Failure of initial therapy
Patient concordance with prescribed therapy is a significant determinant of success. Apparent failure of a treatment modality often reflects poor concordance with prescribed therapy, with either incorrect application of topical treatments, insufficient duration of use or premature termination owing to side-effects. Other apparent reasons for treatment failure include P. acnes antibiotic resistance and incorrect diagnoses (e.g. rosacea or acne variants). Treatment plans must be agreed with the patient, anticipated side-effects and the need for a number of months of treatment explained. As disease activity may fluctuate, a few courses of treatment may be required.
The optimal strategy for the treatment of acne vulgaris should include an induction phase followed by a maintenance phase, often supported by adjunctive treatments and/or cosmeceuticals. More often than not, maintenance therapy is not initiated and in the author’s opinion this is vital to long-term success to reduce the risk of recurrence. The use of adjuvant skincare is integral to the management of acne. Treatment should incorporate an appropriate daily skincare regimen to cleanse, soothe and moisturise the skin7,8.
Poor prognostic factors for acne include family history, persistent or late-onset disease, hyperseborrhoea, androgenic triggers, truncal acne, and relapse following isotretinoin.
Topical therapies
Topical therapies are the mainstay of treatment of mild-to-moderate acne. Patients should be advised of how to use their therapy, gradually building up from low to higher concentrations using increasing durations of application, from a few hours initially to overnight, to up to twice daily in some cases.
Topical benzoyl peroxide has both keratolytic and antimicrobial properties through its bactericidal effects and by inhibiting the release of reactive oxygen species (ROS). It can therefore be applied to inflammatory and non-inflammatory lesions. Unlike antibiotics, use of concurrent benzoyl peroxide reduces the risk of development of antibiotic-resistant strains of P. acnes, making it a useful adjunct to other agents. Tolerance is limited by local irritation, which causes a dose-dependent dermatitis and bleaching of both skin and clothes. Lower dose formulations and the choice of vehicle can lead to better tolerability9.
For predominantly non-inflammatory (comedonal) acne, topical retinoids (adapalene, isotretinoin, tretinoin) are of particular use1,9. Retinoids are vitamin A agonists, the mechanisms of action of which include: keratolytic, anti-inflammatory activity, anti-proliferative effect, inhibition of the release of ROS, down-regulation of the innate immune response, and inhibition of the dermal matrix degradation. These actions make retinoids valuable in the treatment of any form of acne vulgaris. Side-effects include dryness of the skin and local irritation. Clinical trials on the microcomedo, the natural precursor of comedones, have shown that retinoids significantly reduce microcomedo counts. Topical (and systemic) retinoids are contraindicated in pregnancy owing to their teratogenicity (see below).
Predominantly inflammatory acne warrants the use of topical antibiotics (such as clindamycin, erythromycin) to reduce P. acnes colonisation of the pilosebaceous unit and the ensuing inflammation. Effectiveness of such agents is improved and the chance of bacterial resistance is decreased by concurrent use of benzoyl peroxide or retinoids. Where retinoids cannot be tolerated, salicylic acid and azelaic acid can provide additional keratolytic action.
Newer fixed-dose combination therapies, combining two of the above classes of agent, allow more rapid resolution and greater efficacy than a single agent by aiming to treat the maximum number of underlying aetiological factors. It also leads to greater patient adherence to therapy. A topical retinoid in combination with an antimicrobial agent (either benzoyl peroxide or topical antibiotic) are usually used as the first-line therapy for most patients with acne.
Dapsone is a sulfone antibiotic with both anti‑inflammatory and anti-bacterial effects, and a topical formulation has recently been introduced (not available in the UK) that has shown good efficacy in clinical trials.
Combined oral contraceptive
The role of androgens in acne vulgaris has been well‑established. Androgen receptors on keratinocytes and sebocytes mediate hyperkeratinisation and play a role in sebaceous gland development. Dihydrotestosterone (DHT) and dehdroepiandrosterone sulphate (DHEAS) are the most commonly implicated androgens in acne. The use of combined oral contraceptives in acne has been shown to be effective in multiple systemic reviews and currently form part of acne management of the adult-type female acne10.
In females, a useful initial adjunct, where there are no contraindications, is the introduction of a combined (oestrogen-containing) oral contraceptive pill. By increasing the levels of sex hormone-binding globulin, such agents reduce both total androgen and free testosterone plasma concentrations, and can be useful in the presence or absence of hyperandrogenic states, such as polycystic ovarian syndrome (PCOS). The contraceptive pill may be combined with anti-androgen drugs, such as spironolactone or flutamide for greater efficacy. The effects are also the result of blocking of the androgen receptors on the sebaceous glands. It should be noted that progesterone-only contraceptive agents can exacerbate acne, owing to non-selective agonism of both progesterone and androgen receptors. Comprehensive endocrinological assessment is not necessary for the majority of female patients with acne. However, this may be indicated where there are clinical features of hyperandrogenism, such as recalcitrant acne, infrequent menses, hirsutism, infertility, acanthosis nigricans, or truncal obesity. Indications for hormonal therapy in females with acne include proven ovarian or adrenal hyperandrogenism, recalcitrant acne, acne not responding to or relapsing following isotretinoin therapy, PCOS, the presence of alopecia, and marked hyperseborrhoea10,11.
