A pilot study to determine the safety and efficacy of monochromatic excimer light in the treatment of vitiligoStacy M. Chimento
Vitiligo is a chronic depigmentary disorder characterized by the loss of melanin and decreased melanocytes in the epidermis of affected skin. This defect results in well-circumscribed white macules or patches, which tend to expand over time. Classified as focal, segmental, generalized, or universal, these lesions can affect any part of the body, but are typically found on the hands, joints, legs, and face. The disease prevalence is approximately 1% to 2%, and its progression is variable among affected individuals. Although more common among young people, it has no age, sex, or racial predilection. (1) The exact etiology is currently unknown; however, it appears that multiple factors play a significant role in its development.
Phototherapy is a common treatment for vitiligo. More specific wavelengths of light, such as those found in narrow-band ultraviolet B (UVB) are the treatment of choice in diseases involving large surface areas. Focal disease requires a different approach to minimize exposure to ultraviolet light on healthy skin while still providing repigmentation to lesional skin. Excilite [mu][TM] (DEKA, Florence, Italy) is a 308-nm light source studied in the treatment of psoriasis, atopic dermatitis, vitiligo, and, more recently, mycosis fungoides. The aim of this pilot study was to evaluate the clinical efficacy and safety of the 308-nm excimer light device in treating vitiligo, and to assess the maintenance of repigmentation following treatment.
Subject and Methods
Subjects receiving medical care for vitiligo in the dermatology clinic at the University of Miami (Florida) were asked to participate in the study. They were subsequently screened for inclusion and exclusion criteria. Demographic information with a detailed history of duration, progression, and prior treatments of vitiligo was obtained, and a physical exam was performed. Patients were then assessed for Fitzpatrick skin phototypes.
Subjects were eligible for enrollment if they were between the ages of 18 and 85 years, with clinically stable localized, segmental, or acrofacial vitiligo of less than 5 years duration with no more than 65% of the total surface body area affected. Children, prisoners, pregnant women, and those over the age of 85 were ineligible to participate in the study. Subjects also were excluded if they had received photochemotherapy or topical treatment within 4 weeks or systemic therapy within 6 weeks of the onset of the study. Subjects with a history of untreated cutaneous malignancy, history or evidence of other skin conditions that would interfere with the evaluation of the study light therapy, or those who obtained an excessive amount of ultraviolet light during the day were excluded. The study did not enroll subjects who had or were participating in any other research within 30 days prior to the onset of this study, nor those who were unable to return for follow-up visits.
In this pilot study, the efficacy and safety of the Excilite [mu] device was tested prospectively on 10 patients (4 males and 6 females) with stable localized, segmental, and acrofacial vitiligo. Participants were exposed to 10 weeks (a total of 18 treatments) of targeted phototherapy with Excilite [mu], followed by 5 weeks of observation to assess the stability of repigmentation. The study protocol was reviewed and approved by the institutional review board, and written consent was obtained from all participants.
Materials and Intervention
Targeted phototherapy was performed with a 308-nm xenon chloride excimer light source (Excilite [mu]) manufactured by DEKA M.E.L.A. in Florence, Italy. This tabletop system is approved by the FDA and safe for Fitzpatrick skin phototypes 1 through 6. It consists of a power density of 50 mW/[cm.sup.2], with irradiation fields of 30, 6, and 1 [cm.sup.2].
The same physician administered the therapy at each of the 18 treatments. To determine the minimal erythema dose (MED), 3 separate, adjacent areas of unaffected skin on the buttock of all participants were initially phototested with the device by exposing them to 3 small dose increments. For protective measures, sunscreens with an SPF 30 were applied to the perilesional unaffected skin of all subjects prior to treatments. A baseline photograph of the vitiliginous lesions was taken prior to the onset of therapy, with subsequent photos taken after each session, and during the 12 to 15-week follow-up visits.
Subjects received twice weekly treatments on non-consecutive days during weeks 1 through 8, and once weekly treatments during weeks 9 and 10. The initial fluency for each patient was 70% of the calculated MED with the following dose increments: 40% increase every other session on treatments 1 to 4, 30% increase every other session on treatments 4 to 8, and a 20% increase every other session on treatments >8. Post-exposure, follow-up visits occurred on weeks 12 and 15.
Adverse effects (erythema, burning, and blistering) were documented after each session. Treatments were omitted if symptomatic erythema developed. The dose was reduced by 10% for asymptomatic erythema.
Once per week during the treatment period and on weeks 12 and 15 of the follow-up period, photographs were taken and the participants and the treating physician assessed the target areas according to the amount of repigmentation with the following scale: 0=no repigmentation, 1=poor repigmentation (1%-25%), 2=moderate repigmentation (25%-50%), 3=good repigmentation (50%-75%), 4=excellent repigmentation (>75%).
After study completion, an independent observer reviewed the photographs to assess response, according to the same scale.
A light acceptability questionnaire (Table 1) grading the laser on a 5-point scale was administered on the final day of treatment or earlier if the subject exited the study prior to termination.
A total of 12 subjects met inclusion criteria and entered the study from September 2005 to February 2006, with 2 withdrawing in the first 2 weeks due to time constraints. One of the 10 subjects had incomplete visits due to transportation issues but remained in the program and received some treatment. Demographic data are summarized in Table 2, including target treatment sites and previous treatments. Patient ages ranged from 21 to 61 years, with a mean age of 39.9 years. Sixty percent of the subjects had skin type 3, 20% had skin type 4, and 20% had skin type 6.
Repigmentation was seen by week 2 in 60% of the subjects, according to patient assessment, and in 50% of the subjects, according to the treating physician and independent observer assessments. Response was not site dependent. According to the independent observer, 5 subjects achieved 25% to 50% repigmentation, and 3 subjects reached up to 25% repigmentation (Table 3). Two patients did not repigment. In contrast to the independent observer, the patients' own assessments showed higher rates of repigmentation: 2 subjects achieved 51% to 75% repigmentation, 5 subjects had 25% to 50% repigmentation, and 3 had 1% to 25% repigmentation. During the 5-week follow-up period, all patients maintained the same level of repigmentation, regardless of evaluator.
Safety and Tolerability
Mild to severe erythema and perilesional tanning were noted, and in 1 case blistering was seen. The patient with blistering had dramatic repigmentation with the healing of the blisters. The rating of comfort of treatment and overall assessment of the treatment ranged from favorable to highly favorable as noted by the light acceptability questionnaire results.
Conventional treatment for vitiligo includes topical immunomodulators, topical steroids, psoralens with ultraviolet A (PUVA) irradiation, UVB (narrow-band (NB) and broadband (BB)), and surgical modalities, such as tattooing and melanocyte grafting. Many therapeutic failures exist despite full exploitation of this list both singly and in combination. Phototherapy may require long treatment times and frequencies, often ending in less than optimal results. (2) The adverse effects include phototoxicity, blistering, burning, and often unnecessary irradiation of nonlesional skin.
Psoralens with ultraviolet A has been used commonly for patients needing treatment for a large body surface area, but the psoralens are not always well tolerated, and the long-term carcinogenic risk in vitiligo has not yet been established. El Mofty et al reported that the addition of psoralens does not increase efficacy when combined with phototherapy and that psoralen plus BB-UVB is as effective as PUVA in the treatment of vitiligo. (3,4) PUVA treatments can last from several months to 1 year and according to some studies less than 20% of patients will experience complete repigmentation. (5,6)
Currently, the gold standard treatment in patients with vitiligo affecting 65% body surface area or more is NB-UVB, a focused UVB spectrum of 311 to 313 nm. Narrow-band UVB is well tolerated in children and adults. It produces satisfactory results with a more attractive side effect profile: no oral supplements or safety goggle use (outside of treatment time). In a comparative study of PUVA and NB-UVB in the treatment of vitiligo, Parsard et al showed the superiority of NB-UVB in regards to stability of lesions and color match of repigmentation with unaffected skin. (7) Westorhof et al used NB-UVB 2 to 3 times per week for 4 to 12 months, and found partial repigmentation in 67% of patients receiving NB-UVB versus 46% of patients treated with topical PUVA. (8) Furthermore, a meta-analysis comparing BB-UVB (57% of patients responded), NB-UVB (63% of patients responded), and oral methoxsalen with UVB (51% of patients responded) suggested that among all of the treatments available at the time of the study, patients had a better outcome when exposed to NB-UVB. (2) The most recent study by Yones et al further demonstrated the superiority of NB-UVB to oral PUVA therapy in patients with nonsegmental vitiligo with a maintenance of repigmentation after 12 months of therapy. (9)
The 308-nm xenon chloride excimer laser has been shown to be biologically similar to NB-UVB with the specific wavelength being 6 times more erythmogenic than the narrow-band spectrum. The excimer laser has been found to be effective in the management of localized psoriatic lesions and may be superior to NB-UVB in these lesions simply because it can deliver high doses of light to selective plaques without affecting normal perilesional skin. (10-12) The same concept applies to vitiligo; while NB-UVB is an efficacious treatment, a more focused light source decreases UV irradiation to non-lesional skin. Excimer laser treatment of vitiligo was first reported by Baltas et al in a case study of a patient with localized disease. (13) Since then, numerous publications have reported efficacy of the excimer laser in the repigmentation of vitiliginous plaques. The rate and stability of repigmentation after the induction of therapy with the excimer laser for vitiligo had been shown to be satisfactory. Spencer reported a degree of pigmentation in as early as 2 to 4 weeks with the laser (57% in 6 treatments and 82% in 12 treatments), (6) but later, Leone showed maintenance of therapeutic benefit 12 months posttreatment when the 308-nm monochromatic excimer light source (MEL), a duration superior to other modalities, was used. (14)
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The 308-nm excimer light as used in this study may be a promising option for those unresponsive to other forms of treatment. (15,16) Compared to the excimer laser, Excilite [mu] has a lower power density (50 mW/[cm.sup.2]), a larger irradiation area (up to 30 [cm.sup.2]), and a potentially shorter duration of light exposure until initial repigmentation. (17) It has been shown to be an effective treatment in psoriasis and atopic dermatitis without adverse reactions. (18,19) In 54 patients with palmoplantar psoriasis treated with Excilite p once every 7 to 14 days for 4 months, 31 patients (57%) achieved full remission, a partial remission was achieved in 13 patients (24%), and moderate improvements were seen in 10 patients (19%). (17)
No studies thus far have been performed in the US evaluating the efficacy of Excilite [mu] in vitiligo. In one European study, Leone et al used the floor model, Excilite [mu], that consisted of a large irradiation field to treat 37 patients with acrofacial, focal, segmental, and generalized vitiligo. (14) With twice-weekly sessions over 6 months, 35 patients (95%) exhibited signs of repigmentation within the first 4 to 8 treatments with adverse events limited to transient erythema. After 3 months, 32% of the patients achieved >75% repigmentation and 57% achieved 51% to 75% repigmentation. Patients that did not respond to therapy with NB-UVB responded after 5 to 7 treatments. Those that ultimately responded did so early in the treatment protocol. Only 6 patients upgraded their repigmentation score from between 51% and 75% to >75% repigmentation after 6 months. The authors concluded that the Excilite [mu] may offer quicker results with a minimal number of sessions to see initial repigmentation because it can deliver higher energy flows in less time thus decreasing overall cumulative dose exposure.
[FIGURES 5 & 6 OMITTED]
The tabletop unit of the Excilite [mu] system was used to deliver excimer light in the pilot study and found a more rapid onset of repigmentation. According to the independent observer, 50% of the subjects responded by the second week of treatment. With a treatment protocol of just over 2 months, 5 of the patients already had good results at 25% to 50% repigmentation and 3 had fair results at 1% to 25% repigmentation. Extrapolation of this data according to the experience of Leone et al suggests that these responders will continue to respond for up to 6 months.
Neither skin type nor location correlated with response. Of the 6 skin type 3 patients, an equal number had no, fair, and good repigmentation (Table 2). Of the good responders, an equal number had skin types 2, 4, and 6. While the most dramatic response was in the skin type 6 patient with generalized vitiligo that received treatment on the face (Figures 1 and 2), remarkable repigmentation was also seen in 1 patient with localized lesions to the chin (Figures 3 and 4) and another with lesions on both hands (Figures 5 and 6). While the 2 nonresponders both had periorificial disease, another participant with perioral disease had rapid and good repigmentation.
Patients rated the treatment sessions comfortable and adverse events were limited to transient pink or red erythema with 1 episode of blistering that also led to a dramatic response as seen in Figures 1 and 2.
The limitations of the study were few. Wood's light examination of the lesions for the independent observer was not collected. Such imaging might allow more accurate assessments of repigmentation. Also the study had only 10 patients limited to 3 different skin types, even though the Excilite [mu] system is approved for all skin types by the FDA. The lack of skin types 1 and 2 may be due to the absence of clinically relevant diseases in these fair colors.
The 308-nm Excilite [mu] was found to be a safe and rapidly acting therapeutic modality in skin types 3 through 6 for stable vitiligo. While Leone et al achieved greater repigmentation scores with the same system, the discrepancy is likely attributable to the average number of treatments received by those patients: twice that of this study. Furthermore, those patients who ultimately responded well could be identified by early repigmentation as shown in this cohort. The Excilite [mu] may be a valuable option for patients with limited vitiligo.
Funding for this research study was provided by DEKA M.E.L.A. Sri.
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ADDRESS FOR CORRESPONDENCE
Paolo Romanelli MD
University of Miami Department of Dermatology
1444 Northwest 9th Avenue
Miami, FL 33136
Stacy M. Chimento BA, (a) Meggan Newland MD, (a) Carlos Ricotti MD, (a) Steven Nistico MD, (b) Paolo Romanelli MD (a)
a. Department of Dermatology and Cutaneous Surgery, University of Miami Miller School of Medicine, Miami, FL
b. Department of Dermatology, University of Tor Vergata, Rome, Italy
Table 1. Light acceptability questionnaire. Rate statements A and B with the favorability scale 1-5. A. Comfort of the laser during application B. Overall assessment of the laser 1 = highly favorable 2 = favorable 3 = neutral 4 = unfavorable 5 = highly unfavorable Table 2. Patient characteristics. Sex/Age Skin Duration Patient (years) Type (years) Treatment Site 1 F/45 4 1 Back, flank 2 M/21 6 4 Generalized 3 M/22 3 2 Perinasal, perioral 4 F/50 3 2 Hands 5 F/39 3 4 Eyelids, perioral 6 F/61 3 1 Neck, shoulders 7 F/35 6 2 Lips, perioral 8 M/55 4 4-5 Nose, chin 9 F/34 3 4 Nose, chin, ears 10 M/37 3 2 Chin Appearance of Patient Prior Treatments Repigmentation (Week) 1 Topical calcineurin inhibitor 2 2 Topical steroids, topical calcineurin 2 inhibitor; PUVA x 2 months 3 Topical calcineurin inhibitor n/a 4 Topical calcineurin inhibitor 2 5 Topical calcineurin inhibitor; PUVA n/a 6 None 2 7 Topical calcineurin inhibitor 2 8 Topical calcineurin inhibitor; Unknown 4 laser treatment 9 Topical calcineurin inhibitor; 4 Over-the-counter Cuban solution 10 Topical steroids 5 Table 3. Repigmentation and Fitzpatrick skin typing (according to independent observer assessment). Final Grade of Number of Patients Repigmentation Total Skin Type 3 Skin Type 4 Skin Type 6 0 2 2 -- -- 1 4 2 -- -- 2 6 2 2 2 3 -- -- -- -- 4 -- -- -- --
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