Dermatologic Therapy, Vol.

25, 2012, 472476 Printed in the United States All rights reserved

2012 Wiley Periodicals, Inc.

DERMATOLOGIC THERAPY
ISSN 1396-0296

THERAPEUTIC HOTLINE
Clinical efcacy of a novel topical formulation for vitiligo: compared evaluation of different treatment modalities in 149 patients
Gionata Buggiani*, Dionigi Tsampau, Jana Hercogov, Riccardo Rossi, Benedetta Brazzini & Torello Lotti*
*School of Medicine, University of Florence, Azienda Sanitaria Firenze, Florence, Italy, Dermatology Department, 2nd Medical Faculty, Charles University, Prague, Czech Republic and The Imperial College, London, United Kingdom

ABSTRACT: Current vitiligo treatments are not always satisfactory for both patients and dermatologists. Recently, combination therapies have been introduced in order to obtain better results and reduce risks in the management of the disease. Novel efcacious products are needed to improve the therapeutic possibilities of dermatologists in the respect of safety for the patients. The objective of the present study was to evaluate the effects of a novel topical in a gel formulation containing phenylalanine, cucumis melo extract, and acetyl cysteine in vitiligo. The present study used an open observational study to evaluate the efcacy and safety of the investigated product, given alone or in combination with 311-nm narrow band microphototherapy. Results were compared with those obtained treating a matched patient population with microphototherapy alone and with clobetasol propionate 0.05% ointment alone. One hundred forty-nine patients suffering from symmetrical vitiligo affecting less than 10% of the skin surface were evaluated. Patients affected by acral vitiligo only were excluded from the analysis. Treatment duration was scheduled for 12 weeks. Excellent repigmentation (>75%) was achieved by 3873% of patients, depending on the treatment regimen. Mild to moderate side effects were observed only in patients treated with clobetasol 0.05% ointment. The tested gel formulation showed a good efcacy in improving vitiligo repigmentation. No side effects were observed. KEYWORDS: phototherapy, treatments, vitiligo

Introduction
Vitiligo is a commonly acquired, idiopathic, and progressive disorder characterized by the appearAddress correspondence and reprint requests to: Gionata Buggiani, MD, Private Practitioner of Dermatology and Venereology via Leonardo da Vinci, 66 50053 Empoli (Florence), Italy, or e-mail: g.buggiani@gmail.com.

ance of amelanotic patches of variable size involving the skin and the mucous membranes, with different disease patterns. Its etiology remains unknown, and its pathogenesis is still poorly understood (1). To date, the available medical and surgical treatments for vitiligo remain merely suboptimal as several patients respond poorly or show continued progression of the disease in spite

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of the treatment. People affected by vitiligo have a remarkable reduction of quality of life, mainly caused by the color contrast between the healthy pigmented skin and the depigmented vitiligo patches, which gives the patients the well-known leopard-like skin appearance (2,3). Medical and surgical treatments have been proposed. Nonsurgical repigmentation therapies are well established. Among these, both the use of high-potency topical corticosteroids (e.g., clobetasol propionate 0.05% ointment, betamethasone dipropionate 0.05% cream) and narrow band ultraviolet (UV) B irradiation represent, for the majority of specialists worldwide, the most effective monotherapies, even if not always advisable because of the local (and general) side effects of the topical corticosteroids (4,5). Recently, a large study of treatment comparison has been published (6) showing that a combined regimen using both highpotency corticosteroids and focused narrowband UVB may be considered the gold standard for the treatment of vitiligo both in terms of efcacy and safety. Surgical methods are only indicated when medical treatments fail (7).

with skin phototypes II and III, during 12 weeks, assuring that patients were not undergoing other relevant sun or articial lamp exposure and/or corticosteroids or other immunosuppressive treatments during entire study period. To obtain signicant results, the present authors decided to perform a compared analysis, evaluating four groups of patients: 1. Group A: 37 subjects treated with Re-Pigmenta gel alone, twice a day for 12 weeks. 2. Group B: 43 subjects treated with UVB microphototherapy equipment (Bioskin, Centro Salute Montecatini s.r.l. Montecatini Terme (PT), Italy) alone, once a week for 12 weeks. 3. Group C: 36 subjects treated with an association of Re-Pigmenta gel twice a day plus Bioskin once a week, for 12 weeks. 4. Group D: 33 subjects treated with clobetasol propionate 0.05% ointment, twice a day for 12 weeks.

UVB microphototherapy equipment (Bioskin) and treatment algorithm

Bioskin is a phototherapy device consisting of a short arc generator emitting a beam of visible and ultraviolet radiations, ltered by a particular interference lter in order to obtain UVB narrow band only. The time of emission is regulated by the operator, which acts on a time-controlled shutter. Bioskin can provide a spectrum of intensity up to 400 mW/cm2 with an emission spectrum ranging from 300 to 320 nm, and a peak emission at 311 nm (narrow band UVB). According to the extent of vitiligo patches, different conical hoods (with diameters ranging from 1 to 5 cm) can be applied at the end of the optical ber, to obtain different light spot diameters. Patients were irradiated once a week for 12 consecutive weeks. During each microphototherapy session, all vitiligo patches were irradiated (excluding genital areas and mucous membranes). Although Bioskin equipment can provide a large spectrum of intensity (0400 mW/cm2), in this study the intensity of 50 mW/cm2 was used for all patients during all sessions, modifying the time of exposure on the different body areas. The initial dose of irradiation was 20% less than the minimum erythema dose evaluated on a vitiliginous area at least 3 days before the beginning of the treatment. During the following sessions the dose was increased by 20% in every session until the development of erythema was noted. When erythema developed, the dose of the

Aim of the study

The aim of this open study was to evaluate, in the context of the noncorticosteroid-based topical treatments, the safety and efcacy of a novel topical formulation containing Phenylalanine, Cucumis melo extract and acetyl cysteine (Re-Pigmenta gel, ALGENA s.r.l., Milano, Italy), in the treatment of symmetrical vitiligo affecting less than 10% of the skin surface.

Patients and methods

This open study included 149 subjects, aged 1872, affected by symmetrical vitiligo with long-term, stable or active lesions, involving 10% or less of the skin. Exclusion criteria were vitiligo on the hands and/or feet only (acral vitiligo alone), use of systemic corticosteroids or immunesuppressive agents in the last 10 weeks, use of any local treatments in the last 4 weeks before study initiation, known abnormal reactions to UVB irradiation, pregnancy, and breast-feeding. All patients provided written informed consent after proper counseling. The study was performed on a Caucasian population of Italian, Czech, and English origins

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next session was diminished by 20% only in the erythematous areas. The patient population had skin phototypes II or III. The MED of lesional skin in these patients was between 180 and 810 mJ/cm2 evaluated with an intensity of irradiation of 50 mW/cm2. Table 1 shows the mean doses irradiated during each session on the different body areas.

Table 1. Irradiation doses of the different body areas during each microphototherapy session
Area Eyebrows Face Chest Arms Legs Hands Feet Mean dose (mJ/cm2) 70 120 220 300 280 500 480

Evaluation of the treatment

Photographs of the patients in standard poses and under Woods light were conducted for each patient during the rst clinical visit and every month study period (FIGS. 1 and 2). The response

Depending of the body area, different mean doses of irradiation have been used, because of the different minimal erythema dose of each ad every site, in order to avoid side effects while maintaining the effectiveness of the repigmenting technique.

FIG. 1. Vitiligo in a female patient, before and after treatment (Woods light).

FIG. 2. Vitiligo in a male patient, before and after treatment (Woods light).

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Table 2. Percentage of repigmentation in subgroups of patients

Repigmentation rates (percentage) Treatment groups (n of patients) Group A: Re-Pigmenta gel alone (37) Group B: Bioskin alone (43) Group C: Re-Pigmenta + BIOSKIN (36) Group D: Clobetasol propionate 0.05% (33)

Excellent (>75) 38.4 61.1 73.5 56.2

Marked (5075) 23.6 20.3 15.6 25.7

Moderate (2550) 30.2 9.9 5.4 15.3

Minimal (<25) 7.8 8.7 5.5 2.8

Number of patients treated: 149. No switching between therapies was allowed. No dropout has been reported.

to treatment was estimated by comparing the photographs making use of planimetry.

Results
The duration of the clinical study was 12 weeks (January 2011 through April 2011). The number of the patients recruited was 149. The totality of patients involved concluded the study. After 12 weeks, excellent repigmentation (>75%) was achieved by 38.4% of patients in Group A, 61.1% of patients in Group B, 73.5% of patients in Group C, and 56.2% of patients in Group D. Marked repigmentation (5075%) was evident in 23.6% of patients in Group A, 20.3% of patients in group B, 15.6% of patients in Group C, and 25.7% of patients in Group D. Moderate results (2550% repigmentation) were seen in by 30.2% of patients in Group A, 9.9% of patients in Group B, 5.4% of patients in Group C, and 15.3% of patients in Group D. Minimal (<25%) or no response has been reached in by 7.8% of patients in Group A, 8.7% of patients in Group B, 5.5% of patients in Group C, and 2.8% of patients in Group D. Mild to moderate side effects (teleangiectasias, hypertrichosis, skin atrophy) were observed only in patients treated with clobetasol 0.05% ointment. Results are shown on FIG. 3 and Table 2.

FIG. 3. Satisfactory repigmentation rates (repigmentation

>75%) as observed at the end of the study among patients in the four different treatment groups.

Comment
Conicting data are present in the literature about the therapeutical use of topical acetyl cysteine (8), phenylalanine (6), and cucumis melo extract in vitiligo (9,10). In particular, the usefulness of the latter is still debated. However, on the basis of the results of the present open study and following patients opinion, the present authors think that the concomitant presence of the three actives in a single product may be of particular help in selected vitiligo patients. Moreover, especially when used

in association with narrow band 311 nm Bioskin microphototherapy, it could represent a valuable therapeutic protocol, according to the criteria of efcacy, safety, and compliance. As can be clearly seen from the results of the current open study, the monotherapy regimen with Re-Pigmenta gel is satisfactory in about 1/3 of cases, less than clobetasol or Bioskin alone. Clobetasol propionate 0.05% ointment caused some side effects, which, in spite of the achievable results, may affect the compliance of patients and lead to an early treatment dropout. Moreover, the vast majority of the dermatologists and of the patients does not accept long-term use of potent corticosteroid creams. The association of Re-Pigmenta gel and Bioskin microphototherapy leads to good results in terms of patients compliance, disease repigmentation and safety.

References
1. Lotti T, Hautmann G, Hercogov J. Vitiligo: disease or symptom? From the confusion of the past to current doubts.

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In: Lotti T, Hercogov J, eds. Vitiligo. Problems and solutions. New York, NY, Basel: Marcel Dekker, Inc, 2004: 114. Ongenae K, Beelaert L, van Geel N, Naeyaert JM. Psychosocial effects of vitiligo. J Eur Acad Dermatol Venereol 2006: 20 (1): 18. Lotti T, Hanna D, Buggiani G, Urpe M. The color of the skin: psycho-anthropologic implications. J Cosmet Dermatol 2005: 4 (3): 219220. Lotti T, Menchini G, Andreassi L. UV-B radiation microphototherapy. An elective treatment for segmental vitiligo. J Eur Acad Dermatol Venereol 1999: 13 (2): 102108. Grimes PE. New insights and new therapies in vitiligo. JAMA 2005: 293 (6): 730735. Lotti T, Buggiani G, Troiano M, et al. Targeted and combination treatments for vitiligo. Comparative evaluation of different current modalities in 458 subjects. Dermatol Ther 2008: 21 (Suppl. 1): S20S26. 7. Falabella R. Vitiligo: problems and surgical solutions. In: Lotti T, Hercogov J, eds. Vitiligo. Problems and solutions. New York, NY, Basel: Marcel Dekker, Inc, 2004: 293312. 8. Park ES, Kim SY, Na JI, et al. Glutathione prevented dopamine-induced apoptosis of melanocytes and its signaling. J Dermatol Sci 2007: 47 (2): 141149. 9. Yuksel EP, Aydin F, Senturk N, Canturk T, Turanli AY. Comparison of the efcacy of narrow band ultraviolet B and narrow band ultraviolet B plus topical catalase-superoxide dismutase treatment in vitiligo patients. Eur J Dermatol 2009: 19 (4): 341344. 10. Schallreuter KU, Panske A, Chiuchiarelli G. Ineffective topical treatment of vitiligo with Cucumis melo extracts. Int J Dermatol 2011: 50 (3): 374375.

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