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 Table of Contents  
REVIEW ARTICLE
Year : 2015  |  Volume : 2  |  Issue : 1  |  Page : 9-20

Narrowband ultraviolet B and beyond: Evolving role of phototherapy in vitiligo


Department of Dermatology, Venereology and Leprology, Postgraduate Institute of Medical Education and Research, Chandigarh, India

Date of Web Publication26-Jun-2015

Correspondence Address:
Sunil Dogra
Department of Dermatology, Venereology and Leprology, Postgraduate Institute of Medical Education and Research, Sector 12, Chandigarh - 160 012, Punjab
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/2349-5847.159387

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  Abstract 

Vitiligo is an acquired depigmentation disorder with great impact on patient's appearance and quality of life. Till date, the etiology of vitiligo remains elusive, which makes it difficult to have curative therapies. Photochemotherapy (psoralen and ultraviolet A) long remained the mainstay of treatment of vitiligo, until the advent of narrowband ultraviolet B (NBUVB) phototherapy, which revolutionized the treatment of vitiligo with better results, tolerability and side effect profile than the former. It has been used favorably, both alone as well as in combination with other agents like topical calcineurin inhibitors, Vitamin-D analogs, oral and topical corticosteroids, antioxidants, etc. Recently, various new phototherapeutic modalities like excimer light and laser have come into use with encouraging results. In this article, we review the journey of NBUVB so far and highlight the current status of other new phototherapy modalities in the treatment of vitiligo.

Keywords: Excimer laser, excimer light, narrowband ultraviolet B, phototherapy, vitiligo


How to cite this article:
Arora AK, Dogra S. Narrowband ultraviolet B and beyond: Evolving role of phototherapy in vitiligo. Pigment Int 2015;2:9-20

How to cite this URL:
Arora AK, Dogra S. Narrowband ultraviolet B and beyond: Evolving role of phototherapy in vitiligo. Pigment Int [serial online] 2015 [cited 2019 May 22];2:9-20. Available from: http://www.pigmentinternational.com/text.asp?2015/2/1/9/159387


  Introduction Top


Vitiligo is an acquired disorder of depigmentation characterized by loss of melanocytes from the epidermis affecting 0.1-4% of the world's population. [1],[2],[3],[4] It is a psychologically devastating disease with a significant impact on a patient's quality of life. [5],[6],[7],[8] There are multiple hypotheses regarding the etiopathogenesis of vitiligo, with most evidence supporting autoimmune, cytotoxic, oxidative stress and neurohumoral mechanisms, [9],[10] and current treatment modalities attempt to address one or more of these possible etiologies. [11],[12] Psoralen and ultraviolet A (PUVA) introduced in 1948, remained the mainstay of vitiligo management, [13] until Westerhof and Nieweboer-Krobotova,[14] in 1997, introduced narrowband ultraviolet B (NBUVB) in the treatment of vitiligo. NBUVB has effectively replaced PUVA therapy due to its superior efficacy and better side-effect profile. [14],[15],[16] Lately, targeted phototherapy (excimer light and laser), [17],[18] and helium-neon laser (low-level laser therapy), [19] especially for localized vitiligo, have come into use. In this article, we review the existing literature about the current status of various modalities of phototherapy individually and in combination with other therapies in the treatment of vitiligo.


  Historical Aspects Top


The first report of the use of 'phototherapy' in the treatment of skin disorders dates from 1400 BC from India when patients with vitiligo were given certain plant extracts, Ammi majus and Psoralea corylifolia (whose active ingredients included psoralens) and then exposed to the sun. [20] The modern day phototherapy came into existence in 1903 when Niels Finsen used UV irradiation for treating lupus vulgris. [21] It was a long journey from use of plant extracts with sunlight exposure to use of PUVA therapy for psoriasis in 1974. [22] In 1978, came the broadband UVB for the treatment of psoriasis but could not achieve popularity for the lack of efficacy. [23] Meanwhile in 1988 van Weelden et al. [24] and Green et al. [25] introduced NBUVB for psoriasis, which in 1997 was used for the 1 st time in treatment of vitiligo. [14] The beginning of 21 st century saw the advent of excimer laser and excimer light in the treatment of vitiligo which overcame the shortcomings of NBUVB, but at the cost of being more expensive and inability to treat large areas.

Since NBUVB has overall surpassed PUVA in the treatment of vitiligo, [26] the latter is not discussed in this article.


  Narrowband Ultraviolet B: The Journey so Far Top


Equipment: The phototherapy unit and the latest handheld devices

A potential advance in UVB-based phototherapy has been the introduction of fluorescent bulbs (Phillips model TL-01) that deliver UVB in the range of 310-315 nm, with a peak at 312 nm. It has a relatively narrow spectrum of emission which when compared with the older broadband UVB source has a reduction in erythemogenic wavelengths in the 290-305 nm range and 5-6 fold increased emission of the longer UVB wavelengths. A wide variety of TL-01 equipment is routinely available [Table 1].
Table 1: Types of NBUVB equipments available


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Narrowband ultraviolet B phototherapy cabins contain fluorescent TL-01 (100 W) tubes as the source of irradiation. NBUVB cabins available commercially either incorporate TL-01 alone or in combination with UVA tubes. Recently available Home phototherapy unit, SS-01UV phototherapy instrument (Shanghai Sigma High-tech Co. Ltd, Shanghai, China) bears two Philips TL-9 W/01 lamps. The equipment delivers NB-UVB rays of wavelength spectrum 310-315 nm, with a maximum of 311 nm and radiant intensity of ~ 10 mW/cm 2 , over a 9 × 7 cm area for the therapy of localized body areas. [27]

Mechanism of action of narrowband ultraviolet B

Narrowband ultraviolet B may exert its effects in vitiligo in a two-step process. Both steps may occur simultaneously, the first being stabilization of the depigmenting process and the second, stimulation of residual follicular melanocytes. [28],[29]

Immunomodulation

The well-documented immunomodulating effects of UV radiation can explain the stabilization of the local and systemic abnormal immune responses, thereby stabilizing depigmentation. [30] The major molecular target for UVB is nuclear DNA, with absorption by nucleotides leading to induction of various DNA photoproducts, notably pyrimidine dimers. [31] NBUVB has been shown to induce immunosuppressive effects including induction of interleukin-10, reduced natural killer cell activity, and lymphoproliferation. [32],[33],[34] It also induces isomerization of urocanic acid from the trans to the cis form, which may be important in the immunomodulatory effects of NBUVB. [35]

Migration of melanocytes from the outer hair root sheath

It is likely that NBUVB, similar to PUVA therapy, stimulates the dopa-negative, amelanotic melanocytes in the outer hair root sheaths, which are activated to proliferate and migrate outward to adjacent depigmented skin resulting in perifollicular repigmentation and subsequently these melanocytes migrate downward to the hair matrices to produce melanin. [29] This was substantiated recently by Awad, who reported that melanocyte precursors can be demonstrated histopathologically and immunologically on tissue samples after ultraviolet therapy that are capable of proliferation and migration into depigmented epidermis to repopulate it with new generations of melanocytes. [36]

Stimulation of basic fibroblast growth factor

Wu et al., demonstrated that NBUVB irradiation stimulates the release of basic fibroblast growth factor (bFGF) and endothelin-1 (ET-1) from keratinocytes, which induces melanocyte proliferation. They also found that NBUVB irradiation stimulates the expression of focal adhesion kinase and matrix metalloproteinase-2 (MMP-2) in melanocytes. This leads to enhanced melanocyte migration and overcomes the deleterious effects of vitiligo associated IgG on cell migration, melanin formation, and tyrosinase expression. [37],[38]

Role of Vitamin-D

Of late, the role of calcium imbalance, [39] Vitamin-D receptor-Apa-1 polymorphism, [40] and low levels of circulating 25-OH Vitamin-D [41] has been implicated in the etiopathogenesis of vitiligo. Molecular studies have shown that Vitamin-D modulates melanogenesis at cellular level by inducing tyrosinase enzyme and immature melanocytes in bulge region to produce melanin. [42],[43] Interestingly, patients receiving NBUVB have shown an increase in the serum levels of 25(OH) Vitamin-D indicating the role of Vitamin-D in NBUVB-induced repigmentation. [44]

Dosing schedule

Correctly dosing a UV-based therapy regimen is of immense importance while treating patients with vitiligo. Photoadaptation refers to the phenomenon by which increasing doses of radiation (in this case, UV radiation) after initial treatment are required to cause the same level of effect on the skin. This phenomenon is seen in about two-thirds of patients with vitiligo. [45] In this regard, minimal erythema dose (MED) testing is often done, which requires incremental doses of UVB to be irradiated on small areas of the skin until erythema is noted. It has been shown that there is an increase in MED (about 49% on an average) with successive treatments. [45] This forms the basis of gradually increasing the radiation dose in successive treatments. Hexsel et al. [45] also showed that there was a greater degree of UV-induced DNA damage on the vitiliginous skin as compared to normal skin, after receiving same degree of radiation exposure, as shown by presence of 40-45% more of cyclobutane pyrimidine dimers (CPD) per megabase of DNA (which indicate DNA damage) in vitiliginous skin as compared to normal skin. However, the rate of clearance of CPD Dimmers (that indicate DNA repair) was same in vitiliginous skin and normal skin. Thus, patients with vitiligo should be treated on a 48-h dosing schedule to allow adequate DNA repair to take place, and 24-h dosing schedules should be avoided.

Dosing regimen

There are two dosing regimens that are most commonly used; one based on the calculation of MED and the other based on Fitzpatrick skin type [46],[47] [Table 2] and [Figure 1].
Table 2: Dosing guidelines schedule for NBUVB


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Figure 1: Treatment algorithm of narrowband ultraviolet B therapy in vitiligo.[47] *Means if treatment taken 5 times a week or daily

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However, the doses can be modified depending on local experience and skin type tolerance.

Efficacy of narrowband ultraviolet B in vitiligo

In 1997, Westerhof and Nieuweboers-Krobotova, [14] in their comparative study, showed that 67% of patients undergoing NBUVB phototherapy showed repigmentation compared with 46% of patients receiving topical PUVA after 4 months of therapy. Yones et al.[48] compared twice weekly NBUVB to PUVA therapy in two groups of patients with vitiligo and showed that NBUVB treatment resulted in greater than 50% repigmentation in 64% of patients, while PUVA resulted in a similar degree of pigmentation in only 36% of patients. In addition, the color match for NBUVB was noted to be superior to PUVA. [48] Another study by Bhatnagar et al.[49] compared the mean repigmentation for therapy resistant sites (hands and feet) in patients exposed to NBUVB versus PUVA; it showed that after approximately 6 months of treatment (thrice weekly), 68% of repigmentation was possible using NBUVB versus 54% using PUVA. [49] Besides better results, cosmetically better color match and stability of repigmentation, there are many other advantages of NBUVB therapy over PUVA [Table 3].
Table 3: Advantages of NBUVB over PUVA[15,16,49]


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Njoo et al. in a study of 51 children with vitiligo reported more than 75% overall repigmentation in 27 patients (53%) after 1-year of treatment with NBUVB. [50] In 2005, Kanwar and Dogra [51] studied the efficacy of NBUVB in 26 children with generalized vitiligo where patients were treated 3 times/week with NBUVB for a maximum period of 1-year. At the end of 1-year of therapy, 15 (75%) patients developed marked to complete repigmentation whereas moderate and mild repigmentation was noted in four (20%) and one (5%) patients, respectively. An average of 34 (±2) treatment visits were required to achieve 50% repigmentation. Thus, they concluded that NBUVB is an effective and well-tolerated treatment option for childhood vitiligo. [51]

Natta et al. [52] found NBUVB to be effective in 42% patients recalcitrant to topical therapy and PUVA. The perifollicular pattern has been shown to be the most common pattern of repigmentation associated with NBUVB as is also seen with other UV based therapies like PUVA therapy and excimer laser. [53],[54]

Home based phototherapy

Recently, home based NBUVB regimens, using instruments like SS-01 UV phototherapy instrument, Dermfix 1000™ NBUVB and Waldmann™ NBUVB 109, have been tried with the advantage of ease of application at home, thereby, avoiding frequent visits to a hospital-based phototherapy unit over several months. This modality makes phototherapy available to individuals who cannot afford this treatment because of logistical reasons; however, it may not be financially affordable by patients in resource poor developing countries. It is a useful option for localized lesions and can be used to target new lesions at the earliest. Shan et al. [55] reported excellent repigmentation in 27 of 36 cases with face and neck lesions, 16 of 43 cases with truncal vitiligo and 9 of 34 patients with limb lesions following treatment with SS-01 UV phototherapy. Lesions on the hands and feet were, however, resistant to treatment. Eleftheriadou et al. [56] did a pilot study (HI-Light trial: Home Intervention of Light therapy) to assess the efficacy of home based phototherapy and the feasibility of large multi-center trial of handheld NBUVB phototherapy for the treatment of vitiligo at home. Authors demonstrated a strong willingness of participants in the study, very good treatment adherence and repigmentation rates providing evidence of feasibility for a definitive trial with comprehensive training package and treatment protocol.

Patient selection and long-term prognosis

Certain factors determine good patient response to NBUVB and should be kept in mind while selecting patients for phototherapy and discussing prognosis with the patients. These factors have been enumerated in [Table 4].
Table 4: Factors determining good response to NBUVB in vitiligo[57,58]


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As far as the stability of repigmentation with NBUVB is concerned, not enough long-term studies are published on this in the literature. Sitek et al. [59] found that 11 of 31 patients with generalized vitiligo achieved stable repigmentation; however, only five patients (16%) experienced >75% stable repigmentation 2 years after cessation of, up to 1-year of phototherapy. Scherschun et al. [60] reported that two out of six patients successfully treated with NBUVB experienced relapses, one during treatment, and one shortly after cessation of treatment. For the other four patients, remission was reported however, neither the duration of follow-up nor the extent of vitiligo was mentioned in the study. Natta et al. [52] reported relapse of disease in four out of nine patients who had achieved >50% repigmentation in follow-up of 3-24 months post-treatment. [52]

Combination therapies

Treatment with NBUVB in combination with topical calcineurin inhibitors (TCIs), topical Vitamin-D analogs (VDAs), antioxidants and other therapies has attracted the interests of various physicians all over the world. Newer agents like afamelanotide are being developed and combined with NBUVB. [61] These combination therapies aim to: (i) synergistically improve the efficacy; and (ii) shorten the duration and total dosage of light therapy with earlier and greater total repigmentation.

Narrowband ultraviolet B and topical calcineurin inhibitors

Topical calcineurin inhibitors have been studied in combination with NBUVB by various authors. [62],[63],[64],[65],[66],[67],[68] TCIs are presumed to induce repigmentation by modulating the immune response as well as by inducing melanocyte prolifetation and migration. Tacrolimus has been found to suppress levels of tumor necrosis factor-alpha (TNF-α), [69],[70] a pro-inflammatory cytokine, [71] which also suppresses melanin production. [72] Tacrolimus may also stimulate melanocyte proliferation (via stem cell factor, which is lower in vitiliginous lesions), [70],[71] migration (via MMP-9) [73] and melanin synthesis. [74] ET-1 that is increased by phototherapy augments the proliferation and migration of melanocytes and hence NBUVB and topical calcineurin inhibitors exhibit synergism. [72]

Two randomized controlled trials by Nordal et al. [62] and Esfandiarpour et al. [63] have reported a statistically significant improvement in NBUVB efficacy by combining it with TCIs. Nordal et al., treated half-side of patients with tacrolimus ointment (0.1%) once daily and half-side with placebo ointment and gave whole body NBUVB twice or thrice weekly for at least 3 months. The median repigmentation was greater on the tacrolimus side as compared to the placebo side (42% vs. 29%; P = 0.005). [62]

Esfandiarpour et al., treated two groups of 25 patients each NBUVB thrice a week for 3 months. In addition to phototherapy, one group applied pimecrolimus 1% cream twice a day and the control group applied placebo cream. After 12 weeks of treatment, repigmentation of the facial lesions was higher in patients treated with combined pimecrolimus and NBUVB compared with the placebo plus NBUVB group (64.3 vs. 25.1%) (P < 0.05%). There was no statistically significant difference in the repigmentation rate between the two groups on other body areas. [63]

Other studies with smaller sample size have found better pigmentation in NBUVB and tacrolimus arm although the difference was not statistically significant. [64],[66] In a recent study from India, though repigmentation was slightly better in the lesions treated with combination of NBUVB and tacrolimus than phototherapy alone (33% vs. 28%), the overall difference was not statistically significant. [65] However, more than 50% lesions were at resistant sites in this study.

There is a perceived risk of skin carcinogenesis with the combination of UVB exposure and TCIs, but Tran et al. [75] and Park et al. [76] have separately shown that the combination of TCI with NBUVB is safe on long-term basis and is not associated with increased risk of carcinogenesis.

Vitamin-D analogs

Vitamin-D analogs are also believed to induce repigmentation in vitiligo by a combination of immune modulation and effects on melanocytes. Immunomodulatory mechanisms entail induction and recruitment of T regulatory cells, [77] inhibition of T cells and proinflammatory cytokines such as TNF-α and interferon-g, [78] and inhibition of T-cell infiltration into the skin by suppressing cutaneous lymphocyte-associated antigen expression on T cells. [79],[80] VDAs also play a role in melanocyte differentiation, maturation, [78] migration [81],[82],[83] and melanogenesis, [78],[84] or by modifying defective calcium homeostasis in the epidermal unit. Both calcipotriene and its vehicle have been reported to have a photoprotective effect. [64],[65]

Therefore, they should not be applied immediately before irradiation. They may be applied at any time up to 2 hours before or immediately after irradiation. [85],[86],[87]

In 2003, Dogra and Parsad [88] first reported that the combination of NBUVB with calcipotriene in the treatment of vitiligo is effective and well-tolerated and results in faster pigmentation. Leone et al. [89] found greater mean repigmentation scores at all monthly follow-ups during 6 months of treatment with twice weekly NBUVB and once daily 4ug/g tacalcitol ointment (P < 0.0005). Goktas et al. [90] reported statistically significant better results with combination (NBUVB + calcipotriol) therapy versus NBUVB alone (51% vs. 39%, P = 0.0006).

However, various other studies [91],[92],[93],[94] have reported no additional benefit of combining VDAs with NBUVB. Therefore, further studies are required to reach a definite conclusion regarding the synergistic effect of these two modalities.

Oral and topical antioxidants

The role of increased oxidative stress in the pathogenesis of vitiligo has led to the use of oral as well as topical antioxidants in the treatment of vitiligo. [10],[95] Topical preparations containing catalase and superoxide dismutase have been studied with NBUVB in several case series. Topical application of pseudocatalase (Mn/ethylenediaminetetraacetic acid-bicarbonate complex) and calcium in combination with low-dose broadband UVB resulted in complete repigmentation on the face and back of the hands in 90% of patients. [95] Elgoweini and Nour El Din [96] concluded that mean number of treatments required to achieve >50% repigmentation was decreased (16 vs. 20 sessions) by adding oral antioxidants to NBUVB. Dell'Anna et al. [97] found that a tablet containing Vitamins E and C, alpha-lipoic acid, polyunsaturated fatty acids and cysteine monohydrate resulted in more subjects achieving >75% repigmentation compared to NBUVB alone (47% vs. 18%, P < 0.05). In another study, NBUVB was combined with oral administration of polypodium leucotomus extract, which is known to have antioxidative and immunomodulating properties. In the combination treatment group, a trend towards an increased repigmentation in the head and neck area was observed, which nearly reached statistical significance. [98]


  Miscellaneous Top


Afamelanotide

Afamelanotide is a potent and longer-lasting synthetic analog of naturally occurring melanocyte stimulating hormone. In a recent study involving 4 patients, Grimes et al. [99] showed that combined therapy of NBUVB and afamelanotide is likely to promote melanoblast differentiation, proliferation and eumelanogenesis leading to faster and deeper repigmentation (at least > 50%) in each case within 2 days to 4 weeks.

5-fluorouracil

In a recent study, multiple sessions of intra-dermal 5-fluorouracil have also shown to improve NBUVB efficacy, with 48% of subjects achieving > 75% repigmentation compared to 7% of subjects treated with NBUVB alone. [100]

Laser

Erbium laser dermabrasion has been hypothesized to result in a greater depth of radiation penetration into the dermis, where it can stimulate melanocyte stem cells and also result in delivery of greater doses of radiation. [101] This principle was proven effectively when traditionally UV-resistant sites on the hands, feet, and bony prominences were treated with NBUVB with prior Erbium laser dermabrasion. Statistically significant results were obtained with 46% of lesions achieving >50% repigmentation with preceding 2940-nm erbium laser dermabrasion compared to 4.2% of control lesions (P < 0.0001). [101] However, adverse effects like delayed healing (up to 3 weeks in one patient), edema lasting for 2-15 days when extremities were treated, and hypertrophic scarring hampered the overall patient satisfaction. Ablative fractional CO 2 laser treatment prior to NBUVB has also shown to significantly improve its efficacy on the hands and feet in subjects refractory to conventional therapies, based on physician and patient improvement scores. [102]

Shin et al. hypothesized that fractional CO2 laser improved NBUVB efficacy as various cytokines and growth factors that may induce melanocytes are secreted as part of the wound healing process following laser surgery. [102] Adverse effects like pain, burning sensation, erythema/edema and crusting were noticed after laser treatment; however, they subsided in few days. [102] They, unlike Bayoumi et al., [101] did not report scarring with prior laser treatment.

These studies suggest a need to explore the synergistic role of lasers with NBUVB in the treatment of vitiligo, especially on traditionally UV-resistant sites.

Oral minipulse

Rath et al.[103] compared four treatment groups of patients with progressive vitiligo: steroid oral minipulse (OMP) alone, betamethasone in a dose of 0.1 mg/kg body weight twice weekly on 2 consecutive days for 3 months followed by tapering of the dose by 1 mg every month over the following 3 months, OMP with PUVA, OMP with NBUVB, and OMP with broadband-UVB. The results showed that OMP was not useful on its own but had some value as an adjuvant therapy for PUVA and NBUVB. [103]


  Adverse Effects of Narrowband Ultraviolet B Top


Although NBUVB has notably fewer adverse effects when compared to PUVA therapy, it has been known to cause phototoxic reactions and tanning. [104] Erythema is the most common early side effect with incidence varying from 10% to 94% according to the protocol. [105] Pruritus, although also a common side-effect of TL-01 therapy, sometimes reflects the underlying disease process. [106] Reactivation of herpes simplex virus can occur with UVB treatment, and precautionary measures should be taken in those with a history of this condition. [107] Exposure keratitis and conjunctivitis can also occur with NBUVB therapy. [105] Chronic NBUVB exposure is likely to increase photoaging and the risk of carcinogenesis. However, as discussed earlier, the photocarcinogenic effect of NBUVB has not been proven.


  Targeted Phototherapy: Monochromatic Excimer Laser and Light Top


Targeted phototherapy implies delivering light to localized diseased areas of skin. Since only the affected area is exposed to radiation, higher doses of radiation can be used to achieve better and faster results with lower total cumulative dose and hazards of phototoxicity. Also, it can be used to treat difficult to reach areas like skin folds. Recently, new UV sources that emit wavelengths effective for the treatment of vitiligo in a targeted fashion are becoming popular. Xenon chloride laser, popularly known as an excimer laser (EL), is a 308 nm laser that was initially used for treating psoriasis . [108],[109] However, as its operational wavelength is close to that used in NBUVB, it is used to treat vitiligo as well. This laser offers the advantage of delivering high doses of light to localized areas. [110],[111] It was first used successfully in vitiligo by Baltas et al. [112] in 2001. In 2002 Spencer et al. [17] concluded that the degree of repigmentation in a period of 2-4 weeks is much higher than that achieved with any other current vitiligo therapy. Taneja et al. [113] and Choi et al. [114] also showed beneficial results with excimer laser with non acral lesions responding the best. Two studies compared the efficacy of excimer laser to NBUVB, and found that the excimer laser caused more significant and quicker repigmentation. [115],[116] However, neither of the two studies was controlled nor used a standardized scoring method.

The monochromatic excimer light (308 nm MEL) may present some advantages over the laser. Firstly, it gives a larger irradiation field that enables to treat larger areas at a time. Secondly, lower power density leads to reduced risk of accidents due to overexposure, suggesting a better safety profile. The excimer lamp was found to give equivalent pigmentation as compared with an excimer laser. In 2003, Leone et al. reported that 35/37 (95%) patients showed signs of repigmentation within first eight sittings of MEL and excellent and good repigmentation in 18 and 16 patients, respectively. [18] They also showed that three patients who did not respond to previous treatments with NBUVB showed excellent repigmentation after 308 nm MEL therapy. They proposed that this might be possible due to the difference in the mode of action of these two sources, with 308 nm MEL device delivering higher energy fluences to the target tissue in less time as compared to NBUVB devices.

The repigmentation rate was between 25% and 50% over the entire body, and between 50% and 75% for vitiligo lesions not located at bony prominences or extremities. [117] Interestingly, investigators also noted that MEL induced more erythema than EL suggesting that despite identical 308 nm peak wavelength, EL and MEL might possess different photobiological properties. Similarly, Shi et al. [118] also found that the repigmentation rates with excimer lamp were same as those with laser (79% vs. 87.5%, P > 0.05). A retrospective study of 80 patients with segmental vitiligo (SV) treated with EL showed that 75-99% repigmentation was achieved in 23.8% of cases and 50-74% repigmentation in 20% of cases. [119] This report indicates that besides surgical methods, EL might be an option for SV patients, with the degree of repigmentation positively correlating with treatment duration, cumulative dose, and shorter disease duration. [119]

Patient Selection and dosing schedule

Location of lesions seems to be the best predictor of response: Lesions on the face, trunk respond to a greater extent than lesions on extremities with lesions on hands and feet having the least favorable prognosis. [120],[121] Furthermore, in the study by Ostovari et al., [120] although all UV-sensitive areas responded more or less in the same way, among UV-resistant areas, knees, elbows, and wrists responded significantly better than hands, ankles and feet. Two studies reported a better outcome in patients with darker skin (type III-VI vs. I-II), but no statistical analysis was performed for the confirmation of this observation. [122],[123] Sessions are performed 2-3 times a week for a period of 4-36 weeks. Repigmentation occurs faster with the thrice weekly treatment, but the ultimate rate of repigmentation seems to depend on the total numbers of sessions and not on their frequency. [124] Similar efficiency was revealed for EL treatment in children, with 50% of treated lesions achieved >50% of repigmentation. [125]

Combination therapy

Topical tacrolimus

Passeron et al. [126] reported that at UV-sensitive areas, combination therapy of tacrolimus 0.1% ointment and EL resulted in repigmentation rate of 75% or more in 77% of lesions compared with 57% of lesions treated with EL monotherapy. However, in UV-resistant areas, the above percentages became 60% and 0%, respectively (P < 0.05), showing clear superiority of adding topical tacrolimus on UV resistant sites. Similarly, Kawalek et al. [122] showed that addition of topical tacrolimus to EL therapy produced statistically significant better repigmentation as compared to EL with placebo cream (75% vs. 20%). Short-term side effects were generally unaffected by the addition of tacrolimus except for stinging and moderate lesional and perilesional hyperpigmentation, which subside within 3 weeks. [122],[126]

Topical steroids

Topical hydrocortisone butyrate has been shown to have some benefit in conjunction with EL as Shown by Sassi et al., [127] in which 43% of patients receiving topical hydrocortisone showed greater than 75% repigmentation as compared to 16% of patients who received EL monotherapy.

Topical calcipotriol

In a recent pilot study of 9 patients, Goldinger et al. [123] reported that the addition of topical calcipotriol to EL did not enhance the efficacy of laser treatment alone.

Adverse effects

EL laser has been found to be well-tolerated with mild to severe erythema being the most common adverse effect; blisters and pruritus are reported very rarely. [128]


  Newer Trends Top


Recently, newer forms of unconventional phototherapy have been tried in the treatment of vitiligo with varying results. In a study published in 2010, Mahmoud et al. [129] compared the reaction of skin following irradiation with UVA1 (340-400 nm) and broadband visible light in normal individuals with skin types IV-VI. Using diffuse reflectance spectroscopy, the investigators showed that melanin value increased in a dose-dependent manner following UVA1 or visible light exposure. However, in a recent study, El-Zawahry et al. [130] compared UVA1 phototherapy with NBUVB and concluded that UVA1 was less efficient than NBUVB and thus had a limited value as a monotherapy in vitiligo. Yu et al.[131] showed that visible light produced by a helium-neon laser (633 nm) was able to induce melanocyte migration and proliferation. Few years later, Lan et al.[132] used the same low-level laser light source to cause repigmentation in SV. It is believed that the dermatomal distribution of SV implies a neural dysregulation, making it slightly different to treat than NSV. The helium-neon laser has been found to modify the adrenergic dysregulation of cutaneous blood flow seen in SV. [133] Following treatment with helium-neon laser, more than 50% repigmentation was noted in 60% of patients with head and neck SV, repigmentation beginning after 16-17 treatments. [131],[133] Recently, Yu et al. [134] used 635 nm low-energy laser for SV treatment with the main goal to identify factors predicting treatment outcome. [134] In this study, 7 of 14 patients responded to the treatment (response was defined as achieving at least 25% of repigmentation) thus confirming the efficiency, although limited, of visible light in SV treatment. Importantly, the authors concluded that evaluation of noninvasive cutaneous blood flow with and without prior visible light irradiation on cold-stressed SV lesions may serve as a treatment response predictor. [134] Lan et al., [135] in a recent study, concluded that tacrolimus can be synergistically combined with helium-neon laser without any increased photocarcinogenic risk. [135]

Hartmann et al., [136] recently tried UVB intense pulse light source with peak emission at 311 nm (Relume-Mode, Lumenis) in a right-left comparative study where phototherapy was given once weekly on left side and tacrolimus was applied twice daily on right side. They concluded that long term treatment with either of the two modalities proved to be comparably effective.


  Conclusion Top


Phototherapy is nothing short of a boon for vitiligo patients being safe, effective and noninvasive. With newer forms of phototherapy being tried, a number of evolving effective treatment options for vitiligo are being added to the therapeutic armamentarium of the present day dermatologist. Further research into the clinical and molecular levels of the pathogenesis of vitiligo is required to pave way for the undiscovered treatment modalities for vitiligo that may be beneficial for patients in future.

 
  References Top

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Introduction
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