P. acnes

The pilosebaceous follicles are the target sites for acne. The pathophysiology of acne centers on interplay of follicular hyperkeratinization, increased sebum production, action of Propi-onibacterium acnes (P. acnes) within the follicle, and production of inflammation (Table 11.1). 

The earliest morphological change in the sebaceous follicle is an abnormal follicular epithelial differentiation, which results in ductal hypercornification. Cornified cells in the upper section of the follicular canal become abnormally adherent. Comedones represent the retention of hyperproliferating ductal keratinoc-ytes in the duct. Several factors have been implicated in the induction of hyperproliferation sebaceous lipid composition, androgens, local cytokine production (IL-i, EGF) and bacteria (P. acnes). 

P. acnes is an anaerobic diphteroid that populates the androgen-stimulated sebaceous follicles and is a normal constituent of the cutaneous microflora even if acne is not infectious, the commensal P. acnes acts in acne pathogenesis. Three pieces of evidence support the role of P. acnes in acne 1) higher counts of P. acnes in individuals with acne than in those without acne 2) correlation between the reduction of P. acnes counts and the clinical improvement of the disease and 3) correlation between development of acne and presence of antibiotic-resistant P. acnes organisms. P. acnes products mediate the formation of comedones and contribute to their rupture, leading to extrusion of... 

Susceptibility to acne is also due to genetic factors. It does not follow Mendelian rules however, if both parents had severe acne when adolescents, their children are likely to present with clinical acne in puberty. Genetic factors play an important role in determining the size and the activity of sebaceous glands, while exogenous factors such as colonization of P acnes modulate the clinical expression of acne. Racial differences also exist. Caucasians are more prone to severe acne than black people. 

Benzoyl peroxide exercises a potent antimicrobial activity through the release of free oxygen radicals. It suppresses P. acnes in sebaceous follicles much faster than antibiotics, leading to a rapid reduction of the inflammatory lesions number. P. acnes does not develop resistance to benzoyl peroxide, which maintains its efficacy after years of use. Benzoyl peroxide seems to have a mild comedolytic effect while it is not... 

Azelaic acid is effective on P. acnes suppression, even if less than benzoyl peroxide. The anti-inflammatory effect of azelaic acid seems to be related to a decreased production of reactive oxygen species by neutrophils. Azelaic acid may also regulate the ductal cell keratinization, reducing the number of comedones, ft is not sebosuppressive. 

Systemic antibiotics are indicated for moderate-severe inflammatory acne not responding to topical treatments. Systemic antibiotics act on 1) suppression of P. acnes growth 2) inhibition of bacterial lipases 3) reduction of free fatty acids and 4) reduction of inflammation. Oxytetracycline and its derivatives are the most commonly used oral antibiotics. Second-generation tetracyclines such as minocycline, doxy-cycline and lymecycline present longer half-lives, enhanced bacterial activity and lower... 

Propionibacterium acnes (P. acnes), an anaerobic organism, is also found in the normal flora of the skin. This bacteria proliferates in the mixture of sebum and keratinocytes and can result in an inflammatory response producing a closed comedo or whitehead. More severe acne lesions such as pustules, papules, and nodules can also form with inflammatory acne and result in significant scarring if treated inadequately (Fig. 62-2). 

Benzoyl peroxide is easy to use and recommended as first-line therapy in the treatment of mild to moderate noninflammatory acne. Benzoyl peroxide has a comedolytic effect that increases the rate of epithelial cell turnover and helps to unclog blocked pores. It also has antibacterial activity against P. acnes, which appears to be the main reason for the effectiveness of this product.13... 

Topical antibacterials directly suppress P. acnes and are also first-line agents used in the treatment of mild to moderate inflammatory acne.3,16... 

Moderate to severe acne can be effectively treated with oral antibiotics, especially when treatment with topical therapy has failed. Because of their ability to decrease P. acnes colonization, oral antibiotics can prevent acne lesions from developing.8 Improvement of symptoms is generally evident at 6 to 10 weeks, with maximum benefits occurring after 6 months of therapy.23... 

Benzoyl peroxide may be used to treat superficial inflammatory acne. It is a nonantibiotic antibacterial that is bacteriostatic against P. acnes. It is decomposed on the skin by cysteine, liberating free oxygen radicals that oxidize... 

Concomitant use of an antibacterial agent with tretinoin can decrease keratinization, inhibit P. acnes, and decrease inflammation. A regimen of benzoyl peroxide each morning and tretinoin at bedtime may enhance efficacy and be less irritating than either agent used alone. 

Development of P. acnes resistance to erythromycin may be reduced by combination therapy with benzoyl peroxide. 

Clindamycin inhibits P. acnes and provides comedolytic and antiinflammatory activity. 

Isotretinoin (Accutane) decreases sebum production, changes sebum composition, inhibits P. acnes growth within follicles, inhibits inflammation, and alters patterns of keratinization within follicles. 

Tetracyclines inhibit P. acnes, reduce the amount of keratin in sebaceous follicles, and have antiinflammatory properties (inhibiting chemotaxis, phagocytosis, complement activation, and cell-mediated immunity). Drawbacks to tetracyclines include hepatotoxicity and predisposition to infections (e.g., vaginal candidiasis). Other adverse effects include GI disturbances, photosensitivity, tooth discoloration in children, and inhibition of skeletal growth in the developing fetus. Tetracyclines must not be combined with systemic retinoids because of an increased risk of intracranial hypertension. / Tetracycline is the least expensive agent in this class and is often... 

Weldon et al.5 used Raman in the surface-enhanced mode (SERS) to monitor bacterial (P. acnes) hydrolysis of triglycerides in lipid mixtures that model sebaceous gland secretions. While technically not a process monitor, it paves the way for methods to monitor specific moieties in very complicated matrices. 

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