Strategic Targets in Acne, Update 2025: The Microcomedone Is Not Just a Plug, It Is an Egg.

Background: Maintaining homeostasis in the upper pilosebaceous unit in acne-prone skin has emerged as the primary goal for effective and long-term acne management.

Summary: In this review, we describe advances in acne research that have helped redefine the strategic targets for new topical acne treatments, providing the basis for new therapeutic strategies that may allow this goal to be achieved.

Key Messages: First, we describe the results of studies analyzing apparently uninvolved skin from individuals with acne, using sequential skin surface biopsies. These studies led to the identification of subclinical lesions, referred to as microcomedones, as the root of all subsequent acne lesions, and thus clinically non-lesional acne skin as the strategic target for new acne therapies. We then describe the concept of the comedo switch, in which exposure of progenitor cells in the pilosebaceous unit to comedogenic factors in acne-prone skin leads to the formation of microcomedones. Previously considered as an "inert plug", the microcomedone rather appears to be "an egg" that can grow into acne lesions.