Acne: acne vulgaris

Acknowledgements: I would like to thank Professor Bill Cunliffe, Dr. Alison Layton (Consultant Dermatologist at the Harrogate and District Foundation Trust), Dr. Daron Seukeran (Consultant Dermatologist at James Cook University Hospital), Dr Tom Poyner (retired GPwSI in Teesside) and the British Skin Foundation, which funds high-quality research into skin disease and skin cancer.

The aetiology of acne has four major features

• 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
  • And the patients cellular (especially lymphocytes) response within the dermis, which responds to pro-inflammatory cytokines spreading from the duct to the dermis

Factors which 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 endocrinological disorders
     
• UV 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 (refer to the related conditions at the top of this page)
     
• 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, 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
     
• 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

• 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

• The vast majority of patients with acne do not require investigations
   
• Free testosterone levels should be checked in patients suspected of having Polycystic Ovarian syndrome (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 (refer to the chapter on hyperandrogenism for more information)
     
• 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-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
     
• 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 chapter on hyperandrogenism for more information

Key management principles

• Provide patients with a patient information leaflet
   
• 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 eg 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 referred to in steps 2 and 3 (below) should also be referred
  • Ideally patients with scarring should be referred as semi-urgent and seen within six weeks 
     
• For patients with mild-moderate acne:
  • Topical preparations containing benzoyl peroxide 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 Propionibacterium 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 (see images below)
     

Treatment ladder

Step 1: treatment of comedonal acne (figures 6 and 7 above)

• 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 (eg Isotrex ®) 
  • Although topical retinoids should be avoided in pregnancy they are safe to use in all other patients including sexually active women
• Second line - azelaic acid 
   

Step 2: treatment of mild to moderate papular / pustular acne (figures 8-10 above)

• Use a fixed dose combination treatment, ideally containing benzoyl peroxide (BPO), which reduces bacterial resistance, with either a topical retinoid or topical antibiotic
  • ​First line - Epiduo gel (adapalene + BPO)
  • Second line - Duac ® gel (clindamycin + BPO)
  • Other options
    • Treclin ® gel (clindamycin and tretinoin)
    • Erythromycin combinations - Aknemycin ® Plus solution, Isotrexin ® gel
• As in step one above, 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 (figure 11 above)

• 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 OD (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 od (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 (in both groups tetracyclines are contraindicated)
    • The dose of erythromycin is 500 mg BD, or, clarithromycin 250 mg BD - smaller doses are required in patients aged under 12 years
  • Trimethoprim
    • Again 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
  • It is therefore recommended that antibiotics should be stopped after three months, however, the patient should remain on their topical agent
  • 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-severe acne in a woman

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

For an overview of treatment in Primary Care please refer to Acne – Primary Care Acne Treatment Pathway 
 

Acne in pregnancy

The following are usually regarded as being safe, should the physician and patient feel it necessary, to prescribe during pregnancy:

• Benzoyl peroxide preparations
• 2% topical erythromycin
• If the acne is troublesome and not responding to topical treatments consider oral erythromycin, 500 mg BD
   

Step 5: referral to Secondary Care or GPwSI

• Who to refer
  • 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 BD or trimethoprim 300 mg BD
  • 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 dermatologists
  • 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 6-12 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 ie a potent or super-potent steroid cream or ointment carefully applied, Haelan ® tape (fludroxycortide) 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

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