Comparison of efficacy of narrow band UVB therapies with UVB alone, in combination with calcipotriol, and with betamethasoneand calcipotriol in vitiligo

Objective: The purpose of this study is to compare the efficacy of three therapies in the treatment of non-segmental vitiligo: a combination of topical calcipotriol, narrowband-ultraviolet B (NB-UVB), and betamethasone therapies; a combination of NB-UVB and topical calcipotriol; and NB-UVB alone. Material and methods: Forty-five patients with non-segmental vitiligo presenting to our Dermatology clinic were recruited to participate in the study. Patients were randomly divided into three groups. For each patient the size of the depigmented areas was assessed according to the rule of nines. The first group was treated with a combination of topical calcipotriol, NB-UVB, and betamethasone therapies. The second group was treated with a combination of NB-UVB and topical calcipotriol and third group was treated with NB-UVB alone. Since the patients' vitiligo lesions had similar phototypes, all patients were started with 0.1 j/cm², regardless of their skin phototype. The dose of NB-UVB was increased 10% in each session and no further increment was done after reaching 2.5 j/cm². Treatment effectiveness was evaluated according to the percentage improvement in repigmentation. The quality of life of the patients was measured by the Dermatology Life Quality Index (DLQI). Results: The patients were aged from 13 to 55 years (mean: 25.29). The duration of disease ranged from 3 months to 20 years. Family history was positive for vitiligo in 10 patients (22.2%). The percentage of recovery after treatment was 63.33% ± 7.55 in group 1, 60.67% ± 5.75 in group 2, and 46.67% ± 7.98 in group 3. There was no statistically significant difference between groups 1 and 2, and groups 2 and 3, but there was a statistically significant difference between groups 1 and 3 (p = 0.0048). Conclusions: In conclusion, NB-UVB-alone therapy and the combined therapies are effective treatment options in the treatment of vitiligo. Future studies with larger groups are warranted to confirm our results.

Keywords: vitiligo; narrow-band UVB; calcipotriol; betamethasone

Vitiligo is an acquired, idiopathic pigmentation disorder of the skin. Vitiligo-related skin lesions are characterized by well-demarcated and depigmented macules. It is the most common cause of leukoderma in the world ([1]). The pathogenesis of vitiligo may be related to genetic, autoimmune, neuronal and cytotoxic factors ([[1]]). There are several treatment options available for vitiligo, but a definite and ideal treatment of vitiligo has not yet been discovered. Many factors such as age, life style, clinical type of vitiligo, previous treatments and their side effects should be taken into account while tailoring of treatment for vitiligo ([[1], [3]]).

Narrowband-ultraviolet B (NB-UVB) is a band of UV radiation with a wavelength of 311 nm ([4]). UVB induces mitogenesis and migration in melanocytes mediated by several factors such as IL-1, TNF alpha, and leukotriene C4 ([[5]]). Calcipotriol is a synthetic derivative of calcitriol or vitamin D ([7]). Defective calcium transport systems in vitiliginous melanocytes and keratinocytes affect the tyrosinase activity that eventually inhibits melanin formation ([[8]]). Topical corticosteroids are effective in the treatment of limited vitiligo areas and are usually first-line therapy in children ([10]).

In this study we compared the efficacy of three treatments; a combination of topical calcipotriol, NB-UVB and betamethasone therapies; a combination of NB-UVB and topical calcipotriol; and NB-UVB alone.

Forty-five patients with non-segmental vitiligo presenting to our dermatology clinic were recruited for our study. The patients were in the age range of 13 and 55 years, had involvement of a lesion larger than 10% of the body area, and had received no treatment except application of moisturizing cream and sun cream. The participants were randomized over the three treatment regimes. All the patients participating in the study gave informed consent. Patients having cataracts; liver and/or kidney dysfunction; who were pregnant; who had hypercalcemia, hypercalciuria and kidney stones; who had malignancy, or had a history of photosensitivity or photosensitive disorders were not given NB-UVB therapy.

Before starting the treatment, the patient's age, sex, duration of existing lesions, and family history of vitiligo were recorded. A photograph of each patient was taken before and after the treatment. The size of the depigmented areas in each patient was assessed according to the rule of nines. In this system, the body is divided into 11 sections including head, right arm, left arm, chest, abdomen, upper back, lower back, right thigh, left thigh, right leg, and left leg. The sum of these sections accounts for 99% of the body with the genital region making up the last 1%.

Patients were divided randomly into three groups. Group 1 was treated with a combination of topical calcipotriol, NB-UVB, and betamethasone therapies. Group 2 was treated with a combination of NB-UVB and topical calcipotriol. Group 3 was treated NB-UVB alone.

NB-UVB with wavelengths from 311 to 313 nanometers was applied in the Waldmann 5040 KL cabin that contains Waldman f 85/100w-UV 0.1 (310–315 nm) fluorescent tube. Patients received NB-UVB therapy three times a week and the study ended after 6 months of treatment. Since all the vitiligo lesions had similar phototypes, all patients were started on 0.1 j/cm2 regardless of their skin type. The dose was increased by 10% in each session and no further increment was done after reaching 2.5 j/cm2. If the patient developed severe erythema and burns, one therapy session would be skipped, and the next session would be undertaken with the previous dose level. During NB-UVB therapy, patients' eyes were protected with filter glasses. The patients who had eyelid lesions were instructed to close their eyes in the cabin and during the therapy. Sun protective cream was recommended after NB-UVB therapy. Topical moistening cream was given to the patients who had developed dry skin. Patients were followed up during subsequent 6 months after the therapy. The male genital region and melanocytic lesions were covered during therapy. Since topical calcipotriol may block UV, which affects the efficacy of NB-UVB therapy, the calcipotriol was applied to the patients' skin 2 h after therapy.

The effectiveness of the treatment was evaluated according to the percentage improvement in repigmentation. Repigmentation improvement was evaluated as follows: poor ≤25%, moderate = 26–50%, good = 51–75% and excellent ≥75 %. The quality of life was evaluated before and post treatment using the Dermatology Life Quality Index (DLQI). Visual Analogue Scale (VAS) (0–10, 0 = absent, 10 = worst vitiligo) was used to measure the patients' subjective view of the impact of living with vitiligo. The repigmenting effects of the therapies were also measured with VAS by the patients with vitiligo.

The comparison of the groups was carried out using the non-parametric Kruskal–Wallis test. The correlation between categorical features was determined by the chi square test, and constant features were analyzed by Spearman's rank correlation coefficients. In all the statistical analysis, the level of significance was 5% and 1%. SSPS software (version 16) was used for the statistical analysis.

In our study, each group consisted of 15 patients. Of the total 45 patients, 20 were male (44.4%) and 25 female (55.6%); age ranged from 13 to 55 (mean: 2.29). There was no statistical difference in the ages of the group (p = 0.113). The duration of disease ranged from 3 months to 20 years. The demographic characteristics of the participants are given in Table I. In terms of the percentage of recovery after treatment there was no statistical difference between groups 1 and 2, and groups 2 and 3, but there was a statistically significant difference between groups 1 and 3 (p = 0.0048) (Table II) (Figure 1A and B).

Table I. Patients' characteristics.

3 Significant p value < 0.05.

Table II. Recovery rate in groups.

4 Statistical significance: differences between groups with different letters; p < 0.05.

Graph: Figure 1. (A) The patient before treatment with betamethasone plus calcipotriol plus narrow-band UVB therapies. (B) The patient after treatment with betamethasone plus calcipotriol plus narrow-band UVB therapies.

The mean DLQI scores before and after treatment in relation to the treatment efficacy in the groups are summarized in Table III. The mean values of the DLQI in each group after treatment were statistically significant lower than the values before treatment (p < 0.01). The change in VAS scores of the patients during treatment was measured. The mean values of VAS in each group showed a statistically significant decrease after treatment (p < 0.01) (Table III).

Table III. Scores of Dermatology Life Quality Index (DLQI) and Visual Analogue Scale (VAS) before and after treatment.

NB-UVB therapy in vitiligo was first used by Westerhof and Nieuweboer-Krobotova in 1997. They showed the efficacy of UVB in vitiligo patients who had had generalized vitiligo for more than 3 months ([11]). Njoo et al. applied NB-UVB therapy to 51 children, aged from 4 to 16 years. In their study group, 27 patients (53%) developed more than 75% repigmentation ([12]). In a study by Scherschun et al., 11 patients with vitiligo received NB-UVB three times a week. Seven patients (71.4%) who completed the therapy had more than 75% repigmentation ([13]). In our study, the starting dose was 0.10 j/m² and was increased by 10% in each session up to a dose of 2.5 j/m². The mean of the repigmentation rate was 46.67%. The therapy was well tolerated and none of the patients had to discontinue the treatment; this was due to the low starting dose and small increments of dose. Yones et al. compared the efficacy of psoralen-UVA (PUVA) therapy and NB-UVB therapy in a randomized double-blind study of 56 patients with vitiligo. In their study NB-UVB and UVB were found to be superior to PUVA in producing >50% repigmentation ([14]).

In a study by Kanwar et al., 14 generalized vitiligo patients received NB-UVB therapy. After 1-year therapy, 10 patients had significant or complete repigmentation, and four had developed mild to moderate degrees of repigmentation. The repigmentation region had a perfect color matching to the patient's healthy skin. They stated that NB-UVB therapy was effective and safe ([15]). Akman et al. showed that 45% of their patients who received NB-UVB alone therapy developed complete repigmentation after a mean of 48 sessions. The NB-UVB therapy was well tolerated ([16]). In our NB-UVB alone therapy group, the complete or significant recovery rate was 46.67%. Our results were similar to those of Akman et al., but lower than that of Kanwar et al. The latter's higher success rate may be related to their longer therapy duration and their patients being darker skinned.

The combination therapy of NB-UVB and calcipotriol was shown to be more effective than NB-UVB alone. However, there are few studies in the literature concerning combination therapy ([[17]]). The first combined study was undertaken by Dogra et al. in 2003. In their study, they applied NB-UVB to a 20-year-old patient, and increased the dose by 20% in each session. Calcipotriol was applied on the right side and placebo on the left side. After 6 months, there was complete recovery on the right side, but only 50% repigmentation on the left side ([18]). Kullavanijaya et al. performed a comparison study on 20 vitiligo patients. All patients received NB-UVB therapy three times a week, and calcipotriol was applied on the left side. No side effect was seen and 47% of the patients had significant repigmentation with the combined therapy ([17]). Goktas et al. in their study involving 24 patients with generalized vitiligo compared the clinical efficacy of NB-UVB alone and NB-UVB plus topical calcipotriol. The treatment was continued for 6 months. The average response rate was 51% in the combined group, and 39% in the NB-UVB alone group. They concluded that the combined therapy of NB-UVB and topical calcipotriol was more effective than NB-UVB-alone therapy ([19]). In our study, NB-UVB alone therapy and combined therapy of NB-UVB and topical calcipotriol were assessed separately. The repigmentation rate was high in the combined therapy group, but there was no statistically significant difference between these two groups.

In contrast to our study, a prospective single-blinded (investigator) study demonstrated no additional effect of topical calcipotriol on NB-UVB phototherapy in 20 patients with generalized vitiligo ([20]).

Hartmann et al. compared NB-UVB and broad-band UVB phototherapy in combination with calcipotriol or a placebo. The combination of topical calcipotriol and broad-band UVB did not improve the treatment efficacy of UVB phototherapy in nine patients with vitiligo ([21]). In our study, the same significant improvement of the quality of life after treatment is seen as in results of the study by Hartman et al. Nordal et al. confirmed that the combination of NB-UVB and a different drug (tacrolimus ointment) is more effective than NB-UVB treatment alone in patients with vitiligo ([22]).

In our study the recovery rate was 63.33% in the topical calcipotriol, NB-UVB, and the betamethasone therapy group. This group had the best outcome and there was a statistically significant difference between this group and the NB- UVB-alone group. To the best of our knowledge, this is the first study examining the combination of betamethasone plus calcipotriol plus NB-UVB therapies. This combination therapy provides earlier repigmentation with a lower UVB dose and thus, lesser UVB-related side effects are seen. Earlier pigmentation and less side effect will decrease the duration and cost of the treatment.

In conclusion, NB-UVB-alone therapy and combined therapies are effective options in the treatment of vitiligo. The addition of calcipotriol or betamethasone + calcipotriol to the NB-UVB phototherapy is more effective in improvement in skin repigmentation than NB-UVB monotherapy. However, further studies are required that focus on the optimal duration of therapy and the patient's condition over the long term.

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.