Acne Vulgaris

Introduction

Acne vulgaris is a chronic inflammatory disease of the pilosebaceous unit, affecting the vast majority of adolescents to some degree and persisting into adulthood in a significant minority, particularly women. It typically begins around puberty as rising androgen levels stimulate the sebaceous glands, though a smaller proportion of cases have their onset in adulthood.¹

Despite being extremely common, acne is not a trivial condition to dismiss as a normal part of growing up. It causes genuine physical scarring that is permanent once established, and its psychological impact - on self-esteem, social confidence and mental health - is frequently disproportionate to its physical severity. Early, adequately intensive treatment reduces both of these risks, which is why current UK guidance favours starting effective combination treatment promptly rather than working through weaker options first.²

Pathophysiology

Four interacting processes drive acne, and every class of treatment targets at least one of them.

1. Increased sebum production - androgens (chiefly testosterone and its more potent metabolite dihydrotestosterone) stimulate sebaceous gland activity, which is why acne appears at puberty and can be treated hormonally
2. Follicular hyperkeratinisation - abnormal shedding of keratinocytes lining the follicle causes them to stick together rather than desquamate normally, blocking the follicular opening and forming a comedone
3. Colonisation with Cutibacterium acnes (formerly Propionibacterium acnes) - this normally commensal, anaerobic organism proliferates in the lipid-rich, oxygen-poor blocked follicle⁷
4. Inflammation - C. acnes triggers innate immune activation via toll-like receptors, and the follicle wall can rupture, releasing its contents into the surrounding dermis and provoking the inflammatory lesions - papules, pustules, nodules and cysts - that follow the initial comedone

Risk factors

• Puberty and adolescence - the commonest period of onset, driven by rising androgen levels
• Female sex in adulthood - adult-onset or persistent acne is more common in women, often with a perimenstrual flare
• Polycystic ovary syndrome - acne, hirsutism and irregular periods together should prompt consideration of an underlying androgen excess disorder
• Family history - acne severity has a significant genetic component
• Drugs - corticosteroids (topical and systemic), anabolic steroids, lithium, phenytoin, and some progestogen-only contraceptives can induce or worsen acne
• Comedogenic cosmetics and oil-based skincare products
• Mechanical friction or occlusion - for example under sports equipment or tight clothing (acne mechanica)

Clinical features

Acne affects the face, chest and upper back - the areas with the highest density of sebaceous glands - and presents with a mixture of non-inflammatory and inflammatory lesions.

Grading severity

Grading (mild, moderate or severe) is based on the balance and number of comedonal versus inflammatory lesions and directly determines where to start treatment.²

Post-inflammatory erythema and hyperpigmentation are common after lesions resolve, especially in darker skin tones, and can persist for months even after the acne itself is controlled - a point worth explaining early, since patients otherwise assume treatment has failed.

Clinical examination

• Distribution and lesion mix - face, chest, back; proportion of comedonal versus inflammatory lesions
• Scarring - look specifically for ice-pick, rolling and boxcar scars, since established scarring changes the urgency of referral
• Signs of hyperandrogenism - hirsutism, irregular menstrual cycles, acanthosis nigricans, or male-pattern hair loss, prompting consideration of polycystic ovary syndrome
• Psychological impact - ask directly about mood, self-consciousness and impact on school, work or social activities

Differential diagnosis

• Rosacea - affects an older age group, centred on the central face with erythema and telangiectasia, and characteristically has no comedones
• Perioral dermatitis - grouped papules and pustules around the mouth, often related to topical corticosteroid overuse
• Folliculitis - monomorphic pustules centred on hair follicles, without comedones, sometimes related to occlusion or a specific organism
• Acne mechanica - comedones and papules at a site of chronic friction or occlusion, for example under a chin strap
• Drug-induced (steroid) acne - monomorphic papules and pustules appearing shortly after starting a corticosteroid, without the comedone-to-inflammatory-lesion progression of ordinary acne
• Keratosis pilaris - rough, gooseflesh-like papules typically on the upper arms and thighs rather than the face

Investigations

Acne is diagnosed clinically and does not routinely require investigation. Targeted tests are used only where an underlying cause or a treatment-related risk needs to be assessed.

• Hormonal profile (testosterone, LH, FSH, SHBG) and pelvic ultrasound - if hirsutism, irregular periods or other signs suggest polycystic ovary syndrome or another androgen excess disorder
• Pregnancy test - mandatory before starting isotretinoin or, for many prescribers, a retinoid, in anyone who could become pregnant
• Baseline and monitoring bloods for isotretinoin - lipid profile and liver function before starting and periodically during treatment
• Skin swab - rarely needed, but can help exclude Gram-negative folliculitis in someone who deteriorates on long-term antibiotics

Management

Treatment is chosen according to severity, and current NICE guidance favours starting with an effective combination rather than a single weaker agent, to reduce the time to control and the risk of scarring.²

Topical therapy - mild-to-moderate acne

• Fixed-dose combination of a topical retinoid (adapalene or tretinoin) and benzoyl peroxide - first-line for most patients, targeting hyperkeratinisation and C. acnes respectively
• Topical antibiotic (clindamycin) combined with benzoyl peroxide - an alternative first-line combination, particularly if retinoids are not tolerated (retinoids are teratogenic and should be avoided in pregnancy)
• Azelaic acid - a useful alternative with a favourable safety profile, including in pregnancy, and it also helps post-inflammatory hyperpigmentation³

Oral therapy - moderate acne not responding to topicals

• Oral tetracycline (lymecycline, doxycycline) for 12 weeks, always combined with a topical retinoid and/or benzoyl peroxide - never as antibiotic monotherapy, and never combined with a topical antibiotic
• Avoid tetracyclines in pregnancy, breastfeeding and children under 12 due to effects on developing bone and teeth; erythromycin is the alternative in these groups
• Re-assess at 12 weeks - continuing beyond this without clear benefit is discouraged because of resistance

Hormonal therapy

The combined oral contraceptive pill is an option for women who also want contraception, particularly where acne has a clear perimenstrual pattern or coexists with hirsutism suggesting an androgen-driven component. Co-cyprindiol (an anti-androgen with an oestrogen) is more effective but carries a higher venous thromboembolism risk and is generally reserved for women not responding to other options, used for a limited course.

Isotretinoin - severe or resistant acne

Oral isotretinoin is the most effective treatment available, acting on all four elements of the pathophysiology, and is reserved for severe nodulocystic acne, acne causing scarring, or acne resistant to adequate courses of the above.^5,6 It is prescribed under specialist (usually dermatology) supervision only.

Complications

• Scarring - ice-pick (narrow, deep), rolling (broad, undulating) and boxcar (sharply demarcated, box-like) scars, which are permanent once formed and much easier to prevent than to treat
• Post-inflammatory hyperpigmentation or erythema, especially prominent and slow to fade in darker skin tones
• Acne fulminans - a rare, abrupt, severe presentation with ulcerating, haemorrhagic nodules, fever and systemic upset, occasionally with arthralgia; a medical emergency needing urgent specialist referral and systemic corticosteroids alongside isotretinoin
• Acne conglobata - severe, interconnected nodules, abscesses and sinus tracts, usually on the trunk, without the systemic features of acne fulminans
• Psychological impact - depression, anxiety, social withdrawal and reduced self-esteem, which correlate poorly with objective severity and should be assessed directly rather than assumed from the visible extent of disease⁸

Red flags

Prognosis

Most acne improves substantially by the mid-to-late twenties as androgen-driven sebum production settles, though a meaningful proportion of adults, especially women, continue to have some degree of acne into their thirties and forties.¹

With appropriate, adequately intensive treatment started early, the great majority of patients achieve good control and avoid permanent scarring. The main determinants of a poor long-term outcome are delay in starting effective treatment, under-treatment with antibiotic monotherapy allowing resistance to develop, and failure to refer promptly once nodulocystic or scarring disease is present - all of which are avoidable with the stepwise approach above.