What’s New in Melasma Treatment

成大醫院皮膚科

趙曉秋醫師

Introduction Melasma is an irregular brown or

grayish-brown facial hypermelanosis, often affecting women, especially those living in areas of intense UV radiation

The precise cause of melasma remains unknown; however, there are many possible contributing factors

Introduction

Melasma is sometimes used interchangeably with the term ‘‘chloasma,’’ which is a hyperpigmentation that often results from pregnancy or changes in uterine and ovarian hormones

Melasma, however, can have a variety of possible causes. The common contributing factors include genetic predisposition, pregnancy, use of oral contraceptives, endocrine dysfunction or hormone treatments,and exposure to UV light.

Epidemiology

90% of sufferers are women

Affects all race groups and skin types mainly skin types IV - VI

Predominates Hispanics, Caribbeans, Asians, Orientals

Areas of high UV exposure

5 - 6 million women in USA have melasma

50 - 70% of pregnant women in the USA, usually in 2nd or 3rd trimester

>80% of pregnant women in Mexico

Jimbow; Minamitsuji. Dermat Ther 2001;14:35–45. Grimes. Arch Dermatol 1995; 131: 1453 – 7.

Aetiology - Predisposing Factors

Genetic susceptibility: 20% to 70%

Solar radiation

Hormonal changes pregnancy

oral contraceptive use

hormone replacement therapy

Anti-epilepsy medication

Thyroid dysfunction

Grimes. Arch Dermatol 1995; 131: 1453 – 7.

Ultraviolet exposure

• Ultraviolet exposure is a major triggering and aggravating factor in the development of melasma, since it has a well known ability to stimulate proliferation of melanocytes, their migration, and melanogenesis.

• However, UV-induced hyperpigmentation usually recovers spontaneously, whereas melasma does not.

• Recently, Kim et al. detected down-regulation of the H19 gene on microarray analysis of hyperpigmented and normally pigmented skin in patients with melasma.

Kim NH, Lee CH, Lee AY. H19 RNA downregulation stimulated melanogenesis in melasma. Pigment Cell Melanoma Res. 2010 Feb;23(1):84-92.

H19 gene

• H19 is a gene for a long noncoding RNA, found in humans and elsewhere.

• H19 has a role in the negative regulation (or limiting) of body weight and cell proliferation.

• This gene also has a role in the formation of some cancers and in the regulation of gene expression.

• The H19 gene is expressed exclusively on one parental allele in a phenomenon known as imprinting H19 is only transcribed from the maternally inherited allele; the paternal H19 allele is not expressed.

• The mechanism of induction of melasma by estrogen may be related to the presence of estrogen receptors on the melanocytes that stimulate cells to produce more melanin

• increased serum concentrations of luteinizing hormone

• Characteristic clinical features of melasma are symmetry of hyperpigmentation and distribution related to trigeminal nerves, which suggest that the neural involvement may play a role in the pathogenesis of pigmentation.

• Bak et al. found higher levels of neural endopeptidase in melasma lesions and suggest that neuroactive molecules, including nerve growth factor, are critical factors for the pathogenesis of melasma

Aetiology

Cosmetics and drugs containing phototoxic agents (eg, antiseizure medications) have also been linked to melasma.

Some cases of melasma could be stress induced, because the release of melanocyte-stimulating hormone can be influenced by stress.

• Human melanocytes may respond to angiogenic factors because normal human melanocytes express functional receptors for vascular endothelial growth factor (VEGF)

• In some types of melasma, a pronounced telangiectatic erythema confined to melasma-lesional skin has been observed.

• Increased vascularity is one of the major histologic findings in melasma.

• These findings may explain the effects of localized microinjection of plasmin inhibitor tranexamic acid, and good therapeutic efficacy of vascular lasers in the treatment of melasma

Melanin is produced in melanocytes and stored in melanosomes within the keratinocytes.

The number, melanin content, and location of these melanized cells (along with oxygenated and deoxygenated hemoglobin) help determine the color of the skin.

Melanosomes contain tyrosinase, a copper-containing enzyme, that catalyzes the conversion of L-tyrosine to L-dopa and L-dopa to L-dopa-quinone in melanin synthesis.

Tyrosine（酪胺酸）----> DOPA（多巴） -

--> Melanin

Tyrosinase （酪胺酸酵素）

Pigmentation Pathway

Histopathology

Epidermal melasma (70% cases)

Most common and most treatable form

Increased Melanin mainly in the basal and suprabasal layers

Dermal melasma (10 - 15%)

Melanin in melanophages located in the dermis

Mixed pattern (10 - 15%)

Treatment results depend on pigment localization

Histology

Melasma lesional skin

93% moder/severe elastosis

84% increased melanocytes

Increased melanin at all level of the epidermis

Dermal melanin in 36% with increased dermal melanin and melanophages (12%)

Perilesional normal skin 70% mild/moder elastosis

No increase in melanocytes

Melanin not increases in the epidermis

Dermal melanin noted in 36% of perilesional cases in Korean skin

Melasma: Histopathological Characteristics in 56 Korean Patients Br J Dermatol 2002; 146: 228-237 (Kang WH)

Wood’s lamp examination Epidermal type

darkening of color when examined, as the light emitted by Wood’s lamp is absorbed by the excess melanin

Dermal type

not show this accentuation

Mixed type

color enhancement with Wood’s light is seen is some places of the skin, but not others

Wood’s light inapparent

Type of

melasma

Clinical features

Epidermal

Well-defined border

Dark brown colour

Appears more obvious under black light

Responds well to treatment

Dermal Ill-defined border

Light brown colour

Unchanged under black light

Responds poorly to treatment

Mixed Combination of light and brown patches

Partial improvement with treatment

Melasma Global Severity Scale (GSS)

0 = Clear 1 = Mild 2 = Moderate 3 = Severe

Evolution Chronic disorder lasting for many years

UV radiation is major triggering factor in all cases

Relapses are common especially during the summer with remissions during the winter months

Hyperpigmentation usually persists after pregnancy

Dificult to achieve PERMANENT and COMPLETE clearance

Quality of Life

Not life threatening disease Melasma has a Very Significant Impact on Patients

(Psychological and emotional) Three life domains more affected: social, recreation and

leisure, and emotional well-being Some countries (India, Pakistan): significant psychosocial

impact. Women with melasma have difficulty finding a husband and can be left by their husband if they develop visible pigmentary disorder

Embarrassment and stigma : hispanic Effective treatment can dramatically improve patients’ quality

of life

Balkrishnan R et al. Cosmetic Dermatol 2003; 16: 25 - 30 / T. Fitzpatrick et al. 1987: 794 - 876 / Balkrishnan B et al.

Improvement QoL with effective treatment of facial melasma In press - Poster AAD 2004

General Management

Because of its refractory and recurrent nature, melasma is often difficult to treat.

The goals of treatment often include

prevention or reduction in the severity of recurrence

reduction of the affected area

improvement in the cosmetic defect

reduced time to clearance

fewest possible side effects

General Management The principles of therapy include

Protection from UV light

Inhibition of melanocyte activity and melanin synthesis

Disruption and removal of melanin granules

Assist in the clearing of melasma include Discontinuation of birth control pills

Discontinuation of Scented cosmetic products, and phototoxic drugs

Use of broad-spectrum (UVA/UVB) sunscreens

Near-visible light and UV photoprotection in the treatment of melasma: a double-blind randomized trial

• Visible light (VL) can induce pigmentary changes similar to those caused by UV radiation on darker-skinned patients.

• Sixty-eight patients with melasma were randomized in two groups to receive either UV-VL sunscreen or UV-only sunscreen, both with sun protection factor ≥ 50, over 8 weeks. All patients received 4% hydroquinone as a depigmenting treatment.

Photodermatol Photoimmunol Photomed. 2014 Feb;30(1):35-42.

• Sixty-one patients concluded the study.

• At 8 weeks, the UV-VL group showed 15%, 28% and 4% greater improvements than the UV-only group in MASI scores, colorimetric values and melanin assessments, respectively

• Treatment of melasma is a challenge. Despite various therapeutic modalities including topical bleaching creams, chemical peels, laser and light treatments, there still remains a subset of patients unresponsive to those therapies

• Outcomes are variable and may be associated with side effects such as irritation and scarring.

Therapeutics

Keratinocyte Removal

Melanocyte Secretory Function

Topical Corticosteroid

Tretinoin

Melanosome Transfer

Tyrosinase

Chemical Peels Glycolic Acid Salicylic Acid Trichloracetic

Tretinoin

Halder R, Nordlund JJ. In Nordlund JJ, et al, eds: The Pigmentary System. Physiology and Pathophysiology.

Oxford University Press; New York. 1998.

Hydroquinone, Azelaic Acid

Kojic Acid

Hydroquinone (HQ)

Hydroquinone (HQ) remains one of the most prescribed agents for melasma and is considered the gold standard of therapy, especially for epidermal melasma (has been in use for >50 years)

The epidermal type generally has a good response to topical therapy, whereas skin with mainly dermal deposition of melanin responds poorly.

Hydroquinone Improvement with HQ (monotherapy) is

usually observed at 4-6 weeks

Plateau at approximately 4 months

• HQ inhibits the conversion of 3,4-dihydroxyphenylalanine (DOPA) to melanin by tyrosinase inhibition

• Inhibits RNA and DNA synthesis in melanocytic cells, and degrades melanosomes

Katsambas AD, Stratigos AJ. Depigmenting and bleaching agents: coping with hyperpigmentation. Clin Dermatol. 2001;19(4):483-8.

Hydroquinone

Efficacy

Penetration may be increased with concomitant use of tretinoin or glycolic acid

5% much better than 2% at melanosomes in animal studies

Can concentration to 10%, but risk of irritation and ochronosis also increases

Side effects

Irritant / Contact dermatitis

Post-inflammatory hyperpigmentation

Chronic use of high concentrations of HQ (≥5%) have been reported to produce ochronosis and colloid milium

Engasser PG, et al., J Am Acad Dermatol 1981; 5:143 / Arndt KA, et al., JAMA 1965; 194:117

• Since 2001, HQ has been banned in the European Unit (EU) as an ingredient in cosmetics.

• The EU decision was based on its mid-term side effects, mainly exogenous ochronosis and leukoderma-en-confetti.

• During the past decade, concerns over the safety of HQ have increased. Its use has been connected with toxicity and mutagenicity, and an increased incidence of exogenous ochronosis

Twenty-fourth directive 2000/6/EG Publication nr L 056, European Union; 2000. Westerhof W, Kooyers TJ. Hydroquinone and its analogues in dermatology – a potential health risk. J Cosmet Dermatol.2005;4(2):55-9. Enguita FJ, Leitao AL. Hydroquinone: environmental pollution, toxicity, and microbial answers. Biomed Res Int. 2013;2013:542168.

Hydroquinone • Physicians found no significant difference in skin

lightening between hydroquinone (4%) compared with 20% azelaic acid and with 5% ascorbic acid in separate trials.

• It has been recommended that if no improvement is evident after an initial 2 months of use, then the drug should be discontinued; however, in some cases it can take as long as 6 months for a change to appear

Balina LM, Graupe K. The treatment of melasma: 20% azelaic acid versus 4% hydroquinone cream. Int J Dermatol 1991;30:893-5. Espinal-Perez LE, et al. A double-blind randomized trial of 5% ascorbic acid vs 4% hydroquinone in melasma. Int J Dermatol 2004;43:604-7.

Tretinoin • Tretinoin appears to be more effective than placebo in

lightening melasma by objective measures in those with light and dark skin.

Time to clinical improvement 24-40 weeks

Irritant dermatitis common: up to 88% of patients develop irritation from monotherapy

Mode of action

Disperse keratinocyte pigment granules

Interfere with pigment transfer

Accelerate epidermal turnover

Inhibit the induction of tyrosinase, DOPAchrome conversion factor, and melanogenesis

Griffiths CE, et al. Topical tretinoin (retinoic acid) improves melasma: a vehicle-controlled, clinical trial. Br J Dermatol 1993;129:415-21. Kimbrough-Green CK, et al. Topical retinoic acid (tretinoin) for melasma in black patients. Arch Dermatol 1994;130:727-33.

Tretinoin Topical Tretinoin 0.1% (Retinoic Acid) Improves Melasma. A Vehicle-Controlled, Clinical Trial

0%

10%

20%

30%

40%

50%

60%

70%

TRETINOIN PLACEBO

Results: Significantly more tretinoin subjects were rated as improved or much improved (68%) compared with 5% of the vehicle group at week 40

Adverse Reactions: • 88% Tretinoin (20% severe) • 29% Vehicle

Griffiths. Br J Dermatol 1993;128:415-421

Corticosteroids Mode of action

Non-selective inhibition of melanogenesis

Anti-inflammatory: decrease prostaglandin and leukotriene synthesis

In topical association, decreased irritation of active agents

Cytotoxic or cytotatic for epidermis: decrease epidermal turnover

Efficacy 1

Not used alone in hyperpigmentary disorders

Re- appearance of melasma (7/10)

Safety May cause skin atrophy, acne, telangiectasia, rosacea

Kanwar A Et al. Dermatology 1994; 188 : 170

Azelaic acid: Mechanism of action

AzA has anti-inflammatory, antibacterial, and antikeratinizing effects, which make it useful in a variety of dermatologic conditions

9 carbon straight chain dicarboxylic acid, which acts on hyperactive and abnormal melanocytes by competitively inhibiting tyrosinase

Part of its effect may result from its inhibitory effects on reactive oxygen species ROS), allowing for a reduction in oxidative tissue injury at sites of inflammation and in melanin formation

Azelaic acid

Balina and Graupe - 1991

20% azelaic acid equivalent to 4% hydroquinone in a 24-week (6 m) double blind study of women from S. America

65% good to excellent responses in azelaic acid group vs. 72% in hydroquinone group

Verallo-Rowell et al- 1989

20% azelaic acid found to be significantly better than 2% hydroquinone in 132 Filipino women treated for 6 months

Irritant dermatitis common (1% to 5% )

Balina LM, et al., Int J Dermatol 1991; 30:893 Verallo-Rowell VM, et al., Acta Derm Venereol (Stockh) 1989; 143(suppl):58

Kojic acid

Both kojic acid and HQ are tyrosinase inhibitors, the combination should be expected to augment efficacy

Kojic acid and 2% HQ are similarly effective in melasma

Garcia A, Fulton JE, Dermatol Surg 1996; 22:443

Other topical therapies Vitamine C / vitamine E

Promotes conversion of melanin to colorless leucomelanin

Vitamin E seems to act synergistically with Vitamin C

Ineffective in certain vehicle bases because of lack of stability

Niacinamide

Down-regulates melanogenesis by decreasing melanosome transfer

Well tolerated

Glabridin (光甘草定 ): licorice root extract (Glycyrrhiza glabla L):

Inhibits tyrosinase

Anti-inflammatory (geycerrhinetic acid)

L-ascorbic acid (vitamin C)

• Several forms of topical vitamin C are used to treat melasma in 5 to 10% concentrations and can be formulated with other depigmenting agents, such as HQ.

• Other advantages of vitamin C include antioxidant effects and photo protective properties.

• The weakness of ascorbic acid is its chemical instability and the hydrophilic nature limits its skin penetration.

• Magnesium ascorbyl phosphate, ascorbyl palmitate and sodium ascorbyl phosphate are stable derivatives of ascorbic acid.

• Iontophoresis has been used to promote percutaneous absorption of vitamin C into the skin.

• Vitamin-C iontophoresis appears significantly more effective than distilled water iontophoresis on objective assessment although the participants in the study could not tell the difference.

Huh CH, et al. A randomized double-blind placebo-controlled trial of vitamin C iontophoresis in melasma. Dermatology 2003;206:316-20.

• In the trial of a botanical extract, Gigawhite (Dutch State Mines, Alpaflor, The Netherlands) 5%, no significant differences to placebo were seen on subjective assessment by the physicians, although colorimeter analysis showed that the side treated with Gigawhite was significantly lighter.

Francisco-Diaz J. et al. A double-blind randomized placebo controlled trial on the efficacy and safety of botanical exact (Gigawhite 5% solution) in the treatment of melasma. JPDS 2004;13:18-23.

Other topical therapies Liquiritin (甘草甙 )

Linoleic acid (亞麻油酸 )：加速酪胺酸脢在細胞

內分解的速度

Thioctic acid (硫辛酸 )

Competitive inhibitor of tyrosinase

Inhibits intermediate metabolites between dopaquinone and indolic species

Soybean extract

Inhibits protease-activated receptor 2 (PAR-2)

Reduces keratinocyte phagocytosis of melanosomes from melanocytes

Tranexamic Acid

Tranexamic acid reduces hyperpigmentation in melasma patients

Inhibits melanin sysnthesis in melanocytes by interfering with the interaction of melanocytes and keratincytes through inhibition of the plasminogen/plasmin system

Maeda K, Tomita Y. J Health Sci 2007; 53:389-396

Combination therapy: HQ, tretinoin, and a steroid

Kligman and Willis published clinical results in 1975 (dexamethasone 0.1%, hydroquinone 5%, tretinoin 0.1%)

Individual components acted together to improve efficacy and minimize adverse events

Tretinoin reduces the atrophogenic effects of the steroid

Tretinoin facilitates the epidermal penetration of

hydroquinone

The steroid helps reduce irritation caused by tretinoin

Kligman AM, Willis I. Arch Dermatol. 1975;111:40-48.

Combination therapy: HQ, tretinoin, and a steroid

Daily application for 5-7 weeks resulted in complete lightening

Results were significantly less favorable if any one component was omitted

Type of corticosteroid influence the effect on pigmentation (2% hydrocortisone less effective than dexamethasone)

No cases of atrophy were seen

Kligman AM, Willis I. Arch Dermatol. 1975;111:40-48.

Combination therapy: HQ, tretinoin, and a steroid

Taylor et al. with 641 patients, investigated the effects of 4% HQ in combination with 0.05% tretinoin (RA), and 0.01% FA. This combination (Tri-Luma) is currently approved in the United States for the treatment of melasma.

This multicenter, randomized, investigator-blind, 8-week trial found that significantly more of the patients treated with RA, HQ, and FA (77%) experienced complete or near complete clearing when compared with each of the dual therapies (HQ + FA, RA + FA, RA + HQ) (P < .001).

Cutis 2003;72:67–72 Cutis 2003;72:67–72

Tri-Luma® cream Long-term safety studies

Hydroquinone 4%, tretinoin 0.05%, fluocinolone acetonide 0.01%:

a safe and efficacious 12-month treatment for melasma Torok H, Jones T, Rich P, Smith S, Tschen E. Cutis 2005; 75: 57-62

Large 12-month extension study of an 8-week trial to evaluate the safety and efficacy of triple combination (TC) cream in melasma patients previously treated with TC cream or one of its dyads

Torok H, Taylor S, Baumann L, Jones T, Weider J, Lowe N, Jarratt M, Rich P, Pariser D, Tschen E, Martin D, Menter A, Weiss J . J Drugs Dermatol. 2005; 4(5): 592-7

Efficacy results

% of patients

81%

79%

73%

60 65 70 75 80 85

Month 12

Month 6

Month 1

% of patients cleared or nearly cleared

Chloasma – Maintenance regimens

Melasma is a relapsing disease, there is few data on how to maintain efficacy after acute treatment

Median time to relapse (time when 50% of the Subjects experience recurrence) after abrupt cessation of daily Tri-Luma® treatment: 58 days

Chemical peels

• Superficial chemical peeling agents are beneficial in the management of epidermal melasma and may be used in combination with other forms of melasma treatment.

• The peel solution is selected according to patient’s needs, skin type and sensitivities.

• Because of their superficial action, superficial peels can be used in nearly all skin types

• Medium-depth peels may be an alternative treatment in refractory cases of severe melasma.

• All types of chemical peels, but mainly alpha-hydroxy

• acids, beta-hydroxy acid, salicylic acid, Jessner’s original and modified solutions, and trichloroacetic acid are used alone or in combination with other depigmenting agents.

• The response of melasma to chemical peels is rather unpredictable and there is a tendency for changes in pigmentation after chemical peel, especially in dark skinned individuals.

A Double-Blind, Placebo Controlled Clinical Trial Evaluating the Efficacy and Safety of a New Skin

Whitening Combination in Patients with Chloasma

• ferulic acid, Ginkgo Biloba, lipohydroxyacid (LHA), niacinamide and La Roche-Posay thermal spring water in a vehicle base.

Journal of Cosmetics, Dermatological Sciences and Applications, 2014, 4, 92-98

Changes of both hemi-MASI over time as a function of time. Hemi-MASI 95% confidence intervals evolution over time differences between both treatments are significant (*p < 0.05) at 6 weeks, and highly significant (***p <0.001) at 12 weeks. Red line corresponds to placebo formula and blue line totest formula.

Laser treatment

Melasma has a variable response to Q-switched ruby laser (694 nm), and most studies report poor results, with recurrences soon after treatment

Melasma does not respond well to dye laser

Neodymium:YAG was not effective

-----

Laser and light therapies

• Melanosomes are the primary target of the laser-induced damage, and melanin is the main chromophore.

• It is important to choose wavelengths between 630 nm and 1100 nm which are preferentially absorbed by melanin, and pulse duration between 40 ns and 750 ns

• Epidermal melasma can be treated with ablative lasers, such as carbon dioxide (CO2) laser and erbium (Er):YAG laser.

• Non-ablative 1,550 nm fractional laser therapy has been reported to improve melasma.

Rivas S, Pandya AG. Treatment of melasma with topical agents, peels and lasers: an evidence-based review. Am J Clin Dermatol. 2013;14(5):359-76.

• Q-switched (QS) lasers deliver their energy in nanosecond pulses, hence they selectively target melanosomes.

• The 1064 nm QS-Nd:YAG is the most widely used laser for melasma. The number of treatments varies from 5 to 10 at 1-week intervals.

• Encouraging results have been observed in the treatment of the dermal-type melasma by using a novel 694-nm QS ruby fractional laser.

Lee DB, Suh HS, Choi YS. A comparative study of low fluence 1064-nm Q-switched Nd:YAG laser with or without chemical peeling using Jessner’s solution in melasma patients. J Dermatolog Treat. 2014;25(6):523-8.

Treatment of melasma by low-fluence 1064 nm Q-switched Nd:YAG laser

• Fifty patients with melasma underwent 15 weeks of weekly treatments, using a Q-switched Nd:YAG laser (RevLite; HOYA ConBio, Freemont, CA, USA) at 1064 nm with an 8-mm spot size, and a fluence of 2.8 J/cm2.

• average with improvement rate of 50–74%.

Journal of Dermatological Treatment, 2014; 25: 212–217

Combination treatment of low-fluence 1,064-nm Q-switched Nd: YAG laser with novel intense pulse light in Korean melasma

patients: a prospective, randomized, controlled trial.

• Twelve patients underwent 6 treatment sessions of concomitant IPL-F and LF-QS-Nd:YAG laser (combination group), and 12 patients underwent 6 treatment session of IPL-F alone (IPL only group).

• Partial melasma area and severity index (MASI) scores were evaluated by 2 dermatologists using digital photography.

Dermatologic Surgery 2014; 40(8), 842–850

• In the combination group, the partial MASI score has significantly decreased by 47% at 1 month after the treatment (p < .05) and 50% at 2 months after the last treatment (p < .01).

• At 1 month and 2 months after the treatment, the decrease in the partial MASI score of the combination group was significantly larger than that of the IPL only group (p < .05).

• In both groups, treatment with IPL-F and LF-QS-Nd:YAG laser was well tolerated.

A comparative study of low-fluence 1064-nm Q-switched Nd:YAG laser with or without chemical peeling using Jessner’s solution in

melasma patients

• Total of 52 patients were included. Patients who received 10 sessions of 1064-nm QSNYL plus chemical peeling with placebo (group A) in a two-week interval and those who received 10 sessions of 1064-nm QSNYL plus chemical peeling with Jessner’s solution (group B)

• At 8 weeks, the mean MASI score decreased from 8.684.06 to 8.603.88 in group A and from 8.983.72 to 7.132.57 in group B, showing a significant difference (p<0.001).

• at 20 weeks, there was no significant difference J Dermatolog Treat, 2014; 25(6): 523–528

• Melasma treatment with pulsed dye laser and the newer antiangiogenic lasers (copper bromide laser) is based on the theory that melasma occurs due to the interaction between cutaneous vasculature and melanocytes.

• These lasers can be used in patients with melasma and pronounced telengiectasia

Lee HI et al. Clinicopathologic efficacy of copper bromide plus/yellow laser (578 nm with 511 nm) for treatment of melasma in Asian patients. Dermatol Surg. 2010;36(6):885-93.

• A combination of lasers can be beneficial for dermal melasma.

• Ablative lasers remove the epidermis; this can be followed by the use of the Q switched pigment selective laser which reaches deeper layers of the dermis (dermal melanophages) without causing serious side effects.

Intense pulsed light therapy

IPL is an effective therapeutic choice for the removal of melanocytic lesions, especially those epidermal in nature; however, long-term sun protection and bleaching creams should be used after treatment of patients with mixed melasma, because of a higher risk of PIH

• A study by Figueiredo Souza et al. found that a single session of IPL combined with stable fixed-dose triple combination treatment is a safe and effective treatment for refractory mixed and dermal melasma

• A new type of intense pulsed light with pulse in- pulse (PIP) mode (multiple fractionated subpulses in one pulse width), may be a safe and promising treatment for melasma

What can Fraxel treat ?

FDA-Cleared Indications

Dermatological procedures requiring the coagulation of soft tissue

Treatment of periorbital wrinkles Photocoagulation of pigmented lesions including

lentigos (age spots), solar lentigos (sun spots), and dyschromia

Resurfacing Melasma Acne scars and surgical scars Actinic keratosis (2007)

The efficacy in melasma treatment using a 1410 nm fractional photothermolysis laser

Adverse reactions 20 mJ, 5% coverage (n = 120)

20 mJ, 20% coverage (n = 120)

P-value

Erythema 41 (34.17%) 92 (76.67%) 0.000

Dryness 36 (30.00%) 62 (51.67%) 0.006

PIH on melasma area

7 (5.83%) 18 (15.00%) 0.020

PIH on whole face 10 (8.33%) 17 (14.16%) 0.851

Acneiform eruption 16 (13.33%) 15 (12.50%) 0.886

• Many techniques have been developed to improve transdermal drug delivery, such as skin needling, electroporation, sonophoresis, and iontophoresis, which are able to improve stratum corneum layer permeability and to enhance penetration of topical agents through the skin.

• monopolar RF with a medium frequency electrical pulse (480 kHz) and low-frequency (10 Hz) current system. This allows for the creation of real electropores because of polarity inversion of cell membranes.

Melanin Scores Recorded by Mexameter at the Baseline (T0), 1 Month After Treatment (T1) and 6 Months After Treatment (T2)

Is Topical Zinc Effective in the Treatment of Melasma? A Double-Blind Randomized Comparative Study

• Ninety-three women with melasma were randomized to receive zinc sulfate 10% or hydroquinone 4% solutions once daily for 2 months.

• Topical zinc therapy is not highly effective in reducing the severity of melasma

Dermatol Surg 2014;40:33–37

Conclusion

• At present, there is no universally effective treatment for melasma.

• The mainstay of treatment is use of sunscreens along with topical medications that suppress melanogenesis.

• Topical hydroquinone alone or in stable fixed-dose triple combination topical therapy is the first line of treatment

• Chemical peels are considered second-line therapy for refractory cases, and laser and light are considered the third-line treatment.

• Nowadays, there are no controlled studies investigating the efficacy and safety of multiple novel and experimental agents.