Treatment Guideline Chart
Melasma is an acquired hypermelanosis skin disorder that commonly affects women than men. It is characterized by irregular light to dark brown macules occurring in the sun-exposed areas of the face, neck and arms.
It occurs most commonly with pregnancy and with the use of contraceptive pills.
Other factors implicated in the etiopathogenesis are photosensitizing medications, mild ovarian or thyroid dysfunction and certain cosmetics.
Solar and ultraviolet exposure is the most common important factor in its development.

Melasma Treatment


Azelaic acid

  • 10, 15, 20 and 35% preparations are used to lessen pigmentation
  • A natural dicarboxylic acid that has antiproliferative and cytotoxic effects on melanocytes
    • Acts by several mechanisms including inhibition of tyrosinase, cell membrane-associated enzyme thioredoxin reductase, specific mitochondrial dehydrogenases and DNA synthesis
  • Reduction in melasma intensity may be seen after 1-2 months with continuous application for up to 8 months
    • Studies have shown that efficacy of Azelaic acid for melasma is comparable to that with Hydroquinone
  • May be used in combination with other agents

Chemical Peels

  • Eg Glycolic acid, Lactic acid, Mandelic acid, Phytic acid, Resorcinol, Salicylic acid, Trichloroacetic acid, Jessner's solution (Glycolic acid plus Trichloroacetic acid)
  • Recommended as alternative therapy if topical agents and triple combination therapy are not effective
  • Improves the response rate of patients to topical therapy
  • Performed by applying chemical agents to the skin to induce progressive exfoliation of the superficial layers of the skin

Alpha Hydroxy acid (Glycolic acid, Lactic acid)

  • Inhibits tyrosinase activity
  • Also effective as adjunctive agents to topical treatments
  • Studies showed that lactic acid works well against epidermal melasma

Salicylic acid

  • Inhibits tyrosinase activity
  • More effective when used in combination with topical treatments

Topical Corticosteroids

  • Eg 0.01% Fluocinolone acetate
  • Used as part of triple combination therapy if previous combinations were ineffective
  • Clobetasol was found to rapidly clear melasma pigmentation but the mechanism of action is not fully understood and it is not recommended for prolonged use to due local side effects

Topical Depigmenting Agent


  • Has been used for the treatment of hyperpigmentation for many decades
  • A hydroxyphenolic compound that inhibits the conversion of dihydroxyphenylalanine (DOPA) to melanin by inhibition of tyrosinase
    • Also inhibits DNA and RNA synthesis, induces degradation of melanosomes and promotes destruction of melanocytes
  • Commonly used at concentrations ranging from 2-5%, higher concentrations provide greater efficacy but with greater skin irritation
  • Can cause permanent depigmentation when used at high concentrations for a long period of time
  • May be used in combination with other agents

Kojic acid

  • A non-phenol depigmenting agent used as an alternative treatment for patients allergic to Hydroquinone
  • Tyrosinase inhibitor that chelates copper at the enzyme’s active site
  • With high sensitizing potential


  • A phenolic depigmenting agent used as alternative treatment for Hydroquinone-intolerant patients
  • Competitively inhibits tyrosinase while sparing melanocytes
  • Usually used for solar lentigines when given in combination with Tretinoin

Topical Retinoids


  • 0.05-1% preparations are known to reduce pigmentation
  • Inhibits tyrosinase transcription as well as dopachrome conversion thereby interrupting melanin synthesis
  • Effective as monotherapy but better results are seen when used in combination with 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 and solution


  • Alternative treatment for Tretinoin-intolerant patients
  • 0.1% preparations are used for long-term melasma treatment
  • Modulates follicular epithelial cell differentiation by binding to specific nuclear retinoic acid receptor proteins
  • Studies show that Adapalene is equally efficacious compared to Tretinoin

Adjunctive Therapies

Ascorbic acid (Vitamin C)

  • Alternative treatment to Hydroquinone that provides skin lightening with less adverse effects
  • Directly inhibits tyrosinase, thereby reducing melanin production in melanocytes


  • A derivative of Hydroquinone used as an alternative treatment to Hydroquinone
  • Inhibits tyrosinase, 5,6-hydroxyindole-2-carboxylic acid, and melanosome maturation

Niacinamide (Nicotinamide, Vitamin B3)

  • Used as adjunctive therapy for melasma due to its skin lightening and brightening effect
  • Inhibits melanosome transfer after melanin synthesis by modulating the protease-activated receptor (PAR)-2

Tranexamic acid

  • Acts as a plasmin inhibitor that prevents UV-induced pigmentation
    • Also inhibits melanogenesis: prevents plasminogen binding to keratinocytes which in turn reduces prostaglandin and arachidonic acid production needed for melanogenesis
  • May be given orally, subcutaneously, or topically; topical formulation often in combination with other agents
  • Further studies are needed to prove the efficacy of Tranexamic acid for melasma

Other Agents

  • Plant extracts (Licorice, Grape seed, Orchid, Aloe vera, Soybean, Coffeeberry, Green tea, marine algae), Indomethacin, Soybean extract, Vitamin E, Rucinol, Gigawhite, Pyocyanidin (Pycnogenol)
  • Thiamidol, Malassezin, Cysteamin, Methimazole, Metformin and Melatonin are also being investigated for their ability to affect development of pigmentation

Combination Therapies

  • Employed to increase efficacy and reduce side effects
  • Fixed dose (o.1%) triple combination therapy with Hydroquinone, Retinoic acid and 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 and increasing keratinocyte proliferation
    • Addition of corticosteroids to a combined therapy involving Hydroquinone decreases the irritative effects of the hypopigmenting agents, as well as inhibiting melanin synthesis by decreasing cellular metabolism
    • Dual combination therapy with Hydroquinone and Glycolic acid or single agent therapy with 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 and Retinoic acid
    • Hydroquinone and Azelaic acid
    • Mequinol and Tretinoin
    • Hydroquinone, Glycolic acid and/or Kojic acid

Non-Pharmacological Therapy


  • Use of sunscreens that block UVA and UVB light are highly recommended
    • Broad spectrum sunscreen with sun protection factor (SPF) >30 coverage is recommended

Camouflage make-up

  • Heavy coverage of lesions while blending with unaffected skin color may help

Physical Therapies


  • May be an option because melanocytes are susceptible to freezing


  • 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 which often responds poorly

Laser Therapy

  • Eg Q-switched (QS) lasers, fractional lasers
  • Used as second-line treatment in cases resistant to other therapies
  • Combination of QS + fractional carbon dioxide (CO2) and QS + IPL are recommended for all skin types
    • Positive results were seen with the use of pulsed CO2 laser with Q-switched alexandrite laser


  • Can be used to enhance treatment outcome of topical agents (eg vitamin C, platelet-rich plasma, depigmentation serums)
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