Dr Brian Malcolm outlines the many options available to GPs for treating acne, and when referral to secondary care for consideration of other therapies becomes necessary

Acne is almost a universal problem affecting, to some degree, 85% of adolescent females and 95% of adolescent males,1,2 although it is only considered ‘clinically significant’ in approximately 15%–20% of these cases (in both sexes). Peak severity is seen between the ages of 14 and 17 years in females, and 16 and 19 years in males. It would be a misperception, however, to consider acne as a disease occurring purely in adolescence, with studies reporting an incidence of 7%–17% beyond the age of 25 years.3 About 20% of neonates will also have an acneiform rash, which is usually self-resolving after a few months and is a consequence of maternal hormones. Therefore, it is essential that the primary care physician has a good understanding of acne pathogenesis in order to treat this disease effectively and proportionately.

Despite the high prevalence of acne, its exact aetiology remains relatively poorly understood and it is best thought of as a complex interplay of androgen hypersensitivity, ductal hypercornification and occlusion, bacterial colonisation, and subsequent activation of inflammatory mediators leading to a chronic inflammatory process within the pilo-sebaceous unit. Genetic influences also play an important role.4

Diagnosis

Acne rarely poses diagnostic dilemmas. Clinically, the features include comedones, both open (blackheads) and closed (whiteheads), papules, and pustules. More significant disease can involve the development of nodules, cysts, tracks, and a variety of scars (atrophic, ice pick, hypertrophic, and keloid). It is vital that the healthcare professional is reliably able to recognise these various morphologies and how the condition is expressed in any one patient in order to tailor appropriate treatment plans to the individual.

Occasionally, there can be diagnostic difficulties, particularly in more mature patients in whom several conditions can co-exist. Rosacea (previously and confusingly termed acne rosacea) can be differentiated from acne by the presence of telangiectasia, the absence of comedones, and a history of flushing. Perioral dermatitis produces an acneiform rash, but the lesions are monomorphic, with a characteristic circumoral pattern of distribution, with sparing of the immediate vermilion border; this condition also has a strong association with the use of topical steroids.

Acne can also be caused or exacerbated by drugs, such as steroids, lithium, and phenytoin, or—as in the case of chloracne and pomade acne—by exposure to chemicals. The currently observed increase in the number of adult women presenting with acne is thought to be partly related to the increased popularity of slow-release hormone contraception methods, some of which have acne listed as a common side-effect (the individual summary of product characteristics should be referred to for further information). Acne is also a clinical feature of polycystic ovarian syndrome (PCOS), which can affect up to 10% of women to some degree.

Assessment

Patients with acne will normally present to their GP as the first point of contact. Frequently, younger patients are presented by concerned parents, and are often mute and reluctant to engage. The primary care physician is in an excellent position to raise the issue of acne opportunistically, even when it is not the presenting complaint, but this must be done skilfully and sensitively with patients in this group, who frequently lack confidence and have a poor body image. It is important to take acne seriously from the first consultation, to establish rapport, and to be realistic about treatment goals. The patient must be assured that although it is not possible to talk in terms of ‘cure’, there are effective treatments for all grades of acne.

During such consultations, the opportunity should be taken to explore the myths of poor diet or lack of hygiene as being major influences on the occurrence of acne; indeed, the ‘black’ in blackheads is melanin pigment, not ‘dirt’! At this point, there may have already been significant expenditure on commercial products, which promise much, but fail to deliver.

According to the European Dermatology Forum (EDF) guideline, two broad aspects of acne can be assessed:5

  • objective disease activity, which looks at the visible signs of acne
  • impact on the patient’s quality of life.

However, objectively assessing acne is inherently difficult. The EDF guideline provides further information about the acne grading systems available, but states that, although many methods and scales have been developed, there remains no consensus and little validation of these.5 The Leeds acne grading scale remains the most popular and resilient tool.6

The patient should be thoroughly examined to establish the extent of the acne, including the presence of any scarring and sub-cutaneous disease. All acne-prone areas should be examined. Mild facial involvement may coincide with a ‘lunar landscape’ over the back.
A physical examination can diffuse feelings of infectiousness and ugliness.

Finally, an assessment of the psychological impact of acne should be carried out. This should never be underestimated, particularly in adolescents. The distress caused is often disproportionate to the objective clinical severity. It has been well established that acne can have long-term effects on life achievement, both in work and social spheres, and particularly in females.7,8 The social and psychological disabilities equate to those reported for asthma, arthritis, diabetes, and epilepsy.9 An accompanying parent will often give an added insight into these aspects.

Treatment

Although there is a huge volume of literature available on acne vulgaris, there still remains much to do in terms of providing a completely comprehensive evidence base for the treatment of this condition. The EDF guideline represents the most valuable and current summary of the best evidence available, and reference to this guideline5 will be made throughout this section of the article.

There are a huge number of options in the therapeutic toolbox for acne, but fundamentally there have not been any truly significant advances in the development of novel treatment options for 30 years. Most of the more recent preparations are simply variations or combinations of established treatments, although these can result in greater efficacy and compliance, and the evidence base for their use has significantly progressed. However, the available treatments and how they work must be thoroughly understood by the prescribing physician. Does the patient manifest predominantly comedonal acne or inflammatory acne, or a combination of both? Is there already established or significant scarring? As in the management of hypertension, we must use treatments to target these varying aspects of acne.

The EDF summary of therapeutic recommendations for comedonal acne, mild-to-moderate papulopustular acne, severe papulopustular/moderate nodular acne, and severe nodular/conglobate acne are shown in Table 1.

Comedonal acne

Treatment options for comedonal acne essentially revolve around vitamin A derivatives. Topical retinoids are at their most effective against open comedones.5 As the comedone plays a central pathogenic role in acne, retinoid preparations should be considered as part of the treatment regimen in most patients, but currently in the author’s clinical experience this does not appear to happen. They are available in creams, gels, and lotion formulations, and in various strengths to account for the variety of skin types. Perseverance by the patient is often required in order to develop a tolerance to local irritation. Adapalene appears to be the best tolerated of the available formulations. Retinoid preparations should be avoided during pregnancy, even when topically applied, because of concerns about teratogenicity.10

Isotretinoin

Isotretinoin, prescribed in secondary care, is a highly effective and fundamentally safe treatment when properly monitored and supervised. It remains the best treatment for severe inflammatory acne.5 The vast majority of patients are able to tolerate the treatment and complete the course. It is no longer considered overly expensive, and health economic models reinforce its cost effectiveness. The threshold for prescribing has patently reduced over the years. Concerns relating to its impact on mental health, self-harm, and even suicide, have been intermittently highlighted, particularly in the media. However, these risks have been carefully evaluated and remain very small.5 There are regulatory requirements for prescribing isotretinoin to females with potential fertility, and a pregnancy prevention programme must be strictly adhered to. In the author’s own clinical experience, approximately 70%–80% of patients require only a single course of treatment.

Anti-inflammatory treatments

Since the 1930s, preparations containing various dilutions of benzoyl peroxide (BPO) have been the mainstay of topical treatments for acne. They are primarily antimicrobial, but their mode of action does not encourage resistance to develop. Various formulations, such as gels, creams, and washes, are available over the counter. There is no evidence that strengths above 5% are more efficacious, and these can cause greater irritation.11 Preparations of BPO may bleach both skin and clothing. It is logical to combine BPO preparations with antibiotics to discourage the emergence of bacterial resistance. Other topical preparations for inflammatory acne include azelaic acid, which can be particularly useful when there is pigment disruption, and nicotinamide, a vitamin B derivative, although there is a lack of evidence supporting efficacy for these two agents.

Antibiotics

There is a lack of good ‘head-to-head’ evidence-based data as to which topical preparations are most effective in terms of antibiotic or inflammatory effect. Topical monotherapy with antibiotics is generally not recommended because of the risk of antibacterial resistance.5 Systemic antibiotics are often introduced for more established acne. However, there is no evidence that systemic antibiotics are more effective as monotherapies than topical preparations,5 or that higher doses are advantageous. The EDF guideline suggests considering the use of a combination of topical and systemic antibiotics. Systemic antibiotics, however, are more practical for truncal involvement when topical preparations can pose logistical problems.

Ironically, systemic antibiotics are often cheaper than their topical equivalents. Systemic antibiotics include tetracyclines, erythromycin, and trimethoprim (the use of trimethoprim for acne is off-licence, and the patient’s informed consent should be obtained and documented). The EDF guideline states that doxycycline and lymecycline should be selected in preference to minocycline and tetracycline.5

The suggested doses for oxytetracycline and erythromycin (not recommended by the EDF guideline but in common usage) are 1 g daily in divided doses. Alternative treatments are lymecycline 408 mg once daily, doxycycline 50–100 mg daily, and trimethoprim 200 mg twice daily. The treatment cycle should have a minimum duration of 2–3 months, which may be extended according to response, but should be subject to a regular interval review with the aim of discontinuation when good clinical improvement has been achieved.12

Pharmacokinetics indicate that oxytetracycline and erythromycin would be best prescribed as four-times-daily regimens, but practicality suggests twice-daily regimens are more likely to be adhered to; what is lost in theoretical bioavailability is gained in terms of enhanced compliance. The higher cost of once-daily tetracycline preparations may be justified because of greater compliance. The use of minocycline as a first-line antibiotic should be discouraged because it does not provide greater efficacy and is a more expensive agent, with potentially serious side-effects such as autoimmune hepatitis, a lupus-like syndrome; it can also induce a pigment change, which can be very persistent. Tetracyclines should be avoided during pregnancy and breast-feeding and in children under the age of 12 years whose dentition is not fully established.10

Important principles for best practice in reducing bacterial resistance are shown in Box 1. Healthcare professionals should be aware that resistance to Propionibacterium acnes (P. acnes), the main bacterium implicated in the cause of acne, is much higher with erythromycin.

A range of topical antibiotic preparations, including tetracyclines, erythromycin, and clindamycin also have an anti-inflammatory action. Although in vitro studies often show alarming rates of resistance of P. acnes to antibiotic treatments, clinical efficacy is often still observed, showing that the anti-inflammatory actions of these preparations are an important factor.

The most cost-effective treatment is a combination of systemic oxytetracycline and topical BPO. Additional contraceptive measures are NOT required. Both erythromycin and BPO are considered safe to use during pregnancy.

Combined treatments

Topical and systemic treatments can be combined; many topical preparations are a combination of a retinoid, BPO, and topical antibiotics. Such combinations can help to simplify treatment regimens. The main side-effects of all topical preparations relate to skin irritancy and are most evident in the older topical retinoid preparations. The best evidence for efficacy in mild to moderate inflammatory acne is for combination treatments of either BPO with clindamycin, or BPO with adapalene.5

Hormonal treatments

Co-cyprindiol, which contains cyproterone acetate 2 mg and ethinylestradiol 35 µg, is licensed for the treatment of severe acne and moderately severe hirsutism.10 It is also a reliable oral contraceptive, but is unlicensed for this indication. Co-cyprindiol is associated with a risk of thromboembolic phenomena, but can be a useful adjunct to acne treatment, particularly in older females. Treatment should be discontinued three or four menstrual cycles after the acne has resolved, and thereafter an acne-friendly combined oral contraceptive pill should be introduced. Oestrogen has an inherently anti-androgenic effect, and since androgens are the hormones that ‘fuel’ acne, this anti-androgenic effect tends to improve acne.

Table 1: Summary of therapeutic recommendations from the European Dermatology Forum5*†
Recommendations are based on available evidence and expert consensus. Available evidence and expert voting led to classification of strength of recommendation.
Comedonal acne Mild-to-moderate papulopustular acne Moderate-to-severe papulopustular/ moderate nodular acne Severe nodular/ conglobate acne§
High strength of recommendation Adapalene + BPO (f.c) or
BPO + clindamycin (f.c)
Isotretinoin* Isotretinoin*
Medium strength of recommendation Topical retinoid Azelaic acid or
BPO or
topical retinoid or
systemic antibiotic + adapalene§§
Systemic antibiotics? + adapalene§§or systemic antibiotics? + azelaic acid††or + systemic antibiotics + adapalene + BPO (f.c.) Systemic antibiotics? + azelaic acid
Low strength of recommendation Azelaic acid or BPO Blue light or
oral zinc or
topical erythromycin + isotretinoin (f.c.) or
topical erythromycin + tretinoin (f.c.) or
systemic antibiotic†?+ BPO** or
systemic antibiotic†? + azelaic acid§§ or
systemic antibiotics†? + adapalene + BPO (f.c.)‡‡
Systemic antibiotics|? + BPO** Systemic antibiotics? + BPO** or
systemic antibiotics? + adapalene‡‡§§or systemic antibiotics? + adapalene + BPO (f.c.)‡‡
Alternatives for females Hormonal antiandrogens + topical treatment or
hormonal antiandrogens + systemic antibiotics
Hormonal antiandrogens + systemic antibiotics
  • BPO=benzoyl peroxide; f.c.=fixed combination
  • *limitations can apply that may necessitate the use of a treatment with a lower strength of recommendation as a first-line therapy (e.g. financial resources/ reimbursement limitations, legal restrictions, availability, drug licensing)
  • in case of more widespread disease/moderate severity, initiation of a systemic treatment can be recommended
  • adapalene to be preferred over tretinoin/isotretinoin
  • §systemic treatment with corticosteroids can be considered
  • ?doxycycline and lymecycline
  • low strength of recommendation
  • **indirect evidence from a study also including chlorhexidine, recommendation additionally based on expert opinion
  • ††indirect evidence from nodular and conglobate acne and expert opinion
  • ‡‡indirect evidence from severe papulopustular acne
  • §§only studies found on systemic antibiotic + adapalene, isotretinoin and tretinoin can be considered for combination treatment based on expert opinion
  • European Dermatology Forum. Guideline on the treatment of acne. 2011. Reproduced with kind permission. Available at: www.euroderm.org/images/stories/guidelines/Guideline-on-the-Treatment-of-Acne.pdf.

Box 1: Principles for best practice in reducing antibiotic resistance

  • The treatment cycle should be up to 6 months but requires regular review
  • If further treatment is required then the same antibiotic can be re-used
  • There is no evidence to support the efficacy of switching antibiotics
  • Either short intervening courses of topical antibacterials such as BPO, or co-prescription with BPO may help to eradicate resistant organisms or help prevent their emergence
  • Avoid concomitant oral and topical treatment with chemically dissimilar antibiotics
  • Do not use antibiotics as monotherapy
  • There is no evidence to support the efficacy of switching antibiotics.
  • BPO=benzoyl peroxide

Referral to secondary care

Referral to secondary care should be considered if patients have:

  • a severe variant of acne such as acne fulminans or Gram-negative folliculitis
  • severe nodulocystic acne and could benefit from oral isotretinoin
  • severe social or psychological problems, including a morbid fear of a deformity (dysmorphophobia)
  • moderate acne that has failed to respond to treatment including topical and systemic therapies over a period of at least 6 months (failure is probably best based upon a subjective assessment by the patient)

or if patients are:

  • at risk of, or developing, scarring despite primary care therapy
  • suspected of having an underlying endocrinological cause for the acne (such as polycystic ovary syndrome) that needs assessment
  • people with deeply pigmented skin who are at risk of post-inflammatory pigmentary disturbance.

Urgent secondary care referral is occasionally required in rare cases of acne conglobata or fulminans. Such conditions are rare but can progress rapidly; patients may be systemically unwell and can be at risk of severe scarring unless treated promptly.

In addition, there are a number of physical treatments and other second-line drugs that may be offered, usually in a secondary care setting. These include cryotherapy, cautery, hyfrecation, and aspiration and injection of acne cysts with triamcinolone. Other second-line drugs (in addition to isotretinoin) include dapsone, spironolactone, and cyproterone. Laser and blue light treatments also have their advocates. However, there is a lack of good evidence to support the physical treatments that are available.

Treatment for post-acne scarring remains firmly entrenched in the private sector.

Summary

Acne is a very common condition, the treatment of which remains largely the remit of primary care in the UK. It carries significant psychosocial morbidity. A better understanding of the pathogenesis and clinical presentations, as well as clarity with respect to which patients to refer and when, will lead to more effective targeted treatment regimens and better patient outcomes.

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written by Dr David Jenner, NHS Alliance GMS contract/PBC Lead
  • Acne is a common condition and is usually managed in primary care
  • Local care pathways agreed between specialists and CCGs should identify which patients should be referred to specialist care and when
  • Local formularies should identify the most clinically effective and cost- effective agents for practices to prescribe
  • Community-based specialist dermatology nurses could be commissioned to help support and educate primary care clinicians to manage patients effectively without referral to secondary care unless this is necessary
  • Tariff costs for dermatology outpatients: £106 (new), £69 (follow up).a
awww.gov.uk/government/publications/payment-by-results-pbr-operational-guidance-and-tariffs
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