A Practical Guide to Modern Melasma Treatment

Melasma is a chronic, relapsing disorder of hyperpigmentation that can affect all races and genders but disproportionately affects women and individuals with skin of color.^1,2 Melasma typically presents as bilateral, asymptomatic, brown to gray-brown macules or patches on the face. While the condition itself is benign, the psychosocial impact can negatively affect quality of life.³ In addition, melasma may be difficult to distinguish from other facial pigmentary disorders including lichen planus pigmentosus, post-inflammatory hyperpigmentation, erythema dyschromicum perstans, and drug-induced hyperpigmentation.⁴ Misdiagnosis or other diagnostic delays can further impact patients’ quality of life.

Diagnosis and Management

A recently published Delphi consensus study, which included expert opinions from 38 dermatologists across 11 countries, provides structured guidance for the diagnosis and management of melasma.⁵ Consensus was reached regarding the use of Wood lamp testing to assess extent and severity of the condition, dermoscopy for distinguishing melasma from other disorders of dyspigmentation, and biopsy for atypical presentations.⁵ Consensus was also reached regarding therapeutic options with a foundational component of therapy being broad-spectrum UVA, UVB, and visible light photoprotection. Effective topical treatment therapies included triple combination cream (hydroquinone, tretinoin, and fluocinolone acetonide), azelaic acid, and vitamin C, while oral tranexamic acid was considered an effective oral treatment. Triple combination cream was ultimately identified as first-line therapy, while adjunctive procedural treatments including chemical peels and energy-based devices may be considered in select refractory cases.

Pathogenesis

With regard to disease pathogenesis, melasma has previously been considered a primarily melanocyte-driven process initially triggered by ultraviolet (UV) radiation and visible light, which upregulate melanin-stimulating receptors on melanocytes, eventually resulting in increased hormone binding and melanin production.⁶ More recent studies have identified the importance of a vascular component to the pathogenesis of melasma, with increased blood vessel number, density, and size, and telangiectatic erythema seen in melasma lesional skin.⁷ UV radiation works in conjunction with this process, initiating a vascular-pigmentary cascade by upregulating VEGF, FGF, and IL-8 and triggering angiogenesis.^8,9 Recognition of the vascular contribution has direct therapeutic implications, as anti-vascular therapies such as tranexamic acid, pulsed dye laser, and Q-switched neodymium doped yttrium aluminum garnet (QS-Nd:YAG) laser have resulted in reduction in vascular markers, erythema, and pigment severity in patients with melasma.^10-13 Oral tranexamic acid (TXA), which inhibits plasmin, has demonstrated significant reductions in modified Melasma Area and Severity Index (mMASI) scores in randomized trials. Dosing regimens of 250 mg twice daily for 12 weeks have shown meaningful improvement with sustained response and relatively low relapse rates; higher doses have not been found to confer additional benefits.¹⁴ Additionally, laser therapy with low-fluence QS-Nd:YAG lasers and pulsed dye lasers appears to be most efficacious when vascular features are prominent.^15-18

Summary

Overall, modern management of melasma requires an individualized approach with targeted therapies that incorporate updated knowledge of disease pathogenesis. Addressing the vascular component of melasma, using evidence-based topical therapies, and optimizing photoprotection allows clinicians to improve outcomes for their patients with melasma while minimizing adverse effects. As we continue to learn more about the vascular and inflammatory pathways involved in melasma, treatment strategies that address both the pigmentary and vascular components of the disease may improve long-term outcomes for patients. Future research focused on targeted therapies and predictors of therapeutic response may help inform more tailored therapeutic regimens moving forward.