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 Table of Contents  
EDITORIAL
Year : 2016  |  Volume : 3  |  Issue : 1  |  Page : 1-4

Topical therapy in vitiligo: What is new?


Department of Dermatology and STD, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, India

Date of Web Publication17-Jun-2016

Correspondence Address:
Dr. Devinder Mohan Thappa
Department of Dermatology and STD, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry - 605 006
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/2349-5847.184247

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How to cite this article:
Malathi M, Thappa DM. Topical therapy in vitiligo: What is new?. Pigment Int 2016;3:1-4

How to cite this URL:
Malathi M, Thappa DM. Topical therapy in vitiligo: What is new?. Pigment Int [serial online] 2016 [cited 2019 Jul 20];3:1-4. Available from: http://www.pigmentinternational.com/text.asp?2016/3/1/1/184247


  Introduction Top


Medical and surgical treatments for vitiligo are suboptimal with either poor response or continued the progression of vitiligo despite therapy. As far as medical therapies are considered, high potency topical steroids and narrowband ultraviolet B (NB-UVB) irradiation are considered to be the effective form of monotherapy as per current evidence. Steroids cannot be used for prolonged duration owing to their side effects, and phototherapy may not be a feasible option always.[1],[2]

With increasing research and knowledge on the various pathomechanisms of vitiligo including those related to oxidative stress, cutaneous blood flow, cytokine or neuropeptide-mediated mechanisms,[1] to name a few, a host of new topical agents are being developed to target these mechanisms to induce pigmentation. In addition, various combination therapies are being advocated to improve the efficacy and safety of the treatment. In a study evaluating various combination therapies, it was reported that combined regimen using high potency steroids and focused NB-UVB to be the gold standard therapy for vitiligo with improved efficacy and safety.[2] However, various other combination therapies are widely being reported with claiming better results and reduced risks.

The newer topical agents include piperine, prostaglandin E2 (PGE2) analogs, prostaglandin F2 alpha (PGF2α) analog, basic fibroblast growth factor (bFGF), afamelanotide, capsaicin, Cucumis melo, L-carnosine [1] and an agent that selectively delivers NB-UVB on exposure to sunlight.[3]


  Piperine and Its Synthetic Analogs Top


It is the main alkaloid obtained from Piper nigrum (black pepper) which has been reported to have growth-stimulatory activity in cultured melanocytes and melanocyte proliferation and dendrite formation in mouse models.[1],[4] However, piperine does not stimulate melanin synthesis “per se” but is found to be effective in inducing pigmentation only with concomitant UV radiation. However when combining it with UVA radiation, the application of the agent and irradiation needs to be staggered to avoid photoisomerization.[1],[5]


  Prostaglandin E2 Analogs Top


Prostaglandins play an active role in immunomodulation, melanogenesis, proliferation and maturation of melanocytes with animal studies demonstrating an increased melanocyte density on topical application of PGE2.[6] Twice daily application of PGE2 gel for 6 months has been reported to be a promising option in stable localized vitiligo with significant results and minimal side effects of transient burning sensation.[7] UV light-induced induction of cycloxygenase (COX-2) enzyme, a mitogenic and inflammatory stimuli causing PGE2 production in keratinocytes has been attributed to the therapeutic efficacy of UV light in causing repigmentation in vitiligo.[1]


  Prostaglandin F2 Alpha Analog: Latanoprost, Bimatoprost, and Travoprost Top


Latanoprost, commonly used in the treatment of ocular hypertension was tried in vitiligo based on the presence of irreversible iris pigmentation and reversible periocular hyperpigmentation observed in these patients.[1] PGF2α however, exerts its effect indirectly through induction of COX-2 and PGE2 and has been reported to be a promising therapeutic option for vitiligo in both animal and human studies with increased efficacy when combined with phototherapy.[8],[9] The query on induction of malignant melanoma by latanoprost has been well investigated and excluded.[1]


  Basic Fibroblast Growth Factor Top


Lesional and perilesional vitiligo skin has been reported to have lower expression of cell growth factors like bFGF which is known to have an effect on melanocyte migration and pigment cell proliferation. Moreover, UV irradiation-induced increase in residual cutaneous melanocytes in vitiligo skin has been attributed to increased melanocyte growth factors like bFGF and endothelin-1. However, the role of bFGF in vitiligo is still controversial as its levels were found to be both higher and lower in different subpopulations of vitiligo patients.[1]


  Alpha-Melanocyte Stimulating Hormone Agonistic Analog-Afamelanotide Top


It induces melanogenesis and skin pigmentation by binding to melanocortin-1 receptor (MC1R) which is the key pathway for melanogenesis. Since MC1R is not expressed by melanocyte stem cells, afamelanotide stimulates pigmentation and increases proliferation of melanocytes but has no effect on the differentiation of melanocyte stem cells. On the contrary, phototherapy induces melanoblast differentiation thus afamelanotide when combined with phototherapy can increase the speed and extent of repigmentation in patients who respond to phototherapy. The major limitation of afamelanotide is the potential to induce potent tanning which becomes an issue in fair skinned individuals owing to the sharp contrast in color.[1],[10]


  Capsaicin Top


Obtained from chili peppers, capsaicin is a natural irritant of vanilloid family which has potent anti-inflammatory, antioxidant, and anti-apoptotic properties. Vitiligo is known to be associated with keratinocyte dysfunction and apoptosis which subsequently contributes to melanocyte degeneration. It has been observed that pretreatment with capsaicin and curcumin (obtained from Curcuma longa - turmeric) increased the cellular total antioxidant capacity and decreased reactive oxygen species formation thereby inhibiting keratinocyte apoptosis. Thus, capsaicin and curcumin can prevent and inhibit disease progression and promote repigmentation in vitiligo.[1]


  Cucumis Melo Top


Marketed as Vitix, C. melo is reported to have superoxide dismutase and catalase-like activities when associated with selective UVB therapy. However, the reports on the efficacy of Vitix in vitiligo has been controversial warranting additional well-designed clinical trials.[1],[11]


  L-Carnosine (Beta-Alanyl-L-Histidine) Top


A dipeptide with high antioxidant properties protecting cell membranes from oxidative damage and reducing age-related mitochondrial dysfunction is proposed to be a promising therapeutic agent in vitiligo, as mitochondrial dysfunction resulting in cell damage in vitiligo keratinocytes has been reported to be one of the pathomechanisms in vitiligo. However, it needs further investigation.[1]


  Photocil (Alpha-Glucosyl Hesperidin + diethylaminohydroxybenzoyl Hexyl Benzoate) Top


It is a novel therapeutic agent that has been developed to deliver NB-UVB selectively filtering out the harmful UV radiation when exposed to natural sunlight thereby offering vitiligo patients a convenient phototherapy option improving their compliance.[12],[13]


  Others Top


A new agent comprising a combination of phenylalanine, C. melo extract and acetylcysteine in a gel formulation has been found to be effective in inducing repigmentation either given as monotherapy or in combination with NB microphototherapy.[14]

As mentioned earlier, the current trend is to combine various therapeutic options for improved efficacy and minimizing side effects. The most common combination therapy includes combining various topical agents with phototherapy and/or with lasers and these combinations can be considered a viable option in refractory cases of vitiligo. The well-established combination therapy includes topical steroids or topical calcineurin inhibitors with NB-UVB.[2],[15] The various other recent combination therapies involving topical therapy which has been reported to be effective include the following:

  • Topical calcineurin inhibitors in combination with excimer laser [15]
  • Topical placental extract (placentrex) in combination with NB-UVB phototherapy [16]
  • Topical ethyl vallinate cream in combination with NB-UVB phototherapy [17]
  • Tetrahydrocurcuminoid cream in combination with targeted NB-UVB phototherapy [18]
  • Erbium-doped yttrium aluminum garnet (Er-YAG) laser ablation and topical 5-flurouracil cream in combination with NB-UVB phototherapy [19]
  • Fractional carbon dioxide (CO2) laser in combination with topical 5-flurouracil cream [20]
  • Microdermabrasion in combination with topical 5-flurouracil cream [21]
  • Intralesional 5-flurouracil in combination with NB-UVB phototherapy [22]
  • Fractional CO2 laser and potent topical steroids in combination with NB-UVB phototherapy [23],[24]
  • Er-YAG laser dermabrasion and potent topical steroid in combination with NB-UVB phototherapy [25]
  • 4% topical khellin and/or 0.1% tacrolimus in combination with monochromatic excimer light [26]
  • Topical calcipotriol ointment in combination with NB-UVB phototherapy.[27]


Combined treatments have been found to be superior to monotherapies regarding efficacy, early response and safety, especially in difficult to treat areas and refractory cases. However, intolerance to side effects limiting their wide use in some of these combinations, especially those involving lasers need to be considered.

 
  References Top

1.
Lotti TM, Hercogová J, Schwartz RA, Tsampau D, Korobko I, Pietrzak A, et al. Treatments of vitiligo: What's new at the horizon. Dermatol Ther 2012;25 Suppl 1:S32-40.  Back to cited text no. 1
    
2.
Lotti T, Buggiani G, Troiano M, Assad GB, Delescluse J, De Giorgi V, et al. Targeted and combination treatments for vitiligo. Comparative evaluation of different current modalities in 458 subjects. Dermatol Ther 2008;21 Suppl 1:S20-6.  Back to cited text no. 2
    
3.
Wang X, McCoy J, Lotti T, Goren A. Topical cream delivers NB-UVB from sunlight for the treatment of vitiligo. Expert Opin Pharmacother 2014;15:2623-7.  Back to cited text no. 3
    
4.
Faas L, Venkatasamy R, Hider RC, Young AR, Soumyanath A.In vivo evaluation of piperine and synthetic analogues as potential treatments for vitiligo using a sparsely pigmented mouse model. Br J Dermatol 2008;158:941-50.  Back to cited text no. 4
    
5.
Soumyanath A, Venkatasamy R, Joshi M, Faas L, Adejuyigbe B, Drake AF, et al. UV irradiation affects melanocyte stimulatory activity and protein binding of piperine. Photochem Photobiol 2006;82:1541-8.  Back to cited text no. 5
    
6.
Parsad D, Pandhi R, Dogra S, Kumar B. Topical prostaglandin analog (PGE2) in vitiligo – A preliminary study. Int J Dermatol 2002;41:942-5.  Back to cited text no. 6
    
7.
Kapoor R, Phiske MM, Jerajani HR. Evaluation of safety and efficacy of topical prostaglandin E2 in treatment of vitiligo. Br J Dermatol 2009;160:861-3.  Back to cited text no. 7
    
8.
Anbar TS, El-Ammawi TS, Barakat M, Fawzy A. Skin pigmentation after NB-UVB and three analogues of prostaglandin F(2alpha) in guinea pigs: A comparative study. J Eur Acad Dermatol Venereol 2010;24:28-31.  Back to cited text no. 8
    
9.
Anbar TS, El-Ammawi TS, Abdel-Rahman AT, Hanna MR. The effect of latanoprost on vitiligo: A preliminary comparative study. Int J Dermatol 2015;54:587-93.  Back to cited text no. 9
    
10.
Lim HW, Grimes PE, Agbai O, Hamzavi I, Henderson M, Haddican M, et al. Afamelanotide and narrowband UV-B phototherapy for the treatment of vitiligo: A randomized multicenter trial. JAMA Dermatol 2015;151:42-50.  Back to cited text no. 10
    
11.
Schallreuter KU, Panske A, Chiuchiarelli G. Ineffective topical treatment of vitiligo with Cucumis melo extracts. Int J Dermatol 2011;50:374-5.  Back to cited text no. 11
[PUBMED]    
12.
Goren A, Salafia A, McCoy J, Keene S, Lotti T. Novel topical cream delivers safe and effective sunlight therapy for vitiligo by selectively filtering damaging ultraviolet radiation. Dermatol Ther 2014;27:195-7.  Back to cited text no. 12
    
13.
McCoy J, Goren A, Lotti T.In vitro evaluation of a novel topical cream for vitiligo and psoriasis that selectively delivers NB-UVB therapy when exposed to sunlight. Dermatol Ther 2014;27:117-20.  Back to cited text no. 13
    
14.
Buggiani G, Tsampau D, Hercogovà J, Rossi R, Brazzini B, Lotti T. Clinical efficacy of a novel topical formulation for vitiligo: Compared evaluation of different treatment modalities in 149 patients. Dermatol Ther 2012;25:472-6.  Back to cited text no. 14
    
15.
Dang YP, Li Q, Shi F, Yuan XY, Liu W. Effect of topical calcineurin inhibitors as monotherapy or combined with phototherapy for vitiligo treatment: A meta-analysis. Dermatol Ther 2016;29:126-33.  Back to cited text no. 15
    
16.
Majid I. Topical placental extract: Does it increase the efficacy of narrowband UVB therapy in vitiligo? Indian J Dermatol Venereol Leprol 2010;76:254-8.  Back to cited text no. 16
[PUBMED]  Medknow Journal  
17.
Namazi MR, Shotorbani AK. Evaluation of the efficacy of topical ethyl vanillate in enhancing the effect of narrow band ultraviolet B against vitiligo: A double blind randomized, placebo-controlled clinical trial. Iran J Med Sci 2015;40:478-84.  Back to cited text no. 17
    
18.
Asawanonda P, Klahan SO. Tetrahydrocurcuminoid cream plus targeted narrowband UVB phototherapy for vitiligo: A preliminary randomized controlled study. Photomed Laser Surg 2010;28:679-84.  Back to cited text no. 18
    
19.
Anbar TS, Westerhof W, Abdel-Rahman AT, Ewis AA, El-Khayyat MA. Effect of one session of ER: YAG laser ablation plus topical 5fluorouracil on the outcome of short-term NB-UVB phototherapy in the treatment of non-segmental vitiligo: A left-right comparative study. Photodermatol Photoimmunol Photomed 2008;24:322-9.  Back to cited text no. 19
    
20.
Mohamed HA, Mohammed GF, Gomaa AH, Eyada MM. Carbon dioxide laser plus topical 5-fluorouracil: A new combination therapeutic modality for acral vitiligo. J Cosmet Laser Ther 2015;17:216-23.  Back to cited text no. 20
    
21.
Garg T, Chander R, Jain A. Combination of microdermabrasion and 5-fluorouracil to induce repigmentation in vitiligo: An observational study. Dermatol Surg 2011;37:1763-6.  Back to cited text no. 21
    
22.
Abd El-Samad Z, Shaaban D. Treatment of localized non-segmental vitiligo with intradermal 5-flurouracil injection combined with narrow-band ultraviolet B: A preliminary study. J Dermatolog Treat 2012;23:443-8.  Back to cited text no. 22
    
23.
Li L, Wu Y, Li L, Sun Y, Qiu L, Gao XH, et al. Triple combination treatment with fractional CO2 laser plus topical betamethasone solution and narrowband ultraviolet B for refractory vitiligo: A prospective, randomized half-body, comparative study. Dermatol Ther 2015;28:131-4.  Back to cited text no. 23
    
24.
Vachiramon V, Chaiyabutr C, Rattanaumpawan P, Kanokrungsee S. Effects of a preceding fractional carbon dioxide laser on the outcome of combined local narrowband ultraviolet B and topical steroids in patients with vitiligo in difficult-to-treat areas. Lasers Surg Med 2016;48:197-202.  Back to cited text no. 24
    
25.
Bayoumi W, Fontas E, Sillard L, Le Duff F, Ortonne JP, Bahadoran P, et al. Effect of a preceding laser dermabrasion on the outcome of combined therapy with narrowband ultraviolet B and potent topical steroids for treating nonsegmental vitiligo in resistant localizations. Br J Dermatol 2012;166:208-11.  Back to cited text no. 25
    
26.
Bagherani N. The efficacy of 308 nm UV excimer light as monotherapy and combination therapy with topical khellin 4% and/or tacrolimus 0.1% in the treatment of vitiligo. Dermatol Ther 2016;29:137-8.  Back to cited text no. 26
    
27.
Khullar G, Kanwar AJ, Singh S, Parsad D. Comparison of efficacy and safety profile of topical calcipotriol ointment in combination with NB-UVB vs. NB-UVB alone in the treatment of vitiligo: A 24-week prospective right-left comparative clinical trial. J Eur Acad Dermatol Venereol 2015;29:925-32.  Back to cited text no. 27
    



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  In this article
Introduction
Piperine and Its...
Prostaglandin E2...
Prostaglandin F2...
Basic Fibroblast...
Alpha-Melanocyte...
Capsaicin
L-Carnosine (Bet...
Photocil (Alpha-...
Others
Cucumis Melo
References

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