Parametric modeling of narrowband UV-B phototherapy for vitiligo using a novel quantitative tool: the Vitiligo Area Scoring Index. The efficacy of combined PUVA and low-dose azathioprine for early and enhanced repigmentation in vitiligo patients. Treatment of vitiligo vulgaris with narrow band UVB (311 nm) for one year and the effect of addition of folic acid and vitamin B12. Double-blind placebo-controlled study of autologous transplanted epidermal cell suspensions for repigmenting vitiligo. Comparison of systemic PUVA and NB-UVB in the treatment of vitiligo: an open prospective study. Efficacy of autologous transplantation of noncultured epidermal suspension in two different dilutions in the treatment of vitiligo. Randomized, double-blind clinical trial to evaluate the efficacy of topical tacalcitol and sunlight exposure in the treatment of adult nonsegmental vitiligo. Optimal weekly frequency of 308-nm excimer laser treatment in vitiligo patients. Is the efficacy of psoralen plus ultraviolet A therapy for vitiligo enhanced by concurrent topical calcipotriol? A placebo-controlled double-blind study.
There is currently no quantitative tool for evaluating vitiligo treatment response using parametric methods.
                To develop and apply a simple clinical tool, the Vitiligo Area Scoring Index (VASI), to model the response of vitiligo to narrowband UV-B (NB-UV-B) phototherapy using parametric tests.
                Prospective, randomized, controlled, bilateral left-right comparison trial.
                North American tertiary care, university-affiliated phototherapy center.
                Patients older than 18 years with stable vitiligo involving at least 5% of their total body surface in a symmetric distribution.
                Treatment with NB-UV-B was given 3 times a week to half of the body on all patients for either 60 treatments or 6 months. The contralateral side served as a no-treatment control.
                Repigmentation was assessed using the VASI, which was based on a composite estimate of the overall area of vitiligo patches at baseline and the degree of macular repigmentation within these patches over time. The VASI was validated separately against physician and patient global assessments. The overall reductions in VASI for NB-UV-B and control groups were modeled by multilevel regression with random effects and compared parametrically.
                The VASI scoring correlated well with both patient and physician global assessments (P =.05 and P<.001, respectively, using ordinal logistic regression). The extent of repigmentation after 6 months on the treated side was 42.9% (95% confidence interval, 26.7%-59.0%) vs 3.3% (95% confidence interval -19.3% to 30.0%) on the untreated side (P<.001). A significant difference between control and NB-UV-B groups was apparent within the first 2 months of therapy. The legs, trunk, and arms were much more likely to repigment than the feet and hands.
                The VASI is a quantitative clinical tool that can be used to evaluate vitiligo parametrically. Patients treated with NB-UV-B can be expected to achieve approximately 42.9% repigmentation of their vitiligo after 6 months of treatment, with the greatest response being achieved over the trunk and nonacral portions of the extremities. Immunosuppressive agents are used widely in the treatment of vitiligo. Corticosteroids are used either alone or as adjuvant therapy by many practitioners. Cyclophosphamide and cycloporine-A have also been used with variable success. Azathioprine may have the potential for the treatment of vitiligo alone or in combination with other modalities.
                To compare the efficacy of combined low-dose azathioprine and oral PUVA therapy versus oral PUVA therapy alone for the treatment of vitiligo.
                A total of 60 vitiligo patients were randomized to receive either azathioprine (0.6-0.75 mg/kg) and oral PUVA therapy (group 1) or oral PUVA therapy alone (group 2). Patients were followed for 4 months. A graph transparency with squares of 2.5 x 2.5 mm was used to measure the rate of repigmentation after 4 months of therapy.
                Perifollicular repigmentation started after a mean of five sessions in group 1, and eight sessions in group 2. The mean total repigmentation rate after 4 months was 58.4% for group 1 and 24.8% for group 2. No serious side effects were seen during or after treatment.
                Azathioprine may potentiate the repigmentary effects of PUVA therapy in vitiligo patients. A limitation of the study is the lack of validated measures for vitiligo assessment. Narrow band UVB is succeeding psoralen and UVA irradiation as the main treatment of vitiligo vulgaris in several European countries. Vitamin B12 and folic acid deficiency in some vitiligo patients has prompted researchers to investigate the efficacy of these vitamins in the treatment of vitiligo. In the present controlled study we investigated the value of narrow band UVB phototherapy in the treatment of vitiligo and the possible additive effect of vitamin B12 and folic acid. Twenty-seven patients with long-term stable vitiligo were included and randomized in a "UVB only" (UVB) or "UVB combined with vitamin B12 and folic acid" (UVB+) group. Patients were irradiated thrice weekly for one year, whilst repigmentation was carefully monitored. In 92% (25/27) of the patients up to 100% repigmentation was seen. Repigmentation was notable in lesions on the face, neck and throat, lower arm, chest, back and lower legs, whilst repigmentation on the hands, wrists, feet and ankles proved to be minimal. Maximum repigmentation rates did not differ significantly between the UVB group and the UVB+ group. Our study reconfirms that narrow band UVB phototherapy is an effective treatment for vitiligo and shows that co-treatment with vitamin B12 and folic acid does not improve the outcome of treatment of vitiligo with narrow band UVB phototherapy. To investigate the efficacy of epidermal noncultured cellular grafting in patients with vitiligo and the role of postinflammatory, spontaneous, or UV-induced pigmentation in obtaining repigmentation.
                A prospective, randomized, double-blind, placebo-controlled study.
                Ambulatory patients in an institutional practice. Patients were followed up for 3 to 12 months.
                A total of 33 paired, symmetrically distributed leukodermic lesions, all resistant to therapy, were observed in 28 patients. Nineteen patients appeared to have a stable vitiligo (group 1), whereas there was doubt about the stability of the disease in 9 patients (group 2).
                After laser ablation, a hyaluronic acid-enriched cellular graft was applied to 1 lesion while the paired lesion received placebo. Three weeks later all lesions were exposed to UV irradiation twice per week for approximately 2 months.
                Primarily, the percentage of repigmentation was assessed after 3, 6, and 12 months using a digital image analysis system. The repigmentation pattern was also evaluated after 1 and 3 months.
                A strongly significant difference between cellular grafts and placebo was observed after 3, 6, and 12 months (P<.001, P = .002, and P = .002, respectively). In group 1, repigmentation of at least 70% of the treated area was achieved in 55%, 57%, and 77% of the actively treated lesions 3, 6, and 12 months after treatment, whereas in group 2 repigmentation of at least 70% of the treated area was not observed at any time point. The repigmentation pattern was diffuse in 94% of the responding patients.
                After a strict preoperative selection for disease stability, transplantation resulted in repigmentation of at least 70% of the treated area in most actively treated vitiligo lesions. Repigmentation was primarily caused by the transplanted melanocytes. Vitiligo is a common pigmentary disorder with great cosmetic and psychological morbidity. No treatment available is a definitive cure. Systemic psoralen and ultraviolet A (PUVA) has been the mainstay of treatment. Narrow-band ultraviolet B (NB-UVB) has been recently introduced. Although retrospective comparative study of systemic PUVA and NB-UVB has been published from our centre, no prospective study has been reported to date.
                To investigate the position of NB-UVB vis-à-vis PUVA in terms of efficacy, time to repigment and adverse effects and to help decide if one therapy has an advantage over another in the treatment of vitiligo.
                It was a randomized, open, prospective study of 50 patients divided equally in TMP PUVA and NB-UVB groups. The study period was from January 2004 to June 2005.
                The mean degree of repigmentation attained in the NB-UVB group was 52.24% over a mean treatment period of 6.3 months, whereas in the PUVA group it was 44.7% in a mean period of 5.6 months (P=0.144). After excluding the results of therapy-resistant sites, that is, hands and feet, the mean degree of repigmentation in the NB-UVB group was 67.57%, whereas in the PUVA group it was 54.2% (P=0.007).
                NB-UVB performed better in comparison to TMP PUVA in terms of mean total repigmentation when traditionally considered therapy-resistant sites were excluded. Previous reports have shown the effectiveness of a basal layer cell suspension in the treatment of stable vitiligo; however, there has been no mention in the literature until now of the optimal number of melanocytes required in an autologous noncultured epidermal suspension for transplantation to obtain early and acceptable results.
                In this randomized prospective study, we compared the efficacy of two different dilutions to determine the optimum density of melanocytes required for transplantation to achieve early and cosmetically acceptable results. We enrolled 20 patients with stable vitiligo with a body surface area involvement of< 10%.
                Fifty per cent of patients in Group A (where the recipient area transplanted was approximately three times the size of the donor area, and the density of melanocytes transplanted per square millimeter was approximately 231.60+/- 27.03) showed marked (> 75%), 20% moderate, 10% mild, and 20% minimal repigmentation (or no response). In Group B (where the recipient area was increased to five-fold the donor area), none of the patients showed marked, 10% showed moderate, 20% showed mild, and 70% showed either minimal or no repigmentation. The density of melanocytes transplanted in this group was 154.90+/- 27.65/mm(2). The extent of repigmentation was significantly greater (P< 0.05) in Group A than in Group B, and the density of melanocytes in the suspension was also significantly greater (P< 0.01) in Group A than in Group B.
                We contend that the minimum number of melanocytes required to produce satisfactory repigmentation is probably in the range of 210-250/mm(2). Vitiligo is a common skin disease which is difficult to treat. Approximately half of patients acquire the disease before the age of 20 years. This disease has a high stigmatizing impact but no ideal, aetiology-oriented, effective therapy has been found to date. Tacalcitol and other vitamin D analogues have been shown to have stimulating activity both on immunomodulatory mediators and on melanocytes in lesional skin.
                To investigate the efficacy and safety of tacalcitol ointment plus sunlight exposure in the treatment of nonsegmental vitiligo.
                A single-centre, randomized, double-blind, vehicle-controlled study including 80 patients with nonsegmental vitiligo was carried out in a specialized outpatient dermatology clinic within a tertiary care, university-affiliated hospital in Spain. Efficacy was assessed by quantification of the lesional repigmentation area at the end of the study compared with the baseline. Tacalcitol (n = 40) or matching placebo ointment (n = 40) was applied once a day at night. Daily exposure to sunlight for 30 min was performed. Treatment was continued for 4 months. The response of the lesions was clinically verified every 2 weeks by a blinded medical investigator. All adverse effects were recorded.
                Eighty adult patients with nonsegmental vitiligo were recruited. Over 16 weeks, 64 patients completed the study requirements. There was no significant difference in the repigmentation response at the 16-week time point between the vehicle + sunlight exposure and the tacalcitol + sunlight exposure groups. No reduction in the size of the lesions > 25% was observed in the tacalcitol-treated patients. No serious adverse effects were observed.
                The combination of tacalcitol with heliotherapy has no additional advantages compared with heliotherapy alone. Recently the beneficial effect of excimer laser treatment has been reported for patients with vitiligo. The influence of treatment frequency on this effect is not clear.
                To determine the optimal frequency of 308-nm excimer laser therapy for vitiligo.
                In this prospective, university-based hospital study over 12 weeks we enrolled 14 patients. Each had at least three stable vitiligo lesions in the same body area. The three stable vitiligo lesions in each subject were randomly assigned to receive excimer laser treatment once (1 x), twice (2 x) and three times (3 x) weekly, respectively. The initial ultraviolet (UV) dose was 50 mJ cm(-2) less than the 308-nm minimal erythematous dose in vitiligo skin. The UV dose was increased at each treatment session according to the erythematous response to the previous treatment.
                Thirteen subjects were treated for at least 6 weeks; seven were treated for all 12 weeks. At 6 weeks, the repigmentation rates for treated lesions were 8% (1/13) after 1 x weekly treatment, 23% (3/13) after 2 x weekly treatment and 62% (8/13) after 3 x weekly treatment (P = 0.0134; 3 x vs. 1 x weekly); at 12 weeks, these rates were 46% (6/13), 62% (8/13) and 69% (9/13), respectively (P = NS; 3 x vs. 1 x weekly). Repigmentation initiation correlated with treatment number, regardless of frequency (P = NS). As shown by Kaplan-Meier analysis, repigmentation occurred earliest in the most frequently treated lesions (P = 0.0336). At 12 weeks, the projected repigmentation rates for 1 x, 2 x and 3 x weekly treatment approached each other (60%, 79% and 82%, respectively); the mean repigmentation grades (on a scale of 0-5) for 1 x, 2 x and 3 x weekly treatment were 1.7, 2.4 and 3.3, respectively (P = 0.018; 3 x vs. 1 x weekly). Laser-induced repigmentation persisted in most cases over the entire follow-up of 12 months after the end of treatment.
                308-nm excimer laser therapy is effective against vitiligo. Although repigmentation occurs fastest with 3 x weekly treatment, the ultimate repigmentation initiation seems to depend entirely on the total number of treatments, not their frequency. However, treatment periods of more than 12 weeks may be necessary to obtain a satisfactory clinical repigmentation, particularly when vitiligo lesions are treated only 1 x or 2 x compared with 3 x weekly. Encouraging results of previous uncontrolled trials suggest that calcipotriol may potentiate the efficacy of psoralen plus ultraviolet (UV) A (PUVA) therapy in patients with vitiligo.
                We performed a placebo-controlled double-blind study to investigate whether the effectiveness of PUVA treatment could be enhanced by combination with topical calcipotriol in the treatment of vitiligo.
                Thirty-five patients with generalized vitiligo enrolled in the study. Symmetrical lesions of similar dimensions and with no spontaneous repigmentation on arms, legs or trunk were selected as reference lesions. In this randomized left-right comparison study, calcipotriol 0.05 mg g(-1) cream or placebo was applied to the reference lesions 1 h before PUVA treatment (oral 8-methoxypsoralen and conventional UVA units) twice weekly. Patients were examined at weekly intervals. The mean number of sessions and the cumulative UVA dosage for initial and complete repigmentation were calculated.
                Twenty-seven patients (nine women, 18 men; mean +/- SEM age 29.8 +/- 13.5 years) were evaluated. The mean +/- SEM cumulative UVA dose and number of UVA exposures for initial repigmentation were 52.52 +/- 6.10 J cm(-2) and 9.33 +/- 0.65 on the calcipotriol side, and 78.20 +/- 7.88 J cm(-2) and 12.00 +/- 0.81 on the placebo side, respectively (P < 0.001). For complete repigmentation, respective values were 232.79 +/- 14.97 J cm(-2) and 27.40 +/- 1.47 on the calcipotriol side and 259.93 +/- 13.71 J cm(-2) and 30.07 +/- 1.34 on the placebo side (P = 0.001). Treatment with calcipotriol and PUVA resulted in significantly higher percentages of repigmentation for both initial (81%) and complete pigmentation (63%), compared with placebo and PUVA (7% and 15%, respectively).
                Our results have shown that concurrent topical calcipotriol potentiates the efficacy of PUVA in the treatment of vitiligo, and that this combination achieves earlier pigmentation with a lower total UVA dosage.
This review has found some evidence from individual studies to support existing therapies for vitiligo, but the usefulness of the findings is limited by the different designs and outcome measurements and lack of quality of life measures. There is a need for follow-up studies to assess permanence of repigmentation as well as high quality randomised trials using standardised measures and which also address quality of life.