Acne Second Line Treatments

Acne second line treatments are those that are usually prescribed by a doctor or nurse after trying self-selected treatments from a pharmacy or supermarket. They will usually contain ingredients licensed to be prescribed only by a health professional.

Nicotinamide (P or GSL)

This is part of the vitamin B (B3) group and has an anti-inflammatory effect on the skin. It can either be prescribed or purchased from a pharmacist. Some patients report that it is very well tolerated when applied to the skin. In the UK there is a cream containing vitamin B3 which is marketed as Freederm.

Topical retinoids (POM)

The chemical name is tretinoin or isotretinoin; both are similar and are based on vitamin A. However, vitamin A creams alone will not achieve the same results because they would need to be used in very high doses, and vitamin A is difficult to keep stable without it ‘going off’ quickly.

This type of treatment has an effect on the development of skin cells and is therefore used in conditions where the hair canal in the skin is blocked or plugged. Its major effect is on the non-inflammatory lesions of acne (black heads and whiteheads). With regular use topical retinoids will cause softening and expulsion of the black heads and also help to prevent them from re-forming.

As retinoid creams and gels can also cause sensitivity to sunlight, always apply a sunscreen if using them on the skin during the day. If you have been advised to apply the cream once a day, then try using it just at night to reduce the exposure to UV daylight.

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Adapalene (POM)

This topical gel is not exactly retinoid but is chemically similar. It can be very helpful on both inflamed and non-in flamed acne. Some patients report that it causes less irritation than some other prescribed topical creams.

Topical antibiotics (POM)

The most commonly used topical agents include the antibiotics tetracycline, erythromycin or clindamycin. These are usually prescribed in an alcoholic solution. They are sometimes mixed in a more soothing lotion or gel formulation. If you know that you would prefer a gel to a lotion, then tell your doctor or nurse before they give you your prescription.

Topical antibiotics work by reducing the level and number of bacteria on the skin. While also reducing the inflammation which is commonly present around the acne spots themselves. They are particularly useful in mild to moderate acne. The antibiotic should be applied twice a day (or as otherwise directed) to all affected areas. Topical antibiotics when used alone have little direct effect on the non-inflamed type of spots (blackheads and whiteheads) so if you have the none inflammatory type of acne as well, then ask your doctor or nurse to prescribe something else in addition which will help the blocked pores.

In general, antibiotics are very well-tolerated by the skin and have few side-effects. Scientific research has proven that applying antibiotics to the skin can be as helpful as taking them by mouth.

Combined topical antibiotics (POM)

To boost the benefits of antibiotics, some pharmaceutical companies have developed acne treatments that combine the antibiotic with other anti-acne ingredients. These have been shown in clinical trials to be better than single active ingredients alone. The added ingredients are usually one of the following:

  • Benzoyl peroxide
  • Zinc
  • Tretinoin
  • Adapalene

Azelaic acid (POM)

This comes in a cream formulation. While it was prescribed quite commonly in the past, it is not very popular as an acne treatment now, and tends to be used in those who have not responded to other treatments. Azelaic acid works well both as an antibacterial treatment and also to help reduce the build-up of dead skin cells. It is not an antibiotic so it doesn’t have the problem of patients becoming resistant to it. As it also targets melanin in the skin, it can be very useful in those who have developed post acne pigmentation (darkened patches of skin colouring). Darker skin types are most likely to develop this type of pigmentation problem, so it is worth asking to try this treatment if you fit into that category.

Zinc sulphate (GSL)

Zinc sulphate capsules at a dose of 220 mg three times a day is a rather old-fashioned treatment for acne but can be quite helpful. The zinc may be used in combination with antibiotics (see above) to improve the effect. It has been shown to promote healing of wounds, such as leg ulcers, but the exact method by which he works in acne is unknown.

Zinc may cause stomach upsets and possibly nausea or diarrhoea. New effervescent preparations seem to help reduce the side-effects. Zinc is also the ingredient in one of the topical antibiotic preparations, with study suggesting it gives a boost to the antibiotic, helping to reduce resistance. This antibiotic and zinc combination is called Zindaclin (in the UK) and contains zinc and clindamycin. An explanation for this added benefit seems hard to find as the way that zinc works in the skin is still not fully understood.

Understanding more about acne medications

There is a combination of over 100 treatments currently available on prescription from your doctor. Some of these will be branded products, meaning that they will be given a brand name by the manufacturer and marketed under this brand name. An example of this is the drug known in the UK has Duac. This is the name given to the brand, but the generic ingredients are benzoyl peroxide 5% and clindamycin 1%. Clindamycin is an antibiotic. As brand names change from time to time, this website focuses on the generic name of the drugs. The generic name will always be included in the medicines information leaflet, also known as the patient information leaflet that comes with your medicine. This includes those medicines that you may have bought from a pharmacy or supermarket. Many people do not bother to read this information, but it is worth taking a few minutes to read through the leaflet to help you understand the following:

  • The possible side-effects that you might experience
  • What the medicine has been prescribed/licenced for
  • How the medicine may interact with other medicines or supplements that you may be taking
  • How to take the treatment to get the maximum benefit from it

It is common for doctors to mix treatments to give the maximum benefit from a variety of key ingredients. This combination may be a mixture of antibiotics with a cream to use on the skin at the same time.

Antibiotic tablets

Some doctors or nurses prefer to prescribe tablets for treating acne. Likewise, some people prefer to take medication by mouth. More recent prescribing guidelines support the use of both topical and oral treatments together. There are many types of antibiotics that are particularly useful for treating acne. As a general rule, these should be given for a period of time, usually no less than six months.

The most common types of antibiotics used are: tetracycline is (of which minocyline is one), erythromycin, minocycline and trimethoprim. These fight the bacteria present in inflamed acne and also help to reduce redness and swelling. They will not, however help with the non-inflamed type of acne and should therefore be taken at the same time as using topical gels, creams or lotions more suitable for this type of acne. Antibiotic tablets do not help black heads or whiteheads.

Taking antibiotics correctly

Taking some types of antibiotics properly may require swallowing them on an empty stomach. To ensure the maximum benefit, tetracycline or oxytetracycline should be taken one hour before food and two hours after last eating. Tetracycline absorption is also be affected by milk, including milk in foods or drinks such as tea coffee. If you have erratic eating habits, ask the doctor or nurse to ensure that the antibiotic they prescribed is not affected by food or drink.

Some antibiotics may reduce the effectiveness of the contraceptive pill for a few weeks when you first start the course. If you are currently taking the contraceptive pill you should discuss this with your doctor if there is a possibility of your becoming pregnant. It is not unusual to experience some degree of stomach upset when taking antibiotics, especially with erythromycin. If they affect you in this way, then talk to your doctor, especially if you are taking other medications such as the contraceptive pill.

Tetracycline

The usual recommended dosage of oxytetracycline is 1 G (1000mg) a day. This will usually mean that you will be need to take up to 4 tablets in one day. Sometimes it will be given in two 500 mg doses, but as the antibiotics do not last long in the system, you may need to space the time out evenly between taking them. If minocycline is being used the normal dose is 50-100 mg a day, and doxycycline, which also falls into this category, is taken at a dose of 100 mg a day. Another type of tetracycline is called limecycline (Tetralysal), which is prescribed at a dose of 408 mg once daily. It is claimed that this antibiotic is better absorbed by the body and is not affected by consuming milk or milk products.

There are reports of increasing resistance to the P.acne is so it is better to use most antibiotics in this group in conjunction with other anti-acne products that don’t contain antibiotics.

Erythromycin and clindamycin

Erythromycin is often prescribed for inflammatory acne. It is considered to be safe to use in pregnancy and during breastfeeding and is therefore used in preference to the tetracyclines by some doctors for women of childbearing age, or even during pregnancy and breastfeeding. Like oxytetracycline, erythromycin should be started at a dose of 1 g a day – usually prescribed in two daily doses of 500 mg. Clindamycin is an antibiotic which is not commonly used to treat acne, but may still be helpful. In low doses, the chances of developing side-effects are reduced. However there is potential for clindamycin to cause serious side effects; the main one of these is known as pseudomembranous colitis. If you experience diarrhoea whilst taking clindamycin and you should consult your doctor urgently because this may be a symptom of pseudomembranous colitis (inflammation of the gut).

Trimethoprim

Trimethoprim can also be used to help acne and is usually prescribed doses of 400 to 600 mg a day, taken in divided doses. It is very effective in acne and used by many dermatologists, but it is not technically licenced for the treatment of acne. Some people feel sick when they take this medicine and may develop unwanted side-effects such as a rash. If this happens to you, then consult your doctor immediately.

Antibiotic resistance

For the last few decades, antibiotics have remained the most commonly prescribed agent for treating acne. Many millions of prescriptions for oral antibiotics are dispensed each year.

Various studies are showing how increasing numbers of patients are becoming resistant to antibiotics. One study reported in the British Journal of Dermatology suggested that up to 51% of 4724 patients had shown resistance. With the increasing rate of antibiotic resistance, this figure is likely to grow even higher. Many researchers and scientists who study microbiology report their fears over the widespread use of antibiotics. They are urging doctors and nurses to rethink the current acne treatment policy of using an antibiotic so readily.

Other studies seem to show a similar pattern of resistance that is growing steadily as more antibiotics are prescribed. This resistance applies to either tablets or creams/lotions and gels applied to the skin. Anyone taking any type of long-term antibiotics (four weeks plus) will have an increased risk of developing a resistance to them. Resistance can happen in a number of ways and to some antibiotics more readily than to others. One of the types most likely to result in resistance is erythromycin, followed by tetracyclines.

If your bacteria have become resistant to certain types of antibiotics, your acne may get worse. A way you might notice this is if you notice that taking your antibiotics no longer seems to help your skin, or altenatively if they fail to work at all, despite taking them correctly and giving them long enough to work. If this is the case, make a note of the name of the antibiotic and tell your doctor or nurse so they can record that you are no longer responding to it. Be aware that doctors don’t always routinely make a note of this, so prompting them to do so might help you next time you need an antibiotic.

It is possible to spread the resistant bacteria to other people through every day is contact. This might be in hugs or cuddling when there is skin contact. Microbiologists have noticed that this contact can result in the other person also becoming resistant to the same antibiotic. This can be seen more in siblings and could explain why a certain antibiotic fails to work, despite the patient taking it as prescribed or never having taken it before.

Further studies on bacteria have resulted in some simple guidelines to how this resistance may be reduced.Following the golden rules below will help.

Golden rules of taking antibiotics

  • Always complete the course. By failing to finish a course, or by simply taking a tablet on a ‘when I remember to’ basis, it is possible to increase the chance of the P.acnes becoming resistant, as well as not giving them enough chance to work.
  • Use benzoyl peroxide as a washout at least once a week. In laboratory tests the benzoyl peroxide works by eliminating the resistance, making some experts recommend that every person taking antibiotics for acne should also use benzoyl peroxide at least once a week.
  • Never share your antibiotics with anyone else as it may cause unwanted side-effects.
  • Doxycycline is the antibiotic most likely to make the skin sensitive to sunlight (phototoxic). Use a good, oil free sunscreen if taking this antibiotic, even in cloudy weather.
  • Tetracycline antibiotics are not suitable for children under 13 or pregnant women as they can cause staining of the teeth and bone development problems.

 

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Contraceptive pills

In women who require contraception, the combined contraceptive pill can be used without problems for those who have acne in the majority of cases and it can significantly improve acne. However, the minipill and progesterone only contraceptives, such as the contraceptive injection Depo-Provera, should be avoided as they can trigger or worsen existing acne. Some women report that the contraceptive pill has given them acne, so discuss any skin changes with your doctor or nurse during your pill checks.

Co-Cyprindiol (POM) - Dianette in the UK

Co-cyprindiol is a contraceptive pill that contains a medium dose of oestrogen, but also a drug called cyproterone acetate that combats the effects of testosterone in the body. It is marketed as Dianette in the UK and is often prescribed for women who have acne and other signs of excessive testosterone such as excessive hair or obesity.

It is not uncommon to see a flare up of the acne in the early stages of taking this treatment. However, it may take longer than the usual guidance of two months to start to see an improvement, so persevere before giving up. For some women, it may take up to 4 months to see the full benefit.

Although this treatment can make a significant improvement, it is prescribed only until the acne clears. Like the majority of other acne treatments, this one does not cure the acne; it simply masks it, although it can do so very well. Coming off it just when the skin can look so good does seem to be illogical, speak to your doctor or nurse if this worries you.

While this treatment can work well for some women, it can have the opposite effect for others. Like many other contraceptives, it may also give rise to mood swings, and unwanted weight gain, headaches or even more serious side-eefects such as blood clots and heart problems. Be aware that coming off this treatment can result in the acne returning, as badly as it was before the treatment started, so it is advisable to discuss using a topical treatment as a crossover which will help reduce any active acne flare ups.

If you require contraception at the same time as being prescribed this treatment, inform the person who has prescribed it for you as it can be prescribed free in England. As with all other contraceptive pills, be especially aware if you experience any dull throbbing pains in the legs or chest. Take any unusual pain seriously and report it to your doctor or practice nurse immediately.

Case study -Sandra

"I found the pill Dianette really fantastic, although it took a long time to kick in. I almost gave up on it but then started to see my skin improved so dramatically that I stuck with it and felt like a new woman – I kept raving about my miracle cure and was recommending it everyone knew who had acne, (even boy wanted to know if he could try it!). But the bad news came when my GP told me I would have to come off it because I had been on it for longer than I was meant to (I had been on it for two years). I felt disappointed, but because my skin was so good, I thought I didn’t need it any more anyway. I was so shocked when, within just three weeks, my skin got noticeably worse. It was just awful looking at my acne return. Within about two months it was like I had never taken the treatment at all. I was devastated. I went back to my doctor in tears and begged her to put me back on it. Luckily she agreed, after we discussed all the risks of going back on it again and for taking it longer than recommended. That was over two years ago now and I’m frightened she will take me off it again. We talked about it last time I went to see her and she has suggested that I take a course of antibiotics whilst I come off the pill to help protect the skin from another acne flare-up. I will have to come off it eventually, so this sounds like good advice." 

Isotretinoin (Roaccutane or Accutane)

This is a controversial acne treatment that is considered, by some to be a very powerful last line option.

Newspapers have both hailed its miracle benefits and condemned its reputed nasty side-effects. This section will take a look at the facts behind the headlines and allow you to draw your own conclusions.

Who’s it for?

Under tight European guidelines this drug, based on a synthetic form of vitamin A, can be prescribed only under the supervision of a consultant dermatologist. UK guidance on when this tablet can be prescribed is quite clear and patients suitable for it should fulfil the following criteria:

  1. They have not responded to at least two courses of antibiotics
  2. The presence of nodulo-cystic acne (the type most likely to scar)
  3. They have evidence of acne scars
  4. They are psychologically distressed by their acne

How it works

Isotretinoin targets the sebacious glands and, in effect, shrinks them. This also has an effect upon the oil (sebum) production itself. The skin, soon after starting treatment, begins to have reduced levels of oil, which will often result in the skin becoming excessively dry. This dryness will often become more obvious through the course of treatment. Ironically, it may require the use of emollients usually reserved for dry skin to help maintain a normal balance.

Although the main way isotretinoin works is by targeting the oil glands, it also works on the skin cells, affecting how they are shed and reducing their blocking action within the hair follicle. As a result of these two effects, the main attraction for the bacteria on the skin is wiped out. The bacteria have nowhere to multiply so the redness, inflammation and pus- filled spots disappear.

A usual course of isotretinoin will last between four and six months, depending on how well the skin response. One course alone is often enough, and while repeated courses can be given, the skin is usually so improved that it is not necessary. For some, it may be likely they will need to use acne medication in the future, but the acne is usually much less severe and easier to manage.

Side-effects

While the side-effects listed below are not the only ones, they are considered the most common. The chances of getting one or more from the list below is high, unlike with many other medicines. Anticipating the side-effects and taking steps to ensure they are either counteracted or carefully managed can help a person maintain a sense of control over their skin as well as side-effects. The main side-effects are:

  • Dryness of the skin on the nose, eyes and lips. Sometimes the skin may become cracked and very dry, which may lead to bleeding in these areas
  • Headaches
  • Hair thinning (reversible)
  • Muscle aches and pains
  • Sensitivity to sunlight
  • Serious risks of abnormalities to an unborn baby, including death of the foetus

Managing side-effects

Acne flare-ups:

It is usual to experience a flare-up of acne anywhere between 10 days and six weeks into taking isotretinoin. This can be very distressing for a lot of patients; however, if it is expected, it is less likely to produce feelings of despondency. If any flare-up persists beyond this period, or if the acne worsens rather than improves overall, then speak to your dermatologist or dermatology nurse about it. For some people a short course of steroids may be given to help reduce a flare-up, or the dose may be adjusted to help reduce side-effects.

Danger in pregnancy:

All women of childbearing age will be given careful counselling by a dermatologist or assigned to a specialist dermatology nurse who will support them during the course of medication. Women must be aware that the drug is incredibly dangerous to unborn babies, and taking it at the same time bank as pregnancy are often results in abnormalities or miscarriage. This can happen with even taking a single isotretinoin tablet, so it’s dangers cannot be overstated. Despite careful contraceptive planning and monthly pregnancy tests being carried out during the full course of treatment, some women have still fallen pregnant. This treatment does not have an effect on future fertility and is generally considered safe to try for a baby three months after completing a course, so anyone wishing for a baby needn’t feel this treatment isn’t for them. The monthly pregnancy tests taken under the supervision of either the dermatologist or dermatology nurse are time-consuming but serve as a reminder of how important avoiding pregnancy is during treatment.

Dryness:

Dryness of the eyes nose and lips is very common. To help prepare for this, buy plenty of lip balm (any type will do) and make sure that there is enough to allow for everyday life. For example, put one in the car, in your handbag, in schoolbags and jackets, by the bed, next to the computer - to be able to grab in an instant. Applying plenty of lip balm will help reduce extreme drying and cracked lips, which may lead to bleeding. Lip balm, or simple petroleum jelly (Vaseline), can also be used in the nose to keep it moist. Artificial eye drops can help keep the eyes from overdrying. Some doctors recommend avoiding the use of contact lenses during this time, so make sure you have up-to-date prescription pair of glasses ready to wear if needed.

Sun sensitivity:

Reducing the chances of sensitivity to sunlight can be helped by applying plenty of oil free sunscreen, ideally a minimum of factor 30, whatever the weather. This should be used every day during the course of treatment and applied regularly as directed.

Waxing and exfoliating:

Oral isotretinoin makes the skin more fragile and liable to scar. Plucking of hair and waxing should be avoided completely during the course and for one month afterwards.

Muscle aches and pains:

Muscle aches and pains are more common in those who are highly active. If you are a keen sports man or woman, tell the doctor when isotretinoin is prescribed and be prepared to experience some muscle pains and aches. If your sport is seasonal, such as football, discuss starting a course of isotretinoin at the end of the season to reduce the amount of exercise and physical stress the body undertakes during this period.

Isotretinoin and depression

Much of the publicity surrounding this treatment also includes concerns about depression. All UK dermatologists are well aware of this potential side-effect and should always counsel patients before starting a course. In a few cases where depression has been reported as a side-effect, some people have taken their own lives or been deeply affected by a sudden onset of depressive symptoms where they felt bad enough to want to take their own life. It is not really possible to tell who might feel like this on a course, and certainly many patients report no such side-effect at all.

One study at Boston University in the year 2000 questioned 20,000 acne patients. Some were using isotretinoin for the acne, others antibiotics. The team of research scientists compare the risk of depression between the two groups and found that it was comparable in both.

However, in cases where patients report experiences thing depressive symptoms while taking isotretinoin, there seems to be a slightly increased risk of suicidal feelings occurring in those who have had a previous episode of depression before taking isotretinoin. Also some patients have reported feelings of anxiety or aggressive behaviour. For this reason, the treatment should be used with caution in these people and only after careful consideration of all the risks and benefits.

Any serious changes in mood may be difficult to notice when it happens to you; being able to get an outside perception will be very helpful, especially if the changes are gradual. It might help to enlist someone you trust before starting a course of isotretinoin to be your ‘mood gauge’; ask them to share an honest opinion on any signs of changes that may indicate depression. These changes may be subtle or obvious (or completely absent of course), but it has given many worried parents, friends and patients a degree of reassurance to know there is someone looking out for them in this way. As part of this agreement you may wish to discuss what to do should you show such signs and draw up your own depression action plan to decide in advance about anything you will want to do, even if that means having to withdraw from treatment. All this can be discussed both with your chosen person and your doctor or nurse who has prescribed the treatment.

Is isotretinoin the right treatment for me?

This is up to each individual. A decision on whether to take it or not should depend upon full discussion with a dermatologist and consideration of whether the benefits are believed outweigh the risks sufficiently. If a person who is offered this treatment has one of the types of acne described in the article on variations of acne known as acne conglobata or acne fulminans, and if they are fully aware of the side-effects and how to manage them, then weighing up the pros and cons might be straightforward. Nobody should tell another person whether they think it is right for them; this includes doctors and nurses, some of whom have reportedly scared patients because they are ignorant of the drugs benefits and focus only on the risks. A decision to take it should be based firstly upon medical opinion. If the doctor prescribing it is satisfied that the treatment is appropriate for the type of acne, then each patient must decide for themselves. Sometimes it may not feel right, or the patient may feel very anxious about taking it. In the circumstances it might be sensible to try alternative prescribed acne medications and defer a decision about isotretinoin to another time.

Some helpful questions to ask yourself may include:

  • Am I satisfied that I have given other treatments a good enough chance to really work?
  • Did I take all use them as I should’ve done?
  • Is my skin scarring?
  • Am I so unhappy with how I look that it is significantly affecting my self-esteem?
  • Do I understand the benefits versus the risks? Have I put the right questions to the right people?
  • Should I try an alternative acne treatment first? What other options might I have? Am I prepared to put up with the side-effects?

Isotretinoin cannot be guaranteed to work for everybody, but it is still considered a gold standard treatment for hard-to-treat, scarring acne. While it may not give a permanent solution, it can help to knock the acne switch down a notch or two reducing the size of the oil-producing glands. Some doctors have reported that between 30 and 50% of people taking a course of isotretinoin find that their acne returns to some degree. However, further courses can be offered.

Taking a second or third course of isotretinoin

Some dermatologists see patients for a second, third or even fourth time following the initial course of this treatment. Taking more than one course is acceptable unless the first course gave rise to concerns about side-effects including depression. For some, the acne does return but not as aggressively as before, and a course of other prescribed treatment will be sufficient to keep it firmly under control. There will usually need to be a gap between courses to give the skin a chance to recover and to make a reassessment before a decision to re-prescribe is taken.

Case study – Lottie

"My skin had been getting worse in my last couple of years at school. I was given the nickname ‘Spotty Lottie’, which seemed to stick and really got on my nerves. I was self-conscious about my skin and found myself making excuses not to go out when it was really bad. I remember one spot I had which was evil – it was literally on the end of my nose and not only was it is huge, it was really, really painful. It was all I could see on the outside of my vision and for me it was the last straw.

I had tried loads of other things for my skin. Dianette worked really well but my family named me ‘the nightmare child from hell’ when I was on it and I had to come off it before my family disowned me! I think all my feelings about my skin came to a head with that last huge boil. I decided that I really had to sort it out so I would never have to look in the mirror and feel so repulsed again.

My doctor was really helpful and he referred me to the consultant dermatologist who suggested that I try Roaacutane (isotretinoin). I had an appointment with the nurse who spent a long time with me going over everything I might need to know about it, and was asked to take a pregnancy test there and then so I could get started on the treatment straight away. I didn’t think it would happen that fast, but I felt I had been given enough time to ask my questions and appreciate the importance of not getting pregnant. I decided that I would abstain from sex during my treatment just to be sure – that’s how important it was me it was to me to clear my skin up!

I had a couple of hitches during the course. Firstly my skin became so dry that I found it almost impossible to keep it moist; then my lips tried so badly that they would bleed every morning – I felt like a smile was my biggest torture – so I decided to give up smiling to (actually I learnt that I smiled more than I thought by having to do this!). I found a brilliant intensive care at little balm and use loads of it – every day, every hour, every time I ate or drank anything – and it did help.

When I started at university I had to move away. As I have been instructed to go and see the nurse each month and give a pregnancy test, this was going to be very difficult – my university was 170 miles away. Luckily – the dermatology nurse at the hospital, Julie, was brilliant and we made an arrangement with my university doctor that my results would be faxed to the dermatology unit in my home town; they would then issue the prescription which would be sent to me. This was the best solution, and although it was a pain for everyone it did work out well in the end.

That was five years ago and my skin is absolutely great now – it’s what I would class as normal and I feel like I’ve been liberated. My eyes can still be itchy at times; especially the skin around the eyes which never seems to be anything but dry, but being spot free is great. I can live with the scarring, but I can’t imagine not having taken the isotretinoin – the thought of still having skin like that is really depressing."

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