Skin concern spotlight: Acne

What is acne?

Acne is a disorder of the pilosebaceous unit – the hair follicle and oil gland

It typically affects the face (99% of people affected with acne), chest (15%), and back (60%).

How common is acne?

Acne is extremely common: almost every adolescent will experience acne to some degree.

It can persist beyond the teenage years or recur at a later date. The majority of cases resolve by age 25. 

15% of women and 5% of men continue to have acne during adulthood.

What causes Acne?

Acne is due to excess sebum combined with excess desquamated epithelial cells, which then cause follicular plugging and distension.

(Sebum is the light yellow, oily substance that is secreted by the sebaceous glands that help keep the skin and hair moisturized. Sebum is made up of triglycerides, free fatty acids, wax esters, squalene, cholesterol esters, and cholesterol)

The distended follicle is called a microcomedo.

The microcomedo expands in size to form either an open (blackhead) or closed (whitehead) comedone.

A bacteria called Propionibacterium acnes proliferates in the follicle. 

This causes an inflammatory reaction which weakens the wall of the follicle. 

Eventually the wall ruptures, and the sebum-keratin mixture leaks into the dermis, provoking an immunological reaction.

As a result, inflammatory lesions develop – papules, pustules, nodules and cysts.

Scarring can occur as a result of recurrent rupture and re-epithelialisation of cysts.

What are the risk factors for significant acne?

Genetics seem to play a role.

A positive family history means that significant acne is more likely

Hormones affect acne:

Sebum production is androgen (male sex hormone) driven. Note – females also have male sex hormones, just to a much lower degree than men. 

The sebaceous glands of people with acne may have an increased response to normal levels of plasma androgens.

Acne is often worse in women with PCOS (who often have higher testosterone levels than other women) and during the pre-menstrual phase.

Any condition with abnormal androgen levels can result in acne, such as testosterone therapy, anabolic steroid misuse or Cushing’s disease.

Progestogenic contraceptives can reduce a protein called sex hormone binding globulin (SHBG usually lowers testosterone levels) and therefore can make acne worse. 

The vast majority of patients do not need any investigations, but occasionally blood tests are recommended – for example testosterone levels can be checked if PCOS is suspected.

No specific foods are implicated.

There is some evidence that dairy-rich or high GI diets may be associated with acne, although other studies show no link.

Obesity may increase the risk of acne, as obesity can affect the hormone profile. 

Smoking is associated with more severe acne.

Medications that can aggravate acne include lithium, ciclosporin, carbamazepine and azathioprine.

Stress: There have been small studies suggesting a link between severity of acne and exam stress.

Classification of acne:

Acne can be categorised as mild, moderate and severe:

Mild – total lesion count <30. Mainly non-inflammatory comedones. Usually confined to the face

Moderate – mixture of non-inflammatory comedones and inflammatory papules and pustules. May extend to the shoulders and back.

Severe – nodules and cysts (nodulocystic acne), inflammatory papules and pustules. 

Acne conglobate is an uncommon form of severe acne where there are abscesses.

Severe acne is defined as >5 cysts, or total comedone count >100, or inflammatory lesion count >50, or total lesion count >125

Acne general / lifestyle advice:

To reduce acne, it is best to avoid smoking and follow a healthy diet. 

Excessive facial cleansing can make symptoms worse by exacerbating inflammation, particularly astringent or exfoliative products. 

Only a gentle cleanser should be used.

Avoid oily cosmetics; use water-based products instead. 

Avoid picking or squeezing the spots – this will worsen inflammation and can introduce infection. 

Treatment options:

Inflammatory acne lesions take 4-8 weeks to completely heal, which is in line with the natural cell turnover of the epidermis. 

This is why there is a delay in onset of benefit when using any new acne treatment.

Treatments can be either topical (applied to the skin), or systemic (taken in pill form).

Topical options:

• Retinoids – for example Adapalene
• Antibiotics – clarithromycin or erythromycin 
• Benzoyl peroxide (BPO) – This is the only over the counter (not requiring a prescription) ingredient with evidence of efficacy for acne. It can be used in combination with either a retinoid or antibiotic. 
• Azelaic acid 20% – can be tried if the above do not help.

Systemic options:

• The combined oral contraceptive pill 
• Antibiotics – tetracyclines, erythromycin or trimethoprim 
• Androgen receptor blockers – e.g. spironolactone, cyproterone acetate, flutamide (prescribed in secondary care only – i.e. by a dermatologist rather than a GP)
• Isotretinoin (secondary care only)

Topical retinoids:

These are vitamin A derivatives.

They are anti-inflammatory, and comedolytic (reduce comedones) 

They can also reduce post-inflammatory hyperpigmentation in darker skin

They can be irritant; side effects can include transient redness and skin peeling. 

If this is troublesome, the frequency or strength can be reduced.

Adapalene 0.1%  – 0.3% is usually the best tolerated retinoid for acne. It is the usual first line treatment.

One brand of adapalene is “Differin”.

Treatment may be needed for several months and should be continued until no new lesions develop. 

Retinoids cannot be used by pregnant women.

Topical antibiotics:

Examples are clindamycin and erythromycin.

Mode of action – antimicrobial, anti-inflammatory

These are usually a second line treatment, if BPO or topical retinoids have failed to adequately control symptoms.

Rather than stopping BPO or retinoids, topical antibiotics are ADDED to the treatment. 

The risk of developing antibiotic resistance is a concern. To reduce this risk, a topical antibiotic SHOULD be used alongside another topical treatment such as BPO, but NOT be used at the same time as systemic antibiotics. 

It is advisable to limit the duration of topical antibiotic use to 12 weeks if possible.

Benzoyl peroxide:

This is available without a prescription.

Mode of action – comedolytic, antimicrobial, anti-inflammatory

This kills bacteria and helps prevent antibiotic resistance. It also has more of an anti-inflammatory effect compared to retinoids.

It is available of strengths from 2.5% to 10%. A usual starting concentration is 5%.

Stinging, peeling, and redness can happen and are worse if the skin is especially greasy. Side effects are greater at higher strengths.

BPO can be used every other day and then built up to use every day. 

Bleaching of clothes, hair and bedding can occur. 

BPO causes retinoids other than adapalene to become unstable.

Retinoids and BPO can be applied separately – one in the morning and one at night.

Both can be irritant however so this may not be tolerated.

These treatments will cause skin redness when first used but this should settle after about 2 weeks.

Azelaic acid 20%:

Mode of action – comedolytic, antimicrobial, anti-inflammatory

This has a weaker evidence base for efficacy than other topical agents – so is a second line treatment. 

It is less irritating than retinoids or BPO and hence better tolerated. It is generally used as an alternative for those who cannot tolerate other treatments.

It can be used in all severities of acne.

In some people it can cause temporary hypopigmentation (lighter skin), especially in those with darker skin. It can transiently lighten skin and this may be seen as a benefit in those with post-inflammatory hyperpigmentation

Systemic treatments: Oral Antibiotics:

The first line systemic treatment is usually an antibiotic in the tetracycline family, such as lymecycline.

Tetracyclines have less resistance problems and more anti-inflammatory properties than other Abs.

All tetracyclines and contraindicated in pregnancy, breastfeeding and children under 12.

Tetracyclines can cause dyspepsia and sensitivity to light.

If tetracyclines cannot be used, a macrolide such as erythromycin is the next choice. There are higher levels of bacterial resistance to this.

Oral antibiotics should be used in conjunction with either topical retinoids or BPO to reduce the risk of resistance developing. 

They should not be used concurrently with topical antibiotics.

Generally, maximum benefit will be achieved by 3 months. However, some people respond more slowly so they can sometimes be continued for 6 months in total.

There is little value in continuing beyond this due to the increased risk of resistance.

Further courses of the same antibiotic may be needed in the future. 

Systemic treatments: Oral hormonal treatments:

Mode of action: Reduced androgenic (male sex hormone) effect on follicles.

A standard contraceptive pill can be used for acne. It can take up to 6 months to help.

If a standard pill does not help, Co-cyprindiol (eg Dianette) contraceptive pill can be used. 

This has more of an effect on acne as it contains the anti-androgen hormone cyproterone acetate.

It also helps hirsuitism (excess hair, which can occur with PCOS)

It is not the first choice, as it has a greater risk of causing blood clots than other forms of the contraceptive pill. 

It should be ceased 3-4 menstrual cycles after the acne has resolved; and maintenance therapy can then be with a standard contraceptive pill. 

Systemic treatments: Oral isotretinoin (Roaccutane):

Mode of action: Reduced sebum production, anti-inflammatory.

Isotretinoin is only initiated by specialists, due to the pre-treatment counselling and monitoring required.

It is highly effective, but has a significant side effect burden. Redness and dry skin are very common. More rarely, colitis, pancreatitis, hepatitis, or high cholesterol can occur.

It can cause birth defects, and so reliable contraception is essential during use and for 1 month afterwards.

Blood tests are required before and during treatment

It can also affect vision, and airline pilots will not be able to continue their job while taking isotretinoin.  

Acne treatment in pregnancy:

As retinoids and some antibiotics are unsafe in pregnancy, a typical treatment regime for a pregnant woman involves BPO and topical erythromycin.

Key points of acne treatment:

• Topical retinoids such as Adapalene 0.1 – 0.3% are first line treatment, but benzoyl peroxide 2.5% – 10% can be used instead, and this doesn’t need a prescription.
• Azelaic acid 20% is less effective, but causes less irritation than retinoids or BPO so is a gentler alternative to them.
• Topical antibiotics are the next step up – they can be used in combination with a retinoid or BPO
• Topical and oral antibiotics should not be used together.
• The contraceptive pill can help acne in women. Anti-androgen pills are most effective but have greater risks that the standard pill.
• Isotretinoin (Roaccutane) is very effective, but initiated by specialists only due to its side effects and risks. 

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