What are the causes and treatment options for melasma?

Causes and Treatment of Melasma

Causes of Melasma

Melasma is a multifactorial disorder of hyperpigmentation caused by the interaction of ultraviolet radiation exposure, hormonal influences (pregnancy, oral contraceptives, estrogen-progesterone therapy), genetic predisposition, and skin inflammation in susceptible individuals. 1, 2

Primary Etiologic Factors

• UV radiation exposure is the major environmental trigger, with even minimal sunlight sustaining melanocytic activity and causing repigmentation of treated areas 3, 4
• Hormonal alterations including pregnancy, oral contraceptives, estrogen-progesterone therapies, and thyroid dysfunction are well-established causative factors 1, 5, 6
• Genetic predisposition plays a significant role, with family history being a key risk factor 1
• Skin inflammation from contact dermatitis, cosmetics, phototoxic drugs, anti-seizure medications, and esthetic procedures can trigger melasma in predisposed individuals 2, 6

Pathophysiology

• The condition involves hyperfunctional melanocytes with increased melanin production in epidermal basal and suprabasal layers and/or dermis 5, 6
• Increased expression of tyrosinase-related protein-1 drives eumelanin synthesis 5
• Structural alterations include basement membrane damage, increased vascularization, mast cell proliferation, fibroblast senescence, and nearly 300 differentially expressed genes compared to healthy skin 4, 2

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Treatment Algorithm for Melasma

Step 1: Foundation Therapy (All Patients)

Strict sun protection with broad-spectrum sunscreen SPF 50+ is absolutely essential and must be the foundation of any melasma treatment regimen. 7, 8, 9

• Apply broad-spectrum sunscreen SPF 50+ and reapply every 2-3 hours during outdoor exposure 7, 8
• Wear wide-brimmed hats (>3-inch brim) when outdoors 7
• Seek shade during peak UV hours (10 AM to 4 PM) 7, 8
• Use UV-protective clothing with tight weave fabrics and darker colors 7
• Avoid tanning beds and sunlamps completely 7
• Counsel patients to avoid smoking, which damages treatment outcomes 7, 8

Step 2: First-Line Topical Therapy

• Hydroquinone (topical depigmenting agent) inhibits enzymatic oxidation of tyrosine to dopa and suppresses melanocyte metabolic processes 3, 1, 5
• Tretinoin can be used alone or combined with hydroquinone 7, 1, 5
• Triple combination formulations containing hydroquinone, tretinoin, and corticosteroids show increased efficacy compared to monotherapy 7, 1, 5
• Azelaic acid is an alternative topical agent with proven efficacy 10, 5

Important caveat: Hydroquinone requires skin sensitivity testing before use and may produce unwanted cosmetic effects if not used as directed; avoid contact with eyes and mucous membranes 3

Step 3: Advanced Treatment for Inadequate Response After 8-12 Weeks

If first-line therapy fails after 8-12 weeks, intradermal platelet-rich plasma (PRP) injections are the most effective treatment for melasma, demonstrating superior efficacy compared to all other advanced therapies including tranexamic acid. 8, 9

PRP Treatment Protocol

• Administer four intradermal PRP treatment sessions every 2-3 weeks with injections spaced 1 cm apart 8
• Follow-up evaluation one month after the last treatment 8
• PRP demonstrates mean mMASI score reduction of 45.67% improvement 7
• Patient satisfaction rates exceed 90% with PRP treatment 7

Adjunctive Oral Therapy

• Oral tranexamic acid 250 mg twice daily combined with PRP shows even higher total efficacy (90.48%) compared to tranexamic acid alone (73.68%) with lower disease recurrence rates 7, 8
• This combination maintains normal levels of VEGF and α-MSH while reducing recurrence 7

Alternative Procedural Options

• Microneedling may be more effective than intradermal PRP injections in some patients 7, 9
• Radiofrequency microneedling: three treatment sessions spaced at least 21 days apart 7
• Chemical peels serve as good adjunctive therapy 1, 5

Step 4: Maintenance Therapy

Melasma must be managed as a chronic condition requiring lifelong maintenance to prevent recurrence. 7, 8

• Continue strict sun protection indefinitely 7, 8, 3
• Maintenance PRP treatments every 6 months as needed 7, 8
• Intermittent use of topical agents for maintenance 8
• Regular follow-ups to monitor for recurrence 7

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Measuring Treatment Success

• Use modified Melasma Area and Severity Index (mMASI) scores to objectively track improvement 7, 8
• Decreases in MASI >60-90% indicate moderate improvement; >90% indicates excellent response 7
• Patient satisfaction assessment should complement objective measurements 7

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Critical Pitfalls to Avoid

• Forgetting sunscreen reapplication after swimming, sweating, or after 2-3 hours of continuous exposure leads to treatment failure 7
• Discontinuing treatment too early is a common mistake; melasma requires long-term maintenance therapy due to high recurrence rates 8, 4
• Using hydroquinone without proper patient counseling about sun avoidance, as even minimal sunlight exposure will cause repigmentation of bleached areas 3
• Applying hydroquinone to broken or inflamed skin can cause temporary irritation (pruritus, burning, stinging) due to its low pH 10