What is the recommended management for melasma, including first‑line and second‑line therapies and precautions for pregnant or breastfeeding patients?

Melasma Treatment

Start with triple combination cream (hydroquinone 4%, tretinoin 0.05%, and fluocinolone acetonide 0.01%) combined with strict broad-spectrum sunscreen (SPF 50+) as first-line therapy for melasma. 1, 2

First-Line Treatment Protocol

Photoprotection (Essential Foundation)

• Apply broad-spectrum sunscreen with minimum SPF 30, preferably SPF 50+, reapplied every 2-3 hours during outdoor exposure 1, 2
• Wear wide-brimmed hats (>3-inch brim) when outdoors 1, 2
• Seek shade during peak UV hours (10 a.m. to 4 p.m.) 1, 2
• Use UV-protective clothing with tight weave fabrics and darker colors 1, 2
• Avoid tanning beds and sunlamps completely 1, 2

Topical Therapy

• Triple combination cream remains the most effective topical treatment, superior to monotherapy 3
• Tretinoin can be used alone (0.05%-0.1%) or combined with hydroquinone (2-4%) for enhanced efficacy 1, 4, 3
• Corticosteroids are combined with hydroquinone and tretinoin in triple formulations to reduce irritation and enhance penetration 1, 2
• Hydroquinone monotherapy (2-4%) is also effective as a standalone agent 4, 3

Critical caveat: Never use monobenzyl ether of hydroquinone in melasma therapy 4

Second-Line Treatment for Inadequate Response

Intradermal Platelet-Rich Plasma (PRP) Injections

If first-line therapy fails after adequate trial (typically 8-12 weeks), intradermal PRP injections demonstrate superior efficacy compared to all other advanced treatments, including tranexamic acid injections. 1, 2

• Administer 4 intradermal PRP treatment sessions spaced every 2-3 weeks 2
• Inject intradermally at 1 cm intervals across affected areas 2
• Follow-up evaluation one month after the last treatment 2
• Expect significant improvement within 6 weeks as measured by modified Melasma Area and Severity Index (mMASI) scores 1, 2
• PRP shows mean mMASI score reduction of 45.67% improvement 1
• Patient satisfaction rates exceed 90% 1

Adjunctive Oral Tranexamic Acid

• Consider oral tranexamic acid 250 mg twice daily, particularly when combined with PRP injections 1, 2
• PRP combined with oral tranexamic acid demonstrates higher total efficacy (90.48%) compared to tranexamic acid alone (73.68%) with lower disease recurrence rates 1, 2
• Oral tranexamic acid is a promising systemic treatment for moderate and severe recurrent melasma 3

Alternative Procedural Options

• Microneedling may be more effective than intradermal PRP injections for melasma treatment in some patients 1, 2
• Needle depth should be set between 0.25 mm and 2.5 mm 2
• Apply compounded topical anesthetic at least 30 minutes before microneedling 2
• Ensure skin is well lubricated with topical agent or PRP to prevent pulling sensation 2
• Microneedling carries very low risk of post-inflammatory hyperpigmentation in Fitzpatrick skin types III-VI, markedly lower than laser therapy 2
• Minimal downtime (24-48 hours) 2
• Avoid microneedling over tattoos or permanent makeup 2

Important safety consideration: In individuals with Fitzpatrick skin types IV-VI, laser therapy is associated with markedly higher risk of adverse pigmentary outcomes—including burns, post-inflammatory hyperpigmentation, and hypopigmentation—and should be avoided or employed only with extreme caution 2

Maintenance Therapy

• Maintenance treatments every 6 months are required as melasma is a chronic condition with high recurrence rates 1, 2
• Continue sun protection and topical therapy indefinitely 2
• Disease recurrence rates are lower with PRP combination therapy 1

Measuring Treatment Success

• Use standardized mMASI scores to objectively track improvement 1, 2
• Decreases in MASI >60-90% indicate moderate improvement 1, 2
• Decreases in MASI >90% indicate excellent response 1, 2
• Patient satisfaction assessment should complement objective measurements 1, 2

Special Populations: Pregnancy and Breastfeeding

Hormonal Considerations

• Avoid topical estradiol in patients with history of melasma, as it can worsen the condition 5
• Patients should suspend use of oral contraceptives and other agents that promote skin pigmentation 4
• However, exogenous hormones (oral contraceptives, hormone replacement therapy) may be used in women with diagnosed melasma if needed for other indications 6

Treatment During Pregnancy

• Strict photoprotection remains the cornerstone 1, 2
• Most topical agents (hydroquinone, tretinoin, corticosteroids) have limited safety data in pregnancy and should be used with caution or avoided 7
• Sunscreen and physical sun protection measures are safe and essential 1, 2

Critical Pitfalls to Avoid

• Discontinuing treatment too early—melasma is a chronic condition requiring long-term maintenance therapy 2
• Forgetting to reapply sunscreen after swimming, sweating, or after 2-3 hours of continuous exposure 1, 2
• Failing to address hormonal influences (pregnancy, oral contraceptives, hormone replacement therapy) that may limit treatment success 2
• Using laser therapy in darker skin types (Fitzpatrick IV-VI) without extreme caution 2
• Counsel patients to avoid smoking, which can worsen melasma 1, 2
• Sun avoidance for first 24 hours after microneedling procedures 2
• Refrain from using facial creams or products containing strong fragrances for 24 hours post-procedure 2