Pathogenesis of Acne Vulgaris:What’s New, What’s Interesting and What May Be Clinically Relevant

Acne vulgaris is a common disorder of the pilosebaceous unit clinically resulting in inflammatory (papules,pustules, nodules) and noninflammatory lesions(open and closed comedones). The impact of this chronic disease is far-reaching as it affects 40-50 million people in the United States and touts a worldwide prevalence rate of 80 percent.^1,2 The pathogenesis is multifactorial with four primary pathogenic factors including excess sebum production, Propionibacterium acnes (P. acnes) colonization, follicular hyperkeratinization and release of inflammatory mediators into the skin.³ With a continuous influx of new information regarding acne pathogenesis, this article aims to summarize recent advances in acne pathogenesis and new acne treatments based on those findings.

Do inflammatory events precede comedone formation, or are microcomedones the precursor for all acne lesions, leaving inflammation as a secondary process? Although there is general consensus on the major pathogenic factors in acne, the theories behind the sequence of events in acne lesion formation have been challenged. Traditionally, acne lesions are thought to initially develop from the formation of a keratin plug, activation of sebaceous glands by androgens and P. acnes proliferation which is then followed by induction of the innate immune response and resulting inflammation^.4 The microcomedone is thought to be the primary acne lesion which can then develop into an inflammatory or noninflammatory lesion. The formation of comedones develops from ductal keratinocyte hyperproliferation and abnormal differentiation.⁵ In fact, nuclear proliferation and hyperproliferation/abnormal differentiation was demonstrated utilizing Ki67 and Keratin 16 (K16) markers.⁵ Ki67 is increased in actively cycling cells in the basal keratinocytes of follicular walls in microcomedones and comedones.⁵ Ki67 also confirmed ductal hyperproliferation in unaffected follicles in nearby areas of acne prone skin, lending support to the theory that hypercornification precedes inflammation.⁶ In a recent study tracking the evolution of acne lesions using serial digital photographs, researchers confirmed comedonal origin of most inflammatory lesions; however, 28 percent appeared to arise de novo.⁷

Conversely, research of cellular, vascular and proliferative markers via immunohistochemical studies displayed inflammatory events preceding hyperkeratinization.⁸ In fact, an increase in CD4+ T cells and macrophages was found in clinically uninvolved pilosebaceous follicles of acne prone skin.⁸ Elevated levels of proinflammatory cytokine interleukin-1 (IL-1) was evident perifollicularly.⁸ Furthermore, aberrant integrin expression in uninvolved skin and around inflamed lesions lends additional support that inflammatory events may precede hyperproliferation.⁸

P. acnes is a gram-positive commensal organism found in sebaceous follicles, but can also be an opportunistic pathogen as a major player in the development of acne vulgaris. P. acnes has long been implicated as one of the major contributing factors in the pathogenesis of acne. What is traditionally known is that P.