Acne

Introduction to Acne

(see below for detailed articles and advice)

Acne is a chronic skin disorder in which there is inflammation of the sebaceous gland at the base of hair follicles in the skin.

Types

The most common type of acne is sometimes known as acne vulgaris, which almost always develops during puberty. Chemical acne is caused by exposure of the skin to certain chemicals and oils. This results in the development of acne in areas where the chemical has come into contact with the skin, such as on the thighs. Certain prescribed drugs, such as corticosteroid drugs, can also cause acne.

Causes

Acne spots are caused by the obstruction of hair follicles by excess sebum (the oily substance secreted by the sebaceous glands). Bacteria multiply in the follicle, causing inflammation. Hormonal changes at puberty, including increased levels of androgen hormones (male sex hormones) in both males and females, stimulate the production of sebum. There may also be a genetic pre-disposition to acne.

Symptoms

Acne develops in areas in which there is a high concentration of sebaceous glands, mainly the face, centre of the chest, upper back, shoulders, and around the neck. Milia (whiteheads), comedones (blackheads), nodules (firm swellings under the skin), and cysts (larger, fluid-filled swellings) are the most common types of spot. Some, particularly cystic spots, leave scars.

Treatment and Outlook

There is no instant cure for acne, although washing the affected areas at least twice a day with a mild soap may help to keep it under control. Over-the-counter topical drug treatments such as benzoyl peroxide or azelaic acid are often effective. Prescribed topical antibiotic drugs or retinoic acid (a derivative of vitamin A) are used to treat moderate acne. Alternative treatment is with oral antibiotics, often tetracycline drugs. In very severe cases, isotretinoin may be given under hospital supervision. In all cases, exposure to ultraviolet light (either natural or artificial) may also be beneficial. However, it is important not to burn the skin. Acne improves slowly over time, and it often clears up by the end of the teenage years, but it may continue even up to the age of 50 and beyond. 

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Longer article about acne

What is acne?

Acne (acne vulgaris, common acne) is a disease of the hair follicles of the face, chest, and back that affects almost all males and females during puberty; the only exception being teenage members of a few primitive isolated tribes living in Neolithic societies. It is not caused by bacteria, although bacteria play a role in its development. It is not unusual for some women to develop acne in their mid- to late-20s.

Acne appears on the skin as...

  • congested pores ("comedones"), also known as blackheads or whiteheads,
  • tender red bumps also known as pimples or zits, pustules,
  • and occasionally as cysts (deep pimples, boils).

You can do a lot to treat your acne using products available at a drugstore or cosmetic counter that do not require a prescription. However, for tougher cases of acne, you should consult a physician for treatment options.

What causes acne?

No one factor causes acne. Acne happens when sebaceous (oil) glands attached to the hair follicles are stimulated at the time of puberty by elevated levels of male hormones.

Sebum (oil) is a natural substance which lubricates and protects the skin. Associated with increased oil production is a change in the manner in which the skin cells mature so that they are predisposed to clog the follicular openings or pores.

The clogged hair follicle gradually enlarges, producing a bump. As the follicle enlarges, the wall may rupture, allowing irritating substances and normal skin bacteria access into the deeper layers of the skin, ultimately producing inflammation.

Inflammation near the skin's surface produces a pustule; deeper inflammation results in a papule (pimple); deeper still and it's a cyst.

If the oil breaks though to the surface, the result is a "whitehead."

If the oil accumulates melanin pigment or becomes oxidized, the oil changes from white to black, and the result is a "blackhead." Blackheads are therefore not dirt and do not reflect poor hygiene.

Here are some factors that don't usually play a role in acne:

  • Heredity: With the exception of very severe acne, most people do not have the problem exactly as their parents did. Almost everyone has some acne at some point in their life.
  • Food: Parents often tell teens to avoid pizza, chocolate, greasy and fried foods, and junk food. While these foods may not be good for overall health, they don't cause acne or make it worse. Although some recent studies have implicated milk and pure chocolate in aggravating acne, these findings are very far from established.
  • Dirt: As mentioned above, "blackheads" are oxidized oil, not dirt. Sweat does not cause acne, therefore, it is not necessary to shower instantly after exercise for fear that sweat will clog pores. On the other hand, excessive washing can dry and irritate the skin.
  • Stress: Some people get so upset by their pimples that they pick at them and make them last longer. Stress, however, does not play much of a direct role in causing acne.

In occasional patients, the following may be contributing factors:

Physical Pressure:

In some patients, pressure from helmets, chin straps, collars, suspenders, and the like can aggravate acne.

Drugs:

Some medications may cause or worsen acne, such as those containing iodides, bromides, or oral or injected steroids (either the medically prescribed prednisone [Deltasone, Orasone, Prednicen-M, Liquid Pred] or the steroids that bodybuilders or athletes take). Other drugs that can cause or aggravate acne are anticonvulsant medications and lithium (Eskalith, Lithobid), which is used to treat bipolar disorder. Most cases of acne, however, are not drug related.

Occupations:

In some jobs, exposure to industrial products like cutting oils may produce acne.

Cosmetics:

Some cosmetics and skin-care products are pore clogging ("comedogenic"). Of the many available brands of skin-care products, it is important to read the list of ingredients and choose those which have water listed first or second if you are concerned about acne. These "water-based" products are usually safe.

What other skin conditions can mimic acne?

Rosacea

This condition is characterized by pimples but not comedones and occurs in the middle third of the face, along with redness, flushing, and superficial blood vessels. It generally affects people in their 30s and 40s and older.

Pseudofolliculitis

This is sometimes called "razor bumps" or "razor rash." When cut close to the skin, curly neck hairs bend under the skin and produce pimples. This is a mechanical problem, and treatment involves shaving less (growing a beard, laser hair removal). Pseudofolliculitis can, of course, occur in patients who have acne, too.Folliculitis Pimples can occur on other parts of the body, such as the abdomen, buttocks, or legs. These represent not acne but inflamed follicles. If these don't go away on their own, doctors can prescribe oral or external antibiotics, generally not the same ones used for acne.

Gram-negative folliculitis

Some patients who have been treated with oral antibiotics for long periods develop pustules filled with bacteria resistant to the antibiotics which have previously been used. Bacterial culture tests can identify these germs, leading the doctor to prescribe different antibiotics or other forms of treatment.

When should you start acne treatment?

Everyone gets acne at some time, the right time to treat it is when it bothers you or when the potential for scarring develops. This can be when severe acne flares suddenly, for mild acne that just won't go away, or even when a single pimple decides to show up the week before your prom or wedding. The decision is yours.

What can you do about acne on your own?

Think back to the three basic causes of acne and you can understand why the focus of both home treatment and prescription therapy is to (1) unclog pores, (2) kill bacteria, and (3) minimize oil. But first a word about...

Lifestyle:

Moderation and regularity are good things, but not everyone can sleep eight hours, eat three good meals, and drink eight glasses of water a day. You can, however, still control your acne even if your routine is frantic and unpredictable.Probably the most useful lifestyle changes you can make are to never to pick or squeeze pimples. Playing with or popping pimples, no matter how careful and clean you are, nearly always makes bumps stay redder and bumpier longer. People often refer to redness as "scarring," but fortunately it usually isn't in the permanent sense. It's just a mark that takes months to fade if left entirely alone.

Open the pores

Cleansing and skin care

Despite what you read in popular style and fashion magazines, there is no magic product or regimen that is right for every person and situation.

  • Mild cleansers: Washing once or twice a day with a mild cleansing bar or liquid (for example, Dove, Neutrogena, Basis, Purpose, and Cetaphil are all inexpensive and popular) will keep the skin clean and minimize sensitivity and irritation.
  • Exfoliating cleansers and masques: A variety of mild scrubs, exfoliants, and masks can be used. These products contain either fine granules or salicylic acid in a concentration that makes it a very mild peeling agent. These products remove the outer layer of the skin and thus open pores. Products containing glycolic or alpha hydroxy acids are also gentle skin exfoliants.
  • Retinol: Not to be confused with the prescription medication Retin-A, this derivative of vitamin A can help promote skin peeling.

Kill the bacteria

  • Antibacterial cleansers: The most popular ingredient in over-the-counter antibacterial cleansers is benzoyl peroxide.
  • Topical (external) applications: These products come in the form of gels, creams, and lotions, which are applied to the affected area. The active ingredients that kill surface bacteria include benzoyl peroxide, sulfur, and resorcinol. Some brands promoted on the Internet and cable TV (such as ProActiv) are much more costly than identical products you can buy in the drugstore.
  • Benzoyl peroxide causes red and scaly skin irritation in a small number of people, which goes away as soon as you stop using the product. Keep in mind that benzoyl peroxide is a bleach, so do not let products containing benzoyl peroxide leave unsightly blotching on colored clothes, shirts, towels, and carpets.

Reduce the oil.

You cannot stop your oil glands from producing oil (unless you mess with your hormones or metabolism in ways you shouldn't). Even isotretinooin(Roaccutane, see below) only slows down oil glands for a while; they come back to life later. What you can do is to get rid of oil on the surface of the skin and reduce the embarrassing shine.

Use a gentle astringent/toner to wipe away oil. (There are many brands available in pharmacies, as well as from manufacturers of cosmetic lines.) Products containing glycolic acid or one of the other alpha hydroxy acids are also mildly helpful in clearing the skin by causing the superficial layer of the skin to peel (exfoliate). Masks containing sulfur and other ingredients draw out facial oil. Antibacterial pads containing benzoyl peroxide have the additional benefit of helping you wipe away oil.

What are other things you can do for acne?

Cosmetics:

Don't be afraid to hide blemishes with flesh-tinted coverups or even foundation, as long at it is water-based (which makes it noncomedogenic). There are many quality products available.

Facials:

While not absolutely essential, steaming and "deep-cleaning" pores is useful, both alone and in addition to medical treatment, especially for people with "whiteheads" or "blackheads." Having these pores unclogged by a professional also reduces the temptation to do it yourself.

Pore strips:

Pharmacies now carry, under a variety of brand names, strips which you put on your nose, forehead, chin, etc., to "pull out" oil from your pores. These are, in effect, a do-it-yourself facial. They are inexpensive, safe, and work reasonably well if used properly.

Toothpaste?

One popular home remedy is to put toothpaste on zits. There is no medical basis for this. Ditto for vinegar.

What is a good basic skin regimen?

These are all good basic skin regimens that may help with the acne battle: Cleanse twice daily with a 5% benzoyl peroxide wash. An alternative for those who are allergic to benzoyl peroxide is 2% salicylic acid. Apply a gel or cream containing 5% benzoyl peroxide; an alternative is sulfur or resorcinol. At night, apply a spot cream containing sulfur to the affected areas. Use a light skin moisturizer and water-based oil-free makeup.

What can the doctor do for acne?

If you haven't been able to control your acne adequately, you may want to consult a primary-care physician or dermatologist. The goal of treatment should be the prevention of scarring (not a flawless complexion) so that after the condition spontaneously resolves there is no lasting sign of the affliction.

Here are some of the options available:

Topical (externally applied) antibiotics and antibacterials:

These include erythromycin (E-Mycin, Eryc, Ery-Tab, PCE, Pediazole, Ilosone), clindamycin (BenzaClin, Duac), sulfacetamide (Klaron), and azelaic acid (Azelex or Finacea). Retinoids: Retin-A (tretinoin) has been around for years, and preparations have become milder and gentler while still maintaining its effectiveness. Newer retinoids include adapalene (Differin) and tazarotene (Tazorac). These medications are especially helpful for unclogging pores. Side effects may include irritation and a mild increase in sensitivity to the sun. With proper sun protection, however, they can be used even during sunny periods. In December 2008, the U.S. FDA approved the combination medication known as Epiduo gel, which contains the retinoid adapalene along with the antibacterial cleanser benzoyl peroxide. This once-daily prescription treatment was approved for use in patients 12 years of age and older.

Oral antibiotics:

Doctors may start treatment with tetracycline (Sumycin) or one of the related "cyclines," such as doxycycline (Vibramycin, Oracea, Adoxa, Atridox and others) and minocycline (Dynacin, Minocin). Other oral antibiotics that are useful for treating acne are cefadroxil (Duricef), amoxicillin (Amoxil, DisperMox, Trimox), and the sulfa drugs. Problems with these drugs can include allergic reactions (especially sulfa), gastrointestinal upset, and increased sun sensitivity. Doxycycline, in particular, is generally safe but can sometime cause esophagitis (irritation of the esophagus, producing discomfort when swallowing) and an increased tendency to sunburn. Despite many people's concerns about using oral antibiotics for several months or longer, such use does not "weaken the immune system" and make them more susceptible to infections or unable to use other antibiotics when necessary. Recently published reports that long-term antibiotic use may increase the risk of breast cancer will require further study, but at present they are not substantiated. In general, doctors prescribe oral antibiotic therapy for acne only when necessary and for as short a time as possible.

Oral contraceptives:

Oral contraceptives, which are low in estrogen to promote safety, have little effect on acne one way or the other. Some contraceptive pills have been to shown to have modest effectiveness in treating acne. Those FDA approved for treating acne are Estrostep, Ortho Tri-Cyclen, and Yaz. Most dermatologists work together with primary physicians or gynecologists when recommending these medications.

Spironolactone (Aldactone):

This drug blocks androgen (hormone) receptors. It can cause breast tenderness, menstrual irregularities, and increased potassium levels in the bloodstream. It can help some women with resistant acne, however, and is generally well-tolerated in the young women who need it.

Cortisone injections:

To make large pimples and cysts flatten out fast, doctors inject them with a form of cortisone. Isotretinoin: (Accutane was the original brand name; there are now several generic versions in common use, including Sotret, Claravis, and Amnesteem.)

Isotretinoin

Isotretinoin is an excellent treatment for severe, resistant acne and has been used on millions of patients since it was introduced in Europe in 1971 and in the U.S. in 1982. It should be used for people with severe acne, chiefly of the cystic variety, which has been unresponsive to conventional therapies like those listed above. The drug has many potential serious side effects and requires a number of unique controls before it is prescribed. This means that isotretinoin is not a good choice for people whose acne is not that bad but who are frustrated and want "something that will knock acne out once and for all." Used properly, isotretinoin is safe and produces few side effects beyond dry lips and occasional muscle aches. This drug is prescribed for five to six months.

Fasting blood tests are monitored monthly to check liver function and the level of triglycerides, substances related to cholesterol, which often rise a bit during treatment, but rarely to the point where treatment has to be modified or stopped. Even though isotretinoin does not remain in the body after therapy is stopped, improvement is often long-lasting. It is safe to take two or three courses of the drug if unresponsive acne makes a comeback. It is, however, best to wait at least several months and to try other methods before using isotretinoin again.

Isotretinoin has a high risk of inducing birth defects if taken by pregnant women. Women of childbearing age who take isotretinoin need two negative pregnancy tests (blood or urine) before starting the drug, monthly tests while they take it, and another after they are done.

Those who are sexually active must use two forms of contraception, one of which is usually the oral contraceptive pill. Isotretinoin leaves the body completely when treatment is done; women must be sure to avoid pregnancy for one month after therapy is stopped. There is, however, no risk to childbearing after that time.

Other concerns include inflammatory bowel disease and the risk of depression and suicide in patients taking isotretinoin.

Government oversight has resulted in a highly publicized and very burdensome national registration system for those taking the drug. This has reinforced concerns in many patients and their families have that isotretinoin is dangerous. In fact, large-scale studies so far have shown no convincing evidence of increased risk for those taking isotretinoin compared with the general population. It is important for those taking this drug to report changes in mood or bowel habits (or any other symptoms) to their doctors. Even patients who are being treated for depression are not barred from taking isotretinoin, whose striking success often improves the mood and outlook of patients with severe disease.

Laser treatments:

Recent years have brought reports of success in treating acne using lasers and similar devices, alone or in conjunction with photosensitizing dyes. It appears that these treatments are safe and can be effective, but it is not clear that their success is lasting. At this point, laser treatment of acne is best thought of as an adjunct to conventional therapy, rather than as a substitute.

Chemical peels:

Whether the superficial peels (like glycolic acid) performed by aestheticians or deeper ones performed in the doctor's office, chemical peels are of modest, supportive benefit only, and in general, they do not substitute for regular therapy.

Treatment of acne scars:

For those patients whose acne has gone away but left them with permanent scarring, several options are available. These include surgical procedures to elevate deep, depressed acne scars and laser resurfacing to smooth out shallow acne scars. Newer forms of laser resurfacing ("fractional resurfacing") are less invasive and heal faster than older methods, although results are less complete and they may need to be repeated three or more times. These treatments can help, but they are never completely successful at eliminating acne scars.

Acne in detail - medical article written for doctors - (technical article and language)

This is a polymorphic inflammatory disease of the pilosebaceous follicles, predominantly affecting the skin of the face and trunk. It is one of the most common skin diseases encountered by community physicians and dermatologists. Acne can present at any age, from neonates to mature adults, but is most prevalent and most severe during adolescence with 30% of teenagers requiring medical treatment.

The pathogenesis of acne relates to an increase in androgen-mediated sebum production, follicular hyperkeratosis, proliferation of Propionibacterium acnes, and inflammation. There appear to be three phases in the development of acne, an innate immune response mediated by IL-1α, followed by microcomedo formation, and then visible inflammation associated with a specific delayed-type hypersensitivity response.

Hyperkeratinization of the sebaceous duct is mediated by IL-1α and tumour necrosis factor-α (TNF-α) from keratinocytes and T lymphocytes. The result is hyperproliferation of keratinocytes, reduced apoptosis, and consequent hypergranulosis. The sebaceous follicle becomes blocked with dense keratin and so evolves the microcomedo, considered to be the precursor to both the noninflammatory (blackheads/whiteheads) and inflammatory lesions seen in acne. P. acnes colonize the skin surface and pilosebaceous ducts and bind to the Toll-like receptor 2 (TLR-2) on monocytes and neutrophils, leading to the induction of macrophage or keratinocyte secretion of IL-12. This results in the differentiation of T cells, leading to the activation of Th 1 cells when they encounter their antigen in the dermis.

The resulting inflammatory lesions embrace papules and pustules in most cases, but deeper inflamed lesions may present as acne nodules. When examining acne it is useful to adopt a grading system so that improvements can be quantified. Scars frequently occur in acne and are not necessarily related to the severity of the inflamed acne lesions.

Management

Assessment of the acne should include a thorough history, including details of family history, duration of acne, previous therapies, and response to treatments, along with careful physical examination. The majority of patients do not have an endocrine problem relating to their acne, however, polycystic ovary syndrome should be considered in women who have persistent/late-onset disease particularly if this coexists with other signs of hyperandrogenism such as hirsutism, irregular menses, or infertility. Cushingoid features, androgenic alopecia, acanthosis nigricans, and deepening of the voice may also reflect hyperandrogenism. These patients frequently have insulin resistance and are at increased risk of developing type 2 diabetes and possibly cardiovascular disease. Late-onset adrenal hyperplasia can also trigger late-onset acne in both sexes. Table 1 summarizes the investigations used to confirm or refute these diagnoses.

Response to treatment can be slow and patients must be encouraged to adhere to the chosen treatment regimen. Acne and scarring can result in significant psychological and social disability in predisposed individuals, e.g. anxiety, depression, social isolation, and interpersonal difficulties.

Topical therapies form the mainstay of treatment for mild to moderate acne. The choice of preparation will depend on the type of acne present (Table 2). Topical retinoids treat noninflammatory and inflammatory acne. They reverse hypercornification and induce proliferation of the follicular epithelium, thus helping to ‘unplug’ the follicle. The less anaerobic conditions that result lead to a reduction in P. acnes. Given the central role of the microcomedo in the early development of both noninflammatory and inflammatory lesions, most patients require a topical retinoid as part of their treatment regime. Retinoids are also now being considered for maintenance therapy. Skin irritation is a common side effect but is less problematic with the newer retinoids (topical isotretinoin and adapalene). Irritation is minimized by using lower concentrations for shorter durations. Topical retinoids are contraindicated in pregnancy.

Table 1 Investigating the underlying endocrine abnormalities implicated in acne
Cause Investigations
Polycystic ovary syndrome Day 1–5 of menstrual cycle:
Total and free testosterone
LH/FSH
SHBG
Ultrasonography of ovaries (not mandatory but may help to support the clinical impression)
Congenital adrenal hyperplasia 17-Hydroxyprogesterone
DHEAS
Cortisol levels
Cushing’s syndrome Dexamethasone suppression test
Gonadal or adrenal tumours Total and free testosterone
DHEAS

DHEAS, dehydroepiandrosterone sulphate; LH/FSH, luteinizing/follicle-stimulating hormone ratio; SHBG, sex-hormone binding globulin.
Table 2 Topical therapies for acne: impact on aetiology

 

  Inflammation Comedogenesis Reduction in Propionibacterium acnes
BPO +++ + +++
Retinoids
  • Tretinoin
  • Isotretinoin
  • Adapalene
  • +
  • +
  • ++
  • +++
  • ++
  • ++
  • –
  • –
  • –
Antibiotics
  • Erythromycin
  • Tetracycline
  • Clindamycin
  • +++
  • +++
  • +++
  • ±
  • ±
  • ±
  • +++
  • +++
  • +++
Combination therapies
  • Zinc/erythromycin
  • BPO/erythromycin
  • Isotretinoin/erythromycin
  • BPO/clindamycin
  • +++
  • +++
  • ++
  • +++
  • +
  • +
  • +
  • +
  • +++
  • +++
  • +++
  • +++

BPO, benzoyl peroxide.

Benzoyl peroxide (BPO) is a powerful antimicrobial agent. It decomposes to release free oxygen radicals in the sebaceous follicles, which have bactericidal and anti-inflammatory effects. BPO is active against fully sensitive and resistant strains of P. acnes. One high quality, randomized controlled trial demonstrated that BPO was as effective as oral oxytetracline and minocycline in mild/mild to moderate acne. BPO is available alone in concentrations of 2.5 to 10% and in combination with agents including hydroxyquinoline, erythromycin, and clindamycin. Lower concentrations are as effective as 10% and less irritant. Infrequently an allergic contact dermatitis occurs. BPO can bleach clothes and hair, so patients should be informed.

Topical antibiotics both reduce P. acnes and are anti-inflammatory through suppressing leucocyte chemotaxis and decreasing a proportion of proinflammatory free fatty acids and surface lipids. Topical erythromycin and clindamycin have been shown to be as effective as BPO in mild acne and are seemingly equally effective in treating moderate facial acne. As topical antibiotics drive bacterial resistance, they should be avoided as monotherapy over prolonged periods.

Evidence supports a direct correlation between P. acnes resistance and failure to respond to oral antibiotic treatment. Resistance to erythromycin can be reduced by using a combination of erythromycin and zinc or erythromycin and BPO peroxide.

Azelaic acid has some effect on inflamed acne lesions as it can reduce the number of P. acnes. It may be irritant and, rarely, photosensitivity can occur. Nicotinamide gel represents an alternative topical anti-inflammatory therapy; it has been shown to be as effective as 1% clindamycin gel and has the advantage of not promoting bacterial resistance.

Topical treatments can work synergistically when used in combination. Topical antibiotics and BPO are more effective than BPO as a single therapy. When combined with zinc, topical erythromycin has increased therapeutic efficacy. When retinoids are used in combination with antimicrobial agents, the combination produces faster results and significantly greater reductions in acne lesions. Compliance may be enhanced by using combinations products.

Table 3 Systemic antibiotics for acne—dosage and adverse effects
Drug Dosage Adverse effects
Oxytetracycline 500 mg twice a day Rare onycholysis, photosensitivity, benign intracranial hypertension
Erythromycin 500 mg twice a day Gastrointestinal upset, nausea, diarrhoea all fairly common
Minocycline 100–200 mg daily Headaches (dose dependent), pigmentary changes, autoimmune hepatitis/lupus erythematosus-like syndromea
Doxycycline 100–200 mg daily Photosensitivity (dose dependent)
Lymecycline 300–600 mg daily Less than minocycline
Trimethoprim 200–300 mg twice a day Rare hepatic/renal toxicity agranulocytosis

ANA, antinuclear antibody; LFT, liver function test; p-ANCA, perinuclear antineutrophilic cytoplasmic antibody.

a Advise, monitor LFTs, ANA, and p-ANCA in ‘at risk’ patients or when treatment is prolonged (>6 months). Cyclines are contraindicated in pregnancy and in children below 12 years.

Systemic therapy is used for moderate to severe acne, or mild to moderate acne associated with scarring or significant psychosocial disability and/or failure to respond to topical treatment when it may be given in combination with topical therapy. Systemic antibiotic therapy (Table 3) reduces the number of P. acnes and S. epidermidis and proinflammatory mediators in the microcomedo. It also modulates the host response to these stimuli. Patients with marked seborrhoea and truncal acne respond less well to antibiotics. If oral antibiotics are to be incorporated into a regimen containing oral contraceptives, patients should still be warned about the possible decreased efficacy of the oral contraceptive, although, with the exception of rifampicin, there is currently no evidence to support the fact that commonly prescribed antibiotics either reduce blood levels and/or the effectiveness of oral contraceptives. Based on efficacy, safety, and bacterial resistance, cyclines should be used in preference to other classes of antibiotics. Oxytetracycline needs to be taken 30 min pre-food and not with milk to ensure adequate absorption. Second generation cyclines such as lymecycline (300–600 mg/day) and doxycycline (100–200 mg/day) may ensure better compliance and both have a better side effect profile than minocycline. Cyclines are contraindicated in children below 12 years of age and in pregnancy as they can affect dentition and result in inhibition of skeletal growth in the fetus.

The increasing incidence of P. acnes resistance to erythromycin and the link between erythromycin resistant P. acnes and reduced therapeutic response has resulted in the recommendation that erythromycin should be restricted. Erythromycin 1 g daily is the antibiotic of choice in pregnancy. Trimethoprim 200 to 300 mg daily is a third-line option for patients who have failed to respond to alternative antibiotics.

Combining topical and systemic treatment aids more rapid efficacy and potentially reduces the length of exposure to antibiotics, so reducing the likelihood of emerging antibiotic resistance. Antibiotic resistant P. acnes were first detected in the United States of America in the late 1970s. The worldwide incidence of antibiotic resistant P. acnes has increased significantly over the last decade. Carriage of resistant P. acnes can result in reduced therapeutic response to antibiotics. This is true for both erythromycin and tetracycline.

To reduce emerging resistance, oral antibiotics should only be used for 6 to 12 weeks in the first instance and only for as long as there is further clinical improvement. If the patient relapses after discontinuing the antibiotics, the same antibiotic should be restarted where possible. The addition of topical BPO can be used to try and eliminate resistant organisms.

Hormonal therapies can help females with acne whether or not their serum androgen levels are normal. They aim to reduce circulating androgen levels and/or block androgen receptors. Possible options are oestrogens, androgen receptor blockers, or agents designed to decrease the endogenous production of androgens by the ovary or adrenal gland. The oestrogen component of oral contraceptives increases sex hormone binding globulin, thus decreasing free testosterone in healthy women. Oestrogens also decrease production of ovarian androgens by suppressing secretion of pituitary gonadotropins. The progestin component of oral contraceptives minimizes the risk of endometrial cancer. However, progestins like norethisterone have intrinsic androgenic activity so may aggravate acne. Drospirenone 3 mg combined with ethinylestradiol 30 µg has been shown to have a superior effect to a third generation combined pill. However, it is not licensed in the United Kingdom as a treatment for acne.

Cyproterone acetate (CPA) has been shown to reduce sebum production and comedogenesis. CPA (2 mg) in combination with 35 mg ethinylestradiol has a licence for the treatment of severe acne in the United Kingdom and achieves significant improvement in 75 to 90% of female patients. Treatment is frequently required for 6 months before a response is seen. The relative thromboembolic risk with co-cyprindiol is slightly higher than that linked to nonantiandrogenic combined oral contraceptives but no higher than those containing third generation progestins.

Spironolactone acts as an androgen receptor blocker and inhibits 5α-reductase. In doses of 50 to 100 mg twice daily it reduces sebum production and improves acne. Side effects are dose-related and include potential hyperkalaemia, irregular menstrual periods, breast tenderness, headache, and fatigue. Although tumours have been reported in rodent models treated with spironolactone, this drug has not been directly linked with cancer in humans. There is a risk of feminization of a male fetus and thus pregnancy should be avoided.

Isotretinoin is a synthetic form of vitamin A and is effective in severe inflammatory acne that has failed to respond to other treatments. Oral isotretinoin is the only agent that impacts on the four main aetiological factors driving acne. It is a lipid soluble drug, hence its absorption is enhanced when administered with food. Oral isotretinoin should not be combined with tetracyclines as both can lead to benign intracranial hypertension. Mucocutaneous problems are the most common side effect of oral isotretinoin, including cheilitis, irritant dermatitis, and blepharoconjunctivitis. These side effects are dose dependent. Oral isotretinoin is a potent teratogen and women of childbearing age should not start therapy until a negative pregnancy test has been obtained, ideally 2 to 3 days prior to menstruation. Adequate contraception is essential for fertile, sexually active females before, during, and up to 5 weeks post-therapy. A recent European directive recommends mandatory pregnancy testing prior to the start of treatment and 5 weeks post-therapy and advocates monthly pregnancy testing throughout the treatment period. Baseline blood tests including fasting lipids and liver function should be done pretherapy and are recommended at 1 month, then 3-monthly throughout the treatment course. Adverse psychiatric events such as mood swings, depression, and suicidal ideation have been reported as possible idiosyncratic reactions to isotretinoin and must be highlighted. Epidemiological studies have not demonstrated a definite causal relationship between psychological effects and isotretinoin, but the association of depression with isotretinoin has not been satisfactorily investigated.

A number of small studies have trialled lasers, photodynamic therapy, and phototherapy with either clear blue or mixed blue-red light/radiation in inflammatory acne. Whereas some success has been reported, optimum regimes are still being assessed.

Unusual acne variants

Acne excoriée

This occurs frequently in adolescent girls and young women. Patients pick their skin leading to inflammatory lesions. Treatment can be difficult, psychological problems should be investigated, and underlying acne lesions managed with standard acne treatment. Successful treatment with habit reversal has been reported.

Dysmorphophobia

This occurs in a small number of acne patients. The patient’s perception of their acne is disproportionate to their physical signs. There is often associated depression and/or obsessional neurosis. The acne should be treated in the standard fashion and psychiatric collaboration is important.

Drug-induced acne

This is well recognized. Corticosteroids are the most common offenders. Steroid acne has a monomorphic appearance and consists of noninflammatory and inflammatory lesions. Other drugs implicated include anticonvulsants, lithium, and the novel epidermal growth factor receptor (EGFR) inhibitors currently used for solid tumours.

Cosmetic acne

Various cosmetic ingredients induce comedones, in particular lanolins, petrolatum, and certain vegetable oils. Hair pomades can produce a monomorphic, low-grade acne.

Infantile acne

This is rare but may result in scarring if left untreated. Patients develop inflammatory lesions, particularly on the cheeks, usually after 3 months of age. These can evolve into deep-seated nodules and sinus tracts. Treatment is similar to adult acne, but tetracyclines should be avoided due to the risk of discoloured teeth. Topical therapies and/or oral erythromycin (125 mg twice daily) or trimethoprim (100 mg twice daily) can be used safely.

Gram-negative folliculitis

This occurs as a complication of any long-term topical or oral antibiotic therapy. It is characterized by sudden onset of multiple pustules, often localized periorally and perinasally. This results from overgrowth of Gram-negative organisms including Escherichia coli, proteus, pseudomonas, and klebsiella. The offending antibiotic should be stopped and changed to oral trimethoprim or ampicillin. Oral isotretinoin generally produces a more rapid and permanent response.

Acne conglobata

This is an uncommon severe form of acne characterized by acne nodules, interconnecting sinuses, grouped comedones, and extensive scarring. Treatment is difficult and the problem usually runs a chronic course. Isotretinoin is usually the preferred therapy. Concomitant short courses of antibiotics and oral steroids may be required to control acute exacerbations.

Acne fulminans

This is rare, most frequently affecting adolescent boys. Acute erosive inflammatory lesions occur predominantly on the trunk. Associated systemic symptoms including fever, weight loss, arthralgia, and myalgia are evident. The aetiology is uncertain, but the presence of microscopic haematuria, erythema nodosum, increased response to P. acnes antigen on skin tests, and depressed response to intradermal purified protein derivatives are in favour of an abnormal immunological response. Oral prednisolone is the treatment of choice followed by the cautious introduction of systemic isotretinoin. A number of cases of acne fulminans have been triggered by anabolic steroids and testosterone.

Pyoderma faciale

This disorder is more common in adult women and often occurs in the context of emotional stress. These patients are not systemically unwell but the appearance of the disorder often adds considerably to the stress. Treatment with prednisolone reducing over 4 to 6 weeks and the daily application of moderate to potent topical steroid for 1 week will help. Isotretinoin should be introduced after 1 week, and, if tolerated, can be gradually increased.

SAPHO

This is the acronym for synovitis, acne, pustulosis, hyperostosis, and osteitis in which a group of overlapping joint diseases occur in conjunction with palmoplantar pustulosis and, less frequently, with psoriasis, acne, and inflammatory bowel disease.

Conclusions and the future

Acne is a common inflammatory skin disease often associated with significant psychosocial morbidity. Early effective intervention prevents emotional and physical scarring. Understanding of pathophysiology allows topical and systemic therapies to be combined logically to target the individual aetiological factors.

Research into the pathogenesis has defined acne as a T-cell mediated dermatosis. The possibilities for using immunomodulatory therapies and specific anti-inflammatory treatments are open to further developmental research studies and controlled trials. In theory, a TLR-2 antagonist, IL-1α antagonist, and cytokine therapy could be possible candidates for future acne treatment. Other possibilities include insulin sensitizing agents, 5α-reductase type 1 inhibitors, and possibly new anti-inflammatory agents such as lipoxygenase inhibitors.