Dermatology Online Journal

Calcipotriol and PUVA as treatment for vitiligo
F Cherif¹, MI Azaiz¹, A Ben Hamida², A Ben Osman Dhari¹
Dermatology Online Journal 9 (5): 4

1. Department of Dermatology, La Rabta Hospital, Tunis, Tunisia.2. Department of Preventive Medicine, University of Tunis, Tunisia. faika.cherif@voila.fr

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Abstract

We performed a prospective study to evaluate efficacy of the combination of calcipotriol and psoralen plus ultraviolet A (PUVA) in the treatment of vitiligo. Twenty-three patients with essentially bilateral symmetrical lesions of vitiligo were included. Calcipotriol (0.005 %) ointment was applied twice daily over the right side of the body, and the other side was not treated. PUVA was performed three times per week. All patients received at least fortyfive sessions of PUVA. Patients were evaluated clinically and photographed all fifteen weeks. At the fifteenth session, 69 percent of the patients had minimal to moderate improvement on the calcipotriol side compared to 52 percent on the PUVA-only side (p = 0.015). At the forty-fifth session, 52 percent showed marked improvement on the calcipotriol side compared to 30 percent on the PUVA-only side (p = 0.13), with more intense repigmentation on calcipotriol-treated areas. Treatment was well tolerated, and no adverse effect was noted. This combination was an effective treatment for vitiligo, especially in initiating repigmentation.

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Introduction

Vitiligo is an acquired depigmentation disorder affecting about 1 percent of the population [1]. It usually affects younger patients and can be associated with great cosmetic and social problems. A large variety of therapeutic agents are being tried for the treatment of vitiligo, but an optimal treatment is not yet available. Recent studies reported an increased response rate for vitiligo patients treated with the combination of PUVA and calcipotriol [2, 3].

This study examines the efficacy of this combination in the treatment of vitiligo.

Methods

We enrolled 23 patients (16 females and 7 males) with essentially bilateral symmetrical lesions of vitiligo in a prospective trial over an 18-month period. The mean age of the patients was 36 years (range 19-73 yrs). Of these patients, 78 percent were classified as prototype IV or V. The median duration of disease was 11 years (range 1-31 yrs). All patients gave informed consent. The patients were advised to apply calcipotriol (0.005 %) twice daily over the right side of the body; the left side was not treated with calcipotriol. To prevent UVA inactivation, calcipotriol was applied after PUVA on phototherapy days.

An oral dose of 0.6 mg/kg 8-methoxypsoralen was given 2 hours before PUVA, 3 times per week. Waldman 7001K equipment was used as the UVA source. The PUVA was given to both sides while the calcipotriol was used only on the right side. The UVA treatment schedule was 0.5 J/cm² at the start of therapy. It was progressively increased to 5J/ cm². This dose maintains moderate-asymptomatic erythema in vitiliginous patches. To insure uniform treatment between patients, all of them were kept at this dose for the remainder of the sessions. Response to the treatment was evaluated clinically and by keeping photographic records at the start of therapy and all fifteen weeks. All patients received at least fortyfive sessions of PUVA.

Improvement was recorded as minimal (< 25 %); moderate (26-50 %); marked (> 50 %) or complete. The chi-square test was applied. All adverse events observed were recorded. Calcium and phosphorus serum levels were determined at the beginning and at the end of treatment.

Results

The 23 patients completed at least the fortyfive courses. For unresponsive patients (n = 5), the PUVA was then interrupted. All have lesions in the acral regions. At the fifteenth session, 16 patients (69 %) showed minimal to moderate improvement on calcipotriol-treated sides as compared to 12 patients (52 %) on nontreated sides (p = 0.015): Table 1.

Table 1: Response of patients at the fifteenth session (p = 0.015)

	No response	Minimal	Moderate	Marked
Calcipotriol + PUVA     (n = 23)	7	9	7	0
PUVA     (n = 23)	11	12	0	0

Figure 1a	Figure 1b
Figures 1a and 1b. Bilateral lesions of vitiligo in a patient before treatment (a) right, (b) left.

Figure 2a	Figure 2b
Figures 2a and 2b. Repigmentation at the 15th session (a) in calcipotriol treated sides (b) in non-treated calcipotriol sides. Greater areas of repigmentation in (a).

Table 2: Response of patients at the forty-fifth session (p = 0.13)

	No response	Minimal	Moderate	Marked
Calcipotriol + PUVA     (n = 23)	5	1	5	12
PUVA     (n = 23)	5	2	9	7

At the forty-fifth session, 12 patients (52 %) showed marked improvement of the calcipotriol-treated side, whereas 7 patients (30 %) showed similar improvement of the PUVA-only side (p = 0.13): Table II. When repigmentation was complete, it was more intense in calcipotriol-treated areas. Mild irritation at the calcipotriol application site was reported by 2 patients (8.7 %). No significant difference was found between pre- and post-treatment levels of serum calcium and phosphorus.

Figure 3a	Figure 3b
Figures 3a and 3b. forty-fifth session: The patient showed repigmentation in the two sides (a, b).

Figure 4
Figure 4. Complete repigmentation but more intense in the right side.

Conclusions

Current treatment modalities for repigmenting vitiliginous macules are unsatisfactory [4]. Psoralen plus ultraviolet A (PUVA) appears to be the best method for achieving repigmentation [4], although variable results are reported [5]. Recent studies reported the efficacy of the combination of PUVA and topical calcipotriol [2, 3, 6, 7, 8].

Our study recorded a faster response in vitiligo lesions treated with PUVA and calcipotriol (p = 0.015) with more intense repigmentation in the calcipotriol treated side. However, lesions in acral regions did not respond to this therapy. The addition of topical calcipotriol to PUVA treatment was not associated with serious side effects.

Recent advances in the pathophysiology of vitiligo demonstrate defective calcium homeostasis in vitiliginous skin [9, 10].

Calcipotriol is a synthetic analogue of 1,25-dihydroxyvitamin D₃. Most of the biological actions of calcipotriol and other vitamin D analogs are mediated by the vitamin D receptor [11, 12]. Many types of cells have vitamin D receptors, including keratinocytes, melanocytes, fibroblasts, and immune-system cells of the skin [6, 12]. The vitamin D receptor functions as a ligand-induced transcription factor, regulating the rate of gene expression involved in the control of calcium homeostasis and bone remodelling, control of hormone secretion, inhibition of cell growth, and induction of cell differentiation [13, 14, 15]. Calcipotriol is also an immunomodulator that interacts with cells, especially antigen-presenting cells [12, 16, 17, 18, 19]. The effect of calcipotriol on melanocytes may be direct or by means of these immunomodulatory actions.

Our study supports the efficacy of PUVA and topical calcipotriol, especially in initiating repigmentation. This combination may shorten the duration of UVA exposure, leading to decreases in the dose-dependent side effects related to PUVA [6].

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