Integration: Unifying Concept
Acne is a multifactorial condition that involves a complex interplay between the folliculosebaceous unit influenced by sebum production, inflammation, hyperkeratinization, and bacterial proliferation (i.e., Propionobacterium acnes). The precise sequence of events remains largely unclear. The infundibular epidermis. i.e., the infundibulum, seems to be the prime locale for catalyzation of the inflammatory cascade.
Infundibulum-centered acne vulgaris and variants rely heavily upon innate immunity. The spectrum of its severity ranges from comedones and inflamed papules that resolve without residua to fluctuant and draining sinuses that heal with disfiguring scars. Inflammatory cells, neutrophils chief among them, appear early in and around the infundibular zone. Comedogenesis is driven by innate factors such as Toll-like receptor 2 activation and influenced by interleukin secretion by keratinocytes (i.e., IL-1α). If the collection of neutrophils is confined to an infundibulum, the lesion is a pustule. If the process is more florid and the collection of neutrophils is so great that much of an infundibulofollicular unit is obscured by it, pseudocarcinomatous proliferation of infundibular keratinocytes develops in an attempt to contain it. The result is an inflammatory cascade with one or more of a constellation of acne conglobata, acne keloidalis, or acne fulminans. Although considered the tetrad of follicular occlusion, it seems increasingly less likely that a single pathologic process drives acne vulgaris, conglobata, keloidalis, dissecting cellulitis, and hidradenitis suppurativa; however, all may be present in one person, suggesting common denominators.
Dreno B, Gollnick HP, Kang S, et al. Global Alliance to Improve Outcomes in Acne. Understanding innate immunity and inflammation in acne: implications for management. J Eur Acad Dermatol Venereol 2015 Jun;29 Suppl 4:3-11.
Selway JL, Kurczab T, Kealey T, Langlands K. Toll-like receptor 2 activation and comedogenesis: implications for the pathogenesis of acne. BMC Dermatol 2013 Sep 6; 13:10.