Acne vulgaris: clinical review

Prompt diagnosis and initiation of treatment are an important part of successful therapy in patients who have acne, with a particular focus on psychological impact and avoidance of scarring.

Section 1: Epidemiology and aetiology

Most young people between the ages of 15 and 17 years are affected by acne, and in 20% of these patients, it is classified as moderate or severe.1,2

Severity is correlated to pubertal maturity in both boys and girls. Acne commonly begins in the early teens, but has been reported in younger patients, perhaps owing to a decreasing average age of puberty. In some cases, the condition persists into adulthood, but the reason for this is unclear. 

Approximately 64% of those in their twenties and 43% of those in their thirties have some visible acne.3 It is more prevalent and more severe in male teenagers, but more frequent and persistent in the adult female population. 

Acne has been associated with significant morbidity and psychological distress, with studies linking the disease to a number of abnormalities, including depression, anxiety and suicidal ideation. It is a condition that has a significant impact on the socioeconomic potential of populations.

Aetiology


Mild acne where typical comedones confirm the diagnosis.

The risk factors and genes linked to acne remain unclear.4 A positive family history has been shown to double the risk of significant acne. 

The link with ethnicity also remains unclear, although patients with darker skin are more prone to postinflammatory hyperpigmentation and various subtypes (for example, pomade acne). The role of diet, especially high glycaemic index foods and dairy products, is being investigated. 

Other risk factors associated with acne are sunlight, skin hygiene, high-androgen states, occlusion of the skin surface with, for example, clothing or greasy products, hot, humid conditions and certain drugs, such as antiepileptics, anticancer drugs, steroids and digoxin. Digoxin is associated with severe comedonal acne (chloracne), but not common acne.

Acne vulgaris affects the pilosebaceous unit.5 It involves four key mechanisms, broadly driven by the innate immune system:6 

  • Inflammatory mediators released into the skin by lymphocytes and macrophages stimulate pilosebaceous unit
  • Alteration and up-regulation of the keratinisation process, leading to formation of comedones (blocked hair follicles) 
  • Increased androgen-dependent production of altered sebum (which is usually up-regulated by androgens and inhibited 
  • by systemic retinoids)
  • Follicular colonisation by Proprionibacterium acnes, which further drives sebum-mediated inflammation and forms a biofilm, contributing to comedone development

Androgens play an important part in the pathogenesis of acne, such that puberty has been associated with its onset. Patients with excess androgen states have a higher prevalence
of acne, for example, those with congenital adrenal hyperplasia, polycystic ovary syndrome or hormonal tumours. 

Furthermore, those with androgen-deficient or androgen-insensitive states do not tend to develop the disease. 

Key learning points
  • Acne is the most common skin disorder and should be treated promptly 
  • Antibiotics should not be used as a sole agent for treating the condition
  • Topical retinoids should be used in a stepwise fashion and patients should be warned about the initial skin irritation 
  • Clinicians should always consider the psychological impact that acne has on patient

Section 2: Making the diagnosis

Most commonly, acne lesions are distributed on the face, but they can involve the neck, back and chest, corresponding with areas where most pilosebaceous units are present.7 

The disease features both inflammatory (papules and pustules) and non-inflammatory (open and closed comedones, pseudocysts) lesions, which may be tender to palpation. Acne is also associated with seborrhoea (increased oil production). 

Recently healed lesions may leave erythematous macules, postinflammatory hyperpigmentation and scarring, hence the importance of prompt treatment. 

Of particular note while taking a history of acne is to establish the presence of any of the risk factors mentioned in section 1, as well as the degree of potential psychological impact on the patient.

Acne is a clinical diagnosis. Lack of presence of comedones or atypical presentation should prompt referral to a dermatologist. It can be classified as mild, moderate or severe,8 but a well-defined classification system has not been established (see box 1).

Box 1: assessing acne severity
Mild acne
  • Less than 20 comedones or
  • Less than 15 inflammatory lesions or
  • Total lesion count less than 30
Moderate acne
  • 20-100 comedones or
  • 15-50 inflammatory lesions or
  • Total lesion count 30-125
Severe acne
  • >5 cysts or
  • Total comedone count >100 or
  • Total inflammatory lesion count >50 or
  • Total lesion count >12

Section 3: Managing the condition


Moderate acne with papules and pustules.

There are a large number of products and combinations available to treat acne.7 Most of the guidelines approach initial treatment similarly, depending on the severity of the lesions and whether they are inflammatory or non-inflammatory. 

If the patient has mainly comedonal acne, retinoids form the basis of treatment. If they have mainly inflammatory/pus-filled lesions, antibiotics seem to be more effective. There is a lack of comparative studies and evidence-based guidelines for acne – current guidance relies more on expert opinion. 

Topical treatments

Before topical treatments are started, a careful history should be taken to identify what patients are using on their skin. Some who might have had eczema in the past may be using ointments which can cause or exacerbate acne. Clothing may irritate the skin and reduce the efficacy of topical treatments.  

Topical treatments effectively treat mild acne and only work where applied, by reducing the development of new lesions. OTC preparations, such as benzoyl peroxide 2.5% or 5%, are usually recommended first-line for non-inflammatory acne. 

Topical antibiotics act directly on P acnes and reduce inflammation. Used alone, they are less effective for non-inflammatory acne and promote resistance, so are usually used in combination, most commonly with benzoyl peroxide.

Topical retinoids, such as tretinoin, adapalene and isotretinoin, act to decrease abnormal keratinisation and have some anti-inflammatory properties, so can be used for both inflammatory and non-inflammatory acne. 

All topical retinoids can cause a localised skin reaction and may temporarily worsen acne, which can be reduced by starting with lower-strength preparations and titrating the dose or frequency. Combination therapies are also available with benzoyl peroxide and most recently, clindamycin. 

Oral treatments 

Oral antibiotics are reserved for severe acne, acne unresponsive to treatment, acne predominantly found on the trunk, or in patients who are more likely to scar. No antibiotic clears acne completely, but they can be effective in reducing the number of inflammatory lesions. There is no conclusive evidence to suggest one antibiotic is more effective than another, so choice is largely based on side-effect profiles and cost. 

The most commonly used agents are tetracyclines, such as doxycycline and lymecycline. Alternatives include trimethoprim and erythromycin. They are usually used for long periods at low doses, which has raised concerns about resistance. 

Antibiotics should not be used as a single oral agent. The risk of resistance can be decreased with concomitant use of benzoyl peroxide or topical retinoids. Data from a large RCT suggest that six to eight weeks is an appropriate time to assess response, after which antibiotics should be discontinued if deemed ineffective.9  

Combined oral contraceptives (COCs) containing an estrogen (ethinylestradiol) and a progestogen are commonly prescribed for women who have acne, owing to the antiandrogenic and antisebaceous gland activity effects of estrogen. 

Progestogen-only preparations often worsen acne and should therefore be avoided. COCs are an excellent choice if women are also seeking oral contraception. Similarly, the antiandrogenic properties of spironolactone make this another treatment available to physicians. 

The most effective medication, resulting in clinical cure in about 85% of cases, involves the use of oral isotretinoin. The medication has a broad side-effect profile and can cause cheilitis, dry skin, nosebleeds, temporary worsening of lesions, photosensitivity and increased serum lipids. 

Although these side-effects are rarely a reason to stop treatment, the use of isotretinoin is usually reserved for severe nodulocystic scarring acne. 

Owing to its teratogenic effects, isotretinoin should be given with contraception for women of childbearing age. Additionally, physicians should be aware that there is a possible link between the drug and the development of depression. This is a hospital-only prescription and guidelines are in place, especially regarding pregnancy prevention.10

Psychological support

In addition to the physical symptoms, acne’s effect on quality of life should be considered. The degree of psychological impairment may not correspond to the severity of the acne.11

Most commonly, acne can lead to feelings of anger, anxiety and depression, which may benefit from psychological support. Psychological morbidity may be difficult to appreciate and even more difficult to manage, given the lack of resources. This is especially important because acne tends to peak in the teenage years, a crucial time for building self-esteem and confidence. 

Some patients may be non-compliant with their medication, may manipulate lesions by picking, squeezing or piercing, or may have self-inflicted lesions on the skin. 

These patients are often diagnosed with acne excoriée and may benefit from behaviour-changing therapies (habit reversal) or psychotherapy.12 

Management of complications


Severe nodulocystic acne should be referred for oral isotretinoin

Before treating acne complications, physicians should ensure that any active acne has been successfully treated. The residual erythema that many patients experience may be unusually persistent. The other main complications of acne that require treatment are scarring and hyperpigmentation. 

Two main types of scar can develop in acne – atrophic and hypertrophic.13 Although the pathogenesis of scarring is not fully understood, there are multiple treatments available. These include chemical peels, dermabrasion/microdermabrasion, punch techniques, laser treatment, dermal grafting and needling. Some of these are also used for cases of active acne. 

Hypertrophic scars can be treated using combined therapies with silicone gels, intralesional steroid therapy, cryotherapy and surgery. Treatment for postinflammatory hyperpigmentation should be started early. First-line therapy uses topical depigmenting agents, such as hydroquinone, in addition to photoprotection with sunscreen.14

  • James Leveson is a final year medical student, King’s College London; Dr Karolina Gholam is a paediatric dermatology consultant, Great Ormond Street Hospital, London

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References

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  2. Rademaker M, Garioch J, Simpson N. BMJ 1989; 298: 1217-19
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  4. Ballanger F, Baudry P, N’Guyen J et al. Dermatology 2006; 212: 145-9
  5. Degitz K, Placzek M, Borelli C et al. J Dtsch Dermatol Ges 2007; 5: 316-23
  6. Das S, Reynolds R. Am J Clin Dermatol 2014; 15: 479-88
  7. Williams H, Dellavalle R, Garner S. Lancet 2012; 379: 361-72
  8. Lehmann H, Robinson K, Andrews J et al. J Am Acad Dermatol 2002; 47: 231-40
  9. Ozolins M, Eady E, Avery A et al. Lancet 2004; 364: 2188-95
  10. Goodfield M, Cox N, Bowser A et al. Br J Dermatol 2010; 162: 1172-9
  11. Law M, Chuh A, Lee A et al. Clin Exp Dermatol 2010; 35: 16-21
  12. Fried R, Wechsler A. Dermatol Ther 2006; 19: 237-40
  13. Fabbrocini G, Annunziata M, D’Arco V et al. Dermatol Res Pract 2010; 893080
  14. Davis E, Callender V. J Clin Aesthet Dermatol 2010; 3: 20-31

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