Melasma (1 of 8) 1 Patient presents w/ symmetric hyperpigmented macules, which can be confl uent or punctate suggestive of melasma 2 DIAGNOSIS No ALTERNATIVE Does clinical presentation DIAGNOSIS confirm melasma? Yes A Non-pharmacological therapy • Patient education • Camoufl age make-up • Sunscreen B Pharmacological therapy Monotherapy • Hydroquinone or • Tretinoin TREATMENT Responding to No treatment? See next page Yes Continue treatment © MIMSas required Not all products are available or approved for above use in all countries. Specifi c prescribing information may be found in the latest MIMS. B94 © MIMS 2019 Melasma (2 of 8) Patient unresponsive to initial therapy MELASMA A Non-pharmacological therapy • Patient education • Camoufl age make-up • Sunscreen B Pharmacological therapy Dual Combination erapy • Hydroquinone plus • Tretinoin or • Azelaic acid Responding to Yes Continue treatment treatment? as required No A Non-pharmacological therapy • Patient education • Camoufl age make-up • Sunscreen • Laser therapy • Dermabrasion B Pharmacological therapy Triple Combination erapy • Hydroquinone plus • Tretinoin plus • Topical steroid Chemical peels 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 mostMIMS important factor in its development Not all products are available or approved for above use in all countries. Specifi c prescribing information may be found in the latest MIMS. B95 © MIMS 2019 Melasma (3 of 8) 2 DIAGNOSIS Diagnosis is based on clinical characteristics Physical Exam • Patient presents w/ well-demarcated tan to brown macular hyperpigmentation • Based on clinical pattern may be classifi ed to: MELASMA - 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 both Classifi 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 THERAPY Patient Education • Avoid sunlight exposure - Wear protective clothing when going outdoors • Oftentimes resolved after pregnancy or discontinuation of oral contraceptive pills Sunscreens • Use of sunscreens that block UVA & UVB light are highly recommended - Broad spectrum sunscreen w/ SPF >30 coverage is recommended Camoufl age make-up • Heavy coverage of lesions while blending w/ unaff ected skin color may help Physical erapies Cryosurgery • May be an option because melanocytes are susceptible to freezing Dermabrasion/Microdermabrasion • May be used for dermal melasma Intense 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 poorly Laser 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 - © MIMS Positive results were seen w/ the use of pulsed CO2 laser w/ Q-switched alexandrite laser Not all products are available or approved for above use in all countries. Specifi c prescribing information may be found in the latest MIMS. B96 © MIMS 2019 Melasma (4 of 8) B PHARMACOLOGICAL THERAPY Azelaic 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 MELASMA 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 agents Chemical 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 skin Alpha 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 melasma Salicylic 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 ective Topical Depigmenting Agent Hydroquinone • 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 agents Kojic 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 potential Mequinol • 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/ Tretinoin Topical Retinoids Tretinoin • 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 irritatingMIMS than gels & solution Not all products are available or approved for above use in all countries. Specifi c prescribing information may be found in the latest MIMS. B97 © MIMS 2019 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 • Modulates follicular epithelial cell diff erentiation by binding to specifi c nuclear retinoic acid receptor MELASMA Actions: proteins • Studies show that Adapalene is equally effi cacious compared to Tretinoin Adjunctive erapies Ascorbic 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 melanocytes Arbutin • A derivative of Hydroquinone used as an alternative treatment to Hydroquinone • Action: Inhibits tyrosinase, 5,6-hydroxyindole-2-carboxylic acid, & melanosome maturation Niacinamide (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-2 Tranexamic 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 melasma Others • Plant extracts (Licorice, Grape seed, Orchid, Aloe vera, Soybean, Coff eeberry, Green tea, marine algae), Indomethacin, Vitamin E,