer-blinded split-lesion trial. In each patient two similar square test regions were randomized to either ablative FLT at 10 mJ/microbeam, coverage 35% to 45%, and topical bleaching (to prevent laser-induced postinflammatory hyperpigmentation), or topical bleaching alone (to allow comparison of the regions). At 3- and 6-month follow-up, clearance of hyperpigmentation was assessed by physician global assessment, reflectance spectroscopy, melanin index, patient global assessment, patient satisfaction, and histology. RESULTS: At 6-month follow-up, physician global assessment improved in the FLT region (P < .05). Reflectance spectroscopy, melanin index, number of melanocytes, and amount of dermal melanin did not significantly differ between the regions. Patient global assessment and patient satisfaction were 5.0 and 5.9 (visual analog scale score, 0-10), respectively. Side effects were postinflammatory hyperpigmentation (n = 3), erythema (n = 3), burning sensation (n = 3), crusting (n = 3), edema (n = 2), and blistering (n = 2). LIMITATIONS: Limitations include the small number of patients, treatment in spring, possibly suboptimal laser settings, and the combined usage of FLT and a bleaching agent. CONCLUSION: Ablative FLT was moderately effective in some patients with BN. However, postinflammatory hyperpigmentation and relatively negative patient-reported outcomes still preclude ablative FLT from being a standard therapy. Larger studies with different laser settings will be required to optimize this treatment modality.

Heme oxygenase-1 expression protects melanocytes from stress-induced cell death: implications for vitiligo.

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.

Nonablative 1550-nm fractional laser therapy versus triple topical therapy for the treatment of melasma: a randomized controlled pilot study.

BACKGROUND: Various treatments are currently available for melasma. However, results are often disappointing. OBJECTIVE: We sought to assess the efficacy and safety of nonablative 1550-nm fractional laser therapy and compare results with those obtained with triple topical therapy (the gold standard). METHODS: Twenty female patients with moderate to severe melasma and Fitzpatrick skin types II to V were treated either with nonablative fractional laser therapy or triple topical therapy (hydroquinone 5%, tretinoin 0.05%, and triamcinolone acetonide 0.1% cream) once daily for 8 weeks in a randomized controlled observer-blinded study. Laser treatment was performed every 2 weeks for a total of 4 times. Physician Global Assessment was assessed at 3 weeks, 3 months, and 6 months after the last treatment. RESULTS: Physician Global Assessment improved (P < .001) in both groups at 3 weeks. There was no difference in Physician Global Assessment between the two groups. Mean treatment satisfaction and recommendation were significantly higher in the laser group at 3 weeks (P < .05). However, melasma recurred in 5 patients in both groups after 6 months. Side effects in the laser group were erythema, burning sensation, facial edema, and pain; in the triple group side effects were erythema, burning, and scaling. LIMITATIONS: Limitations were: small number of patients; only one set of laser parameters; and a possible difference in motivation between groups. CONCLUSIONS: Nonablative fractional laser therapy is safe and comparable in efficacy and recurrence rate with triple topical therapy. It may be a useful alternative treatment option for melasma when topical bleaching is ineffective or not tolerated. Different laser settings and long-term maintenance treatment should be tested in future studies.

Non-ablative 1,550 nm fractional laser therapy versus triple topical therapy for the treatment of melasma: a randomized controlled split-face study.

BACKGROUND: Melasma is a uichronic, often relapsing skin disorder, with poor long-term results from all current therapies. OBJECTIVE: To assess efficacy and safety of non-ablative 1,550 nm fractional laser therapy (FLT) as compared to the gold standard, triple topical therapy (TTT). STUDY DESIGN: Twenty-nine patients with melasma were included in a randomized controlled observer-blinded study with split-face design. Each side of the face was randomly allocated to either 4-5 non-ablative FLT sessions (15 mJ/microbeam, 14-20% coverage) or TTT (hydroquinone 5%, tretinoin 0.05%, triamcinolone acetonide 0.1% cream). TTT was applied once daily for 15 weeks until the last FLT session. After this last treatment, patients were asked to apply TTT twice weekly on both sides of the face during follow-up. Improvement of melasma was assessed by patient's global assessment (PGA), patient's satisfaction, physician's global assessment (PhGA), melanin index, and lightness (L-value) at 3 weeks, and at 3 and 6 months after the last treatment. RESULTS: Mean PGA and satisfaction were significantly lower at the FLT side (P<0.001). PhGA, melanin index, and L-value showed a significant worsening of hyperpigmentation at the FLT side. At the TTT side, no significant change was observed. At 6 months follow-up, most patients preferred TTT. Side effects of FLT were erythema, burning sensation, edema, and pain. Nine patients (31%) developed PIH after two or more laser sessions. Side effects of TTT were erythema, burning sensation, and scaling. CONCLUSIONS: Given the high rate of postinflammatory hyperpigmentation, non-ablative 1,550 nm fractional laser at 15 mJ/microbeam is not recommendable in the treatment of melasma. TTT remains the gold standard treatment.