What is the recommended treatment for melasma?

Treatment of Melasma

The most effective first-line treatment for melasma is triple combination cream containing 4% hydroquinone, 0.05% tretinoin, and 0.01% fluocinolone acetonide, with 77-94% of patients achieving clear or almost clear skin. 1, 2

Treatment Algorithm

First-Line Therapy

1. Triple combination cream (4% hydroquinone, 0.05% tretinoin, 0.01% fluocinolone acetonide)

   • Apply once daily for 8-12 weeks
   • 77-94% efficacy rate for achieving clear or almost clear skin 1, 2
   • Monitor for mild skin irritation, dryness, and erythema

2. Mandatory sun protection

   • Broad-spectrum SPF 70 or higher daily
   • Inadequate sun protection is the most common reason for treatment failure 1
   • Continue indefinitely, even after clearing

Second-Line Options (if no improvement after 8-12 weeks)

1. Alternative topical agents:

   • Azelaic acid (15-20%)
   • Kojic acid
   • Non-hydroquinone formulations containing:
     • Tranexamic acid
     • Vitamin C
     • Arbutin
     • Niacinamide 1

2. Oral tranexamic acid

   • 250 mg twice daily for moderate to severe cases resistant to topical therapy
   • Requires monitoring for thromboembolic risk 1

3. Chemical peels

   • Glycolic acid or salicylic acid
   • 3-4 sessions spaced one month apart 1

4. Platelet-rich plasma (PRP) therapy

   • Intradermal injections
   • Protocol: once monthly for 3-5 sessions
   • Shown to be more effective than intradermal tranexamic acid 1

Monitoring and Follow-up

• Evaluate response every 4-6 weeks using standardized photography
• Assess using Melasma Area and Severity Index (MASI) score
• Adjust treatment if no improvement after 8-12 weeks 1
• Consider intermittent hydroquinone use for recurrences

Important Considerations and Pitfalls

Depth of Pigmentation

• Determine if melasma is epidermal, dermal, or mixed to guide treatment
• Epidermal: appears brown/black, responds better to treatment
• Dermal: appears blue, more resistant to treatment
• Mixed: most common type, may require combination approaches 1, 3

Skin Type Considerations

• Higher risk of post-inflammatory hyperpigmentation in darker skin types
• Use caution with aggressive treatments in Fitzpatrick skin types IV-VI 1

Safety Concerns

• Hydroquinone limitations:

  • Avoid prolonged use beyond 6 months due to risk of ochronosis (blue-black discoloration)
  • Carcinogenesis concerns have led to restrictions in many countries 1

• Laser therapy cautions:

  • Use with extreme caution in darker skin types
  • Risk of worsening hyperpigmentation and causing atrophic scarring 1

Common Pitfalls

1. Discontinuing treatment too early (melasma is chronic and often recurs)
2. Inadequate sun protection (critical for preventing recurrence)
3. Using aggressive treatments that can worsen hyperpigmentation
4. Not addressing underlying hormonal factors when present 1, 3

Pathophysiology Insights

Melasma involves complex pathology beyond simple melanin overproduction, including:

• Photoaging
• Increased mast cells
• Increased vascularization
• Basement membrane damage
• Nearly 300 genes differentially expressed from healthy skin 3

This complex pathophysiology explains why treatment is often challenging and requires a multi-modal approach with strict adherence to therapy and photoprotection.