Have You EverWondered How Acne Lesions Develop? Wonder No More

In this episode of Derms and Conditions, host James Q. Del Rosso, DO, examines the pathophysiology of acne vulgaris, tracing how advances in our understanding of the disease have shaped treatment approaches. He reviews the four key components of acne development—sebum production, follicular hyperkeratinization, Cutibacterium acnes proliferation, and inflammation—with particular attention to the role of androgens in initiating the cascade of events that leads to acne lesion formation.

Dr Del Rosso begins with a historical perspective on acne management, discussing how early treatment strategies focused primarily on reducing bacterial proliferation and follicular hyperkeratinization. He revisits the introduction of benzoyl peroxide, topical retinoids, and antibiotics, highlighting how subsequent research revealed additional mechanisms of action, including the direct anti-inflammatory properties of retinoids and tetracycline antibiotics.

The discussion then turns to the role of the skin as an endocrine organ and its ability to locally produce androgens from circulating precursors. Dr Del Rosso explains how androgen receptor activation stimulates sebaceous gland activity, contributing to increased sebum production and creating conditions that favor Cutibacterium acnes proliferation and inflammation. Importantly, these processes can occur even in patients with normal circulating androgen levels.

Building on these mechanisms, Dr Del Rosso considers how available therapies address different components of acne pathophysiology. He discusses the introduction of topical clascoterone, an androgen receptor inhibitor, as an opportunity to target the sebum-related component of acne development alongside established topical therapies. He also reviews the distinct role of oral isotretinoin and its effects across multiple pathogenic pathways.

Tune in to the episode for a closer look at how the interconnected mechanisms of acne development inform treatment selection, the rationale for combining therapies with complementary mechanisms of action, and how this understanding can support discussions with patients about their treatment regimens.