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Major features of acne

Androgen-induced seborrhoea (excess grease)

  • The more sebum (grease) the greater degree of acne
  • Sebum is produced by the pilosebaceous glands, which are predominantly found on the face, back, and chest
  • Evidence suggests that in most patients, the seborrhoea is due to increased response of the sebaceous glands to normal levels of plasma androgens.

Comedone formation (blackheads, whiteheads, and microcomedones), which is known as comedogenesis

  • Is due to an abnormal proliferation and differentiation of ductal keratinocytes
  • It is controlled, in part, by androgens
  • In pre-pubertal subjects, comedones are seen early and they precede the development of inflammatory lesions.

Colonisation of the pilosebaceous duct with Propionibacterium acnes (P. acnes)

  • Is a later stage in the development of acne lesions (especially inflammatory lesions)
  • The seborrhoea and comedone formation alter the ductal micro environment, which results in colonisation of the duct
  • P. acnes is the most important organism.

Production of inflammation

  • This is a complex process involving an interaction between:
    • biological changes occurring in the duct as a result of comedone formation and P. acnes colonisation of the duct
    • the patient's cellular (especially lymphocytes) response within the dermis, which responds to pro-inflammatory cytokines spreading from the duct to the dermis.

Factors that can/might modify acne

Hormonal factors

  • About 70% of females will notice an aggravation of the acne just before or in the first few days of the period
  • Polycystic ovarian syndrome (PCOS)/other endocrine disorders.

Ultraviolet light

  • Can benefit acne.

Stress

  • This is a controversial issue—there is some evidence that stress makes acne worse but data to support this view is limited
  • Stress may manifest itself as acne excoriee, where patients, usually females, habitually scratch the spots the moment they appear.

Diet

  • Although the evidence for a link between diet and acne is not strong, some people with acne have reported improvement in their skin when they follow a low-glycaemic index diet, which can be achieved by:
    • increasing the consumption of whole grains, fresh fruits and vegetables, fish, olive oil, and garlic
    • decreasing the consumption of high-glycaemic index foods such as sugar, biscuits, cakes, ice creams, and bottled drinks.

Cosmetics

  • Caused by oil-based cosmetics
  • Pomade acne is caused by hair pomades, with comedonal and papulopustular acne on the forehead and temples.

Drugs

  • The following drugs may cause acne:
    • topical and oral corticosteroids
    • anabolic steroids
    • lithium
    • ciclosporin
    • iodides taken orally, which may be part of some homoeopathic therapies.

Clinical findings

  • Greasy skin (seborrhoea)
  • Non-inflamed lesions ie comedones—blackheads and whiteheads (these can be difficult to see, stretching the skin usually helps)
  • Inflamed lesions—papules, pustules, and nodules
  • Scarring, which may be due to:
    • loss of tissue, the so-called atrophic or ice pick scar
    • increased fibrous tissue, the so-called hypertrophic or keloid scar
  • Pigmentation, which can be a problem especially in dark skin.

Investigations

  • The vast majority of patients with acne do not require investigations, apart from under the following circumstances
  • Free testosterone levels should be checked in patients suspected of having PCOS, which is suggested by:
    • oligomenorrhoea (less than nine periods a year)
    • hirsutism
    • free testosterone levels may be elevated between the levels of 3–5 nmol/l (see the PCDS website for more information on hyperandrogenism)
  • Another condition that needs to be considered from time-to-time is late onset (non-classical) congenital adrenal hyperplasia, which may have the following features:
    • clinical features in childhood include precocious puberty, acne and accelerated bone age
    • clinical features in adolescent and adult females include persistent acne, moderate-to-severe hirsutism, menstrual irregularity/fertility problems and a short stature
    • there is often a family history
    • patients normally have biochemical evidence of hyperandrogenism. Test for serum levels of 17-hydroxyprogesterone levels in the follicular phase around 9 am.

Endocrinopathy

  • Patients suspected of having a more serious underlying endocrinopathy, including those found to have a testosterone level greater than 5 nmol/l, or with other features of virilisation, should be referred urgently to an endocrinologist. Such cases are very rare. Please refer to the PCDS website for more information on hyperandrogenism.

Management

Key management principles

  • Provide patients with information, useful resources include the British Association of Dermatologists website: www.bad.org.uk/for-the-public/patient-information-leaflets
  • The primary aim of acne treatment is to prevent or minimise scarring; once scarred the skin will never return to normal. Accordingly:
    • patients with severe acne, e.g. nodular scarring acne should be referred immediately
    • papular/pustular acne can also scar, as such patients starting to scar who do not respond to the treatments mentioned in steps 2 and 3 (see 'Treatment ladder') should also be referred
    • ideally patients with scarring should be referred as semi-urgent and seen within 6 weeks
  • For patients with mild-to-moderate acne:
    • topical preparations containing benzoyl peroxide (BPO) and/or topical retinoids are an essential part of the treatment. It is important to explain to the patient that such treatments will dry the skin and cause local irritation. In order to reduce adverse effects, patients may wish to start using the treatments two to three evenings (or nights) a week and gradually increase the frequency and duration of applications
    • there are increasing levels of P. acnes resistance to antibiotics, especially erythromycin, the use of which should be restricted
  • The type of acne is important. For example, there are some variants such as sandpaper acne and macrocomedonal acne that respond poorly to conventional treatment
  • It is important to have a way of monitoring response to treatment. This could be done as follows:
    • serial photography is perhaps the best method
    • using standardised grading methods.

Treatment ladder

Step 1: treatment of comedonal acne

  • First line—a topical retinoid
    • a topical retinoid is needed as this reduces comedonal activity
    • choices include adapalene (Differin®), adapalene combined with benzoyl peroxide 2.5% (Epiduo®), or isotretinoin (e.g. Isotrex®)
    • although topical retinoids should be avoided in pregnancy, they can be safely used in non-pregnant women of childbearing age even if they are not on contraception, as long as they stop treatment as soon as they become pregnant (or if they believe there is a chance they may be pregnant)
  • Second line—azelaic acid.

Step 2: treatment of mild to moderate papular/pustular acne

  • Use a fixed-dose combination treatment, ideally containing BPO, which reduces bacterial resistance, with either a topical retinoid or topical antibiotic
    • first line—Epiduo® gel (adapalene and BPO)
    • second line—Duac® gel (clindamycin and BPO)
    • other options:
      • Treclin® gel (clindamycin and tretinoin)
      • erythromycin combinations—Aknemycin® Plus solution
  • As in step one, it is important to explain to the patient that both BPO and topical retinoids will dry the skin and cause local irritation. In order to reduce adverse effects, patients may wish to start two to three evenings (or nights a week) and gradually increase the frequency and duration of applications.

Step 3: not responding to the above and/or more widely distributed acne

  • Combine systemic antibiotics with an appropriate topical agent, preferably BPO to reduce bacterial resistance. If patients cannot tolerate BPO, use a topical retinoid
  • Antibiotic choice:
    • tetracyclines:
      • lymecycline 408 mg o.d. (Tetralysal®) is a good first-line antibiotic as compliance is good (it can be taken with food) and bacterial resistance is less than with first-generation tetracyclines
      • review the patient in six weeks. If the response is poor then change to doxycycline 100 mg o.d. (can take with food). Doxycycline can occasionally cause a photosensitive eruption
      • minocycline is rarely used due to the increased risk of hepatotoxicity and lupus-like conditions
    • macrolides:
      • should generally be avoided due to high levels of P. acnes resistance
      • they are first line in pregnancy and in children under the age of 12 years (tetracyclines are contraindicated in both of these patient groups)
      • the dose of erythromycin is 500 mg b.d., or, clarithromycin 250 mg b.d.—smaller doses are required in patients aged under 12 years
    • trimethoprim:
      • there are concerns of bacterial resistance, so this treatment may best be reserved for young children who do not tolerate macrolides
  • Duration of treatment:
    • the evidence suggests that there is little additional benefit in using antibiotics for more than three months, and in addition, prolonged use increases the resistance of P. acnes
    • antibiotics should be stopped after 3 months; however, the patient should remain on their topical agent (either BPO, a topical retinoid, or a combination i.e. Epiduo® gel)
    • the antibiotic course could be repeated in the future if needed
    • if the patient does not respond to two types of antibiotics, especially if they are starting to scar, the patient should be referred for consideration of isotretinoin.

Step 4: treatment of moderate-to-severe acne in a woman

  • Dianette®:
    • if no contraindications, consider adding to the topical/systemic treatments referred to above
    • may be of particular value in patients with significant endocrinopathies such as PCOS.

For an overview of treatment in primary care please refer to the PCDS website.

Acne in pigmented skin

  • Acne is no more common or severe in pigmented skin, but post-inflammatory hyperpigmentation can be significant and often persists for months to years. As such, early and more aggressive treatment is advocated, including early referral for consideration of isotretinoin
  • Secondary acne can be a result of cultural practices—hair oil can induce pomade acne on the forehead and skin lightening products containing topical steroids can cause a steroid-induced acne
  • Topical retinoids, benzoyl peroxide and azelaic acid play an important role in the treatment of the comedonal aspects of acne. If used daily they often cause dryness and irritation, which in pigmented skin can lead to further hyperpigmentation. Accordingly these treatments should initially be used for shorter periods of time (e.g. in an evening and washed off before bed) and perhaps less frequently (e.g. every second or third day). If tolerated the duration and/or frequency of treatment can be increased—if used in this way then as well as treating the comedones they may help treat hyperpigmentation rather than aggravate it.

Acne in pregnancy

  • The following are usually regarded as being safe, should the physician and patient feel it necessary, to prescribe during pregnancy:
    • BPO preparations
    • 2% topical erythromycin
    • if the acne is troublesome and not responding to topical treatments, consider oral erythromycin 500 mg b.d.

Step 5: referral to secondary care or GPwSI

  • Criteria for referral:
    • severe acne—refer early
    • moderate acne only partially responding to treatment and starting to scar and/or causing significant hyperpigmentation (more common in patients with brown or black skin)
    • patients with associated and severe psychological symptoms, regardless of the physical signs
  • Treatment options once referred:
    • oral isotretinoin (see below)
    • high-dose oral antibiotics such as lymecycline 408 mg b.d. or trimethoprim 300 mg b.d
    • Dianette® with additional cyproterone acetate (50–100 mg/10 days)
    • short courses of oral corticosteroids may be required.

Prescribing isotretinoin in the community

  • The current Medicines and Healthcare products Regulatory Agency (MHRA) view on isotretinoin prescribing is as follows (March 2007):
    • the summary of product characteristics in the licence for isotretinoin states that it can be prescribed by, or under supervision of, physicians with expertise in the use of systemic retinoids for the treatment of acne and a full understanding of the risks of isotretinoin and monitoring requirements. This wording is chosen for compliance with other European states but in the United Kingdom refers to consultant dermatologist
    • consultant dermatologists and experienced GPwSIs working within an integrated service may wish to develop a locally agreed care pathway and accreditation process to facilitate the prescribing of isotretinoin in the community. However, they need to be mindful that this is an 'off-licence' indication and be cognisant of the MHRA view. They may also wish to seek the advice of their professional indemnity organisation.

Management of scarring

  • Up to 50% of scars (especially smaller scars) may improve naturally over six to 12 months. Treatment of established scars is difficult and while some patients will benefit from treatment others will not. Patients should only be referred to dermatologists/plastic surgeons familiar with treating scars. Funding will vary depending on local commissioning arrangements.

Atrophic scars

  • The development of ablative lasers combined with appropriate surgical techniques has led to a significant improvement in the way that certain atrophic scars can be treated
  • Punch excision of small atrophic scars, which can be very helpful prior to resurfacing
  • For deep scars—scar revision may help
  • Other options include intradermal injections of collagen or compounds, which stimulate collagen synthesis.

Hypertrophic/keloid scars

  • Silicone gels applied to scars can be prescribed by general practitioners
  • Local steroids for a trial period of two to three months. Look closely for side-effects such as skin thinning and telangiectasia. Treatments can be administered as topically, i.e. a potent or super-potent steroid cream or ointment carefully applied, Haelan® (fludroxycortide) tape, or by using intradermal triamcinolone given as an injection
  • Pulsed dye laser, which can reduce the redness of scars and flatten them. This procedure is only possible through specialised hospital departments.

 

Full guideline:

Primary Care Dermatology Society, PO Box 789, Rickmansworth, WD3 0NU (Tel—0333 939 0126)

Primary Care Dermatology Society. Acne vulgaris. Available at: www.pcds.org.uk/clinical-guidance/acne-vulgaris

Published date: December 2016.

Last updated: 31 March 2020.