Acne Vulgaris Management and Pathophysiology

Acne vulgaris arises from the interplay of excess sebum production, abnormal follicular keratinisation, microbial colonisation and a dysregulated immune response within the pilosebaceous unit. Hyperactivity of sebaceous glands under hormonal influence increases lipid secretion, which combines with desquamated keratinocytes to form microcomedones. Cutibacterium acnes, a skin commensal, can proliferate in these lipid-rich environments and release enzymes and proinflammatory mediators that activate pattern-recognition receptors, notably Toll-like receptor 2, on keratinocytes and immune cells. This leads to local cytokine release, recruitment of Th17 and Th1 lymphocytes and neutrophils, and lesion formation ranging from non-inflammatory comedones to inflamed papules and nodules. Traditional management employs topical retinoids to normalise desquamation, topical and systemic antibiotics to reduce bacterial load, hormonal therapies to modulate sebum output and systemic retinoids for severe disease. However, concerns over antimicrobial resistance, teratogenicity and adverse effects have driven research towards precision-targeted interventions. Emerging strategies focus on modulation of C. acnes strain composition, inhibition of specific microbial enzymes, antagonism of inflammatory pathways and refinement of systemic agents to balance efficacy with safety. Novel delivery systems, peptide-based inhibitors and microbiome-informed therapies promise to complement established regimens, reduce resistance pressure and improve long-term outcomes.

Research from Nature Portfolio

Recent studies have elucidated how functional divergence of a bacterial hyaluronidase enzyme shapes skin health or acne. Two variants, HylA and HylB, derive from a common ancestral enzyme but differ in their degradation of hyaluronic acid within the follicular microenvironment. HylA generates high-molecular-weight fragments that robustly activate Toll-like receptor 2-mediated inflammation, whereas HylB yields smaller disaccharides with minimal proinflammatory effect. Structural and phylogenetic analysis revealed key active-site differences driving these activities. In murine models, inhibition or immunisation against HylA significantly attenuated lesion formation, indicating that selective targeting of virulent enzyme variants offers a precision approach to therapy without disturbing beneficial microbial functions.

Acne Vulgaris Management and Pathophysiology publication trend

The graph below shows the total number of articles in acne vulgaris management and pathophysiology across all publications each year (not limited to Nature Index journals).

Technical terms

Pilosebaceous unit: The hair follicle together with its associated sebaceous gland.

Sebum: The lipid-rich secretion of sebaceous glands that lubricates skin and hair.

Commensal: A microorganism that coexists with the host without normally causing disease.

Hyaluronidase: An enzyme that degrades hyaluronic acid, altering extracellular matrix and immune signalling.

Cytokines: Small proteins released by cells to regulate immunity, inflammation and cell communication.

Th17 cells: A subset of T helper lymphocytes characterised by production of interleukin 17, important in inflammatory responses.

References

1. Functional divergence of a bacterial enzyme promotes healthy or acneic skin. Nature Communications (2023).
2. Hyaluronic acid-FGF2-derived peptide bioconjugates for suppression of FGFR2 and AR simultaneously as an acne antagonist. Journal of Nanobiotechnology (2023).
3. Treatment Modalities for Acne. Molecules (2016).
4. Potential Role of the Microbiome in Acne: A Comprehensive Review. Journal of Clinical Medicine (2019).
5. IL-17/Th17 Pathway Is Activated in Acne Lesions. PLOS ONE (2014).