Is There a Place for Biologics in Acne?

Abstract

Acne vulgaris is a chronic inflammatory skin condition with a multifactorial pathogenesis involving follicular hyperkeratinization, sebaceous gland dysregulation, microbial dysbiosis-particularly involving Cutibacterium acnes and Staphylococcus epidermidis-and complex immune-mediated mechanisms, on which T helper cell 1 (T_h1) and T_h17 pathways are central players. This evolving understanding has led to the exploration of biologic therapies targeting cytokines such as tumor necrosis factor-alpha (TNFα), interleukin (IL)-1, IL-17, and IL-23. However, clinical trials to date have not demonstrated efficacy of biologics in moderate to severe acne. In contrast, some case reports and studies suggest clinical improvement with TNFα and IL-17A inhibitors in severe, treatment-resistant acne, although these presentations often overlap with hidradenitis suppurativa (HS), raising questions about diagnosis and underlying disease mechanisms. Furthermore, in various monogenic autoinflammatory syndromes where "acne-like" lesions are part of the clinical spectrum, biologic therapies have shown effectiveness. These observations suggest that in such contexts, the lesions may reflect HS or HS-like pathology rather than true acne, potentially explaining the therapeutic benefit of biologicals in this context. This review synthesizes current insights into the immunopathogenesis of acne and critically evaluates the rationale, evidence, and limitations of biologic therapy in its treatment. While biologics hold promise in defined inflammatory dermatoses, their role in the management of acne vulgaris remains unproven and may be limited to specific phenotypes that overlap with autoinflammatory or HS-related conditions.

Fig. 1

Pathophysiology of acne. This schematic illustrates the key cellular and molecular events contributing to acne pathogenesis, centered around the PSU. Cutibacterium acnes (C. acnes) and Staphylococcus epidermidis (S. epidermidis) represent major microbial components of the skin microbiota. While C. acnes promotes inflammation through virulence factors (e.g., lipases, hyaluronidase, CAMP factor) and biofilm formation, S. epidermidis can antagonize C. acnes and suppress inflammation via TLR3 signaling inhibition. Dysbiosis between these species contributes to pathological immune responses. Keratinocytes undergo hyperproliferation, abnormal differentiation, and TLR-mediated immune activation, contributing to follicular plugging. Sebocytes, under the influence of androgens and IGF-1, produce excessive and compositionally altered sebum enriched in inflammatory lipids and FFAs, which further activate immune pathways. The interaction of C. acnes with keratinocytes and sebocytes leads to the production of pro-inflammatory cytokines (e.g., TNFα, IL-1β, IL-6, IL-8, IL-36, hBD2), driving T_h1/T_h17 adaptive immune responses and resulting in chronic inflammation. These responses contribute to epithelial barrier dysfunction, granuloma formation, and tissue damage, ultimately promoting acne lesion formation and persistence. This figure emphasizes the interplay between microbial factors, lipid metabolism, epithelial responses, and immune activation, and highlights potential targets for biologic interventions aimed at modulating microbial composition, cytokine activity, and sebocyte function. CAMP Christie–Atkins–Munch–Petersen, FFA free fatty acid, hBD human beta defensin, IGF insulin-like growth factor, IL interleukin, PSU pilosebaceous unit, ROS reactive oxygen species, TNFα tumor necrosis factor-alpha, T_h T helper cell, TLR Toll-like receptor