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What you need to know about acne

Hospital practitioner in dermatology Dr Iain Henderson answers GP Dr Mandy Fry’s questions on retinoids, rosacea and the Pill

Hospital practitioner in dermatology Dr Iain Henderson answers GP Dr Mandy Fry's questions on retinoids, rosacea and the Pill

1 We all know that women taking isotretinoin need to use contraception due to its teratogenic effects. Does it have similar effects on sperm? If so, what should we be advising male patients contemplating starting a family?

41234712Studies have shown that isotretinoin does not influence the formation or quality of sperm in humans. So you can tell male patients that it shouldn't affect their ability to have healthy children now or in the future. Very low levels of isotretinoin are present in the semen of men taking it but too little to harm his unborn child.

But you should advise men about the teratogenic effects and warn them not to share the drug with anyone, particularly women. Also warn them not to donate blood while taking isotretinoin and for a month after stopping, as donated blood could be given to a pregnant woman.

Other possible side-effects for either sex include aches and pains especially during vigorous exercise, mood changes, dryness of the skin, eye irritation and hair changes. As the capsules have gelatin in them, some vegans may decide to try alternative treatments. It's important to measure and monitor lipid and liver enzyme levels, so check whether they have a needle phobia.

2 What role do topical retinoids play in the treatment of acne? Are they suitable for use in primary care?

The topical retinoids tretinoin and isotretinoin and the retinoid-like compound adapalene are very useful for treating mild to moderate acne in primary care. They have three modes of action:

• they inhibit the formation of comedones

• they are keratolytic

• they have an anti-inflammatory action – especially adapalene.

The most common side-effect is skin dryness and irritation, but this can be kept to a minimum if it is used for a short period – 15-20 minutes initially – before washing it off, then building it up to several hours or overnight. Adapalene is less irritating than the others so may be better tolerated.

Topical retinoids can cause photosensitisation so advise patients to use them at night although they don't bleach clothes and hair like benzyl peroxide products.

They are useful maintenance products because of their anti-comedogenic properties. Any patients using cosmetics or moisturisers should be advised to use non-comedogenic and non-astringent products.

There's no information on topical retinoids in pregnancy so the manufacturers advise they should not be used by pregnant women unless essential and that women of child-bearing age should use contraception.

3 I understand the efficacy of certain antibiotics – such as oxytetracycline – is impaired by dairy products. Is this true for minocycline too? If so how should we advising patients to take it? Which oral antibiotic would you recommend as a first line treatment?

Oxytetracycline 500mg twice daily is a good first-line antibiotic for acne but, as you say, the absorption can be affected by dairy products and also antacids, calcium and iron. If taken 30 minutes before food – or at least two hours after – it can be an effective and cheap treatment.

Minocycline is highly fat-soluble so doesn't have this problem but the manufacturers suggest swallowing the capsules with plenty of water either sitting or standing to reduce the risk of oesophageal irritation or ulceration.

Minocycline has dropped down the pecking order in recent times because of long-term side-effects such as discolouration of skin and teeth and more rarely a lupus-like syndrome and eosinophilic pneumonitis.

Alternatives to oxytetracycline where concordance and efficacy are a problem are lymecycline, which has a convenient once-daily dose of a 408mg capsule equivalent to 300mg tetracycline base. Its efficacy is similar to minocycline but it has fewer potential ide-effects and is cheaper.

Another tetracycline is doxycycline 50-100mg daily but warn patients about photosensitivity with this. Erythromycin 500mg twice daily can be useful in female patients who may become pregnant.

4 Are there any issues around rising rates of antibiotic resistance that are specific to the treatment of acne? If so how should they impact on GP management?

A Health Technology Assessment carried between 1998 and 2000 found that there was Propionibacterium acnes resistance in acne patients in general practice – 18% resistance to tetracyclines, 41% to clindamycin and 47% to erythromycin. There is less resistance to lymecycline.

This is an increase over the past 20 years and is of concern. It may be associated with reduction in clinical efficacy although the concentration of the oral antibiotic in the sebum is a factor. Topical antibiotics can reach concentrations that may overcome any resistance.

Benzoyl peroxide is known to prevent, eliminate or reduce bacterial resistance so combining this with a topical antibiotic could help. A combination product such as Duac has been shown to be more effective than using the two active ingredients (clindamycin and benzoyl peroxide) separately. It has also been shown to improve skin where it has been colonised by antibiotic-resistant P. acnes. If there are predominantly non-inflammatory lesion, a topical retinoid or topical antibiotic combination could be tried.

5 Which of the many topical preparations would you recommend?

There are various topical preparations.

Benzoyl peroxide products can be bought over the counter and possess antibacterial, anti-inflammatory and keratolytic properties. The main side-effects are skin irritation and bleaching of hair and clothes. Applying a 2.5% preparation for up to 30 minutes each day then washing it off and building it up may reduce the irritation. There are no comparable studies of different strengths but there appears to be no significant benefit with higher strengths and more skin irritation.

Retinoids are anti-inflammatory, keratolytic and inhibit comedone formation. I use them for maintenance therapy if it is mainly comedonal acne but females need adequate contraception.

Azelaic acid is keratolytic and has some antibacterial properties so is a useful alternative where the patient can't tolerate the skin irritation of the first two as it is less of an irritant.

Nictonamide (Nicam) is another preparation to keep up your sleeve.

6 What about topical antibiotics? If I'm using a topical antibiotic in combination with an oral one is it best to use the same antibiotic or different ones?

Topical antibiotics I tend to use are clindamycin and erythromycin. Combining them with a retinoid or benzoyl peroxide gives better efficacy than using the two ingredients separately – for example, Duac (clindamycin and benzoyl peroxide) or Isotrexin (erythromycin and isotretinoin).

It's better to use the same antibiotic topically and systemically if possible to reduce the risk of resistance.

7 Are oral antibiotics or the combined oral contraceptive Pill likely to be more effective for teenage girls with acne? Are there any features of the acne itself, rather than the individual patient's preference, that could help predict the response to treatment?

If topical therapies alone are not improving the acne or if it is widespread – including the back and chest – I would try an oral antibiotic first as any combined Pill will have progestogen in it.

The products containing lower doses of oestrogen and third-generation progestogens tend to be more skin-friendly and reduce the risk of thromboembolism when compared with higher-dose oestrogen and second-generation progestogens – but acne is still listed as a possible side-effect.

Dianette is a combination of ethinyestradiol 35mg and cyproterone acetate 2mg, which is a progestional anti-androgen that blocks the androgen receptor. It is licensed for severe acne.

It is useful in women who have acne secondary to elevated androgen levels such as polycystic ovarian syndrome where hirsutism is also a problem.

Women who are on tetracyclines should avoid becoming pregnant or breast-feeding as they can cause foetal and infant staining of the teeth and enamel hypoplasia. So it's acceptable to use oral antibiotics and the Pill in combination.

8 Talking of Dianette, we used to believe that women could only use it for a limited period of time even if it was being particularly effective. Is that view still widely held? What underpins it? Which Pill would you use next if acne remains a problem?

The therapeutic indication for Dianette is severe acne that has been refractory to prolonged oral antibiotic therapy. It shouldn't be used solely as a contraceptive.

The length of treatment will vary with the response but nine months to a year is a reasonable trial period. If there are no contraindications it can be continued for three to four cycles after the acne has resolved. Also use concomitant topical therapy during this time. If the severe acne recurs repeated courses can be given.

The alternatives I'd use are the more oestrogen-dominant ones – for example those with third-generation progestogens such as Yasmin, Cilest and desogestrel (Marvelon and Mercilon).

Women who start long-term oral antibiotics while on the Pill should take extra precautions for the first three weeks while the gut flora builds up resistance.

If the woman is already on long-term antibiotics and starts the Pill, no additional precautions are necessary as the gut will have already built up resistance.

9 In women with a history of problematic acne how would you advise them if they are considering choosing a long acting reversible form of contraception? If their skin condition deteriorates with a LARC such as Implanon or an IUS will it improve immediately if they switch contraceptive?

The three types of long-acting reversible contraceptives (LARCs) that contain progestogens are intramuscular (Depo-Provera and Noristerat), intradermal (Implanon) and intrauterine (Mirena). There are also copper wire intrauterine devices.

Depo-Provera contains medroxyprogesterone and Noristerat norethisterone both of which are more androgenic than third-generation progestogens so can increase sebum production. A US study showed that about 10% of women on these discontinued treatment because of acne.

Implanon contains etonogestrel, which is androgenic but the NICE guidance on LARC summary of evidence on Implanon states that non-comparative studies report that acne may develop or improve during Implanon use.

The Mirena IUCD contains levonorgestrel and a study showed that the incidence of acne with it was double that of copper wire IUDs but this was 1% compared with 0.5%.

You should inform the patient that there is an increased likelihood of developing acne but very few women have it removed for this reason.

Removing Implanon or Mirena will reduce the progestogen levels quickly and so the androgen levels and sebum production should also reduce quickly.

10 Treatment is often guided by patient preference which is itself guided by the acne's psychological impact.

But I often see patients whose levels of distress seem to be disproportionate to their appearance. Is there any evidence to support this observation? Does psychological help have a role for these people?

Acne can have a significant psychological impact that does not always correlate well with the severity of the disease.

One study reported rates of body dysmorphic disorder of 14-21% in patients with acne.

Assessment of psychological factors should be a part of management. Ask the patient how the acne makes them feel and how it affects work, school, relationships and quality of life. Does it stop them doing anything?

You can direct the patient to websites and organisations that explain the condition. If there is evidence of low mood and avoidance of daily activities because of their acne then counselling may help.

The PHQ-9 depression questionnaire may pick up depression and if there is significant depression referral to mental health services would be appropriate. If there is evidence of dysmorphia or severe psychological symptoms then consider a referral to a dermatologist.

11 Patients are often confused by the myriad products for acne that are available OTC? Which products, or particular ingredients, have a sound evidence base? Are there any ‘natural' or alternative products that have been proven to be effective?

OTC products usually have one or more of the following ingredients in them – benzoyl peroxide, salicylic acid or nicotinamide.

Benzoyl peroxide is the most effective ingredient and products can contain 2.5-10% w/w. The higher the concentration the more likely it is to irritate the skin so I would advise patients to start with 2.5% initially. Well-known products with benzoyl peroxide in them include Acnecide and the Oxy, Panoxyl and Clearasil ranges.

Nicotinamide 4% w/w can be found in Nicam gel and Freederm, which are useful alternatives if skin irritation is a problem.

Salicylic acid is an old traditional keratolytic and Acnisal contains 2% w/w.

Other products have resorcinol or chlorocresol in them which are antiseptics.

Echinacea has a skin cleansing property if patients wish to try a ‘natural' solution.

12 How common is acne rosacea? What treatments do you recommend and how long do they need to be used for?

A Swedish study of 809 office workers showed the prevalence of rosacea in Caucasian women as 14% and 5% in men.

A more recent study from Harvard Medical School showed a prevalence of 16% in Caucasian women. It is said to have an even higher incidence in Celtic populations.

Men tend to get more of the eye and lymphoedema/rhinophyma complications.

Broad-spectrum long-term antibiotics similar to the ones to treat acne are the mainstay of treatment. Duration of treatment varies. Some cases resolve after a two-month course but some need long-term therapy. From my experience rosacea often recurs when treatment is stopped.

A low-dose oral doxycycline treatment has FDA approval in the US and is awaiting approval here.

If the patient wishes a topical alternative, topical metronidazole gel or cream or azelaic acid gel (Finacea) or cream (Skinoren) can be tried. Oral retinoids can be used in severe and recalcitrant cases.

Prominent telangectasia can be treated by laser and dermabrasion can be used for prominent rhinophyma. If flushing is the main symptom, clonidine 25-50mcg bd can be tried. Remember that rosacea can also result in eye symptoms such as blepharitis, conjunctivitis and keratitis. These are usually helped by the systemic treatment.

Dr Iain Henderson is a GP in Glasgow and hospital practitioner in dermatology, and represents the Primary Care Dermatology Association on the Dermatology Council for Scotland

Competing interests Dr Henderson chaired the Acne Working Group for developing acne management guidelines. The group was supported by Stiefel, a GlaxoSmithKline company.

What I will do now What I will do now

Dr Mandy Fry considers the responses to her questions
The advice about gradually building up the duration of use for topical preparations such as adapalene to minimise the problem of skin irritation will be a very helpful practical tip.
I think I'll also consider the use of nicotinamide in those for whom this is a particular problem.
It's interesting, but not surprising, that antibiotic resistance in acne is increasing and it seems that lymecycline may be a useful option – although I am not sure how this would work with the advice to try to use the same topical antibiotic as that used systemically.
I'll also continue to use topical preparations alongside Dianette and continue to encourage women, once their acne is controlled, to consider trying an alternative Pill that may have fewer adverse effects. It also seems that LARCs, particularly the IUS and Implanon, are reasonably well tolerated from an acne perspective and that – even if it worsens the condition – problems will resolve quickly after stopping.
I hadn't previously thought about advising patients on isotretinoin to avoid blood donation, particularly for one month after stopping, and I am sure this will have wider implications and also be true for other medications.
I had also not considered eye symptoms as being a feature of acne rosacea. It's also useful to know that systemic treatments can be helpful in rosacea as it may influence my treatment choices.
Dr Mandy Fry is a GP in Cirencester, Gloucestershire, and senior primary care lecturer at Oxford Brookes University

thps Acne

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