Melasma Treatment

Azelaic Acid

• 10, 15, 20 & 35% preparations are used to lessen pigmentation
• Actions: A natural dicarboxylic acid that has antiproliferative & cytotoxic effects on melanocytes
  • Acts by several mechanisms including inhibition of tyrosinase, cell membrane-associated enzyme thioredoxin reductase, specific mitochondrial dehydrogenases & DNA synthesis

• Effects: 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
• Recommended as alternative therapy if topical agents & 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)

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

Salicylic acid

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

Topical Corticosteroids

• Eg 0.01% Fluocinolone acetate
• 0.01% preparation
• Used as part of triple combination therapy if previous combinations were ineffective

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 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
• 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 with 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
• 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 & solution

Adapalene

• Alternative treatment for Tretinoin-intolerant patients
• 0.1% preparations are used for long-term melasma treatment
• Actions: 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
• 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 (Vitamin B3)

• Used as adjunctive therapy for melasma due to its skin lightening & brightening effect
• 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 ultraviolet-induced pigmentation
  
  • Also inhibits melanogenesis: prevents plasminogen binding to keratinocytes which in turn reduces prostaglandin & 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

Others

• Plant extracts (Licorice, Grape seed, Orchid, Aloe vera, Soybean, Coffeeberry, Green tea, marine algae), Indomethacin, Soybean extract, Vitamin E, Rucinol, Gigawhite, Pyocyanidin (Pycnogenol)

Combination Therapies

• Employed to increase efficacy & reduce side effects
• Fixed dose triple combination therapy with 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 effects of the hypopigmenting agents, as well as inhibiting melanin synthesis by decreasing cellular metabolism
  • Dual combination therapy with Hydroquinone & 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 & Retinoic acid
  • Hydroquinone & Azelaic acid
  • Mequinol & Tretinoin
  • Hydroquinone, Glycolic acid &/or Kojic acid

Sunscreens

• Use of sunscreens that block UVA & UVB light are highly recommended
  • Broad spectrum sunscreen with SPF >30 coverage is recommended

Camouflage make-up

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

Physical Therapies

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 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 CO₂ & QS + IPL are recommended for all skin types
  • Positive results were seen with the use of pulsed CO₂ laser with Q-switched alexandrite laser