Recommendations for treatment are based on international guidelines [ICSI, 2006; Strauss et al, 2007] and narrative reviews [Webster, 2002; James, 2005; Ravenscroft, 2005; Zaenglein and Thiboutot, 2006; Acne Working Group, 2008], and reflect published data from randomized controlled trials (RCTs) where available, and otherwise, expert opinion.

Referral

• Referral of all people with severe acne vulgaris is consistent with Referral advice: A guide to appropriate referral from general to specialist services, published by the National Institute for Health and Clinical Excellence (NICE) [NICE, 2001]. This is recommended in order to alleviate pain and psychological distress, and to prevent or limit scarring.

Oral antibiotics

• Oral antibiotics are universally recommended by experts for the treatment of severe acne, or extensive acne that would be difficult to treat with a topical drug [Dreno et al, 2004; ICSI, 2006; Strauss et al, 2007].
• Oral tetracyclines are recommended first-line. There is good evidence from placebo-controlled trials that tetracycline is effective at reducing lesion counts and severity. Although there is a lack of placebo-controlled trials to verify the efficacy of the other standard tetracyclines, there is evidence from comparative trials that there is likely to be a class effect.
• Oral erythromycin should be reserved for use when tetracyclines are contraindicated.
• There is a lack of evidence from placebo-controlled trials to verify the efficacy of erythromycin, although evidence from comparative trials indicate it is probably as effective as tetracyclines.
• However, there is evidence from observational and controlled studies that there are particular problems with the development of bacterial resistance to erythromycin.
• Minocycline is increasingly not recommended for the treatment of acne vulgaris as other tetracyclines are regarded as being as effective, and less expensive with a better safety profile [DTB, 2006; DTB, 2009].

Combining oral and topical drugs

• There is little evidence from RCTs to confirm the effectiveness of combining oral and topical treatment, but expert consensus supports this practice [Dreno et al, 2004].
• Combining an oral antibiotic with a topical retinoid targets both inflammatory and non-inflammatory lesions, and inhibits the formation of microcomedones (the precursors of acne).
• For long-term use (such as over 3 months), addition of benzoyl peroxide should be considered, to prevent the development of bacterial resistance [Ozolins et al, 2005].
• Oral and topical antibiotics should never be combined (as this increases the risk of antibiotic resistance without giving additional benefit) [Dreno et al, 2004].

Combined oral contraceptives (COCs)

• COCs are recommended as a first-line adjunctive treatment for women who have acne [ICSI, 2006; Strauss et al, 2007]. There is good evidence from placebo-controlled trials that COCs are effective in reducing lesion count, acne severity, and the woman's perception of the condition [Arowojolu et al, 2007].
• Co-cyprindiol is licensed for 'severe acne, refractory to prolonged oral antibiotic therapy; or moderately severe hirsutism' [ABPI Medicines Compendium, 2008a]. However, some experts suggest it may be appropriate to use it in suitable women before antibiotics are tried, and this is commonly done in practice.

These are pragmatic recommendations that are in line with expert opinion from international [ICSI, 2006] and national [Acne Working Group, 2008] guidelines.

Referral criteria for acne vulgaris are based on Referral advice: A guide to appropriate referral from general to specialist services, published by the National Institute for Health and Clinical Excellence (NICE). For people requiring referral 'immediately' or 'soon', NICE specify that 'Health authorities, trusts, and primary care organizations should work to local definitions of maximum waiting times in each of these categories. The multidisciplinary advisory groups considered a maximum waiting time of 2 weeks to be appropriate for the urgent category' [NICE, 2001].

Treatment options that are available in secondary care include:

Oral isotretinoin

• Oral isotretinoin is an effective option in secondary care [MHRA, 2008]. It must not be initiated in primary care, except under the care of a dermatology specialist. The manufacturer's Summary of Product Characteristics states that isotretinoin 'should only be prescribed by, or under the supervision of, physicians who have expertise in the use of systemic retinoids for the treatment of severe acne, and a full understanding of the risks of isotretinoin therapy and of the monitoring requirements' [ABPI Medicines Compendium, 2008b].
• Oral isotretinoin is an extremely effective treatment for acne. It is used for severe acne conditions such as nodulocystic acne, acne conglobata, scarring, or persistent acne that does not respond adequately to standard treatment or is causing significant psychological problems [Wolf, 2002].
• It is associated with potentially serious adverse effects, including teratogenicity. However, research has shown that concerns about links between isotretinoin and depression or suicide are not established [Chia et al, 2005; Magin et al, 2005b].

Laser treatment

• Laser treatment is sometimes used in the treatment of acne in secondary care. Lasers primarily work by targeting Propionibacterium acnes in the sebaceous glands. However, at present the evidence for laser therapy is limited and more trials are needed to evaluate its effectiveness [Jordan et al, 2000; Bhardwaj et al, 2005; Hamilton et al, 2009].
• Laser treatment may also be indicated for post-acne scarring.
• Lasers are expensive and their availability is limited.

Surgical treatment

• Various surgical and medical techniques may be used for the treatment of very severe acne in secondary care [Brown and Shalita, 1998].
• Purulent nodules can be incised and drained of pus.
• Comedones can be cauterized. Alternatively, comedone extraction is a technique in which entire comedones are removed. Usually this is done following several weeks of topical treatment.
• Large, tender nodules can be treated with an intralesional injection of a corticosteroid such as triamcinolone. This rapidly reduces inflammation and reduces lesion size.
• Surgical treatment of scarring is more problematic. If there is extensive superficial scarring, dermabrasion may be performed by a plastic surgeon to improve the appearance of the skin [Sharpe, 1995], although this procedure is now less common.

Providing reassurance

• The prognosis of acne is good for most people, with less than 12% of women and 3% men being affected after 25 years of age. However, the condition should not be trivialized, as it may last for several years and have a negative psychological impact in some people. A balanced understanding of the disease course and its impact on everyday life is required [Acne Working Group, 2008].

Myths about acne

• Experts believe that dispelling 'myths' is an integral component of the management of acne [ICSI, 2006].
• Evidence on the myths about acne is based mainly on poor-quality data from uncontrolled trials and observational studies, and expert opinion.
• There is insufficient evidence from observational studies or controlled trials to indicate that changes in diet, use of hygiene measures, or exposure to sunlight is beneficial in the management of acne.
• There is a consensus of expert opinion that stress does not cause acne, although it is widely believed it can exacerbate the psychological reaction to acne [ICSI, 2006].

Advice on hygiene measures

• Recommendations on hygiene measures are based on consensus of experts [Webster, 2002; ICSI, 2006].

Over-the-counter (OTC) treatments

• Most OTC products are not recommended because there is a lack of evidence from clinical trials to support their efficacy [Sharpe, 1995; Brown and Shalita, 1998; Ravenscroft, 2005; Strauss et al, 2007].
• Salicylic acid is a common ingredient in OTC acne treatments. It is a keratolytic drug that has some anti-comedone activity, but there is a lack of evidence from controlled trials to confirm this, and it is considered less effective than the topical retinoids.
• Abrasives (such as aluminium oxide) and sulphur (available combined with resorcinol, as Eskamel^®) have been used historically, but lack evidence from controlled trials. Some products containing aluminium oxide are abrasive and can irritate inflamed skin.
• Nicotinamide (available as Nicam^®) has been reported as being as effective as topical clindamycin in open-label cohort studies [Dos et al, 2003; Sardesai and Kambli, 2003], but CKS identified no randomized controlled trials to confirm this.
• However, there is substantial placebo-controlled trial evidence to support the use of benzoyl peroxide in the treatment of acne.

Complementary and alternative medicine (CAM)

• There is little evidence to support the use of CAM in the treatment of acne.
• A review of CAM treatments for acne found an overall lack of good quality evidence of beneficial effect; studies were limited in number and most were methodologically poor or underpowered [Magin et al, 2006].
• One systematic review (search date: October 2002) found two trials that investigated the efficacy of herbal remedies in acne [Martin and Ernst, 2003]. Both studies were small and of poor methodological quality.
• One trial compared tea tree oil with benzoyl peroxide. There was no placebo group and the study lacked the statistical power to show equivalence or superiority of the regimens.
• In the other trial, the herb Ocimum gratissimum (dissolved in alcohol and added to oil) was compared with benzoyl peroxide and placebo. However, as various concentrations were investigated, the groups were too small to allow any firm conclusions.