Melasma. Biology of melanocyte Dendritic cell at basal layer of epidermis Dendritic cell at basal layer of epidermis Produce melanin and send to surrounding.

MelasmaMelasma

Biology of melanocyteBiology of melanocyte

Dendritic cell at basal layer of Dendritic cell at basal layer of epidermisepidermis

Produce melanin and send to Produce melanin and send to surrounding keratinocytesurrounding keratinocyte

Epidermal melanin unit Epidermal melanin unit (melanocyte:keratinocyte) = 1:36(melanocyte:keratinocyte) = 1:36

Biology of melaninBiology of melanin

Synthesis from melanosomeSynthesis from melanosome Transport to keratinocyte via Transport to keratinocyte via

dendritic process of melanocytedendritic process of melanocyte 2 type2 type

: eumelanin: eumelanin

: pheomelanin: pheomelanin

Melanin synthesisMelanin synthesis

BindingBinding

Melanocyte Melanocortin 1 Melanocyte Melanocortin 1

stimulating hormone receptorstimulating hormone receptor

adenylase cyclaseadenylase cyclase

Tyrosinase cAMPTyrosinase cAMP

Melanin synthesisMelanin synthesis

TyrosineTyrosine

tyrosinasetyrosinase

DopaDopa

Dopa quinoneDopa quinone

Eumelanin Eumelanin PheomelaninPheomelanin

Melanin synthesisMelanin synthesis

MSH MSH

MC1R mutation of MC1RMC1R mutation of MC1R

Eumelanin PheomelaninEumelanin Pheomelanin

Melanin transferMelanin transfer

PhagocytosisPhagocytosis

: melanin transfer to dermis: melanin transfer to dermis

: phagocytose by melanophage: phagocytose by melanophage EndocytosisEndocytosis

: melanin transfer to keratinocyte via: melanin transfer to keratinocyte via intercellular spaceintercellular space

MelasmaMelasma

Acquired bilateral symmetrical Acquired bilateral symmetrical hypermelonosishypermelonosis

Irregular light to gray brown macule Irregular light to gray brown macule and patchand patch

Ill defined marginIll defined margin Involved sun exposure areaInvolved sun exposure area Most common in women Most common in women

Melasma is a common acquired Melasma is a common acquired pigmentary disorder that occurs pigmentary disorder that occurs mainly in women (more than 90% of mainly in women (more than 90% of cases) of all racial and ethnic groups, cases) of all racial and ethnic groups, but particularly affects those with but particularly affects those with Fitzpatrick skin types IV–VIFitzpatrick skin types IV–VI

Distribution of melasmaDistribution of melasma

Central facial pattern (63%) : cheek, Central facial pattern (63%) : cheek, forehead, nose, chinforehead, nose, chin

Malar pattern (21%) : cheek, noseMalar pattern (21%) : cheek, nose Mandibular pattern (16%) :chinMandibular pattern (16%) :chin

Cause of melasmaCause of melasma

Light : UVA, UVB, visible lightLight : UVA, UVB, visible light Hormone : pregnancy, contraceptiveHormone : pregnancy, contraceptive pillpill Drug : dilantin, anti-malarial drug, Drug : dilantin, anti-malarial drug,

tetracycline, minocyclinetetracycline, minocycline Cosmetic :Cosmetic : perfume, colorperfume, color GeneticGenetic Malnutrition : liver dysfunction, B12 def.Malnutrition : liver dysfunction, B12 def.

Type of melasmaType of melasma

Epidermal melasmaEpidermal melasma Dermal melasmaDermal melasma Mixed epidermal dermal melasmaMixed epidermal dermal melasma

The use of a Wood’s lamp can often be The use of a Wood’s lamp can often be very beneficial in determining the very beneficial in determining the location of melanin deposition showing location of melanin deposition showing enhancement of color contrast in enhancement of color contrast in lesional skin for the epidermal type, but lesional skin for the epidermal type, but not the dermal types. The mixed type not the dermal types. The mixed type has enhancement in some areas of has enhancement in some areas of lesional skin, but not in other areas.2 lesional skin, but not in other areas.2

Estrogen may play a role in melasma Estrogen may play a role in melasma induction(OCP,HRT,pregnancy)induction(OCP,HRT,pregnancy)

Pregnancy induced melasma will Pregnancy induced melasma will recover after some months recover after some months

Epidermal melasmaEpidermal melasma

Light or dark brown colorLight or dark brown color Melanin deposition in basal, Melanin deposition in basal,

suprabasal layer of epidermissuprabasal layer of epidermis Larger melanocyte with more Larger melanocyte with more

noticeable dendritic process noticeable dendritic process

Dermal melasmaDermal melasma

Blue gray colorBlue gray color Perivascular melanophage at Perivascular melanophage at

superficial and middermissuperficial and middermis Melanin granule in dermisMelanin granule in dermis

Whether the melanin is deposited in Whether the melanin is deposited in the epidermis or dermis is important the epidermis or dermis is important therapeutically because dermal therapeutically because dermal hyperpigmentation is much more hyperpigmentation is much more challenging to treatchallenging to treat

Postinflammatory Postinflammatory Hyperpigmentation (PIH)Hyperpigmentation (PIH)

PIH represents a pathophysiologic PIH represents a pathophysiologic response to cutaneous inflammation, response to cutaneous inflammation, such as acne, atopic dermatitis, such as acne, atopic dermatitis, lichen planus, and psoriasis. Similar lichen planus, and psoriasis. Similar to melasma, it is more obvious in to melasma, it is more obvious in patients with brown or black skin. It patients with brown or black skin. It has no gender or age predominance.has no gender or age predominance.

The lesions are characteristically The lesions are characteristically limited to the site of the preceding limited to the site of the preceding inflammation and have indistinct, inflammation and have indistinct, feathered borders.7 Melanocytes can feathered borders.7 Melanocytes can either be stimulated by the either be stimulated by the inflammatory process to become inflammatory process to become hypertrophic, thus secreting more hypertrophic, thus secreting more melanin, or the number of melanin, or the number of melanocytes can increasemelanocytes can increase

. Epidermal hyperpigmentation (e.g., . Epidermal hyperpigmentation (e.g., associated with acne) occurs when associated with acne) occurs when increased melanin is transferred to increased melanin is transferred to keratinocytes while dermal keratinocytes while dermal pigmentation (e.g., associated with pigmentation (e.g., associated with lichen planus and cutaneous lupus lichen planus and cutaneous lupus erythematosus) occurs when the erythematosus) occurs when the basement membrane is disrupted and basement membrane is disrupted and melanin falls into the dermis and melanin falls into the dermis and resides within melanophageresides within melanophage

Therapeutic goals for Therapeutic goals for hyperpigmentation include hyperpigmentation include promoting the degradation of promoting the degradation of melanosomes, inhibiting the melanosomes, inhibiting the formation of melanosomes, and formation of melanosomes, and retarding the proliferation of retarding the proliferation of melanocytes.melanocytes.

Because sun exposure is an Because sun exposure is an important etiologic factor in important etiologic factor in hyperpigmentation, all patients hyperpigmentation, all patients should use daily, broad-spectrum, should use daily, broad-spectrum, high SPF sunscreens and minimize high SPF sunscreens and minimize sun exposure.sun exposure.

Effective therapyEffective therapy

Retard melanocyte proliferationRetard melanocyte proliferation Inhibit melanosome formationInhibit melanosome formation Promote melanosome degradationPromote melanosome degradation

TreatmentTreatment

AvoidanceAvoidance SunscreenSunscreen Medication : hydroquinone, azelaic Medication : hydroquinone, azelaic

acid, retinoic acidacid, retinoic acid Chemical peelingChemical peeling DermabrasionDermabrasion Laser Laser

Topical Treatments for Topical Treatments for MelasmaMelasma

In those patients with epidermal type In those patients with epidermal type melasma, there are multiple melasma, there are multiple treatments available (see Table 2).6 treatments available (see Table 2).6 Topical agents include phenols, e.g., Topical agents include phenols, e.g., hydroquinone (HQ); retinoids, e.g., hydroquinone (HQ); retinoids, e.g., tretinoin; azelaic acid; kojic acid (KA); tretinoin; azelaic acid; kojic acid (KA); and glycolic acid (GA).and glycolic acid (GA).

hydroquinonhydroquinon

2%–4% has been widely used for 2%–4% has been widely used for melasma therapy. melasma therapy.

inhibits the conversion of dopa to inhibits the conversion of dopa to melanin by inhibitin theactivity of melanin by inhibitin theactivity of tyrosinase.tyrosinase.

may interfere with DNA and RNA may interfere with DNA and RNA synthesis, degrade melanosomes, synthesis, degrade melanosomes, and destroy melanocytes. and destroy melanocytes.

Reports of contact dermatitis in up to Reports of contact dermatitis in up to 25%25%

As an itchy eruptionAs an itchy eruption

it is best to be tested in a hidden part it is best to be tested in a hidden part before usebefore use

Side-effects included irritant and allergic Side-effects included irritant and allergic contact dermatitis, PIH, nail bleaching contact dermatitis, PIH, nail bleaching and rarely, ochronosis-like and rarely, ochronosis-like pigmentation.pigmentation.

retinoidsretinoids

0.05-0.1%0.05-0.1% inhibiting tyrosinase inhibiting tyrosinase

transcription,interrupting melanin transcription,interrupting melanin synthesis.synthesis.

While tretinoin may be effective in While tretinoin may be effective in reducing melasma, it typically takes reducing melasma, it typically takes at least 24 weeks to see clinical at least 24 weeks to see clinical improvement. improvement.

azelaic acidazelaic acid

1)11)15%–20%) a C9 dicarboxylic acid, is a 5%–20%) a C9 dicarboxylic acid, is a reversible inhibitor of tyrosinase reversible inhibitor of tyrosinase

2) shown to be as effective as HQ 4% but 2) shown to be as effective as HQ 4% but without its side effects.without its side effects.

3) The combination of azelaic acid with 3) The combination of azelaic acid with 0.05% tretinoin or 15%–20% glycolic acid 0.05% tretinoin or 15%–20% glycolic acid may produce earlier, more pronounced may produce earlier, more pronounced skin lightening. Adverse effects include skin lightening. Adverse effects include pruritus, mild erythema, scaling, and pruritus, mild erythema, scaling, and burning.burning.

KOJIC ACIDKOJIC ACID

KA 2% KA 2% is generally equivalent to is generally equivalent to other therapies but may be more other therapies but may be more irritating.irritating.

Glycolic acid Glycolic acid

GA 5%–10% is an alpha-hydroxy acid GA 5%–10% is an alpha-hydroxy acid . It decreases pigment by many . It decreases pigment by many

mechanisms including thinning the mechanisms including thinning the stratum corneum, enhancing stratum corneum, enhancing epidermolysis, dispersing melanin in epidermolysis, dispersing melanin in the basal layer of the epidermis, and the basal layer of the epidermis, and increasing collagen synthesis in the increasing collagen synthesis in the dermis. dermis.

, HQ 5%, tretinoin 0.1%, and , HQ 5%, tretinoin 0.1%, and dexamethasone 0.1%, was first dexamethasone 0.1%, was first introduced in 1975 and termed the introduced in 1975 and termed the Kligman formulaKligman formula

combination of HQ 4%, tretinoin 0.05%, combination of HQ 4%, tretinoin 0.05%, and fluocinolone acetonide 0.01% (Tri-and fluocinolone acetonide 0.01% (Tri-Luma®, Galderma) proved better than Luma®, Galderma) proved better than any combination of two of the above any combination of two of the above agents, with 77% of patients showing agents, with 77% of patients showing complete or nearly complete clearingcomplete or nearly complete clearing

Clinically significant improvement was Clinically significant improvement was noted as early as 4 weeks with noted as early as 4 weeks with maximum results at 8 weeks.maximum results at 8 weeks.

The most common adverse effects The most common adverse effects were mild local irritation, erythema, were mild local irritation, erythema, and skin peelingand skin peeling

GA peels to a topical regimen of HQ GA peels to a topical regimen of HQ 2%, GA 10% and tretinoin 0.05% 2%, GA 10% and tretinoin 0.05% cream in PIH patientscream in PIH patients

Laser treatment for Laser treatment for melasmamelasma

Target chromophore is melaninTarget chromophore is melanin Should destroy melanocyte in hair Should destroy melanocyte in hair

folliclefollicle Good in dermal and mix melasmaGood in dermal and mix melasma

Laser treatment for Laser treatment for melasmamelasma

Epidermal melanin removal : lPL, PDLEpidermal melanin removal : lPL, PDL Dermal melanin removal : Q-Dermal melanin removal : Q-

switched Ruby, Q-switched switched Ruby, Q-switched Alexandrite, Q-switched Nd:YAGAlexandrite, Q-switched Nd:YAG

FraxelFraxel

Epidermal melanin removalEpidermal melanin removal

No recovery timeNo recovery time Repigmentation after removalRepigmentation after removal

Dermal melanin removalDermal melanin removal

Minimal downtimeMinimal downtime Side effect : transient erythema, Side effect : transient erythema,

hypopigmentationhypopigmentation Repigmentation from melanin in Repigmentation from melanin in

melanophagemelanophage

FraxelFraxel

Epidermal and dermal ablationEpidermal and dermal ablation MEND formation and eliminated MEND formation and eliminated

through skinthrough skin Induce melanophage disruption and Induce melanophage disruption and

release melanin granule into dermisrelease melanin granule into dermis Downtime 3-7 dDowntime 3-7 d Long term improvementLong term improvement

Chemical peelingChemical peeling

With AHA like TCA,Salycilic acid,and With AHA like TCA,Salycilic acid,and ……