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Important Note: The following information is provided for your education. It should not be relied upon for personal diagnosis or treatment. If you believe that a particular therapy applies to you or someone you care about, be sure to consult a doctor before trying it.
   

Vitiligo Research: 2002-2006
  
Ned Tijdschr Geneeskd. 2006 Sep 9;150(36):1976-81.
[The practice guideline 'vitiligo']
[Article in Dutch]
Menke HE, van Everdingen JJ.
Sint Franciscus Gasthuis, afd. Dermatologie, Rotterdam.

A working group of the Dutch Society for Dermatology and Venereology (NVDV), in collaboration with the Dutch Institute for Health Care Improvement (CBO), has written an evidence-based guideline for the treatment of vitiligo. A distinction is made between generalised or non-segmental vitiligo and localised, including segmental, vitiligo. In patients with generalised vitiligo phototherapy (especially narrow-band ultraviolet B) is the treatment of first choice while in localised vitiligo, this is surgery, particularly autologous skin transplantation (Thiersch grafting, the use of blister epidermis and cell suspensions). However, on the basis of the results of the treatments proposed in the guideline, the working group cannot advise dermatologists to propose a particular treatment to each vitiligo patient they see. On the other hand, the working group is of the opinion that, based on a proper medical examination and an assessment of the disease burden, well-considered advice--and in some cases therapy--should be given to every vitiligo patient who requests it. The benefit of the guideline is that it provides clarity to dermatologists, general practitioners and patients regarding the therapeutic possibilities and limitations.

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Tidsskr Nor Laegeforen. 2006 Sep 21;126(18):2370-2.
[Vitiligo—loss of cutaneous pigmentation]
[Article in Norwegian]
Sitek JC.
Hudavdelingen, Rikshospitalet-Radiumhospitalet, 0027 Oslo. jsitek@rikshospitalet.no

BACKGROUND: Vitiligo is an acquired pigmentary skin disorder that affects 0.5-2% of the population. Many patients contact their physician and alternative therapists for help. This review article presents an update of knowledge about vitiligo and is aimed at physicians that treat this patient group. METHOD: The article is based on literature identified on PubMed, textbooks in Dermatology and supplemented by clinical experience. RESULTS AND INTERPRETATION: Vitiligo is characterized by the absence of melanocytes in skin and hair follicles. The pathogenesis is complex with genetic, autoimmune and toxic contributors. Clinically well-defined milk-white maculae are seen in the skin, with a wide variety of spread and distribution. The debut of vitiligo is often in childhood and adolescence. Investigations indicate that vitiligo affects quality in life for both children and adults. Treatment of vitiligo is a challenge. Phototherapy with narrowband UVB or topical therapy with tacrolimus ointment or potent steroids may be indicated in some cases, but the effect is not well documented.

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Harefuah. 2006 Jul;145(7):483-5, 552, 551.
[Long-term effects of PUVA therapy on Israeli patients with vitiligo]
[Article in Hebrew]
Vussuki E, Ziv M, Rosenman D, David M.
Department of Dermatology, Rabin Medical Center, Petah Tikva, Israel. evusuki@clalit.org.il

BACKGROUND: Long-term treatment of psoriasis patients with PUVA (psoralen and ultraviolet A) is associated with an increased risk of photoaging and non-melanomic skin cancer, and perhaps of melanoma as well. Very little information is available on the long-term effects of PUVA treatment on vitiligo patients in general, and specifically on the risk of developing skin tumors. Among vitiligo patients treated with PUVA or heliotherapy, only a few cases of squamous cell carcinoma (SCC) have been described. OBJECTIVE: The objective of this research is to examine the long-term effects of PUVA treatment among vitiligo patients and the incidence of long-term side effects, including various types of skin cancers. PATIENTS AND METHODS: The medical files of all patients treated with PUVA at the Rabin Medical Center and the Emek Medical Center between 1982 and 1996 were surveyed. Each patient was interviewed by telephone and then invited to come in for a medical examination. RESULTS: A total of 28 out of 31 patients completed the questionnaire, and 12 of them were also examined. The average age of the patients was 47 years (range 25-84). The average amount of radiation to which each patient was exposed was 546.8 J/cm2 (range 26.5-1561), with a median of 336.8 J/cm2. The average number of treatments per patient was 84.2 (median 77). The average time that elapsed since beginning the treatment was 11 years (range 7-20), and the average time since treatment ended was 9.4 years (range 2-23). Partial or total repigmentation was experienced by 60% of the patients. In 18% of the patients, total or almost total repigmentation was seen, which lasted an average of 46 months. No skin cancer of any kind was seen in any of the patients. CONCLUSION: A recurrence of the illness was seen in all the vitiligo patients who had responded to PUVA treatment. Long-term treatment with PUVA for vitiligo patients does not entail photoaging damages or increased risk of skin cancer.

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Photomed Laser Surg. 2006 Jun;24(3):354-7.
Treatment of vitiligo using the 308-nm excimer laser.
Hadi S, Tinio P, Al-Ghaithi K, Al-Qari H, Al-Helalat M, Lebwohl M, Spencer J.
Department of Dermatology, Mount Sinai School of Medicine, New York, New York 10029, USA. Suhail.Hadi@mssm.edu

OBJECTIVE: The aim of this study was to study the effectiveness of the 308-nm xenon chloride excimer laser in the treatment of vitiligo and to determine factors that favor a good response to treatment. BACKGROUND DATA: Targeted phototherapy using the 308-nm xenon chloride excimer laser represents an effective therapy for the management of vitiligo. However, studies on a large number of patients are few despite the increasing use of the excimer laser to treat patients with vitiligo. METHODS: A retrospective chart review of 97 patients with chronic stable vitiligo was done with a total of 221 vitiligo patches treated. RESULTS: Out of 221 vitiligo patches treated, 50.6% showed 75% pigmentation or more, 25.5% achieved 100% pigmentation of their patches, and 64.3% showed 50% pigmentation or more. Lesions on the face responded better than lesions elsewhere. CONCLUSION: The 308-nm xenon chloride excimer laser is an effective and safe modality for the treatment of vitiligo, with good results achieved in a relatively short duration of time.

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Int J Dermatol. 2006 Jun;45(6):747-50.
Autologous melanocyte transfer via epidermal grafts for lip vitiligo.
Gupta S, Goel A, Kanwar AJ, Kumar B.
>From the Department of Dermatology, Venereology, and Leprology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.

Background Vitiligo of the lips is a common concern of great psychologic consequence. Medical therapies are often ineffective due mainly to the absence of hair follicles. The transfer of melanocytes or melanocyte-bearing skin by a surgical procedure may repigment this condition. Only a few surgical modalities have been successful in this "difficult to treat" site. Objective To assess the effectiveness of autologous melanocyte transfer by epidermal grafts for lip vitiligo and to review the literature on the surgical correction of lip vitiligo. Methods Twenty-six vitiligo patients (20 women and six men; age range, 13-43 years; mean, 26.8 years) having 31 affected lips with stable disease were included in the study. The suction blisters were raised using our own modified device on the lateral aspect of the thigh. The roofs of the blisters were transferred to the dermabraded recipient area. The dressing, together with the grafts, was removed on day 8. Patients were given photochemotherapy for 6 weeks. In addition, meta-analysis of the published literature on the surgical management of lip vitiligo was also performed. Results Complete repigmentation was observed in 27 of the 31 lip areas (87%) in 23 of 25 patients (92%) in whom a follow-up for 6 months or more was available. Complications observed were persistent hyperpigmentation in 12 lips and reactivation of herpes in one patient. Minimal hyperpigmentation was seen in most of the remaining lips. The results of the meta-analysis revealed that the success rate varies from 32.5% to 100% with various surgical procedures. Conclusion Autologous melanocyte transfer is an effective and safe therapeutic option for stable vitiligo of the lips. It is cosmetically more acceptable, as there is no abnormal keratinization, which is a problem associated with dermo-epidermal grafts.

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Int J Dermatol. 2006 Jun;45(6):649-55.
Repigmentation of vitiligo with punch grafting and narrow-band UV-B (311 nm)—a prospective study.
Lahiri K, Malakar S, Sarma N, Banerjee U.
>From the Pigmentary Disorder Unit, Rita Skin Foundation, Calcutta, India.

Background Phototherapy is already established as an effective mode of therapy in vitiligo. An evidence-based study was carried out of the effect of narrow-band (311 nm) ultraviolet-B (NB-UV-B) radiation in 66 surgically treated patients with recalcitrant vitiligo in whom autologous mini-punch grafting was deployed. Methods A total of 2613 grafts were placed over 108 lesions on 17 regions in 66 individuals (39 females and 27 males) with stable, refractory vitiligo. The age range was 21-48 years. Postsurgically, they were exposed to a suberythemal dose of NB-UV-B (311 nm). Different parameters of surgical repigmentation were documented. Results Successful repigmentation was achieved in 57 (86.36%) cases. The appearance of repigmentation (AOR) time in different regions varied between 14 and 32 days, with an overall average of approximately 20.6 days. Maximum pigment spread (MPS) reached 12 mm with an average of 6.5 mm. The relationship between the donor graft area and area of surgical repigmentation was also calculated. Cobblestoning was the most common (31.8%) complication, but improved with time and/or interference. Conclusions Punch grafting in combination with phototherapy (NB-UV-B, 311 nm) was found to be an easy, safe, inexpensive, and effective method of repigmenting static and stubborn vitiligo. Different facets of punch grafting-induced and phototherapy-aided surgical repigmentation were taken into consideration. The area of repigmentation, MPS, and relationship between the donor graft area and area of surgical repigmentation were documented.

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J Dermatol. 2006 May;33(5):338-43.
Narrow-band ultraviolet B as monotherapy and in combination with topical calcipotriol in the treatment of vitiligo.
Arca E, Tastan HB, Erbil AH, Sezer E, Koc E, Kurumlu Z.
Department of Dermatology, Gulhane Military Medical Academy, School of Medicine Etlik, Ankara, Turkey. earca@gata.edu.tr

Vitiligo is a common, idiopathic, acquired, depigmenting disease characterized by loss of normal melanin pigments in the skin. The most interesting treatment methods for extensive vitiligo involve psoralen plus ultraviolet A (PUVA) therapy and ultraviolet (UV)-B phototherapy, particularly narrow-band UV-B. In this randomized and comparative study, we investigated the safety and efficacy of narrow band ultraviolet B as monotherapy and in combination with topical calcipotriol in the treatment of generalized vitiligo. Of the 40 vitiligo patients enrolled in the study, 15 were treated with the calcipotriol plus narrow-band UV-B (NBUVB) and 25 with narrow band UV-B alone. The patients were randomized into two NBUVB treatment groups. The first group, consisting of 24 patients (all male), received only NBUVB treatment; the second group, consisting of 13 patients (all male) applied 0.05% topical calcipotriol ointments twice daily. Both groups were irradiated with NBUVB (311 nm). In the NBUVB group, the percentage of the body surface affected was reduced from 27.21 +/- 10.41% to 16.25 +/- 8.54% after a mean of 30 treatment sessions. The mean repigmentation percentage was 41.6 +/- 19.4%. In clinical evaluation (moderate and marked/complete response was accepted as an effective treatment), 19 patients (19/24; 79.17%) had clinically good results. In the NBUVB plus calcipotriol group, the percentage of the body surface affected was reduced from 23.35 +/- 6.5% to 13.23 +/- 7.05% after a mean of 30 treatment sessions. The mean repigmentation percentage was 45.01 +/- 19.15%. In clinical evaluation (moderate and marked/complete response was accepted as an effective treatment), 10 patients (10/13; 76.92%) had clinically good results. Statistically significant intragroup reductions from the baseline percentage of the body surface affected were seen at the endpoint of treatment for the two treatment groups (P < 0.001). However, there was no statistically significant difference between the two treatment groups at the end of therapy with respect to the reduction of repigmentation rates (P > 0.05). The present study reconfirmed the efficacy of NBUVB phototherapy in vitiligo. It can be a therapeutic option considered in the management of patients with vitiligo. However, addition of topical calcipotriol to NBUVB did not show any advantage.

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J Eur Acad Dermatol Venereol. 2006 May;20(5):558-64.
The efficacy of excimer laser (308 nm) for vitiligo at different body sites.
Hofer A, Hassan AS, Legat FJ, Kerl H, Wolf P.
Medical University of Graz, Department of Dermatology, Graz, Austria. angelika.hofer@meduni-graz.at

BACKGROUND: The treatment with XeCl-excimer laser generated 308-nm UVB radiation has shown promising results in patients with vitiligo. OBJECTIVE: In this controlled, prospective trial we studied the primary efficacy (start and grade of repigmentation) and patient's satisfaction of XeCl-excimer laser for treatment of vitiligo patches at different body sites and re-evaluated the achieved repigmentation 12 months after the end of therapy. METHODS: Twenty-five patients with generalized or localized vitiligo with a total of 85 lesions at different body sites were enrolled in this study. Vitiligo patches were treated with 308-nm XeCl-excimer laser 3 times a week for 6 to 10 weeks. The overall repigmentation grade of each treated lesion was evaluated once a week on a 5 point scale rating from 0 (no repigmentation), 1 (1-5%), 2 (6-25%), 3 (26-50%), 4 (51-75%), to 5 (76-100%). RESULTS: Twenty-four patients completed the study. Within 6 to 10 weeks of treatment 67% of the patients (16/24) developed follicular repigmentation of at least one of their vitiligo lesions. Lesion repigmentation started after a mean of 13 treatments in lesions located on the face, trunk, arm, and/or leg (high-responder location), and after a mean of 22 treatments in lesions located on the elbow, wrist, dorsum of the hand, knee, and/or dorsum of the foot (low-responder location). Untreated control lesions and lesions located on the fingers did not achieve any repigmentation. After 10 weeks of treatment repigmentation of more than 75% was found in 25% (7/28) of lesions of the high-responder location group versus 2% (1/43) of lesions of the low-responder location group. In most cases, laser-induced repigmentation was persistent, as determined 12 months after the end of treatment. CONCLUSIONS: 308-nm excimer laser is an effective modality for the treatment of vitiligo. However, similar to other non-surgical treatment modalities, the therapeutic effect is mainly dependent on the location of vitiligo lesions.

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Int J Dermatol. 2006 Apr;45(4):411-7.
Dermatosurgical techniques for repigmentation of vitiligo.
Rusfianti M, Wirohadidjodjo YW.
Dermatovenereology Department, School of Medicine, Gadjah Mada University, Sardjito Hospital, Yogyakarta, Indonesia.

There are a number of dermatosurgery techniques available to achieve repigmentation of vitiligo, such as suction blister grafting, split-thickness skin grafting, punch grafting, follicular grafting, cultured-melanocytes transplantation, and noncultured-melanocytes transplantation. Each method has advantages and disadvantages. As there are no specific data available from the prospective studies in this field it is uneasy to recommend which surgical approach to vitiligo offers the best result. According to a systematic review by Njoo et al.,(17) suction blister and split-thickness skin grafting have the highest rates of success (87%), while the average success rates for other methods varied from 13% to 53%. Punch grafting has the highest rate of adverse effects, including cobblestoning appearance (27%) and scar formation (40%) in the donor site. Accordingly, it is also mandatory to appropriately select vitiligo patients in order to achieve a complete and permanent repigmentation.

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J Eur Acad Dermatol Venereol. 2006 Mar;20(3):269-73.
Effect of topical calcipotriol, betamethasone dipropionate and their combination in the treatment of localized vitiligo.
Kumaran M, Kaur I, Kumar B.
Department of Dermatology, Venereology and Leprology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.

Background Treatment of vitiligo is a challenge. Steroids are known to be effective but are associated with serious adverse effects. Many uncontrolled studies have shown calcipotriol to be a promising therapeutic modality in vitiligo. Objective To conduct a randomized trial to evaluate the effect of topical calcipotriol ointment (0.005%) and betamethasone dipropionate (0.05%) cream, given alone or in combination, in treatment of localized vitiligo. Methods Forty-nine patients with vitiligo affecting 5% of their skin were recruited. Patients were randomized into three groups. Group I patients were treated with betamethasone dipropionate (0.05%) cream twice daily. Group II patients were treated with calcipotriol ointment (0.005%) twice daily, and group III with betamethasone dipropionate (0.05%) in the morning and calcipotriol (0.005%) in the evening. Results Forty-five patients completed the study period of 3 months with 15 patients in each group. No patient achieved excellent (> 75%) pigmentation. Marked (50% to 75%) repigmentation was observed in 2 (13.3%), 1 (6.7%) and 4 (26.7%) patients in groups I, II and III, respectively. Moderate (25-50%) repigmentation was observed in 7 (46.7%), 5 (33.3%) and 7 (46.7%) patients in groups I, II and III, respectively. Patients with < 25% pigmentation were termed as minimal pigmentation or no response. The mean time for initial pigmentation to appear was 9.04 +/- 2.0 weeks in group I, 10.18 +/- 1.6 weeks in group II and 5.17 +/- 2.4 weeks in group III (P < 0.01). The acquired pigmentation in the lesions was more stable in group III as compared with patients in groups II and I (P < 0.01). Side-effects in the form of atrophy and lesional burning sensations were more common in group I when compared with groups II and III (P < 0.05). Conclusion Combined therapy appeared to give a significantly faster onset of repigmentation along with better stability of the achieved pigmentation and with lesser number of side-effects.

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Clin Exp Dermatol. 2006 Mar;31(2):200-5.
Tacalcitol and narrow-band phototherapy in patients with vitiligo.
Leone G, Pacifico A, Iacovelli P, Vidolin AP, Picardo M.
Phototherapy Unit, S. Gallicano Dermatological Institute, IRCCS, Rome, Italy.

Background. Vitiligo is a skin disease characterized by loss of normal pigmentation in the skin. Several treatments exist but none is really effective. Recently, perturbations of calcium homeostasis in vitiliginous epidermis have been described. Aim. Based on these findings, the aim of this prospective, randomized, open-label study was to compare the effectiveness of narrow-band ultraviolet B (NB-UVB) phototherapy alone and the combination of NB-UVB and topical application of the vitamin D(3) analogue tacalcitol in the treatment of vitiligo. Methods. In total, 32 subjects with generalized vitiligo and symmetrical lesions were enrolled in the study. Subjects were instructed to apply tacalcitol ointment daily to the lesion on the side randomly selected to receive combination therapy. All subjects received NB-UVB phototherapy on a twice-weekly schedule. Results. Addition of topical tacalcitol to NB-UVB treatment improved the extent of repigmentation and increased the response rate in patients with vitiligo compared with NB-UVB treatment alone. Conclusion. Application of tacalcitol ointment in combination with twice-weekly NB-UVB phototherapy is an effective alternative treatment for patients with generalized vitiligo.

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Am J Clin Dermatol. 2006;7(1):7-12.
Topical macrolide immunomodulators : a role in the treatment of vitiligo?
Tjioe M, Vissers WH, Gerritsen MJ.
Department of Dermatology, Radboud University, Nijmegen Medical Centre, Nijmegen, The Netherlands.

Recently, topical macrolide immunomodulators have been successfully introduced in the treatment of atopic dermatitis. With the growing interest in this new line of topical immunosuppressants, research into the efficacy of these medicines in other T-cell-mediated skin diseases, such as psoriasis, lichen planus, and even vitiligo, is expanding rapidly. It is generally accepted that autoimmune factors play an important role in vitiligo. In this article, the possible use and mechanism of topical macrolide immunomodulators in the treatment of vitiligo are discussed, together with the current state of clinical studies and case reports. These limited reports indicate that topical macrolide immunomodulators may play a role in the treatment of vitiligo, particularly in areas where use of potent corticosteroids is contraindicated.

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J Eur Acad Dermatol Venereol. 2006 Feb;20(2):175-7.
Psoralen-ultraviolet A vs. narrow-band ultraviolet B phototherapy for the treatment of vitiligo.
Parsad D, Kanwar AJ, Kumar B.
Department of Dermatology, Venereology and Leprology, Postgraduate Institute of Medical Education & Research, Chandigarh, India.

Background Although many treatment modalities have been tried for the treatment of vitiligo, none is uniformly effective. Psoralen phototherapy (psoralen ultraviolet A (PUVA)) is established as efficacious treatment for vitiligo. Recently, narrow-band UVB (NBUVB) has been reported to be an effective and safe therapeutic option in patients with vitiligo. Objective To compare the efficacy of PUVA and NBUVB in the treatment of vitiligo. Design and setting Retrospective analysis of 69 patients with vitiligo who were treated either with PUVA or NBUVB at the pigmentary clinic of the Dermatology Department of the Postgraduate Institute of Medical Education and Research, Chandigarh, India. Outcome measures The following variables were compared between the two groups of patients: repigmentation status, number of treatments for marked to complete repigmentation in existing lesions, appearance of new lesions or increase in size of existing lesions, adverse effect of therapy, stability of repigmentation and colour match. Results In PUVA-treated group, 9 patients showed marked to complete repigmentation (23.6%) and 14 patients showed moderate improvement (36.8%), whereas in NBUVB-treated group, 13 patients showed marked to complete repigmentation (41.9%) and 10 patients showed moderate improvement (32.2%). A statistically significantly better stability and colour match of repigmentation with surrounding skin was seen in NBUVB-treated patients. Conclusion We showed that NBUVB is more effective than PUVA and repigmentation induced with NBUVB is statistically significantly more stable.

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Clin Dermatol. 2006 Jan-Feb;24(1):33-42.
Use of the 308-nm excimer laser for psoriasis and vitiligo.
Passeron T, Ortonne JP.
Department of Dermatology. Archet 2 Hospital, 06202 NICE Cedex 3, France.

The 308-nm excimer laser represents the latest advance in the concept of selective phototherapy. It emits a wavelength in the UV-B spectrum and thus shares the same indications as conventional phototherapy. Like other laser devices, the 308-nm excimer laser emits a monochromatic and coherent beam of light, can selectively treat a lesion while sparing surrounding healthy skin, and can deliver high fluencies. Clinicians have taken advantage of these properties to treat dermatologic disorders since 1997, with psoriasis and vitiligo attracting most attention. Initially, high fluencies (minimal erythemal dose, 8-16) were used, with excellent clinical results, to treat psoriasis vulgaris. The significance of side effects and the potential long-term carcinogenic risk associated with such fluencies have resulted in medium doses (about 3 minimal erythemal dose) being recommended, however. Interestingly, taking advantage of the selectivity of the laser, newer treatment protocols adapt the dose to the lesion and not to the minimal erythemal dose, as is the case for conventional phototherapies. Many prospective study series have also shown the efficacy and the good tolerance of the 308-nm excimer laser in the treatment of localized vitiligo. Induced rates of repigmentation seem to be higher than with narrowband UV-B. Moreover, the selectivity of the treatment prevents irradiation of healthy skin and limits unsightly tanning of surrounding skin. Aesthetically pleasing results are usually not achieved in extremities and bony prominences, which are not good indications for this technique. Combining the 308-nm excimer laser with 0.1% tacrolimus ointment has provided very interesting results, which need to be confirmed in larger series. The absence of actual data concerning the long-term risk for skin cancer after this treatment means that it should be considered with caution. Combination with topical steroids appears to be synergistic and potentially reduces long-term side effects; again, prospective data are lacking.

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Cochrane Database Syst Rev. 2006 Jan 25;(1):CD003263.
Interventions for vitiligo.
Whitton M, Ashcroft D, Barrett CW, Gonzalez U.

BACKGROUND: Around 1% of the world's population has vitiligo, which causes a loss of skin colour in patches. The methods currently available to treat vitiligo are largely unsatisfactory and vary widely between cultures and within health systems. OBJECTIVES: To assess the effects of interventions used to manage vitiligo. SEARCH STRATEGY: We searched the Cochrane Skin Group Specialised Register, the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, AMED and other databases (last searched September 2004). Reference lists of articles and conference proceedings were searched. Authors of reviews were contacted. SELECTION CRITERIA: Randomised controlled trials (RCTs). DATA COLLECTION AND ANALYSIS: At least two reviewers independently assessed study eligibility and methodological quality and carried out data extraction. The included studies compared different interventions and used different outcome measures so we considered it inappropriate to combine their results. MAIN RESULTS: Nineteen trials with a total of 1350 participants were included. The RCTs generally had low numbers of participants and only RCTs of repigmentation and not other methods of managing vitiligo were able to be included.In one study, potent topical steroids resulted in better repigmentation than placebo and they were also better than oral psoralens plus sunlight in another study (RR 4.70 95% CI 1.14 to 19.39) although their long-term use is limited by adverse effects. Two studies suggested that topical calcipotriol enhanced repigmentation rates from PUVAsol and PUVA when compared with placebo. Another two studies showed higher repigmentation rates with oral PUVAsol versus placebo plus sunlight (RR 19.20 95% CI 1.21 to 304.50 in 79 adults and RR 2.29 95% CI 1.14 to 4.58 in a study of 50 children). The safety of these interventions was poorly described and none of the studies was able to demonstrate long term benefits. Very few studies were carried out on children or included segmental vitiligo. No trials evaluating micropigmentation, melanocyte transplantation, depigmentation or cosmetic camouflage could be found. Despite the fact that the main impact of vitiligo is psychosocial only one study on psychological therapy was found and it is awaiting assessment. AUTHORS' CONCLUSIONS: This review has found some evidence to support existing therapies for vitiligo, but the different designs and outcome measurements, lack of quality of life measures and adverse effect reporting in the studies limit the usefulness of their findings. There is a pressing need for high quality randomised trials using standardised measures of repigmentation and which address relevant clinical outcomes including quality of life.

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Int J Dermatol. 2006 Jan;45(1):63-5.
Treatment of vitiligo with broadband ultraviolet B and vitamins.
Don P, Iuga A, Dacko A, Hardick K.
Department of Dermatology, Metropolitan Hospital Campus of New York Medical College, NY, USA.

BACKGROUND: While oral psoralen plus ultraviolet A (PUVA) remains the most popular therapeutic modality for vitiligo, recent reports have shown that narrowband ultraviolet B (UVB) also induces significant repigmentation. In this study we evaluated the efficacy of broadband UVB on actively spreading, progressive vitiligo in patients who had been followed for many months (12 or more) in our practice, who continued to depigment despite treatment. METHODS: Nine patients with actively spreading vitiligo were exposed to broadband UVB 2-3 times per week at a starting dose of 20-30 mJ/cm(2). Radiation was increased by 10-20 mJ/cm(2) per session with adjustments for symptomatic erythema or missed visits. In addition, patients took vitamin C 500 mg twice a day (BID), vitamin B(12) 1000 microg BID and folic acid 5 mg BID. The response to treatment and side-effects were assessed at each visit. The patient's response to treatment and progress were assessed by photographs and by physician evaluation of body surface area (BSA) (using the Rule of 9s) involved at monthly intervals. Photographs were taken and estimations of BSA by physical examination made at the start and finish of the trial and then compared by the physicians involved in the study. RESULTS: Broadband UVB halted the progression of vitiligo in all nine patients and in general induced repigmentation early after 8-12 treatments (6-8 weeks). After 2-8 months of treatment, nine of nine patients achieved good (51-75%) or excellent response (76-100%). The percentage of repigmentation varied with length of treatment and anatomic site. CONCLUSIONS: This study confirms the only published report that broadband UVB is effective on actively spreading vitiligo. Since it is more cost effective than narrowband UVB and has numerous advantages compared to oral PUVA, broadband UVB may offer an alternative for future treatment of vitiligo. The role of vitamins in this therapy remains to be determined.

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Indian J Dermatol Venereol Leprol. 2005 Nov-Dec;71(6):393-7.
A study of autologous melanocyte transfer in treatment of stable vitiligo.
Pandya V, Parmar KS, Shah BJ, Bilimoria FE.
Department of Dermatology, Civil Hospital and BJ Medical College, Ahmedabad, India. vbpandya@rediffmail.com

BACKGROUND: Replenishing melanocytes selectively in vitiliginous macules by autologous melanocytes is a promising treatment. With expertise in culturing melanocytes, it has now become possible to treat larger recipient areas with smaller skin samples. AIM: To study the extent of repigmentation after autologous melanocyte transplantation in patients with stable vitiligo. METHODS: The melanocytes were harvested as an autologous melanocyte rich cell suspension from a donor split thickness graft. Melanocyte culture was performed in selected cases where the melanocyte cell count was insufficient to meet the requirement of the recipient area. These cells were then transplanted to the recipient area that had been superficially dermabraded. RESULTS: An excellent response was seen in 52.17% cases with the autologous melanocyte rich cell suspension (AMRCS) technique and in 50% with the melanocyte culture (MC) technique. CONCLUSION: Autologous melanocyte transplantation can be an effective form of surgical treatment in stable but recalcitrant lesions of vitiligo.

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J Autoimmune Dis. 2005 Nov 22;2(1):11 [Epub ahead of print]
Phenytoin as a novel anti-vitiligo weapon.
Namazi MR.

Vitiligo is a psychologically devastating clinical conundrum which affects approximately 1% of the general population. The exact cause of the illness is an enigma, but several hypotheses about its pathogenesis are advanced. The autoimmune hypothesis proposes an autoimmune attack against melanocytes. Although anti-melanocyte autoantibodies have been demonstrated in vitiligo, recent research casts doubt on their pathogenic role and instead supports the involvement of cell-mediated autoimmune response in the pathobiology of this disorder, which is characterized by increase of suppressor T-cells and decrease of the helper/suppressor ratio in association with the presence of type-1 cytokine secreting cytotoxic T cells in the vicinity of disappearing melanocytes, The neural hypothesis proposes that increased release of norepinephrine, a melanocytotoxin, from the autonomic nerve endings in the microenvironment of melanocytes injures these cells. Moreover, norepinephrine induces the catecholamine degrading enzyme monoamine oxidase (MAO), which favors the formation of toxic levels of hydrogen peroxide in the vicinity of melanocytes. Another theory suggests that abnormal permeability of melanosome membrane, which normally prevents the diffusion of toxic melanin precursors into the cytoplasm, may cause melanocyte damage. Phenytoin, the widely-used anticonvulsant, has been employed both topically and systemically in the treatment of some dermatological disorders. The drug has been shown to significantly suppress mitogen-induced activation of lymphocytes and cytotoxic T lymphocyte activity and to polarize the immune response toward the type-2 pathway. It also significantly decreases suppressor T cells and increases the helper/suppressor ratio. At high concentrations, the drug inhibits the release of norepinephrine and the activity of MAO. Moreover, phenytoin is suggested to interact with membrane lipids, which may promote stabilization of the membranes. The hydantoin moiety of phenytoin exerts a direct stimulatory action on melanocytes; facial hyperpigmentation is a recognized side effect of orally administered phenytoin. Altogether, the above evidence suggests that phenytoin could be therapeutically effective against vitiligo. As phenytoin stimulates collagen production and inhibits its breakdown, its concomitant use with topical steroids could prevent steroid-induced skin atrophy while potentiating the anti-vitiligo effect of these agents.

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J Dtsch Dermatol Ges. 2005 Nov;3(11):874-82.
[New and established indications for phototherapy with narrowband UVB]
[Article in German]
Berneburg M, Brod C, Benedix F, Rocken M.
Universitats-Hautklinik, Eberhard-Karls-Universitat Tubingen, Liebermeisterstrasse 25, D-72076 Tubingen, Germany. Mark.Berneburg@med.uni-tuebingen.de

Phototherapy with ultraviolet (UV) irradiation of wavelengths between 280 and 320 nm (UV-B) is a safe and effective treatment for a variety of inflammatory skin diseases. In addition to standard broad band UVB, narrow band phototherapy with fluorescent bulbs emitting near monochromatic UV between 310-315 nm has become an important treatment for diseases such as psoriasis, atopic dermatitis or vitiligo. Other diseases respond favorably to narrow band UV-B phototherapy, the number of potential indications for such phototherapy is continuously growing. The differential effects of narrow band UV-B phototherapy in comparison to other UV phototherapies, as well as new and established indications for this treatment modality are reviewed.

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Int J Dermatol. 2005 Oct;44(10):841-5.
Long-term follow-up study of 142 patients with vitiligo vulgaris treated by autologous, non-cultured melanocyte-keratinocyte cell transplantation.
Mulekar SV.
Noble Clinic: Pune - India. dr_mulekar@vsnl.com

BACKGROUND: Vitiligo vulgaris patients are difficult to treat surgically owing to large area involvement. Larger areas can be treated with the help of in vitro cultured melanocytes. These techniques are complex. In most of the studies published to date the number of patients reported is low and follow-up period short. OBJECTIVE: To evaluate long-term efficacy and safety of melanocyte-keratinocyte cell transplantation in large number of vitiligo vulgaris patients. METHODS: A simpler and modified method based on that of Olsson and Juhlin has been used. It uses shave biopsy skin sample up to 1/10th the size of recipient area. Skin sample is incubated, cells mechanically separated using trypsin-EDTA solution, and then centrifuged to prepare a suspension. Cell suspension is then applied to a dermabraded de-pigmented skin area and collagen dressing given to keep it in place. RESULTS: One hundred and forty-two patients with vitiligo vulgaris were treated and observed for a period up to 6 years. Eighty (56%) patients showed excellent, 15 (11%) showed good, 13 (9%) showed fair and 34 (24%) showed poor repigmentation, which was retained till the end of the respective follow-up period.

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Dermatol Surg. 2005 Oct;31(10):1277-84.
Surgical approaches for stable vitiligo.
Falabella R.
Department of Dermatology, Universidad del Valle, Hospital Universitario del Valle, Centro Medico Imbanaco, Carrera 38A, No. 5A-100, Cali, Colombia. rafalabe@emcali.net.co

BACKGROUND: Vitiligo therapy is difficult. Depending on its clinical presentation, unilateral or bilateral vitiligo lesions respond well with different repigmentation rates, according to age, affected anatomic area, extension of lesions, time at onset, timing of depigmentation spread, and other associated factors. When stable and refractory to medical treatment, vitiligo lesions may be treated by implanting pigment cells on depigmented areas. OBJECTIVE: To describe the main events of depigmentation and the fundamentals of surgical techniques for repigmenting vitiligo by implanting noncultured cellular or tissue grafts, in vitro cultured epidermis-bearing pigment cells, or melanocyte suspensions. METHODS: A description of the available techniques for repigmentation of vitiligo is done, emphasizing the most important details of each procedure to obtain the best repigmentation and minimize side effects. RESULTS: With most of these techniques, adequate repigmentation is obtained, although there are limitations when applying some methods to clinical practice. CONCLUSIONS: Restoration of pigmentation may be accomplished with all available surgical procedures in most anatomic locations, but they are of little value for acral areas. Unilateral vitiligo responds well in a high proportion of patients, and bilateral disease may also respond when stable. Appropriate patient selection is important to achieve the best results.

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Int J Dermatol. 2005 Sep;44(9):736-42.
Narrow-band UVB vs. broad-band UVB therapy in combination with topical calcipotriol vs. placebo in vitiligo.
Hartmann A, Lurz C, Hamm H, Brocker EB, Hofmann UB.
>From the Department of Dermatology, University of Wurzburg, Germany.

Background Recently, it has been shown that UVB phototherapy may be more effective than UVA in the treatment of vitiligo. Currently, however, no studies have compared the efficacy of UVB(311 nm) and broad-band UVB therapy. Calcipotriol has recently been reported to be effective adjunctive treatment for vitiligo, enhancing the efficacy of 8-methoxypsoralen plus UVA (PUVA) therapy. Methods Ten patients were enrolled in the study; nine completed the 12 months of therapy. The upper part of the body was treated twice weekly with UVB(311 nm) and the lower part with broad-band UVB. Calcipotriol was applied onto the vitiligo lesions of the right side of the body and placebo on the left side. Repigmentation was documented by photography, planimetry, and Vitiligo Disease Activity (VIDA) score. The quality of life was measured by the Dermatology Life Quality Index (DLQI). Results After 7-16 weeks, six of the nine patients showed initial repigmentation on the side treated with UVB(311 nm). After 6 months of treatment, none of the patients showed repigmentation on the areas treated with broad-band UVB, which prompted us to apply UVB(311 nm) all over the body. At the end of 12 months, two patients showed > 75% repigmentation, two showed 51-75%, two showed 26-50%, and three showed 0-25%. In all patients with progressive vitiligo (seven of the nine patients), disease activity was stopped. Remarkably, vitiligo lesions treated with calcipotriol initially showed delayed repigmentation compared with control areas; however, there was no therapeutic difference between calcipotriol and placebo, both in combination with UVB(311 nm), by the end of the study. The DLQI score improved significantly by an average of 28%. Conclusion UVB(311 nm) therapy was effective in the treatment of vitiligo, whereas broad-band UVB had no effect. Combination with calcipotriol ointment was not superior to UVB(311 nm) monotherapy. The quality of life significantly improved with narrow-band UVB(311 nm) phototherapy.

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Dermatol Surg. 2005 Aug;31(8 Pt 1):928-31; discussion 931.
Micropigmentation: tattooing for medical purposes.
Garg G, Thami GP.
Department of Dermatology and Venerology, Government Medical College and Hospital, Chandigarh, India.

BACKGROUND: Micropigmentation, also known widely as tattooing, is being commonly used esthetically to camouflage various medical conditions related to dermatology and plastic surgery. OBJECTIVE: The aim was to review the procedure of tattooing and its various latest medical indications. METHODS: Peer review of the literature on micropigmentation through a MEDLINE search was done to enumerate its various medical indications. RESULTS: The literature review revealed widespread acceptance of micropigmentation for a spectrum of diseases of cosmetic importance, especially in mucosal vitiligo. Micropigmentation is also being used for various medical indications, such as burn scars, alopecia areata, and nipple-areola reconstruction. CONCLUSIONS: The procedure is relatively easy, provides permanent camouflage, and is generally devoid of any significant adverse effects. However, a number of infections can be transmitted from one patient to another if the universal precautions for sterilization of instruments used for micropigmentation are not adhered to.

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Clin Dermatol. 2005 Jul-Aug;23(4):424-9.
Autografts and cultured epidermis in the treatment of vitiligo.
Pianigiani E, Andreassi A, Andreassi L.
Department of Dermatologic Sciences, University of Siena, Policlinico Le Scotte, 53100 Siena, Italy.

Skin transplants can be a useful and efficacious method to treat vitiligo. The aim is to repopulate areas lacking melanocytes with functional cells taken from normally pigmented areas. Several procedures have been devised and tested: some consist in the simple transfer of epidermis sampled and implanted as is, whereas others are based on the transplantation of disaggregated and manipulated cells. The therapeutic success of the former methods is partly determined by the ability and experience of the surgeon performing the operation, whereas the results of the latter methods mainly depend on the laboratory facilities and abilities of the personnel who manipulate the cells to be transplanted. The transplantation of cultured cells is the most fascinating and promising procedure but requires the observance of still not completely predictable procedures. The use of biological material of animal origin and the use of factors to stimulate cell proliferation, such as growth factors and promoting agents, are other points that require attention.

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Br J Dermatol. 2005 Jul;153(1):163-6.
A randomized placebo-controlled double-blind study of levamisole in the treatment of limited and slowly spreading vitiligo.
Agarwal S, Ramam M, Sharma VK, Khandpur S, Pal H, Pandey RM.
Department of Psychiatry, All India Institute of Medical Sciences, New Delhi 110 029, India.

BACKGROUND: A previous uncontrolled, open trial of levamisole in patients with limited and slowly spreading vitiligo had shown that new lesions did not develop in 94% of patients after 2-4 months of treatment with the drug. OBJECTIVES: To assess the efficacy of levamisole in the treatment of slowly spreading, limited vitiligo. METHODS: In a randomized double-blind trial at the Department of Dermatology and Venereology, All India Institute of Medical Sciences, New Delhi, India, 60 patients with vitiligo involving < 2% of the body surface area and with slowly spreading disease (defined as one to five new lesions in the previous month or six to 15 new lesions in the previous 3 months) were randomly allocated to receive oral levamisole 150 mg or placebo on two consecutive days in a week. Children received oral levamisole 100 mg. All patients applied mometasone furoate 0.1% cream on the depigmented macules once daily. Patients were evaluated monthly for 6 months. The main outcome measure was the occurrence of new lesions, counted at each monthly visit. The secondary outcome measures comprised: (i) a dermatology-specific instrument, the Dermatology Life Quality Index or Children's Dermatology Life Quality Index questionnaires, which were completed by the patients at baseline and at every visit, and (ii) a general health questionnaire, the World Health Organization Quality of Life Brief Questionnaire, which was completed at baseline and at the end of the study. RESULTS: Forty-three patients completed 6 months of follow-up. The mean +/- SD number of new lesions that developed during the study period of 6 months was 1.9 +/- 2.0 (range 0-8) in the levamisole group and 1.8 +/- 2.0 (range 0-7) in the placebo group (P = 0.92). The proportion of patients who did not develop any further new lesions for the remainder of the study period was higher in the levamisole group at all the monthly evaluation points, although it was statistically significant (P = 0.05) only at the fourth month. Improvement in quality of life was similar in both groups. CONCLUSIONS: The study indicates that levamisole is not as effective in arresting disease progression as was observed in a previous open study. A study with a larger sample size is necessary to determine if levamisole is truly superior to placebo in this respect.

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Clin Exp Dermatol. 2005 Jul;30(4):332-6.
Narrow-band UVB for the treatment of generalized vitiligo in children.
Kanwar AJ, Dogra S.
Department of Dermatology, Venereology and Leprology, Postgraduate Institute of Medical Education and Research, Chandigarh, India. ajkanwar@sify.com

Vitiligo usually begins in childhood with approximately half of the patients manifesting onset of disease prior to the age of 20 years. Treatment options in this age group are few and have disappointing response rates. This study was designed to evaluate the role of narrow-band UVB in the treatment of generalized vitiligo in children. Twenty-six children (aged 5-14 years) with generalized vitiligo (minimal extent of depigmentation of 5% of the skin) were treated three times per week with narrow-band UVB therapy for a maximum period of 1 year. Of 26 patients, 6 were lost to follow up and 20 (7 males, 13 females) completed the study. At the end of 1 year of therapy, 15 (75%) patients developed marked to complete repigmentation. Moderate and mild repigmentation was noted in four (20%) and one (5%) patients, respectively. An average number of 34 (+/- 2) treatment visits was required to achieve 50% repigmentation. Adverse events were mild and transient. Narrow-band UVB is an effective and well-tolerated treatment option for childhood vitiligo.

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Pediatr Dermatol. 2005 May-Jun;22(3):257-61.
Useful treatment of vitiligo in 10 children with UV-B narrowband (311 nm).
Brazzelli V, Prestinari F, Castello M, Bellani E, Roveda E, Barbagallo T, Borroni G.
Department of Human and Hereditary Pathology, Institute of Dermatology, University of Pavia, Policlinico S. Matteo IRCCS, Pavia, Italy. vbrazzelli@libero.it

We report our experience with UV-B narrowband (UV-B-NB) therapy in children affected by vitiligo. We studied 10 Caucasian Italian children (six boys, four girls, mean age 9.7 years +/- 2.67). Treatment mean term was 5.6 months; frequency was three times a week on nonconsecutive days or only twice a week, because of school or family duties. The percentage of repigmentation was evaluated by comparing photographs taken before, during, and after the treatment, and showed a repigmentation level higher than 75% in five patients (5/10, 50%) and between 26% and 75% in three patients (3/10, 30%). Of our patients, 80% had a satisfactory response to phototherapy. Adverse events were limited and transient. No significant relationships between repigmentation grades and variables such as skin type, positive family history, and disease extension were observed. Some areas responded better than others; the best results were shown on the face and neck. Perhaps we studied too few patients to be conclusive, but the results obtained so far seem to indicate that children affected by recent vitiligo have a better response to the therapy. We feel that UV-B-NB therapy is a valuable and safe option for the treatment of pediatric vitiligo, and should be started as soon as possible.

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Br J Dermatol. 2005 May;152(5):981-5.
Optimal weekly frequency of 308-nm excimer laser treatment in vitiligo patients.
Hofer A, Hassan AS, Legat FJ, Kerl H, Wolf P.
Department of Photodermatology, Medical University Graz, Auenbruggerplatz 8, A-8036 Graz, Austria.

Summary Background 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. Objectives To determine the optimal frequency of 308-nm excimer laser therapy for vitiligo. Methods 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. Results 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. Conclusions 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.

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Dermatol Surg. 2005 Apr;31(4):436-41.
Comparison of Minipunch grafting versus split-skin grafting in chronic stable vitiligo.
Khandpur S, Sharma VK, Manchanda Y.
Department of Dermatology and Venereology, All India Institute of Medical Sciences, New Delhi, India. shaifalikhandpur@eth.net

BACKGROUND: Minipunch grafting (MPG) and split-skin grafting (SSG) are common outpatient procedures for the surgical treatment of chronic stable vitiligo. However, there is a paucity of literature comparing the two procedures by the same group of investigators. OBJECTIVE: To compare the two techniques in patients with chronic stable localized vitiligo. METHODS: Sixty-four patients with stable vitiligo of 6 months duration were randomized into two groups to be taken up for MPG or SSG in a representative patch followed by PUVAsol therapy for 3 months. They were evaluated 3 months postoperatively for the degree of repigmentation and side effects. RESULTS: In the MPG group, 644 grafts, 2.5 mm in size, were placed on a total vitiliginous area of 521.25 cm2, whereas in the SSG group, 153 grafts covered a 1,489 cm2 recipient area. Three months postoperatively, in the first group, 15 cases (44.1%) showed very good to excellent (> 75%) repigmentation compared with 25 cases (83.3%) in group 2. Following MPG, 81 grafts (12.57%) were rejected. Cobblestoning was the main side effect, occurring in 13 cases (38.23%), and a variegated appearance was observed in 7 (20.58%) patients. The complications noted after SSG were achromic fissuring in four (13.3%) cases, graft contracture in four grafts (2.61%) in three patients, and rejection of seven grafts (4.57%) in one case; tire-pattern appearance in two patients (6.6%); milia formation in four (13.3%) patients; and depigmentation of the grafts in two (6.6%) cases. In both groups, superficial scarring was noted at the donor site in all cases, whereas hypertrophic scarring occurred in 3 (10%) patients after SSG. CONCLUSION: SSG carries a distinct advantage over MPG in producing excellent cosmetic matching over larger areas using fewer grafts, especially over the face and extremities.

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Photodermatol Photoimmunol Photomed. 2005 Apr;21(2):79-83.
No additional effect of topical calcipotriol on narrow-band UVB phototherapy in patients with generalized vitiligo.
Ada S, Sahin S, Boztepe G, Karaduman A, Kolemen F.
Department of Dermatology, Faculty of Medicine, Hacettepe University, Ankara, Turkey. siminada@hotmail.com

BACKGROUND/PURPOSE: There is no definite cure for vitiligo; however, treatment responses with photobiological modalities are quite acceptable. Of all these, narrow-band UVB phototherapy was proposed rather recently. Calcipotriol has been shown to have stimulating activity on melanogenesis besides immunomodulatory and anti-inflammatory effects. This study was performed to determine whether adding topical calcipotriol to narrow-band UVB phototherapy enhances the efficacy of treatment. METHODS: In this prospective, single-blinded (investigator), right-left comparison clinical study, 20 patients with generalized vitiligo were enrolled. Symmetrical lesions with similar sizes, bilaterally distributed on arms, legs, hands, feet or trunk were selected as reference lesions. In addition to narrow-band UVB, totally 96 treatment sessions, received two or three times weekly, the patients were asked to apply 0.005% topical calcipotriol on the selected side of the reference lesions twice daily. Then, they were monitored at the end of every 24-session interval. RESULTS: Cosmetically acceptable repigmentation was observed in 55% (11/20) of the patients without taking calcipotriol into account. There was statistically significant better response on the side that calcipotriol was not applied at the 24th session (P < 0.05). No statistically significant difference was found between the calcipotriol-treated and non-treated sides at 48th, 72th, and 96th sessions (P > 0.05). CONCLUSION: Our data confirm that, narrow-band UVB phototherapy is effective by itself in vitiligo, and show that adding topical calcipotriol does not improve treatment outcome.

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Eur J Dermatol. 2005 Mar-Apr;15(2):88-91.
Topical 0.05% clobetasol propionate versus 1% pimecrolimus ointment in vitiligo.
Coskun B, Saral Y, Turgut D.
Firat University Faculty of Medicine, Department of Dermatology, Elazig-Turkey. basakkc@hotmail.com

Vitiligo is a common skin condition resulting from loss of normal melanin pigments in the skin which produces white patches. Topical corticosteroids are indicated for the treatment of limited areas of vitiligo. Pimecrolimus, which inhibits calcineurin, has recently been shown to be effective for the treatment of vitiligo. We performed a prospective study to evaluate the efficacy of the 0.05% clobetasol propionate and 1% pimecrolimus in the treatment of vitiligo. Ten patients with virtually bilateral symmetrical lesions of vitiligo were included. 0.05% clobetasol propionate was applied twice daily over the lesion on right side of the body, and topical 1% pimecrolimus was applied twice daily over the lesion on left side of the body. It was determined that both treatment modalities resulted in a comparable rate of repigmentation. Response to treatment was varied according to the anatomical location of the lesions where better results were seen on the trunk and extremities. Results from this pilot study indicate that topical 1% pimecrolimus is as effective as clobetasol propionate in restoring skin disfiguring due to vitiligo. For a better conclusive statement further studies involving larger groups of patients should be performed.

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Drugs. 2005;65(4):447-59.
New treatment modalities for vitiligo: focus on topical immunomodulators.
Kostovic K, Pasic A.
Department of Dermatology and Venerology, Zagreb University Hospital Center, Salata 4, Zagreb, HR-100000, Croatia. kreso.kostovic@zg.htnet.hr

The development of effective treatment modalities for vitiligo is dependent on an understanding of the events leading to depigmentation. However, the exact pathogenesis of vitiligo is still mostly unknown. Abnormalities in both humoral and cell-mediated immunity have been documented in vitiligo patients and they present a basis for using immunomodulating agents, such as corticosteroids and macrolide immunomodulators, in the treatment of vitiligo. Macrolide immunomodulators, such as tacrolimus and pimecrolimus, which can be used topically, are known as topical immunomodulators (TIMs). TIMs inhibit the action of calcineurin, and consequently inhibit T-cell activation and the production of various cytokines; this is considered the working mechanism of action of TIMs in vitiligo. Several small studies and case reports on the use of TIMs in vitiligo have been published so far. Tacrolimus achieves better results on the face and neck than on other body areas.Particular advantages of TIMs are safety in treating these areas because of lack of skin atrophy and good tolerability. The incidence of application site adverse events in vitiligo seems to be lower than in the treatment of atopic dermatitis. On the face and neck, TIMs may become a useful tool in the treatment of adults and children with vitiligo despite possibly lower efficacy than topical corticosteroids. Further, larger, controlled clinical studies are warranted to determine the definite role of TIMs as monotherapy or in combination with other modalities in the treatment of vitiligo.

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Skin Pharmacol Physiol. 2005 Jan-Feb;18(1):3-11.
Safety and efficacy of fluticasone propionate in the topical treatment of skin diseases.
Roeder A, Schaller M, Schafer-Korting M, Korting HC.
Ludwig-Maximilians-Universitat Munchen, Klinik und Poliklinik fur Dermatologie und Allergologie, Frauenlobstrasse 9-11, DE-80337 Munich, Germany. Alexander.Roeder@lrz.uni-muenchen.de

Fluticasone propionate - the first carbothioate corticosteroid - has been classified as a potent anti-inflammatory drug for dermatological use. It is available as 0.05% cream and 0.005% ointment formulations for the acute and maintenance treatment of patients with dermatological disorders such as atopic dermatitis, psoriasis and vitiligo. This glucocorticoid is characterized by high lipophilicity, high glucocorticoid receptor binding and activation, and a rapid metabolic turnover in skin. Although skin blanching following fluticasone propionate exceeds that of corticosteroids of medium strength, several clinical trials demonstrate a low potential for cutaneous and systemic side-effects, even in difficult-to-treat areas like the face, the eyelids and intertriginous areas. Even among paediatric patients with atopic dermatitis, fluticasone propionate proved to be safe and effective. These pharmacological and clinical properties are reflected by the high therapeutic index of this glucocorticoid. Copyright 2005 S. Karger AG, Basel.

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Int J Dermatol. 2005 Jan;44(1):57-60.
Narrow-band UVB for the treatment of vitiligo: an emerging effective and well-tolerated therapy.
Kanwar AJ, Dogra S, Parsad D, Kumar B.
Department of Dermatology, Venereology, and Leprology, Postgraduate Institute of Medical Education and Research, Chandigarh, India. sundogra@hotmail.com

BACKGROUND: Vitiligo is an acquired depigmentation disorder of great cosmetic importance, affecting 1% of the general population. Photochemotherapy is the most commonly used treatment modality in extensive vitiligo, but is associated with many short- and long-term side-effects. Recently, narrow-band ultraviolet B (NBUVB) therapy has been reported to be an effective and safe therapeutic option in patients with vitiligo. We studied the efficacy and safety of NBUVB (311 nm) therapy in Indian patients with generalized vitiligo. METHODS: Fourteen patients (six males and eight females), aged 12-56 years, with generalized vitiligo, were treated thrice weekly with NBUVB radiation therapy for a maximum period of 1 year. RESULTS: At the end of 1 year, 10 patients (71.4%) had marked to complete repigmentation and two each (14.3%) had moderate or mild repigmentation. Repigmentation sites showed an excellent color match. The response to therapy was correlated with the sites of involvement, duration of disease, and compliance to therapy. Adverse events were limited and transient. CONCLUSION: NBUVB therapy is effective and safe in Indian patients with vitiligo. Long-term follow up is required, however, to establish the stability of repigmentation.

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J Eur Acad Dermatol Venereol. 2005 Jan;19(1):56-60.
Quality of life in vitiligo patients after treatment with long-term narrowband ultraviolet B phototherapy.
Tjioe M, Otero M, van de Kerkhof P, Gerritsen M.
Department of Dermatology, University Medical Centre St Radboud, Nijmegen, the Netherlands.

ABSTRACT Long-term treatments for chronic diseases such as vitiligo need to be evaluated for their clinical efficacy. Assessment of the quality of life (QOL), however, may provide the most relevant information on the actual benefit for these patients. In this study we evaluated QOL after long-term narrowband ultraviolet (UV) B for the treatment of vitiligo. All patients, with long-term stable vitiligo vulgaris, who were treated at our clinic during the last 4 years received specifically for this study a designed QOL questionnaire, which included questions about general well-being, camouflage and psychosocial aspects; 71.4% of the patients responded. Most patients indicated an improvement on a psychological level, but an increase in camouflaging. The present study shows that, after long-term narrowband UVB phototherapy, skin appearance does not play a major role in the life of vitiligo patients, while well being only improved in a minority of patients.

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Int J Clin Pharmacol Res. 2004;24(1):11-4.
Calcipotriol in the treatment of childhood vitiligo.
Gargoom AM, Duweb GA, Elzorghany AH, Benghazil M, Bugrein OO.
Dermatology Department, Jamahiriya Hospital, Benghazi, Libya.

Eighteen patients with a clinical diagnosis of vitiligo, aged between three and 12 years (mean 8.9 years), were enrolled in this study in order to evaluate the efficacy and tolerability of topical calcipotriol in the treatment of childhood vitiligo. Six patients (33.3%) were males and 12 were females (66.7%). Fourteen patients (77.8) had focal vitiligo, two (11.1%) had mucosal vitiligo and two (11.1%) had segmental vitiligo. The face was involved in 11 patients (61.1%). The treatment was applied twice daily as 50 microg/gm cream in nine patients and as ointment in the remaining patients. Treatment assessment was carried out clinically at 2 weeks, and then monthly for 4-6 months. Four patients (28.6%) were excluded from the study (one due to irritation and three due to lost contact in follow-up). Fourteen patients (71.4%) completed the treatment course (> 3 months). Of the treated patients, ten (77.8%) showed improvement and four patients (22.2%) had no response. Among responders, three patients (21.4%) showed complete resolution, four (28.6%) showed 50%-80% improvement and three patients (21.4%) showed 30% to < 50% improvement. Only one patient (5.5%) developed irritation. In conclusion, calcipotriol is an effective treatment in vitiligo. Better results are obtained with ointment than with cream. Calcipotriol can be helpful in children in whom potent steroids and PUVA are not advisable.

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J Am Acad Dermatol. 2004 Nov;51(5):760-6.
Tacrolimus ointment promotes repigmentation of vitiligo in children: a review of 57 cases.
Silverberg NB, Lin P, Travis L, Farley-Li J, Mancini AJ, Wagner AM, Chamlin SL, Paller AS.
Department of Dermatology, Division of Pediatric Dermatology, St Luke's-Roosevelt Hospital Center, New York, NY, USA.

BACKGROUND: Vitiligo is an autoimmune disorder characterized by loss of pigmentation. Phototherapy and application of topical corticosteroids are most commonly prescribed. However, these therapies are often not effective and use of corticosteroids on the face may lead to cutaneous atrophy, telangiectasia, and ocular complications. OBJECTIVE: We sought to assess the efficacy of topical tacrolimus ointment in the treatment of pediatric vitiligo. METHODS: A retrospective review was performed of 57 pediatric patients with vitiligo at two clinical sites. Patients were treated with tacrolimus ointment for at least 3 months. Clinical responses were documented during clinic visits, and by pretacrolimus and posttacrolimus photography. RESULTS: At least partial response was noted to tacrolimus ointment on the head and neck in 89%, and on the trunk and extremities in 63% of patients. Facial vitiligo of the segmental type showed the best response rate. Two patients initially experienced burning on application. CONCLUSIONS: Topical tacrolimus ointment is an effective alternative therapy for childhood vitiligo, particularly involving the head and neck.

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Photodermatol Photoimmunol Photomed. 2004 Oct;20(5):248-51.
Topical calcipotriene and narrowband ultraviolet B in the treatment of vitiligo.
Kullavanijaya P, Lim HW.
Department of Dermatology, Henry Ford Hospital, 2999 West Grand Boulevard, Detroit, MI 48202, USA.

BACKGROUND: Treatment of vitiligo, despite significant advances made in the past few years, remains to be a challenge. Narrowband ultraviolet (NB-UVB) has emerged as an important therapeutic option for this condition. OBJECTIVE: To evaluate whether the combination of calcipotriene ointment and NB-UVB could enhance the efficacy of NB-UVB alone. METHODS: An open, bilateral comparison study was performed in 20 patients with symmetrical vitiligo between August 2001 and October 2002. All patients received NB-UVB three times per week. Calcipotriene ointment was applied to lesions on the left side of the body. Response was graded visually as significant (66-100% repigmentation), moderate (26-65%), mild (10-25%), and minimal (< 10%). RESULTS: Seventeen patients (six females, 11 males) completed the study. Eight patients (8/17=47%) had significant repigmentation after 67-180 treatments, six patients (35%), one patient (6%), and two patients (12%) had moderate, mild, and minimal repigmentation after 40-160, 57, and 14-21 treatments, respectively. Nine of the 17 patients had an appreciably better improvement on the NB-UVB and calcipotriene side by 29-114 treatments. In six of these patients, differences were still observed at the end of the study period. No side effects were noted. CONCLUSION: Combination therapy of topical calcipotriene and NB-UVB is a therapeutic option that could be considered in the management of patients with vitiligo.

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Arch Dermatol. 2004 Oct;140(10):1211-5.
Long-term follow-up study of segmental and focal vitiligo treated by autologous, noncultured melanocyte-keratinocyte cell transplantation.
Mulekar SV.
Noble Clinic, Pune, India. dr_mulekar@vsnl.com

OBJECTIVE: To evaluate long-term efficacy and safety of melanocyte-keratinocyte cell transplantation in the management of segmental and focal vitiligo. DESIGN: A simpler and modified method based on that of Olsson and Juhlin was performed. This method uses a shaved biopsy skin sample up to one tenth the size of the recipient area. The skin sample is incubated, and the cells are mechanically separated using trypsin-EDTA solution and then centrifuged to prepare a suspension. Cell suspension is then applied to the dermabraded depigmented skin area, and a collagen dressing is applied to keep it in place. PATIENTS: Fifty patients with segmental and 17 with focal vitiligo were treated. One patient with segmental and 2 with focal vitiligo did not attend any follow-up visits. The remaining patients were observed for a period of up to 5 years. INTERVENTION: Autologous, noncultured melanocyte-keratinocyte cell transplantation. MAIN OUTCOME MEASURE: Repigmentation was graded as excellent with 95% to 100% pigmentation, good with 65% to 94%, fair with 25% to 64%, and poor with 0% to 24% of the treated area. RESULTS: In the segmental vitiligo group, 41 patients (84%) showed excellent, 3 (6%) good, and 5 (10%) poor pigmentation, which was retained until the end of the respective follow-up period. In the focal vitiligo group, 11 patients (73%) showed excellent, 1 (7%) fair, and 3 (20%) poor pigmentation, which was retained until the end of the respective follow-up period. CONCLUSIONS: Melanocyte-keratinocyte cell transplantation is a simple, safe, and effective surgical therapy. Patients with segmental and focal vitiligo can experience a prolonged disease-free period, which may extend through the rest of their lives.

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Arch Dermatol. 2004 Oct;140(10):1203-8.
Double-blind placebo-controlled study of autologous transplanted epidermal cell suspensions for repigmenting vitiligo.
van Geel N, Ongenae K, De Mil M, Haeghen YV, Vervaet C, Naeyaert JM.
Department of Dermatology, Ghent University Hospital, 9000 Ghent, Belgium.

OBJECTIVES: 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. DESIGN: A prospective, randomized, double-blind, placebo-controlled study. SETTING: Ambulatory patients in an institutional practice. Patients were followed up for 3 to 12 months. PATIENTS: 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). INTERVENTION: 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. MAIN OUTCOME MEASURES: 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. RESULTS: 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. CONCLUSIONS: 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.

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Arch Dermatol. 2004 Sep;140(9):1065-9.
Topical tacrolimus and the 308-nm excimer laser: a synergistic combination for the treatment of vitiligo.
Passeron T, Ostovari N, Zakaria W, Fontas E, Larrouy JC, Lacour JP, Ortonne JP.
Department of Dermatology, Hopital de l'Archet 2, Nice, France. t.passeron@free.fr

OBJECTIVE: To compare the efficacy of combined tacrolimus and 308-nm excimer laser therapy vs 308-nm excimer laser monotherapy in treating vitiligo. DESIGN: Comparative, prospective, randomized, intraindividual study. PATIENTS: Fourteen patients, aged 12 to 63 years, with Fitzpatrick skin types II to IV. INTERVENTION: For each patient, 4 to 10 target lesions were chosen. The treatment applied to each target lesion was randomized by drawing lots. Each lesion was treated twice a week by the 308-nm excimer laser, for a total of 24 sessions. Initial fluences were 12 mcal/cm(2) (50 mJ/cm(2)) less than the minimal erythemal dose in vitiliginous skin. Then, fluences were increased by 12 mcal/cm(2) every second session. Moreover, topical 0.1% tacrolimus ointment was applied twice daily on target lesions receiving the combined tacrolimus and excimer laser treatment (group A). Group B target lesions received only excimer laser monotherapy. For each treated lesion, the untreated lesion on the opposite side served as the control. Tolerance was evaluated by a visual analog scale, and secondary events were recorded at each session. MAIN OUTCOME MEASURE: Treatment efficacy, which was blindly evaluated by 2 independent physicians by direct and polarized light photographs taken before and after treatment. RESULTS: Forty-three lesions were treated (23 in group A and 20 in group B). All patients completed the study. Repigmentation was observed in all group A lesions (100%) and in 17 (85%) of the 20 group B lesions. Repigmentation was not observed in the untreated lesions (control group). A repigmentation rate of 75% or more was obtained in 16 (70%) of the 23 group A lesions and in 4 (20%) of the 20 group B lesions. In UV-sensitive areas (the face, neck, trunk, and limbs, with the exception of bony prominences and extremities), 10 (77%) of 13 group A lesions had a repigmentation rate of 75% or more vs 4 (57%) of 7 group B lesions. In classically UV-resistant areas, 6 (60%) of 10 group A lesions had a repigmentation rate of 75% or more vs 0 of the 13 group B lesions. The mean number of sessions necessary for an improvement of repigmentation was 10 in group A and 12 in group B. Adverse effects have been limited, and tolerance was excellent. CONCLUSIONS: The combination treatment of 0.1% tacrolimus ointment plus the 308-nm excimer laser is superior to 308-nm excimer laser monotherapy for the treatment of UV-resistant vitiliginous lesions (P<.002). The efficacy and the good tolerance of the 308-nm excimer laser in monotherapy for treating localized vitiligo were also confirmed, but this treatment regimen should be proposed only for UV-sensitive areas.

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Lasers Surg Med. 2004;35(2):152-6.
Treatment of vitiligo by 308-nm excimer laser: an evaluation of variables affecting treatment response.
Ostovari N, Passeron T, Zakaria W, Fontas E, Larouy JC, Blot JF, Lacour JP, Ortonne JP.
Department of Dermatology, Hopital de l'Archet 2, Nice, France.

BACKGROUND AND OBJECTIVES: To determine the true efficacy of the 308-nm excimer laser for the treatment of vitiligo, while taking into account confounding factors such as anatomic site of treatment, age, sex, skin type, MED, and duration of evolution of the vitiligo. STUDY DESIGN/MATERIALS AND METHODS: Thirty-five patients with vitiligo were included. Each lesion was treated twice a week by the 308-nm excimer laser for a maximum of 24 sessions. Efficacy was blindly evaluated by two independent physicians. RESULTS: Repigmentation was noted in 46 plaques/52 (88.5%). Repigmentation rate (75%) was obtained in 14 (26.9%). In "UV sensitive" areas (face, neck, trunk), 8/14 lesions (57.1%) had a repigmentation rate, 75% versus 6/38 (15.8%) in "UV resistant" areas (bony prominences and extremities) (P = 0.031). No relationship could be established between response to the treatment and the following variables: age, sex, skin type, MED, and duration of evolution of the vitiligo (respectively, P = 1, 0.666, 0.566, 0.628, 0.521). CONCLUSIONS: An aesthetically reasonable result is achieved essentially in "UV sensitive" areas, thus appearing to be the appropriate places of choice for this treatment.

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Pediatr Dermatol. 2004 Jul-Aug;21(4):495-8.  

Calcipotriene and corticosteroid combination therapy for vitiligo. 
Travis LB, Silverberg NB. 
Department of Dermatology, St. Luke's-Roosevelt Hospital Center, New York, New York.
 
Corticosteroids and photochemotherapy, using a combination of psoralen and ultraviolet A (PUVA) exposure, are the most widely prescribed therapies for vitiligo. These treatments are not uniformly effective and many patients have inadequate responses. Calcipotriene has been shown to be effective in adults and children with psoriasis when used as monotherapy and in combination with corticosteroids and phototherapy. We hypothesized that since the mechanisms of action for calcipotriene and corticosteroids are different, patients may develop more repigmentation with a combination of the two agents, while decreasing the side effects from both agents. Twelve patients with vitiligo (average age 13.1 years) were advised to use topical corticosteroids in the morning and topical calcipotriene in the evening. Of the 12 patients, 83% responded to therapy, with an average of 95% repigmentation by body surface area. Four of the patients who responded had previously failed trials of topical corticosteroids alone. All of the patients in this group had repigmentation. Eyelid and facial skin responded best to this therapy. None of the patients had adverse reactions to the treatment. Our results show that topical calcipotriene in combination with corticosteroids can repigment vitiligo, even in those patients who were previous topical corticosteroid failures.
 
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J Am Acad Dermatol. 2004 Jul;51(1):52-61.  
Topical tacrolimus therapy for vitiligo: therapeutic responses and skin messenger RNA expression of proinflammatory cytokines. 
Grimes PE, Morris R, Avaniss-Aghajani E, Soriano T, Meraz M, Metzger A. 
Vitiligo and Pigmentation Institute of Southern California, and the Division of Dermatology, David Geffen School of Medicine, University of California, Los Angeles, USA. pegrimesmd@earthlink.net
 
BACKGROUND: Previous studies have documented humoral and cell-mediated immunologic defects in patients with vitiligo. OBJECTIVE: This 24-week study assessed the efficacy and safety of tacrolimus 0.1% ointment in patients with generalized vitiligo as well as the pretreatment and post-treatment expression of cytokines in the depigmented and normal skin of patients compared with controls. METHODS: Twenty-three patients were enrolled in this investigation, and 19 patients completed the study; 8 were male and 11 were female. Fifteen age-, race-, and sex-matched control subjects were also included. Patients were treated with tacrolimus 0.1% ointment applied twice daily. Repeat evaluations were performed at 4, 8, 12, 16, 20, and 24 weeks. Three-millimeter punch biopsy specimens were taken from the depigmented, non-sun-exposed skin and adjacent normal skin of patients at baseline and 24 weeks, and from normal, non-sun-exposed skin of controls. Cellular messenger RNA expression for interleukin 2 (IL-2), IL-4, IL-10, tumor necrosis factor alfa (TFN-alpha), and interferon gamma (IFN-gamma) were determined by real-time quantitative polymerase chain reaction. RESULTS: At 24 weeks, 17 of 19 patients (89%) achieved varying levels of repigmentation. There was a statistically significant decrease in overall disease severity scores at 24 weeks. Thirteen patients (68%) had greater than 75% repigmentation of face and/or neck lesions. Signs and symptoms of irritation were minimal. At baseline, compared with healthy controls, vitiligo patients demonstrated a statistically significant increase in the expression of IFN-gamma in involved and adjacent uninvolved skin (P=.05 and P=.02, respectively); significantly increased TNF-alpha expression in involved and uninvolved skin (P=.01 and P=0.02, respectively); and significantly increased IL-10 expression in involved and uninvolved skin (P=.01 and P=.04, respectively). Posttreatment, TNF-alpha expression decreased in the depigmented and adjacent uninvolved skin (P <.001). There was no statistically significant change in IL-10 or IFN-gamma posttreatment. These data suggest that tacrolimus 0.1% ointment is a safe and effective therapy for patients with vitiligo. It further suggests that an imbalance in local cytokine expression may play a role in the pathogenesis of vitiligo. Suppression of TNF-alpha after topical tacrolimus application may be associated with repigmentation of vitiligo.
 
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J Am Acad Dermatol. 2004 Jul;51(1):68-74.  

Treatment of vitiligo by transplantation of cultured pure melanocyte suspension: analysis of 120 cases. 
Chen YF, Yang PY, Hu DN, Kuo FS, Hung CS, Hung CM.
Department of Dermatology, Show Chwan Memorial Hospital, Changhua City, Taiwan. yufuc@hotmail.com
 
BACKGROUND: Despite the availability of various medical treatments for vitiligo, a large percentage of patients fail to achieve satisfactory results. Surgical techniques offer a potential solution for patients with vitiligo who fail to respond to medical treatments. OBJECTIVE: We evaluated the practicality in treating vitiligo by using cultured autologous pure melanocytes and investigated the different results among stable localized vitiligo, stable generalized vitiligo, and active generalized vitiligo. METHODS: In all, 120 patients with vitiligo were treated with transplantation of autologous cultured pure melanocyte suspension after carbon-dioxide laser abrasion. RESULTS: Patients with stable localized vitiligo experienced the highest percentage of excellent repigmentation with 84% achieving 90% to 100% coverage, followed by 54% of patients with stable generalized vitiligo, whereas only 14% of patients with active generalized vitiligo experienced good repigmentation. Age and sex of the patients, and size and location of the lesions, did not show significant influence on the results of transplantation. CONCLUSION: Autologous cultured pure melanocyte suspension combined with carbon-dioxide laser abrasion is an effective treatment for patients with stable vitiligo who fail to respond to medical treatments, especially for those with stable localized vitiligo.
 
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Dermatol Surg. 2004 Jul;30(7):983-6.  
The use of the 308-nm excimer laser for the treatment of vitiligo. 
Hadi SM, Spencer JM, Lebwohl M. 
Department of Dermatology, Mount Sinai School of Medicine, New York, NY 10029, USA. smhadi@Dr.com
 
BACKGROUND: Recent reports show that 308-nm excimer laser may be an effective and safe method for the treatment of vitiligo, which is usually resistant to other available treatment methods. OBJECTIVE: The objective was to study the effectiveness of the new 308-nm excimer laser for the treatment of vitiligo. METHODS: A retrospective chart review of thirty-two patients with 55 spots of vitiligo were enrolled; a population-based sample was studied that included men and women, adults and children, with different ethnic backgrounds. The treatment was started with the lowest dose, which is 100 mJ/cm(2) (comparable to one minimal erythema dose value and one multiplier). Depending on Fitzpatrick skin type, the dose was raised gradually in a stepwise fashion. In skin types I to II, the same does was repeated twice before going up to avoid burns. Patients were treated for 30 sessions, or 75% repigmentation, whichever comes first. RESULTS: Overall 55 spots were treated: 29 (52.8%) had 75% pigmentation or greater, and 35 (63.7%) had 50% pigmentation or greater. The best results were on the face: of the 21 spots treated 15 (71.5%) had 75% pigmentation, and 16 (76.2%) had 50% pigmentation or greater. Other areas (neck, extremities, trunk, and genitals) had moderate response in comparison to the face. The least response was on the hands and feet; of the 5 spots treated only 20% showed 50% pigmentation or more. CONCLUSION: Slightly more than 50% of the patients tested showed 75% or more pigmentation of their lesions, after 30 treatments or less; most of the responders had Fitzpatrick skin type III and above. All the untreated patches (controls) remained unchanged. This demonstrates that the 308-nm excimer laser is an effective method of treatment for vitiligo.
 
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Arch Dermatol. 2004 Jun;140(6):677-83.  
Parametric modeling of narrowband UV-B phototherapy for vitiligo using a novel quantitative tool: the Vitiligo Area Scoring Index. 
Hamzavi I, Jain H, McLean D, Shapiro J, Zeng H, Lui H. 
Division of Dermatology, Department of Medicine, Vancouver Coastal Health Research Institute, University of British Columbia, Vancouver, Canada.
 
BACKGROUND: There is currently no quantitative tool for evaluating vitiligo treatment response using parametric methods. OBJECTIVE: 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. DESIGN: Prospective, randomized, controlled, bilateral left-right comparison trial. SETTING: North American tertiary care, university-affiliated phototherapy center. PATIENTS: Patients older than 18 years with stable vitiligo involving at least 5% of their total body surface in a symmetric distribution. INTERVENTION: 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. MAIN OUTCOME MEASURE: 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. RESULTS: 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. CONCLUSIONS: 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.
 
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J Postgrad Med. 2004 Apr-Jun;50(2):131-9.  
Topical immunomodulators in dermatology. 
Khandpur S, Sharma VK, Sumanth K. 
Department of Dermatology and Venereology, All India Institute of Medical Sciences, New Delhi - 110 029, India. shaifalikhandpur@eth.net
 
Topical immunomodulators are agents that regulate the local immune response of the skin. They are now emerging as the therapy of choice for several immune-mediated dermatoses such as atopic dermatitis, contact allergic dermatitis, alopecia areata, psoriasis, vitiligo, connective tissue disorders such as morphea and lupus erythematosus, disorders of keratinization and several benign and malignant skin tumours, because of their comparable efficacy, ease of application and greater safety than their systemic counterparts. They can be used on a domiciliary basis for longer periods without aggressive monitoring. In this article, we have discussed the mechanism of action, common indications and side-effects of the commonly used topical immunomodulators, excluding topical steroids. Moreover, newer agents, which are still in the experimental stages, have also been described. A MEDLINE search was undertaken using the key words "topical immunomodulators, dermatology" and related articles were also searched. In addition, a manual search for many Indian articles, which are not indexed, was also carried out. Wherever possible, the full article was reviewed. If the full article could not be traced, the abstract was used.
 
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Toxicol Appl Pharmacol. 2004 Mar 15;195(3):298-308.
Toxic effects of ultraviolet radiation on the skin.
Matsumura Y, Ananthaswamy HN.
Department of Dermatology, Kansai Medical University, Osaka 570-8507, Japan. matsumy@takii.kmu.ac.jp

Ultraviolet (UV) irradiation present in sunlight is an environmental human carcinogen. The toxic effects of UV from natural sunlight and therapeutic artificial lamps are a major concern for human health. The major acute effects of UV irradiation on normal human skin comprise sunburn inflammation (erythema), tanning, and local or systemic immunosuppression. At the molecular level, UV irradiation causes DNA damage such as cyclobutane pyrimidine dimers and (6-4) photoproducts, which are usually repaired by nucleotide excision repair (NER). Chronic exposure to UV irradiation leads to photoaging, immunosuppression, and ultimately photocarcinogenesis. Photocarcinogenesis involves the accumulation of genetic changes, as well as immune system modulation, and ultimately leads to the development of skin cancers. In the clinic, artificial lamps emitting UVB (280-320 nm) and UVA (320-400 nm) radiation in combination with chemical drugs are used in the therapy of many skin diseases including psoriasis and vitiligo. Although such therapy is beneficial, it is accompanied with undesirable side effects. Thus, UV radiation is like two sides of the same coin--on one side, it has detrimental effects, and on the other side, it has beneficial effects.

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Cutis. 2004 Mar;73(3):163-7.
The psychological aspects of vitiligo.
Silvan M.
Department of Dermatology, St. Luke's-Roosevelt Hospital Center, New York, New York 10025, USA. mes57@columbia.edu

Dermatologists are likely to be confronted with patients who present with a wide range of psychiatric issues and problems. Writers on psychocutaneous medicine have described a variety of conditions that represent the interplay between the psyche and the soma. Vitiligo is one such disease and will be the focus of this article. Specifically, 3 areas will be examined: (1) the psychological impact vitiligo has on patients, (2) how psychological factors contribute to the etiology and course of the illness, and (3) the benefits of offering adjunctive psychological treatment. By exploring these aspects of vitiligo in more detail, I hope to illustrate the profound importance psychological factors play in this disease and the value of incorporating a psychological approach in its treatment.

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Clin Exp Dermatol. 2004 Mar;29(2):180-4.
Treatment of vitiligo with local khellin and UVA: comparison with systemic PUVA.
Valkova S, Trashlieva M, Christova P.
Department of Dermatology and Venereology, Department of Public Health, Medical University, Pleven, Bulgaria.

Vitiligo is an idiopathic leukoderma often with a progressive course causing destruction of melanocytes. The best methods for achieving cosmetically acceptable re-pigmentation of affected skin appear to be both local and systemic PUVA. They may, however, cause serious side effects, which is an argument for conducting research into new, equally effective photo-chemotherapeutic agents. One of these agents is khellin. We conducted a pilot study in 33 patients to evaluate the effectiveness of local KUVA and systemic PUVA therapy for vitiligo and to compare them in terms of the degree of re-pigmentation, duration of treatment, number of procedures, total UVA dose and side effects. Local KUVA required longer duration of treatment and higher UVA doses. KUVA-induced re-pigmentation depended on the age of the patients (r = -0.61, P = 0.001), and better results were achieved with younger individuals [% re-pigmentation = 81.76 - (1.48 x age in years)]. No side effects were observed in cases of local KUVA treatment. Erythema, itching and gastro-intestinal disturbances occurred with some patients treated with PUVA. The results demonstrate that local KUVA may effectively induce re-pigmentation of vitiligo-affected skin areas to a degree comparable to that achieved when using systemic PUVA, provided that treatment duration is long enough.

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Clin Exp Dermatol. 2004 Mar;29(2):133-7.
Treatment of vitiligo with the 308 nm excimer laser.
Esposito M, Soda R, Costanzo A, Chimenti S.
Department of Dermatology, University of Rome 'Tor Vergata', Italy.

Several therapeutic modalities have been proposed for the treatment of vitiligo either to achive repigmentation in the lesions or to stabilize the disease. Narrow-band UVB therapy has been shown to be effective and safe for use in the management of vitiligo; its wavelength is not so different from 308 nm XeCl excimer laser radiation. We present an open and uncontrolled pilot study of 24 patients (12 men, 12 women) in whom vitiligous patches were treated twice a week, for 9 months with 308 nm XeCl laser radiation. Seven of the 24 patients showed greater than 75% repigmentation, six patients showed repigmentation of between 25 and 75% and six patients showed less than 25% repigmentation. In five patients no signs of repigmentation were noted. The therapeutic benefit was stable during the 12-month follow-up period. Although these results are promising, treatment has so far been limited to small numbers of patients and a short follow-up period. Other prospective studies are needed to assess the efficacy of this treatment modality.

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Chin Med J (Engl). 2004 Feb;117(2):199-201.
Topical melagenine for repigmentation in twenty-two child patients with vitiligo on the scalp.
Xu AE, Wei XD.
Department of Dermatology, Third People's Hospital of Hangzhou, Hangzhou 310009, China.

BACKGROUND: The purpose of this study was to evaluate the efficacy of topical melagenine for repigmentation in child patients with vitiligo on the scalp. METHODS: Twenty-two child patients with vitiligo on the scalp were treated with 1.2 mg/ml aqueous melagenine in combination with 20 minutes of infrared exposure twice daily. RESULTS: In 4 patients (18.2%), melagenine treatment in combination with infrared exposure led to complete recovery; in 6 patients (27.3%), treatment was shown to be effective; in 8 patients (36.3%), treatment led to improvements in patient condition; and only 4 patients (18.2%) showed no response after 1 - 2 treatment sessions. The general effective rate of melagenine-infrared combination treatment was 45.5% for the children with vitiligo on the scalp, and treatment was accompanied by minimal side effects. CONCLUSION: Melagenine may be efficacious and a safe treatment option for childhood vitiligo affecting the scalp.

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Dermatol Surg. 2004 Feb;30(2):130-5.
Combined excimer laser and topical tacrolimus for the treatment of vitiligo: a pilot study.
Kawalek AZ, Spencer JM, Phelps RG.
Department of Dermatology Department of Pathology, Division of Dermatologic Surgery, Mount Sinai School of Medicine, New York, New York.

BACKGROUND. : Vitiligo is an acquired skin disorder that is characterized by well-defined, often symmetric white patches. Although current therapeutic modalities are directed toward increasing melanocyte melanin production, few treatment modalities address the immunologic nature of the disease. OBJECTIVE. : To determine whether excimer laser, a known therapeutic modality, in combination with tacrolimus, a topical immunomodulator, accelerate response time and/or improve the degree of response in patients with this disorder. METHODS. : Eight subjects diagnosed with vitiligo were recruited to participate in this institutional review board-approved double-blind, placebo-controlled study. Twenty-four symmetric vitiliginous patches (elbows, knees) from eight subjects received excimer laser treatment three times per week for 24 treatments or 10 weeks. Additionally, topical tacrolimus 0.1% ointment (Protopic) and placebo (Aquaphor) were applied to randomized patches (left or right) twice daily throughout the length of the trial. Vitiliginous patches were monitored with photographs at baseline, every 2 weeks, and 6 months after treatment. Biopsies were performed on subjects with significant results. RESULTS. : Twenty vitiliginous patches from six subjects qualified for evaluation. Fifty percent of patches treated with combination excimer laser and tacrolimus achieved a successful response (75% repigmentation) compared with 20% for the placebo group. Subjects who responded successfully repigmented faster (19%) with combination therapy compared with excimer laser alone. Additionally, three subjects experienced transient hyperpigmentation in lesions treated with combination therapy. CONCLUSION. : Combining topical immunomodulators with known phototherapeutic modalities may represent a key advancement in the treatment of disease.

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Drugs. 2004;64(1):89-107.
Hypopigmentary skin disorders: current treatment options and future directions.
Hartmann A, Brocker EB, Becker JC.
Department of Dermatology, University Hospital Wuerzburg, Wuerzburg, Germany.

Alterations of skin and hair pigmentation are important features that have warranted treatment from ancient history on up to modern time. In some cultures, even today patients with vitiligo are regarded as social outcasts and are affected considerably both emotionally and physically. This article presents current options and future directions for the treatment of hypopigmentary disorders. Whereas with congenital disorders, such as albinism and phenylketonuria, no causal therapy has been established up to now, several treatment options for acquired hypopigmentary disorders have been investigated. In particular, in vitiligo, one of the most prevalent hypopigmentary disorders, a number of treatment modalities have been employed in the past 30 years. However, most of them are only able to palliate, not cure, the disease. Depending on the distribution of the hypopigmented lesions (localised or generalised) and the state of the disease (active or stable), several therapeutic options, for example phototherapy, surgical skin grafts, autologous melanocyte transplantation and immunomodulators, can be applied alone or in combination. For phototherapy, because of unfavourable results and adverse effects, ultraviolet (UV) A has been largely replaced by narrow-band UVB for repigmentation of generalised vitiligo. Although immunomodulators, such as corticosteroids, have been used both topically and systemically over the past 3 decades for the treatment of disseminated vitiligo, they are only suitable for the treatment of acrofacial and localised forms because of adverse effects. Hence, new immunomodulatory agents, such as calcineurin antagonists, have recently been introduced as new promising tools to treat acquired hypopigmentary disorders. However, all therapeutic approaches are hampered by the fact that the pathophysiology of hypopigmentary disorders is still poorly understood.

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J Am Acad Dermatol. 2004 Jan;50(1):63-7.
Clinical study of repigmentation patterns with different treatment modalities and their correlation with speed and stability of repigmentation in 352 vitiliginous patches.
Parsad D, Pandhi R, Dogra S, Kumar B.
Department of Dermatology, Postgraduate Institute of Medical Education and Research, Chandigarh, India. dprs@satyam.net.in

Because the etiopathogenesis of depigmentation in vitiligo is still obscure, the source of pigmentation in the repigmentating lesion and its stability is also not fully known. Several authors have shown on histopathology and electron microscopy predominantly a perifollicular spread of pigment. The aim of this study was to clinically assess the types of repigmentation patterns obtained with different treatment modalities and their correlation with speed and stability of repigmentation. A total of 125 patients with vitiligo on treatment with psoralens (topical and systemic psoralen-UVA [PUVA]), steroids (both topical and systemic), and topical calcipotriol, alone or in combination were enrolled. Representative lesions of vitiligo excluding mucosal sites were selected in each patient and photographed at baseline. Repigmentation was assessed and labeled as marginal, perifollicular, diffuse, or combined. The preselected patches were evaluated at 3 months to assess the speed of repigmentation. Retention of pigment (stability) was noted at 6 months, after the stoppage of active treatment. Of the 352 vitiligo patches selected, 194 (55%) showed predominant perifollicular repigmentation, of which a majority (127; 65.5%) were on systemic PUVA and 35 (18%) were on topical PUVA. Diffuse pigmentation was observed in 98 patches (27.8%) of which 66 (67.3%) were on topical steroids. Marginal repigmentation was seen in 15, of which the majority (80%) were on systemic PUVA and topical calcipotriol. Of the 28 total lesions showing marked repigmentation at 3 months, 22 lesions pigmented in a diffuse manner, 2 in a perifollicular pattern, and 4 showed a combined type of repigmentation. On follow-up, marginal repigmentation was the most stable (93.3%), followed by perifollicular (91.7%) and combined type (84.4%). Diffuse repigmentation was the least stable (78.5%). Psoralens predominantly exhibit a perifollicular pattern of repigmentation and steroids (topical/systemic), a diffuse type. The speed of repigmentation is much faster when initial repigmentation is of the diffuse type as compared with follicular repigmentation. The marginal and perifollicular repigmentation is more stable than the diffuse type of repigmentation.

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Dermatol Surg. 2004 Jan;30(1):49-53.
A comparative study of punch grafting followed by topical corticosteroid versus punch grafting followed by PUVA therapy in stable vitiligo.
Barman KD, Khaitan BK, Verma KK.
Department of Dermatology and Venereology, All India Institute of Medical Sciences, New Delhi, India.

BACKGROUND: Punch grafting followed by PUVA is an established therapy for stable vitiligo, but punch grafting followed by topical corticosteroid has never been evaluated. OBJECTIVE: The aim of this study was to evaluate the efficacy of topical corticosteroid in perigraft pigmentation and to compare it with perigraft pigmentation after PUVA in patients with stable vitiligo. METHODS: Fifty patients with stable vitiligo of various clinical types were subjected to punch grafting. In a randomized case study, these patients were divided into two groups: One group received post punch-grafting PUVA (group I) and the other group post punch-grafting topical application of fluocinolone acetonide 0.1% (group II). During the follow-up period of 6 months, six patients were lost to follow-up, and two patients were excluded from the study; 42 patients were evaluated for pigment spread and side effects. RESULTS: In group I, the average pigment spread was 6.38 mm, whereas in group II, it was 6.94 mm, showing a slightly higher pigment spread in group II, which was statistically not significant (P=0.301). There was no difference in response to therapy in patients having segmental vitiligo as compared with nonsegmental vitiligo. Cobblestoning, depigmentation of the grafts, infection, and graft displacement were the important side effects seen in some patients in both the groups. CONCLUSION: The study shows that the pigment spread with topical corticosteroid is comparable to that with PUVA. However, the studies with long-term follow-up are required to establish this. The advantages of topical corticosteroid are that its use is easy, less cumbersome, cheaper, and more cost effective than PUVA.

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Acta Dermatovenerol Croat. 2003;11(3):163-70.
Treatment of vitiligo: current methods and new approaches.
Kostovic K, Nola I, Bucan Z, Situm M.
Department of Dermatology and Venerology, Sisters of Mercy University Hospital, Vinogradska cesta 29, HR-10000 Zagreb, Croatia. kreso.kostovic@zg.hinet.hr

Vitiligo is an acquired idiopathic hypomelanotic disorder characterized by circumscribed depigmented maculae. It can be treated in many ways. The choice of therapy is individually adjusted depending on various factors, such as the patient age, type and stage of disease, and affected body site. Current treatment modalities include psoralen with exposure to ultraviolet A (PUVA) radiation therapy, narrow-band UVB therapy, topical corticosteroids, depigmentation therapy with monobenzylether of hydroquinone, and surgical treatments (minigrafting, thin split-thickness grafting, suction blister grafting, micropigmentation). There are also some new treatment modalities, such as 308-nm excimer laser, vitamin D analogues, tacrolimus, depigmentation with Q-switched ruby laser, and grafting of cultured melanocytes.

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Dermatol Online J. 2003 Dec;9(5):4.
Calcipotriol and PUVA as treatment for vitiligo.
Cherif F, Azaiz MI, Ben Hamida A, Ben O, Dhari A.
Department of Dermatology, La Rabta Hospital, Tunis, Tunisia. faika.cherif@voila.fr

We performed a prospective study to evaluate efficacy of the combination of calcipotriol and psoralen plus ultraviolet A (PUVA) in the treatment of vitiligo. Twenty-three patients with essentially bilateral symmetrical lesions of vitiligo were included. Calcipotriol (0.005 %) ointment was applied twice daily over the right side of the body, and the other side was not treated. PUVA was performed three times per week. All patients received at least forty five sessions of PUVA. Patients were evaluated clinically and photographed all fifteen weeks. At the fifteenth session, 69 percent of the patients had minimal to moderate improvement on the calcipotriol side compared to 52 percent on the PUVA-only side (p = 0.015). At the forty-fifth session, 52 percent showed marked improvement on the calcipotriol side compared to 30 percent on the PUVA-only side (p = 0.13), with more intense repigmentation on calcipotriol-treated areas. Treatment was well tolerated, and no adverse effect was noted. This combination was an effective treatment for vitiligo, especially in initiating repigmentation.

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Pigment Cell Res. 2003 Oct;16(5):590-1.
IL-38 Surgical treatment of vitiligo.
Naeyaert JM, Geel N, Ongenae K.
Ghent University Hospital, Department of Dermatology, Gent, Belgium.

Vitiligo is a common acquired disorder of pigmentation. Therapy for active or stable, non-treated vitiligo is medical (local corticosteroids, immunomodulators and vitamin D derivatives and systemic or topical photo(chemo)therapy). Surgical treatment is suitable for stable disease, resistant to medical therapy. The basic principle in surgical grafting is to transplant autologous melanocytes from a pigmented donor area to a depigmented acceptor area. Both tissue and cellular grafts have been used with some success. We undertook a randomized double blind placebo controlled study of autologous non-cultured epidermal cells for repigmenting vitiligo patches in order to assess the efficacy and safety of this technique and to get insight into the mechanisms of repigmentation. Twenty-eight patients with vitiligo, resistant to previous medical treatment, were included. Thirty-three symmetrical, paired lesions were treated. The donor area for the epidermal cells was the buttock area where a thin split-thickness graft was harvested with a hand-held dermatome. The sheet was trypsinized and resuspended in a low-calcium melanocyte medium enriched with hyaluronic acid. Meanwhile, the acceptor areas were anaesthesized with EMLA cream, and the epidermis was abraded with a CO2 laser (Coherent). One of the paired lesions received the full cellular suspension, the other the suspension without cells. Repigmentation was measured at 3, 6 and 12 months using digitalized image analysis. In 19 patients with stable vitiligo according to anamnestic and clinical data, 70% repigmentation was achieved in 55%, 57% and 77% of patients 3, 6 and 12 months after treatment respectively. In a second group of 9 patients clinical follow-up casted doubts on the stable nature of their vitiligo. Percentages of repigmentation were 0% at all times in this group. The pattern of repigmentation was diffuse, not perifollicular. We conclude that transplantation of autologous epidermal cell suspensions results in repigmentation of >70% in the majority of patients with stable disease. Repigmentation is caused by the transplanted cells, as a role of post-inflammatory pigmentation, UV-induced pigmentation and spontaneous pigmentation is of minimal importance.

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Pigment Cell Res. 2003 Oct;16(5):590.
IL-37 Lasers in pigmentary disorders.
Dierickx CC.
Visiting Lecturer, Harvard Medical School, Boston, MA, Consultant, Department of Dermatology, Ghent University Hospital, Belgium; Director Laser Clinic, Boom, Belgium.

A variety of lasers can be used to target melanin in the skin. The fundamental principle behind laser treatment of cutaneous pigmentation is selective destruction of undesired pigment with minimal collateral damage. This destruction can be achieved by the delivery of high energy at the absorptive wavelength of the selected chromophore1. The approach with lasers for the treatment of cutaneous pigmentation depends on the localization of the pigment, (epidermal, dermal or mixed), the way it is packaged (intracellular or extracellular) and the nature of the pigment. Short-pulsed lasers, including the Q-switched ruby laser, the Q-switched Nd-YAG laser, the Q-switched alexandrite laser and the 510 nm pulsed pigment laser, as well as millisecond pigment lasers have been utilized in the treatment of pigment disorders. Electron microscopic evaluation has demonstrated that melanosome destruction is occurring after treatment with the short pulsed lasers2 and melanocyte destruction occurs after treatment with the millisecond lasers3. Among the benign pigmented lesions which do react well are ephelifes (freckles) pigmented actinic keratosis, nevus of Ota, nevus of Ito, and 'blue' nevus. Varying results are obtained in so-called 'cafe au lait'-maculae, congenital and acquired nevocellular nevi, nevus spilus and nevus of Becker. Treatment of congenital and acquired nevi nevocellulares is still controversial because of the possibility of incomplete destruction of deeper situated nevi cells and the possibility of masking. Hyperpigmentation like melasma and post-inflammatory hyperpigmentation only show moderate reactions. One has to realise that laser treatment itself can result in post-inflammatory hyperpigmentation. Narrow-band UVB phototherapy has been shown to be a safe and effective treatment for vitiligo, Recently, a 308 nm UVB excimer laser and a filtered UV source to treat localized vitiligo have been developed. The laser is a XTRACTM XeCl excimer laser (PhotoMedex, Radnor PA) and the filtered UV source is the B Clear (Lumenis). UV lesion-directed treatment for localized vitiligo could have considerable advantages over conventional UVB treatment, including fewer treatments, lower cumulative doses resulting in a greater risk/benefit ratio4.

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Arch Dermatol. 2003 Oct;139(10):1303-10.
Erbium:YAG laser and cultured epidermis in the surgical therapy of stable vitiligo.
Guerra L, Primavera G, Raskovic D, Pellegrini G, Golisano O, Bondanza S, Paterna P, Sonego G, Gobello T, Atzori F, Piazza P, Luci A, De Luca M.
Laboratory of Tissue Engineering, Istituto Dermopatico dell'Immacolata, Rome, Italy.

OBJECTIVE: To induce complete and reproducible repigmentation of large "stable" vitiligo lesions by means of autologous cultured epidermal grafts using a rapid, simple, and minimally invasive surgical procedure. DESIGN: Achromic epidermis was removed by means of appropriately settled erbium:YAG laser, and autologous epidermal grafts were applied onto the recipient bed. Melanocyte content was evaluated by dopa reaction. The percentage of repigmentation was calculated using a semiautomatic image analysis system. SETTING: A biosafety level 3-type cell culture facility, a surgical ambulatory department, and a dermatological department in a hospital. PATIENTS: Twenty-one patients with different types of vitiligo were admitted to the study and treated with autologous cultured epidermal grafts. Inclusion criteria were failure of at least 2 standard medical approaches; no therapy for at least 12 months; no progression of old lesions or appearance of new lesions; no Koebner phenomenon within the past 18 months; and no autoimmune disorders. RESULTS: The average percentage of repigmentation in 21 patients was 75.9% (1759.7 cm2 repigmented/2315.8 cm2 transplanted). Three patients showed a reactivation of their vitiligo and did not show repigmentation. The remaining 18 patients, with 43 distinct lesions, showed an average percentage of repigmentation of 90% (1759.7 cm2 repigmented/1953.4 cm2 transplanted). CONCLUSIONS: Under appropriate conditions, cultured epidermal grafts induce complete repigmentation of stable vitiligo lesions. Erbium:YAG laser surgery can supply a fast and precise tool for disepithelialization, hence allowing treatment of large vitiligo lesions during a single surgical operation.

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J Am Acad Dermatol. 2003 Sep;49(3):473-6.
Narrowband ultraviolet B radiation therapy for recalcitrant vitiligo in Asians.
Natta R, Somsak T, Wisuttida T, Laor L.
Division of Dermatology, Department of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand. ranrj@mahidol.ac.th

BACKGROUND: Narrowband ultraviolet B (NBUVB) has recently been reported to be effective therapy for vitiligo. However, reports on its efficacy in recalcitrant vitiligo are lacking. OBJECTIVE: Our objective was to assess the efficacy of NBUVB in patients with vitiligo who did not respond to either topical therapy or oral psoralen plus ultraviolet A (PUVA). METHOD: This was a retrospective analysis of patients with vitiligo who were treated with NBUVB from February 1998 to January 2001. They received NBUVB treatment 2 times per week, with an initial dose of 100 mJ/cm(2). The dose was increased by 10% to 20% per treatment for 20 treatments. The dose was then increased by 2% to 5% per treatment until 50% repigmentation was observed or persistent erythema developed. The treatment was continued until maximum repigmentation was achieved. The treatment was terminated if the patient showed less than 25% improvement after 40 to 50 exposures. RESULTS: There were 60 patients: 22 men and 38 women, aged 11 to 61 years. The mean duration of vitiligo was 8.2 +/- 7.1 years. There were 53 cases of generalized and 7 cases of localized vitiligo. The lesions covered from less than 5% to 50% of body surface. Twenty-five patients were skin type III, 33 patients were skin type IV, and 2 patients were skin type V. Every case had been previously treated with topical steroid with or without topical psoralen with solar light exposure. Thirty-six patients (60%) had been treated with oral PUVA before NBUVB therapy. After NBUVB treatment, 25 of 60 patients (42%) achieved more than 50% repigmentation on face, trunk, arms, and legs. However, hand and foot lesions showed less than 25% repigmentation in all cases. There was no significant difference between the responders and nonresponders in age, sex, duration of diseases, and skin type. The response rate of patients who had not been previously treated with PUVA was significantly higher than that of patients who had been previously treated with PUVA (67% vs 36%, P =.003). CONCLUSION: This retrospective, open study demonstrated that NBUVB therapy was effective in 42% of Asian patients with recalcitrant vitiligo without serious side effect. The only clinical parameter that could differentiate nonresponders from responders was previous exposure to PUVA.

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Int J Dermatol. 2003 Aug;42(8):658-62.
308-nm excimer laser for the treatment of localized vitiligo.
Taneja A, Trehan M, Taylor CR.
Department of Dermatology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.

BACKGROUND AND OBJECTIVE: Vitiligo is commonly treated with PUVA, and more recently, narrow-band UVB (NBUVB) phototherapy. Given the proximity of the wavelengths of NBUVB (311 nm) and the excimer laser (308 nm), we undertook a clinical trial to test the efficacy of this device. METHODS: Twice-weekly 308-nm UV-B radiation was given to selected vitiligo lesions for a maximum of 60 treatments. These lesions had been unsuccessfully treated previously with at least one other method of treatment. Initial doses were 100 mJ/cm2 with increments of 10-25%. Improvement was assessed on a visual scale via serial photographs. RESULTS: Subjects tolerated the treatment well. Improvement varied with body site. After 60 treatments, lesions on the hands and feet showed grade 2 improvement in 2/10 subjects and grade 1 in 8/10. For the axillae, there was grade 4 improvement in 1/3 subjects and grade 2 improvement in 2/3 by treatment 60. The face demonstrated the most rapid repigmentation with grade 4 repigmentation seen in 3/5 subjects by 40 treatments and grade 3 in 2/5 by 30 treatments. There were no adverse effects. CONCLUSIONS: The user-friendly 308-nm excimer laser allows targeted treatments of localized vitiligo.

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Photodermatol Photoimmunol Photomed. 2003 Aug;19(4):164-8.
Narrow-band ultraviolet B treatment for vitiligo, pruritus, and inflammatory dermatoses.
Samson Yashar S, Gielczyk R, Scherschun L, Lim HW.
Department of Dermatology, Henry Ford Health System, Detroit, MI 48202, USA.

BACKGROUND: Narrow-band ultraviolet B (NB-UVB) therapy has been used successfully for the treatment of inflammatory and pigmentary skin disorders including atopic dermatitis, psoriasis, mycosis fungoides, polymorphous light eruption, and vitiligo. METHODS: This is a retrospective review of the treatment outcomes of 117 consecutive patients with vitiligo, pruritus, and other inflammatory dermatoses, excluding those with psoriasis and CTCL, who were treated with NB-UVB between 1998 and 2001 at our institution. RESULTS: Approximately 80% of all patients showed improvement in their condition. NB-UVB phototherapy was well tolerated, with no serious adverse effects. In patients with vitiligo, 6.4% had an abnormal thyroid-stimulating hormone level and 6.5% had anemia. CONCLUSION: NB-UVB may be considered as a viable therapeutic option in the treatment of vitiligo, pruritus, and other inflammatory dermatoses. Long-term adverse effects and cost-benefit analysis of NB-UVB therapy compared to other treatment modalities remain to be determined.

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Zhongguo Zhong Xi Yi Jie He Za Zhi. 2003 Aug;23(8):596-8.
[Clinical observation on treatment of vitiligo with xiaobai mixture]
[Article in Chinese]
Liu ZJ, Xiang YP.
Department of Dermatology, First Affiliated Hospital, Nanhua University, Hunan 421001. liuzj71@sohu.com

OBJECTIVE: To observe the therapeutic effect of Xiaobai Mixture (XBM) in treating vitiligo. METHODS: Seventy-four patients with vitiligo were randomly divided into the XBM group treated with XBM and the control group treated with 8-MOP. The therapeutic effect, nail-fold microcirculation, plasma endothelin-1, serum immunoglobulin were observed and compared. RESULTS: The therapeutic effect of XBM was better than that of 8-MOP (P < 0.05). XBM could also obviously improve the nail-fold microcirculation, elevate the plasma endothelin-1 level and lower the serum IgG (P < 0.01). CONCLUSION: XBM has superiority in treating vitiligo.

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Acta Dermatovenerol Croat. 2003;11(3):163-70.
Treatment of vitiligo: current methods and new approaches.
Kostovic K, Nola I, Bucan Z, Situm M.
Department of Dermatology and Venerology, Sisters of Mercy University Hospital, Vinogradska cesta 29, HR-10000 Zagreb, Croatia. kreso.kostovic@zg.hinet.hr

Vitiligo is an acquired idiopathic hypomelanotic disorder characterized by circumscribed depigmented maculae. It can be treated in many ways. The choice of therapy is individually adjusted depending on various factors, such as the patient age, type and stage of disease, and affected body site. Current treatment modalities include psoralen with exposure to ultraviolet A (PUVA) radiation therapy, narrow-band UVB therapy, topical corticosteroids, depigmentation therapy with monobenzylether of hydroquinone, and surgical treatments (minigrafting, thin split-thickness grafting, suction blister grafting, micropigmentation). There are also some new treatment modalities, such as 308-nm excimer laser, vitamin D analogues, tacrolimus, depigmentation with Q-switched ruby laser, and grafting of cultured melanocytes.

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Eur J Dermatol. 2003 Jul-Aug;13(4):372-6.
Open trial of topical tacalcitol [1 alpha 24(OH)2D3] and solar irradiation for vitiligo vulgaris: upregulation of c-Kit mRNA by cultured melanocytes.
Katayama I, Ashida M, Maeda A, Eishi K, Murota H, Bae SJ.
Department of Dermatology, Nagasaki University School of Medicine, 1-7-1, Sakamoto, Nagasaki, Japan. nkatayam@net.nagasaki-u.ac.jp

Vitiligo vulgaris is a common skin disease, however some cases show poor clinical responses to topical steroid ointment or PUVA therapy. Such regimens are generally avoided in the treatment of facial lesions or in pediatric cases because of the undesirable side effects. To confirm the excellent response to combination therapy with topical vitamin D3 ointment and solar irradiation for vitiligo achieved in the initial patients, we conducted an open trial on other patients, most of whom had poor clinical responses to the prior therapies. Fifteen patients (9 men and 6 women) with vitiligo vulgaris were enrolled in this study. Each patient was instructed to sunbathe for 30 minutes within 1 hour after topical application of the tacalcitol [1 alpha 24(OH)(2)D(3)] ointment or cream to the skin lesions every day. Six of 15 patients showed a fair and excellent clinical response to the combination therapy (more than 30% clearance of the vitiligo). The clinical effect was more apparent in patients with a history of less than 5 years of vitiligo (4 of 6 cases) in contrast to those with a history of more than 5 years (2 of 9 cases). In vitro experiments revealed that tacalcitol upregulated the expression of c-Kit mRNA by melanocytes irradiated with linear polarized infrared, UVA or short period solar irradiation. These results suggest that combination therapy with topical vitamin D(3) ointment and solar irradiation can be used as an alternate therapy for vitiligo vulgaris.

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J Am Acad Dermatol. 2003 Jul;49(1):99-104.
Epidermal grafting in vitiligo: influence of age, site of lesion, and type of disease on outcome.
Gupta S, Kumar B.
Department of Dermatology, Venereology, and Leprology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.

BACKGROUND: The success of suction blister epidermal grafting may be influenced by various factors, all of which have not been studied to date. OBJECTIVE: We sought to determine the influence of age of the patient, site of vitiligo patch, and type of disease on the outcome of the procedure in our patients and in the cumulative data derived from literature analysis. METHODS: This was a retrospective, uncontrolled case series and literature review of suction blister epidermal grafting in patients with stable and recalcitrant vitiligo. All published studies of suction blister epidermal grafting in vitiligo involving 10 or more patients were included in the literature analysis. RESULTS: The procedure was performed in 143 patients. However, sufficient length (6 postoperative months) of follow-up was available in only 117 patients, and only these patients were included for analysis. Only limited information was available about various factors in the majority of published studies. The success rates for generalized and segmental/focal disease in this study were 53% (confidence interval [CI] 42-64) and 91% (CI 81-100), respectively (P <.001), and in the literature, 61% (CI 46-76) and 88% (CI 82-94), respectively (P <.01). The success rates in patients aged < 20 years and >or= 20 years in this study were 82% (CI 67-97) and 58% (CI 48-68), respectively (P <.05), and in the literature, 100% and 66% (CI 56-76), respectively (P <.05). There was no significant difference in the success rates achieved on different body sites in this study and in the screened literature. Among adverse reactions, hyperpigmentation in 32% (CI 24-40) and 17% (CI 14-20), infection in 6% (CI 2-10) and 0%, and contact dermatitis in 1% (CI 0-3) and 1% (CI 0-2) of patients were observed in this study and in the analyzed literature, respectively. CONCLUSIONS: The results were significantly better in segmental/focal vitiligo than in the generalized type, and in individuals < 20 years of age. However, unlike in medical therapies, localization of the vitiligo patch did not influence the treatment outcome significantly.

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Sheng Wu Yi Xue Gong Cheng Xue Za Zhi. 2003 Jun;20(2):305-7.
[Research of magnetism light compound therapy in clinical application]
[Article in Chinese]
Liu Z, Sun C, Zhang W, Mao J, Yan Y, Fu C.
Second People's Hospital of Jianyang, Jianyang 641421.

This study is aimed to evaluate the clinical application of the millimeter wave and magnetism light compound therapy. The EHF-98B MMW. RL compound therapy apparatus made in the University of Electronic Technology(Chengdu) was used in 171 patients. The superficial, skin lesions or the visceral reflected skin regions (acupoints) were directly exposed to the light from the apparatus. All the cases were divided into five groups, namely skin mucosa superficial lesions, trauma of the bone and joint soft tissue, surgical incision, ENT infections, and rare intricate diseases. The therapeutic effects observed in the groups were analyzed and evaluated by means of 4 levels. As for the 171 patients, the cure rate was 42.7% (73 patients), the effective rate 25.1%(43 patients), the improvement rate 31%(53 patients), and no effect constituted 1.2%(2 patients). The total effective rate was 98.8%. This therapy was especially effective for treating chronic cervicitis, cervical erosion, soft tissue trauma, surgical incision. Also it was effective for treating some rare intricate diseases, e.g. sterility, vitiligo, Behcet disease. So the millimeter wave and magnetism light compound therapy may find wide clinical applications.

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Dermatol Ther. 2003 Jun;16(2):114-22.
Biofeedback, cognitive-behavioral methods, and hypnosis in dermatology: Is it all in your mind?
Shenefelt PD.
Division of Dermatology and Cutaneous Surgery, Department of Internal Medicine, College of Medicine, University of South Florida, Tampa, Florida.

Biofeedback can improve cutaneous problems that have an autonomic nervous system component. Examples include biofeedback of galvanic skin resistance (GSR) for hyperhidrosis and biofeedback of skin temperature for Raynaud's disease. Hypnosis may enhance the effects obtained by biofeedback. Cognitive-behavioral methods may resolve dysfunctional thought patterns (cognitive) or actions (behavioral) that damage the skin or interfere with dermatologic therapy. Responsive diseases include acne excoriee, atopic dermatitis, factitious cheilitis, hyperhidrosis, lichen simplex chronicus, needle phobia, neurodermatitis, onychotillomania, prurigo nodularis, trichotillomania, and urticaria. Hypnosis can facilitate aversive therapy and enhance desensitization and other cognitive-behavioral methods. Hypnosis may improve or resolve numerous dermatoses. Examples include acne excoriee, alopecia areata, atopic dermatitis, congenital ichthyosiform erythroderma, dyshidrotic dermatitis, erythromelalgia, furuncles, glossodynia, herpes simplex, hyperhidrosis, ichthyosis vulgaris, lichen planus, neurodermatitis, nummular dermatitis, postherpetic neuralgia, pruritus, psoriasis, rosacea, trichotillomania, urticaria, verruca vulgaris, and vitiligo. Hypnosis can also reduce the anxiety and pain associated with dermatologic procedures.

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Dermatol Ther. 2003 Jun;16(2):106-13.
From medical herbalism to phytotherapy in dermatology: back to the future.
Dattner AM.
Integrative Medicine and Dermatology, New Rochelle, New York.

Plant-based therapeutic preparations are cyclically returning to complement dermatologic therapy. They serve as therapeutic alternatives, safer choices, or in some cases, as the only effective treatment. Folk medicine tradition provides different indicators for use than the medical disease model. Advantages of multiple synergistic components of crude extracts are discussed, as well as herbs already used in dermatology. Bitter digestive stimulants are used for vitiligo. Bioflavinoids from buckwheat and horse chestnut are used for varicose veins, and silymarin is used for liver protection. Gotu kola and sarsaparilla are used for inflammatory skin conditions. Oregon grape root has synergistic antibacterial, anti-inflammatory, and bile-stimulating properties which make the crude extract useful in acne. Philosophical differences in herbology compared to medicine exist in the application of science toward improving elimination and strengthening the host as opposed to destroying the vector or manifestation of the disease.

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Clin Exp Dermatol. 2003 May;28(3):285-7.
Effectiveness of oral Ginkgo biloba in treating limited, slowly spreading vitiligo.
Parsad D, Pandhi R, Juneja A.
Department of Dermatology, Postgraduate Institute of Medical Education and Research, Chandigarh, India. dprs@satyam.net.in

For effective treatment of vitiligo, it is as important to arrest the progression of the disease as it is to induce repigmentation. Recently, oxidative stress has been shown to play an important role in the pathogenesis of vitiligo. Ginkgo biloba extract has been shown to have antioxidant and immunomodulatory properties. In a double-blind placebo-controlled trial, we evaluated the efficacy of G. biloba extract in controlling the activity of the disease process in patients with limited and slow-spreading vitiligo and in inducing repigmentation of vitiliginous areas. Fifty-two patients were assigned to two treatment groups (A and B) in a double-blind fashion, but only 47 patients could be evaluated, because one patient in group A and four patients in group B withdrew for reasons unrelated to the study. Patients in group A were given G. biloba extract 40 mg three times daily whereas patients in group B received placebo in similar doses. A statistically significant cessation of active progression of depigmentation was noted in patients treated with G. biloba (P = 0.006). Marked to complete repigmentation was seen in 10 patients in group A, whereas only two patients in group B showed similar repigmentation. The G. biloba extract was well tolerated. G. biloba extract seems to be a simple, safe and fairly effective therapy for arresting the progression of the disease.

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J Eur Acad Dermatol Venereol. 2003 May;17(3):299-302.
Is the combination of calcipotriol and PUVA effective in vitiligo?
Baysal V, Yildirim M, Erel A, Kesici D.
University of Suleyman Demirel, School of Medicine, Department of Dermatology, Isparta, Turkey.

OBJECTIVE: The objective was to compare the effectiveness of psoralen plus ultraviolet A (PUVA) and the combination of PUVA and topical calcipotriol in the treatment of vitiligo. BACKGROUND: There are several reports on the response rate of patients with vitiligo treated with the combination of PUVA and calcipotriol or calcipotriol alone. SUBJECTS AND METHODS: Twenty-two patients with generalized vitiligo were taken into the study. PUVA treatment was applied on a twice-weekly schedule. Calcipotriol cream was applied to one of the two symmetrical lesions of each patient twice daily. RESULTS: Our results showed that the addition of topical calcipotriol to PUVA treatment did not lead to a significant increase in response rate of patients with vitiligo compared with PUVA treatment alone.

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Arch Dermatol. 2003 May;139(5):581-5.
A double-blind randomized trial of 0.1% tacrolimus vs 0.05% clobetasol for the treatment of childhood vitiligo.
Lepe V, Moncada B, Castanedo-Cazares JP, Torres-Alvarez MB, Ortiz CA, Torres-Rubalcava AB.
Dermatology Department, Dr Ignacio Morones Prieto Hospital Central, Universidad Autonoma de San Luis Potosi, 2405 V Carranza Avenue, Zona Universitaria, 78210 San Luis Potosi, Mexico.

OBJECTIVE: To assess the safety and efficacy of topical 0.1% tacrolimus vs 0.05% clobetasol propionate. DESIGN: Randomized double-blind trial. SETTING: Department of Dermatology, Hospital Central Dr Ignacio Morones Prieto, San Luis Potosi, Mexico. PARTICIPANTS: From 20 children with vitiligo, 2 symmetrical lesions of about the same size and evolution time were selected. They were devoid of any topical or systemic therapy for 2 months prior to inclusion.Interventions Treatment with topical tacrolimus and clobetasol for a 2-month period. MAIN OUTCOMES MEASURES: The grade of repigmentation was evaluated by color slides at baseline and again at every 2-week visit. The slides were analyzed by 2 clinicians unrelated to the study and by a morphometric digitalized computer program. Characteristics of pigment, time of response, symptoms, telangiectasias, and atrophy were evaluated every 2 weeks. RESULTS: Eighteen (90%) of the 20 patients experienced some repigmentation. The mean percentage of repigmentation was 49.3% for clobetasol and 41.3% for tacrolimus. Lesions in 3 patients using clobetasol presented atrophy, and 2 lesions incurred telangiectasias; tacrolimus caused a burning sensation in 2 lesions. CONCLUSIONS: Tacrolimus proved almost as effective as clobetasol propionate to restore skin color in lesions of vitiligo in children. Because it does not produce atrophy or other adverse effects, tacrolimus may be very useful for younger patients and for sensitive areas of the skin such as eyelids, and it should be considered in other skin disorders currently treated with topical steroids for prolonged periods.

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Plast Reconstr Surg. 2003 Mar;111(3):1291-8.
Carbon dioxide laser resurfacing and thin skin grafting in the treatment of "stable and recalcitrant" vitiligo.
Acikel C, Ulkur E, Celikoz B.
Division of Plastic and Reconstructive Surgery and Burn Unit, Gulhane Military Medical Academy, Haydarpasa Hospital, 81327 Uskudar, Istanbul, Turkey. cengizacikel@ixir.com

Various surgical methods have been used in the treatment of small stable vitiliginous areas, but there is no established surgical approach for larger vitiligo areas and therapy-resistant anatomic sites, such as the hands. Two years ago, we successfully treated large burn scar depigmentation areas at different anatomic sites using carbon dioxide laser resurfacing and thin (0.2 to 0.3 mm) skin grafting. The purpose of this study was to investigate the effectiveness of our method in treating large, stable, and recalcitrant vitiligo areas. Thirteen anatomic sites of seven male patients, whose ages ranged from 20 to 22 years, were treated. The locations of the treated areas were as follows: seven areas on the dorsum of the hands, two areas on the forearms, two areas in the pretibial region, one area on the lateral thigh, and one area in the presternal region. The surface area of treated vitiligo sites ranged from 0.5 to 6 percent of total body surface area (mean, 2.5 percent). Skin graft take was excellent in all patients except for one. The follow-up period for these patients ranged from 6 to 18 months, with an average follow-up period of 14 months. Early and complete repigmentation was achieved and the color match was good or excellent in all patients. No depigmentation occurred again in the treated areas or graft donor sites. In conclusion, with careful patient selection and delicate surgical technique, our method was effective in treating large areas of vitiligo over the extremities and dorsum of hands, which were refractory to other therapies and could not be hidden.

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J Eur Acad Dermatol Venereol. 2003 Mar;17(2):171-7.
Narrow-band UV-B micro-phototherapy: a new treatment for vitiligo.
Menchini G, Tsoureli-Nikita E, Hercogova J.
Department of Dermosciences, University of Florence, Florence, Italy. g.menchini@dermatologia.it

BACKGROUND: Vitiligo is a common, acquired, often familial, melanocytopenic disorder with focal depigmentation of the skin. There are several new treatments, that appear to have higher success rates than previous therapies for the treatment of vitiligo. Among these, the most promising one appears to be narrow-band UV-B therapy. OBJECTIVE: The aim of this open study is to evaluate the efficacy of the BIOSKIN micro-phototherapy in the treatment of vitiligo in 734 patients. SUBJECTS AND METHODS: Seven hundred and thirty-four individuals affected by vitiligo (segmental and non-segmental) were treated for 12 months with a new device called BIOSKIN that can produce a focused beam of narrow UV-B (microphoto-therapy) on vitiligo patches only. Photographs of the subjects were taken at the beginning of the therapy and every month thereafter for 12 months. The response to treatment was estimated in two comparable photographs using planimetry. The duration of the clinical study was of 2 years and 8 months. At the end of this period 734 patients had received each a mean of 24 sessions of treatment during a period of 12 months. RESULTS: Five hundred and ten subjects (69.48%) of the 734 achieved normal pigmentation on more than 75% of the treated areas. In particular, 112 of these were totally repigmented. One hundred and fifty-five (21.12%) individuals achieved 50-75% pigmentation of the treated areas, and 69 (9.40%) showed less than 50% repigmentation. No patients showed acute or chronic relevant adverse effects. CONCLUSION: BIOSKIN UV-B microphototherapy seems highly effective in restoring pigmentation in patients affected by vitiligo. As no side-effects have been observed, this could represent the treatment of choice for vitiligo limited to less than 30% of the skin surface.

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Photodermatol Photoimmunol Photomed. 2003 Feb;19(1):1-4.
Photo(chemo) therapy for vitiligo.
Roelandts R.
Photodermatology Unit, University Hospital St Raphael, Kapucijnenvoer 33, 3000 Leuven, Belgium. rik.roelandt@uz.kuleuven.ac.be

Vitiligo has always been difficult to treat. Several modes of treatment are available, but the therapeutic effect varies greatly, and rarely does one achieve complete repigmentation. One of the most efficient treatment methods is photo(chemo) therapy. Already in ancient Egypt, vitiligo lesions were treated with extracts of the Ammi maius plant followed by exposure to the sun. This principle is at the basis of the photochemotherapy or PUVA therapy, whereby UVA irradiations are given 2 h after administration of 8-methoxypsoralen, a photosensitizer. Another efficient treatment form is UVB phototherapy, particularly narrow-band UVB. This not only gives good therapeutic results but also has the advantage of eliminating the need for a photosensitizer. All these treatments must be applied for many months to be efficient. They can also be combined with various surgical skin-grafting techniques. A newer approach is targeted UVB phototherapy, whereby xenon-chloride lasers or monochromatic excimer light is used.

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Int J Dermatol. 2003 Feb;42(2):132-6.
Melanocyte-keratinocyte cell transplantation for stable vitiligo.
Mulekar SV.
Noble Clinic, Pune, India. dr_mulekar@vsnl.com

BACKGROUND: Vitiligo is a common disorder with a worldwide prevalence of 1-2%. In India the psychological and social impact of the disease is significant and is detrimental to patients. OBJECTIVE: To evaluate the usefulness of epidermal cell transplantation in the treatment of vitiligo. METHODS: A simpler and modified method based on that of Olsson and Juhlin has been used. It utilizes a shave biopsy skin sample of up to one-tenth the size of the recipient area. The skin sample is incubated, the cells mechanically separated using trypsin EDTA solution, and then centrifuged to prepare a suspension. The cell suspension is then applied to the derm-abraded depigmented skin area and collagen dressing is applied to keep it in place. RESULTS: One hundred and twenty-two patients with generalized vitiligo, 43 with segmental and 19 with focal vitiligo were treated and observed for a period of 1 year. In the generalized vitiligo group 65 (53%) showed excellent pigmentation, 10 (8%) showed good pigmentation, 11 (9%) showed fair pigmentation and 28 (23%) patients showed poor pigmentation. Eight (7%) patients did not follow up. Thirty-six (84%), five (12%) and two (4%) patients showed excellent, good and poor pigmentation, respectively, in the segmental vitiligo group. Thirteen (69%) and five (26%) patients showed excellent and poor results, respectively, in the focal vitiligo group. One (5%) patient did not appear for follow up. Recurrence was observed in 15 patents. CONCLUSION: This surgical treatment gives its best results in segmental and focal vitiligo, even with large affected areas, and in at least 50% of patients with generalized vitiligo, thus improving their appearance.

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Cutis. 2003 Feb;71(2):158-62.
Tacrolimus ointment 0.1% produces repigmentation in patients with vitiligo: results of a prospective patient series.
Tanghetti EA.
Center for Dermatology and Laser Surgery, Sacramento, California, USA. et@mgci.com

The cause of the selective melanocyte destruction in vitiligo may be due to an autoimmune disorder. A series of 15 patients with vitiligo were treated with a topical immunomodulator, tacrolimus ointment 0.1%, twice daily for a minimum of 45 days. Thirteen patients (87%) experienced at least partial repigmentation, and 3 of those patients had greater than 75% repigmentation. Patients with the greatest treatment response likely benefited from concomitant natural sunlight exposure. Further studies investigating the safety and efficacy of tacrolimus ointment either as monotherapy or in combination with other therapeutic measures are warranted.

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Eur J Dermatol 2003 Jan-Feb;13(1):34-9
Melanocyte transplantation for the treatment of vitiligo: effects of different surgical techniques.
Issa CM, Rehder J, Taube MB.
Medical School, University of Campinas, UNICAMP, Rua Um, 230 Recreio dos Cafezais CEP 13278-300 Valinhos, PO Box: 128, S o Paulo, Brasil.

This paper presents the results of a pilot clinical trial study, conducted on 11 patients with stable vitiligo at the vitiligo outpatient clinic of The Unicamp University Hospital, between March 2000 and December 2001. This study was in accordance with the ethical standards of the Institutional Review Board. The patients were concomitantly treated with four different types of surgical techniques in 44 areas randomly chosen. There was a 90-day follow-up period. The following treatments were carried out: only cryotherapeutic treatment (OC); cryotherapy plus melanocyte culture medium (CM); cryotherapy plus transplantation of non-cultured melanocytes and keratinocytes (KM); and cryotherapy plus transplantation of cultured melanocytes (CC). The appearance of repigmentation and its evolution were followed all along the treatments. In the case of OC and CM no repigmentation occurred. Progressive repigmentation was observed over a period of 90 days in the case of KM and CC. In these two groups there was a significant reduction in the achromic areas during this time but no significant difference was found between the two treatments.

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J Invest Dermatol 2003 Jan;120(1):56-64
Helium-neon laser irradiation stimulates migration and proliferation in melanocytes and induces repigmentation in segmental-type vitiligo.
Yu HS, Wu CS, Yu CL, Kao YH, Chiou MH.
Department of Dermatology, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan. dermyu@kmu.edu.tw

Low-energy helium-neon lasers (632.8 nm) have been employed in a variety of clinical treatments including vitiligo management. Light-mediated reaction to low-energy laser irradiation is referred to as biostimulation rather than a thermal effect. This study sought to determine the theoretical basis and clinical evidence for the effectiveness of helium-neon lasers in treating vitiligo. Cultured keratinocytes and fibroblasts were irradiated with 0.5-1.5 J per cm2 helium-neon laser radiation. The effects of the helium-neon laser on melanocyte growth and proliferation were investigated. The results of this in vitro study revealed a significant increase in basic fibroblast growth factor release from both keratinocytes and fibroblasts and a significant increase in nerve growth factor release from keratinocytes. Medium from helium-neon laser irradiated keratinocytes stimulated [3H]thymidine uptake and proliferation of cultured melanocytes. Furthermore, melanocyte migration was enhanced either directly by helium-neon laser irradiation or indirectly by the medium derived from helium-neon laser treated keratinocytes. Thirty patients with segmental-type vitiligo on the head and/or neck were enrolled in this study. Helium-neon laser light was administered locally at 3.0 J per cm2 with point stimulation once or twice weekly. The percentage of repigmented area was used for clinical evaluation of effectiveness. After an average of 16 treatment sessions, initial repigmentation was noticed. Marked repigmentation (>50%) was observed in 60% of patients with successive treatments. Basic fibroblast growth factor is a putative melanocyte growth factor, whereas nerve growth factor is a paracrine factor for melanocyte survival in the skin. Both nerve growth factor and basic fibroblast growth factor stimulate melanocyte migration. It is reasonable to propose that helium-neon laser irradiation clearly stimulates melanocyte migration and proliferation and mitogen release for melanocyte growth and may also rescue damaged melanocytes, therefore providing a microenvironment for inducing repigmentation in vitiligo.

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J Biomed Sci 2002 Nov-Dec;9(6):564-73
Melanocyte destruction and repigmentation in vitiligo: a model for nerve cell damage and regrowth.
Yu HS.
Department of Dermatology, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan, ROC.

Melanocytes (MCs) are melanin-producing cells of the skin that are derived from neural crest cells. Vitiligo vulgaris is a common depigmentation disorder resulting from the destruction of functional MCs in the affected skin. The three prevailing pathomechanisms of vitiligo are the immune hypothesis, the neural hypothesis and the autocytotoxic hypothesis. None of these mechanisms has been conclusively proven. Melanoblasts (MBs) in the outer root sheath of the hair follicles are the reservoir cells for repigmentation. Recovery from vitiligo is initiated by activation and proliferation of these MBs, followed by upward migration to the nearby epidermis that forms perifollicular pigmentation islands. Migration, proliferation and differentiation of MCs and MBs are regulated by keratinocyte-derived factors and some coat color genes. Any therapy for vitiligo must explain not only the repopulation of MCs but also their functional development. In patients with vitiligo, MCs are destroyed in the skin, the eyes, and possibly the ears. However, the concept of vitiligo as a systemic disease will be clearly established only when the mechanisms involved in vitiligo are identified. Recent advances in the fields of neural crest cell culture and molecular genetics have opened new perspectives in the understanding of vitiligo. Not only will this result in better treatments for vitiligo patients, but possibly will also provide a key to triggering nerve cell regrowth in other nervous diseases. Copyright 2002 National Science Council, ROC and S. Karger AG, Basel

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Acta Derm Venereol 2002;82(5):369-72
Treatment of vitiligo vulgaris with narrow band UVB (311 nm) for one year and the effect of addition of folic acid and vitamin B12.
Tjioe M, Gerritsen MJ, Juhlin L, van de Kerkhof PC.
Department of Dermatology, University Medical Center Nijmegen, The Netherlands. M.Tjioe@derma.azn.nl

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.

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Br J Dermatol 2002 Nov;147(5):893-904
Long-term follow-up of leucoderma patients treated with transplants of autologous cultured melanocytes, ultrathin epidermal sheets and basal cell layer suspension.
Olsson MJ, Juhlin L.
Department of Medical Sciences, Section of Dermatology and Venereology, University Hospital, SE-751 85 Uppsala, Sweden. mats.olsson@medsci.uu.se

BACKGROUND: In vitiligo and piebaldism the lack of melanin in the epidermis is due to the fact that melanocytes are missing. The patients suffer psychologically and the white areas have lost the part of the skin barrier protection normally provided by the melanocytes. Medical treatments are ineffective in many of the patients, and surgical methods have therefore been developed. OBJECTIVES: It is important to investigate the long-term results and factors that might influence the outcome of melanocyte transplantations in order to form a basis for guidance in the selection of patients who will benefit most from the treatments. METHODS: A follow-up of 132 patients who had been treated by transplantation on 176 occasions in total, 1-7 years previously, was carried out by questionnaires and clinical examinations. We investigated the responses in five types of leucoderma to three different transplantation methods: autologous cultured melanocytes, ultrathin epidermal sheets and basal layer cell suspension. RESULTS: Stable types of leucoderma, i.e. segmental vitiligo and piebaldism, responded in most cases with 100% repigmentation, regardless of the surgical method used. For these types of leucoderma surgery seems to be the method of choice. The largest group, vitiligo vulgaris, was thoroughly scrutinized and three statistical models were used to analyse the data. The ultrathin epidermal sheet method gave somewhat better overall results, but was the method that gave the worst outcome in knee and elbow areas, emphasizing the importance of the right choice of method depending on the anatomical location to be treated. Irrespective of the method, fingers and elbows were the most difficult areas to repigment. The trunk and the arms and legs (not including elbows and knees) responded best. Patients with increasing and/or extensive vitiligo vulgaris more often showed incomplete repigmentation. They also had a lower chance of retaining their repigmentation compared with those with less extensive vitiligo. Patients in whom untreated white lesions had increased in recent years tended to respond less well to transplantation compared with patients with unchanged or decreased lesions. Within the vitiligo vulgaris group, patients with short disease duration or with small total vitiligo area responded best to transplantation. The subgroup of vitiligo vulgaris patients with hypothyroidism tend to respond less well to the transplantation and they were generally older at vitiligo onset. This information is of great importance for the selection of patients and when informing about the chances of improvement after transplantation. Slight hyperpigmentation was common, especially when ultrathin epidermal sheets had been used. No scars or indurations were seen in treated areas. CONCLUSIONS: Transplantations are the methods of choice in stable types of leucoderma. Progressive, widespread vitiligo vulgaris should never be selected for transplantation.

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Pigment Cell Res 2002 Oct;15(5):331-4
Approaches to repigmentation of vitiligo skin: new treatment with ultrasonic abrasion, seed-grafting and psoralen plus ultraviolet A therapy.
Tsukamoto K, Osada A, Kitamura R, Ohkouchi M, Shimada S, Takayama O.
Department of Dermatology, Yamanashi Prefectural Central Hospital, Kofu, Yamanashi, Japan. k-tsukamoto@ych.pref.yamanashi.jp

Vitiligo vulgaris is a common disease throughout the world although its pathogenesis is not yet known. The most frequent treatment used for vitiligo is PUVA (psoralen plus ultraviolet A) and topical steroids but against stable refractory vitiligo, various other surgical techniques have been developed such as autografting, epidermal grafting with suction blisters, epithelial sheet grafting, and transplantation of cultured melanocytes. We have discovered a new method using ultrasonic abrasion, seed-grafting and PUVA therapy. The ultrasonic surgical aspirator abrades only the epidermis of recipient sites. This easily and safely removes only the epidermis, even on spotty lesions or intricate regions which are difficult to remove using a conventional motor-driven grinder or liquid nitrogen. Epidermal seed-grafting can cover more area than sheet-grafting, and subsequent PUVA treatment can enlarge the area of pigmentation with coalescence of adjacent grafts. In this article, we provide a general overview of the current surgical therapies including our method for treating stable refractory vitiligo.

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Int J Dermatol 2002 Aug;41(8):482-7
Rapid initiation of repigmentation in vitiligo with Dead Sea climatotherapy in combination with pseudocatalase (PC-KUS).
Schallreuter KU, Moore J, Behrens-Williams S, Panske A, Harari M.
Department of Biomedical Sciences, Clinical and Experimental Dermatology, University of Bradford, West Yorkshire, BD7 1DP, UK. K.Schallreuter@bradford.ac.uk

BACKGROUND: Low catalase levels and cellular vacuolation in the epidermis of patients with vitiligo support major oxidative stress in this compartment. There is now in vivo evidence for increased epidermal hydrogen peroxide (H(2)O(2)) accumulation in this patient group by utilizing noninvasive Fourier Transform Raman spectroscopy (FT Raman). Epidermal H(2)O(2) can be removed with a topical application of narrow band UVB activated pseudocatalase cream (PC-KUS). (Mn/EDTA-bicarbonate complex, patent No. EPO 58471 1 A), yielding initiation of repigmentation. Dead Sea climatotherapy is another successful treatment modality for vitiligo, but the mode of action has escaped definition so far. METHODS: Epidermal hydrogen peroxide (H(2)O(2)) was assessed in vivo before and after 21 days treatment at the Dead Sea using noninvasive Fourier-Transform Raman spectroscopy. The effectiveness of repigmentation was followed in 59 patients with vitiligo by comparing Dead Sea climatotherapy alone with the combination of Dead Sea climatotherapy/pseudocatalase cream (PC-KUS) as well as Dead Sea climatotherapy/placebo cream. Clinical repigmentation was documented by standardized black/white photography using non-UV coated bulbs as flashlight and by color photography. RESULTS: This study on 59 patients who had vitiligo for an average time of 17 years (range 3-53 years) confirmed in vivo H(2)O(2) accumulation in mM concentrations in the epidermis of untreated patients. Furthermore, we demonstrated a pseudocatalase activity after 15 min of Dead Sea bathing, but the decrease of epidermal H(2)O(2) levels was significantly less compared to narrowband UVB activated pseudocatalase cream (PC-KUS). Initiation of repigmentation was already observed between day 10 and day 16 after a combination of Dead Sea climatotherapy/pseudocatalase cream compared to conventional pseudocatalase monotherapy (8-14 weeks) and Dead Sea climatotherapy alone (5-6 weeks). CONCLUSION: The results of this study show a significantly faster initiation of repigmentation in vitiligo after a combination of short-term climatotherapy (21 days) at the Dead Sea in combination with a pseudocatalase cream (PC-KUS) compared to either conventional climatotherapy at the Dead Sea alone or with placebo cream in combination with climatotherapy. This combined therapy is significantly faster in repigmentation than narrowband UVB activated pseudocatalase cream (PC-KUS) treatment alone. The results of this study support the necessity of epidermal H2O2 removal as well as the influence of solar UV-light in the successful treatment of vitiligo.

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Am J Clin Dermatol 2002;3(5):301-8
Vitiligo: a manifestation of apoptosis?
Huang CL, Nordlund JJ, Boissy R.
Department of Dermatology, University of Cincinnati, Pavilion A, Ohio 45267-0523, USA.

Vitiligo is a common cutaneous disorder that has significant biological and social consequences for those affected. It is characterized by a loss of melanocytes from the epidermis, which results in the absence of melanin, i.e. depigmentation. There are numerous hypotheses about the etiology of vitiligo, but no data to definitively prove one theory over another. It is likely that there are numerous causes for the loss of these melanocytes. One way to approach the identification of the etiology is to determine the mechanism by which the melanocytes are destroyed. The two known mechanisms for the destruction of cells are necrosis and apoptosis. One purpose of this paper is to review the extant data that might suggest which of the two mechanisms is operative against melanocytes in patients with vitiligo. The histological data, and some laboratory data, support apoptosis, rather than necrosis, as the mechanism for removal of melanocytes. Apoptosis can be induced by a variety of factors, including immune cytokines, some environmental chemicals (for example substituted hydroquinones such as monobenzone) or other molecular mechanisms. Current therapies, such as corticosteroids and ultraviolet light, do affect apoptosis in a variety of ways. Confirmation of apoptosis as a mechanism, and identification of how apoptosis is initiated to produce vitiligo, can serve as a basis for devising medications that might stop the progression of the disorder. The problem of vitiligo would be essentially solved if there was a medication that is well tolerated in children, adults and pregnant women, and that would halt the progression of the depigmentation. The study of apoptosis, mechanisms of its induction, and the ways to block apoptosis, is one possible way to find both the causes of depigmentation and medications to prevent its progression.

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J Am Acad Dermatol 2002 May;46(5):727-31
Treatment of vitiligo with the 308-nm excimer laser: a pilot study.
Spencer JM, Nossa R, Ajmeri J.
Division of Dermatologic Surgery, Mount Sinai School of Medicine, New York, NY 10029, USA.

BACKGROUND: Present vitiligo therapies require many months of treatment and often result in disappointing outcomes. Common therapeutic options include phototherapy with psoralens plus ultraviolet A (UVA) radiation and broadband or narrowband UVB radiation phototherapy. Some of these modalities require regular phototherapy sessions several times a week for up to a year to achieve a therapeutic response. Targeted phototherapy with single-wavelength laser light is a treatment alternative that may prove to be a time-efficient and effective therapeutic option for the management of vitiligo. METHODS: This intervention study was designed as a before and after trial with a single arm. Twenty-nine patches of vitiligo from 18 patients (6 males and 12 females) were treated at the start of the study. Vitiligo patches were treated by using a 308-nm xenon-chloride excimer laser. Lesions were treated 3 times a week for a maximum of 12 treatments. Treatment was withheld if sunburn was observed and held until resolution. All patients had untreated vitiligo patches that served as control sites. RESULTS: Twenty-three vitiligo patches from 12 patients received at least 6 treatments and resulted in some repigmentation in 57% of the treated patches. Eleven vitiligo patches from 6 patients received all 12 treatments and resulted in some repigmentation in 82% of the treated patches. Untreated control patches remained unchanged. CONCLUSION: This degree of repigmentation in a period of 2 to 4 weeks is much higher than that achieved with any other present vitiligo therapy. The xenon-chloride excimer laser may represent a new treatment modality for the management of stable vitiligo.

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Clin Exp Dermatol 2002 Mar;27(2):104-10
Psoralen photochemotherapy (PUVA) is only moderately effective in widespread vitiligo: a 10-year retrospective study.
Kwok YK, Anstey AV, Hawk JL.
Photobiology Unit, Department of Environmental Dermatology, St John's Institute of Dermatology, St Thomas' Hospital, London SE1 7EH, UK.

A 10-year retrospective analysis of the use of psoralen photochemotherapy (PUVA) in the treatment of vitiligo was undertaken at the St John's Institute of Dermatology, London, UK. Of 97 patients included in this study, eight had complete or almost complete repigmentation, 59 moderate to extensive repigmentation, and 30 showed little or no response. However, 24 of those who had responded to PUVA with extensive repigmentation did not consider their response satisfactory because of persistence of vitiligo at cosmetically sensitive sites, and poorly matching, speckled repigmentation. Fifty-seven patients who initially improved with PUVA therapy subsequently relapsed, in most cases within a year of stopping treatment. Relapses in 22 patients were on the same cutaneous sites as previously affected, while vitiligo at new sites developed in 20 patients and both new and old sites were affected in a further 15 patients. Patients who retained their pigmentation after 2 years appeared to have a better chance of permanent remission. The only statistically significant prognostic indicator of relapse was patient age at the start of treatment, younger patients tending to retain their pigmentation longer than older patients. This study emphasizes the need for careful patient counselling before PUVA therapy as this treatment seldom achieves extensive repigmentation that is cosmetically acceptable, and treatment response is often followed by relapse.

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Eur J Dermatol 2002 Jan-Feb;12(1):24-6
The effects of vitamin E on the skin lipid peroxidation and the clinical improvement in vitiligo patients treated with PUVA.
Akyol M, Celik VK, Ozcelik S, Polat M, Marufihah M, Atalay A.
Department of Dermatology, Medical Faculty of Cumhuriyet University, 58140-Sivas, Turkey. makyol@cumhuriyet.edu.tr

Solar-simulated UV-irradiation causes changes in the enzymic antioxidant defence system in the human epidermis. The aim of this study was to investigate the effects on the skin lipid peroxidation and clinical improvement in vitiligo patients treated with PUVA. The first group of patients was treated for six months with psoralen plus UV-A (n = 15). The second group of patients was treated for six months with psoralen plus UV-A vs vitamin E (900 IU daily perorally) (n = 15). There was no significant difference in the clinical improvement between the group of patients who were treated with PUVA and vitamin E and the group of patients treated with PUVA alone (p > 0.05). Statistical analysis revealed a significant difference between the levels of lipoperoxides before and after treatment in the first group (p < 0.05), but there was no significant difference between the levels of lipoperoxides before and after treatment in the second group (p > 0.05). According to our results, vitamin E may prevent oxidative distress resulting from PUVA therapy, but does not affect the clinical improvement of the vitiligo lesions.

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Dermatol Surg 2001 Nov;27(11):969-70
Depigmentation therapy with Q-switched ruby laser after tanning in vitiligo universalis.
Kim YJ, Chung BS, Choi KC.
Department of Dermatology, Chosun University Hospital, Gwangju, Korea. yjkim@mail.chosun.ac.kr

BACKGROUND: In vitiligo universalis, repigmentation therapy is seldom effective. Besides, bleaching cream which is often used in depigmentation therapy may lead to several serious complications. OBJECTIVE: Q-switched (QS) ruby laser can destroy melanosomes in melanocytes and keratinocytes by selective photothermolysis. METHODS: We have attempted to destroy melanocytes by using the QS ruby laser after tanning in a patient with extensive vitiligo. RESULTS: The patient had excellent results with no evidence of repigmentation after 1 year. CONCLUSION: Depigmentation therapy with QS ruby laser after tanning is an effective and safe way of removing remnants of normal pigmentation in patients with vitiligo universalis.

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Dermatol Surg 2001 Oct;27(10):873-6
Modified technique of autologous noncultured epidermal cell transplantation for repigmenting vitiligo: a pilot study.
Van Geel N, Ongenae K, De Mil M, Naeyaert JM.
Department of Dermatology, Ghent University Hospital, Ghent, Belgium.

BACKGROUND: Several reports have demonstrated that grafting of autologous melanocytes from normally pigmented donor skin can be used for repigmentation of achromic macules in vitiligo. OBJECTIVE: To investigate a modified approach in which noncultured autologous melanocytes and keratinocytes are grafted on superficially laser dermabraded vitiligo lesions in a suspension enriched with hyaluronic acid. METHODS: Four patients with stable vitiligo were treated using a noncultured melanocyte-keratinocyte suspension. The cellular suspension was grafted on vitiliginous lesions previously dermabraded with a CO2 laser. To improve the viscosity and fixation of the cellular suspension hyaluronic acid was added. Three weeks after grafting, psoralen plus ultraviolet A (PUVA) or ultraviolet B (UVB) therapy was started. Residual leukodermic areas were subsequently retreated. RESULTS: Repigmentation was observed within 2-4 weeks and continued to increase for 3 months after treatment. In all patients, 85-100% repigmentation was achieved. A temporary slight color mismatch was visible in all patients. The most homogeneous repigmentation was obtained 5 months after treatment. CONCLUSION: This modified procedure seems to be a simple and promising treatment for larger vitiliginous areas.

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Dermatol Surg 2001 Oct;27(10):855-6
Epidermal grafting after chemical epilation in the treatment of vitiligo.
Kim CY, Yoon TJ, Kim TH.
Department of Dermatology, College of Medicine, Gyeongsang National University and Gyeongsang Institute of Neuroscience, Chinju, Republic of Korea.

BACKGROUND: Vitiligo on hairy areas like the scalp and eyebrows is frequently associated with leukotrichia and repigmentation by photochemotherapy is usually difficult because of a deficient melanocyte reservoir. Although epidermal grafting to supply melanocytes is very effective for stable vitiligo, hair growth inhibits successful transfer of melanocytes from grafted epidermis in dense hair-bearing regions. OBJECTIVE: To investigate the effectiveness of preoperative chemical epilation to improve the results of epidermal graft by suction blister on hairy areas. METHODS: Two patients who had vitiligo with leukotrichia on the face and scalp were treated with epidermal grafting using suction blister after chemical epilation. Two weeks after the graft they were treated with topical psolaren plus ultraviolet A (PUVA) therapy. RESULTS: Epidermal grafting was performed successfully, and successful repigmentation of the skin with significant improvement of leukotrichia was observed in each of two patients. CONCLUSION: Chemical epilation followed by epidermal grafting is a safe, easy, and effective treatment for vitiligo affecting hairy regions.

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Am J Clin Dermatol 2001;2(3):167-81
Vitiligo. Pathogenesis and treatment.
Njoo MD, Westerhof W.
Department of Dermatology, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.

Vitiligo is an acquired skin disorder caused by the disappearance of pigment cells from the epidermis that gives rise to well defined white patches which are often symmetrically distributed. The lack of melanin pigment makes the lesional skin more sensitive to sunburn. Vitiligo can be cosmetically disfiguring and it is a stigmatizing condition, leading to serious psychologic problems in daily life. It occurs worldwide in about 0.5% of the population and it occurs as frequently in males as it does in females. The cause is unknown, but might involve genetic factors, autoimmunity, neurologic factors, toxic metabolites, and lack of melanocyte growth factors. Since a causative (gene) treatment is not (yet) available, current modalities are directed towards stopping progression and to achieving repigmentation in order to repair the morphology and functional deficiencies of the depigmented skin areas. Many treatments have been used for some time; however; there are some new developments: narrowband ultraviolet (UV) B (311 nm) therapy, the combination of corticosteroid cream + UVA therapy, and the transplantation of autologous pigment cells in various modalities. In widespread vitiligo, residual pigment can be removed by depigmentation agents. Sunscreens, camouflage products, and good guidance may help the patient cope better with the disease.

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J Dermatol 2001 Sep;28(9):461-6
Vitiligo: a retrospective comparative analysis of treatment modalities in 500 patients.
Handa S, Pandhi R, Kaur I.
Department of Dermatology, Venereology & Leprology, Postgraduate Institute of Medical Education & Research, Chandigarh, India.

The major non-surgical re-pigmenting therapies for vitiligo include psoralens and corticosteroids, used both topically and systemically. In an attempt to determine the best therapeutic option, we compared the efficacy of various treatment regimens used in our department for the treatment of vitiligo. We report herein our results with six different regimens used in our clinic. Data from five hundred vitiligo patients who attended the pigmentary disorders clinic at the Nehru Hospital, PGI, Chandigarh, was analysed. For the purpose of analysis, patients were arbitrarily divided into two groups based upon the body surface area (BSA) involved: Group A (<10% BSA involved) and B (>10% BSA involved). Group A was further divided into three subgoups of patients depending upon what treatment they received: R-I [topical clobetasol propionate+sun exposure]; R-II [topical psoralen+sun exposure (topical PUVASOL)]; R-III [topical psoralen+UVA (topical PUVA)]. Group B was also subdivided into three subgroups of patients who received: R-IV [oral dexamethasone pulse therapy + sun exposure]; R-V [systemic psoralen + sun exposure (systemic PUVASOL)]; R-VI [systemic psoralen + UVA (systemic PULVA)]. Patients who had undergone, one of the above mentioned regimens and had a regular monthly follow up until total re-pigmentation or for at least one year, whichever was earlier, were included in the final assessment of the therapeutic efficacy of that regimen. At the end of the study in Group A, 207 (89%) patients out of 232 on R-I; 73 (93%) out of 78 on R-II, and 15 (79%) out of 19 patients on R-III showed moderate to excellent re-pigmentation, respectively. In group B, 45 (81%) patients out of 55 on R-IV, 48 (84%) out of 57 on RV, and 22 (84%) patients out of 26 on R-VI showed moderate to excellent re-pigmentation. Statistically, in Group A, R-I & II were significantly better than R-III. However in Group B, there was no significant difference in the responses to R-IV, V, and VI. A positive family history of vitiligo did not seem to affect the response rate. Potent topical steroids used along with sun exposure and topical PUVASOL were the most effective forms of therapy for localised vitiligo. For the generalised form of the disease, we concluded that all the systemic modalities, oral steroids, PUVASOL and PUVA, are equally efficacious over a period of one year. Phototoxic reactions were, however, more common with PUVASOL.

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Br J Dermatol 2001 Sep;145(3):476-9
Topical calcipotriol as monotherapy and in combination with psoralen plus ultraviolet A in the treatment of vitiligo.
Ameen M, Exarchou V, Chu AC.
Unit of Dermatology, Imperial College of Science, Technology and Medicine, Hammersmith Hospital, Du Cane Road, London W12 0HS, UK.

BACKGROUND: Recent advances in the pathophysiology of vitiligo have demonstrated defective calcium homeostasis in depigmented skin. 1,25-Dihydroxyvitamin D3 may be involved in the regulation of melanin synthesis, and receptors for 1,25-dihydroxyvitamin D3 have been demonstrated on melanocytes. OBJECTIVES: We conducted an open study to determine the efficacy and tolerability of calcipotriol cream as monotherapy and in conjunction with psoralen plus ultraviolet A (PUVA) in the treatment of vitiligo. METHODS: Twenty-six patients with vitiligo affecting 5-40% of their skin were recruited. Twenty-two were treated with twice-daily topical calcipotriol monotherapy (50 microg g(-1)) and four were placed on combination treatment with twice-daily topical calcipotriol 50 microg g(-1) in conjunction with topical or oral 8-methoxypsoralen PUVA three times weekly. RESULTS: Treatment was well tolerated at all sites and no adverse effects were reported. After a therapy time of 3-9 months (mean 6 months), 77% (17 of 22) of those treated with monotherapy showed 30-100% improvement, and three of the four patients on combination treatment showed good response. CONCLUSIONS: Topical calcipotriol appears to be an effective and well-tolerated treatment for vitiligo and can be safely used in conjunction with PUVA, but controlled studies are necessary to exclude the possibility of spontaneous repigmentation.

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Br J Dermatol 2001 Sep;145(3):472-5
Is the efficacy of psoralen plus ultraviolet A therapy for vitiligo enhanced by concurrent topical calcipotriol? A placebo-controlled double-blind study.
Ermis O, Alpsoy E, Cetin L, Yilmaz E.
Department of Dermatology, Akdeniz University School of Medicine, 07070 Antalya, Turkey.

BACKGROUND: 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. OBJECTIVES: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.


 
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