melasma (1 of 8)

B94

Melasma (1 of 8)

1Patient presents w/ symmetric hyperpigmented

macules, which can beconfl uent or punctate suggestive of melasma

Not all products are available or approved for above use in all countries.Specifi c prescribing information may be found in the latest MIMS.

A Non-pharmacological therapy• Patient education• Camoufl age make-up • Sunscreen

B Pharmacological therapyMonotherapy• Hydroquinone or• Tretinoin

Yes

No

2DIAGNOSIS

Does clinical presentation confirm melasma?

Responding to treatment?

No

Yes

Continue treatment as required

ALTERNATIVE DIAGNOSIS

TREATMENTSee next page

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B95

Melasma (2 of 8)

Patient unresponsive to initial therapy

A Non-pharmacological therapy• Patient education• Camoufl age make-up• Sunscreen

B Pharmacological therapyDual Combination � erapy• Hydroquinone plus• Tretinoinor• Azelaic acid

A Non-pharmacological therapy• Patient education• Camoufl age make-up• Sunscreen• Laser therapy • Dermabrasion

B Pharmacological therapyTriple Combination � erapy• Hydroquinone plus• Tretinoin plus• Topical steroidChemical peels

Responding to treatment?

Yes Continue treatment as required

No

1 MELASMA

• Acquired hyperpigmentary skin disorder characterized by irregular light to dark brown macules occurring in the sun-exposed areas of the face, neck & arms - Occurs most commonly w/ pregnancy (chloasma) & w/ the use of contraceptive pills - Other factors implicated in the etiopathogenesis are photosensitizing medications, genetic factors, mild ovarian or thyroid dysfunction, & certain cosmetics

• Most commonly aff ects Fitzpatrick skin phototypes III & IV• More common in women than in men• Rare before puberty & common in women during their reproductive years • Solar & ultraviolet exposure is the most important factor in its development


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B96

Melasma (3 of 8)


2 DIAGNOSIS

Diagnosis is based on clinical characteristicsPhysical Exam• Patient presents w/ well-demarcated tan to brown macular hyperpigmentation• Based on clinical pattern may be classifi ed to:

- Centrofacial is the most common type w/ macules & patches on the cheek, forehead, upper lip, nose & chin - Malar appears on cheeks & nose - Mandibular lesions are over the ramus of the mandible

• Pigment may also have a bluish appearance• Severity may be measured using the Melasma Area & Severity Index (MASI), which relies on 4 areas involved:

forehead, right malar region, left malar region, & chin - Grades the area involved & degree of pigmentation

Wood’s Lamp Exam• Used to visually localize the excessive melanin to the epidermis, dermis, or bothClassifi cation• Epidermal

- Light brown, w/ enhancement of pigmentation under Wood’s light - Melanin increase in basal, suprabasal & stratum corneum layers w/ highly dendritic & pigmented melanocytes - Epidermal pigment is more amenable to treatment than dermal pigment

• Dermal - Ashen or bluish-gray, no enhancement of pigmentation under Wood’s light - Perivascular melanophages on the superfi cial & deep dermis w/ less hyperpigmentation in the epidermal layer

• Mixed - Dark brown, enhancement is seen in some areas only - Melanin deposition found in epidermis & dermis

• Indeterminate - Inapparent under Wood’s light - Melanin deposition found in dermis

A NON-PHARMACOLOGICAL THERAPYPatient Education• Avoid sunlight exposure

- Wear protective clothing when going outdoors• Oftentimes resolved after pregnancy or discontinuation of oral contraceptive pillsSunscreens• Use of sunscreens that block UVA & UVB light are highly recommended

- Broad spectrum sunscreen w/ SPF >30 coverage is recommendedCamoufl age make-up• Heavy coverage of lesions while blending w/ unaff ected skin color may helpPhysical � erapiesCryosurgery• May be an option because melanocytes are susceptible to freezingDermabrasion/Microdermabrasion• May be used for dermal melasmaIntense Pulsed Light (IPL)• May be used as adjuvant treatment to topical therapy• Epidermal types respond better to IPL than deeper pigmented lesions w/c often responds poorlyLaser � erapy• Eg Q-switched (QS) lasers, fractional lasers• Used as second-line treatment in cases resistant to other therapies• Combination of QS + fractional CO2 & QS + IPL are recommended for all skin types

- Positive results were seen w/ the use of pulsed CO2 laser w/ Q-switched alexandrite laser

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B97

Melasma (4 of 8)

B PHARMACOLOGICAL THERAPYAzelaic Acid• 10, 15, 20 & 35% preparations are used to lessen pigmentation• Actions: A natural dicarboxylic acid that has antiproliferative & cytotoxic eff ects on melanocytes

- Acts by several mechanisms including inhibition of tyrosinase, cell membrane-associated enzyme thioredoxin reductase, specifi c mitochondrial dehydrogenases & DNA synthesis

• Eff ects: Reduction in melasma intensity may be seen after 1-2 mth w/ continuous application for up to 8 mth - Studies have shown that effi cacy of Azelaic acid for melasma is comparable to that w/ Hydroquinone

• May be used in combination w/ other agentsChemical Peels• Eg Glycolic acid, Lactic acid, Mandelic acid, Phytic acid, Resorcinol, Salicylic acid, Trichloroacetic acid• Recommended as alternative therapy if topical agents & triple combination therapy are not eff ective • Improves the response rate of patients to topical therapy• Performed by applying chemical agents to the skin to induce progressive exfoliation of the superfi cial layers

of the skinAlpha Hydroxy Acid (Glycolic acid, Lactic acid) • Actions: Inhibits tyrosinase activity• Also are eff ective as adjunctive agents to topical treatments• Studies showed that lactic acid works well against epidermal melasmaSalicylic acid• Actions: Inhibits tyrosinase activity • More eff ective when used in combination w/ topical treatments Topical Corticosteroids• Eg 0.01% Fluocinolone acetate • Used as part of triple combination therapy if previous combinations were ineff ectiveTopical Depigmenting AgentHydroquinone• Has been used for the treatment of hyperpigmentation for many decades• Actions: A hydroxyphenolic compound that inhibits the conversion of DOPA to melanin by inhibition of

tyrosinase - Also inhibits DNA & RNA synthesis, induces degradation of melanosomes & promotes destruction of melanocytes

• Commonly used at concentrations ranging from 2-5%, higher concentrations provide greater effi cacy but w/ greater skin irritation

• Can cause permanent depigmentation when used at high concentrations for a long period of time• May be used in combination w/ other agentsKojic Acid• A non-phenol depigmenting agent used as an alternative treatment for patients allergic to Hydroquinone• Action: Tyrosinase inhibitor that chelates copper at the enzyme’s active site• With high sensitizing potentialMequinol• A phenolic depigmenting agent used as alternative treatment for Hydroquinone-intolerant patients• Action: Competitively inhibits tyrosinase while sparing melanocytes• Usually used for solar lentigines when given in combination w/ TretinoinTopical RetinoidsTretinoin• 0.05-1% preparations are known to reduce pigmentation• Actions: Inhibits tyrosinase transcription as well as dopachrome conversion thereby interrupting melanin

synthesis• Eff ective as monotherapy but better results are seen when used in combination w/ other compounds• Typically takes at least 2 months to see clinical improvement• May also increase pigmentation secondary to irritation• Cream forms are generally less irritating than gels & solution


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B98

Melasma (5 of 8)

B PHARMACOLOGICAL THERAPY (CONT’D)Adapalene• Alternative treatment for Tretinoin-intolerant patients• 0.1% preparations are used for long-term melasma treatment• Actions: Modulates follicular epithelial cell diff erentiation by binding to specifi c nuclear retinoic acid receptor

proteins• Studies show that Adapalene is equally effi cacious compared to TretinoinAdjunctive � erapiesAscorbic Acid (Vitamin C)• Alternative treatment to Hydroquinone that provides skin lightening w/ less adverse eff ects• Action: Directly inhibits tyrosinase, thereby reducing melanin production in melanocytesArbutin• A derivative of Hydroquinone used as an alternative treatment to Hydroquinone• Action: Inhibits tyrosinase, 5,6-hydroxyindole-2-carboxylic acid, & melanosome maturationNiacinamide (Nicotinamide, Vitamin B3)• Used as adjunctive therapy for melasma due to its skin lightening & brightening eff ects• Action: Inhibits melanosome transfer after melanin synthesis by modulating the protease-activated receptor

PAR-2Tranexamic Acid• Actions: Acts as a plasmin inhibitor that prevents UV-induced pigmentation

- Also inhibits melanogenesis: prevents plasminogen binding to keratinocytes w/c in turn reduces prostaglandin & arachidonic acid production needed for melanogenesis

• May be given orally, subcutaneously, or topically; topical formulation often in combination w/ other agents• Further studies are needed to prove the effi cacy of Tranexamic acid for melasmaOthers • Plant extracts (Licorice, Grape seed, Orchid, Aloe vera, Soybean, Coff eeberry, Green tea, marine algae),

Indomethacin, Vitamin E, Rucinol, Gigawhite, Pyocyanidin (Pycnogenol)Combination � erapies• Employed to increase effi cacy & reduce side eff ects• Fixed dose triple combination therapy w/ Hydroquinone, Retinoic acid & corticosteroids provides greater

therapeutic success than monotherapy - Most widely used combination therapy - Addition of Tretinoin 0.05-0.1% prevents the oxidation of Hydroquinone, as well as improving epidermal penetration, allowing pigment elimination & increasing keratinocyte proliferation

- Addition of corticosteroids to a combined therapy involving Hydroquinone decreases the irritative eff ects of the hypopigmenting agents, as well as inhibiting melanin synthesis by decreasing cellular metabolism

- Dual combination therapy w/ Hydroquinone & Glycolic acid or single agent therapy w/ 4% Hydroquinone, 0.1% Tretinoin or 20% Azelaic acid are used in patients who develop sensitivity to triple combination therapy

• Other combination therapies include: - Hydroquinone & Retinoic acid - Hydroquinone & Azelaic acid - Mequinol & Tretinoin - Hydroquinone, Glycolic acid &/or Kojic acid


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B99

Melasma (6 of 8)

Dosage Guidelines

EMOLLIENTS, CLEANSERS & SKIN PROTECTIVES1

Drug Available Strength Dosage Remarks

Arbutin Cream Apply to aff ected area 12 hrly

Adverse Reactions • Irritant contact dermatitis, erythema, occasional

photosensitivity• Paradoxical hyperpigmentation w/ high concSpecial Instructions• Use w/ caution in patients <12 yr

Glycolic acid Cream, soap Apply to aff ected area 12 hrly


photosensitivitySpecial Instructions• Clean area prior to application and pat dry• Avoid contact w/ eyes & other mucous membranes

Kojic acid Cream Apply to aff ected area 12-24 hrly


photosensitivitySpecial Instructions• Clean area prior to application and pat dry• Use w/ caution in patients <12 yr• Avoid contact w/ eyes

1Combination w/ other emollients are available. Please see latest MIMS for specifi c formulations.

All dosage recommendations are for non-pregnant & non-breastfeeding women, & non-elderly adults w/ normal renal & hepatic function unless otherwise stated.

Not all products are available or approved for above use in all countries.Products listed above may not be mentioned in the disease management chart but have been

placed here based on indications listed in regional manufacturers’ product information.Specifi c prescribing information may be found in the latest MIMS.

ACNE TREATMENT PREPARATIONS


Azelaic acid (micronized)

15% gel20% cream

Apply to aff ected area 12 hrly x 6 mth

Adverse Reactions • Usually resolve w/ continued use or by decreasing

frequency of application: Skin irritation, pruritus, burning

• Hypopigmentation, photosensitivitySpecial Instructions• Avoid exposure to excessive sunlight or UV radiation• Avoid contact w/ eyes

Mandelic acid 40% soln Apply a few drops on cleansed face & leave for 10-20 minWash off w/ cold water afterwards

Adverse Reactions • Irritation, rednessSpecial Instructions• Test on a small area of the skin behind the ear prior to

application• Avoid contact w/ eyes• Apply sunscreen & avoid sun exposure during use

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B100

All dosage recommendations are for non-pregnant & non-breastfeeding women, & non-elderly adults w/ normal renal & hepatic function unless otherwise stated.



Melasma (7 of 8)

Dosage Guidelines

EMOLLIENTS, CLEANSERS & SKIN PROTECTIVES1 (CONT’D)


Licorice extract

Cream, lotion, serum

Apply to aff ected area 12 hrly


photosensitivitySpecial Instructions• Clean area prior to application and pat dry• Avoid contact w/ eyes

Niacinamide (Nicotinamide)

Topical cream

Apply to aff ected area 12 hrly

Adverse Reactions • Dry skin, erythema, burning sensation, irritationSpecial Instructions• Wash face thoroughly prior to application• Avoid sun exposure during use

Tranexamic acid

Topical gel Apply to aff ected area 12 hrly

Adverse Reactions • Skin irritation, erythema, pruritus, burningSpecial Instructions• Use w/ caution in patients at risk for thrombotic

complications

1Combination w/ other emollients are available. Please see latest MIMS for specifi c formulations.

OTHER DERMATOLOGICALS


Hydroquinone 2% cream, gel4% cream, gel

Apply to aff ected areas 12 hrly

Adverse Reactions• Irritant dermatitis, contact dermatitis,

mild burning, transient erythema, postinfl ammatory pigmentation, ochronosis & nail bleaching

Special Instructions• Test for skin sensitivity before using

product by applying to small area of unbroken skin (minor redness is not a contraindication, but discontinue if itching, vesicle formation, or excessive infl ammatory response occurs)

• Contraindicated in patients <12 yr• Discontinue use if no lightening eff ect

is noted after 2 mth of treatment• Discontinue if a gradual blue-black

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B101

Melasma (8 of 8)

COMBINATION THERAPIES


Hydroquinone/ glycolic acid

Hydroquinone 2%,Glycolic acid 4%,Hydroquinone 2%,Glycolic acid 10%,

Apply once daily during night time to the aff ected area

Adverse Reactions • See individual componentsSpecial Instructions• See individual components

Hydroquinone/ tretinoin/ fl uocinoloneacetonide

Hydroquinone 4%,Tretinoin 0.05%,Fluocinoloneacetonide 0.01%

Apply once daily 30 min before bedtime on lesions & 0.5 cm of surrounding skin

Adverse Reactions • See individual componentsSpecial Instructions• See individual components

Hydroquinone/ tretinoin/mometasone furoate

Hydroquinone 2%,Tretinoin 0.025%,Mometasone furoate 1%

Apply once daily in the evening to the aff ected area

Adverse Reactions • Dry skin, cracked skin around the

nose & eyes, erythemaSpecial Instructions• Contraindicated in patients <12 yr• Avoid contact w/ eyes, mouth, nose

angle, thin skin, or mucous membranes

• Avoid sun exposure during treatment

OTHER DERMATOLOGICALS (CONT’D)


Pyocyanidin1 24 mg soft-gelatin cap

24 mg PO 12-24 hrly Adverse Reactions• GI eff ects (GI upset)Special Instructions• Take w/ food

Topical Retinoid Preparations

Tretinoin(Retinoicacid)

0.01% cream, gel0.025% cream, gel0.05 % cream, gel, lotion, soln0.1% cream0.1% soln0.04% microsphere gel0.1% microsphere gel

Apply 24 hrly at bedtime

Adverse Reactions • Usually resolve w/ decreasing

frequency of application: Stinging, feeling of warmth, erythema, peeling

• Edema, blistering, crusting of the skin, temporary hypo- or hyperpigmentation, photosensitivity

Special Instructions• Start w/ weaker formulation &

increase concentration as tolerated• Avoid exposure to excessive sunlight

or UV radiation

Dosage Guidelines

All dosage recommendations are for non-pregnant & non-breastfeeding women,& non-elderly adults w/ normal renal & hepatic function unless otherwise stated.



Please see the end of this section for the reference list.

1Available in combination w/ vitamins. Please see latest MIMS for specifi c formulations.

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melasma (1 of 8)

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