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 Table of Contents  
ORIGINAL ARTICLE
Year : 2020  |  Volume : 4  |  Issue : 2  |  Page : 210-216

Evaluation of fractional carbon dioxide laser-assisted drug delivery of calcipotriol plus betamethasone versus bimatoprost in the treatment of vitiligo


Department of Dermatology, Venereology and Andrology, Faculty of Medicine, Al-Azhar University, Cairo, Egypt

Date of Submission16-Feb-2020
Date of Decision29-Feb-2020
Date of Acceptance01-Mar-2020
Date of Web Publication29-Jun-2020

Correspondence Address:
MBBCh Ahmed M.M Abdelrazik
Department of Dermatology, Venereology and Andrology, Faculty of Medicine, Al-Azhar University, Cairo
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/sjamf.sjamf_23_20

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  Abstract 


Introduction Vitiligo is a disease in which melanocytes (pigment-producing cells) are damaged or destroyed resulting in a patchy loss of pigment from areas of skin. Vitiligo patches can appear anywhere on the skin, but commonly affected sites include the areas around the orifices, the genitals, or any sun-exposed areas such as the face and the hands. The hair and, rarely, the eyes may also be affected.
Aim The aim of the work is to evaluate the efficacy of transepidermal drug delivery by CO2 fractional laser of calcipotriol plus betamethasone versus bimatoprost in the treatment of vitiligo.
Patients and methods This study included 20 patients with vitiligo. The patients were selected from the Outpatient Clink of Dermatology and Venereology Department in Al-Hussien University Hospital from March 2019 to September 2019.
Results Comparison between the first and the second patches was done. In each patient, two patches were selected and classified as follows: side A is the right side, and it was treated with fractional CO2 laser followed by topical bimatoprost (0.03%) drops, and side B is the left side, and it was treated with fractional CO2 laser followed by topical calcipotriol (0.05 mg/g) plus betamethasone (0.5 mg) ointment. The repigmentation grade showed a statistically significant increase in the second patch: regarding the right side, there were five (25%) patients of grade 0, 10 (50%) patients of grade I, three (15%) patients of grade II, one (5%) patient of grade III, and one (5%) patient of grade IV (the mean response was 21±23.7, with minimum response of 0 and maximum response of 80). Regarding the left side, there were three (15%) patients of grade 0, nine (45%) patients of grade I, three (15%) patients of grade II, one (5%) patient of grade III, and four (20%) patients of grade IV (the mean response was 34.8±30.1, with minimum response of 0 and maximum response of 90).
Conclusion From the result of this study, we can conclude that fractional CO2 laser followed by topical calcipotriol (0.05 mg/g) plus betamethasone (0.5 mg) ointment gives better results than fractional CO2 laser followed by topical bimatoprost (0.03%) drops in the treatment of vitiligo.

Keywords: betamethasone and bimatoprost, fractional CO2 laser, vitiligo


How to cite this article:
Abdelrazik AM, El-Khalawany MA, Ibrahim SM. Evaluation of fractional carbon dioxide laser-assisted drug delivery of calcipotriol plus betamethasone versus bimatoprost in the treatment of vitiligo. Sci J Al-Azhar Med Fac Girls 2020;4:210-6

How to cite this URL:
Abdelrazik AM, El-Khalawany MA, Ibrahim SM. Evaluation of fractional carbon dioxide laser-assisted drug delivery of calcipotriol plus betamethasone versus bimatoprost in the treatment of vitiligo. Sci J Al-Azhar Med Fac Girls [serial online] 2020 [cited 2020 Jul 12];4:210-6. Available from: http://www.sjamf.eg.net/text.asp?2020/4/2/210/288270




  Introduction Top


Vitiligo is a disease in which melanocytes (pigment-producing cells) are damaged or destroyed resulting in a patchy loss of pigment from the areas of skin. Vitiligo patches can appear anywhere on the skin, but commonly affected sites include the areas around the orifices, the genitals, or any sun-exposed areas such as the face and the hands. The hair and, rarely, the eyes may also be affected [1],[2],[3].

Several interventions have been used in the treatment of vitiligo including pharmacological interventions (e.g. topical corticosteroids and immunomodulators); various forms of phototherapy (i.e. ultraviolet A, narrowband and broadband ultraviolet B, psoralen and ultraviolet A, excimer laser, and monochromatic excimer light); surgical procedures (grafting, melanocyte transplantation, and micropigmentation); cosmetic measures (depigmentation, cosmetic camouflage, and fake tan); complementary therapies; and psychotherapy. Many published studies describe combination therapies, usually combining a light source with another form of treatment to enhance repigmentation [4].

The vitamin D3 analog, calcipotriol, has been used topically in vitiligo, where modulation of the local immune response on specific T cell activation occurs. It also influences melanocyte maturation and differentiation and up-regulates melanogenesis through pathways activated by specific ligand receptors, such as endothelin receptor and c-kit [5].

Betamethasone dipropionate is a synthetic glucocorticoid used for the treatment of vitiligo owing to its anti-inflammatory and immunomodulating effects [6].

Follow-up studies of patients withdrawn from bimatoprost treatment show that the increased iridial pigmentation is irreversible, whereas changes in periocular skin pigmentation are reversible after cessation of therapy [7]. These effects, however, do not seem to be attributed to a direct action of bimatoprost itself on melanogenesis and/or melanocyte proliferation [8].


  Aim Top


The aim of the work is to evaluate the efficacy of transepidermal drug delivery by CO2 fractional laser of calcipotriol plus betamethasone versus bimatoprost in the treatment of vitiligo.


  Patients and methods Top


Patients

This study included 20 patients with vitiligo. An informed consent was taken before inclusion of patients into the study. The patients were selected from the Outpatient Clinic of Dermatology and Venereology Department in Al-Hussien University Hospital from March 2019 to September 2019.

Inclusion criteria

The following were the inclusion criteria:
  1. Patients with stable vitiligo both segmental and nonsegmental.
  2. More or less bilateral symmetrical lesions.


Exclusion criteria

The following were the exclusion criteria:
  1. No previous phototherapy for the last 3 months.
  2. No other dermatological or systemic diseases.
  3. Coagulation and bleeding disorders or on anticoagulants.
  4. Active infections and liver diseases.
  5. Pregnancy and lactation.


Methods

In each patient, two patches were selected including face, neck, chest, abdomen, upper limb, hand, knee, lower limb, and back and classified as side A and side B.
  • Side A: it was the right side, which was treated with fractional CO2 laser followed by topical bimatoprost (0.03%) drops.
  • Side B: it was the left side, which was treated with fractional CO2 laser followed by topical calcipotriol (0.05 mg/g) plus betamethasone (0.5 mg) ointment.


The patches were covered by plastic sheet for occlusion at least 6 h, and patients were instructed to apply each ointment and drops on its patch every night.

Every patient received a session every 2 weeks for a maximum of 3 months (six sessions).

The patients were followed up monthly for 3 months after the end of treatment sessions to detect any recurrence, complications, or worsening of the lesions.

Fractional CO2 laser methodology

  1. Topical anesthetic cream was applied under occlusion for ∼30 min.


Technique of fractional CO2 laser

  1. The machine used will be fractional CO2 (Smartxide dot; DEKA, Deka M.E.L.A. S.r.l., with registered office at Via Baldanzese, No. 17 – 50041 Calenzano (FI), Italy) with following parameters:
    1. Power 10 W.
    2. Dwell time 500 ms.
    3. Dot spacing 500 μm.
    4. Stack 2.


Evaluation of the treatment:
  1. Clinical assessment:
    1. The patients were examined in the first visit and were reviewed every 2 weeks for progress of therapy and the presence of any adverse effects.
    2. Evaluation of pigmentation was done by three independent observers, and the mean was calculated.
      • The repigmentation responses were expressed qualitatively as follows:
      • 0=no change (GO).
      • 0–25%=mild improvement (GI).
      • 26–50%=moderate improvement (G2).
      • 51–75%=good improvement (G3).
      • 76–100%=excellent improvement (G4).
      • The degree of improvement according to the patient opinion: the patients were asked at final visit to rate the overall satisfaction according to whether the patient was not satisfied, slightly satisfied, satisfied, or very satisfied, using the following grades:
      • Grade I=not satisfied.
      • Grade II=slightly satisfied.
      • Grade III=satisfied.
      • Grade IV=very satisfied.
  2. Follow-up assessment:


The patients were followed up monthly for 3 months after the end of treatment sessions to detect any recurrence or complications.

Statistical analysis

Data were analyzed using Statistical Program for the Social Science, version 15.0 (IBM is an American multinational technology company headquartered in New York).). Quantitative data were expressed as mean±SD. Qualitative data were expressed as frequency and percentage.


  Results Top


This study included 20 patients with stable vitiligo who were selected from the outpatient clinic of Dermatology and Venereology Department, Al-Hussien University Hospital.

Regarding age, the mean age of studied patients was 23.5±8.6 years, with minimum age of 12 years and maximum age of 40 years.

Regarding sex, there were eight (40%) males and 12 (60%) females among the studied patients.

Regarding family history, there were 17 (85%) patients with negative family history and three (15%) patients with positive family history.

Regarding duration of disease, the mean duration of studied patients was 2.4±1.08 years, with minimum duration of 1 year and maximum duration of 5 years.

Regarding type of vitiligo, there were 16 (80%) patients with nonsegmental vitiligo and four (20%) patients with segmental vitiligo among the studied patients.

Regarding site, face was affected in four (20%) patients, neck was affected in two (10%) patients, chest was affected in one (5%) patient, abdomen was affected in three (15%) patients, upper limb was affected in two (10%) patients, hand was affected in two (10%) patients, knee was affected in three (15%) patients, lower limb was affected in two (10%) patients, and back was affected in one (5%) patient.

Physician’s evaluation of the results of the study revealed that the first and the second patches showed variable degrees of repigmentation.

One (5%) patient did not show improvement on both patches, whereas 19 (95%) patients showed improvement.

There was a significant difference between the first and the second patches in the onset of the response (P<0.001). The second patch began to respond in the second week, with a mean of 4.79±2.66 weeks, whereas the first patch began to respond from the fourth week, with a mean of 7.89±2.64 weeks.

Comparison between the first and the second patches regarding the repigmentation grade showed a statistically significant increase in the second patch:
  1. Regarding right side, there were five (25%) patients of grade 0, 10 (50%) patients of grade I, three (15%) patients of grade II, one (5%) patient of grade III, and one (5%) patient of grade IV.
    1. The mean response was 21±23.7 with minimum response of 0 and maximum response of 80.
  2. Regarding left side, there were three (15%) patients of grade 0, nine (45%) patients of grade I, three (15%) patients of grade II, one (5%) patient of grade III, and four (20%) patients of grade IV.
    1. The mean response was 34.8±30.1 with minimum response of 0 and maximum response of 90.


Patients were followed up for more 12 weeks. In both patches, five (25%) patients showed more improvement, whereas 15 (75%) patients showed no more improvement, but their repigmentation was maintained.

One patient was upgraded from grade II and became grade IV only in the second patch, whereas the first patch was in the same grade, but the other patients who improved stayed in the same grade.

Comparison between the first and the second patches according to follow-up improvement grade showed statistically significant value (P<0.001).

Regarding right side, there were five (25%) patients of grade 0, eight (40%) patients of grade I, four (20%) patients of grade II, two (10%) patients of grade III, and one (5%) patient of grade IV.

Regarding left side, there were three (15%) patients of grade 0, seven (35%) patients of grade I, three (15%) patients of grade II, one (5%) patient of grade III, and six (30%) patients of grade IV.

Comparison between the first and the second patches according to follow-up clinical improvement percentage showed statistically significant value (P <0.001).

Regarding right side, the mean response was 26.3±26.4, with minimum response of 0 and maximum response of 90.

Regarding left side, the mean response was 45.5±34.7, with minimum response of 0 and maximum response 95 ([Table 1],[Table 2],[Table 3],[Table 4] and [Figure 1],[Figure 2],[Figure 3],[Figure 4]).
Table 1 Description of response of all studied patients

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Table 2 Comparison between right and left sides regarding response

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Table 3 Description of response follow-up of all studied patients

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Table 4 Comparison between right and left sides regarding response follow-up

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Figure 1 Photograph of a 12-year-old female patient with periorbital vitiligo before and after treatment.

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Figure 2 Photograph of a 16-year-old male patient with vitiligo at legs before and after treatment.

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Figure 3 Photograph of a 15-year-old female patient with vitiligo at upper limb before and after treatment.

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Figure 4 Photograph of a 20-year-old female patient with facial vitiligo before and after treatment.

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  Discussion Top


Vitiligo is a common disorder characterized by depigmented cutaneous macules usually devoid of functional melanocytes. These lesions are cosmetically disfiguring and usually cause emotional trauma in both children and adults. Vitiligo affects all races and both sexes almost equally. The population prevalence is estimated to be 0.14–2% in different countries. Vitiligo can develop at any age but the peak incidence is in second or third decade [9].

The aim of this work was to assess the efficacy of fractional CO2 laser-assisted drug delivery of topical combination of calcipotriol (50 μg/g) with betamethasone dipropionate (0.5 mg/g) versus bimatoprost (0.03%) in the treatment of vitiligo.

Our results agreed with Xing and Xu [10] who studied the effect of combined calcipotriol and betamethasone dipropionate ointment in the treatment of vitiligo. In their study, seven (22.6%) patients had no response, seven (22.6%) patients had a minimal response, eight (25.8%) patients had a mild response, six (19.4%) patients had a moderate response, and three (9.7%) patients had an excellent response.

Furthermore, Abdel Latif and Attia [11] studied the effect of monochromatic excimer light versus the topical combination therapy of vitamin D3 analog and steroid in the treatment of nonsegmental vitiligo, by evaluating the results after a period of 12 weeks. The study included 36 patients divided into two groups: group A receiving daily application of combination therapy of calcipotriol 50 µg/g plus betamethasone dipropionate 0.5 mg/g, and group B received 308 nm excimer light. Regarding the quartile grading scale, there was no significant difference in both treatment modalities (P=0.22). In the group A, seven (19.4%) patients showed excellent response with grade IV, four (11.1%) patients showed good response with grade III, 12 (33.3%) patients showed moderate response with grade II, six (16.6%) patients reported poor response with grade I, and seven (19.4%) patients showed no or absent response with grade 0. However in the group B, six (16.6%) patients reported excellent response with grade IV, 10 (27.7%) patients showed good response with grade III, five (13.8%) patients reported moderate response with grade II, seven (19.4%) patients showed poor response with grade I, and eight (22.2%) patients showed no or absent response with grade 0.

Furthermore, Newman and Silverberg [12] performed a study using once-daily application of calcipotriene 0.005% − betamethasone dipropionate 0.064% ointment for repigmentation of facial vitiligo. Two of three children had 76–100% repigmentation of facial vitiligo with once-daily usage after 2 months. Of the 10 adults (aged 28–55 years), one had 100% facial repigmentation in 3 months, one had 76–99% facial repigmentation in 5–9 months, and two had 26–50% repigmentation in 3 months.

A small study was performed by Grimes [13], where bimatoprost 0.03% drops showed efficacy in the treatment of vitiligo. The controlled study was conducted over a 20-week treatment period. Patients were randomized to one of three treatment groups: bimatoprost monotherapy (n=11), bimatoprost plus mometasone (n=10), and mometasone plus placebo (n=11). In the study, 46% of the bimatoprost plus mometasone group responded overall compared with 18% in the bimatoprost monotherapy group, and no patients responded in the mometasone plus placebo group. Greater response rates were observed in both bimatoprost groups compared with the mometasone plus bimatoprost group starting at week 12. There were no differences among groups in signs and symptoms of irritation. Bimatoprost alone or with mometasone provided greater repigmentation than treatment with mometasone alone.

Moreover, Kapoor et al. [14] studied the efficacy and safety of topical PGE2 in treating stable vitiligo. A total of 56 consecutive patients with clinically diagnosed stable vitiligo applied a translucent PGE2 (0.25 mg/g) gel twice daily for 6 months. Evaluation was observed every 2 weeks for 3 months and monthly thereafter up to 6 months. Of the 56 patients enrolled, 27 (48%) had recalcitrant patches. The remaining were fresh untreated cases. A total of 40 (71%) patients included in the study showed evidence of repigmentation at the end of 6 months. Mean onset of repigmentation was at 2 months. Overall, 100% repigmentation was observed in eight (14%) patients, 90% repigmentation in eight (14%), and 75% repigmentation in six (11%). Repigmentation at 75–100% was seen in 10 of 14 facial lesions, three of three neck lesions, two of seven lip lesions, three of five trunk lesions, and one of three genital lesions. Most patients (12 of 16) with upper and lower extremity lesions showed less than 25% repigmentation. Of 19 patients with focal vitiligo, four showed 100% repigmentation, three showed 90% repigmentation, and two showed 75% repigmentation.

In conclusion, topical combination of calcipotriol (50 μg/g) with betamethasone dipropionate (0.5 mg/g) was effective than bimatoprost (0.03%) in treating stable vitiligo. This efficacy was enhanced by combining it with fractional CO2 laser. In addition, this repigmentation was maintained in the follow-up period (12 weeks) after stopping the therapy. Fractional CO2 laser exerts an additive effect in enhancing drug delivery and thereby increases the rate and degree of repigmentation by calcipotriol (50 μg/g) and betamethasone dipropionate (0.5 mg/g) and bimatoprost (0.03%) ointment in vitiligo.


  Conclusion Top


From the result of this study, we can conclude that fractional CO2 laser followed by topical calcipotriol (0.05 mg/g) plus betamethasone (0.5 mg) ointment and topical bimatoprost (0.03%) drops are effective and safe in the treatment of vitiligo. Topical calcipotriol (0.05 mg/g) and betamethasone (0.5 mg) ointment give better results than topical bimatoprost (0.03%).

The combination of fractional CO2 laser followed by topical calcipotriol (0.05 mg/g) plus betamethasone (0.5 mg) ointment and topical bimatoprost (0.03%) was effective in the most resistant sites of vitiligo, for example, face, abdomen, neck, knee, and acral area.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Ezzedine K, Taïeb A, Morice‐Picard F, Jouary T, Cario‐André M, Gauthier Y. Segmental vitiligo as the possible expression of cutaneous somatic mosaicism. Pigment Cell Melanoma Res 2018; 21:646–652.  Back to cited text no. 1
    
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Picardo M, Maresca V, Flori E. Skin phototype: a new perspective. Pigment Cell Melanoma Res 2015; 28:378–389.  Back to cited text no. 2
    
3.
Jin Y, Andersen G, Yorgov D, Ferrara TM, Ben S, Birlea SA et al. Genome-wide association studies of autoimmune vitiligo identify 23 new risk loci and highlight key pathways and regulatory variants. Nat Genet 2016; 48:1418.  Back to cited text no. 3
    
4.
Whitton ME, Pinart M, Batchelor J, Lushey C, Leonardi-Bee J, Gonzalez U. Interventions for vitiligo. Cochrane Database System Rev 2010; 1:6–8.  Back to cited text no. 4
    
5.
Birlea SA, Costin GE, Norris DA. Cellular and molecular mechanisms involved in the action of vitamin D analogs targeting vitiligo depigmentation. Curr Drug Targets 2008; 9:345–359.  Back to cited text no. 5
    
6.
Schake H, Rehwinkel Asadullah K, Cato AC. Insight into the molecular mechanisms of glucocorticoid receptor action promotes identification of novel ligands with an improved therapeutic index. Exp Dermatol 2006; 15:565–573.  Back to cited text no. 6
    
7.
Grierson I, Jonsson M, Cracknell K. Latanoprost and pigmentation. JPN J Ophtlimol 2004; 48:602–612.  Back to cited text no. 7
    
8.
Bergh K, Wentzel P, Stjernschantz J. Production of prostaglandin, by iridial melanocytcs exposed to latanoprost acid, a prostaglandin F(2 alpha) analogue. J Ocul Pharmacol Ther 2002; 18:m391–400.  Back to cited text no. 8
    
9.
Agarwal S, Ojha A, Gupta S. Profile of vitiligo in Kumaun region of Uttarakhand,India. Indian J DermatoL 2014; 59:209.  Back to cited text no. 9
    
10.
Xing C, Xu A. The effect of combined calcipotriol and betamethasone dipropionate ointment in the treatment of vitiligo. J Drugs Dermatol 2012; 11: 52–54.  Back to cited text no. 10
    
11.
Abdel Latif AA, Attia SM. Monochromatic excimer light versus combination of topical steroid with vitamin D3 analogue in the treatment of nonsegmental vitiligo. Dermatol Ther 2015; 28:383–389.  Back to cited text no. 11
    
12.
Newman MD, Silverberg NB. Once daily application of calcipotriene and betamethasone dipropionate ointment for repigmentation of facial vitiligo. Cutis 2011; 88:256–259.  Back to cited text no. 12
    
13.
Grimes PE. Bimatoprost 0.03% solution for the treatment of nonfacial vitiligo. J Drugs Dermatol 2016; 15: 703–710.  Back to cited text no. 13
    
14.
Kapoor R, Phiske MM, Jerajani HR. Evaluation of safety and efficacy of topical prostaglandin E2 in treatment of vitiligo. Br J DermatoI 2009; 160:861–863.  Back to cited text no. 14
    


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4]



 

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