What is the first‑line topical treatment for melasma, including appropriate concentrations of hydroquinone and tretinoin, adjunct corticosteroid use, sun protection, and contraindications such as pregnancy or hypersensitivity?

First-Line Topical Treatment for Melasma

Start with triple combination cream containing hydroquinone 4%, tretinoin 0.05%, and fluocinolone acetonide 0.01% applied once daily at bedtime, combined with broad-spectrum SPF 50+ sunscreen reapplied every 2-3 hours during sun exposure. 1, 2, 3

Treatment Algorithm

Step 1: Initiate Triple Combination Therapy

• Apply triple combination cream (hydroquinone 4%, tretinoin 0.05%, fluocinolone acetonide 0.01%) once daily at bedtime to affected areas 1, 2, 3
• This FDA-approved formulation (Tri-Luma) achieves 77% clear or almost clear results by week 8, with 29% experiencing complete clearing 3
• The corticosteroid component reduces irritation from hydroquinone and tretinoin while enhancing penetration 1, 4
• Continue treatment for at least 8-12 weeks before assessing response 1, 5

Step 2: Implement Strict Photoprotection

• Apply broad-spectrum sunscreen with minimum SPF 50+ every morning 1, 6
• Reapply every 2-3 hours during outdoor exposure, and immediately after swimming or sweating 1, 6
• Wear wide-brimmed hats (>3-inch brim) when outdoors 1
• Seek shade during peak UV hours (10 a.m. to 4 p.m.) 1
• Use UV-protective clothing with tight weave fabrics and darker colors 1
• Avoid tanning beds and sunlamps completely 1

Critical pitfall: Sun protection is the foundation of melasma treatment—failure to reapply sunscreen every 2-3 hours will undermine even the most aggressive topical therapy. 1, 6

Alternative First-Line Regimens

If triple combination cream is unavailable or contraindicated:

• Hydroquinone 4% monotherapy applied twice daily remains highly effective as first-line treatment 7, 2
• Modified Kligman's formula (hydroquinone 5%, tretinoin 0.05%, hydrocortisone acetate 1%) is also very effective 4, 8
• Tretinoin can be used alone or combined with hydroquinone for enhanced efficacy 1, 6

Contraindications and Safety Considerations

Absolute Contraindications

• Pregnancy: Tretinoin is pregnancy category C—avoid all tretinoin-containing products during pregnancy 9
• Known hypersensitivity to hydroquinone, tretinoin, corticosteroids, or any formulation component 9

Relative Contraindications and Precautions

• Darker skin types (Fitzpatrick IV-VI): Triple combination therapy is safe and effective, but avoid laser treatments due to markedly higher risk of post-inflammatory hyperpigmentation, burns, and hypopigmentation 1, 4
• Nursing mothers: Unknown if hydroquinone or tretinoin is excreted in breast milk after topical application 9
• Pediatric use: Safety not established in children <10 years for tretinoin 9

Managing Hormonal Influences

• Women may continue oral contraceptives or hormone replacement therapy when medically indicated, despite potential for pigmentation worsening 1
• Counsel patients that hormonal factors may limit treatment success but should not preclude therapy 1, 6

Expected Adverse Effects and Management

• Common side effects include erythema, peeling, dryness, burning, and mild irritation 9, 2
• These effects are typically mild and occur only at application site 3
• Skin atrophy risk is extremely low—only 2 cases reported across extensive studies of triple combination cream 3
• Avoid concomitant use of keratolytic agents or other photosensitizing agents that may increase irritation 9

When to Escalate to Second-Line Therapy

If inadequate response after 8-12 weeks of triple combination therapy plus strict photoprotection:

• Add intradermal platelet-rich plasma (PRP) injections: 4 sessions spaced every 2-3 weeks 1, 5
• Consider adjunctive oral tranexamic acid 250 mg twice daily for enhanced efficacy (90.48% total efficacy vs. 73.68% with tranexamic acid alone) 1, 5
• Microneedling with PRP may be more effective than intradermal PRP injections alone 1, 6

Long-Term Management

• Melasma is a chronic condition requiring maintenance therapy—discontinuing treatment too early leads to high recurrence rates 1, 5
• Continue sun protection indefinitely 1, 6
• Maintenance treatments every 6 months may be required 1, 5
• Counsel patients to avoid smoking, which worsens melasma 1, 6
• Use modified Melasma Area and Severity Index (mMASI) scores to objectively track improvement: >60-90% reduction indicates moderate improvement, >90% indicates excellent response 1, 6