Laser treatment for further depigmentation in vitiligo

Background In patients with vitiligo, sometimes the greatest part of the skin has already lost its melanocytes. The remaining pigmented patches can be removed by using strong bleaching creams, but many adverse events have been reported with this treatment. Anew depigmentation therapy could be treatment with a Ruby laser. Methods Before treatment, the patients filled out a questionnaire about their vitiligo history. Eight patients with remaining pigmentation of the arms, hands, and face were treated once with a Ruby laser. Patients were monitored for developing repigmentation during the 9 months after treatment. Results In patients with a positive Koebner phenomenon, a permanent state of depigmentation was reached after laser therapy. None of the treated patients showed severe side-effects. Conclusions Ruby laser treatment can be an effective, fast, and safe method for removing cosmetically disturbing remnants of normal pigmentation in vitiligo patients with a positive Koebner phenomenon.     

Immunopolarization of CD4+ and CD8+ T cells to Type-1-like is associated with melanocyte loss in human vitiligo

Vitiligo is an autoimmune condition characterized by loss of epidermal melanocytes. High frequencies of melanocyte-reactive cytotoxic T cells in the peripheral blood of vitiligo patients and the observed correlation between perilesional T-cell infiltration and melanocyte loss in situ suggest the important role of cellular autoimmunity in the pathogenesis of this disease. We isolated T cells from both perilesional and nonlesional skin biopsies obtained from five vitiligo patients, then cloned and analyzed their profile of cytokine production after short-term, nonspecific expansion in vitro. Perilesional T-cell clones (TCC) derived from patients with vitiligo exhibited a predominant Type-1-like cytokine secretion profile, whereas the degree of Type-1 polarization in uninvolved skin-derived TCC correlated with the process of microscopically observed melanocyte destruction in situ. Detailed analysis of broad spectrum of cytokines produced by perilesional- and nonlesional-derived CD4+ and CD8+ TCC confirmed polarization toward Type-1-like in both CD4 and CD8 compartments, which paralleled depigmentation process observed locally in the skin. Furthermore, CD8+ TCC derived from two patients also were analyzed for reactivity against autologous melanocytes. The antimelanocyte cytotoxic reactivity was observed among CD8+ TCC isolated from perilesional biopsies of two patients with vitiligo. Finally, in two of five patients, tetramer analysis revealed presence of high frequencies of Mart-1-specific CD8 T cells in T-cell lines derived from perilesional skin. Altogether our data support the role of cellular mechanisms playing a significant part in the destruction of melanocytes in human autoimmune vitiligo.     

Effect of one session of ER:YAG laser ablation plus topical 5Fluorouracil on the outcome of short‐term NB‐UVB phototherapy in the treatment of non‐segmental vitiligo: a left–right comparative study

Background: NB‐UVB phototherapy is a very important modality in treating vitiligo but the treatment course usually exceeds 1 year. Skin ablation with mechanical dermabrasion with 5Fluorouracil (5FU) was introduced to treat vitiligo in 1983. This was modified replacing the mechanical dermabrasion by erbium‐YAG (ER:YAG) laser ablation and resulted in better prognosis in periungual vitiligo. Purpose: In the present study, we are exploring the effect of the use of ER:YAG laser skin ablation and application of 5FU on the outcome of short‐term NB‐UVB therapy for patients with non‐segmental vitiligo (NSV). Methods: This study included 50 adult patients with a total of 65‐paired symmetrical NSV lesions in different body parts. One side was treated with ER:YAG laser ablation, followed by 5FU application before simultaneous NB‐UVB therapy of both sides for a maximum period of 4 months. The outcome was then evaluated both qualitatively and quantitatively. Results: The overall response to therapy was better using the combination therapy. Fifty patients (78.1%) experienced a moderate‐marked repigmentation response in the combination group compared with 23.4% in the mono‐therapy group. The response was significantly higher when using the combination therapy in different body parts (P value is <0.05), except for feet lesions, which were better but not statistically significant (P value=0.15). Tolerable pain during ablation or at sites of 5FU application was reported in all cases. Transient hyperpigmentation occurred in 30% of cases and 3.1% of lesions healed by a transient slate blue color. Half of the treated periungual lesions showed a temporary tiny brownish spot on nail plates and Köebnerization was not detected in any patient. Conclusion: We concluded that prior use of ER:YAG laser skin ablation, followed by 5FU application before NB‐UVB phototherapy for vitiligo is a safe and tolerable technique that improves the outcome of short‐term NB‐UVB therapy and is expected to increase patient compliance.     

Efficient debridement of necrotic wounds using proteolytic enzymes derived from Antarctic krill: a double-blind, placebo-controlled study in a standardized animal wound model

Wound healing can be accelerated by removing necrotic tissue. Various methods of wound debridement have been developed, including enzymatic debridement. Recently potent proteolytic enzymes were isolated from the intestine of Euphausia superba (Antarctic krill) that might be useful for degrading necrotic tissue. The purpose of this study was to evaluate the debriding properties of krill enzymes, using a specially designed animal model and a computerized analysis system. In 10 female domestic pigs, each weighing 20 kg, 6 artificial ulcers were made on each animal's back using electrokeratome, followed by application of trichloracetic acid. Ulcers were treated twice daily for 7 days with either krill enzymes at different concentrations or with saline. Reduction of necrotic tissue was measured daily using computerized wound analysis. Histological examination included the determination of bromodeoxyuridine incorporation in order to detect cell proliferation as well as routine stains. The debriding effect of krill enzymes at a concentration of ≥ 3.0 casein units per ml was significantly better than saline control treatment ( p < 0.05). The effect was dose dependent, and granulation tissue formation was enhanced. In conclusion, krill enzymes are effective in wound debridement, as measured in this animal model.     

Effects of nitric oxide on the adhesion of human melanocytes to extracellular matrix components

The aim of the present study was to explore whether nitric oxide (NO) interferes with the attachment of human melanocytes to the extracellular matrix (ECM) components. Consequently, the effects have been investigated of the NO-releasing compounds 3-morpholino-sydnonimine (SIN-1) and S-nitroso-glutathione (GSNO) on the in vitro adhesion of human melanocytic cells to fibronectin. The NO donors induced a concentration-dependent reduction in the adhesion of both ⁵¹CrO₄²⁻-labelled melanocytes and melanoma cells to fibronectin. Pigmented M14 melanoma cells were more susceptible to the effect of SIN-1 (half-maximal inhibiting effect at about 0·5 mm) than normal human melanocytes and also than the non-pigmented melanoma cells Mel57 (half-maximal inhibiting effects between 0·9 and 2 mm). This effect of SIN-1 also appeared to be related to the melanin content of normal melanocytes, whereas GSNO was significantly less active. Both flow cytometric analysis and immunocytochemical staining showed expression of neuronal NO synthase in all cell lines. The results of this study suggest that aberrant in vivo production of NO during infection and inflammation may contribute to loss of melanocytes in, for example, vitiligo, by reducing de novo attachment of melanocytes to the ECM. These findings could also be important for understanding the process of metastasis. © 1997 John Wiley & Sons, Ltd.     

Safety and efficacy of combined use of 4-hydroxyanisole (mequinol) 2%/tretinoin 0.01% solution and sunscreen in solar lentigines

The objective of this open-label, noncontrolled study was to evaluate the safety of a combination solution containing 4-hydroxyanisole (mequinol) 2%/tretinoin 0.01% (Solagé) with a sunscreen in the treatment of solar lentigines. The study included a total of 406 subjects for a treatment period up to 24 weeks. Efficacy was evaluated clinically by grading the pigmentation level of the treated areas on the face and forearms. A total of 378 subjects were included in the safety population. Of the 173 subjects with skin-related and treatment-related adverse events, severity was reported as mild in 79 subjects, moderate in 71, and severe in 23. Hypopigmentation was observed in 4 subjects and had definitively resolved in 3 of these subjects at the end of the study or after treatment had been discontinued. Halo hypopigmentation was reported in 16 subjects. No allergic reactions were observed. Efficacy evaluation was based on data for 370 subjects. A total of 325 (88%) subjects had facial target lesions almost clear to clear, and a total of 298 (81%) subjects had forearm target lesions almost clear to clear. Our study shows that the mequinol 2%/tretinoin 0.01% solution is effective, convenient, and safe in the treatment of solar lentigines.