What causes acne and pimples ?

Acne is the most common skin disorder in the United States, affecting 40 to 50 million persons of all ages and races ¹⁾. Acne causes pimples, zits, whiteheads or blackheads. Acne, also known as acne vulgaris, “vulgaris” the medical term for “common”. Common acne is given this name – acne vulgaris – to distinguish it from less common variants of acne (see acne types below).

Acne is thought to be caused by multiple factors. Overproduction of a normal oil on the skin, called sebum, increases under the influence of hormones. Acne is common during puberty when hormones go into overdrive, causing the skin to overproduce sebum. This, coupled with insufficient shedding of exfoliating dead skin cells, plugs hair follicles. The plugged follicle can become inflamed and have increased growth of normal skin bacteria, Cutibacterium acnes (previously called Proprionibacterium acnes) ²⁾. Pimples form when hair follicles under your skin become plugged with oil and dead skin cells ³⁾. Because many oil-producing glands are on the forehead, nose, and chin, this area — the T-zone — is where a person is most prone to pimples. If a pore gets clogged up and closes but bulges out from the skin, you’re left with a whitehead. If a pore gets clogged up but stays open, the top surface can darken and you’re left with a blackhead. Sometimes the wall of the pore opens, allowing sebum, bacteria, and dead skin cells to make their way under the skin — and you’re left with a small, red bump called a pimple (sometimes pimples have a pus-filled top from the body’s reaction to the bacterial infection). Clogged pores that open up very deep in the skin can cause nodules, which are infected lumps or cysts that are bigger than pimples and can be painful. Occasionally, large cysts that seem like acne may be boils caused by a staph infection.

Acne is often confined to the face but it may involve neck, chest and back. Acne affects males and females of all races and ethnicities. Acne affects most teens to some extent. Close to 100% of people between the ages 12–17 have at least an occasional whitehead or blackhead. Acne tends to improve after the age of 25 years but may persist, especially in females. However, acne is not restricted to any age group; adults can also get acne too. In fact, one fifth of women between the ages 25–40 suffer from adult acne. Furthermore, some women who had very little to no acne before age 20 may develop acne in adulthood. The peak for women taking isotretinoin in one study was 24 years of age. While acne is not a life-threatening condition, it can be upsetting and disfiguring.

Acne is characterized by:

• Open and closed uninflamed comedones (blackheads and whiteheads)
• Inflamed papules and pustules
• In severe acne, nodules and pseudocysts
• Post-inflammatory erythematous or pigmented macules and scars
• Adverse social and psychological effects

Severity is classified as mild, moderate or severe.

• Mild acne: total lesion count <30
• Moderate acne: total lesion count 30–125
• Severe acne: total lesion count >125

To help prevent the oil buildup that can contribute to acne, wash your face once or twice a day with a mild soap and warm water. Don’t scrub your face hard with a washcloth — acne can’t be scrubbed away, and scrubbing may actually make it worse by irritating the skin and pores. Try cleansing your face as gently as you can.

If you wear makeup or sunscreen, make sure it’s labeled “noncomedogenic” or “nonacnegenic.” This means it won’t clog your pores and contribute to acne. And when you’re washing your face, be sure you take the time to remove all of your makeup so it doesn’t clog your pores.

If you use hair sprays or gels, try to keep them away from your face, as they also can clog pores. If you have long hair that touches your face, be sure to wash it often enough to keep oil away. And if you have an after-school job that puts you in contact with oil — like in a fast-food restaurant or gas station, for example — be sure to wash your face well when you get home. It also can help to wash your face after you’ve been exercising.

Most pimples form on the face, neck, back, chest, and shoulders – however you can also get acne and pimples on your butt, nose, ear, eyelid and lip. Nearly all of us have acne at some time or another, but it is common in teenagers and young adults. Acne mainly affects adolescents (and can start as young as 8 years old), but acne may persist, begin or become more severe in adulthood. Acne is not serious, but it can cause scars.

Sometimes even though you wash properly and try lotions and oil-free makeup, you can still get acne — and this is totally normal. In fact, some girls who normally have a handle on their acne may find that it comes out a few days before they get their period. This is called premenstrual acne, and about 7 out of 10 women get it from changes in hormones in the body.

No one knows exactly what causes acne. Hormone changes, such as those during the teenage years and pregnancy, probably play a role. Medications such as lithium, cortisone, hormones, iodides, some seizure medications, or isoniazid can also cause acne lesions.

There are many myths about what causes acne. Chocolate and greasy foods are often blamed, but there is little evidence that foods have much effect on acne in most people. Another common myth is that dirty skin causes acne; however, blackheads and pimples are not caused by dirt. Stress doesn’t cause acne, but stress can make it worse.

The Skin

The skin (integument) is the body’s largest and heaviest organ. In adults, the skin covers an area of 1.5 to 2.0 m² and accounts for about 15% of the body weight.

The skin consists of two layers:

1. a stratified squamous epithelium called the Epidermis (Figure 2) and
2. a deeper connective tissue layer called the Dermis (Figure 1).

The accessory structures of skin include hair, nails, and a variety of multicellular exocrine glands. These structures are located in the dermis and protrude through the epidermis to the surface.

Figure 1. Skin and Hair structure

Figure 2. Structure and skin cells of the Epidermis

Figure 3. Acne severity grades

Here are some tips to help prevent acne breakouts and clear them up as fast as possible:

• Wash your face twice a day (no more) with warm water and a mild soap made for people with acne. Gently massage your face with circular motions. Don’t scrub. Overwashing and scrubbing can cause skin to become irritated. After cleansing, the American Academy of Dermatology recommends applying an over-the-counter (no prescription needed) lotion containing benzoyl peroxide.

• Remove your makeup before you go to sleep. When buying makeup, make sure you choose brands that say “noncomedogenic” or “nonacnegenic” on the label. And even if a product is labeled nonacnegenic or noncomedogenic, you should stop using it and talk to your doctor if you notice that it’s irritating your skin or seems to cause breakouts. Throw away old makeup that smells or looks different from when you first bought it.
• Don’t pop pimples. It’s tempting, but here’s why you shouldn’t: Popping pimples can push infected material further into the skin, leading to more swelling and redness, and even scarring. If you notice a pimple coming before a big event, like the prom, a dermatologist can often treat it for you with less risk of scarring or infection.

• Avoid touching your face with your fingers or leaning your face on objects that collect sebum and skin residue like your phone. Touching your face can spread the bacteria that cause pores to become inflamed and irritated. To keep bacteria at bay, wash your hands before applying anything to your face, such as treatment creams or makeup.

• Protect your skin from the sun. It may seem like a tan masks acne, but it’s only temporary. A tan may worsen your acne, not improve it. Tanning also causes damage to skin that will eventually lead to wrinkles and increase your risk of skin cancer.

• If you wear glasses or sunglasses, make sure you clean them frequently to keep oil from clogging the pores around your eyes and nose.

• Keep hair clean and out of your face to prevent additional dirt and oil from clogging your pores.

• If you get acne on your body, try not to wear tight clothes. They don’t allow skin to breathe and may cause irritation. Scarves, headbands, and caps can collect dirt and oil, too.

Treatments for acne include medicines and creams, but acne can be persistent. The pimples and bumps heal slowly and when one begins to go away, others seem to crop up.

Depending on its severity, acne can cause emotional distress and scar the skin. The earlier you start treatment, the lower your risk of such problems.

Acne friendly skin care essential

To get the results you expect from treatment, you’ll also need acne friendly skin care. Without it, your acne can flare, even when you’re treating it.

To help their patients with back acne get the best results, dermatologists recommend the following ⁴⁾:

1) Develop these habits when working out or getting sweaty:

• Wear loose-fitting workout clothes made of cotton or sweat-wicking fabric.
• Wash workout clothes after each use.
• Shower and change clothes ASAP after working out (or doing anything that causes you to sweat).

If you cannot shower immediately, use an oil-free cleansing wipe to gently wipe off your sweaty skin. You’ll also want to change out of sweaty clothes.

2) Cleanse your skin gently. Scrubbing skin with acne may seem best, but this actually worsens acne. When washing your back and applying acne treatment, you want to be gentle.

3) Stop irritating your skin with harsh skin care products. Antibacterial soaps, astringents, and abrasive scrubs can worsen acne. Ditto for loofahs, back brushes, and buff puffs. For best results, you’ll want to use gentle, fragrance-free skin care products.

4) Use oil-free skin care products and cosmetics. The packaging may read “non-comedogenic,” “non-acnegenic,” “won’t clog pores,” or “oil-free.

5) Avoid using anything that rubs against your back, such as a backpack. Anything that rubs against your back can irritate your skin, causing back acne to flare. Swap a backpack for a handheld bag. If you carry a purse on your shoulder, place the strap on your arm.

6) Resist the temptation to pick and pop acne, even on your back. This will only worsen acne.

7) Protect your skin from the sun. People often believe that the sun’s rays will help clear acne, but the sun can actually worsen acne. The sun’s rays tend to darken acne and cause it to last longer.

When shopping for sunscreen, choose one that says the following on the packaging:

• Non-comedogenic (or oil-free)
• SPF 30 (or higher)
• Broad-spectrum protection (UVA/UVB protection)
• Water resistance

You can help clear acne by always wearing oil-free sunscreen when outdoors. You’ll want to apply sunscreen to all skin that clothes won’t cover.

8) Change your sheets and pillowcases weekly. Clean sheets and pillowcases are essential for clearing back acne. You may want to change pillowcases twice a week. By the end of a week, sheets and pillowcases are swarming with dead skin cells and bacteria.

When washing sheets and pillowcases, be sure to use fragrance-free detergent. If you like fabric softener, it, too, should be fragrance-free.

Management of mild acne

Most patients with mild acne can be treated with topical treatment (gels, solutions and lotions) that can be obtained over-the-counter without prescription. Most people just use topical agents for facial skin as they can be difficult to apply to one’s back. Extra vitamins and minerals have not been proved to help.

• Wash affected areas twice daily with a mild cleanser and water or an antiseptic wash.
• Acne products should be applied to all areas affected by acne, rather than just put on individual spots.
• A thin smear should only be applied to dry clean skin at nighttime.
• Acne products may work better if applied in the morning as well.
• They often cause dryness particularly in the first 2–4 weeks of use. This is partly how they work. The skin usually adjusts to this.
• Apply an oil-free moisturizer only if the affected skin is obviously peeling.
• Avoid applying oily cosmetics such as foundation or sunscreen.
• It may take several weeks or even months to see convincing improvement.
• Discontinue using product if severe irritation results. See your doctor for advice.

Acne Cleansers

Acne cleansers help to remove excess oil from the skin, as well as make-up, sweat, and dirt, which can all accumulate on the surface of the skin. Cleansing is important for general skin hygiene too, as it is easy for all of these substances to build up on the skin.

General Tips:

• Do not over-cleanse as it will worsen, and not improve your acne
• Choose appropriate products for your skin type
• Be patient—topical medication takes time to work, and often worsen acne when first used until the skin becomes used to it
• Look for non-comedogenic cleansers cosmetics as they are less likely to aggravate your acne

It is important not to over-cleanse the skin. Acne cleansers can help to reduce oil and dirt, and contains ingredients that help reduce acne. They are an important part of acne treatment and maintenance. It is important to note, however, that more is not better when it comes to acne treatment. For most cleansers, one wash at night should be sufficient, and the skin should be patted dry gently.

Suitable topical agents for mild acne that can be obtained without prescription include:

• Antiseptic washes with triclosan or benoyl peroxide (Acnederm wash™, Benzac™ AC Wash, Dalacin™ T Prewash, Oxy™ Daily Skin Wash)
• Mild salicylic acid preparations to exfoliate and unplug the follicles (Neutrogena® Oil-free Acne Wash and many others)
• Benzoyl peroxide cream/lotion/gel (PanOxyl™ Acne Gel, Brevoxyl™ Cream, Oxy-10™, Clearasil™ Ultra Acne Cream, Benzac AC Gel)
• Azelaic acid (Skinoren™ cream, Acnederm™ medicated lotion, Azclear™ Action Lotion)
• Hydrogen peroxide in stabilised cream (Crystacide®, Crystaderm™)
• Immune defence proteins (Epiology®)
• Tea tree oil, bee venom, polyphenols and other products for which evidence of efficacy is limited.

How to apply medicine to your back

• For treatment to work, you must get it on your back. Investing in a lotion applicator for the back can help you apply the medicine where you want it.
• If you’re not sure where to find one of these, just search online for a “lotion applicator for the back.”

Benzoyl peroxide (emollient foam wash) + Retinoid (adapalene 0.1% gel)

Benzoyl Peroxide (emollient foam wash): This helps to kill the bacteria that cause acne. Used daily, it can help control back acne and reduce flares.

Benzoyl peroxide is an excellent antimicrobial agent in the treatment of acne. It kills Cutibacterium acnes in such a fundamental way that resistance cannot occur. It is over-the-counter (OTC) and usually should be purchased by price as most consumers are happy with the cheaper brands. As with all topical acne treatments, spot treating is not recommended. Apply all over acne-prone skin daily to prevent lesions. You should be aware that benzoyl peroxide bleaches carpet, clothing, and towels–but not skin or hair. The lower doses are preferred, e.g., 2.5-5%. The benzoyl peroxide washes reduce Cutibacterium acnes counts less than the leave-on benzoyl peroxide formulations, but they are more patient-friendly. The longer the contact time (at least 20 seconds) the better. They seem to work best on the face, but not so much on the trunk.

Unfortunately, one study showed that most patient do NOT follow the recommendation to buy and use OTC benzoyl peroxide. In that study of 84 patients told to buy and use a benzoyl peroxide-containing product, only 64% bought an OTC product, and of those products only 32% had benzoyl peroxide as the active ingredient. Thus, only 20% of patient told to buy an OTC benzoyl peroxide-containing product actually did so ⁵⁾. Implications for therapy include better education of the patient, follow up calls to reinforce, specific recommendations for products to purchase and to give benzoyl peroxide as a prescription, e.g. benzoyl peroxide with erythromycin, benzoyl peroxide with adapalene (adapalene 0.1% gel).

Studies show that the key to getting results from a benzoyl peroxide wash is to leave it on your back for 2 to 5 minutes before rinsing it off.

Letting the benzoyl peroxide sit on your skin for a few minutes has two advantages:

1. This approach helps the medicine penetrate your skin. Skin is thicker on the back than on the face.
2. Rinsing it off prevents bleached clothes, sheets, and towels. Benzoyl peroxide is known to bleach fabrics.

You’ll find over-the-counter (OTC) benzoyl peroxide foaming washes in different strengths. Using a product that contains 5.3% benzoyl peroxide is less likely to cause irritated skin, dryness, or peeling.

If you feel that you need stronger medicine, you can start with a foaming wash that contains 10% benzoyl peroxide. That’s the strongest concentration of benzoyl peroxide that you can buy without a prescription.

Retinoid (adapalene 0.1% gel): Using this along with benzoyl peroxide can improve your results. This OTC retinoid can help unclog pores, which will help the benzoyl peroxide work better.

Topical Retinoids

Tretinoin, adapalene, and tazarotene are all excellent topical agents for reducing the blackheads and whiteheads of acne. They are applied once a day, usually at night (with benzoyl peroxide in the morning). Peeling and redness are the main side effects. Tazarotene is the strongest, but also the most irritating. Adapalene may be the least irritating. A combination product of benzoyl peroxide and adapalene (Epiduo in the US) is available and is a nice product. Combining a topical retinoid with a salicylic acid-containing cleanser often causes too much irritation and should be avoided.

Irritation with the use of topical retinoids is common. Strategies to combat this include:

• Starting therapy every other night.
• Delaying the application of the retinoid after washing the face (e.g. 20 min-1 hour).
• Using a mild cleanser instead of soap.
• Using a non-comedogenic moisturizer 2/day.
• Applying a topical steroid (e.g. triamcinolone 0.025% cream) to the face after applying the retinoid.

One split-face study found the addition of triamcinolone 0.025% to the first 4 weeks of 0.05% tretinoin treatment greatly decreased dryness and peeling, increased compliance, and decreased acne severity ⁶⁾. No atrophy was observed.

Dermatologists recommend applying adapalene after you shower or before going to bed. Again, you want to apply it daily.

Topical agents for mild acne which require prescription include:

• Antibiotics, such as clindamycin solution (Topicil™, ClindaTech™) or erythromycin solution (Stiemycin™) and gel (Eryacne™), which are best used with benzoyl peroxide or azelaic acid to reduce the chance of antibiotic resistance
• Retinoids i.e. tretinoin (ReTrieve™, Retin-A™), isotretinoin (Isotrex™), adapalene (Differin™); in some countries, adapalene is available without prescription.

Combination prescription topicals include clindamycin / benzoyl peroxide (Duac™) and adapalene/benzoyl peroxide gel (Epiduo™).

Topical clindamycin and erythromycin have been used for years in the treatment of acne. Unfortunately, that prolonged use has lead to widespread Cutibacterium acnes resistance and their efficacy is now much less.

Lights and lasers including blue light have been found to be safe and helpful for mild to moderate acne when oral medications are unhelpful or unsuitable.

See your doctor or dermatologist for advice if your pimples fail to clear up within six weeks or you have severe acne.

Does putting toothpaste on a pimple make it go away ?

You may have heard this suggestion, but experts on acne say don’t try it.

Toothpaste could make that spot on your skin even more red, irritated, and noticeable. Why? Today, there are so many different kinds of toothpastes — and lots of them contain ingredients that can hurt your skin. It makes sense that you don’t want all that whitening, tartar-reducing stuff on your face.

It’s better to use medicine designed to treat pimples. Try acne creams or gels that contain 1% salicylic acid or 2.5% benzoyl peroxide. Your doctor also can help you deal with pimples and recommend other medicines, if needed.

Can I pop a pimple if I can see the white part ?

If you look in the mirror and see a pimple, don’t touch it, squeeze it, or pick at it. This might be hard to do — it can be pretty tempting to try to get rid of a pimple. But when you play around with pimples, you can cause even more inflammation by popping them or opening them up. More important, though, picking at pimples can leave tiny, permanent scars on your face.

Because popping isn’t the way to go, patience is the key. Your pimple will disappear on its own, and by leaving it alone you’re less likely to be left with any reminders that it was there.

To dry a pimple up faster, apply 5% benzoyl peroxide gel or cream once or twice a day. You can find these over-the-counter treatments at most drugstores, grocery stores, and other stores that sell skin-care products.

If you’re concerned about acne, talk to your doctor or a dermatologist.

I have lots of red marks on my face from squeezing pimples. Is there anything I can do to make them fade ?

Most red or brown marks left after a pimple is popped will eventually fade or disappear, but it may take up to a year for this to happen.

If your acne marks or scars are severe or you’re upset about them, talk to a doctor. Your doctor might be able to suggest things you can do, especially if the marks have also left raised or indented scars.

In the future, try to avoid pimple popping, so that you don’t have to worry about marks or scars.

Does exercise really help your skin and acne ?

Exercise has many benefits, like feeling good about yourself, being in top shape, looking good, and being mentally sharp.

It’s not clear whether exercise helps improve acne, but it definitely doesn’t hurt. The only exception may be the athlete who wears equipment such as protective pads and chin straps on helmets that rub against the skin and may make acne worse in those areas. But fear not, your run-of-the-mill favorite gym T-shirts won’t cause any such problems.

Whether you have a lot of acne or just the occasional zit, exercise may actually help because it increases blood flow, unclogs pores through sweating, and reduces stress, a major acne trigger.

The bottom line is that the benefits of exercising, whether they include acne reduction or not, outweigh the benefits of sitting around on the couch. Who cares if you have great skin and a good complexion if you aren’t taking care of the rest of your body?

Do certain foods cause acne ?

Some studies suggest there is a link between the food we eat and acne. It is very difficult to study the role of diet and acne.

Acne is reported to be less common in people that have a diet with lower glycemic index, e.g., natives from Kitava and Papua New Guinea, the Ache people of Paraguay, Inuits and rural residents of Kenya, Zambia and Bantu. These people tend to become sexually mature at a later age than in the cities where higher glycemic index foods are consumed. Early puberty is associated with earlier onset and more severe acne that tends to peak at the time of full maturity (age 16 to 18).

Several studies, criticised for their quality, have shown benefits in acne from a low-glycemic, low-protein, low-fat and low-dairy diet. The reasons for these benefits are thought to relate to the effects of these foods on insulin and insulin-like growth factor-1 (IGF-1).

Insulin induces male hormones (androgens), glucocorticoids and growth factors. These provoke keratinisation (scaling) of the hair follicle and sebum production. An increase in sebum production and keratinisation is a factor in the appearance of acne.

Foods that increase insulin production

Foods that increase insulin levels have a high glycemic index. The glycemic index is a measurement of how carbohydrates have an effect on our blood sugar levels. When we eat foods with a high glycaemic index, such as white bread and baked goods, our blood sugar level rises. This increases the amount of insulin produced in our body.

Although cow’s milk has a low glycemic index, it contains androgens, oestrogen, progesterone and glucocorticoids, which also provoke keratinisation and sebum production. Milk also contains amino acids (eg arginine, leucine, and phenylalanine) that produce insulin when combined with carbohydrates. Other components of milk that might induce comedones include whey proteins and iodine.

Caffeine, theobromine, and serotonin found in chocolate may also increase insulin production.

Food containing fatty acids

Fatty acids are needed to form sebum. Studies show that some monounsaturated fatty-acids, such as sapienic acid and some vegetable oils, can increase sebum production. However, the essential fatty acids linoleic, linolenic and gamma linolenic acid can unblock the follicles and reduce sebum production.

Suitable food if you have acne

Some people with acne have reported improvement in their skin when they follow a low-glycemic index diet and increase their consumption of whole grains, fresh fruits and vegetables, fish, olive oil, garlic, while keeping their wine consumption moderate.

It’s a good idea to drink less milk and eat less of high glycemic index foods such as sugar, biscuits, cakes, ice creams and bottled drinks. Reducing your intake of meat and amino acid supplements may also help.

Seek medical help if you are concerned about your skin, as changing diet does not always help.

Why does acne eventually clear up ?

We do not understand why acne eventually clears up. It does not always coincide with a reduction in sebum production or with a reduction in the number of bacteria. It may relate to changes in the sebaceous glands themselves or to the activity of the immune system.

Acne Types

• Acne vulgaris: Common acne
• Nodulocystic acne: Nodulocystic acne is a severe form of acne affecting the face, chest and back. It is characterised by multiple inflamed and uninflamed nodules and frequently, scars. It is more common in males. The name implies there are nodules (firm lumps) and cysts (fluid-filled cavities lined by epithelium). However, the fluctuant lesions are not true cysts as there is no lining. They are sometimes called pseudocysts.
• Acne excorieé
• Acne fulminans
• Infantile and childhood acne
• Acne in pregnancy
• Acne due to medicines
• Adult acne
• Acne scarring
• Chloracne
• Comedonal acne
• Follicular occlusion syndrome
• Pyoderma faciale

Why is acne often most severe during teenage years ?

The precise reasons that acne is most severe during the teenage years are being studied. There are several theories.

There are higher levels of sex hormones after puberty than in younger children.

• Sex hormones are converted in the skin to dihydrotestosterone (DHT), which stimulates sebaceous (oil) glands at the base of hair follicles to enlarge.
• The sebaceous glands produce sebum. Changes in sebum composition may lead to acne lesions.
• The activated sebaceous gland cells (sebocytes) also produce proinflammatory factors, including lipid peroxides, cytokines, peptidases and neuropeptides.
• Hair follicles are tiny canals that open into skin pores (tiny holes) on the skin surface. The follicles normally carry sebum and keratin (scale) from dead skin cells to the surface. Inflammation and debris leads to blockage of the skin pores – forming comedones.
• The wall of the follicle may then rupture, increasing an inflammatory response.
• Bacteria within the hair follicle may enhance inflammatory lesions.

While acne is most common in adolescents, acne can affect people of all ages and all races. It usually becomes less of a problem after the age of 25 years, although about 15% of women and 5% of men continue to have acne as adults. It may also start in adult life.

Why is acne worse in some people ?

Some people have particularly severe acne. This may be because of:

• Genetic factors (family members have bad acne)
• Hormonal factors (higher levels of male/androgenic hormones) due to:
• Polycystic ovaries (common). Hyperinsulinaemia and insulin resistance are characteristically found in women with polycystic ovarian syndrome, who are prone to acne among other problems
• Psychological stress and depression
• Excessive corticosteroids eg Cushing disease (rare)
• Enzyme deficiency eg sterol hydroxylase deficiency (very rare)
• Environmental factors such as:
• High humidity causing swelling of the skin
• Cosmetics especially certain moisturisers, foundation and pomades. Watch out for products that contain lanolin, petrolatum, vegetable oils, butyl stearate, lauryl alcohol and oleic acid.
• Pressure from headbands and chin straps (eg “fiddler’s neck”, a condition seen in violin or viola players, where continual pressure from the violin against the neck causes skin irritation)
• Excessive dairy products, meat protein and sugars in the diet. Diets low in zinc or high in iodine can worsen pustular acne.
• Certain medications may provoke acne.
• Much of the individual variation in acne severity is due to variation in the innate immune system and the production of inflammatory mediators such as cytokines, defensins, peptidases, sebum lipids, and neuropeptides. Evidence has emerged that inflammation leads to distension and occlusion of the hair follicle, which then ruptures.

What are the clinical features of acne vulgaris ?

Acne most often affects the face, but it may spread to involve the neck, chest and back, and sometimes even more extensively over the body.

Individual lesions are centred on the pilosebaceous unit, ie the hair follicle and its associated oil gland. Several types of acne spots occur, often at the same time. They may be inflamed papules, pustules and nodules; or non-inflamed comedones and pseudocysts.

Comedones are dilated or widened hair follicles (pores) in the skin. Keratin (skin debris) combines with oil and bacteria to clog the follicles. Comedones (the plural of comedo) can be open (blackheads) or closed by skin (whiteheads), and can occur with acne or without acne.

Superficial lesions

• Open and closed comedones (blackheads and whiteheads)
• Papules (small, tender red bumps)
• Pustules (white or yellow “squeezable” spots)

Deeper lesions

• Nodules (large painful red lumps)
• Pseudocysts (cyst-like fluctuant swellings)

Secondary lesions

• Excoriations (picked or scratched spots)
• Erythematous macules (red marks from recently healed spots, best seen in in fair skin)
• Pigmented macules (dark marks from old spots, mostly affecting those with dark skin)
• Scars or various types

Individual acne lesions usually last less than 2 weeks but the deeper papules and nodules may persist for months. Many acne patients also have oily skin (seborrhea).

Acne Severity (Grade) is classified as mild, moderate or severe.

• Mild acne: <20 comedones;  <15 inflammatory lesions ; Or, total lesion count <30
• Moderate acne: 20–100 comedones;  15–50 inflammatory lesions; Or, total lesion count 30–125
• Severe acne: >5 pseudocysts;  Total comedo count >100; Total inflammatory count >50; Or total lesion count >125

Figure 4. Acne (acne vulgaris)

Figure 5. Severe inflammatory acne lesions with comedones, several papules and pustules, multiple nodules, and scarring

Figure 6. Comedones (blackheads or open comedones)

What causes acne ?

Acne is due to a combination of factors. The exact mechanisms are not fully understood.

• A combination of clogged pores and an infection of the follicles by the bacteria Cutibacterium acnes (C. acnes, formally known as Propionibacterium acnes)
• Comedones, then papules, pustules and nodules are present.
• Cutibacterium acnes resistance to antibiotics is widespread.
• Onset is earlier now. Acne may be the first sign of onset of puberty in children 7 to 11 years of age.
• Acne in an adult woman may be a manifestation of hyperandrogenism. See acne in a woman.
• Associations: insulin resistance in adult men with acne and low-fat/skim milk but not full-fat milk in teenagers with acne ⁷⁾. Acne in late adolescence is associated with an increased risk of prostate cancer later in life ⁸⁾.
• Familial tendency
• Acne bacteria
• Endogenous and exogenous androgenic hormones
• Innate immune activation with inflammatory mediators
• Distension and occlusion of the hair follicles

Flares of acne can be provoked by:

• Polycystic ovarian disease or Polycystic ovary syndrome (PCOS)
• Drugs: steroids, hormones, anticonvulsants, epidermal growth factor receptor inhibitors and others
• Application of occlusive cosmetics
• High environmental humidity
• Diet high in dairy products and high glycemic foods.

How do bacteria affect acne?

At puberty, the number of bacteria on the skin surface increases. These include:

• Cutibacterium acnes (C. acnes, formally known as Propionibacterium acnes)
• Corynebacterium granulosum (also known as Cutibacterium acnes and formally known as Propionibacterium granulosum)
• Staphylococcus epidermidis (coagulase-negative staphylococcus).

The number of malassezia yeasts probably also increases.

However, the severity of a person’s acne does not depend on the number of bacteria on the skin surface or in the sebaceous ducts (the passageway from the oil glands).

The number and activity of Cutibacterium acnes bacteria varies according to oxygen supply, nutrient supply and the pH level of the skin. Some acne lesion are colonized by Cutibacterium acnes and others are not.

The Cutibacterium acnes bacteria can produce active enzymes and innate inflammatory mediators and these may contribute to the activity of acne in some patients. Activation triggers expression of immune response genes. Inflammatory mediators detected in acne lesions colonized by Cutibacterium acnes include:

• Lipases (enzymes that break down fats)
• Proteases (enzymes that break down proteins)
• Hyaluronate lyase (enzyme that breaks down skin ground substance)
• Phosphatase (enzyme that breaks down phosphates)
• Smooth-muscle contracting substances
• Cytokines, such as IL-12 and IL-8, and defensins (these are chemical messengers).

The lipases can convert triglyceride in sebum to free fatty acids. The free fatty acids increase clumping of bacteria in sebaceous ducts and thus the colonisation of the ducts by more of them. The inflammatory mediators provoked by the bacteria penetrate surrounding skin and are a cause of inflammation.

What is the effect of treatment on acne bacteria?

Antimicrobials such as topical benzoyl peroxide and oral tetracyclines suppress Cutibacterium acnes in patients with acne. They also have non-antibiotic anti-inflammatory activity.

Twenty years ago, Cutibacterium acnes was readily killed by erythromycin, clindamycin and the tetracyclines. Unfortunately, after decades of use, widespread antibiotic resistance by Cutibacterium acnes has emerged. These drugs are much less effective. Thus, acne therapy has shifted to emphasizing the use of benzoyl peroxide, the topical retinoids, and oral isotretinoin.

What is the best acne treatment ?

Treatment for acne depends on the patient’s age and sex, the extent and the severity of the acne – mild, moderate or severe, how long your acne has been present, and response to previous treatments.

• Treatment for mild acne includes topical anti-acne preparations, lasers and lights
• Treatment for moderate acne adds acne antibiotics such as tetracyclines and/or antiandrogens such as birth control pill
• Treatment for severe acne may require a course of oral isotretinoin.

General principles of acne treatment

• Acne can be effectively treated, although response may sometimes be slow.
• Where possible, avoid excessively humid conditions such as a sauna, working in an unventilated kitchen or tropical vacations.
• Consider a low-glycemic, low-protein and low-dairy diet (note that the evidence that this helps is weak). Avoid protein or amino acid supplements, particularly if they contain leucine. Eat plenty of fresh fruit and vegetables.
• If you smoke, stop. Nicotine increases sebum retention and increased scale within the follicles, forming comedones (blackheads and whiteheads).
• Minimize the application of oils and cosmetics to the affected skin.
• Abrasive skin treatments can aggravate both comedones and inflammatory lesions.
• Try not to scratch or pick the spots.
• Exposure to sunlight filtered through window glass can help – see information about lasers, lights and acne. To avoid sunburn, protect your skin outdoors using a sunscreen and protective clothing.

Mild acne

• Topical antiacne agents, such as benzoyl peroxide and/or tretinoin or adapalene gel. New bioactive proteins may also prove successful.
• Low-dose combined oral contraceptive
• Antiseptic or keratolytic washes containing salicylic acid
• Light / laser therapy

Topical treatment for acne

Topical treatment for acne is available as washes, solutions, lotions, gels and creams. They may have a single or multiple active ingredients. There are numerous products available in supermarkets and pharmacies. Some require a doctor’s prescription.

Active ingredients may have one or more of the following properties:

• Antibiotics and antiseptics to reduce counts of Cutibacterium acnes bacteria
• Anti-inflammatory effects to calm red, inflamed skin by inhibiting lipase production by Cutibacterium acnes (previously called Proprionibacterium acnes)
• Anti-oxidants to protect cells from damage by free radicals
• Comedolytics to unplug blocked follicles (comedones)
• Keratolytics to peel off surface scale (exfoliants)
• Agents that affect keratinisation, i.e., that normalise skin cell maturation

TOPICAL THERAPIES: OVER THE COUNTER

Benzoyl peroxide

Benzoyl peroxide is an over-the-counter bactericidal agent that comes in a wide array of concentrations and formulations. No particular form has been proven better than another ⁹⁾. Benzoyl peroxide is unique as an antimicrobial because it is not known to increase bacterial resistance ¹⁰⁾. It is most effective for the treatment of mild to moderate mixed acne when used in combination with topical retinoids ¹¹⁾. Benzoyl peroxide may also be added to regimens that include topical and oral antibiotics to decrease the risk of bacterial resistance ¹²⁾. Salicylic acid is present in a variety of over-the-counter cleansing products. These products have anticomedonal properties and are less potent than topical retinoids, but there have been only limited high-quality studies examining their effectiveness ¹³⁾.

Topical retinoids

Topical retinoids are creams, lotions and gels containing one or other of group of medicines derived from Vitamin A. These compounds result in proliferation and reduced keratinisation of skin cells independent of their functions as a vitamin.

Many brand-name creams containing the retinoids retinol and retinaldehyde can be obtained over the counter at pharmacies and supermarkets.

Adapalene gel has received approval from the FDA in the USA for over-the-counter use of acne treatment in patients 12 or older (July 2016).

Adapalene is also available to treat acne in combination with benzoyl peroxide, as Epiduo® gel.

The more potent topical retinoids available on prescription are:

• ReTrieve™ cream (tretinoin)
• Retin-A™ Cream (tretinoin or retinoic acid)
• Retinova™ Cream (tretinoin emollient)
• Isotrex™ Gel (isotretinoin)
• Differin™ Gel, Cream (adapalene)

What are topical retinoids used for ?

Topical retinoids are effective treatments for mild to moderately severe acne. The effect is often noticeable within a few weeks, but it may take 6 weeks or longer before improvement occurs.

Tretinoin has also been shown to reverse some of the changes due to photo-aging, i.e. sun damage. If used long term, it may reduce some fine wrinkles, freckles, solar comedones (whiteheads and blackheads), and actinic keratoses (tender, dry sun-spots).

They may also be used in bleaching creams to reduce pigmentation in melasma.

Topical retinoids can be applied to any area but are most often used on the face, the neck and the back of hands.

Do topical retinoids have any side effects ?

Topical retinoids can irritate the skin, especially when they are first used. This is more likely in those with sensitive skin, resulting in stinging. Excessive use results in redness, swelling, peeling and blistering in treated areas. It may cause or aggravate eczema, particularly atopic dermatitis.

By peeling off the top layer of skin, they may increase the chance of sunburn. Irritation may also be aggravated by exposure to wind or cold, use of soaps and cleansers, astringents, peeling agents and certain cosmetics.

Some people have reported a flare of acne in the first few weeks of treatment. This usually settles with continued use.

Retinoids taken by mouth may cause birth deformities. Manufacturers recommend that topical retinoids are not used in pregnancy or breastfeeding as negative animal studies are not always predictive of human response.

How to use topical retinoids

Follow these instructions carefully ¹⁴⁾:

• Be cautious if you are using other topical acne treatments – ask your doctor if you should stop these.
• In general, a cream is less irritating than a gel. If there is a choice, start with a lower concentration product.
• Use your topical retinoid on alternate nights at first. If you have sensitive skin, wash it off after an hour or so. If it irritates, apply it less often. If it doesn’t, try every night, and if possible twice daily. In most people, the skin gradually gets used to it.
• To reduce stinging, apply it to dry skin, that is, 30 minutes or longer after washing.
• Apply a tiny amount to all the areas affected, and spread it as far as it will go.
• Don’t get it in your eyes or mouth.
• Apply a sunscreen to exposed skin in the morning.
• Wear your usual make-up if you wish, and use gentle cleansers (avoid soap) and apply non-greasy moisturisers as often as required.
• If you have acne, choose oil-free cosmetics.
• If your skin goes scarlet and peels dramatically even with cautious use, the retinoid may be unsuitable for your sensitive skin.
• Tolerance to topical retinoids often develops over time.

Table 1. Selected Non-Antibiotic Topical Therapies for the Treatment of Acne Vulgaris

Agent	FDA pregnancy category	Adverse effects	Available formulations	Estimated cost generic (brand)*
Azelaic acid	B	Hypopigmentation, burning, stinging, tingling, pruritus	Cream (Azelex, 20%; approved for acne vulgaris)	NA ($210)
			Gel (Finacea, 15%; approved for rosacea)
Benzoyl peroxide	C	Dry skin, local erythema	Bar, cream, gel, lotion, pad, wash (2.5% to 10%)	$5 over the counter
				$8 to $36 prescription (NA)
Dapsone	C	Local oiliness, peeling, dryness, erythema	Gel (Aczone, 5%)	NA ($193)
Salicylic acid	C	Dryness, mild skin irritation	Cream, dressing, foam, gel, liquid, lotion, ointment, pad, paste, shampoo, soap, solution, stick (0.5% to 3%)	$5 over the counter

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FDA = U.S. Food and Drug Administration; NA = not available.

Estimated retail price of one month’s treatment based on information obtained at http://www.lowestmed.com and http://www.drugstore.com

Footnote: The U.S. Food and Drug Administration (FDA) has since updated their Pregnancy and Lactation Labeling of Drugs Rule with new changes go into effect on June 30, 2015 ¹⁵⁾. The updated Pregnancy and Lactation Labeling of Drugs Rule removes pregnancy letter categories – A, B, C, D and X. The pregnancy letter categories – A, B, C, D and X will be replaced by a narrative risk summary based on available data. Prescription drugs and biologic products submitted after June 30, 2015, will use the new format immediately, while labeling for prescription drugs approved on or after June 30, 2001, will be phased in gradually. Labeling for over-the-counter (OTC) medicines will not change; OTC drug products are not affected by the final rule.

Table 2. Topical Acne Treatments

Generic	Brand		Strength	Form	Dose
ANTIBACTERIAL/ANTIKERATINIZING
azelaic acid	Azelex	Rx	20%	crm	Children: Not recommended. Adults: Gently massage thin film to affected areas twice daily (AM and PM) to clean, dry skin. Wash hands after use. May decrease to once daily if persistent irritation occurs.
ANTIBACTERIAL/KERATOLYTIC
benzoyl peroxide	Benzac AC	Rx	5%, 10%	water-base gel	Children: Not recommended. Adults: Apply to cleansed area 1−2 times daily
				wash	Children: Not recommended. Adults: Wash affected area 1−2 times daily; rinse
	Benzac‑W	Rx	2.5%, 5%, 10%	aqueous-base gel	Children: Not recommended. Adults: Apply to cleansed area once daily, increase to 2−3 times daily as tolerated
			5%, 10%	wash	Children: Not recommended. Adults: Wash affected area 1−2 times a day; rinse
	Desquam‑X	Rx	5%, 10%	water-base gel	Children: Not recommended. Adults: Massage into cleansed area 1−2 times daily
				water-based wash	Children: Not recommended. Adults: Wash affected areas 1−2 times daily; rinse
	Neobenz Micro	Rx	3.5%, 5.5%	crm	Children: Not recommended. Adults: Apply to cleansed area 1−2 times daily
	Neobenz Micro SD	Rx	5.5%	crm
	Neobenz Micro Wash	Rx	7%	wash	Children: Not recommended. Adults: Wash affected areas 1−2 times daily; rinse
	Riax	Rx	5.5%, 9.5%	foam	Children: Not recommended. Adults: Apply thin layer, and rinse thoroughly 1−3 times daily as tolerated. May reduce to once daily or every other day if dryness or peeling occurs.
KERATOLYTIC
salicylic acid	Phisoderm Anti-Blemish Body Wash	OTC	2%	body wash	Children: Not applicable. Adults: Massage onto skin; rinse
	Phisoderm Anti-Blemish Gel Facial Wash	OTC	2%	gel	Children: Not applicable. Adults: Massage onto skin twice daily; rinse
SULFONE
dapsone	Aczone	Rx	5%	gel	Children: Not established. Adults: Apply pea-sized amount to affected area twice daily (AM & PM). Wash hands after use. Reevaluate if no improvement after 12wks.
			7.5%	gel	Children: Not established. Adults: Apply pea-sized amount to affected area once daily. Wash hands after use. Reevaluate if no improvement after 12wks.
ANTIBIOTICS
clindamycin	Cleocin T	Rx	1%	soln5, pads5, lotion, gel	Children: Not established. Adults: Apply thin film twice daily
	Clindagel	Rx	1%	gel	Children: Not recommended. Adults: Apply thin film once daily
	Clindets	Rx	1%	pledgets5	Children: Not recommended. Adults: Apply thin film twice daily
	Evoclin	Rx	1%	foam3	Children: <12yrs: Not established. Adults: Apply once daily to clean, dry skin
erythromycin	—	Rx	2%	gel	Children: Not established. Adults: Apply thin film 1−2 times daily
				soln, pads3	Children: Not recommended. Adults: Apply with applicator or pads to clean, dry skin twice daily
	Ery 2% Pads	Rx	2%	pledgets3	Children: Not applicable. Adults: Rub over cleansed area twice daily (AM & PM)
sodium sulfacetamide	Klaron	Rx	10%	lotion	Children: Not recommended. Adults: Apply thin film twice daily to affected areas
RETINOIDS
adapalene	Differin	Rx	0.1%	crm6	Children: Not established. Adults: Apply thin film to affected areas once daily after washing. Reduce frequency or discontinue if prolonged or severe irritation occurs.
		OTC	0.1%	gel6
		Rx	0.3%	gel6
			0.1%	lotion
tazarotene	Fabior	Rx	0.1%	foam	Children: Not recommended. Adults: Apply thin layer to clean, dry affected area (face, upper trunk) once daily in PM. Women of childbearing potential: Begin therapy during normal menses.
	Tazorac	Rx	0.05%*, 0.1%	crm, gel	Children: <12yrs: Not established. Adults: Apply thin film of 0.1% strength to lesions on clean, dry face once daily in the PM. Women of childbearing potential: Begin therapy during normal menses.
tretinoin	Atralin	Rx	0.05%	gel2,4	<10yrs: Not recommended. ≥10yrs: Apply sparingly at bedtime to clean skin once daily. Adjust amount and frequency as tolerated.
	Avita	Rx	0.025%	crm, gel	Children: Not recommended. Adults: Apply sparingly to clean, dry skin once daily at bedtime. If irritation develops, adjust dose or frequency as tolerated and needed.
	Retin‑A	Rx	0.025%, 0.05%, 0.1%	crm
			0.01%, 0.025%	gel1
			0.05%	liq3
	Retin‑A Micro	Rx	0.04%, 0.08%, 0.1%	aqueous gel
COMBINATION AGENTS
adapalene/ benzoyl peroxide	Epiduo Forte Gel	Rx	0.3%/2.5%	gel	Children: Not established. Adults: Apply thin film to affected areas of face and/or trunk once daily after washing. Use a pea-sized amount for each area of the face.
	Epiduo Gel	Rx	0.1%/2.5%	gel	<9yrs: Not established. ≥9yrs: Apply thin film to clean affected areas (face, trunk) once daily. Use a pea-sized amount for each area of the face. Reduce frequency or discontinue if prolonged or severe irritation occurs.
clindamycin/ benzoyl peroxide	Acanya	Rx	1.2%/2.5%	gel	Children: Not recommended. Adults: Apply pea-sized amount in a thin layer to clean, dry face once daily. Wash hands after use.
	Benzaclin	Rx	1%/5%	gel	Children: Not recommended. Adults: Apply twice daily
	Duac	Rx	1%/5%	gel	Children: Not recommended. Adults: Apply to clean, dry skin once daily in the evening
	Onexton	Rx	1.2%/3.75%	gel	Children: Not established. Adults: Apply a pea-sized amount once daily
clindamycin/ tretinoin	Ziana	Rx	1.2%/0.025%	gel	Children: Not recommended. Adults: Apply thin film to clean, dry face once daily at bedtime
erythromycin/ benzoyl peroxide	Benzamycin	Rx	3%/5%	gel	Children: Not recommended. Adults: Apply to clean, dry skin twice daily
NOTES
*Only 0.1% indicated for mild to moderate acne vulgaris 1contains cetearyl alcohol; 2contains parabens; 3contains alcohol; 4contains benzyl alcohol; 5contains isopropyl alcohol; 6alcohol‑free

What is Azelaic acid ?

Azelaic acid should be considered for use in pregnant women. The cream formulation (Azelex) is approved by the U.S Food and Drug Administration (FDA) for the treatment of acne vulgaris, but the gel (Finacea) has significantly better bioavailability ¹⁶⁾. It has mixed antimicrobial and anticomedonal effects, and may be effective for the treatment of mild to moderate inflammatory or mixed acne ¹⁷⁾.

What is Dapsone ?

Dapsone is the first agent in a new class of topical acne medications to achieve FDA approval in the past 10 years ¹⁸⁾. Although it is an antibiotic, it likely improves acne by inhibiting inflammation. In studies, dapsone was minimally more effective than placebo in reducing inflammatory and noninflammatory lesions, but it has never been compared with other topical agents ¹⁹⁾. Unlike oral dapsone, there is no evidence that the topical formulation causes hemolytic anemia or severe skin reactions ²⁰⁾.

What are Antiseptics ?

Antiseptics are chemical agents that slow or stop the growth of micro-organisms (germs) on external surfaces of the body and help prevent infections. Antiseptics should be distinguished from antibiotics that destroy micro-organisms inside the body, and from disinfectants, which destroy micro-organisms found on inanimate (non-living) objects. However, antiseptics are often referred to as skin disinfectants.

Most chemical agents can be used as both an antiseptic and a disinfectant. The purpose for which it is used is determined by its concentration. For example hydrogen peroxide 6% solution is used for cleansing wounds, while stronger solutions (>30%) are used in industry as a bleach and oxidising agent.

Antiseptics for acne

Hydrogen peroxide is a bleach and an oxidising agent, which means that when applied to tissues, oxygen is released. It is active against a wide variety of microorganisms. There are no known disease-causing bacteria or fungi that develop resistance to hydrogen peroxide.

Hydrogen peroxide 1% in stabilised cream (Crystacide®) can be used to treat acne. One study showed Crystacide® is as effective as benzoyl peroxide (a commonly used topical treatment for mild to moderate acne).

Uses of antiseptics

Antiseptics are mainly used to reduce levels of microorganisms on the skin and mucous membranes. The skin and mucous membranes of the mouth, nose, and vagina are home to a large number of what are usually harmless micro-organisms. However, when the skin or mucous membranes are damaged or breached in surgery, antiseptics can be used to disinfect the area and reduce the chances of infection. It is also important that people whom are treating patients with wounds or burns adequately wash their hands with antiseptic solutions to minimize the risk of cross infection.

What is Salicylic acid ?

Salicylic acid belongs to a group of medicines known as keratolytics. It is used in the treatment of scaly skin diseases where the skin has become thickened, scaly and flaky. Topical preparations of salicylic acid, either alone or in combination with other medicines, can be used to treat the following common scaly skin conditions:

• Viral warts
• Psoriasis
• Seborrhoeic dermatitis
• Chronic atopic dermatitis
• Lichen simplex
• Ichthyosis
• Acne

How does salicylic acid work ?

In acne, topical salicylic acid helps slow down shedding of the cells inside the follicles, preventing clogging. Salicylic acid also helps break down blackheads and whiteheads.

Salicylic acid works by softening keratin, a protein that forms part of the skin structure. This helps to loosen dry scaly skin making it easier to remove. When salicylic acid is used in combination with other medicines it takes off the upper layer of skin allowing the additional medicines to penetrate more effectively.

Salicylic acid preparations come in many forms and strengths from 0.5% up to 30%. For acne use salicylic acid 0.5% oil-free acne wash (Neutrogena®).

TOPICAL THERAPIES: PRESCRIPTION

Topical retinoids

Topical retinoids are versatile agents in the treatment of acne (Table 3) ²¹⁾, ²²⁾. They prevent the formation and reduce the number of comedones, making them useful against noninflammatory lesions. Topical retinoids also possess anti-inflammatory properties, making them somewhat useful in the treatment of inflammatory lesions ²³⁾. Topical retinoids are indicated as monotherapy for noninflammatory acne and as combination therapy with antibiotics to treat inflammatory acne. Additionally, they are useful for maintenance after treatment goals have been reached and systemic drugs are discontinued. Overall, adapalene (Differin) is the best tolerated topical retinoid. Limited evidence suggests that tazarotene (Tazorac) is more effective than adapalene and tretinoin (Retin-A). There is no evidence that any formulation is superior to another ²⁴⁾.

Table 3. Selected Topical Retinoids for the Treatment of Acne Vulgaris

Agent	FDA pregnancy category	Adverse effects	Available formulations	Estimated cost generic (brand)*
Adapalene (Differin)	C	Local erythema, peeling, dryness, pruritus, stinging	Cream, lotion (0.1%)	$125 ($363)
			Gel (0.1%, 0.3%)
			Adapalene/benzoyl peroxide (Epiduo) gel (0.1%/2.5%)	NA ($269)
Tazarotene (Tazorac)	X	Local erythema, peeling, dryness, pruritus, stinging	Cream, gel (0.05%, 0.1%)	NA ($240)
Tretinoin (Retin-A)	C	Local erythema, peeling, dryness, pruritus, stinging	Cream (0.025%, 0.05%, 0.1%)	$27 ($130)
			Gel (0.01%, 0.025%, 0.05%)	$24 ($19 to $105)
			Microsphere gel (0.04%, 0.1%)	NA ($170)

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FDA = U.S. Food and Drug Administration; NA = not available

*—Estimated retail price of one month’s treatment based on information obtained at http://www.lowestmed.com

Topical antibiotics

Topical antibiotics are used predominantly for the treatment of mild to moderate inflammatory or mixed acne. Clindamycin and erythromycin are the most studied (Table 4) ²⁵⁾, ²⁶⁾, ²⁷⁾. They are sometimes used as monotherapy, but are more effective in combination with topical retinoids ²⁸⁾. Because of the possibility that topical antibiotics may induce resistance, it is recommended that benzoyl peroxide be added to these regimens ²⁹⁾.

Table 4. Selected Topical Antibiotics for the Treatment of Acne Vulgaris

Agent	FDA pregnancy category	Adverse effects	Available formulations	Estimated cost generic (brand)*
Clindamycin	B	Local erythema, peeling, dryness, pruritus, burning, oiliness	Foam, gel, lotion, solution (1.0%)	$12 to $96, depending on formulation ($46 to $213)
			Clindamycin/benzoyl peroxide (Benzaclin) gel (1%/5%, 1.2%/2.5%)	$107 ($210)
			Clindamycin/tretinoin gel (Veltin, Ziana; 1.2%/0.025%)	NA ($180 Veltin, $250 Ziana)
Erythromycin	B	Local erythema, peeling, dryness, pruritus, burning, oiliness	Gel, solution, ointment (2%)	$25 (NA)
			Erythromycin/benzoyl peroxide (Benzamycin) gel (3%/5%)	$62 ($313)

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Note: Topical antibiotics are more effective when combined with a topical retinoid.

FDA = U.S. Food and Drug Administration; NA = not available.

*—Estimated retail price of one month’s treatment based on information obtained at http://www.lowestmed.com.

Lasers and lights therapy for acne

Most acne patients notice an improvement in their acne over the summer, although unfortunately it doesn’t last long. Ultraviolet (UV) light (phototherapy) has long been used in the management of acne, as has superficial radiotherapy. However, the well-established long-term side effects of radiotherapy, and the concerns around the skin cancer risks of ultraviolet light/sun beds, have limited their use. UVB (short wavelength UV) has only short term efficacy. UVA (longer wavelength UV) may increase comedone production.

The last few years however, have seen an increased interest in the use of light and laser therapy for acne. There are two main mechanisms that laser/light treatments may help acne:

• By destroying skin bacteria Cutibacterium acnes (previously called Proprionibacterium acnes) through a photodynamic therapy (PDT) reaction
• By destroying the sebaceous glands / entire pilosebaceous unit

To date, many studies have shown early promise, with improvements in the 50-75% range. However, most of the trials have been fairly small, of short duration and with relatively short follow-up periods. Few have had the opportunity to assess long term outcomes and, very importantly, long term complications/side-effects.

It is difficult to know where lasers/lights will eventually fit in the overall management of acne vulgaris. For some individuals, they are likely to be beneficial, although very few comparative studies have been made with conventional medical treatment. The best device, dose and frequency of treatments are as yet undetermined. There is insufficient evidence to recommend the routine use of these therapies for the treatment of acne ³⁰⁾.

The mechanism of action

It is known that the bacteria present in some acne lesions, Cutibacterium acnes (previously called Proprionibacterium acnes), produce chemicals called porphyrins during their growth and proliferation in the skin pore (follicular unit). These porphyrins may contribute to how non-inflamed acne lesions become inflamed.

It is thought that the two main porphyrins involved are protoporphyrin IX (PpIX) and coproporphyrin III. Both of these chemicals absorb light at 415 nm (the Soret band), which corresponds to the blue range of the visible light spectrum, and to 630 nm, which corresponds to red light.

Photo-excitation of these porphyrins, from exposure to an appropriate light source, will form singlet oxygen (free radicals) within the bacteria, which then selectively destroy them, thereby hopefully improving the clinical signs of the acne. The sebaceous gland is also a target. Differing topical photosensitising agents have been applied to the acne-prone skin to try to specifically damage sebaceous tissues while leaving the epidermis alone, and in an attempt to minimise the side effects of treatment.

Types of light / laser sources

There are a number of light and lasers being investigated. These include:

• Blue and red light sources
• Green light lasers
• Yellow light lasers
• Intense pulsed light (IPL) sources
• Radiofrequency (RF) devices

Blue light machines

There are a number of units that produce ‘Blue’ light. These tend to be high-intensity, narrow-band blue light source in the 405nm-420nm range.

Several studies have shown some benefit:

• 30 patients received x2/week for 5 weeks – 64% decrease acne lesions
• 35 patients x2/week for 4 weeks – 80% of patients had significant improvement
• 40 patients x2/week; 3 months following their last treatment – 43% decrease in inflammatory lesions.
• 12 patients x2/week (6 min); 2 weeks after the final treatment – 40% decrease in papules, 65% decrease in pustules, 62% decrease in comedones
• Multicenter study of blue light system vs. topical 1% clindamycin – blue light therapy was more effective than the topical clindamycin in decrease inflammatory acne lesions.

Green light lasers

At 532 and 532/1064 nm, several green light lasers have been studied.

• 11 patients in a split-face prospective, randomized clinical trial. 4 treatments at 7-9J/cm2 utilizing a 4mm spot size and pulse duration of 20msec with parallel contact cooling. 6-10 passes over the half-treated face.

At 1 month:

• Acne lesion counts decreased 35.9% vs. 11.8%.
• Sebum excretion rate decreased 28.1% vs. 6.4% control

Yellow light sources

These are generally low-fluence pulsed dye lasers at 585-595nm.

• 41 patients, double blind, randomized clinical trial. Acne severity decrease from a score of 3.8 to 1.9 in the pulsed dye lasers group vs. 3.6 to 3.5 in the placebo.
• 40 individuals receiving 1-2 treatments with the pulsed dye lasers. No significant differences.

Intense Pulsed Light

Intense Pulsed Light (IPL) devices use light and heat, known as LHE technology, to trigger the destruction of the P. acnes bacteria.

• 19 patients – 85% had a >50% improvement in their acne vulgaris lesions following x2/week therapy for 4 weeks.
• 14 patients received 5 treatments every 2-4 weeks. 2-3 passes at 10J/cm2. At 6/12, clearance rates of 72% for noninflammatory lesions and 73% for inflammatory lesions.

Lasers that destroy sebaceous glands

Several longer wavelength laser systems have been used to treat inflammatory acne vulgaris by destroying the sebaceous glands including near-infrared lasers, 1320nm CoolTouch®, 1450nm SmoothBeam®, 1540nm erbium glass Aramis® and radiofrequency devices.

1450nm SmoothBeam® laser

• 27 patients. Acne on back, 4 treatments at 3-week intervals. The average fluence used was 18J/cm2
  • At 6/12 – a 98% reduction in inflammatory lesions after 4 treatments.
  • At follow-up – 100% lesion clearance was seen in all but one patient.
• 19 patients with facial acne.
  • 37% reduction after 1 treatment, 58% after 2 treatments and 83% after 3 treatments.

Side effects included transient erythema and oedema. Topical anaesthetics were used to minimize the discomfort.

Indocyanine green (ICG) + diode laser (810nm-900nm)

ICG, a fluorescent dye used for imaging purposes, acts as a sensitizing agent to help target the sebaceous glands. The combined use of ICG with diode lasers showed a reduction in inflammatory acne vulgaris lesions

• 22 patients with acne of the face or back. The targeted areas were stained with the ICG for 5-15 minutes and then irradiated with a diode laser. Multiple treatments were required.

Radiofrequency devices

A monopolar radiofrequency (RF) with ThermaCool® device has been trialled:

• 22 patients were treated twice with the average fluence of 72J/cm2.
  • At 1-8 months – excellent responses were seen in 82%, modest responses in 9%, and no response in 9%
  • Patients were administered topical anaesthesia because treatment with this device can cause a great deal of discomfort
  • Results are not permanent.

Moderate acne

• As for mild acne plus a tetracycline such as doxycycline 50–200 mg daily for 6 months or so
• Erythromycin or trimethoprim if doxycycline intolerant
• Antiandrogen therapy with long-term cyproterone acetate + ethinylestradiol and/or spironolactone, may be considered in women not responding to low-dose combined oral contraceptive, particularly for women with polycystic ovaries
• Isotretinoin is often used if acne is persistent or treatment resistant.

When oral antibiotics are discontinued, control should be maintained long term by continuing topical therapy.

Moderate acne treatment strategies

• Oral tetracycline class antibiotic plus benzoyl peroxide and topical retinoid.
• Don’t give an oral antibiotic alone–without topical therapy–as you always want to transition off oral antibiotics.
• For females, consider hormonal therapy.
• Topical clindamycin or erythromycin should not be given as monotherapy (as it runs the risk of resistance to Cutibacterium acnes)
• If scarring is present or the acne is resistant to the above, give isotretinoin.
• Try to limit any course of an oral antibiotic to 3 months.

The following may also be prescribed:

• High dose oral antibiotics for six months or longer
• In females, especially those with polycystic ovary syndrome (PCOS), oral antiandrogens such as estrogen/cyproterone or spironolactone may be suitable long-term
• Systemic corticosteroids are sometimes used

For moderate disease, e.g., acne with deeper, cystic papulonodules, the use of an oral antibiotic is needed. The tetracyclines are the mainstays of therapy, but again, after decades of use, Cutibacterium acnes resistance has developed and these agents are not nearly as effective as 20 years ago.

• Tetracycline 500 mg oral twice daily (Cutibacterium acnes resistance has made this agent much less effective)
• Doxycycline 100 mg oral twice daily
• Minocycline 100 mg oral twice daily

The typical antibiotics, listed above and below in Table 4, are given for 3 months in combination with topical benzoyl peroxide every morning and a retinoid nightly. After 3 months, if control is achieved, stopping the oral antibiotic is recommended. If one agent is not effective, then the patient may be switched to another. In general, if one tetracycline does not work, it would be more advantageous to switch to either Septra or azithromycin than a different tetracycline. If two sequential oral antibiotics along with topical therapy is not sufficient to provide good control of the acne (and prevent scarring), then a course of isotretinoin is recommended. Anyone who gives isotretinoin must be trained in its use as it is highly teratogenic and has many potential side effects. For adult women, alternative therapies exist.

Physical treatments for acne

• Sunlight is anti-inflammatory and can help briefly. However, exposure to ultraviolet radiation results in ageing skin and can eventually lead to skin cancer.
• Lasers and other light systems using visible light wavengths, appear safe and helpful for acne. Treatment is often delivered twice weekly for four weeks. The effect may be enhanced by use of a photosensitising agent (photodynamic therapy).
• Cryotherapy (freezing treatment) may be useful to control new nodules.
• Intralesional steroid injections can be used to shrink older nodules and pseudocysts.
• Comedones can be expressed or removed by cautery or diathermy (electrosurgery).
• Microdermabrasion can help mild acne.
• Note: X-ray treatment is NO longer recommended for acne, as it may cause skin cancer.

Oral antibiotics

Oral antibiotics are effective for the treatment of moderate to severe acne (Table 5) ³¹⁾. The best-studied antibiotics include tetracycline and erythromycin. Based on expert consensus on relative effectiveness, the American Academy of Dermatology recommends using doxycycline and minocycline (Minocin) rather than tetracycline ³²⁾. Trimethoprim/sulfamethoxazole (Bactrim, Septra) and trimethoprim alone may be used if tetracycline or erythromycin cannot be tolerated. Because of the potential for bacterial resistance with the use of an oral antibiotic, it is recommended that benzoyl peroxide be added to any regimen of oral antibiotics ³³⁾. Tetracycline is preferred over erythromycin because of the higher rates of resistance associated with erythromycin ³⁴⁾.

After individual treatment goals have been met, oral antibiotics can be discontinued and replaced with topical retinoids for maintenance therapy ³⁵⁾. Topical retinoids are sufficient to prevent relapses in most patients with acne vulgaris, especially if the disease was originally classified as mild or moderate. If the patient’s acne was initially classified as severe inflammatory, benzoyl peroxide with or without an antibiotic can be added for maintenance therapy ³⁶⁾.

Table 5. Selected Oral Antibiotics for the Treatment of Acne Vulgaris

Agent	FDA pregnancy category	Adverse effects	Dosage	Estimated cost generic (brand)*
Doxycycline	D	Photosensitivity, pseudotumor cerebri, esophageal irritation	50 to 100 mg once or twice per day	$15 ($71 to $363)
Erythromycin	B	Gastrointestinal upset	250 to 500 mg two to four times per day	$73 to $340 (NA)
Minocycline (Minocin)	D	Vestibular dysfunction, photophobia, hepatotoxicity, lupus-like reaction, pseudotumor cerebri	50 to 100 mg once or twice per day	$21 to $59 ($173 to $675)
Tetracycline	C	Gastrointestinal upset, photosensitivity, pseudotumor cerebri	250 to 500 mg once or twice per day	$8 (NA)
Trimethoprim/sulfamethoxazole (Bactrim, Septra)	C	Allergic reactions	160/800 mg twice per day	$33 ($194)

---

FDA = U.S. Food and Drug Administration; NA = not available
*—Estimated retail price of one month’s treatment based on information obtained at http://www.lowestmed.com
Doxycycline

Doxycycline is widely used at 100 mg oral twice daily. Stomach upset is a common problem as is photosensitivity (look for red skin on the nose and dorsal hands). It should be taken with food and the patient should use sunscreen. In July 2014, the FDA approved Acticlate (doxycycline hyclate 75 mg and 150 mg tablets) for a number of infections including adjunctive therapy in severe acne.

Submicrobial dosing of doxycycline (20 mg oral twice daily) for acne has been evaluated in a few studies and only one that we can find that was placebo controlled. In that the mean change (reduction) in total inflammatory lesions from baseline to the end of treatment (6 months) was 50% in the doxycycline 20 mg oral twice daily group and 30% in the placebo group ³⁷⁾. Another study has been published, but it was not placebo controlled ³⁸⁾. So there is benefit, but it does not seem robust.

Minocycline

Minocycline is widely used at 100 mg oral twice daily. It can cause nausea and dizziness initially, especially in women. There is less photosensitivity than doxycycline, but a higher rate of side effects, e.g., allergic rash, dizziness, blue discoloration of skin, nails, or teeth over the long term, bruises that don’t go away, and hyperpigmentation of the lips or tongue.

Septra DS

Septra DS (double strength) is an excellent antibiotic for acne if the tetracyclines fail and the patient prefers to avoid isotretinoin. It contains 160 mg trimethoprim and 800 mg sulfamethoxazole and is given orally twice daily with topical benzoyl peroxide morning and a retinoid nightly. Unfortunately, it has several major drawbacks. First, there is a 4% risk of allergic rash in women and 2% in men. For this reason, patients may take only one pill a day for the first 10 days. If no rash, then they can go on to taking it twice daily. Second, widespread use of this agent may lead to antibiotic resistance, making it less useful for other more serious infections.

Azithromycin

Various reports have suggested benefit with azithromycin in acne.

• Pulsed oral azithromycin (500 mg/day over three consecutive days every 2 weeks) was used in conjunction with low-dose isotretinoin in one study.
• In Egypt, one study showed resistance of Cutibacterium acnes lowest to azithromycin (compared with doxycycline, clindamycin, and erythromycin)
• In another study, the following was used: three monthly pulses of azithromycin 500 mg for 3 consecutive days.
• Azithromycin, 500 mg orally thrice weekly for 8 weeks

Risk of Long-Term Antibiotics for Acne

Long-term use of oral antibiotics greatly increases the risk of antibiotic resistance. But does the long-term use of an oral antibiotic for acne in some way adversely affect the health of the patient? In one small study, the odds of reporting pharyngitis was 3 times more likely in patients receiving oral antibiotics for acne than in controls.

Oral isotretinoin

Isotretinoin (13-cis retinoic acid) is a vitamin-A derivative (retinoid). The liver naturally makes small quantities of isotretinoin from vitamin-A, but the drug dermatologists prescribe is made synthetically. Isotretinoin was developed in the 1950s, but only started being used in the mid 1970s. The original brand names were Accutane® and Roaccutane®, but there are now many generic versions on the market, of varying potency.

In acne, isotretinoin:

• Reduces sebum production
• Shrinks the sebaceous glands
• Reduces follicular occlusion
• Inhibits growth of bacteria
• Has anti-inflammatory properties.

Oral isotretinoin is FDA-approved for the treatment of severe recalcitrant acne. Evidence suggests that it is also useful for less severe acne that is treatment resistant ³⁹⁾. The usual dosage for severe treatment-resistant acne is 0.5 to 1.0 mg per kg per day for about 20 weeks, or a cumulative dose of 120 mg per kg ⁴⁰⁾. Initial flare-ups can be minimized with a beginning daily dosage of 0.5 mg or less per kg ⁴¹⁾. Total cumulative doses of less than 120 mg increase relapse rates, and doses of more than 150 mg increase the incidence of adverse effects without producing greater benefits ⁴²⁾. Approximately 40 percent of patients achieve long-term remission with a 120-mg cumulative dose, 40 percent require retreatment with topical therapy or oral antibiotics and 20 percent require retreatment with isotretinoin ⁴³⁾. Patients with moderate acne may respond to lower dosages (0.3 mg per kg per day) and experience fewer adverse effects ⁴⁴⁾.

Physicians, distributors, pharmacies, and patients must register in the iPLEDGE program (http://www.ipledgeprogram.com) before using isotretinoin. This program was established to prevent pregnancy in patients taking the medication. Isotretinoin is a potent teratogen (an agent which causes malformation of an embryo) and is associated with abnormalities of the face, eyes, ears, skull, central nervous system, cardiovascular system, thymus, and parathyroid glands. Negative pregnancy tests are mandated before starting therapy, then monthly before receiving a prescription refill, immediately after taking the last dose and one month after taking the last dose. The use of isotretinoin has been suggested to worsen depression and increase the risk of suicide, but no causal relationship has been established ⁴⁵⁾. Required laboratory monitoring during therapy includes a complete blood count, fasting lipid panel, and measurement of liver transaminase levels. Common adverse effects include headaches, dry skin and mucous membranes, and gastrointestinal upset ⁴⁶⁾.

What is the usual dose of isotretinoin?

The range of doses used each day for acne is less than 0.1 to over 1 mg/kg body weight. Some patients may only need a small dose once or twice a week. A course of treatment may be completed in a few months or continue for several years.

It is common to start at a lower dose initially, e.g. 0.5 mg/kg/day, for a month to get the patient used to the medication, and prevent flaring. If there are no symptomatic or laboratory issues and no crusted acne flaring at one month, the patient may be advanced to 1 mg/kg/day and stay at that for the rest of the course, till the face is clear. For acne, some prescribers have targeted a total cumulative dose of 120–140 mg/kg, in the hope of reducing relapse, but the evidence for this remains controversial. The general trend has been to use lower dosages, unrelated to body weight (eg 10 mg/day).

If there is significant inflammation and crusting at the outset, an even lower dose, e.g. 0.1 mg/kg/day is recommended. As the inflammation clears, the dose may be advanced.

Blasiak et al published a study of 180 patients at a single institution ⁴⁷⁾. At one year follow up, those who had received 220 mg/kg total dose were less likely to have relapsed than those that received less than 220 mg/kg. However, these patients had higher side effects persistent at 1 year e.g. decreased hearing and muscle pains. Also, to get this level of total dose, you either have to give high daily doses, e.g. 120 mg/day as in this study or go for 7-8 months at 1 mg/kg/day.

In one study ⁴⁸⁾, the treatment regimen consisted of isotretinoin, fixed 20 mg daily, and duration of treatment-based on the weight of patient, until total cumulative dose of 120 mg/kg was achieved. This lead to a treatment duration from 10-22 months. The relapse (five year follow up) was only 8%. One significant drawback to this approach is the longer exposure to a highly teratogenic drug for female patients of child-bearing potential.

What predicts patients with acne more likely to relapse?

• Early onset (e.g. if a 12-year-old needs isotretinoin, a second course of isotretinoin will probably be needed before age 16.)
• Severe acne, male, truncal acne
• Women with hyperandrogenism

The key determinant of relapse of acne after a course of isotretinoin is age.

Age at Treatment	Need for 2nd course
10-11 years	35-40%
12-14 years of age	20%
15 and older	10-15%

The individual dose prescribed by the dermatologist for acne depends on:

• Prescriber preference
• Patient body weight
• The specific condition being treated
• Severity of the skin condition
• Response to treatment
• Other treatment used at the same time
• Side effects experienced.

All forms of isotretinoin except Absorica should be taken with a fatty meal or milk after food to help with its absorption. Taking isotretinoin with food doubles absorption ⁴⁹⁾. Absorica (isotretinoin-lidose) is isotretinoin combined with a material that improves absorption. Thus, Absorica can be taken with or without food. Isotretinoin may be taken on an empty stomach, but absorption may be halved. There is no particular advantage in splitting the dose over the day.

For how long is isotretinoin taken?

Most patients should be treated until their skin condition clears and then for a further few months. However, courses have often been restricted to 16–30 weeks (4–7 months) to minimise risk of teratogenicity (risk of congenital abnormalities), and to comply with local regulatory authorities. Isotretinoin may be prescribed for years, usually in low dose or intermittently.

Does acne ever fail to clear on isotretinoin?

Although isotretinoin is usually very effective for acne, occasionally it responds unexpectedly slowly and incompletely. Poor response is associated with:

• Macrocomedones (large whiteheads)
• Nodules (large, deep inflammatory lesions)
• Secondary infection
• Smoking
• Polycystic ovarian syndrome
• Younger age (< 14 years).

Options available to slow responders include:

• Electrocautery of comedones
• Prolonged course of isotretinoin
• Additional treatment with oral antibiotics and oral steroids.

Can isotretinoin be used again if acne recurs?

At least fifty per cent of patients with acne have a long lasting response after a single adequate course of isotretinoin. In others, acne may recur a few months to a few years after the medication has been discontinued. Relapse is more common in females than in males, and in patients > 25 years of age. These patients may receive one or more further courses of isotretinoin.

Long-term treatment (> 1 year) is often used for patients with:

• Persistent acne
• Seborrhoea
• Rosacea
• Scalp folliculitis
• Skin cancer.

Contraindications to isotretinoin

• Isotretinoin must not be taken in pregnancy, or if there is a significant risk of pregnancy.
• Blood donation by males and females on isotretinoin is not allowed in case the blood is used for a pregnant woman.

Precautions when taking isotretinoin

• Isotretinoin should be used with caution during breastfeeding.
• Commercial pilots may be subject to flying restrictions if they take isotretinoin.
• High dose isotretinoin in very young children has been associated with premature epiphyseal closure, leading to shorter stature (this is not seen in low dose used for the treatment of acne).

Special precautions for pilots considering isotretinoin

Good night vision is important for airline pilots and those flying after dark. Night vision may be affected by isotretinoin. True decreased night vision may occur, but is rare. When it does occur, it usually does so within several weeks of starting the isotretinoin. Pilots taking isotretinoin or considering a course of isotretinoin must report to their national aviation authority to discuss how this treatment affects their flying privileges.

Monitoring isotretinoin

• Pregnancy must be excluded before and during treatment with isotretinoin

In an otherwise healthy individual, blood tests are generally not needed. However, consider the following if using high dose (1 mg/kg/day), prolonged courses (> 12 months), or if patients have specific risk factors (eg, family history of dyslipidaemia, higher risk of viral hepatitis, etc):

• Pregnancy test baseline and monthly for females of childbearing potential.
• Cholesterol and triglyceride levels: Baseline, and 8 weeks.
• Liver function tests: Baseline and 8 weeks.
• Blood count.
• Additional tests should be done if any are abnormal.

Isotretinoin may cause hypertriglyceridemia, and patients with baseline elevated triglyceride are at particular risk. Hypertriglyceridemia for 4-5 months is not thought to convey significant cardiac risk. However levels above 800-1000 can trigger pancreatitis, although this is rare. Patients have been known to tolerate triglyceride levels in the 4000’s mg/dl without experiencing pancreatitis. In fact, pancreatitis during isotretinoin therapy is more likely idiosyncratic and unassociated with hypertriglyceridemia. In a meta-analysis covering the last 46 years ⁵⁰⁾, 25 cases of pancreatitis in patients on isotretinoin were found but only four had hypertriglyceridemia associated.

Therefore, baseline fasting triglyceride levels should be measured. If elevated, retesting 4 weeks into isotretinoin therapy is in order. It has been argued that patients with normal baseline triglyceride and no other risks for hypertriglyceridemia do not need further monitoring ⁵¹⁾. In fact, that paper goes further and states that “baseline triglyceride monitoring is unnecessary for typical teenagers if they have no other risk factors for elevated triglycerides.” However, the current consensus for all patients on isotretinoin is to measure fasting triglycerides at baseline and if normal, to retest at 2 months. For any patients with significant hypertriglyceridemia, dose reduction, diet modification and rarely, additional medications are in order. For example, gemfibrozil is very effective in treating retinoid induced hyperlipidemia ⁵²⁾. A typical gemfibrozil dose would be 600 mg twice daily (30 minutes before the morning and evening meals).

Gamma-Glutamyl Transferase (GGT) may be a more useful test for the liver. Creatine kinase (CK) elevations (from muscle, e.g., young athletic men) are relatively common. It may make sense to monitor creatine kinase (CK) in athletically active patients ⁵³⁾.

Oral isotretinoin may cause an elevation of liver enzymes, however any changes are typically asymptomatic and transient and can resolve even with continuing therapy. Clinically apparent liver injury due to isotretinoin is exceedingly rare. Elevations in liver function tests during isotretinoin therapy may be unrelated and alcohol consumption, the taking of supplements (e.g., protein, creatine, or herbal extracts) or intercurrent illness should be excluded ⁵⁴⁾. The isotretinoin should be stopped if liver function test levels are greater than 2-3x normal and any abnormalities should be followed until they normalize.

A reversible myopathy has been seen ⁵⁵⁾. In one study of 89 patients with acne treated with isotretinoin ⁵⁶⁾, elevated creatine kinase (CK) levels were found in five patients. Maximum serum creatine kinase (CK) values ranged between 292 and 569 IU/l. Only one patient out of five had myalgia and four patients were completely asymptomatic. Males that exercise vigorously are at highest risk of elevated creatine kinase (CK) levels. For any values over 1000, the patient may be told hold the isotretinoin until levels improve, cut back on exercising and drink plenty of fluids.

Should isotretinoin be stopped before surgery?

Although there is concern that isotretinoin could interfere with wound healing, the overall the risk described in the larger and better reported studies is relatively small or absent ⁵⁷⁾ and ⁵⁸⁾.

Contraception in females considering isotretinoin

Isotretinoin must NOT be taken in pregnancy because of a very high risk of serious congenital abnormalities in the baby. Caution needs to be used during breast-feeding as it enters the breast milk and might affect the baby.

All females who could biologically have a child should take the following precautions during treatment with isotretinoin and for four weeks after the medication has been discontinued:

• Abstinence. The most reliable method of avoiding pregnancy is not to have sex. No method of contraception is completely reliable. “Natural” family planning is particularly risky.
  • 19% of those who chose abstinence do not.
  • 34% of those sexually active did not comply with 2 forms of birth control.
  • Abstinence” accounts for 12%-14% of pregnancies in iPledge ⁵⁹⁾.
• If sexually active, two reliable methods of contraception should be used. Discuss contraception with your doctor (general practitioner, family planning specialist, gynaecologist or dermatologist). The combined oral contraceptive, IUD (intrauterine device), progesterone implant, or medroxyprogesterone injections may be suitable.
• The low-dose progesterone mini-pill on its own is not recommended.

A prescription for emergency contraception may be available from a medical practitioner (your family doctor or family planning clinic) or accredited pharmacy. It prevents 85% of pregnancies if taken within 72 hours of unprotected sexual intercourse.

If contraception fails, termination of pregnancy (an abortion) may be advised if pregnancy arises during treatment with isotretinoin or within a month of discontinuing it.

What happens if a pregnant woman takes isotretinoin?

Isotretinoin has a very high chance of resulting in a spontaneous miscarriage or a severe birth deformity if a fetus is exposed to it during the first half of pregnancy. The deformities affect the growth of tissues developing at the time of exposure to the drug:

• Cranium (skull and brain)
• Cardiac (heart)
• Eye, ear
• Limbs.

No contraceptive precautions are necessary for men

Isotretinoin has no effect on sperm or male fertility and has not been shown to cause birth defects in children fathered by men taking it.

What are the side effects and risks of isotretinoin?

The side effects of isotretinoin are dose dependent; at 1 mg/kg/day, nearly all patients will have some side effects, whereas at 0.1 mg/kg/day, most patients will not. The range and severity of the side effects also depends on personal factors and the disease being treated.

Patients with significant liver or kidney disease, high blood fats, diabetes and depression may be advised not to take isotretinoin or to be on a lower dose than usual and to have regular follow-up visits.

Cutaneous and mucocutaneous side effects

Most of the side effects due to isotretinoin are cutaneous or mucocutaneous and relate to the mode of action of the drug. The most common are listed here. When side effects are troublesome, isotretinoin may need to be withheld or the dose reduced.

• Acne flare-up (particularly if starting dose is > 0.5 mg/kg/day)
• Dry lips, cheilitis (sore, cracked or scaly lips) (100% of patients on 1 mg/kg/day)
• Dry skin, fragile skin, eczema/dermatitis (itchy, red patches of skin). Note: atopic eczema may improve.
• Increased sweating
• Dry nostrils, epistaxis (nose bleeds)
• Dry, watery or irritable eyes (especially in contact lens wearers), conjunctivitis, keratitis
• Dry anal mucosa, bleeding at the time of a bowel motion
• Dry genitals, dyspareunia (discomfort during intercourse)
• Facial erythema
• Sunburn on exposure to the sun
• Temporary hair loss
• Brittle nails
• Skin infections: impetigo, acute paronychia, pyogenic granuloma

Treatment of mucocutaneous side effects

• Reduce the dosage (eg, to 5–10 mg/day)
• Emollients, lip balm, petroleum jelly, sunscreen, eye drops and lubricants should be applied frequently and liberally when needed
• Dermatitis can be treated with topical steroids
• Take short, cool showers without using soap
• Use mild or diluted shampoo
• Do not start wearing contact lenses for the first time
• Do not have elective eye surgery while on isotretinoin or for 6 months afterwards.
• Do not have mechanical dermabrasion or ablative laser treatments (eg, CO2 resurfacing) while on isotretinoin or for 6 months afterwards. Other laser and
• light treatments may be performed with care
• Shave rather than wax
• Topical and/or oral antibiotics may be prescribed for impetigo

Other common dose-related side effects of isotretinoin

• Headache
• Myalgia (muscle aches) and arthralgia (joint aches), especially after exercise
• Acute arthritis precipitated by isotretinoin may occur ⁶⁰⁾. In reported cases, onset has been between the 2nd and 10th weeks of therapy and the knees are the most commonly affected joints. This condition is more severe that the usual aches and pains of isotretinoin. In this case, severe disability may result (e.g. difficulty walking). NSAIDs should be given and the isotretinoin stopped.
• Tiredness (lethargy and drowsiness)
• Disturbed night vision and slow adaptation to the dark. Drivers may experience increased glare from car headlights at night
• Hypertriglyceridaemia (high levels of triglyceride in the blood), usually of no clinical relevance
• Irregular or heavy menstrual periods

Rare side effects of isotretinoin

Causality of the listed side effects may not have been confirmed.

• Severe headache with blurred vision due to raised intracranial pressure (Pseudotumor Cerebri).
  • If the patient develops a severe and sustained headache, visual disturbances (e.g. blurry or double vision), and/or ringing in the ears, pseudotumor cerebri should be considered. An urgent evaluation including eye exam looking for papilledema by a qualified physician (usually not the dermatologist!) is in order. Can isotretinoin be considered in patients with a history of pseudotumor cerebri from e.g. minocycline. Three patients with recalcitrant acne and a history of pseudotumor cerebri were successfully treated with isotretinoin ⁶¹⁾. Thus, in patients whose acne truly warrants isotretinoin treatment, a history of pseudotumor cerebri (unrelated to isotretion) may not absolutely preclude its use. Baseline and subsequent ophthalmology or neurology evaluation is key.
• Mood changes and depression. Note: depression is more often related to the skin condition being treated or other health or psychosocial problems.
• Antidepressant medications may be helpful
• Corneal opacities and cataracts
• High-tone deafness
• Accelerated diffuse interstitial skeletal hyperostosis (bony change)
• Abnormal liver function tests or symptomatic hepatitis
• Diarrhoea or bleeding from the bowel
• Pancreatitis
• Allergy to isotretinoin causing liver disease and a febrile illness
• Inflammatory Bowel Disease. There has been much controversy as to whether isotretinoin predisposes to inflammatory bowel disease (IBD). One study did not show any increased risk. In fact, the risk seemed to be decreased ⁶²⁾. Several other recent population studies support no increased risk. There may be some association between acne itself and inflammatory bowel disease.
• Asthma has been reported exacerbated by isotretinoin ⁶³⁾. Indeed, isotretinoin may reduce forced expiratory flow. It is postulated that the drug’s drying effect may lead to irritability of the tracheobronchial tree.
• The development of diffuse idiopathic skeletal hyperostosis (DISH) has been associated with chronic (e.g. multi-year) administration of oral retinoids. However, no increased incidence of DISH has been found with one or a few standard courses of isotretinoin.  One study showed that the bone is not demineralized with a 20 week course of isotretinoin ⁶⁴⁾. Another study however showed that mean bone density was reduced an average of 4.4% after 6 months of isotretinoin 1 mg/kg ⁶⁵⁾. In order to evaluate for DISH in a patient exposed to retinoids for a prolonged period of time (longer that the standard course of isotretinoin, e.g. > 2 years) a lateral of the cervical and lumbar spine may be obtained. Back and/or neck pain and stiffness are symptoms of DISH.

Treatment of systemic side effects

• Drink minimal alcohol
• Take paracetamol for headache and for mild aches and pains
• Seek medical attention early, if unwell

Drug interactions with isotretinoin

Care should be taken with the following medications:

• Vitamin-A (retinoic acid): side effects are cumulative and could be severe. Beta-carotene (provitamin-A) is permitted.
• Tetracyclines (including doxycycline, minocycline): these could increase the risk of headaches and blurred vision due to raised intracranial pressure.
• Warfarin: monitor INR carefully.

Oral contraceptives (birth control pills)

Several estrogen-containing oral contraceptives are FDA-approved for the treatment of acne ⁶⁶⁾. These agents generally are considered second-line therapies, but they may be considered first-line treatments in women with adult-onset acne or perimenstrual flare-ups ⁶⁷⁾. A 2009 Cochrane review found that these agents are effective in reducing inflammatory and noninflammatory lesions. However, there is insufficient evidence to recommend one agent over another, including those that are FDA approved versus those that are not. There is also no evidence to support their use over other studied therapies ⁶⁸⁾.

Many contraceptive pills have the effect of lowering testosterone levels, which have the effect of producing excess oil in acne. In some cases, they may mix poorly with certain classes of antibiotics. If taking birth control pills as a form of acne treatment, patients should consult their doctor.

The following are some of the drugs that are approved for acne treatment:

• Alesse® – 0.020mg EE + 0.10mg levonorgestrel

This drug has a relatively low dose of estrogen at 0.02mg compared to most other oral contraceptives, reducing the risk of side-effects. This drug has been shown in clinical trials to be significantly superior to placebo in reducing acne.

• Ortho-Tricyclen® – 0.035mg EE + norgestimate

This drug has been shown in clinical trials to be effective in reducing acne over a span of 6 months. It is approved for treatment of acne in Canada and the United States. In a study monitoring 256 women, 53% of women taking Ortho-Tricyclen® cleared their acne compared to 27% from the placebo group.

• Diane-35® – 0.035mg ethinyl estradiol (EE) + 2.0mg cyproterone acetate (CPA)

Diane-35® has been approved for treatment of acne in Europe for over 25 years, and is currently approved for use in Canada. It acts as an anti-androgen and has an impressive record both in clinical trials and on the market.

Side Effects Of Birth Control Pills

Birth control pills have systemic effects, and can change hormonal balances in the body. Although oral contraceptives are regarded as generally safe, they will often cause minor side-effects, and in rare instances, more serious side-effects.

Common Side Effects:

• Nausea
• Weight gain
• Bloating
• Melasma
• Depression
• Headaches
• Mood swings

Rare but serious side-effects:

• Stroke
• Blood clots
• Heart attacks
• Gallstones
• Thromboembolism
• Retinal artery thrombosis
• Increased blood pressure
• Possible link with breast cancer

Contraindications:

• Men
• History of coronary heart disease
• High cholesterol
• Late renal failure
• Jaundice
• Symptomatic heart valve disease
• Breast cancer
• Smokers

Spironolactone (Aldactone)

Spironolactone (Aldactone) is an androgen receptor blocker with unclear effectiveness in the treatment of acne. It is usually reserved as a second- or third-line agent, or as an alternative to isotretinoin for women who cannot use this medication. A 2009 systematic review found insufficient evidence to recommend the use of spironolactone for the treatment of acne ⁶⁹⁾. Common adverse effects include menstrual irregularities and breast tenderness. It is a potassium-sparing diuretic and may cause severe hyperkalemia. Additionally, it is a potential teratogen (an agent which causes malformation of an embryo) ⁷⁰⁾.

Contraindications for Spironolactone (Aldactone):

• Pregnancy
• Have renal insufficiency
• Have abnormal menstrual bleeding
• Have ovarian cancer
• Have breast cancer
• Have uterine cancer

Acne treatment for adult women

The adult woman with acne tends to primarily have inflammatory lesions (few visible comedones). The distribution of these lesions is typically along the jawline and chin (as opposed to the teenage pattern of acne uniformly distributed on the face). Flaring premenstrually is common. Rosacea should be excluded. Inquiry should be made about menstrual disturbances, impaired fertility, and hirsutism (see also polycystic ovary syndrome).

In one study from Brazil of 835 women with acne, workup showed that 54.56% of the patients had hyperandrogenism and the levels of DHEAS (Dehydroepiandrosterone) were most frequently elevated ⁷¹⁾. One drawback to this study, however, is that the exact criteria of “altered” or abnormal blood tests were not provided.

Causes of Hyperandrogenism in Women

• Polycystic ovary syndrome [PCOS] (80% of all hyperandrogenism in women)
• Androgen-secreting neoplasm (adrenal or ovary)
• Nonclassical congenital adrenal hyperplasia
• HAIR-AN (Hyperandrogenism, insulin resistance, acanthosis nigricans
• Hyperandrogenism and hirsutism
• Exogenous steroid administration

Workup

Blood work for androgens optimally should be obtained during the follicular phase (from menses to ovulation–classically days 1-14), optimally between the fourth and the seventh day of the cycle (day 1 is the first day of the period, day 14 is ovulation), and oral contraceptives should be discontinued for at least two months prior to this testing. The blood draw should be in the morning (highest level of testosterone), preferably before 8:30 AM and fasting.

Full hormonal workup can include DHEAS, free testosterone, sex-hormone binding globulin, prolactin, 24-hour urine cortisol, 17-OH progesterone, thyroid-stimulating hormone (TSH), pregnancy test, follicle-stimulating hormone (FSH) and luteinizing hormone (LH), and pelvic ultrasound.

Treatment for adult woman acne

• The usual conventional approaches: benzoyl peroxide, a topical retinoid, oral antibiotics, and isotretinoin.
• Dospirenone-containing birth control pills (e.g., Yasmin, Yasminelle, Yaz, Beyaz, Ocella, Zarah, Daylette, and Angeliq) are FDA-approved for the treatment of acne.
• Spironolactone 50-100 mg/day (do not give along with trimethoprim-sulfamethoxazole due to risk of hyperkalemia.)
• Cyproterone acetate-containing birth control pills are not FDA-approved in the US, but show benefit for both acne and hirsutism.

Women with acne often do well using conventional approaches to acne therapy (e.g., topical retinoids, benzoyl peroxide, minocycline, etc.) If these fail, isotretinoin is usually given. In those women who relapse after a course of isotretinoin, hormonal workup and therapy is most helpful.

Drospirenone

Drospirenone-containing birth control pills are effective for both acne and hirsutism. Drospirenone is a derivative of spironolactone and at usual doses, is equivalent to 25 mg of spironolactone. Because drospirenone can cause hyperkalemia, caution should be taken when patients are on other medications that may increase the potassium.

The absolute risk of venous thromboembolism in events/100,000 woman-years is ⁷²⁾:

• 6-92 for traditional levonorgestrel-containing birth control pills
• 23-137 for drospirenone-containing birth control pills
• 200 for pregnancy

Spironolactone

• 50-100 mg/day for acne.
• Side effects include menstrual irregularities and rarely hyperkalemia.
• Do not give along with trimethoprim-sulfamethoxazole–increases risk hyperkalemia.
• In pregnancy, can feminize the male fetus.
• Spironolacone is okay for lactating women.
• Typically given with drospirenone-containing (or traditional) birth control pills.

Spironolactone is relatively safe and may be given to the woman already on a drospirenone-containing (or traditional) birth control pill. One study of 200 person-years of exposure to spironolactone and 506 person-years of followup over 8 years found no serious illnesses thought to be attributed to spironolactone ⁷³⁾. With respect to breast, uterus, ovarian, and cervical cancer, there does not seem to be evidence of increased risk with spironolactone ⁷⁴⁾. One study found the combination of spironolactone 100 mg/day and drospirenone/ethinyl estradiol 30 ug efficacious, safe, and well-tolerated ⁷⁵⁾. Do not, however, give spironolactone along with trimethoprim-sulfamethoxazole. That combination in one study was more than 12 times likelier than spironolactone/amoxicillin to cause hyperkalemia. In the elderly, giving trimethoprim-sulfamethoxazole to a patient on spironolactone puts them at risk for sudden death.

Prior to starting spironolactone, the potassium, pregnancy test, DHEAS, and free testosterone may be checked. Note that even though these women are thought to have a hormonal connection to their acne, the hormone levels are usually normal. Spironolactone (e.g., 50-100 mg/day) may be started. Side effects the patient should be made aware of include headache, lethargy, menstrual irregularities (usually not a problem if the patient is on a birth control pill), hyperkalemia, breast tenderness, and decreased sex drive. These side effects are less common at 100 mg/day or less. Women who wish to become pregnant, who are on antihypertensives, cardiac drugs, or diuretics should not take spironolactone. The patient needs to wait at least 3 months to see the full effect. Some women will note decreased facial oiliness. Women with baseline low blood pressure may have trouble with lightheadedness and even syncope. The blood pressure should be monitored at followup visits.

A national acne expert recommends spironolactone for all females with acne (as young as 11 years of age) who fail to respond to 3 months of a topical benzoyl peroxide and a retinoid. He may give it alone or in combination with birth control pills. If this is not sufficient to control the acne after 3 months, he moves on to isotretinoin.

One Expert’s Acne Algorithm for Females of any Age.

• Topical benzoyl peroxide and a retinoid for 3 months.
• Add spironolactone x 3 months
• Add birth control pill x 3 months
• If the above fails, monotherapy with isotretinoin.

Not that this totally eliminates the use of antibiotics for acne.

Severe acne

• Referral to a dermatologist
• If fever, arthralgia, bone pain, ulcerated or extensive skin lesions, blood count should be arranged and referral is urgent
• Oral antibiotics are often used in higher doses than normal
• Oral isotretinoin is usually recommended in suitable patients

Treatment for severe acne requires oral treatment. Patients should be under the care of a dermatologist.

Many patients will be treated with oral isotretinoin. Isotretinoin is the treatment of choice. See oral isotretinoin treatment above.

Treatment of Acne Scars

The term “scarring” refers to a fibrous process in which new collagen is laid down to heal a full-thickness injury. It affects 30% of those with moderate or severe acne vulgaris. It is particularly common in nodulocystic acne, acne conglobata and acne fulminans. It may also be a long-term consequence of infantile acne.

To reduce the chance of scarring, seek treatment for your acne early. Severe acne can often be cured.

Acne scarring is common but surprisingly difficult to treat. In general, treatment of acne scars is a multistep procedure. First, examination of the patient is necessary to classify the subtypes of scarring that are present. Then, the patient’s primary concerns are elicited, and the patient is offered a menu of procedures that may address the various components of the scarring process. It is important to emphasize to the patient that acne scarring can be improved but never entirely reversed.

Acne Scar Treatment Facts:

• Ideally, acne should be quiescent or controlled before treating scars
• Treatments for scars depend on the specific scar type
• Treatment also depends on your skin type.
• Embarrassment from is most often due to facial scars – effective treatment can lead to an improvement in self-image and confidence
• Scars on the chest and back will also respond to treatment

What are the features of acne scarring ?

Unfortunately, true acne scars never completely disappear, although their appearance usually improves with time. They can be disguised with make-up (cosmetic camouflage).

The following types of scar occur in acne:

• Ice-pick scars – these are deep, narrow, pitted scars
• Rolling scars – broad depressions with sloping edge
• Boxcar scars – broad depressions with with sharply defined edges
• Atrophic scars – flat, thin scars or depressed scars (anetoderma)
• Hypertrophic or keloid scars – thick lumpy scars

How skin doctors treat acne scars ?

It is crucial to communicate the fact that acne scars are seldom completely or almost completely removed, and that several procedures may be required to collectively provide the optimal correction. The patient’s willingness to incur downtime must also be clarified since some procedures, like ablative resurfacing, may require post-treatment resting at home for up to 2 weeks. Patients with active acne should not be treated for acne scarring. Many acne scarring treatments, like resurfacing, excision, and subcision, can exacerbate acne, even stimulating the production of nodulocystic lesions. Those with active acne should be reassured that the physician is not abandoning them, and remains interested in treating their acne scarring. First, however, they must undergo treatment for their acne, which should be quiescent for at least 6 months to 1 year before therapy for the scarring is begun.

Finally, darker-skinned patients with Fitzpatrick skin types IV-VI are at risk for procedure-related hyperpigmentation. Asian, Mediterranean, and African-American patients can have diffuse, widespread hyperpigmentation lasting a year or more after laser resurfacing. Excision procedures can induce a similar problem. In susceptible patients, nonablative resurfacing, fillers, and subcision may be preferred, unless the patient is otherwise a candidate for ablative resurfacing, and also indicates a willingness to endure protracted hyperpigmentation.

Non-surgical Treatment For Acne Scars

There are several non-surgical treatment options that may be appropriate for your acne scars:

Skin Camouflage/Cover-up:

For patients with active acne, acne staining, and scars – effective camouflage foundation can improve the appearance of the skin rapidly. Choose products that are non-comedogenic and non-acnegenic and have your tones matched by a skin-care expert to achieve that matte, flawless appearance.

Topical Creams: (Tretinoin):

Can improve your acne, reduce staining and improve fine scars by causing gentle exfoliation and by encouraging collagen production.

Chemical Peels (AHA peels):

Can improve overall skin tone and luster, but do little for scars, it works best if you get a series of at least six peels, having one every 1-2 weeks.

Skin Fillers/injectables:

Materials are injected into the depressed area of the scar to elevate it to the level of the normal surrounding skin. This treatment is best for scars with smooth shoulders such as thumbprint or rolling scars. Evaluating whether individual scars will respond to fillers is easily done by placing slight tension at the scar edge – if this improves the appearance of the scars, fillers will help. There are temporary and permanent fillers – examples are: Artecoll®, Zyplast®, Restylane®, and HylaForm®.

Non-ablative collagenosis:

New laser and radiofrequency devices are being evaluated for enhancing collagen formation in deeper skin layers without damaging the skin surface. It is possible that these treatments may also prove useful in acne scarring.

Surgical Treatment Options For Acne Scars

1. Microdermabrasion:

It uses very fine aluminum crystals to achieve light exfoliation of the skin. This is helpful for staining and very fine scars. It also works best if you get a series of at least 6, having one every 1-2 weeks.

2. Photorejuvenation:

Using laser or broadband visible light, 5-6 treatments that are performed every 3-4 weeks. This treatment improves mild acne scarring by causing new collagen formation.

3. Scar Revision:

Surgical removal (excision) of acne scars is especially effective for ice pick and boxcar scars. The excision may be in the form of a punch that is closed with sutures that are removed about 7 days later. The end result is replacement of a circular scar with a linear suture scar.

Another technique called subcision uses a sharp instrument to undercut the tethered bases of scars. In this case, the overlying skin is not cut so there is no need for sutures. Further improvement can then be achieved by injecting filler substances into the subcised regions.

4. Resurfacing:

a) Ablative Laser Treatments: – Laser resurfacing (CO2 laser, Erbium Yag laser): These resurfacing lasers remove the surface layer of skin and cause a zone of heat injury. The healing process allows for reformation with younger less scarred skin and deeper layer of new collagen formation.

b) Dermabrasion: – This is a mechanical procedure in which a rapidly rotating wire or brush is used to strip off the surface irregularities of skin. Felt by most experts to be the most effective primary treatment for extensive scarring, it can be used in conjunction with fillers and excision.

Treatment options according to acne scar type

Ice pick and boxcar scars

• Dermabrasion
• Laser resurfacing
• Punch grafting for deep scars
• TCA CROSS (Chemical Reconstruction Of Skin Scarring) uses precisely placed 50–100% trichloracetic acid
• Subcision®: a surgical technique in which the fibrous band under the scar is divided, allowing the skin to return to its normal position
• Larger scars can be excised (cut out) and the defect closed to form a scar in a thin line

Atrophic and rolling scars

• Soft tissue augmentation techniques such as hyaluronic acid, collagen, gelatin matrix and fat implants
• Dermabrasion
• Skin needling
• Laser resurfacing (Er:YAG and ablative fractional lasers)

Hypertrophic scars

• Potent topical steroids applied under occlusion to the scar for a few weeks
• Intralesional steroid injections into the body of the scar
• Silicone gel dressings applied for 24 hours a day continously for some months
• Skin needling
• Cryotherapy (freezing)
• Surgical revision

Unfortunately, hypertrophic or keloid scars are particularly prone to recur even after apparently successful treatment.

Treatment Modalities for Acne Scars

Among the therapeutic tools for treatment of acne scarring are resurfacing methods, fillers, and other dermal remodeling techniques. These methods can be adapted to treat specific acne scar types.

Resurfacing

Resurfacing options include:

• Ablative resurfacing with carbon dioxide or erbium: yttrium aluminum garnet (Er:YAG) laser, medium- depth to deep chemical peel, dermabrasion, or plasma
• Nonablative and partially ablative resurfacing with fractional laser, infrared laser (1,320nm neodymium:YAG (Nd:YAG), 1,450nm diode, or 1,540nm erbium:Glass)

Ablative Resurfacing

Ablative resurfacing entails removal of the epidermis and partial thickness dermis, and is considered by most as the gold standard for pitted scars and some box-car scars. While ablative resurfacing is most effective if it is deep, thereby removing as much as possible of the depressed scar, it cannot be so deep as to destroy the base of the hair follicles; such destruction could impede skin regrowth, and induce scar formation at the treated site. Carbon dioxide resurfacing is the most effective but also most operator-dependent method for deep ablative resurfacing ⁷⁶⁾. Dermabrasion is possibly even more effective, but this is another procedure that is very technique dependent. Deep phenol (Baker-Gordon) peels, also highly effective, have fallen out of favor because of the associated cardiac risk and the frequency of porcelain-white postinflammatory hypopigmentation. Definitive ablative resurfacing results in 2 weeks of patient downtime, during which period re-epithelialization occurs ⁷⁷⁾. More superficial resurfacing with the Er:YAG laser or plasma can provide recovery within 1 week, but deeper acne scars may be less improved.

Nonablative Resurfacing

Nonablative resurfacing with laser and lights warms the dermis and can provide modest improvement of acne scarring by stimulating collagen remodeling. All subtypes of acne scars can be improved by nonablative therapy. Among the lasers used for this indication are devices originally developed for other uses, such as pulsed-dye lasers, intense pulsed light devices, and Q-switched Nd:YAG lasers. However, more recently nonablative devices have been optimized to specifically target textural irregularities. For example, a series of treatments with infrared lasers can significantly improve uneven contour associated with acne scarring ⁷⁸⁾. These treatments are typically uncomfortable and may require oral and/or topical analgesics.

Similarly, fractional resurfacing is quite effective in the treatment of acne scarring. Fractional resurfacing is a minimally ablative technique that creates microscopic zones of dermal injury in a grid-like pattern ⁷⁹⁾. Because only a small proportion of the skin surface is treated at one time, and since the stratum corneum is not perforated, recovery is quick. However, a series of treatments is needed.

Fillers

During the past 5 years, many new injectable prepackaged soft-tissue augmentation materials have become available in the US. Among these are the so-called linear fillers, which permit fine correction of individual lines and depressions: human collagen, hyaluronic acid derivatives, calcium hydroxylapatite (off-label use), and silicone (off-label use).

Injectable linear fillers can enable short-, medium-, or long-term correction of acne scars. Large-particle fillers such as calcium hydroxylapatite have a longer persistence in vivo and are appropriate for larger areas of rolling scars; thicker fillers must be injected no higher than the dermal subcutaneous junction. Collagen or hyaluronic acid products can be injected directly beneath individual pitted or box-car scars, or be used to buttress areas of rolling scars. Patients should be advised that the duration of action varies, with collagen lasting 2-3 months, hyaluronic acid products, 4-6 months, and calcium hydroxylapatite, 1 year. Volumetric fillers, such as poly-L-lactic acid, may not be appropriate for acne scars, except for rolling scars. By definition, volumetric fillers are designed to correct skin and subcutaneous wasting over wide areas rather than individual fine textural abnormalities.

Injectable silicone is a controversial product gaining new acceptance as a filler for correction of acne scars, especially pitted and box-car scars ⁸⁰⁾. Now approved by the US FDA for intraocular tamponade, medical-grade silicone is used off-label for permanent correction of acne scars. To avoid delayed hypersensitivity and immune reactivity, very small aliquots of 0.01ml, known as “microdroplets”, are used, and placement is sparse. Repeat treatments with small quantities enable gradual complete correction. The inconvenience of numerous treatments, as well as the theoretical risks of adverse events are mitigated by the promise of permanence.

Excision and Subcision

Ice-pick and box-car scars may also be removed by surgical excision. This technique may entail punch excision of a given small acne scar with a punch biopsy instrument of equal or slightly greater diameter. Then one or two 5.0 or 6.0 simple interrupted sutures are used to close the resulting defect, with the attendant transformation of a round, indented scar into a flat slit-like scar. Larger linear box-car scars can be excised by elliptical excision and repaired by bilayered closure. Sufficient eversion is necessary to avoid recurrence of an indented groove.

Alternatively, after punch excision of a small scar, the defect may be filled by a punch graft. Harvested from another area, commonly the postauricular sulcus, a punch graft is pressed into the created defect and either sutured or glued in place. Punch grafting creates a secondary defect and risks poor color and texture match between donor and recipient sites. However, by filling the deadspace at the excision site, punch grafting may reduce the likelihood that scar excision and closure will fail because of excessive tension in the closure.

Subcision treats rolling scars by separating the fibrous bands securing them to the deep dermis ⁸¹⁾. A sharp device, often an 18-gauge Nokor® needle with a spear-like tip, is inserted at an angle into the dermis at a distance of 1–2cm from the scar. The needle tip is aimed upward, tenting but not puncturing the skin, and is advanced to a point under the scar. Backward and forward rasping of the underside of the dermis beneath the scar is used to sever fibrous bands while initiating a reactive fibrosis that gradually, over several weeks, propels the depressed scar upwards. Bruising following subcision can last 1–2 weeks, but the procedure is well-tolerated with local infiltration of anesthetic. A benefit of subcision is the absence of any epidermal injury, except for minute needle insertion points.

Treatment Modalities for Color Change due to acne scars

Laser and light sources can be used to improve acne-associated color change, especially erythema. Difficult-to-correct textural abnormalities associated with acne scarring can be camouflaged by reducing the ring of redness around such scars. The redness accentuates the depth of the scar and focuses the observer’s attention, but removal of the redness can make the scar seem less deep and noticeable, even if the depth and size are objectively unchanged. Pulsed-dye laser ⁸²⁾, KTP laser, and intense pulsed light devices can be used for treatment of peripheral redness around acne scars. Usually, 3–4 or more treatments are required, at approximately 1 month intervals.

Brown discoloration around acne scars tends to occur in darker-skinned patients and is usually postinflammatory. As with all postinflammatory hyperpigmentation, the treatment of choice is the passage of time. Managing any residual active acne is also crucial, as further acne lesions will give rise to additional pigmentation. In some cases, a topical bleaching agent, such as 4% hydroquinone, may be appropriate adjuvant therapy.

What is the outlook for acne ?

Acne tends to improve after the age of 25 years but may persist, especially in females.

Treatment with isotretinoin can lead to long-term remission in many patients.

Home remedies for acne and pimples

Many over-the-counter (OTC) acne products are available to treat mild to moderate acne or periodic breakouts. They include cleansing lotions, gels, foams and towelettes, leave-on products, and treatments or kits.

How do you know which one is best for you ?

Before you decide, learn how over-the-counter (OTC) acne products work and what ingredients to look for. Then develop a gentle skin care regimen to treat and prevent acne.

The Food and Drug Administration warns that some popular over-the-counter (OTC) acne products can cause a serious reaction, including throat tightness and swelling of the face, lips or tongue. This type of reaction is quite rare, so don’t confuse it with the redness, irritation or itchiness that may occur where you’ve applied such products.

Active ingredients in acne products

Acne products work in different ways, depending on their active ingredients. Some OTC acne products work by killing the bacteria that cause acne inflammation. Others remove excess oil from the skin or speed up the growth of new skin cells and the removal of dead skin cells. Some acne products do a combination of these things.

Here are common active ingredients found in OTC acne products and how they work to treat acne.

• Benzoyl peroxide. This ingredient kills the bacteria that cause acne, helps remove excess oil from the skin and removes dead skin cells, which can clog pores. OTC benzoyl peroxide products are available in strengths from 2.5 to 10 percent. Possible side effects include dry skin, scaling, redness, burning and stinging, especially if you have sensitive skin. Be careful when applying benzoyl peroxide, as it can bleach hair and clothing.
• Salicylic acid. This ingredient helps prevent pores from becoming plugged. OTC salicylic acid products are available in strengths from 0.5 to 5 percent. Possible side effects include mild stinging and skin irritation.
• Alpha hydroxy acids. Two types of alpha hydroxy acids that are used in nonprescription acne products are glycolic acid and lactic acid. Alpha hydroxy acids are synthetic versions of acids derived from sugar-containing fruits. They treat acne by helping to remove dead skin cells and reduce inflammation. Alpha hydroxy acids also stimulate the growth of new, smoother skin. This helps improve the appearance of acne scars and gives the impression of smaller pores.
• Sulfur. Sulfur removes dead skin cells that clog pores and helps remove excess oil. It’s often combined with other ingredients, such as salicylic acid, benzoyl peroxide or resorcinol. Products containing sulfur may cause dry skin. And some products have an unpleasant odor.

Choosing an effective acne product

The acne product that’s best for you depends on many factors, including your skin type, the type and severity of your acne, and your skin care preferences. Here are some general guidelines for choosing and using acne products:

1. Begin with benzoyl peroxide. If you’re not sure which acne product to buy, start with one that contains benzoyl peroxide. It’s effective and well-tolerated by most people. Give it a few days before expecting to see results. Check product labels for the type and amount of its active ingredient. Stronger isn’t always better with benzoyl peroxide. In some cases, a 2.5 percent product works as well as those with stronger concentrations — and with fewer side effects.
2. Start with lower strength acne products. This can help minimize redness, dry skin and other skin problems. If needed, slowly — over several weeks — increase the strength of the product you use and how often you use it. This helps your skin adjust to the treatment gradually.
3. Use products with different active ingredients to treat stubborn acne. Acne ingredients work in different ways, so you may find it helpful to use varying products and ingredients to treat stubborn acne. Apply one product in the morning and a different one at night to prevent skin irritation.
4. Be patient. Treating acne with acne products takes time and patience. It may take two or three months of daily use of an acne product to see results. And acne may look worse before it gets better.
5. Experiment with what works. You may need to try different products with varying active ingredients before you find what works for you.

Skin care tips when using acne products

Acne products are just one step in your skin care routine. When using acne products:

1. Wash problem areas twice daily. Use a gentle nonsoap cleanser and don’t overdo it. Excessive washing and scrubbing can worsen acne. Scrubs that dissolve during washing are the least abrasive. Scrubs with ground fruit pits and aluminum oxide tend to be more abrasive.
2. Try cleansing cloths or towelettes. These are gentle alternatives to cleansers and washes. Cloths with an open weave are good for dry, sensitive skin. Cloths with a tighter weave are better at removing dead skin cells.
3. Consider pore-clearing adhesive pads. These products (Biore Deep Cleansing Pore Strips, others) are intended to remove dirt, oil and plugs from pores. You apply the strip to wet skin, let it dry and then peel it off. Further study is needed to prove their use in treating and preventing acne. Don’t use them more than once every three days.
4. Don’t use too much. Apply just enough acne product to cover the problem areas and apply it just after cleansing the skin. Some cloths and towelettes come with benzoyl peroxide and other active ingredients in them, so you don’t need to apply more product with these active ingredients after cleansing.
5. Use an oil-free, water-based moisturizer. This helps alleviate dry, peeling skin.
6. Avoid oily cosmetics, sunscreens and hair products. Use products labeled water-based or noncomedogenic.
7. Don’t pick or squeeze blemishes. Infection or scarring may result.
8. Watch what touches your face. Keep your hair clean and off your face. Also avoid resting your hand or phone against the side of your face.

If your acne doesn’t improve after two or three months of home treatment, consider seeing your doctor or a skin specialist (dermatologist) for a prescription lotion or medication.

OTHER THERAPIES

Some natural treatments may be helpful in reducing acne inflammation and breakouts:

Topical treatments

• Tea tree oil. Gels containing at least 5 percent tea tree oil may be as effective as lotions containing 5 percent benzoyl peroxide, although tea tree oil might work more slowly. Possible side effects include minor itching, burning, redness and dryness. Tea tree oil should be used only topically.
• Bovine cartilage. Creams containing 5 percent bovine cartilage, applied to the affected skin twice a day, may be effective in reducing acne.

Oral treatments

• Zinc. The mineral zinc plays a role in wound healing and reduces inflammation, which may help improve acne. It may cause a metallic taste, bloating and diarrhea.
• Brewer’s yeast. A specific strain of brewer’s yeast, called Hansen CBS, seems to help decrease acne when taken orally. It may cause gas (flatulence).

Talk with your doctor about the pros and cons of specific treatments before you try them.

Table 6 summarizes other therapies that are used in the treatment of acne, with varying levels of evidence to support their use.

Table 6. Miscellaneous Therapies for the Treatment of Acne

Therapy	Evidence
Acupuncture	Ah-shi acupuncture is no better than general acupuncture treatment
Avoidance of chocolate or sugar consumption	No evidence of effectiveness
Biofeedback	May enhance response to medical treatment for acne
Chemical peel (glycolic/salicylic acid)	No studies of effectiveness
Comedo removal	May help with treatment-resistant comedones and provide short-term reductions in the number of noninflammatory lesions
Intralesional steroids	May improve individual large cystic lesions
Microdermabrasion	No evidence of effectiveness
Tea tree (Melaleuca alternifolia) oil	Effective for total lesion reduction of papules, pustules, and comedones in mild to moderate acne

[Sources ⁸³⁾, ⁸⁴⁾, ⁸⁵⁾, ⁸⁶⁾, ⁸⁷⁾]