Acne Treatments

The descriptions below are general guidance on using best acne treatment. When deciding on the type of topical treatment to use, assessment of the type of acne the patientis presenting with is important, e.g. is it inflammatory or non-inflammatory or a mixture of the two. It is also important to bear in mind the patient’s lifestyle and what sort of treatments they are willing and able to tolerate.

Before discussing with the patient the possible treatment options, it is important that the health care professional ensures that the patient is clear about a number of general issues around acne and its treatment. To start with, patients need to be advised that acne is not caused by any of the mythical causes such as poor hygiene, too much sex, eating chocolate or dietary habits in general. As has been described earlier in the chapter, acne is a complex condition caused by the interplay of a number of different physiological factors. It may be helpful to explain this to patients. Some patients may believe that their acne is contagious and this falsehood must be dispelled. Regardless of which treatments are eventually used, there are some general guidelines about acne management that are worth discussing.

General advice on skin care for acne prone skin

• Avoid harsh washing and specifically do not scrub acne affected skin.
• It is best for the skin not to squeeze spots. Certainly, if the lesion is red and not pustular it should be left alone. However, for many patients this is difficult to adhere to, so the following guidance is aimed at causing as little permanent damage as possible to the skin:
• When trying to express the contents of a pustule, stretch the skin on either side of the lesion using a tissue rather than digging in with the nails and squeezing.
• Gentle pressure and squeezing on either side of blackhead is probably the only way to express those lesions. Whiteheads should not be squeezed.
• Stop squeezing if blood is seen.
• Avoid using oily products on the skin. Moisturisers may be needed as the skin between lesions can become dry and tight (especially if drying topical agents are being used). All products should be labelled oil free and non-comodogenic.
• Foundation and cover-up makeup can make acne worse, although lighter non-comodogenic products are likely to be less troublesome.

It is important that patients are aware that there is really no quick treatment option for acne and that results from treatment will only be seen over a prolonged period of time (weeks to months). In addition, due to the number of different processes that are occurring in the development of acne (i.e. increased sebum production, follicular plugging, colonisation by P. acnes and the resulting inflammation), it is often necessary to have a combination of treatments which tackle different elements of the disease process.

In order to optimise the care of patients with acne (and therefore the results they experience), intervention at an early stage is vital. Often it will be a nurse who has the time and skills to undertake this early care. This will ensure that people with acne understand about the process of the disease, how and why to use treatments and importantly how to recognise if the condition is worsening and more intensive interventions are needed, particularly with the aim of preventing scarring.

Topical treatments

Mild to moderate acne

Topical treatments are the first-line treatment for acne. As has been outlined earlier, noninflammatory lesions include microcomedones, open and closed comedones. If these types of lesions predominate, with few or no pustules, acne is usually termed mild. In this instance, the first-line treatments are ones that reduce follicular plugging anti-inflammatory properties are less important. There seems to be consensus that in this situation the best treatment options are topical retinoids (Gollnick et al., 2003).

Topical retinoids

Topical retinoids work by reducing the abnormal desquamation of skin cells into the follicular canal thus reducing the plugging. They work on the very earliest of acne lesions, the microcomedone, thus preventing more mature comedones from developing. They also appear to have some anti-inflammatory properties, although these are not their main mode of action. Finally, because of their impact on the follicular microclimate, they appear to enhance the efficacy of antibacterial products such as benzoyl peroxide (BPO) and topical antibiotics. Because of their action on the microcomedone, retinoids can be considered as maintenance therapy once active lesions have been cleared.

Topical retinoids describe a broad group of pharmaceutical products which are derived from vitamin A. Over the years, a number of different ‘generations’ of retinoids have been developed. Tretinoin and isotretinoin were the first generation; the drawbacks highlighted with these products being skin irritation, delayed and variable responses, photosensitivity and exacerbation of the acne after 2– 4 weeks. In order to get around the problems of skin irritation, a number of different strengths and formulations were developed including the microsphere which was designed to release the tretinoin slowly in a controlled manner. It should be noted that topical isotretinoin has a similar effect to tretinoin, but a very different effect from oral isotretinoin as it has no impact on sebum production.

Adapalene is a newer retinoid (known as third generation) in which the therapeutic action is similar to that of tretinoin, but in which the unwanted side effects of skin irritation and photosensitisation have been reduced. Adapalene also seems to be absorbed into the pilosebaceous duct more effectively than into the rest of the skin surface, thus increasing its efficacy. As yet there is no Cochrane review giving evidence-based guidance as to which retinoid is best to use; however, there has been a research study indicating that whilst efficacy was similar, adapalene had fewer unwanted side effects than tretinoin microsphere gel 0.1%.

Topical retinoids can be used in women of child-bearing age; however, they should be advised to avoid pregnancy whilst using them. Should an individual become pregnant whilst using topical retinoids, they should stop the treatment immediately. Whilst it is unlikely for the topical product to have a systemic effect, this is a sensible precaution.

How to apply a retinoid product?

Usually it is best to apply these at night before going to bed. The patient should be encouraged to wash the skin and dry it gently but completely before applying a thin layer of the product to the whole area to be treated, not just the lesions. Retinoids can be applied to any area of the body where acne is present including chest and back. The choice of the formulation of the product, whether a cream or a gel, will usually depend on personal preference. A gel is likely to dry the skin more and may be helpful if the skin surface is very greasy whereas a cream will be more moisturising and may be helpful if the skin surface has a tendency to get dry. After applying the treatment, the patient should wash their hands. The possible side effects of treatment have already been mentioned including redness, soreness and skin peeling and hypersensitivity to sunlight. If the former is a problem, the severity of the symptoms may be reduced by using a weaker formulation, if one is available, or by starting with less than a once-daily application (perhaps alternate days) and then building up to the required once a day. Patients should be advised to avoid overexposure to the sun and to not make use of sunbeds.

Benzoyl peroxide

BPO is a commonly used product for the management of mild to moderate acne. Many teenagers who have acne will purchase overthe- counter products containing BPO, and are likely to have had varying degrees of success
with them. BPO works by releasing free radical oxygen within the follicle itself; this has a bactericidal effect thus reducing the bacterial load of P. acnes. BPO is therefore an effective antibacterial product and particularly useful when there are inflammatory lesions as well as non-inflammatory lesions. The impact of BPO is enhanced by the use of topical retinoids; they are often used as a combination therapy.

How to use BPO?

Before starting to use the treatment, patients should be made aware that the product can bleach bedding, clothing and even hair, so care should be taken when using it. The main side effect of BPO products is that they cause reddening and soreness of the skin. This is usually mild and can generally be overcome by starting treatments at a low strength and/or using them on alternate days initially. Gradually over time, the frequency can be increased to once or twice daily. If the lower strengths are tolerated and they are not completely clearing the acne, it is worth moving up to the stronger strengths.

The patient should be instructed to wash their skin with a mild cleanser and pat the skin surface completely dry. The product should then be applied all over the affected area, not just to the lesions. The patient should then wash their hands carefully. Another tip if the skin is particularly sensitive is to leave the product on for just a short period of time initially (washing it off after 15 minutes) and then gradually building up increasing amounts of time as the skin tolerates the product.

BPO may be used as part of a combination regime, usually with retinoids. In these instances, BPO should be used in the morning and the topical retinoid in the evening. It is particularly important for the patient to remember to wash their face prior to using each different topical therapy.

Azelaic acid

This has a similar clinical effect to BPO, but causes less irritation and does not have the same tendency to bleach. It has reported antibacterial and comodolytic properties. It is available as a 15% gel and 20% cream

How to use azelaic acid?

It should be applied to clean skin twice daily, preferably in the morning and evening. As with BPO, if the skin is particularly sensitive, a gradual introduction of the product might be helpful.

Nicotinamide

This is a physiologically active form of nicotinic acid which is thought to have anti-inflammatory, bacteriostatic effects on P. acnes and reduce sebum production. It is therefore most useful if there are inflammatory lesions in evidence.

How to use nicotinamide?

It should be applied to clean skin twice daily, preferably in the morning and evening. It may take up to 12 weeks to have a beneficial effect.

Topical antibiotics

If BPO is not tolerated, topical antibiotics particularly topical clindamycin, erythromycin or tetracycline may be used. There are concerns about antibiotic resistance and it is generally recommended that they should not be used as a monotherapy, but instead be used with a retinoid product. Long term use as a maintenance therapy should also be avoided. They have a slower onset than oral antibiotics and are less effective. Some topical antibiotic products already contain BPO and it has been shown that this combination leads to a reduced potential for developing P. acnes resistance.

How long to use treatment for?

All three of the topical treatments in this section need to have been used for 2 months before assessment as to their success or failure is made. During this prolonged period of time, patients will need to have support and encouragement to continue to use treatments. Concordance will be improved with regular contact to discuss how the treatments are feeling on the skin and whether there are any ongoing problems. Ideally, patients should have access to telephone support.

Moderate acne

Moderate acne differs from mild in the number of papular and pustular lesions that are present. These are much greater in number and although there will still be comedones present, the focus of treatment shifts towards managing the high burden of P. acnes which leads to significant inflammatory lesions.

Oral antibiotics

Oral antibiotics are a commonly used treatment for acne, and should be considered as appropriate for moderate to severe cases. Typically, the antibiotics of choice are tetracycline or oxytetracycline. Doxycycline may be considered for people who cannot comply with oxytetracycline or tetracycline. Lymecycline is tetracycline which is taken once daily and has the advantage of not needing to be taken on an empty stomach. Erythromycin might be considered if there is no response to the other antibiotic therapies; however, it has been increasingly associated with resistant strains of propionibacteria which may explain its lack of efficacy. It has been suggested that erythromycin is reserved for patients for whom the cyclines are contraindicated, e.g. when breast feeding or when pregnant. Trimethoprim is a final option but it is an off-licence use and therefore probably only to be initiated by a specialist. Minocycline has historically been the preferred antibiotic; however, safety concerns including a greater risk of a lupus erythematosustype reaction and possible permanent skin pigment changes have meant that it is rarely used. A Cochrane review considered the evidence in relation to the efficacy of minocycline in comparison with other oral antibiotics and showed no significant difference.

An important issue in relation to antibiotic prescribing in acne is that of resistance. It was reported that around 50% of acne sufferers in Europe were colonised with erythromycin- and clindamycin-resistant strains of P. acnes and up to 20% were colonised with cycline-resistant strains. The same paper states that the longer someone is on oral antibiotics, the more likely it is for resistance to develop; they estimate that at the end of a 6 months course of antibiotics, most people would have developed resistant strains of P. acnes. Antibiotic resistance should be considered as a possible cause of failure to respond to treatment, especially if they have been given over a prolonged period of time. Box 10.2 summarises the risk factors associated with developing resistant bacteria. The same article provides a list of recommendations for reducing the likelihood of developing resistant strains of P. acnes. Oxytetracycline and tetracycline are given in 500 mg doses twice a day whereas doxycycline is longer acting, thus given as a once-daily treatment at a dose of 100 mg. Lymecyline taken once a day in a dose of 408mg. Treatment should be given for 3 months before an assessment as to whether it is making any improvement or not.

Risk factors for bacterial resistance

• Long courses of antibiotics
• Multiple course of antibiotics
• Poor compliance with treatment
• Being close to someone who has resistant acne.

If no improvement is seen, the antibiotic should be changed; however, it should be noted that maximum improvement is usually seen at 4–6 months. More severe cases of acne may need oral antibiotics for 2 years or more (but see comments earlier with regards to resistance). Fatty food in particular decreases the absorption of tetracycline and oxytetracycline and to a lesser extent, doxycycline. Patients should be recommended where possible to take the antibiotics on an empty stomach to maximise their therapeutic value.

Recommendations for reducing likelihood of developing resistant bacteria

• Do not use antibiotics where other acne treatments can be expected to bring about the same degree of clinical benefit;
• Use antibiotics according to clinical need (e.g. should not in general be used for mild acne);
• Do not use them as monotherapy;
• Stop the treatment when the health care professional and the patient agree that there is no further improvement or the improvement is only slight;
• Try to avoid using antibiotics beyond 6 months;
• Use BPO either concomitantly or pulsed as an anti-resistance measure;
• Do not swap antibiotics without adequate justification (i.e. if a further course of antibiotics is needed, use the same one)

The most common side effects of these antibiotics are gastrointestinal disturbances which patients should be warned of.

It is generally agreed that clearing inflammatory and comedonal lesions is quicker when oral antibiotics are used in conjunction with topical retinoids and antibacterials. Thus oral treatment is not used instead of topical treatment, but as an additional therapy. The mechanisms for improved efficacy of combined therapy is in part due to the different modes of action of the various therapeutic agents (i.e. they target different aspects of the disease process). However, it is also thought that topical retinoids affect skin permeability thus enhancing topical agent penetration and increasing the cell turnover of the follicular epithelium which allows more systemic antibiotic to be transported to where the P. acnes resides.

Hormonal therapies

The combined oral contraceptive pill (containing both oestrogen and progesterone) has been shown to be effective in reducing both inflammatory and non-inflammatory acne lesions in women. It does not appear that one particular combined oral contraceptive pill is particularly better than any other. However, this therapeutic option is recommended for women who have acne but who also want birth control, and as such this may be a reasonable choice.

Severe acne

In cases of acne that do not respond to the above oral therapies, the final option is oral isotretinoin. Whilst usually reserved for the severe end of the disease scale, if the acne is proving to be particularly scarring either physically or psychologically it may be considered as an option earlier, when the disease is more moderate.

Isotretinoin

Isotretinoin is a unique therapy because it targets all aspects of the acne disease process. Its effects are summarised below:

Effects of isotretinoin

• Decreases the size of, and secretions from, the sebaceous glands;
• Normalises the follicular keratinisation thus preventing follicular plugging and comedone formation;
• Alters the microenvironment of the follicle so that it is not conducive to P. acnes growth;
• Has an anti-inflammatory effect.

Taking isotretinoin can reduce the sebum production by up to 90%; the effect of this is that P. acnes levels decrease significantly. This in turn leads to a significant decrease in inflammatory lesions. Most cases respond to a single 4–6 month course. Pustules clear more rapidly than papules and nodules and those lesions on the face, upper arms and legs clear more quickly than those on the trunk. Beneficial effect may take 1–2 months to notice and occasionally the acne may worsen in this period of time prior to improving. Patients need to be warned of this fact.

Dosing ranges from 0.1–2.0 mg/kg but in reality doses higher than 1.0 mg/kg are rarely used. In order to minimise potential side effects (especially a flare-up of the acne), a starting dose of 0.5 mg/kg/day for the first month may be advisable. If tolerability is not a problem, this dose may be followed by 1 mg/kg per day for the rest of the course. More severe deeper nodular acne may need a longer treatment period.

Side effects

The side effects of oral isotretinoin are significant and require detailed discussion with the patient to ensure full understanding of the implications of taking the drugs. Because one of the therapeutic benefits of isotretinoin is as a drying agent, patients will experience dry skin, chapped lips, dry eyes and a dry mouth. Secondary skin infections with S. aureus can also occur and should be treated with oral antibiotics or antiseptics (depending on the level of infection). Less frequently patients may experience muscle and back aches and mild headaches, although these usually resolve as the treatment progresses. Nosebleeds and skin fragility may occur. There may be a rise in serum lipid levels. Certain symptoms should be taken very seriously and warrant discontinuation of the treatment immediately. These include:

• severe headache
• decreased night vision
• signs of adverse psychiatric events

Generally, the unwanted side effects will resolve once treatment is discontinued.

Both brands of isotretinoin available in Britain contain soya oil. Some patients with peanut allergy may have cross-reactivity with soya and this needs to be discussed. The capsules that encase the active ingredients contain gelatine which may make taking the tablets unacceptable to someone on a vegetarian diet.

Monitoring

Serum lipid and liver function tests (LFTs) should be monitored. LFTs should be measured as a baseline prior to the commencement of treatment and then checked at 4 and 8 weeks (although exact timings will vary depending on local clinical practice). If blood levels are normal at 8 weeks, further monitoring is probably not necessary as long as the dose remains the same.

Because isotretinoin is teratogenic (it can seriously adversely affect the unborn child), women of child-bearing age must have a negative blood pregnancy test before commencement of therapy. Once a negative pregnancy test has been received, therapy should be started after the 2nd or 3rd day of the first menstrual period after the test. Current practice requires women to undergo monthly urine pregnancy tests prior to a further prescription of isotretinoin being given. It should be noted in the patient record that contraception and pregnancy avoidance advice have been discussed and understood by the patient. Different countries have different policies on the issue of pregnancy avoidance. Grewal-Fry outlines the policy in the USA.

Patients may well already be aware of the potential psychological impacts of taking isotretinoin as these have been extensively covered in the popular press. Whilst severe psychiatric changes are unlikely, patients should be counselled about the possibility of mood swings. Acne itself can lead to high levels of anxiety and it is not always possible to categorically identify mental health changes being as a result of isotretinoin. Very occasionally severe psychiatric changes may occur with some reports of depression and suicidal ideation. A more recent study suggested that there is a link between isotretinoin use and depression in those with acne vulgaris. In a commentary on this article, however, the categoric results were debated with the author questioning whether the research methods allowed the conclusions to be drawn. This author states that ‘Firm conclusions regarding the risk of depression associated with isotretinoin cannot be drawn’, although he confirms that discussions about the possibility of depression should be had with the patient. It is important, therefore that patients are asked about their mood and warned of depression as a potential side effect.

Relapse

Relapse can occur post-isotretinoin therapy. A large study (17,351 first time isotretinoin users over a 20-year period) looked at the prescriptions given to this cohort. It identified that 41% of the patients required further acne treatments (isotretinoin or other systemic or topical therapy). Twenty six percent required a second dose of isotretinoin. The authors looked for predictive factors for relapsing and noted that male subjects and those under the age of 16 were more likely to require further treatment with anti-acne medications. Those who had lower doses and shorter courses also seemed more at risk of needing subsequent anti-acne treatments. Generally, it seems to be the case that if relapse is going to occur it occurs most frequently in the first year post-treatment.

Supporting patients who are taking isotretinoin

Patients being prescribed isotretinoin need to be supported throughout their course of treatment. They need advice with regards to managing a range of issues as shown below.

Checklist of topics that need to be discussed with patients on isotretinoin

• Change in mood
• Contraception (in women)
• Dryness: eyes, mouth, lips, nose (nosebleeds), genitalia
• Joint and/or muscle discomfort
• Sun protection/avoidance
• Avoiding Alcohol
• Waxing/exfoliating
• Avoiding planned surgery/cosmetic procedure
• Should not give blood
• Avoid vitamin supplements

It is not possible to totally ameliorate the drying effects of the drug, but certain protective behaviours may help as shown below.

Advice that may help with the drying effects of isotretinoin

• Avoiding activities which dry the skin, e.g. taking hot showers/baths and using soap;
• Using emollients extensively if skin becomes dry;
• Not using exfolliants or topical treatments that will dry the skin further. All topical acne treatments should be stopped;
• Not waxing;
• Having a chapstick handy for dry lips and using this frequently (may need to be hourly);
• Avoiding exposure to UV radiation and not making use of sunbeds. Always using an oil-free sunscreen of at least SPF 15;
• Wearing soft contact lenses or glasses are likely to be more comfortable than hard contact lenses;
• Using hypromellose eye drops;
• Keeping a bottle of water handy at all times, to sip.

The drug’s effect can be significantly enhanced by taking it with food. It is thought that 40% is absorbed if taken with a meal whereas only 20% is absorbed if it is taken on an empty stomach. The drug can be taken as a single dose once a day or divided and taken as two doses at different times of the day. If the drug dose is to be split, it may be helpful for the patient to use a dosing box to ensure they keep track of their tablets.

Preventing pregnancy is key for female patients who are on isotretinoin. Contraceptive advice should be given to all sexually active patients. Teenagers who attend with parents may be unwilling to admit they are sexually active; however, information should still be given. It is advised that one or preferably two types of contraception are used. Depending on the level of advice needed, the woman may need to be referred to a family planning service to ensure that the most effective and suitable contraception is provided. Contraception must be used for a month prior to the planned start of treatment, during treatment and for 5 weeks after the end of treatment. This is because it takes this length of time for the isotretinoin to be excreted from the body completely.

Although very low levels of isotretinoin may be found in the semen of men on the drug, these are not thought to be sufficient to harm an unborn child or their sexual partner.

Newer treatments with less evidence

Photodynamic therapy

A review carried out in 2008 considered the various uses for photodynamic therapy (PDT) including its potential role in the treatment of acne. PDT is a type of light therapy in which a photosensitising drug is applied to the skin and then a light source is shone onto the skin in order to alter, in some way, targeted cells. The light source varies and can be a laser, filtered xenon arc and metal halide lamps, fluorescent lamps and light emitting diodes. When used for treating cancerous lesions, for example basal cell carcinomas, the process of applying the light to the sensitised skin is to kill the cancer cells. In acne treatments, the exact mechanism is not wholly understood but it is thought that the treatment has a number of effects:

• It has an antimicrobial effect on P. acnes.
• It causes selective damage to sebaceous glands.
• It reduces the keratinocyte shedding and therefore follicular blocking.

A number of studies are reported by Morton et al. (2008) showing beneficial results from PDT both immediately after treatment and at various time points after the treatment. Some studies looked at results after one treatment, others after a series of treatments. Some of the studies reported some unpleasant side effects including pain during treatment, severe erythema after treatment, pustular eruptions and epithelial exfoliation. Most of the studies were small. Few trials compare laser light therapy to conventional treatments but in one case where PDT was compared to 1% adapalene gel the results showed that PDT was no better than the gel. The conclusion drawn by Morton et al. (2008) was that whilst this looks like a promising treatment for inflammatory acne on both the face and back, further work needs to be done on determining the most effective treatment protocols.

A Cochrane review looked at the evidence in relation to laser therapy and found that trials of blue light, blue–red light and infrared light were more successful than light alone particularly when multiple treatments were used.

Psychological impact

A brief discussion with teenagers with acne will quickly illuminate the degree to which ‘spots’ can affect their lives. Appearing as it does, during the emotionally turbulent teenage years, responses to acne range from mild annoyance to depression and even suicidal ideation. Not only can acne cause severe psychological hardship, but it can also prevent young people from achieving their full potential as they avoid applying for the job they really want because it means being in the public eye, for example. Whilst some people with acne may require extensive psychological support and intervention, for the majority having someone who takes their problem seriously and works with them to find a treatment regime which works will be all that is required. For this reason, nurses who care for people with acne need to take the time to find out how the disease is impacting on life and work with the person to find a satisfactory therapy. (See Chapter 6 for further information on the psychological impact of skin disease.)

Conclusion

Acne results from a number of pathological processes which have been outlined in this chapter. Treatments need to be matched to the level of disease severity and in particular the type of acne the patient is experiencing. Patients need to have treatments clearly explained to them including descriptions of possible side effects and the length of time they take to have a therapeutic impact.