What is the treatment for resistant melasma?

Treatment of Resistant Melasma

For resistant melasma, intradermal platelet-rich plasma (PRP) injections are the most effective treatment option, demonstrating superior efficacy compared to all other modalities including tranexamic acid injections, with mean mMASI score reductions of 45-54% and patient satisfaction rates exceeding 90%. 1, 2, 3

Treatment Algorithm for Resistant Cases

Step 1: Optimize Foundation Therapy

• Ensure strict broad-spectrum sunscreen use (SPF 50+) reapplied every 2-3 hours during outdoor exposure 1, 2
• Add physical sun protection: wide-brimmed hats (>3-inch brim), UV-protective clothing with tight weave and darker colors, and shade-seeking during peak UV hours (10 AM to 4 PM) 2
• Verify patient has failed adequate trial of triple combination cream (hydroquinone 4%, tretinoin 0.05%, fluocinolone acetonide 0.01%) for at least 12 weeks 4, 5, 6

Step 2: Initiate PRP Injection Protocol

• Administer intradermal PRP microinjections 1 cm apart for 3-5 monthly treatment sessions 2, 3
• Alternative protocol: Four intradermal PRP treatments every 2-3 weeks 1
• Evaluate response one month after the last treatment using modified MASI (mMASI) scores 1, 3

Step 3: Add Systemic Adjunctive Therapy

• Consider oral tranexamic acid 250 mg twice daily in combination with PRP injections 2
• This combination achieves 90.48% total efficacy compared to 73.68% with tranexamic acid alone, with significantly lower recurrence rates 1, 2
• The combination maintains normal VEGF and α-MSH levels while reducing disease recurrence 2

Step 4: Alternative Advanced Option

• If PRP is unavailable or contraindicated, consider fractional 1540-nm erbium-glass laser (four treatments at 3-week intervals) combined with pulse-therapy triple combination cream 7
• This achieves marked clearing (>75%) in 67% of resistant cases at 1 month, though long-term efficacy is limited with 43% showing no improvement at 6 months 7

Measuring Treatment Success

• Use standardized mMASI scores to objectively track improvement 1, 2, 3
• Decreases in MASI >60-90% indicate moderate improvement; >90% indicates excellent response 2
• Complement objective measurements with patient satisfaction assessment 2
• Dermoscopic evaluation can confirm diagnosis and monitor treatment response 3

Maintenance Protocol

• Maintenance PRP treatments every 6 months are essential 1, 2
• Continue strict photoprotection indefinitely 1, 2
• Consider intermittent use of topical agents between maintenance sessions 1
• For patients on triple combination cream maintenance, apply twice weekly after initial clearing; however, most patients (approximately 75%) will relapse and require resumption of daily therapy 8

Critical Pitfalls to Avoid

• Discontinuing treatment prematurely: Melasma is a chronic condition with high recurrence rates requiring long-term maintenance 1, 2
• Inadequate sun protection: Forgetting to reapply sunscreen after swimming, sweating, or after 2-3 hours of continuous exposure undermines all other treatments 2
• Using laser/light therapies as monotherapy: These have mixed results and carry higher risk of post-inflammatory hyperpigmentation, particularly in darker skin types 5, 6
• Failing to counsel patients on avoiding smoking, which negatively impacts treatment outcomes 2

Evidence Strength Considerations

The recommendation for PRP is based on recent high-quality evidence from the American Academy of Dermatology showing statistically significant mMASI reductions with high strength of evidence 1, 2, 3. While triple combination cream remains the most studied treatment overall 5, 6, PRP specifically addresses resistant cases where topical therapy has failed. Chemical peels and laser therapies show inferior or equal results to topicals with higher adverse event risk 5, 6.