Inflammatory Acne Treatment: Review of Current and New Topical Therapeutic Options
January 2016 | Volume 15 | Issue 1 | Supplement | s11 | Copyright © 2016
Joshua A. Zeichner MD
Department of Dermatology, Mount Sinai Hospital, New York, NY
Acne vulgaris (AV) is an inflammatory skin disease characterized by the presence of comedones, papules, pustules, and nodules. Consensus guidelines recommend the use of combination therapy using different drugs with complementary mechanisms of action to best address as many acne pathogenic factors as possible at the same time. Topical acne medications exist as individual agents that may be combined in physician-recommended regimens or as pre-formulated fixed-dose combination products. In addition, there are several new and promising topical therapies currently being developed that work by different mechanisms of action from traditionally used acne therapies. The following review will cover commonly used drugs, newcomers to the market, and what the future holds for the topical treatment of AV.
J Drugs Dermatol. 2016;15(1 Suppl 1):s11-s16.
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Acne vulgaris (AV) is the single most common reason that patients visit dermatologists.1 An estimated 40 to 50 million Americans suffer from it, including 95% of teenage boys and 85% of teenage girls.2,3,4 Acne imparts a significant psychosocial burden, and the effect has been likened to that of systemic diseases such as diabetes, asthma, and epilepsy.5 Body image issues, anxiety, depression, poor self-esteem, and social disturbances affect up to half of adolescents with acne.6,7 For all of these reasons, effective treatments are a necessity.
Acne is an inflammatory disease. Follicular hyperkeratinization,8 sebum production,9 Propionibacterium acnes bacteria colonization,10 and resulting inflammation11,12 all contribute to its pathogenesis. Hyperkeratinization leads to narrowing of the follicular ostium, which in turn allows for sebum accumulation beneath.13,14 It is also thought that P. acnes forms a biofilm in the sebaceous gland further obstructing the follicle.15 P. acnes is a commensal skin organism rather than an infection, and its lipases break down sebum triglycerides into pro-inflammatory free fatty acids16 and activates an innate immune response through toll-like receptor 2 (TLR-2) binding with subsequent production of the pro-inflammatory cytokines TNF-α and IL-1α.17 Collectively this inflammation promotes comedogenesis.18
Traditionally, acne has been categorized as having either “inflammatory” or “non-inflammatory” lesions. Inflammatory lesions include acne papules, pustules, cysts, and nodules. Non-inflammatory lesions, on the other hand, refer to open and closed comedones. The term “non-inflammatory” is still used by convention, but it is in reality a misnomer. Recent data suggest that subclinical perifollicular inflammation actually precedes formation of the microcomedone. This means that comedones are in fact inflammatory lesions. In one 2003 study, investigators took biopsies from clinically normal appearing skin in acne patients. They discovered that while no clinical lesions were observed, sub-clinical elevation of CD4+ T cells, macrophages, vascular adhesion molecules, and pro-inflammatory cytokines were present.19 Moreover, inflammatory lesions may arise from clinically normal appearing skin. Using photographic star tracking software, investigators in another study followed acne lesions on the face during a 30-day period. Inflammatory lesions developed from comedones in 54% of patients, but from normal-appearing skin in 28% of patients.20 Regardless of nomenclature, comendones are in fact inflammatory lesions.
Consensus guidelines recommend combination therapy for the treatment of all but the mildest comedonal acne.21 Enhanced therapeutic benefits can be achieved by combining agents with different but complementary mechanisms of action. The following review will discuss topical medications, alone and in combination, for the treatment of AV, both traditional inflammatory lesions and inflammatory comedonal lesions.
Topical Treatment Options
An algorithmic approach may be used to select the proper acne therapy based on lesion type, severity, and extent of body surface area affected. Topical therapies may be used as a first-line approach for mild to moderate acne or in combination with orals for more severe disease. Prescription topical options include benzoyl peroxide (BPO), topical antibiotics, topical retinoids, and topical dapsone. These are frequently prescribed in various combinations to suit the specific needs of the patient. In general, simpler regimens improve outcomes, as patients