In this highly engaging seminar-in-depth, Cheri Frey, MD, reviewed the pathogenesis of hyperpigmentation and discussed a novel ingredient for the treatment of hyperpigmentation. Disorders of hyperpigmentation are common and can negatively affect patients’ quality of life. For clinicians, it is often difficult to determine the etiology of the hyperpigmentation and determine whether that pigment exists in the epidermis, dermis, or both. Dr Frey discussed two of the most common types of hyperpigmentation, postinflammatory hyperpigmentation (PIH) and melasma. Current treatment options include photoprotection, chemical peels, lasers, and topical bleaching or lightening agents such as hydroquinone, tretinoin, kojic acid, azelaic acid, and arbutin, among others.

Dr Frey reviewed the process of melanogenesis and how this contributes to pigmentary disorders. Tyrosine is converted into levodopa (L-DOPA) and then either pheomelanin or eumelanin by tyrosinase inside of melanosomes. The conversion of tyrosine to L-DOPA is a key rate-limiting step in the melanogenesis pathway and is the most targeted mechanism of action to reduce hyperpigmentation. Dr Frey introduced a novel ingredient, thiamidol, currently being developed as a topical tyrosinase inhibitor. During a screening of 50,000 compounds, thiamidol was found to be the strongest inhibitor of human tyrosinase, stronger than hydroquinone, arbutin, and kojic acid.

Topical thiamidol led to significantly higher melasma severity score reduction compared to hydroquinone 2% in a 12-week split-face, double-blind clinical study. Longer-term studies out to 24 weeks demonstrated continued improvements in melasma with once daily thiamidol use. Dr Frey discussed that thiamidol has also shown efficacy for treating postinflammatory hyperpigmentation in small clinical studies. Importantly, melanin-index scores were not shown to be reduced in perilesional skin, only in lesional skin. Thiamidol also shows promise for the prevention of laser-induced postinflammatory hyperpigmentation.