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Acne

Acne

Most adolescents and young adults show evidence of acne. It is most prevalent between 15 and 24 years, and is more common and more severe in males than in females. Onset peaks early in puberty and usually resolves in males during their early 20s. Females can develop acne for the first time after puberty and are more likely to suffer ongoing acne, which can persist into their 30s and 40s. Acne mainly affects the face, neck, chest, shoulders and upper back; areas which have the highest density of sebaceous glands.To help tailor management, acne lesions can be divided into noninflammatory (open and closed comedones), inflammatory (pustules, red papules, nodules and cysts), and resolving lesions (macules and scars) (see Box 1).

Lesions may be mild, moderate or severe.To help determine the most suitable treatment options, examine for (dominant) lesion type, acne extent and severity. Consider early specialist referral for systemic isotretinoin if acne is severe (cystic, nodular, very inflammatory), scarring, or there is a family history of severe scarring acne. Established scars will not respond to topical or oral treatment.

Types of acne lesions (Box 1)

Pathogenesis

Changes in the pilosebaceous unit combine to cause acne. Androgens control oil (sebum) production (which is necessary for acne, and correlates with severity). Sebum normally reaches the skin via the hair duct. In acne this duct is blocked by a plug of keratin due to focal hypercornification or epidermal thickening, which is partly androgen mediated.Increased numbers of Propionibacterium acnes accumulate under these oily, oxygen-poor conditions. This bacterium contributes to inflammation and scarring, by releasing tissue destructive enzymes and proinflammatory cytokines.

Specific considerations

Minimise aggravating factors: Consider stopping or changing acnegenic drugs (eg anabolic steroids, danazol, some oral contraceptives, oral corticosteroids, phenytoin, isoniazid, iodides, vitamin B₁₂ injections, bromides and lithium).Ensure all topical creams, cosmetics and sunscreens are noncomedogenic and nonacnegenic. Most ‘oil-free’ products are noncomedogenic or less likely to aggravate acne. A noncomedogenic and/or nonacnegenic label claim signifies that this has been confirmed by testing, but even these occasionally aggravate acne in some individuals.

Consider endocrine factors: Look for endocrine abnormalities (eg congenital adrenal hyperplasia) if acne occurs in children under 10 years of age. Most women with acne have entirely normal hormone profiles. Acne can, however, be one of the signs of androgenisation in women and association with hirsutism, obesity and menstrual irregularity should trigger investigation.

Assess emotional and social impact: Acne has been shown to negatively impact on a young person’s quality of life and successful disease control improves wellbeing. The degree of stress and anxiety may be much greater than with other common skin disorders, with psychological impact similar to that of a physically disabling disorder. The emotional and social impact of acne does not necessarily correlate with acne severity. If, during consultation, findings suggest possible psychological concerns or even psychiatric issues a more thorough screen and assessment should be considered. Severe emotional and social impact can lead to social withdrawal, preoccupation with their acne, distorted body image, poor self-confidence and self-esteem, depression and suicide.

Consider occupational issues: Occupational exposures (eg to industrial oils such as those used by mechanics, and halogens) can cause or contribute to acne. Hot, humid working environments can aggravate acne.

General advice for patients

Advise patients not to squeeze whiteheads and papules: Squeezing whiteheads and papules can increase depth and severity of pilosebaceous inflammation, visibly worsening acne and increasing risk of permanent scars.

Dispel myths: Clarification and correction of incorrect beliefs or myths, such as blackheads being due to dirt, can help acne patients focus on useful treatment strategies.

Dietary advice: Several older studies with many limitations did not find dietary factors (including chocolate) to be important. It remains reasonable, however, for individuals to avoid specific foods they have linked with flares.

Sun protection: Ultraviolet light, either natural or in solariums, should not be used to treat acne. Although a third of patients report improvement in summer, the benefits of ultraviolet light are at best small; conversely, ultraviolet light does cause photoageing and immunosuppression, and increases risk of skin cancer. Many acne treatments also make the skin more prone to sunburn. Sun protection should include use of noncomedogenic SPF30+ broad-spectrum sunscreens.

Treatment of acne

Introduction

When choosing therapy, consider lesion type, severity, extent, presence and risk of scarring, disease duration, emotional and social impact, and gender issues such as pregnancy and contraception. The aim of treatment is to unblock comedones and reduce sebum production, Propionibacterium acnes, associated inflammation and tissue destruction. The main therapeutic groups used to treat acne and their principal actions are summarised in Table 1.

Therapeutic groups used to treat acne and their main actions (Table 1)

Topical therapy for acne

Keratolytics

Topical keratolytic agents are used to unblock pores. Salicylic acid (eg salicylic acid 3% to 5% in ethanol 70%) is used for truncal acne due to the large area often involved. For the face a 2% salicylic acid face wash is available.

Retinoids

Retinoids are the most effective treatment for acne. They are also potentially the most irritating and can cause an initial flare, erythema, dryness, scaling, stinging and burning. Tretinoin 0.025% to 0.1%, isotretinoin 0.05% and adapalene 0.1% are all of proven benefit. In trials comparing the beneficial effects of retinoids, adapalene 0.1% is equivalent to tretinoin 0.025%, but tretinoin 0.05% is more effective. There are insufficient data for comparing topical isotretinoin with other topical retinoids.To reduce adverse effects, use a low-irritant cleanser, apply the retinoid sparingly at night, and wash off in the morning to reduce photosensitivity. The visible benefits may take 4 to 8 weeks. Topical retinoids are best avoided in pregnancy; however, if inadvertently used during pregnancy, safety data suggest there is no increase in fetal risk.

Antibiotics and antibacterials

Clindamycin 1% and erythromycin 2% have antibacterial and anti-inflammatory effects and are the least irritating topical agents commonly used for acne. Benzoyl peroxide 2.5% to 5% has similar benefits to these topical antibiotics. At strengths greater than 5%, benzoyl peroxide causes greater irritation and dryness, with no additional benefit. Benzoyl peroxide also causes photosensitivity. Irritation due to benzoyl peroxide is reduced when combined with erythromycin or clindamycin. This combination also has synergistic antibacterial benefits including reducing antibiotic resistance to Propionibacterium acnes.

Systemic therapy for acne

Antibiotics

Systemic antibiotics used in acne include doxycyline, tetracycline, minocycline, and erythromycin.Gastric upset, diarrhoea and vulvovaginal candidiasis are most common with tetracycline, and photosensitivity with doxycycline. Minocycline is no more effective than other tetracyclines, and is associated with rare, idiosyncratic, but potentially severe reactions that may be delayed months or years into therapy. Daily doses greater than 100 mg increase the risk of serious reactions and also minocycline pigmentation.Minocycline should not be a first-line choice, but is useful when other tetracylines are not tolerated or fail to improve acne.Antibiotic resistanceAntibiotic resistance, particularly to erythromycin, is seen by microbiologists as an important potential risk. However, acne is not primarily a bacterial disease with the normal risks of person-to-person spread. Antibiotics are mainly used in acne for their anti-inflammatory actions.To reduce risk of promoting the selection of resistant organisms:

 For mild to moderate facial acne, consider topical retinoids for long-term control.

 Combine antibiotic therapy with topical retinoids or benzoyl peroxide for the face and 3% salicylic acid in 70% ethanol for the trunk. In vitro resistance is reduced by concurrent benzoyl peroxide, and a 6-week course of benzoyl peroxide can restore in vitro antibiotic sensitivity.

 Do not use topical antibiotics for intermittent spot treatment, but prescribe courses of approximately 6-weeks duration for acne exacerbations or while waiting for the beneficial effects of other therapies. Topical antibiotics should be applied regularly to the entire facial regions affected by acne.

 Consider hormonal therapy instead of systemic antibiotics in female acne patients.

 Limit systemic antibiotic courses to 3 to 6 months, re-treat with the same drug if relapse occurs and consider referring patients requiring repeated courses of systemic antibiotics or with suspected antibiotic resistance for dermatological opinion. In vitro microbiological resistance of Propionibacterium acnes to minocycline is uncommon. Systemic erythromycin remains useful in pregnancy, when acne often flares, and in breastfeeding mothers.

Hormones

Hormonal therapies such as oral contraceptives are frequently prescribed for women with acne. The beneficial effects are often slow to develop, but they can be suitable for long-term suppressive therapy. A 3- to 6-month therapeutic trial is recommended.

Oral contraceptivesOral contraceptives can have a variable effect on acne. Many factors influence their overall androgenic actions and better trials are required to clinically assess their relative merits and quantify their effects in acne. Adverse effect profile and affordability also affect choice.Progestogen-only contraceptives (both oral and depot injections) usually make acne worse and should be avoided. Low-dose combined oral contraceptives containing the second-generation progestogen levonorgestrel (eg 100 micrograms of levonorgestrel and 20 micrograms of ethinyloestradiol) generally improve seborrhoea and mild to moderate acne, but higher dose levonorgestrel formulations should be avoided as they usually worsen acne. Oral contraceptives containing low-dose cyproterone acetate, a fourth-generation progestogen, are usually beneficial in acne including in more severe cases. Oral contraceptives containing the third-generation progestogens gestodene and desogestrel are likely to improve acne, as are those containing drospirenone.

Cyproterone acetateWhen acne control with a low-dose cyproterone acetate oral contraceptive is inadequate or when seborrhoea or hirsutism is also present, additional cyproterone acetate (25 to 100 mg daily) is usually of benefit. It should be given cyclically (days 5 to 14 of the menstrual cycle), and can be used in combination with other oral contraceptives. Cyproterone acetate may cause mood swings, breast tenderness and menstrual irregularity.

Spironolactone

Spironolactone has antiandrogenic actions. There is inadequate published evidence to assess its role in acne treatment, but acne experts advocate 50 to 100 mg per day (and 100 mg per day for 6 months is effective in hirsutism). Spironolactone 50 mg per day can be considered when oral contraceptives are contraindicated or not suitable, or 50 to 100 mg per day can be used in combination with an oral contraceptive, particularly when hirsutism and other signs of androgenisation are present. Administer for 6 months and then review; use

Menstrual irregularity and menorrhagia may require addition of a combined oral contraceptive.Spironolactone is not suitable for women planning a pregnancy.

Isotretinoin

Systemic isotretinoin is the treatment of choice for severe cystic acne and acne causing significant scarring. It may also be justified in cases where acne is resistant to other treatments or persistently relapses.Isotretinoin is the only treatment to significantly affect all the known mechanisms associated with acne. A course of isotretinoin is typically 6 to 9 months and results in prolonged remission of acne in up to 85% of patients. It does not work for everyone, and some people require more than one course of treatment.Isotretinoin is a potent teratogen with an extremely high risk of birth defects necessitating careful counselling and very effective measures to avoid pregnancy while on the drug and for one full reproductive cycle after discontinuation, see Retinoids - Getting to know your drugs.All patients develop adverse effects to some degree (see Table 2). The majority of patients develop dry lips, and dryness elsewhere is common especially of the face, hands, eyes and inside the nose. Increased sensitivity to sunlight is a common problem in Australia. These adverse effects are due to reduced oil production and increased epidermal turnover. Many adverse effects decrease through the course of treatment and settle within weeks of discontinuation. Skin and mucosal adverse effects can be minimised with specific topical measures to reduce irritation and moisturise affected areas.Some people taking isotretinoin become depressed, and suicides are reported. This has received significant media coverage. Depression (sometimes leading to suicide) especially affects young people and is more common in young people with acne. However, no definite link between systemic isotretinoin and depression or suicide is proven. Studies looking into mood change have found that overall mood and wellbeing usually improve as acne improves while on isotretinoin. If depression occurs in someone on isotretinoin, there may be no causal relationship and simply stopping isotretinoin may not be sufficient—they should be appropriately assessed and managed for depression and suicide risk.

Adverse effects of isotretinoin (Table 2)

Zinc

Zinc sulfate 200 mg daily has been shown to be beneficial in acne compared to placebo. Adverse effects include nausea, diarrhoea, and oily irritated skin. Oral zinc is less effective than oral antibiotics.Suggested therapy for different presentations of acne

Mild mainly comedonal or papulopustular acne

Apply a topical retinoid or benzoyl peroxide at night. Apply every second night for the first 2 weeks to reduce irritation:

Use a gel in individuals with oily skin, and a cream for those with dry or sensitive skin. To reduce irritation cleanse with a low-irritant, pH-balanced, soap-free cleanser twice a day. Improvement with retinoids should be evident by 6 weeks and increase for up to 6 months. If inadequate control after 6 weeks, add

For mild truncal acne, consider

To reduce risk of antibiotic resistance, apply antibiotic to entire field usually affected by acne, not just to individual lesions (for further information, see antibiotic resistance). Stop topical antibiotics once papular inflammatory component has settled. Use retinoids or benzoyl peroxide for long-term maintenance.

Moderate papulopustular acne +/- trunk involvement +/- nodules

Apply a retinoid or benzoyl peroxide to face at night as for mild comedonal or papulopustular acne (see above), increasing strength and application as tolerated (tretinoin 0.05% cream nightly is more effective than adapalene 0.1%)

If there is no response by 6 weeks or insufficient response by 12 weeks, increase dose or change antibiotic. If antibiotic resistance is suspected, combine with benzoyl peroxide in preference to a retinoid and consider referral for systemic isotretinoin. A 3- to 6-month course of antibiotics is recommended.Females have the option of adding an oral contraceptive with a favourable androgenic profile while on antibiotics or instead of antibiotics. Improvement with oral contraceptives can be slow; a 3- to 6-month trial is recommended.

Moderate to severe acne +/- nodules +/- cysts

For the face, use a topical retinoid at night and an oral antibiotic:

PLUS EITHER

If the cystic acne is particularly severe or there is a family history of cystic scarring acne, start antibiotics, together with an oral contraceptive in females unless contraindicated, and organise early referral for oral isotretinoin.If there is no response by 6 weeks, or if condition improves and then relapses, consider changing the antibiotic, adding a low-androgenic oral contraceptive in females, and/or referral to a dermatologist for isotretinoin therapy. Unless contraindicated, females should have been taking the oral contraceptive for at least one cycle with a negative pregnancy test before starting oral isotretinoin.

Maintenance therapy and follow up

Isotretinoin may lead to a prolonged remission. Other treatments usually only reduce the signs and severity of acne and several years of therapy is common while waiting for resolution with time. A minimum trial of at least 6 weeks is usually necessary before assessing response following a change in therapy. Best results often require combination therapy, which can be expensive over a long period.Oral antibiotics are available through the Pharmaceutical Benefits Scheme and are convenient to take. Concerns regarding antibiotic resistance require objective evaluation of clinical significance and ideal duration of therapy (for further information). A 6-month antibiotic course is usually recommended, which may need to be repeated.Some patients are well controlled on topical preparations, and these are usually suitable for long-term use. However, the expense of some of these preparations can preclude their use.Prior to stabilisation, patients usually need review every 6 to 8 weeks. Once control is achieved, patients can maintain their remission with repeat prescriptions. Stop medication from time to time to determine whether the acne is showing signs of spontaneous remission.Regularly review patients while taking isotretinoin. Repeat tests for lipids and liver function at least once during the course.

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