Clinical Review - Acne vulgaris

Contributed by Dr Anneke Kai, specialist registrar in dermatology, and Dr Sandeep Cliff, consultant dermatologist, St Helier Hospital, Carshalton, Surrey

Acne most commonly affects the back, the face and chest (All photographs: authors images)
Acne most commonly affects the back, the face and chest (All photographs: authors images)

Section 1: Epidemiology and aetiology
Acne vulgaris is one of the most common dermatological conditions worldwide, with more than 80 per cent of all people being affected at some point in their life and up to 14 per cent of UK acne patients seeking advice from their GP.1

It can cause psychosocial problems such as social embarrassment and isolation.2

Acne primarily affects the younger population with a peak incidence of 85 per cent between 12 and 25 years and an equal sex incidence. However, adult acne is not uncommon with around 5 per cent of men and women continuing to have clinical acne into their forties.

White males have been shown to have more severe nodulocystic disease than their black counterparts but the incidence of post-inflammatory hyperpigmentation, keloidal and hypertrophic scarring is higher in patients with pigmented skin.3

Individuals at increased risk of acne include those with endocrine abnormalities, such as polycystic ovarian syndrome (PCOS), hyperandrogenism and hypercortisolism and those with an XXY genotype.

Acne is a multifactorial disorder of the pilosebaceous unit. The face, chest and back are most commonly affected. The exact role of genetic predisposition is unclear. The concordance rate for prevalence and severity of acne between monozygotic twins is very high but the high prevalence of acne in the general population makes it difficult to show that this is attributable to genetics.4

Multifactorial development
Acne may present with highly variable morphologies of non-inflammatory and/or inflammatory lesions. Lesions are thought to result from:

  • Increased sebum production (seborrhoea)
  • Hyperkeratosis within the pilosebaceous duct
  • Colonisation of the pilosebaceous duct with Propionibacterium acnes
  • Release of inflammatory mediators

Sebaceous glands are androgen sensitive and at puberty there is a dramatic increase in sebum production.

One of the initial steps in the pathogenesis of acne is the development of microcomedones. Dead keratinocytes accumulate within follicles, forming a comedone. The comedone then expands and rupture of the wall leads to inflammation.

P acnes are Gram-positive bacteria found within sebaceous follicles. They produce enzymes which contribute to comedone rupture and also release pro-inflammatory mediators.

Although patients with acne have increased numbers of P acnes, the number of organisms does not correlate with the clinical severity of the acne.

Section 2: Making the diagnosis
Non-inflammatory acne is characterised by open and closed comedone formation. Open comedones, also known as blackheads, are papules within a dilated follicle. They are composed of shed keratin and may have a black colour due to melanin deposition and lipid oxidation.

Closed comedones, or whiteheads, are usually small skin or cream-coloured papules with no apparent follicular opening and no associated inflammation. Comedonal acne without inflammation can lead to 'ice pick' scarring.

Inflammatory lesions occur when comedones expand and evolve into papules, pustules, nodules and cysts. Erythematous papules usually range between 1-5mm in diameter, while pustules tend to be similar in size and are filled with sterile white pus.


Acne presents with non-inflammatory and/or inflammatory lesions

Lesions may progress in severity and form nodules, which can be tender and indurated with marked inflammation. Cysts may develop deeper within the skin and are filled with pus and serosanguinous fluid.

In severe nodulocystic acne, these lesions may coalesce to form highly inflamed plaques with sinus tracts (conglobate acne).

Acne fulminans is the most severe form of cystic acne. It is characterised by the abrupt onset of nodular and suppurative acne in association with variable systemic manifestations, such as fever, arthralgia, myalgia and hepatosplenomegaly. Acne fulminans is uncommon and usually affects males 13 to 16 years of age.

The lesions may ulcerate and lead to significant scarring.

Acne excoriee occurs mainly in young women who systematically pick their lesions causing crusted erosions that may scar.

Neonatal acne occurs in more than 20 per cent of newborns and is usually benign and self-limiting. Infantile acne occurs at three to six months of age.

Lesions are mostly comedonal but cystic lesions and nodules may be seen. The condition usually resolves within two years.

Investigations
As the management of acne is affected by the aetiology, it is useful to investigate certain patient groups.

A detailed history can help to identify patients with specific causes, such as drug-induced acne (associated with steroids, phenytoin, lithium and iodides), acne mechanica (caused by physical obstruction, such as a helmet) and occupational acne (for example, chloracne).

Female patients with irregular menses should have a hormone screen to look for PCOS.

Physical examination should reveal patients with features of hyperandrogenism. Prepubertal patients with acne should undergo the appropriate investigations.

Initial tests should include serum levels of total and free testosterone, dehydroepiandrosterone sulphate and 17-hydroxyprogesterone. Patients with features of hypercortisolism need an early morning cortisol level. Patients with PCOS often have a raised testosterone level with an increased LH/FSH ratio.

Skin swabs can be taken when Gram-positive or negative folliculitis is suspected.

Section 3: Managing the condition
The management of acne should be tailored to the aetiology, type and severity. The box below gives an overview of treatments.5

Retinoids
The first-line treatment for comedonal acne is topical retinoids. Retinoids normalise follicular keratinisation, aiding comedone expulsion and preventing new comedones forming.

The most common side-effect is local irritation. A low concentration preparation should be used and the strength increased as necessary. Alternate night application may be used.

Available preparations include adapalene, tazarotene and tretinoin. Night-time application is recommended as tretinoin is photolabile. There is a synergistic comedolytic effect when retinoids are used with topical benzoyl peroxide (BPO).

Although studies have not shown an increased risk of teratogenicity in mothers using topical retinoids, there have been sporadic case reports of birth defects and pregnancy should be avoided while using these preparations.5


Management of acne should be tailored to the aetiology, type and severity of the acne

Antibiotics
Mild to moderate papulopustular acne without scarring can be treated with BPO together with topical retinoids or with topical antimicrobials (antibiotics or azelaic acid).

BPO is a potent bactericidal agent which reduces the levels of P acnes in follicles. It is applied once or twice a day. It can cause an irritant reaction and occasionally a true contact allergy. Bacterial resistance does not develop. The most commonly used topical antibiotics are erythromycin and clindamycin.

Gels and solutions may be more irritating than creams and lotions. The development of resistance is reduced if they are used with BPO.

In moderate papulopustular acne with mild scarring, oral antibiotics may be used alongside topical treatment. First-line antibiotics are usually tetracyclines. Lymecycline, doxycycline and minocycline are more effective than tetracycline. Erythromycin is a second-line agent, although bacterial resistance is a problem. Trimethoprim and azithromycin can be used as third-line agents.

Women of child-bearing age
In females, oral contraceptive pills can improve acne by decreasing free testosterone levels. In patients with PCOS, a contraceptive with the anti-androgen cyproterone acetate can be used.

Spironolactone also has an antiandrogenic effect and may be helpful in some patients with PCOS, however contraception is needed due to the risk of male fetal feminisation.6 The patient will also require BP and serum potassium monitoring.

In severe papulopustular, nodular and conglobate acne, a course of the systemic retinoid isotretinoin may be given under specialist guidance.

Acne fulminans can be treated with oral isotretinoin together with a low dose of oral corticosteroid. Patients need assessment for suitability and pre-treatment counselling regarding potential side-effects.

All females of child-bearing age must be advised about the teratogenic risk and the need for contraception. A negative urine beta-hCG is required before each month-long prescription. Treatment is started at 0.5mg/kg/day and increased as tolerated until a total dose of 120-150mg/kg is reached.

Side-effects include dry skin, sore lips, epistaxis, joint pains, and raised lipids. Pre-treatment and subsequent blood monitoring includes a renal profile, FBC, LFTs and a lipid screen.

Laser and light therapy
Recently laser and light therapy have been used in the treatment of acne.

Although the results of some trials appear encouraging in mild to moderate acne, the overall published data on outcomes is not positive enough for these treatment modalities to be recommended by most dermatologists and they are not generally available on the NHS.

MANAGEMENT OF ACNE
Comedonal acne
Topical retinoids.

Papulopustular acne
Mild: Topical BPO with topical retinoids or topical antimicrobials.

Moderate with mild scarring:
  • For males: oral antibiotics with BPO or topical retinoids.
  • For females: oral anti-androgen contraceptive with BPO and topical antibiotics.
Moderate without scarring:
BPO with topical retinoids and topical antibiotics.

Severe
Oral isotretinoin. For females, add an oral anti-androgen contraceptive

Section 4: Prognosis
All treatment modalities should be used for at least two to three months in order to gauge efficacy. Treatments which lead to an improvement should be continued for four to six months.

Patients with mild to moderate non-scarring acne can be managed in the community.

Patients with treatment-resistant or scarring acne should be referred to secondary care for oral isotretinoin.

In most male patients acne clears by early adulthood with around 5 per cent still having acne at 25 years. Adult acne is more common in women, with 12 per cent still having acne at age 25.

The overall prognosis for acne is good, although the physical scarring and psychosocial impact can be permanent.

Section 5: Case study
Mr S is a 26-year-old Asian male with nodulocystic acne affecting his face, chest and back. He has had acne for seven years and was referred to the dermatology department.

He had tried numerous topical treatments including BPO, adapalene and clindamycin, and had also received prolonged courses of oral lymecycline, oxytetracycline, doxycycline and erythromycin.

Box car scarring
He had inflamed papules and pustules over his cheeks and forehead with keloidal and box car (undulated) scarring and marked post-inflammatory hyperpigmentation.

He also had similar lesions over his upper back and milder lesions on his chest.

Mr S was embarrassed by his physical appearance and felt it undermined his confidence. He was concerned it would hamper his personal relationships and his professional career where he had to deal with members of the public face to face.

He wanted to explore further treatment options for his skin. The scarring nature of his acne made him an ideal candidate for treatment with oral isotretinoin, however his case was complicated by a history of abnormal LFTs.

There was no significant family history of liver problems and a liver ultrasound was normal. A hepatology review suggested that these abnormalities were most likely idiopathic so low-dose isotretinoin was started.

Isotretinoin
Treatment was started at 20mg/day (the patient's weight was 103kg) with careful monitoring of serum LFTs.

After one month of treatment, the number of active inflammatory lesions had decreased significantly.

Mr S had experienced side-effects of dry skin and lips but no other problems.

Repeat LFTs showed no deterioration and he was continued on the same low dosage of 20mg/day. The inflammatory lesions began healing after one month of treatment.

There was marked scarring and post-inflammatory hyperpigmentation over his face, back and chest which made isotretinoin the best treatment choice for him.

Section 6: Evidence base
Research and reviews

A BMJ Clinical Evidence review article on acne vulgaris. The authors conducted a systematic review aiming to answer the question: 'What are the effects of topical and oral treatments in people with acne vulgaris?'

A Review of acne in ethnic skin: Pathogenesis, clinical manifestations and management strategies.

Oral isotretinoin can be used to treat severe nodulocystic acne

    Guidelines

    • There are currently no NICE guidelines on the treatment of acne but advice for GPs on when to refer patients with acne to secondary care can be found in the Referral Advice document published by NICE in 2001 (pages six and seven). This is available at www.nice.org.uk/media/94D/BE/Referraladvice.pdf
    • The British Association of Dermatologists (BAD) has recently published guidelines on the safe use of isotretinoin: Advice on the safe introduction and continued use of isotretinoin in acne in the UK 2010.8 This can be accessed via the BAD website: www.bad.org.uk//site/622/default.aspx

    Key texts

    • Lebwohl M, Heymann W, Berth-Jones J et al. Treatment of skin disease. 3rd edition. Elsevier. 2010 (pages six to 11).

    This book gives a summary of treatment strategies for acne and their underlying levels of evidence.

    • Bolognia JL, Jorizzo JL, Rapini RP. Dermatology, 2nd edition. Mosby. 2008. A more detailed but manageable text on acne can be found in volume one (pages 495-508) of the two-volume textbook. This section gives an excellent and thorough review of pathogenesis, clinical features and management.

    Curriculum
    The RCGP covers this topic in statement 15.10, Skin Problems gponline.com/curriculum

    Online

    An easily accessible resource with details on diagnosis and management of acne, with clinical pictures.

    This is regularly updated (last updated June 2010).

    Reflect on this article and add notes to your CPD Organiser on MIMS Learning

    CPD IMPACT: EARN MORE CREDITS

    These further impact points may allow you to earn more credits by increasing the time spent and the impact achieved.

    • Perform a search of your patients with acne. Determine the male:female ratio. If there are more females than males with acne then consider ways, as a practice, that you could encourage your male patients with acne to attend your surgery for treatment.
    • Attend a meeting (or hold one at your practice) with a local dermatologist to discuss the preferred local and systemic treatments for acne in your area.
    • Review the notes of your patients with acne who are taking isotretinoin. Ensure these patients are having correct regular blood test monitoring.

    REFERENCES
    1. Purdy S, de Berker D. Acne. BMJ 2006; 333(7575): 949-53.

    2. Magin P, Adams J, Heading G et al. Psychological sequelae of acne vulgaris: Results of a qualitative study. Can Fam Physician 2006; 52(8): 979.

    3. Davis E, Callender VD. A Review of acne in ethnic skin: Pathogenesis, clinical manifestations and management strategies. J Clin Aesthet Dermatol 2010; 3(4): 24-38.

    4. Bolognia JL, Jorizzo JL, Rapini RP et al. Dermatology. 2nd edition. Mosby. 2008.

    5. Lebwohl MG, Heymann W, Berth-Jones J et al. Treatment of Skin Disease. 3rd edition. Elsevier. 2010.

    6. Ebede TL, Arch EL, Berson D. Hormonal treatment of acne in women. J Clin Aesthet Dermatol 2009; 2(12): 16-22.

    7. Purdy S, de Berker D. Acne vulgaris. Clin Evid (Online) 2008; 1714.

    8. Goodfield MJD, Cox NH, Bowser A et al. Advice on the safe introduction and continued use of isotretinoin in acne in the UK. Br J Dermatol 2010; 162 (5): 1172-79.

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