Treating Acne Vulgaris: Systemic, Local and Combination Therapy

Laura J Savage; Alison M Layton

Expert Rev Clin Pharmacol. 2010;13(4):563-580.

Benzoyl Peroxide

Benzoyl peroxide is a powerful antimicrobial agent destroying both surface and ductal bacterial organisms and yeasts.^[25] Its lipophilic properties permit penetration of the pilosebaceous duct and its efficacy is largely against superficial inflammatory lesions. Once applied to the skin, BPO decomposes to release free oxygen radicals, which have potent bactericidal activity in the sebaceous follicles and anti-inflammatory action.^[25,26] It also has effects on noninflammatory lesions by reducing follicular hyperkeratosis to some degree.^[27] BPO, as with topical retinoids, have no effect on sebum production.^[28]

Benzoyl peroxide formulations offer a useful approach in acne patients owing to their highly effective bactericidal effect. They are not associated with antimicrobial resistance and are active against fully sensitive and resistant strains of P. acnes.^[15] It is therefore unsurprising that combination preparations of BPO with topical antibiotics have superior activity to monotherapy with a topical antibacterial agent alone against inflammatory and noninflammatory lesions.^[29–31] BPO has also been demonstrated to be as effective as first-line oral antibiotic therapy in mild-to-moderate acne. Ozolins et al. demonstrated similar efficacy with 5% BPO when compared with oral tetracycline and minocycline, making BPO a desirable choice in this group in terms of clinical– and cost–effectiveness and in the prevention of the development of resistant strains of P. acnes.^[32]

Benzoyl peroxide is currently available in a number of different formulations and concentrations (2.5, 4, 5 and 10%), either alone or in combination with various agents including hydroxychloroquine, imidazole, glycolic acid, zinc lactate and topical antimicrobials. Several lower-concentration preparations are commercially available over the counter. Four randomized control trials (RCTs)have examined different concentrations of BPO^[33–36] and no evidence currently supports a dose–response effect. Nevertheless, adverse effects such as irritant dermatitis may prevent the use of high-potency preparations in some patients. This effect can be eased by reducing the frequency of application, and this often subsides as treatment continues. Patients should also be forewarned that BPO can bleach hair and clothing.

A novel combination formulation of 2.5% BPO and 0.1% adapalene has recently been launched in Europe and the USA (Epiduo® [Galderma, Hertfordshire, UK]). A four-arm RCT demonstrated that the combination product was superior (27.5% clear) against monotherapy with 0.1% adapalene alone (15.5% clear) or 2.5% BPO (15.4% clear), which were again superior over the vehicle alone (9.9% clear).^[37] This suggests that 2.5% BPO has similar efficacy to 0.1% adapalene in inflammatory acne, with both agents having a similar side effect profile.

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Table 1. Therapies for acne: impact on etiological factors.
Therapies	Sebum production	Hyper-keratinization	Inflammation	Reduction in Propionibacterium acnes
*Topical therapies*
Retinoids	-	++	+	-
Benzyl peroxide	-	+	++	+++
Antibiotics	-	+	++	+++
Azelaic acid	-	+	+	+/-
Nicotinamide	-	+	+	+/-
*Systemic therapies*
Antibiotics	-	+	+++	+++
Hormonal therapy	++	++	Indirect	Indirect
Retinoids	+++	++	++	++

Adapted from ^[90].

Table 2. Systemic antibiotics used in the treatment of acne vulgaris.
Drug	Dosage (mg)	Prescribing considerations	Propionibacterium acnes resistance	Adverse effects
Oxytetracycline	500 b.i.d.	Inexpensive Take 30 min before food and not with milk	Moderate	Onycholysis Photosensitivity Benign intracranial hypertension
Erythromycin	500 b.i.d.	Inexpensive Take on an empty stomach	High	Gastrointestinal upset (nausea and diarrhea)
Minocycline	100–200 q.d.	Expensive	Moderate and increasing	Headaches^† Pigmentary change Autoimmune hepatitis LE-like syndrome
Doxycycline	100–200 q.d.	Moderate cost	Moderate	Photosensitivity^†
Lymecycline	300–600 q.d.	Moderate cost	Moderate	As minocycline (less frequent)
Trimethoprim	200–300 b.i.d.	Inexpensive	Low/moderate	Hepatic toxicity Renal toxicity Agranulocytosis

^†Dose-dependent effects.
b.i.d.: Twice daily; LE: Lupus erythematosus; q.d.: Once daily.
Adapted from ^[90].

Box 1. Recommendations from the Global Alliance to Improve Outcomes in Acne.
Avoidance of oral or topical antibiotics as monotherapy – combination regimens from the onset of therapy should expedite response and reduce the duration of antibiotic courses, therefore: Combine an antimicrobial with a topical retinoid or a BPO-containing product Limit the use of antibiotics to short periods and discontinue use when no further or significant improvement occurs; Avoid combined oral and topical antibiotics – if required, stay within the same class Do not use antimicrobials as maintenance therapy – opt for a topical retinoid, with BPO added for antimicrobial effect if needed Avoid switching antibiotics without adequate justification – when possible, utilize the original antibiotic for relapses
BPO: Benzoyl peroxide. Adapted from ^[14].

Box 2. Recommendations from the European Directive for prescribing and monitoring isotretinoin.
Indications Severe acne (nodular or conglobata) not responding to appropriate combined antibiotics/topical therapy Not recommended for use in children under 12 years of age
Dosage recommendations Treatment to start at 0.5 mg/kg/day
Monitoring Liver function tests and lipids should be checked prior to 1 month after starting and at 3-monthly intervals throughout the course of therapy
Treatment of scarring Physical and chemical peels, wax depilation and laser therapy should be avoided during and 1 month post-treatment
Adapted from ^[143].

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