IJD
Indian Journal of Dermatology
  Publication of IADVL, WB
  Official organ of AADV
Indexed with Science Citation Index (E) , Web of Science and PubMed
 
Users online: 19  
Home About  Editorial Board  Current Issue Archives Online Early Coming Soon Guidelines Subscriptions  e-Alerts    Login  
    Small font sizeDefault font sizeIncrease font size Print this page Email this page


 
Table of Contents 
THERAPEUTIC ROUND
Year : 2015  |  Volume : 60  |  Issue : 4  |  Page : 364-368
Repigmentation of hypopigmented scars using combination of fractionated carbon dioxide laser with topical latanoprost vs. fractionated carbon dioxide laser alone


1 Department of Dermatology, Skin Diseases and Leishmaniasis Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
2 Department of Dermatology, Skin Diseases and Leishmaniasis Research Center, Isfahan University of Medical Sciences, Isfahan; Department of Dermatology, Medicine Students' Research Committee, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
3 Department of Epidemiology and Biostatistics, School of Medicine, Qom University of Medical Sciences, Qom, Iran
4 Department of Epidemiology and Biostatistics, Isfahan University of Medical Sciences, Isfahan, Iran

Date of Web Publication10-Jul-2015

Correspondence Address:
Dr. Reza Rezaei
Department of Dermatology, Al-Zahra Hospital, Soffeh Boulevard, Isfahan University of Medical Sciences, Isfahan
Iran
Login to access the Email id

Source of Support: This work was supported financially by a grant from Isfahan University of Medical Sciences (research proposal number 392019), Conflict of Interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the manuscript.


DOI: 10.4103/0019-5154.160481

Clinical trial registration IRCT2013123016002N1

Rights and Permissions

   Abstract 

Background: Fractionated carbon dioxide (CO 2 ) can treat hypopigmented scars. Latanoprost is a prostaglandin analog used to treat glaucoma. It can cause adverse effects, such as periocular hyperpigmentation. The aim of this study was to assess the efficacy and safety of latanoprost plus CO 2 laser on the repigmentation of hypopigmented scars. Patients and Methods: 28 patients with hypopigmented scars were divided randomly into two groups. The patients in group A were treated in six sessions (1-month intervals) with 10600-nm fractional CO 2 laser plus latanoprost 0.005% and those of group B fractionated CO 2 laser plus placebo (distilled water). Digital photographs were taken at baseline and 3 months after the last treatment session. The blinded dermatologist compared the photographs and evaluated the efficacy of treatment in the hypopigmented scars using a 4-scale point (grade 1-4). Patient satisfaction was scored from 0 to 10 on a visual analog scale. Results: Follow-up results 12 weeks after the last treatment session demonstrated that 11 of the 14 patients in group A had more than 50% improvement in hypopigmentation The difference in improvement of the two groups was statistically significant (P = 0.027). The mean of the VAS scores of patients in group A was 6.50 ± 1.45 and in group B 4.57 ± 1.6. The difference in mean satisfaction of the two groups was statistically significant (P = 0.003). Side effects were mild and resolved within 1 to 5 days. Conclusion: The fractional CO 2 laser resurfacing plus topical latanoprost can be used as a safe and efficacious method to treat hypopigmented scars.


Keywords: Fractionated carbon dioxide laser, fractionated carbon dioxide laser, hypopigmented scars, latanoprost


How to cite this article:
Siadat AH, Rezaei R, Asilian A, Abtahi-Naeini B, Rakhshanpour M, Raei M, Hosseini SM. Repigmentation of hypopigmented scars using combination of fractionated carbon dioxide laser with topical latanoprost vs. fractionated carbon dioxide laser alone. Indian J Dermatol 2015;60:364-8

How to cite this URL:
Siadat AH, Rezaei R, Asilian A, Abtahi-Naeini B, Rakhshanpour M, Raei M, Hosseini SM. Repigmentation of hypopigmented scars using combination of fractionated carbon dioxide laser with topical latanoprost vs. fractionated carbon dioxide laser alone. Indian J Dermatol [serial online] 2015 [cited 2021 Jun 16];60:364-8. Available from: https://www.e-ijd.org/text.asp?2015/60/4/364/160481

What was known?
Hypopigmented scarring is a common complication but improving the appearance of hypopigmented scars has remained a challenge because of the limited efficacy, variable safety and limited availability of practical treatment options.



   Introduction Top


Hypopigmented scarring is a common complication, particularly in patients who have undergone surgical procedures, deep or medium-depth resurfacing procedures, or have a prior history of traumatic wounds or burns. [1] Improving the appearance of hypopigmented scars has remained a challenge because of the limited efficacy, variable safety and limited availability of effective and practical treatment options with long-lasting results. [1] Several modalities have been implicated to treat hypopigmened scarring including skin grafting, scar excision or revision, cosmetic camouflage, cosmetic tattooing, dermabrasion, chemical peels and various forms of phototherapy and laser resurfacing. The efficacy of these methods is limited, and there is currently no gold standard. [2],[3],[4]

The fractional carbon dioxide (CO 2 ) laser produces multiple zones of microscopic thermal injury, surrounded by viable tissue that provides intact epidermal and dermal cells to migrate into the zone of damage and produce rapid healing and may also improve the texture of the scar and correct atrophy through the remodeling and up-regulation of collagen production. [5],[6],[7],[8]

Latanoprost is a synthetic prostaglandin analog which decreases intraocular pressure and has been associated with periocular skin hyperpigmentation, possibly due to increased melanogenesis; [9],[10] it is also possible that this adverse effect is related to a higher melanocyte density. [11] There is a great need for a safe and effective treatment for both the color and the texture of hypopigmented scars. [7] To the best of our knowledge, the effect of latanoprost plus fractionated CO 2 laser has not been tested on the repigmentation of hypopigmented scars in patients. This study has been performed to evaluate the safety and efficacy of 10,600 nm fractional CO 2 laser (Edge fractional, Jeisys Co., Seoul, South Korea) plus topical latanoprost for the treatment of hypopigmented scars.


   Materials and Methods Top


A double-blind, randomized placebo-control study was done to assess the efficacy of a 6-session fractional CO 2 laser and 24-week topical latanoprost 0.005% treatment on scar repigmentation. The study protocol was approved by the Ethics Committee of Isfahan University of Medical Sciences, Isfahan, Iran. The research project number was 392019. Subjects were 28 otherwise healthy individuals, aged 15 to 50 years, with skin phototype II to IV with hypopigmented scars. Reasons for exclusion were: Pregnancy or intention to become pregnant; breastfeeding; severe systemic diseases; history of having taken systemic retinoid within the previous 6 months; using depigmenting or pigmenting products on the scar site during the preceding 3 months; and allergy or hypersensitivity to any component of the product under investigation.

After written informed consent, the patients were allocated into two groups using a table of random numbers: fractional CO 2 laser plus latanoprost 0.005% (n = 14) (group A), and fractional CO 2 laser plus placebo (n = 14) (group B). On the first visit, a general clinical examination and an interview on medical history and concomitant therapies were performed. Questionnaires that included information about age, sex, time of scar appearance and scar location were completed. The product to be tested was latanoprost 0.005% (50 Mcg/Ml ophtalmic Solution; SinaDarou Co., Iran) packaged in droppers as against the placebo (Distilled water) packaged in identical droppers. Each subject received one of both products with the dose of one drop over an area measuring approximately 2 by 2 cm, twice daily for 24 weeks on the scar locations. The first topical application was performed on site by the investigator and for the first week. After being familiarized with the method of correct application, each subject applied the products at home for the following 23 weeks. At the end, drug accountability was performed to control compliance. Each group underwent six treatment sessions at 1-month intervals of fractional CO 2 laser (Edge fractional, Jeisys Co., Seoul, South Korea). The treatment settings were 400 to 500 mJ, pulse interval 0.03 ms and 0.4-mm density in square shape scan pattern fractional CO 2 laser. Patients were also instructed to avoid the use of any systemic or topical drug during the course of treatment. Photographs were taken using identical camera settings (Canon D30, Canon Inc., Tokyo, Japan), lighting, and patient positioning at baseline and 3 months after the last treatment session.

Two blinded dermatologists performed clinical assessments in a blinded fashion by comparing before and after photographs using a 4-point scale (grade 1, 0-25% = minimal improvement; grade 2, 26-50% = moderate improvement; grade 3, 51-75% = marked improvement; and grade 4, ≥76% = near total improvement). Local tolerance was evaluated at each assessment period (1-month intervals) by direct evaluation for erythema, crusting and desquamation. Also, investigators assessed and recorded possible side effects, including bleeding, pain, pruritus, burning, and contact dermatitis, hypertrichosis at each visit (between 1-month intervals). Three months after the final treatment session, the data were reassessed and analyzed. Patient satisfaction was scored from 0 to 10 on a visual analog scale from (VAS). (0 as no satisfaction and 10 as the best possible satisfaction).

Statistical analysis

Statistical evaluation was done using SPSS ® for Windows version 18.0 (SPSS Inc., II, USA). Ordinal logistic regression was used for comparisons at baseline and during the study.


   Results Top


A total of 28 patients (15 females and 13 males) were included in this study. All patients (100%) completed the study. The basic patient data and clinical characteristics of each group are summarized in [Table 1]. We recruited the eligible patients and designed a flow-chart diagram through our study as shown in [Figure 1]. The mean age of patients in group A was 32.28 ± 10.54 years and in group B 33.42 ± 9.5 years. The difference in mean ages of the two groups was not statistically significant (P = 0.76). Also, there was no significant difference between sex ratios in the two groups (P = 0.73). All patients received six sessions of laser treatment. Follow-up results 12 weeks after the last treatment session demonstrated that 11 of the 14 patients in group A had more than 50% improvement in hypopigmentation [Figure 2] and [Figure 3], [Table 2]. The difference in improvement of the two groups was statistically significant (P = 0.027). With regard to patient satisfaction scores ranging from 0 to 10 on the visual analog scale (VAS), at the end of the study more patients in group A reported greater scales compared to patients in group B, such that statistical analysis revealed a significant difference between the two groups (P = 0.003). The mean VAS scores of patients in group A was 6.50 ± 1.45 and in group B 4.57 ± 1.6. The difference in mean satisfaction of the two groups was statistically significant (P = 0.003). The physician's degree of improvement paralleled patient improvement assessment.
Figure 1: The flow-chart of the study

Click here to view
Figure 2: (a) Hypopigmented facial Leishmaniasis scars on the left cheek at baseline in 45-year-old female (b) Marked improvement in pigmentation 3 month after six fractional resurfacing plus topical latanoprost treatments

Click here to view
Figure 3: (a) Hypopigmented traumatic scars in 15-year-old female in the forehead before treatment (b) Follow-up 3 month after six treatment sessions of fractional resurfacing plus topical latanoprost

Click here to view
Table 1: Clinical charecteristics of each group


Click here to view
Table 2: Follow - up results of the study, 12 weeks after the last session


Click here to view


The longer the interval between scar initiation and treatment, the lower the probability of cure; for each year added to this interval the probability of the individual's placement in the lesser-cured group iss. However, no statistically relevant correlation was observed (P = 0.1). There was a tendency toward higher improvement scores with darker skin phototype although this was not statistically significant (P = 0.13)[Figure 4]. As regards the correlation between skin phototype and satisfactory treatment, it should be said that the probability of placement in the lesser-cured group for individuals with type 2 skin phototype compared with type IV skin phototype individuals ise 3.34 = 28.5 (P = 0.04), and the probability of type III skin phototype individuals' placement in the lesser-cured group in comparison with individuals with type 4 skin phototype is approximately e 1.749 = 5.8 times higher (P = 0.13).
Figure 4: Correlation between skin phototype and satisfactory treatment. Higher improvement scores with darker skin phototype (P=0.13)

Click here to view


Although, there were no serious adverse reactions, there were some reports of erythema, pain and edema following the laser therapy in both groups. We did not observe any case of hypertrichosis throughout the follow-up period.

All patients tolerated the laser treatments well, with a majority experiencing post-treatment edema (1-3 days) and erythema (1-5 days). No long-term adverse effects were observed and no patient gave up the study due to side-effects in either group.


   Discussion Top


This report demonstrates that fractional resurfacing plus topical latanoprost is a potentially effective treatment for hypopigmented scars. Most patients had marked clinical improvement in their hypopigmented scars. So, our observations suggest that latanoprost may be used for treating such scars. Theoretically, the mechanisms of the function of laser resurfacing include tissue ablation, immediate collagen shrinkage, and dermal collagen remodeling. Columns of microscopic ablated epidermis and dermis, after treatment with fractional CO 2 laser, may result in macroscopic epidermal regeneration as evidenced by clinical improvement of scar and skin color and texture. [12] It is possible that fractional resurfacing causes normal melanocytes from surrounding tissue to repopulate this newly resurfaced tissue resulting in increased overall pigmentation. [7] But histologic studies are needed to further elucidate the healing process and confirm the movement of melanocytes into the treated area. [7] Glaich et al., used the 1,550-nm fractional laser to treat seven patients with hypopigmented scars on the face, and found 51% to 75% improvement in six of these patients after two to four treatments. Patients also reported improvement lasting longer than 3 months after the last treatment. [7] Darkening of eyelid skin or other sites around the eye has been reported as an occasional side effect associated with Prostaglandin Analogs therapy (PGAs) (e.g. latanoprost). [13],[14] Latanoprost is a 17 phenyl-substituted analogue of prostaglandin F2 alpha (PGF2 alpha), which is used for open-angle glaucoma and ocular hypertension as an ophthalmic solution because of its efficacy and minimal systemic adverse effects. [15] However, a cause-and-effect relationship has been questioned by some authors because the evidence is based predominantly on case reports. [16] The prostaglandin-associated pigmentation is most noticeable in the skin of the eyelids and can become apparent in a matter of months, although it has been reported that the side effect can take as long as 3 years after the start of prostaglandin treatment to become manifest. [13],[17] The mechanism by which PGA-associated periocular skin pigmentation occurs is unclear. [17] These events seem to involve melanogenesis, without there being obvious melanocyte proliferation, inflammation or melanocyte atypia. [9],[18],[19] It is likely that the PGAs stimulate prostaglandin receptors, such as the FP receptor, to initiate melanogenesis and tissue darkening. [14],[20] Also PGF2_ stimulates the activity and expression of tyrosinase, the ratelimiting enzyme in melanin synthesis, and the PGF2 alpha receptor has been shown to be up-regulated by UV radiation in melanocytes in vitro and in human skin in vivo. [21] The grade of hyperpigmentation increases with increased exposure to the drug, suggesting a possible dose dependency of the PGAs -induced pigmentation. [22] It should be noted that frequent contact of the topical prostaglandin analogue with the skin is a contributing factor to pigmentation and that PGAs -induced pigmentation appeared most frequently after 3 months. [22] Also in our study, patients were instructed to apply topical latanoprost twice a day for 6 months. The results of the Massaki et al. study showed that combining fractionated laser systems with topical bimatoprost, a PGA, and tretinoin or pimecrolimus had significant improvement (>50%) in more than 85% (12/14) of the patients treated. [1] This result is compatible with our study. The limitations of our study were small sample size, lack of histopathologic evaluation and lack of objective methods for result assessment.


   Conclusion Top


In conclusion although Fractional CO 2 laser plus topical latanoprost provides a safe and effective treatment of hypopigmented scarring, further studies are needed to help define the optimal treatment parameters and other potential indications for this topical latanoprost. In future studies the effectiveness of topical latanoprost should be followed as regards the hypopigmented scar alone.



 
   References Top

1.
Massaki AB, Fabi SG, Fitzpatrick R. Repigmentation of hypopigmented scars using an erbium-doped 1,550-nm fractionated laser and topical bimatoprost. Dermatol Surg 2012;38:995-1001.  Back to cited text no. 1
    
2.
Alexiades-Armenakas MR, Bernstein LJ, Friedman PM, Geronemus RG. The safety and efficacy of the 308-nm excimer laser for pigment correction of hypopigmented scars and striae alba. Arch Dermatol 2004;140:955-60.  Back to cited text no. 2
    
3.
Alster T, Zaulyanov L. Laser scar revision: A review. Dermatol Surg 2007;33:131-40.  Back to cited text no. 3
    
4.
Kauvar A, Hruza G. Principles and Practices in Cutaneous Laser Surgery.Miami, FL, U.S.A: Informa Health Care; 2005. p. 841-8.  Back to cited text no. 4
    
5.
Manstein D, Herron GS, Sink RK, Tanner H, Anderson RR. Fractional photothermolysis: A new concept for cutaneous remodeling using microscopic patterns of thermal injury. Lasers Surg Med 2004;34:426-38.  Back to cited text no. 5
    
6.
Laubach HJ, Tannous Z, Anderson RR, Manstein D. Skin responses to fractional photothermolysis. Lasers Surg Med 2006;38:142-9.  Back to cited text no. 6
    
7.
Glaich AS, Rahman Z, Goldberg LH, Friedman PM. Fractional resurfacing for the treatment of hypopigmented scars: A pilot study. Dermatol Surg 2007;33:289-94.  Back to cited text no. 7
    
8.
Nilforoushzadeh MA, Jaffary F, Ansari N, Moradi S, Siadat AH. The comparison between trichloroacetic acid 50% and co (2) laser in the treatment of cutaneous leishmaniasis scar. Indian J Dermatol 2011;56:171-3.  Back to cited text no. 8
[PUBMED]  Medknow Journal  
9.
Kapur R, Osmanovic S, Toyran S, Edward DP. Bimatoprost-induced periocular skin hyperpigmentation: Histopathological study. Arch Ophthalmol 2005;123:1541-6.  Back to cited text no. 9
    
10.
Abdel-Malek ZA, Swope VB, Amornsiripanitch N, Nordlund JJ.In vitro modulation of proliferation and melanization of S91 melanoma cells by prostaglandins. Cancer Res 1987;47:3141-6.  Back to cited text no. 10
[PUBMED]    
11.
Ortiz-Perez S, Olver JM. Hypertrichosis of the upper cheek area associated with travoprost treatment of glaucoma. Ophthal Plast Reconstr Surg 2010;26:376-7.  Back to cited text no. 11
    
12.
Manuskiatti W, Triwongwaranat D, Varothai S, Eimpunth S, Wanitphakdeedecha R. Efficacy and safety of a carbon-dioxide ablative fractional resurfacing device for treatment of atrophic acne scars in Asians. J Am Acad Dermatol 2010;63:274-83.  Back to cited text no. 12
    
13.
Herndon LW, Williams RD, Wand M, Asrani S. Increased periocular pigmentation with ocular hypotensive lipid use in African Americans. Am J Ophthalmol 2003;135:713-5.  Back to cited text no. 13
    
14.
Kook MS, Lee K. Increased eyelid pigmentation associated with use of latanoprost. Am J Ophthalmol 2000;129:804-6.  Back to cited text no. 14
    
15.
Wand M, Ritch R, Isbey EK Jr, Zimmerman TJ. Latanoprost and periocular skin color changes. Arch Ophthalmol 2001;119:614-5.  Back to cited text no. 15
    
16.
Schumer RA, Camras CB, Mandahl AK. Putative side effects of prostaglandin analogs. Surv Ophthalmol 2002;47(Suppl 1):S219.  Back to cited text no. 16
    
17.
Alm A, Grierson I, Shields MB. Side effects associated with prostaglandin analog therapy. Surv Ophthalmol 2008;53(Suppl 1):S93-105.  Back to cited text no. 17
    
18.
Arranz-Marquez E, Teus MA, Saornil MA, Mendez MC, Gil R. Analysis of irises with a latanoprost-induced change in iris color. Am J Ophthalmol 2004;138:625-30.  Back to cited text no. 18
    
19.
Cracknell KP, Grierson I, Hogg P. Morphometric effects of long-term exposure to latanoprost. Ophthalmology 2007;114:938-48.  Back to cited text no. 19
    
20.
Galloway GD, Eke T, Broadway DC. Periocular cutaneous pigmentary changes associated with bimatoprost use. Arch Ophthalmol 2005;123:1609-10.  Back to cited text no. 20
    
21.
Scott G, Jacobs S, Leopardi S, Anthony FA, Learn D, Malaviya R, et al. Effects of PGF2alpha on human melanocytes and regulation of the FP receptor by ultraviolet radiation. Exp Cell Res 2005;304:407-16.  Back to cited text no. 21
    
22.
Centofanti M, Oddone F, Chimenti S, Tanga L, Citarella L, Manni G. Prevention of dermatologic side effects of bimatoprost 0.03% topical therapy. Am J Ophthalmol 2006;142:1059-60.  Back to cited text no. 22
    

What is new?
Fractional CO 2 laser plus topical latanoprost provides a safe and effective treatment of hypopigmented scarring.


    Figures

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

  [Table 1], [Table 2]



 

Top
Print this article  Email this article
 
 
  Search
 
  
    Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
    Article in PDF (797 KB)
    Citation Manager
    Access Statistics
    Reader Comments
    Email Alert *
    Add to My List *
* Registration required (free)  


    Abstract
   Introduction
    Materials and Me...
   Results
   Discussion
   Conclusion
    References
    Article Figures
    Article Tables

 Article Access Statistics
    Viewed8291    
    Printed66    
    Emailed1    
    PDF Downloaded96    
    Comments [Add]    

Recommend this journal