|Year : 2016 | Volume
| Issue : 1 | Page : 1-4
Topical therapy in vitiligo: What is new?
Munisamy Malathi, Devinder Mohan Thappa
Department of Dermatology and STD, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, India
|Date of Web Publication||17-Jun-2016|
Dr. Devinder Mohan Thappa
Department of Dermatology and STD, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry - 605 006
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Malathi M, Thappa DM. Topical therapy in vitiligo: What is new?. Pigment Int 2016;3:1-4
| Introduction|| |
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.,
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, 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. 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  and an agent that selectively delivers NB-UVB on exposure to sunlight.
| Piperine and Its Synthetic Analogs|| |
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., 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.,
| Prostaglandin E2 Analogs|| |
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. 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. 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.
| Prostaglandin F2 Alpha Analog: Latanoprost, Bimatoprost, and Travoprost|| |
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. 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., The query on induction of malignant melanoma by latanoprost has been well investigated and excluded.
| Basic Fibroblast Growth Factor|| |
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.
| Alpha-Melanocyte Stimulating Hormone Agonistic Analog-Afamelanotide|| |
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.,
| Capsaicin|| |
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.
| Cucumis Melo|| |
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.,
| L-Carnosine (Beta-Alanyl-L-Histidine)|| |
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.
| Photocil (Alpha-Glucosyl Hesperidin + diethylaminohydroxybenzoyl Hexyl Benzoate)|| |
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.,
| Others|| |
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.
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., 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 
- Topical placental extract (placentrex) in combination with NB-UVB phototherapy 
- Topical ethyl vallinate cream in combination with NB-UVB phototherapy 
- Tetrahydrocurcuminoid cream in combination with targeted NB-UVB phototherapy 
- Erbium-doped yttrium aluminum garnet (Er-YAG) laser ablation and topical 5-flurouracil cream in combination with NB-UVB phototherapy 
- Fractional carbon dioxide (CO2) laser in combination with topical 5-flurouracil cream 
- Microdermabrasion in combination with topical 5-flurouracil cream 
- Intralesional 5-flurouracil in combination with NB-UVB phototherapy 
- Fractional CO2 laser and potent topical steroids in combination with NB-UVB phototherapy ,
- Er-YAG laser dermabrasion and potent topical steroid in combination with NB-UVB phototherapy 
- 4% topical khellin and/or 0.1% tacrolimus in combination with monochromatic excimer light 
- Topical calcipotriol ointment in combination with NB-UVB phototherapy.
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.
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