The utility of benzoyl peroxide in hydrophase base in the treatment of acne vulgaris

Journal of Drugs in Dermatology, April, 2006 by Jeffrey M. Weinberg

Abstract

Available for more than 5 decades, benzoyl peroxide has been a "workhorse" of acne therapy. The benefits of this agent include reduction in Propionibacterium acnes (P. acnes) with decrease in inflammatory lesions, efficacy as both "leave on" and cleanser formulations and reduced emergence of antibiotic-resistant P. acnes strains. As the effect of benzoyl peroxide on P. acnes is a direct toxic effect rather than as a "true" antibiotic, resistance to benzoyl peroxide does not occur and has never been reported.

Benzoyl peroxide in hydrophase base (Brevoxyl[R] Creamy Washes and Gels) has shown significant efficacy in the treatment of acne, with lower irritancy than other benzoyl peroxide preparations. It is felt that the low irritancy of this product is related to a unique delivery vehicle containing dimethyl isosorbide, which dissolves benzoyl peroxide crystals on the skin. Clinical studies demonstrating the efficacy and safety of benzoyl peroxide in hydrophase base will be reviewed.

Introduction

Acne vulgaris is the most common skin disease among children and adolescents, with estimates indicating that 80% to 95% of adolescents will have acne. (1-3) Acne characteristically involves the face, back, upper chest, and shoulders. Based on data from the National Ambulatory Medical Care Survey 2000, acne vulgaris represented 15.2% of dermatology visits in the US, accounting for 5,256,000 office-based visits among non-federal dermatologists. (4)

The majority of patients are early adolescents and teenagers; however, persistence into later adulthood is not uncommon. Post-teenage acne, especially in females, also occurs in a subset of patients. Goulden et al (5) reviewed the clinical features of post-adolescent acne in 200 patients over the age of 25 years, referred for treatment of acne. Most patients had persistent acne, but true late-onset acne (onset after the age of 25 years) was seen in 28 (18.4%) women and 4 (8.3%) men. Thirty-seven percent of women had features of hyperandrogenicity. One hundred and sixty-four patients (82%) had failed to respond to multiple courses of antibiotics, and 64 (32%) had relapsed after treatment with one or more courses of isotretinoin. External factors, such as cosmetics, drugs, and occupation, were not found to be significant etiological factors. A family history revealed that 100 (50%) patients had a first-degree relative with post-adolescent acne. (5)

Pathogenesis of Acne

The origin of acne vulgaris is complex and incompletely understood. At least 4 pathophysiologic events take place within acne-involved hair follicles: (1) androgen-mediated stimulation of sebaceous gland activity, (2) abnormal keratinization leading to follicular plugging (comedo formation), (3) proliferation of the bacterium Propionibacterium acnes (P. acnes) within the follicle, and (4) inflammation.

Acne vulgaris is the result of the obstruction of specialized follicles (sebaceous follicles), (6,7) which are located primarily on the face and trunk, by excessive amounts of sebum produced by sebaceous glands in the follicles combined with excessive numbers of desquamated epithelial cells from the walls of the follicles. (8-11) The obstruction causes the formation of a microcomedo. This micrcomedo then may evolve into either a comedo or an inflammatory lesion. A resident anaerobic organism, P. acnes, proliferates in the environment created by the mixture of excessive sebum and follicular cells (12,13) and produces chemotactic factors and proinflammatory mediators that may lead to inflammation. (14-20)

Therapies for acne exist that effectively counteract the excess production of sebum, the abnormal desquamation of epithelial cells in sebaceous follicles, and the proliferation of P. acnes. The choice of therapy for an individual patient depends on the extent, severity, and duration of the disease; the type of lesions; and the psychological effects of the disease. (20)

Topical Antimicrobials in Acne

Topical antibacterial agents are an essential part of the armamentarium for treating acne vulgaris. They are indicated for mild-to-moderate acne, and are a useful alternative for patients who cannot take systemic antibacterials. (21) Topical antibacterials such as clindamycin and erythromycin are bacteriostatic for P. acnes, and have also been demonstrated to have anti-inflammatory activities through inhibition of lipase production by P. acnes, as well as inhibition of leukocyte chemotaxis. Benzoyl peroxide is a non-antibiotic antibacterial agent that is bactericidal against P. acnes.

Despite years of widespread use of systemic tetracyclines and erythromycin, change in P. acnes sensitivity to antibiotics was not seen until the early 1980s. (22) The first clinically relevant changes in P. acnes antibiotic sensitivity were found in the US shortly after the introduction of topical formulations of erythromycin and clindamycin. By the late 1980s, P. acnes strains with very high MIC levels for erythromycin and elevated MICs for tetracycline were increasingly found in the UK and the US. Mutations in the genes encoding the 23S and 16S subunits of ribosomal RNA were first identified in the UK and also seen in a recent survey from clinics in Europe, Japan, Australia, and the US. In addition, strains were found in which these known mutations could not be identified, indicating that as yet unidentified resistance mechanisms have evolved. (22)