Anti-Inflammatory Dose Doxycycline Plus Adapalene 0.3% and Benzoyl Peroxide 2.5% Gel for Severe Acne

The pathogenesis of acne is complex, comprised of an interplay between androgens, hyperproliferation of keratinocytes, excess sebum production, and P. acnes. It is now understood that acne is primarily an inflammatory disease.¹ P. acnes is shown to activate innate immunity via the expression of protease activated receptors (PARs), tumor necrosis factor (TNF) α, and toll-like receptors (TLRs), and the production of interferon (INF) γ, interleukins (IL-8, IL12, IL-1), TNF, and matrix metalloproteinases (MMPs).²

Acne treatment guidelines emphasize the inflammatory nature of the disease, recommending multimodal approaches that target inflammation, address hyperkeratinization, and provide antibacterial effects while incorporating strategies to reduce the risk for bacterial resistance. Guidelines endorse use of topical retinoids and topical benzoyl peroxide for the majority of acne patients, especially those receiving oral antibiotics.³Despite therapeutic advancements, options for management of severe acne are somewhat limited; many patients are not candidates for or refuse treatment with isotretinoin. Systemic antibiotics may be indicated; Guidelines emphasize antibiotic stewardship in light of increasing concerns about antibiotic resistance and call for the judicious use of conventional systemic antibiotics.³

Oracea (doxycycline 40mg: 30mg immediate release and 10mg delayed release beads; Galderma) is an anti-inflammatory agent approved for the treatment of the inflammatory lesions of rosacea.⁴ In studies of moderate to severe inflammatory acne, doxycycline 40mg had comparable efficacy and superior safety compared to doxycycline 100mg.⁵ The 40mg dose is below the minimum inhibitory concentration for doxycycline and therefore confers no antibacterial effect. The therapeutic effect is anti-inflammatory only. There is no risk for development of bacterial resistance associated with the use of doxycycline 40mg.