FOCUS ON VITILIGO
|Year : 2014 | Volume
| Issue : 5 | Page : 485-489
|Efficacy of targeted narrowband ultraviolet B therapy in Vitiligo
Department of Dermatology, Government Medical College, Srinagar, Jammu and Kashmir, India
|Date of Web Publication||1-Sep-2014|
CUTIS Skin and Laser Institute, Srinagar, Jammu and Kashmir
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Background: Phototherapy is one of the most effective treatment options in vitiligo. Targeted phototherapy devices are becoming more popular as they offer a lot of advantages over the conventional whole-body phototherapy units. Aims and Objectives: The present study was conducted to assess the efficacy and safety of a targeted narrowband ultraviolet B (NBUVB) device in vitiligo. Materials and Methods: A total of 40 patients of vitiligo were treated with a targeted NBUVB device twice-weekly for a maximum of 30 sessions or until 100% repigmentation, whichever was reached first. The extent of repigmentation achieved was assessed and adverse effects, if any, were also noted down. Results: There were 31 responders (77.5%) who achieved repigmentation ranging from 50% to 100%. The onset of repigmentation was seen as early as the 3 rd dose in some cases and by the 10 th dose in all responders. A total of 97 lesions were treated out of which 45 lesions (46.6%) achieved 90-100% repigmentation. Lesions showing 75% and 50% repigmentation were 14 and 15 in number respectively. 23 lesions failed to show any significant repigmentation at the end of 30 doses. Best response was seen on the face and neck with 20 of the 31 lesions achieving 90-100% repigmentation in this area. Duration of vitiligo was seen to have no statistically significant impact on the repigmentation achieved. Conclusion: Targeted NBUVB phototherapy seems to be an effective treatment option in localized vitiligo with a rapid onset of repigmentation seen as early as 2 nd week of treatment.
Keywords: Phototherapy, treatment, targeted narrowband ultraviolet B phototherapy, vitiligo
|How to cite this article:|
Majid I. Efficacy of targeted narrowband ultraviolet B therapy in Vitiligo. Indian J Dermatol 2014;59:485-9
What was known?
1. Targeted ultraviolet B (UVB) phototherapy is a more recent advancement in the phototherapeutic armamentarium for many dermatological disorders including vitiligo.
2. It is advantageous over whole.body UVB treatment as only the involved skin is irradiated.
| Introduction|| |
Vitiligo is an acquired disorder of skin pigmentation that is associated with tremendous psychological impact on the affected patients. , This impact is more pronounced in people with colored skin as the condition is much more apparent in them.  Among the treatment options available in vitiligo, phototherapy especially narrowband ultraviolet B (NBUVB) is one of the safest and most effective especially in patients with generalized vitiligo. ,, The most important limiting factor of this therapeutic option is the prolonged treatment period required to achieve a significant repigmentation response. In addition, the affected patient needs to come to the phototherapy center thrice a week on non-consecutive days for treatment. Many topical as well as oral agents have also been used in combination with NBUVB to enhance or hasten the repigmentation response. These include tacrolimus, pimecrolimus, calcipotriol, tacacitol, pseudocatalse and placental extract. ,,,,
Targeted phototherapy is the term used when the phototherapeutic device specifically "targets" the lesional skin through special delivery mechanisms while the rest of the skin remains unexposed. An important advantage of this type of phototherapy is that the uninvolved skin remains protected and thus higher energies can be used to achieve a rapid therapeutic effect. , In addition, the treatment can be administered only twice a week or even once a week and each treatment session lasts for seconds only. Therapeutic results obtained are also claimed to be better as there is less contrast between lesional and perilesional skin and the cumulative adverse effects of the whole body irradiation are also avoided.
Many different types of targeted phototherapy devices have been used in vitiligo until date. These include the XeCl excimer laser, excimer lamp and lastly targeted UV devices delivering either broadband ultraviolet B (BBUVB) or NBUVB light. The efficacy of excimer laser and monochromatic excimer lamp has been found to be almost equivalent in terms of causing repigmentation in vitiligo.  Targeted UV light-based therapies employ conventional non-coherent ultraviolet light that is delivered through fiber-optic cable systems specifically to the treatment area. These machines deliver the light energy in seconds and have larger spot sizes. ,, For the present study, we used a portable targeted NBUVB device that uses a short ark metal halide lamp with a filter to produce NBUVB light. The machine delivers NBUVB light over 300-320 nm with a peak at 314 nm [Figure 1].
|Figure 1: (a) Vitiligo on neck. (b) Complete repigmentation after 12 doses of targeted narrowband ultraviolet B treatment|
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| Materials and Methods|| |
This study was conducted in 40 patients of "stable" vitiligo involving less than 5% body surface area (BSA) who were resistant to conventional oral/topical treatment options. For the purpose of the present study "stable vitiligo" was defined as "vitiligo showing no further spread or spontaneous repigmentation over a 3 month period." Patients who were on any topical treatments were given a wash-out period of 3 weeks before enrolment into the study. Patients who had received any other form of phototherapy, patients with photosensitive disorders and patients on any immunosuppressants or immunomodulator drugs for vitiligo were excluded from the study. In addition, pregnant patients and patients with acrofacial vitiligo were also excluded. Ethical clearance was obtained prior to the start of the study and informed consent was obtained from every enrolled patient.
All enrolled patients were of Fitzpatrick Skin Type 3 and 4 and they were treated with a targeted phototherapy device named Levia R professional targeted UVB machine (Lerner Medical Devices Inc., USA). The device delivers targeted NBUVB light with a peak at 314 nm [Figure 1]. The energy range of NBUVB delivered is 5-800 mJ/cm 2 with possible increments of 5 mJ/cm 2 . Delivery of energy is really quick and a dose of 300 mJ/cm 2 is delivered over a span of just 6 s. The machine is a light-weight table-top device weighing just 2.7 kg with a hand-piece of 3 square centimeters in area. In addition, there is a stencil of different shapes and sizes provided with the machine to treat similar-shaped or sized lesions. The machine also provides a separate attachment (Litebrush R ) to treat hairy areas like the scalp and chest/back in males.
All the enrolled patients were treated with twice-weekly exposures to all or some selected vitiligo lesions on non-consecutive days. The initial dose used in every patient was 250 mJ/cm 2 and the energy was increased by 50 mJ/cm 2 after every dose until a faint erythema was obtained. The same dose was then continued until the patient continued to show mild erythema or perifollicular pigmentation. If there was any blistering or painful erythema at any time, the treatment was stopped for 1 week and the dose was reduced by 50 mJ/cm 2 from the last dose received. No topical or oral drug therapy was allowed during the study period and patients were followed-up weekly for any evidence of repigmentation both clinically as well as by repeated digital photographs. Targeted NBUVB was thus continued for a maximum of 30 sessions or complete repigmentation of treated lesions, whichever occurred earlier. Patients who did not show any evidence of repigmentation by the 12 th dose of treatment were not offered further doses and were offered alternate treatment options.
The extent of repigmentation was assessed as per the protocol given in [Table 1]. The results were graded from Grade 1 to Grade 6 as given in [Table 1]. Repigmentation of Grade 5 or 6 (90-100% repigmentation) was labeled as "excellent response" while Grade 3 or Grade 4 repigmentation constituted a "good response." Patients achieving Grade 2 or less (<50%) repigmentation were labeled as poor responders. Adverse events that were monitored included painful erythema, blistering, koebnerization with extension of vitiligo lesions and any others. The repigmentation response was correlated with the duration of the disease, site of the involved lesion and age of the patient. Chi-square test was used for assessing the statistical significance of the results obtained and a P < 0.05 was considered as "statistically significant."
|Table 1: Protocol used to calculate the repigmentation achieved and grading |
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| Results|| |
Most of the patients (39/40) enrolled for the study was suffering from "vitiligo vulgaris" and only 1 patient had segmental/focal type of vitiligo in the study group. Duration of vitiligo ranged from 1 year to 19 years with a mean of 6.42 years.
The age of the enrolled patients ranged from 12 years to 45 years with a mean of 23.4 years. Majority of the patients in the study belonged to the 2 nd and 3 rd decade of life. Female sex was preponderant as there were only 14 males in comparison with 26 females. The age distribution of patients and the response achieved in each age group is given in [Table 2].
Overall, a total of 97 lesions were treated and these were distributed on different parts of the body as given in [Table 3]. For the purpose of this study, no acral lesions were treated or included in the study results.
Compliance to the treatment regimen was excellent and no patient in our group dropped out of the study. The first evidence of repigmentation was seen as early as the 3 rd dose in some cases [Figure 1]. However, the mean number of doses taken for the repigmentation to start was 5.4 (about 3 weeks). No patient who eventually responded to treatment took more than 12 doses to show the first evidence of repigmentation. Both perifollicular as well as marginal pigmentation pattern was seen in the responders, but those showing a poor response could not develop any perifollicular pigmentation.
Complete repigmentation (Grade 6) was achieved in a total of 32 lesions while 13 more lesions showed 90% repigmentation (Grade 5) at the end of the study period [Figure 2]a and b]. Thus, on an overall basis, excellent response (90-100% repigmentation) was seen in 45 (46.4%) lesions. In addition, 14 of the treated lesions showed about 75% repigmentation (Grade 3) while 15 others showed 50% repigmentation (Grade 2). Thus, a good response (50-75% repigmentation) was achieved in 29 lesions (30% of total). In the remaining 23 lesions (23.7%) the repigmentation achieved was 25% or less and the response in these lesions was termed as poor.
|Figure 2: (a) Vitiligo on forearm. (b) Complete repigmentation after 14 doses of targeted phototherapy|
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Time taken to achieve a complete repigmentation of the treated lesion ranged from 4 weeks (8 doses) to 12 weeks (24 doses) with a mean of 13.82 doses. No patient who ultimately achieved a complete repigmentation of the treated lesion needed more than 24 doses to do so. Thus we had some patients in whom the treatment was discontinued after just over a month because the treated lesion had repigmented completely within this time.
Site of the treated lesion seemed to affect the response to treatment and in our study group face and neck area showed the best response followed by the trunk. Out of the 97 lesions treated, 31 lesions were seen on the face and neck area [Table 3]. Out of these, 20 lesions (64.5%) achieved 90-100% repigmentation while 9 more lesions showed a good response (50-75% repigmentation). Thus, only 2 lesions out of 31 on the face and neck area failed to show a significant repigmentation at the end of the treatment period. A total of 27 treated lesions were located on the trunk out of which 11 lesions (41%) achieved 90-100% repigmentation. Percentage of lesions achieving the same amount of repigmentation on upper and lower limbs was 36% and 35.7% respectively [Table 3]. These results were tested for their statistical significance by using Chi-square test and the difference in repigmentation between different sites of the body was found to be statistically significant (Chi-square value of 9.529 and P < 0.05).
We also tried to correlate the response with the duration of vitiligo. Repigmentation achieved in patients with different durations of vitiligo is shown in [Table 4]. Difference in the response between the three groups was tested statistically by using the Chi-square test and was not found to be statistically significant (Chi-square value of 7.75 and P value of 0.1).
The pigmentation achieved was also assessed for the color match with the patient treated. In most of the cases the initial pigmentation was darker than the actual skin tone of the treated patients, but on follow-up the pigmentation went on to match the skin color perfectly.
Adverse effects to the treatment regimen were uncommon and the only adverse reaction noted was intense erythema with a burning sensation that was seen in 4 patients. No blistering reaction was observed in any other patient.
Patients were followed-up for a period of 3 months after the end of treatment regimen to look for the stability of pigmentation achieved. No patient showed any loss of pigmentation achieved over this follow-up period.
| Discussion|| |
Phototherapy has revolutionized the medical management of vitiligo over the last 3 decades and at present, NBUVB phototherapy is considered the treatment of choice in patients with generalized vitiligo. ,, Targeted phototherapy is considered to be more advantageous than whole-body NBUVB treatment especially for localized vitiligo. , This form of treatment is indicated in patients who have a localized vitiligo involving less than 10% BSA and it can be combined with systemic therapies if needed. Among targeted phototherapy devices currently available, excimer laser has been shown to induce the most rapid onset of repigmentation in vitiligo.  The repigmentation achieved with the laser has been seen to be site dependent with the best response seen on the face and neck area. , In addition to excimer laser a monochromatic excimer lamp has also been utilized in the treatment of vitiligo with almost comparable results. ,
As far as the targeted UVB devices are concerned, the UV spectrum delivered varies from one machine to another. These devices include "BClear" that delivers BBUVB, "multiclear" or "dualight" providing UVA and UVB combination and lastly "Bioskin," which gives a NBUVB waveband peaking at 311 nm. Using a BBUVB device Asawanonda et al. demonstrated good results on 29 vitiligo lesions in six patients with the first evidence of repigmentation within 3 weeks and the overall response depending mainly on the site of vitiligo.  In a later study, the authors claimed that the results obtained with the NBUVB spectrum of the device when compared with its BBUVB spectrum were similar in vitiligo.  The authors noted repigmentation in six lesions treated with BBUVB and five lesions treated with NBUVB waveband of the machine at 12 weeks of treatment. Similarity in the overall response to the two different P wavebands was maintained even at 24 th week of treatment.  Another study on targeted BBUVB by Welsh et al. in 12 patients demonstrated an average repigmentation of 66.25% on the face and 31.25% on trunk, neck and genitalia. Onset of repigmentation in this study was seen after an average of 16 sessions (8 weeks) on the face and after 20 sessions (10 weeks) on the trunk and neck. 
Targeted phototherapy with NBUVB has also been labeled as "micro-phototherapy." Lotti et al. reported the efficacy of NBUVB micro-phototherapy in five of the eight patients of segmental vitiligo treated over 6 months.  The device that was used in this study was "Bioskin" which provides an emission spectrum of 300-320 nm with a peak emission at 311 nm. In a later study on the same device, Menchini et al. reported >75% repigmentation in 69.48% of the 734 patients treated over 12 months.  Of these, 112 patients (15.25%) could achieve complete repigmentation of the treated lesions. Treatment with the device was carried out once every 2 week in this study and the first evidence of repigmentation was seen after about 2 months of treatment in the majority of the treated patients.  No significant adverse effects were reported in the study.
We have treated 40 patients with the NBUVB based targeted phototherapy in this study and we have demonstrated an excellent response in the form of 90-100% repigmentation in 46.6% lesions. This is comparable with the results reported with targeted UVB devices in the previous studies. However, we did see an earlier onset of repigmentation in our patients, as early as at 3 rd dose in some cases, with the mean number of doses required being just 5.4 (about 3 weeks). This correlates more with the results achieved with monochromatic excimer light rather than the targeted UVB devices described above. This difference can be explained probably on the basis of the difference in treatment schedule followed. We treated our patients twice every week and kept the 1 st dose constant at 250 mJ/cm 2 with 50 mJ increments at every dose until the onset of erythema/pigmentation. Twice-weekly treatment schedule has been followed by the majority of the authors in clinical studies on targeted phototherapy including monochromatic excimer lamp phototherapy.
Another important observation from our study was that any patient not showing any repigmentation to targeted UVB phototherapy by the 10 th or 12 th dose eventually showed a poor response to treatment. This observation can be of a real practical importance as any patient in whom no repigmentation is demonstrable by the end of 6 weeks of targeted UVB treatment would be unlikely to show any response to treatment eventually and thus would not qualify for continuation of such treatment afterwards.
As with earlier studies on targeted phototherapy, we also saw a statistically significant correlation of the repigmentation achieved with the site of vitiligo. All the previous studies have documented the best repigmenting effect on the face and neck area and that is what was observed in our patients as well. In fact, 64.5% of lesions on the face and neck area showed almost complete (90-100%) repigmentation in our study group. Age of the patients or duration of vitiligo was seen to have minimal effect on the repigmentation response.
The follow-up period of 3 months was too short to really comment on the stability of the pigmentation achieved.
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What is new?
1. Targeted NBUVB phototherapy seems to be one of the most efficacious
treatment options in vitiligo at present.
2. The onset of pigmentation is extremely rapid with the majority of patients
showing the first evidence of repigmentation as early as the 3rd week of
[Figure 1], [Figure 2]
[Table 1], [Table 2], [Table 3], [Table 4]
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