In vitro evaluation of a novel topical cream for vitiligo and psoriasis that selectively delivers NB‐UVB therapy when exposed to sunlight

Ultraviolet‐B (UVB) phototherapy is a well‐established mode of treatment for several types of dermatological disease. For psoriasis and vitiligo, narrow band UVB (NB‐UVB) phototherapy is an effective therapy, demonstrating greater efficacy and safety compared to broadband UVB or psoralen plus UVA treatments. While the treatment efficacy of NB‐UVB artificial light sources is well documented, the long term time and cost commitment of the therapy remains a barrier to treatment adherence. Natural sunlight is an ideal source of accessible UVB radiation; however, exposure to natural sunlight generally results in erythema prior to the accumulation of sufficient dosage of therapeutic wavelengths of UVB. This communication describes a novel topical cream designed to selectively deliver NB‐UVB therapy when exposed to sunlight. The topical cream when combined with natural sunlight could offer patients a more convenient phototherapy option for psoriasis and vitiligo, potentially increasing patient compliance.     

Novel topical cream delivers safe and effective alternative to traditional psoriasis phototherapy

In today's environment of shrinking reimbursement and coverage for many health care procedures, phototherapy for psoriasis has experienced a major decline. Once hailed as the cornerstone of psoriasis therapy, the increasing cost and demanding treatment regimen has resulted in low compliance, limiting access to this safe and effective mode of treatment. We have previously reported on the development and in vitro evaluation of a topical cream that selectively filters solar radiation to deliver narrow‐band ultraviolet B. Here, we present the results of a pilot study in psoriasis patients. After an average of 38 sessions, all patients in the treatment arm responded to therapy. In particular, 43% of the treatment group experienced complete clearance and the remainder experienced at a minimum 50% lesion clearance. In contrast, none of the patients in the placebo arm experienced more than 20% lesion clearance. Our preliminary results demonstrate that the novel topical cream could provide a safe, effective, and convenient alternative to artificial light phototherapy.     

Narrow-band ultraviolet B treatment for vitiligo,pruritus, and inflammatory dermatoses

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.     

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.     

Targeted phototherapy in combination with drug therapy for segmental vitiligo

According to the previous reports, segmental vitiligo usually shows a poor response to phototherapy. Here, we report two cases of recent onset segmental vitiligo that showed good or excellent response to targeted phototherapy in combination with drug therapy. These findings suggest that segmental vitiligo can be improved by combination therapy if its onset is recent.     

Combination of 308-nm xenon chloride excimer laser and topical calcipotriol in vitiligo

BACKGROUND: A large variety of therapeutic agents are being used for the treatment of vitiligo, but treatment remains a challenge. Recently, monochromatic phototherapies such as 311-nm narrowband ultraviolet B therapy and 308-nm xenon chloride excimer laser have been reported to be an effective and safe therapeutic option in children and adult patients with vitiligo. Single reports stipulate that the addition of topically applied calcipotriol to phototherapy increases its effectiveness. OBJECTIVE: The purpose of the present pilot study was to determine if the addition of topical calcipotriol increases the efficacy of the 308-nm xenon chloride excimer in the treatment of vitiligo. METHODS: Ten patients with vitiligo with essentially bilateral symmetrical lesions were enrolled in this prospective right/left comparative, single-blinded trial conducted over a 15-month period. All patients received 308-nm XeCl excimer laser therapy three times weekly. Calcipotriol ointment (Daivonex) was applied to lesions on one side of the body twice daily. RESULTS: After 24 treatments (8 weeks), nine patients were evaluated. Eight patients showed evidence of repigmentation on both body sides, with no significant difference between the body side treated with calcipotriol and excimer laser and the side treated with excimer laser alone. The mean repigmentation rate was 22.4% (1-37%). CONCLUSION: The addition of calcipotriol ointment to 308-nm xenon chloride excimer laser phototherapy does not significantly enhance its efficacy. Small additive effects must be investigated in a larger trial.     

Combination of narrow band UVB and topical calcipotriol for the treatment of vitiligo

BACKGROUND: Narrow band ultraviolet B (NB-UVB) phototherapy has been used successfully for the treatment of vitiligo. Recently, topical calcipotriol has also been claimed to be effective, either as monotherapy or as a part of combination therapies. OBJECTIVE: The aim of the present study was to compare the clinical efficacy of NB-UVB and NB-UVB plus topical calcipotriol in the treatment of vitiligo. METHODS: NB-UVB treatment was given to 24 patients with generalized vitiligo three times weekly. Topical calcipotriol cream was only applied to the lesions located on the right side of the body. Treatment was continued for 6 months. Treatment efficacy was evaluated by determining the average response rates of the lesions at 3-month intervals. RESULTS: The average response rates of patients receiving combination of NB-UVB plus calcipotriol and NB-UVB alone were 51 +/- 19.6% and 39 +/- 18.9%, respectively. The median cumulative UVB dose and number of UVB exposures for initial repigmentation were 6345 mj/cm(2) (range; 2930-30980) and 18 (range; 12-67) for the combination therapy, and 8867.5 mj/cm(2) (range; 2500-30980) and 24 (range; 15-67) for the narrow band UVB therapy, respectively. CONCLUSIONS: These findings indicate that concurrent topical calcipotriol potentates the efficacy of NB-UVB in the treatment of vitiligo. This combination not only provides earlier pigmentation with lower total UVB dosage and less adverse UVB effects, but also reduces the duration and cost of treatment as well.     

Comparison of the efficacy of broad‐band targeted UVB phototherapy and topical psoralen with targeted UVA phototherapy in localized vitiligo

Aim of the study is to compare efficacy of targeted broad‐band UVB phototherapy and topical psoralen with targeted UVA phototherapy treatments in localized vitiligo for 3 months prospectively. The cases with symmetrical vitiligo lesions were included in the study. Broad‐band targeted UVB was applied on one side and targeted UVA phototherapy with topical psoralen on the other side. Twenty‐two patients who were diagnosed with localized vitiligo were enrolled in this study. These cases consisted of 6 (27.3%) females and 16 (72.7%) males aging between 17 and 69 (34.22 ± 14.15). Fifty‐four lesions (27 left, 27 right) were compared for treatments. After the first month of the treatments, the sides of the lesions were compared in order to evaluate improvement. Percentages of success were 25% for targeted broad‐band UVB microphototherapy and 75% for topical psoralen with targeted UVA microphototherapy. When the two treatment methods were compared with each other, a significant difference was found in terms of treatment response (P = .017). At the end of the third month, the success rates were 37.5% for targeted broad‐band UVB microphototherapy and 62.5% for topical psoralen with targeted UVA microphototherapy, however a statistically significant difference was not determined between the two treatments (P > .05). Both targeted broad‐band UVB phototherapy and topical psoralen with targeted UVA phototherapy provided repigmentation for localized vitiligo at the end of the third month. Our investigation shows that both treatments are safe and they provide repigmentation with a limited response.     

Tofacitinib cream plus narrowband ultraviolet B phototherapy for segmental vitiligo in a child

Segmental vitiligo often presents in childhood and tends to be more recalcitrant to therapy than generalized vitiligo. Recently, Janus kinase inhibitors have emerged as a promising treatment option, with some reports suggesting that concomitant ultraviolet light exposure may enhance therapeutic response. Here, we present a child with segmental vitiligo who responded rapidly and completely to treatment with tofacitinib cream plus phototherapy.     

Comparison of NB-UVB combination therapy regimens for vitiligo: A systematic review and network meta-analysis

Background

Vitiligo was an autoimmune disease and some guidelines for the management of vitiligo encouraged the use of NB-UVB combination therapies to enhance repigmentation.

Objectives

To compare the effectiveness of current NB-UVB combination regimen at the improvement in repigmentation through a systematic review and network meta-analysis.

Methods

We searched the electronic databases for randomized controlled trials related to NB-UVB combination therapy for vitiligo till October 2022. STATA15.0 software was applied to carrying out data analysis.

Results

A total of 28 eligible studies involving 1194 participants were enrolled in the analysis. The NMA results revealed that compared with NB-UVB, carboxytherapy [OR = 32.35, 95% CI (1.79, 586.05)], Er: YAG laser+ topical 5% 5-FU [OR = 10.74, 95% CI (4.05, 28.49)], needling/micro-needling [OR = 3.42, 95% CI (1.18, 9.88)], betamethasone intramuscular injection [OR = 3.08, 95% CI (1.17, 8.13)], topical tacrolimus [OR = 2.54, 95% CI (1.30, 4.94)], and oral Chinese herbal medicine compound [OR = 2.51, 95% CI (1.40, 4.50)] integrated with NB-UVB were more efficacious in excellent to complete repigmentation response rate (≥75%). Besides, NB-UVB+ Er: YAG laser+ topical 5% 5-FU [OR = 0.17, 95% CI (0.04, 0.67)] and NB-UVB+ needling/micro-needling [OR = 0.24, 95% CI (0.06, 0.88)] were less likely evaluated as ineffective repigmentation response (≤25%).

Conclusions

All combination therapies ranked higher than NB-UVB monotherapy in inducing successful repigmentation and avoiding failed treatment in patients with vitiligo. Comprehensive consideration, NB-UVB+ Er: YAG laser+ topical 5% 5-FU and NB-UVB+ needling/microneedling would be the preferred therapeutic approaches.     

Photo(chemo)therapy for vitiligo

Vitiligo is a common skin disease characterized by loss of normal melanin pigments in the skin and its pathogenesis is still unclear. Treatment modalities include psoralen plus ultraviolet A, narrow-band ultraviolet B (NB UVB) phototherapy, topical and systemic steroids, topical calcineurin inhibitors, topical vitamin D analogues in monotherapy or in association with phototherapy, and surgical treatment. NB UVB (310-315 nm) radiation is now considered as the 'gold standard' for the treatment of diffuse vitiligo, and treatment with two recently introduced UVB sources that emit 308 nm wavelengths, the 308 nm xenon chloride (XeCl) excimer laser and the 308 nm XeCl excimer light, has also been reported to be effective and might be the treatment of choice for localized disease: this treatment modality has been defined as 'targeted phototherapy.'     

Randomized controlled trial comparing the effectiveness of 308-nm excimer laser alone or in combination with topical hydrocortisone 17-butyrate cream in the treatment of vitiligo of the face and neck

Background Vitiligo is a pigmentary disorder which may have disfiguring consequences. Its treatment remains a challenge. Objectives We designed a parallel‐group randomized controlled trial to compare the effectiveness of 308‐nm excimer laser alone or in combination with topical hydrocortisone 17‐butyrate cream in patients with vitiligo unresponsive to previous treatment with topical steroids or narrow‐band ultraviolet (UV) B phototherapy. Methods Consecutive patients aged 18–75 years with nonsegmental vitiligo localized on the face and/or neck lacking response to previous conventional treatment were eligible. In total, 84 patients (44 women and 40 men, mean age 44 years) were randomized to 308‐nm excimer laser phototherapy twice weekly alone or in combination with topical hydrocortisone 17‐butyrate cream twice daily for three periods of 3 weeks followed by a 1‐week steroid‐free interval. The primary outcome was a reduction of at least 75% of the overall lesional areas as judged by automatic image analysis on reflected UV photographs, conducted blind to treatment assignment, at 12 weeks compared with baseline. Secondary outcomes were clearance, and improvements on Physician’s Global Assessment (PGA) and Skindex‐29 scores. Results A total of 76 (90%) patients completed the study. In an intention‐to‐treat analysis, seven [16·6%; 95% confidence interval (CI) 5·3–27·8%] patients in the excimer monotherapy arm and 18 (42·8%; 95% CI 27·8–57·8%) in the combination arm showed ≥ 75% reduction of vitiligo lesions at 12 weeks (χ² test 6·89, P = 0·0087). Clearance was observed in two (4·7%; 95% CI 1·6–11·2%) and nine (21·4%; 95% CI 9·0–33·8%) patients, respectively (Fisher’s exact test P = 0·04). A significant difference also emerged for PGA scores, while no difference was documented for Skindex‐29. Conclusions Recalcitrant vitiligo of the face and neck may benefit from the combination of excimer laser phototherapy with topical hydrocortisone 17‐butyrate cream.     

Narrow-band ultraviolet B as monotherapy and in combination with topical calcipotriol in the treatment of vitiligo

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.     

Evaluation of the effect of narrow band‐ultraviolet B on the expression of tyrosinase,TYRP‐1, and TYRP‐2 mRNA in vitiligo skin and their correlations with clinical improvement: A retrospective study

Narrowband‐ultraviolet B (NB‐UVB) is considered one of the main therapeutic tools in vitiligo, which is able to induce repigmentation and halt depigmentation. However, little remains known about the effect of NB‐UVB on TYR gene family, the main pigmentary genes, in vitiligo patients. To assess the effect of NB‐UVB on expression of some genes related to the pigmentary problem of vitiligo; tyrosinase (TYR), tyrosinase related protein 1 (TYRP1) and tyrosinase related protein 2 (TYRP2), mRNA levels of those genes were quantitatively evaluated by Real‐Time quantitative Polymerase Chain Reaction (RT‐qPCR) in skin biopsies obtained from 30 patients with nonsegmental vitiligo and five healthy controls. Vitiligo patients were classified into two groups; group 1, involving 12 untreated vitiligo patients and group 2, including 18 vitiligo patients treated by NB‐UVB. The levels of TYR, TYRP‐1, and TYRP‐2 mRNAs in untreated group were significantly lower than in control subjects (P < .001). In NB‐UVB treated group, the three genes were significantly higher than in group 1 (P < .001), however, they were still significantly lower than in the control subjects (P < .001). A significant positive correlation was detected between TYR and TYRP‐2 genes in group 2 (P = .03). This study demonstrated that mRNA level of TYR, TYRP‐1, and TYRP‐2, which decreased in vitiligo, was significantly increased upon treatment with NB‐UVB. Accordingly, the mechanism of depigmentation in vitiligo disease and repigmentation by NB‐UVB treatment may be related to the changes in the expression of these genes.     

Does topical tacrolimus ointment enhance the efficacy of narrowband ultraviolet B therapy in vitiligo? A left–right comparison study

Background: Narrowband ultraviolet B (NB‐UVB) therapy has emerged as one of the most favored treatment options in patients with generalized vitiligo. The aim of combining topical agents is to improve the efficacy of NB‐UVB in causing repigmentation in vitiligo. Aims and objectives: The present study aims to study the effect of combining topical tacrolimus to NB‐UVB therapy in causing repigmentation in vitiligo lesions. Methods: This prospective single‐blind study was performed on 80 patients of generalized vitiligo above 12 years of age who had symmetrically distributed vitiligo lesions on the face, trunk or limbs. The patients applied topical tacrolimus 0.1% ointment twice daily on selected symmetrically distributed lesions on the left side of the body. No topical agent was applied on the corresponding lesions on the right side. The patients also received whole‐body NB‐UVB exposure three times every week on non‐consecutive days according to a set protocol. Lesions selected for the comparison analysis were photographed serially and assessed by a single‐blinded observer for the extent or repigmentation achieved. The extent of repigmentation achieved was calculated on the basis of VASI scoring. The time taken for the initial repigmentation to start, the overall repigmentation achieved as well as any adverse effects were noted down and compared between the selected lesions on the two sides. Results: Seventy‐four patients with 234 symmetrical vitiligo lesions were available for comparison analysis at the end of study period. The mean repigmentation achieved on the left‐sided study lesions was approximately 71% (VASI score of approximately 4.0) as compared with 60.5% on the symmetrically distributed right‐sided lesions (VASI score of 3.4). Moreover, the repigmentation started earlier on the study lesions on left side than on the right‐sided ones. No significant adverse events were reported with the combination treatment. Conclusions: Addition of topical tacrolimus increases the extent of overall repigmentation achieved with NB‐UVB therapy in vitiligo and also reduces the cumulative NB‐UVB dose needed to achieve a therapeutic benefit in affected patients.     

Effect of topical calcineurin inhibitors as monotherapy or combined with phototherapy for vitiligo treatment: a meta‐analysis

Vitiligo is a common skin disease for which immunomodulating calcineurin inhibitors have been considered reasonable treatment. We searched the MEDLINE, Embase, and Cochrane central register of controlled trials databases for articles published prior to September 2014. Thirteen studies were included in the meta‐analysis. After pooling the trials, we concluded that calcineurin inhibitors showed a better therapeutic effect on vitiligo than placebo, according to lesion report (RR = 2.62, 95%CI, 1.39–4.93, p = 0.003) and patient report (RR = 1.42, 95%, 0.87–2.31, p = 0.157). Subgroup analysis was performed to determine whether the combination with phototherapy was a source of heterogeneity. The trial sequence analysis indicated that the results of combined therapy by lesion report were reliable and conclusive. However, in the patient report trials, the frequency of lesions on the hand and foot was higher, and the effect of combined therapy was still not significant. Calcineurin inhibitors showed a better therapeutic effect than placebo in the treatment of vitiligo with phototherapy. However, the typical UV‐resistant sites (i.e., hand and foot) were still difficult to cure even with combined therapy. Because of concerns about photocarcinogenesis, the clinical application of combined therapy should be explored with caution.     

他克莫司软膏联合窄谱中波紫外线治疗面颈部白癜风疗效观察

目的:评价外用0.1%他克莫司软膏联合窄谱中波紫外线(NB-UVB)治疗面、颈部白癜风的临床疗效和不良反应.方法:将82例面颈部自癜风患者随机分成3组.A组:外用0.1%他克莫司软膏联合NB-UVB照射.B组:单独给予NB-UVB照射.C组:单独外用0.1%他克莫司软膏.疗程均为16周.试验结束时依据治疗前、后患者皮损的照片进行疗效评价.结果:治疗结束后,A、B、C3组有效率分别为78.6%(22/28),48.1%(13/27),51.9%(14/27);A组有效率与B、C两组相比.差异有统计学意义(P值均<0.05).A组与C组的复色开始平均时间相比,差异无统计学意义(P>0.05),但二者分别与B组相比,差异均有统计学意义(P值均<0.05).A组、c组中患者不同分期皮损的有效率差异有统计学意义(P<0.05),B组差异则无统计学意义(P>0.05).3组患者中不同部位皮损的疗效比较差异均无统计学意义(P值均>0.05).3组患者治疗部位出现灼热感、瘙痒的概率很低,且症状轻微.结论:他克莫司软膏治疗面、颈部白癜风起效快、疗效好、不良反应少,联合NB-UVB照射能进一步提高疗效.