Melasma and Other Hyperpigmentation Disorders

Andrew F. Alexis, MD, MPH, began by reviewing the multifactorial pathophysiology of melasma, which involves ultraviolet (UV) and visible light exposure, hormonal triggers, vascular changes, and inflammatory signaling. He highlighted recent evidence underscoring the central role of oxidative stress and the JAK–STAT pathway in melanogenesis. Topical therapies remain first-line, with hydroquinone continuing to serve as the gold standard despite limitations such as irritant dermatitis and risk of exogenous ochronosis. Dr Alexis discussed novel non-hydroquinone agents, including cysteamine, thiamidol (a potent human tyrosinase inhibitor), and multitarget cosmeceutical combinations like MB3 (2-MNG, niacinamide, cystoseira extract, and lipohydroxy acid), all of which have shown significant mMASI score reductions comparable to or exceeding hydroquinone-based regimens in clinical studies. 

Dr Alexis then focused on systemic and procedural advances. He reviewed data demonstrating that oral tranexamic acid (TXA), given at 250–325 mg twice daily for three months, can reduce mMASI scores by nearly 50%, with no thromboembolic events reported in large retrospective safety analyses. Adjunctive use of oral antioxidants such as Polypodium leucotomos and combination regimens integrating TXA with topical hydroquinone, retinoids, and kojic acid further improve pigment clearance. Procedural therapies, including glycolic acid peels, microneedling, and fractional 1927 nm thulium laser, enhance epidermal turnover and melanin removal, with best outcomes achieved when paired with maintenance topicals and strict photoprotection using mineral- and iron oxide–based sunscreens. Dr Alexis also highlighted that disorders like lichen planus pigmentosus and acquired dermal macular hyperpigmentation can mimic melasma and may respond to oral isotretinoin and low-energy fractional laser therapy. His concluding message stressed that successful pigment management hinges on personalized, multimodal regimens that address both melanocyte hyperactivity and skin barrier dysfunction.