Treatment of vitiligo with khellin liposomes,ultraviolet light and blister roof transplantation

Background Various surgical and non‐surgical methods are available to treat vitiligo. Surgical techniques such as epidermal blister graft transplantation may be effective for the re‐pigmentation of stable, but refractory vitiligo areas. Khellin has phototherapeutic properties that are similar to those of the psoralens, but with substantially lower phototoxic effects and DNA mutation effects. Its penetration into the hair follicles is enhanced by encapsulating it into liposomes. Subsequent activation of the khellin with UV light stimulates the melanocytes in the hair follicles. Objective The first objective was to evaluate the additional value of combining blister roof transplantation (BRT) with khellin in liposomes and ultraviolet light (KLUV) in the treatment of recalcitrant vitiligo patches. The second objective was to assess patients’ satisfaction. Materials and methods Nineteen patients with vitiligo lesions which did not respond to KLUV treatment for at least a year were treated with BRT followed by KLUV. The transplantation was performed by creating blisters with a suction device, preparing the target site with Erbium laser ablation and the actual transplantation. Locations where randomly assigned. A blinded observer established the results. Results Seventy‐five percent of the patients were satisfied with the cosmetic result. All of the patients would recommend the treatment to other vitiligo patients. More than 75% re‐pigmentation of the vitiligo areas was noted in 47% of the patients according to the blinded evaluation of photographs taken before and after the treatment.     

Treatment of vitiligo with oral 5-methoxypsoralen

Thirty-six patients with vitiligo were treated with oral 5-methoxypsoralen (5-MOP) and subsequently exposed to UVA irradiation. The patients were treated once or twice weekly over a period of 2-10 months, taking 40-60 mg of 5-MOP 2 hours before exposure to UVA light. The amount of exposure to UVA light was slowly increased according to the patient's tolerance. Eleven (31%) patients showed remarkable repigmentation of the areas of vitiligo within six months. Overall, 78% of the patients showed effective repigmentation. Areas of vitiligo on the face and trunk were more responsive to treatment than those on the distal part of limbs. Adverse effects due to the drug included 2 patients with nausea and 1 patient with headache. It is suggested that treatment with systemic 5-MOP is effective, safe, and useful in selected cases of vitiligo.     

Treatment of vitiligo with local khellin and UVA: comparison with systemic PUVA

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.     

Long-term results in the treatment of vitiligo with oral khellin plus UVA

This study was performed to assess the effectiveness and short-term and long-term safety of oral khellin plus UVA (KUVA) in patients with vitiligo. Twenty-eight patients (13 males and 15 females; mean age, 34 years; [age range, 15-51 years]) most with extensive generalized vitiligo of more than 6 months duration had received KUVA at sometime during a 14-year period. The response to treatment (i.e. repigmentation of depigmented areas) was rated retrospectively comparing photographs taken before and after therapy and correlation analysis revealed that it was statistically significantly linked to the number of KUVA treatments (r = 0.833, P = 0.001) and to total cumulative UVA dose (r = 0.840, P = 0.001). Of 17 patients who had continued therapy for longer than 3 months, 7 (41%) had a good response (i.e., more than 70% repigmentation of lesional skin) after a mean of 194 treatments (range, 69-386 treatments) and a mean cumulative UVA dose of 2,036 J/cm2 (range, 690-4,411 J/cm2), whereas lower response grades were observed in the patients with lower treatment numbers. The most common short-term side effect was mild nausea, occurring in 8 of 28 patients (29%), and mainly in the first week(s) of treatment. Follow-up assessment at a mean of 40 months (range, 4-110 months) after the end of KUVA therapy available in 23 of 28 patients revealed no skin cancers or actinic skin damage in any patient. These data indicate that KUVA seems to be safe as well as effective for vitiligo, provided treatment is administered long enough.     

Photochemotherapy with topical khellin and sunlight in vitiligo.

In order to evaluate the efficacy of topical khellin the vitiligo macules of one side only were painted in 41 patients with a 2% solution of khellin in acetone and propylene glycol (90 and 10%, respectively) and exposed to sunlight for a period of 4 months with 3 weekly applications and with exposure times up to 90 min. The macules of the other side were treated in 36 of the 41 patients with acetone and propylene glycol only and sun-exposed with the same schedule, while in the remaining 5 patients they were neither treated with khellin or placebo nor sun-exposed. No significant difference was evidenced between the khellin and placebo-treated sides: no excellent result (repigmentation more than 75% of the affected area) was found, and good results (repigmentation more than 50%) were found in 24.9% of khellin- plus sunlight-treated macules and in 22.3% of placebo- plus sunlight-treated macules.     

Epithelial grafting for vitiligo requires ultraviolet A phototherapy to increase success rate

Background Phototherapeutic techniques were introduced into medical practice by the ancient Egyptians. It is considered a cornerstone in the management of resistant vitiligo; yet, failures are very well known. Recently, the introduction of surgical techniques provided a major development in the management of vitiligo and replaced other conventional unsuccessful therapies. Objectives The aim of this work is to find out if phototherapy, which failed to resolve the vitiligo problem in patients, is still required in the treatment strategy after epithelial grafting of the same cases. Methods Twenty‐five vitiligo patients, nonresponding to classic phototherapy, were treated surgically. Ultrathin Thiersch grafts and suction blister grafts were used. Phototherapy using untraviolet A (UVA) bulbs in combination with psoralen or khellin was used postoperatively immediately after take of grafts onto recipient sites. Results In spite of reactivation of depigmentary effects at grafted areas, phototherapy acted as a stimulator for melanocytic proliferation and function and as an immunosuppressant, halting the melanocytic destructive process. The application of UVA phototherapy resulted in successful treatment in the patients receiving it. Conclusion The success of epithelial grafting in patients with vitiligo can be increased by UVA phototherapy.     

Topical calcipotriol as monotherapy and in combination with psoralen plus ultraviolet A in the treatment of vitiligo

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.     

Monochromatic excimer light 308 nm in monotherapy and combined with topical khellin 4% in the treatment of vitiligo: a controlled study

Vitiligo is an acquired depigmentation disorder affecting 1–4% of the world's population. Conventional therapies include steroids, photosensitive topical agents, surgical treatments, and phototherapy. The aim of the study was to evaluate the efficacy of monochromatic excimer light 308 nm (MEL), both as a monotherapy and in combination with khellin 4% ointment in vitiligo. Forty-height patients (36 male and 12 female) affected with vitiligo were enrolled in this open prospective study. Patients were selected and divided into three groups: group I included 16 patients treated with MEL 308 nm once-weekly and oral vitamin E; group II included 16 patients treated with MEL 308 nm once-weekly combined with khellin 4% ointment (MEL-K) and oral vitamin E; group III (control group) included 16 patients treated only with oral vitamin E. Efficacy was assessed at the end of 12 weeks based on the percentage of repigmentation. Group I (MEL-group) showed a moderate repigmentation in 2/16 (12.5%) patients, good repigmentation in 10/16 (62.5%), and excellent repigmentation in 4/16 (25%) patients. Group II (MEL-K group) presented moderate repigmentation in 2/16 (12.5%) patients, good repigmentation in 5/16 (31.25%), and excellent repigmentation in 9/16 (56.25%). Group III (control group) showed a moderate repigmentation in 3/16 patients (18.75%), a good repigmentation in 1/16 (6.25%) patient, while 10/16 (62.5%) patients did not show signs of repigmentation. The clinical response achieved in group I and II was higher compared with group III (control group) without showing significant differences. MEL 308 nm, alone and/or combined with khellin 4% offered encouraging results and it may be considered a valid therapeutic option worthy of consideration in the treatment of vitiligo.     

自体黑素细胞体外培养移植治疗白癜风

目的 探讨自体黑素细胞体外培养扩增和移植治疗白癜风的疗效.方法 用负压吸疱法在白癜风患者正常皮肤区吸疱取皮,用胰蛋白酶消化皮肤制成细胞悬液,在M2黑素细胞选择性培养基中培养,每周传代1次,经4～5次传代,以免疫荧光和多巴胺染色检测培养细胞的纯度和生物学特性.观察培养的自体黑素细胞移植到白癜风患者皮损区后色素生成效果.结果 黑素细胞能在培养基中选择性生长,经4～5周培养,获得纯的黑素细胞,无成纤维细胞和角质形成细胞污染.16例患者28个皮损区接受了移植治疗,病变皮肤面积从2cm²到200 cm²,1个月后移植区出现部分色素,呈淡红色.所有皮损区在移植后3～5个月均有色素再生,色素水平较周围正常皮肤略深或稍浅,6～8个月时色素恢复稳定,颜色与临近正常皮肤接近.87.5%皮损区色素再生面积超过50%.未见瘢痕和其他不良反应.结论 自体黑素细胞体外培养移植治疗白癜风具有效果好、安全、取较小表皮可以治疗较大面积皮损区的优点.     

Narrow-band UVB311 nm vs. broad-band UVB therapy in combination with topical calcipotriol vs. placebo in vitiligo

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 UVB311 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 UVB311 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 UVB311 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 UVB311 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 UVB311 nm, by the end of the study. The DLQI score improved significantly by an average of 28%. Conclusion UVB311 nm therapy was effective in the treatment of vitiligo, whereas broad-band UVB had no effect. Combination with calcipotriol ointment was not superior to UVB311 nm monotherapy. The quality of life significantly improved with narrow-band UVB311 nm phototherapy.     

Vitiligo Therapy with Oral and Topical Phenylalanine with UVA Exposure

The administration of phenylalanine (Phe) combined with UVA exposure was found to be effective in treating vitiligo. Twenty-one patients with vitiligo were divided in two groups: eleven patients were treated with oral L-Phe in a dose of 100 mg/kg body weight and with UVA exposure and ten patients were treated with oral L-Phe in a dose of 100 mg/kg body weight and with UVA exposure. In addition, in the second group, a cream containing 10% L-Phe was applied to the vitiliginous areas. The best results occurred in the second group. No side effects were found in either group.     

Transplant of cultured autologous pure melanocytes after laser-abrasion for the treatment of segmental vitiligo

Segmental vitiligo is a special type of vitiligo with unilateral distribution of lesions and has a stable course. Clinically, many patients with segmental vitiligo have unsatisfactory responses to topical corticosteroid or UV phototherapy. We have developed a technique for the isolation of melanocytes from a small specimen of normally pigmented skin obtained via a suction blister. The melanocytes can be proliferated in culture and then replanted onto laser-abrased vitiliginous areas. We used this procedure to treat 25 patients with segmental vitiligo that were refractory to medical therapy. The repigmented portion of the total treated area amounted to 95-100% in 21 patients and 65 to 94% in 4 patients. The response rate to treatment was 100% in this study. No scarring or other side-effects developed. The results of this study demonstrate that this method is a valuable tool for the treatment of patients with segmental vitiligo.     

Effects of autologous micrografts on stable bilateral vitiligo: A focus on hand lesions

Vitiligo is an autoimmune skin disorder characterized by depigmented patches of the skin associated with, among several factors, dysregulation and death of melanocytes. Currently, the treatment of vitiligo is based both on the arrest of the progression of active disease and on the stimulation of the skin repigmentation. The aim of this study was to assess the effects of autologous micrografts and narrowband ultraviolet B (NBUVB) phototherapy for skin repigmentation of patients with bilateral stable vitiligo. Autologous micrografts are derived from mechanical disaggregation of small pieces of the patient’s own skin, while phototherapy is a strategy treatment already used. Twenty patients with stable bilateral vitiligo were treated, showing a mean percentage rate of 59.1% at baseline. Combined treatment by autologous micrografts and NBUVB was performed only on the lesions of the hands, and the clinical follow up was performed after 3 and 6 months by photographs taken under Wood’s light. After 6 months, we classed 100% of patients as responders. We also reported a mean of repigmentation rate of 36.7% after 3 months and 64.6% after 6 months of treatment. In particular, six of the 20 patients reached a marked repigmentation rate (75–100%), four moderate (51–75%) and 10 mild (26–50%). No adverse effects were observed and no drugs were administrated as co-adjuvant therapy. These results are suggestive of a potential wide use of autologous micrografts associated with NBUVB phototherapy for the treatment of stable vitiligo.     

Autologous melanocyte–keratinocyte suspension in the treatment of vitiligo

Background In stable vitiligo, several techniques of autologous transplantation of melanocytes are used. Autologous melanocyte transplantation of non‐cultured melanocytes is one of those techniques with variable reported outcomes. Objective The objective of this study was to evaluate the response to autologous melanocyte–keratinocytes suspension transplantation in cases of stable vitiligo. Methods A total of 25 cases of vitiligo were treated by autologous melanocyte–keratinocytes suspension transplantation. After 6–17 months, patients’ response was evaluated according to the extent of pigmentation (excellent 90–100%, good 50–89%, fair 20–49% and poor response <20%). Results Of the 25 patients treated, 22 continued the follow‐up period. Five (23%) patients showed excellent response, 7 (32%) good, 6 (27%) fair and 4(18%) showed poor response. Conclusion Unlike transplantation of cultured melanocytes, which requires experience in culture technique, autologous melanocyte–keratinocytes suspension transplantation is an easy economic technique, which may be used in resistant areas of stable vitiligo.     

个体化培养自体黑素细胞移植治疗白癜风

目的 探讨使用个体化培养基进行自体黑素细胞培养移植治疗白癜风的疗效。方法 负压吸疱获取患者正常表皮片,制成细胞悬液,在Hu16黑素细胞选择性培养基中培养。检测黑素细胞分裂时间（DOT）和黑素含量,根据DOT的大小、黑素含量和细胞形态,调整血清、细胞因子浓度及补充内皮素-1,进行个体化黑素细胞培养。经2 ~ 5次传代后收集黑素细胞,白斑区用超脉冲CO2激光磨削后进行黑素细胞移植,随访观察复色效果。结果 共治疗155例稳定期白癜风患者的204处皮损,进行1次移植119例,进行2 ~ 4次移植36例。应用个体化黑素细胞培养后细胞扩增可达50 ~ 80倍。84.80%的皮损复色面积超过50%,其中52.94%的皮损复色面积超过90%,且复色均匀,未见瘢痕及其他不良反应。性别、年龄、病程长短和皮损面积大小对疗效没有影响。节段型白癜风移植疗效好于寻常型白癜风,两组有效率分别为93.62%和82.16%,痊愈率分别为65.96%和49.04%。手臂和腿部的皮损（不包括肘部和膝盖）移植后痊愈率达73.08%,疗效好于躯干、面颈;肢端皮损疗效最差,痊愈率仅为25.93%。结论 个体化培养技术能提高白癜风患者黑素细胞的培养成功率与细胞扩增倍数。体外培养的自体黑素细胞移植治疗稳定期白癜风疗效肯定,用少量供皮区即可治疗大面积皮损,值得临床应用。     

Treatment of vitiligo with the 308-nm excimer laser: a pilot study

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.     

自体培养黑素细胞移植联合窄谱中波紫外线治疗白癜风疗效观察

目的评估自体纯培养黑素细胞移植联合窄谱中波紫外线(NB-UVB)治疗白癜风的临床疗效。方法应用自体纯培养黑素细胞移植治疗44例非节段型白癜风患者,其中23例患者在移植后2周进行NB-UVB治疗。结果共移植治疗了44例患者,其中联合NB-UVB组23例,两组中(联合NB-UVB组和单纯移植治疗组)获得较好复色效果(复色面积>50%)的患者分别为86.9%、76.2%,有统计学差异(P<0.05);两组的平均复色率分别为78.9%、70.0%。面颈部获得较好复色效果的患者分别为92.3%、90.9%,两组间对比无统计学差异;躯干部获得较好复色效果的患者分别为80.0%、60.0%,两组间对比有统计学差异(P<0.05)。结论自体纯培养黑素细胞联合NB-UVB是治疗白癜风的有效方法之一,且NB-UVB能够提高移植的疗效,尤其是对于局限于躯干的皮损。     

加味桃红四物汤治疗白癜风的临床及实验室研究

目的 观察加味桃红四物汤治疗白癜风的效果并探讨其作用机制。方法 白癜风患者243例，用加味桃红四物汤口服液，每次10mL，3次／d，口服。体外培养的正常人黑素细胞以含药血清作用后测定细胞酪氨酸酶活性、黑素含量和细胞增殖。结果 临床观察显示243例白癜风患者服用加味桃红四物汤后，治愈26例(10．7％)，显效66例(27．2％)，有效76例(31．3％)，无效75例(30．8％)；实验结果显示加味桃红四物汤的含药血清能上调酪氨酸酶活性，提高黑素含量，促进黑素细胞增殖。结论加味桃红四物汤治疗白癜风有明显疗效，其作用可能与刺激黑素细胞黑素合成、上调酪氨酸酶活性、促进细胞增殖有关。     

Phototherapie bei schwerer atopischer Dermatitis Vergleich zwischen herkömmlicher UVA1-Therapie, UVA1-Kaltlicht- und kombinierter UVA-UVB-Therapie

Severe atopic dermatitis, especially when involving the face, does not respond well to conventional therapy. In the present prospective randomized trial, we compared therapeutic efficiency of medium-dose UVA1, medium-dose cold light UVA1 (15 treatment courses with 50 J/cm2 each) and combined UVA-UVB phototherapy. Four (13.3%) of 30 UVA1 treated patients, one (3.4%) of 30 UVA1 cold light treated patients and three (30%) of 10 patients treated with combined UVA-UVB discontinued therapy course before finishing treatment protocol because skin status did not improve or even deteriorated. In the other patients treated over a period of three weeks, skin status improved significantly or even cleared completely in 80.8% of UVA1 treated and in 89.7% of UVA1 cold light treated patients resulting in a significant decrease of the SCORAD-Score (UVA1 group from 68.6 +/- SD 10.9 to 29.8 +/- SD 7.1 and UVA1 cold light group from 72.5 +/- SD 13.4 to 23.8 +/- SD 11.6; p < 0.05 each). In the UVA-UVB treated group, the SCORAD-Score also decreased (from 71.0 +/- SD 9.4 to 41.6 +/- 10.5), but significantly less than in both UVA1 treated groups (p < 0.05 each). Four weeks after completing therapy UVA1 treated patients showed a prolonged therapy benefit as compared to UVA-UVB treated patients. Plasma levels of eosinophil cationic protein and soluble interleukin-2 receptor significantly decreased under UVA1 phototherapy but not under UVA-UVB therapy. Compared to conventional UVA1 phototherapy, UVA1 cold light phototherapy showed advantages due to the absence of potentially proinflammatory effects based on temperature-induced increase of skin blood flow (quantified by Laser doppler scanning) and increased sweat production (determined by the patient using a visual analog scale).