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Acne Vulgaris

(Acne)

By Jonette E. Keri, MD, PhD, Associate Professor of Dermatology and Cutaneous Surgery;Chief, Dermatology Service, University of Miami, Miller School of Medicine;Miami VA Hospital

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Acne vulgaris is the formation of comedones, papules, pustules, nodules, and/or cysts as a result of obstruction and inflammation of pilosebaceous units (hair follicles and their accompanying sebaceous gland). Acne develops on the face and upper trunk. It most often affects adolescents. Diagnosis is by examination. Treatment, based on severity, can involve a variety of topical and systemic agents directed at reducing sebum production, comedone formation, inflammation, and bacterial counts and at normalizing keratinization.

Acne is the most common skin disease in the US and affects 80% of the population at some point in life.

Pathophysiology

Acne occurs through the interplay of 4 major factors:

  • Excess sebum production

  • Follicular plugging with sebum and keratinocytes

  • Colonization of follicles by Propionibacterium acnes (a normal human anaerobe)

  • Release of multiple inflammatory mediators

Acne can be classified as

  • Noninflammatory: Characterized by comedones

  • Inflammatory: Characterized by papules, pustules, nodules, and cysts

Noninflammatory acne

Comedones are sebaceous plugs impacted within follicles. They are termed open or closed depending on whether the follicle is dilated or closed at the skin surface. Plugs are easily extruded from open comedones but are more difficult to remove from closed comedones. Closed comedones are the precursor lesions to inflammatory acne.

Inflammatory acne

Papules and pustules occur when P. acnes colonizes the closed comedones, breaking down sebum into free fatty acids that irritate the follicular epithelium and eliciting an inflammatory response by neutrophils and then lymphocytes, which further disrupts the epithelium. The inflamed follicle ruptures into the dermis (sometimes precipitated by physical manipulation or harsh scrubbing), where the comedone contents elicit a further local inflammatory reaction, producing papules. If the inflammation is intense, grossly purulent pustules occur.

Nodules and cysts are other manifestations of inflammatory acne. Nodules are deeper lesions that may involve > 1 follicle, and cysts are large fluctuant nodules.

Etiology

The most common trigger is

  • Puberty

During puberty, surges in androgen stimulate sebum production and hyperproliferation of keratinocytes.

Other triggers include

  • Hormonal changes that occur with pregnancy or the menstrual cycle

  • Occlusive cosmetics, cleansers, lotions, and clothing

  • High humidity and sweating

Associations between acne exacerbation and diet, inadequate face washing, masturbation, and sex are unfounded. Some studies suggest a possible association with milk products and high-glycemic diets. Acne may abate in summer months because of sunlight’s anti-inflammatory effects. Proposed associations between acne and hyperinsulinism require further investigation. Some drugs and chemicals (eg, corticosteroids, lithium, phenytoin, isoniazid) worsen acne or cause acneiform eruptions.

Symptoms and Signs

Skin lesions and scarring can be a source of significant emotional distress. Nodules and cysts can be painful. Lesion types frequently coexist at different stages.

Comedones appear as whiteheads or blackheads. Whiteheads (closed comedones) are flesh-colored or whitish palpable lesions 1 to 3 mm in diameter; blackheads (open comedones) are similar in appearance but with a dark center.

Papules and pustules are red lesions 2 to 5 mm in diameter. Papules are relatively deep. Pustules are more superficial.

Nodules are larger, deeper, and more solid than papules. Such lesions resemble inflamed epidermoid cysts, although they lack true cystic structure.

Cysts are suppurative nodules. Rarely, cysts form deep abscesses. Long-term cystic acne can cause scarring that manifests as tiny and deep pits (icepick scars), larger pits, shallow depressions, or hypertrophic scarring or keloids.

Acne conglobata is the most severe form of acne vulgaris, affecting men more than women. Patients have abscesses, draining sinuses, fistulated comedones, and keloidal and atrophic scars. The back and chest are severely involved. The arms, abdomen, buttocks, and even the scalp may be affected.

Acne fulminans is acute, febrile, ulcerative acne, characterized by the sudden appearance of confluent abscesses leading to hemorrhagic necrosis. Leukocytosis and joint pain and swelling may also be present.

Pyoderma faciale (also called rosacea fulminans) occurs suddenly on the midface of young women. It may be analogous to acne fulminans. The eruption consists of erythematous plaques and pustules, involving the chin, cheeks, and forehead. Papules and nodules may develop and become confluent.

Diagnosis

  • Assessment for contributing factors (eg, hormonal, mechanical, or drug-related)

  • Determination of severity (mild, moderate, severe)

  • Assessment of psychosocial impact

Diagnosis of acne vulgaris is by examination.

Differential diagnosis includes rosacea (in which no comedones are seen), corticosteroid-induced acne (which lacks comedones and in which pustules are usually in the same stage of development), perioral dermatitis (usually with a more perioral and periorbital distribution), and acneiform drug eruptions (see Table: Types of Drug Reactions and Typical Causative Agents). Acne severity is graded mild, moderate, or severe based on the number and type of lesions; a standardized system is outlined in Table Classification of Acne Severity.

Classification of Acne Severity

Severity

Definition

Mild

< 20 comedones, or < 15 inflammatory lesions, or < 30 total lesions

Moderate

20 to 100 comedones, or 15 to 50 inflammatory lesions, or 30 to 125 total lesions

Severe

> 5 cysts, or total comedone count > 100, or total inflammatory lesion count > 50, or > 125 total lesions

Prognosis

Acne of any severity usually remits spontaneously by the early to mid 20s, but a substantial minority of patients, usually women, may have acne into their 40s; options for treatment may be limited because of childbearing. Many adults occasionally develop mild, isolated acne lesions. Noninflammatory and mild inflammatory acne usually heals without scars. Moderate to severe inflammatory acne heals but often leaves scarring. Scarring is not only physical; acne may be a huge emotional stressor for adolescents who may withdraw, using the acne as an excuse to avoid difficult personal adjustments. Supportive counseling for patients and parents may be indicated in severe cases.

Treatment

  • Comedones: Topical tretinoin

  • Mild inflammatory acne: Topical retinoid alone or with a topical antibiotic, benzoyl peroxide, or both

  • Moderate acne: Oral antibiotic plus topical therapy as for mild acne

  • Severe acne: Oral isotretinoin

  • Cystic acne: Intralesional triamcinolone

It is important to treat acne to reduce the extent of disease, scarring, and psychologic distress.

Treatment of acne involves a variety of topical and systemic agents directed at reducing sebum production, comedone formation, inflammation, and bacterial counts and at normalizing keratinization (see Figure: How various drugs work in treating acne.). Selection of treatment is generally based on severity; options are summarized in Table Drugs Used to Treat Acne. See guidelines of care for the management of acne vulgaris from the American Academy of Dermatology.

Affected areas should be cleansed daily, but extra washing, use of antibacterial soaps, and scrubbing confer no added benefit.

A lower glycemic diet and moderation of milk intake might be considered for treatment-resistant adolescent acne.

Peeling agents such as sulfur, salicylic acid, glycolic acid, and resorcinol can be useful therapeutic adjuncts but are no longer commonly used.

Oral contraceptives are effective in treating inflammatory and noninflammatory acne, and spironolactone (beginning at 50 mg po once/day, increased to 100 mg po once/day after a few mo if needed) is another anti-androgen that is occasionally useful in women. Various light therapies, with and without topical photosensitizers, have been used effectively, mostly for inflammatory acne.

Treatment should involve educating the patient and tailoring the plan to one that is realistic for the patient. Treatment failure can frequently be attributed to lack of adherence to the plan and also to lack of follow-up. Consultation with a specialist may be necessary.

How various drugs work in treating acne.

Drugs Used to Treat Acne

Drug

Adverse Effects

Comments

Topical antibacterials

Benzoyl peroxide 2.5%, 5%, and 10% gel, lotion, or wash

Dry skin

Possible bleaching of clothing and hair

Allergic reactions (rarely)

Comedolytic and antibacterial with very low to no development of resistance

Should be used in all patients if tolerated

Gel product usually preferred

Benzoyl peroxide/erythromycin gel

Must be kept refrigerated

Benzoyl peroxide/clindamycin gel

Clindamycin 1% gel or lotion

Diarrhea (rarely)

Should be avoided in patients with inflammatory bowel disease

Erythromycin 1.5 to 2% (multiple vehicles)

Well-tolerated, but frequent development of bacterial resistance

Topical comedolytics and exfoliants

Tretinoin (0.025%, 0.05%, and 0.1% cream; 0.05% liquid; 0.025% and 0.1% gel)

Skin irritation

Increased sun sensitivity

Initial strength should be 0.025% and, if ineffective, should be increased; if irritation occurs, strength, frequency, or both should be reduced

When tretinoin is started, apparent worsening of acne, with improvement possibly taking 3 to 4 wk to occur

Requires use of protective clothing and sunscreen

Should be avoided during pregnancy

Tazarotene 0.05% or 0.1% cream or gel

Skin irritation

Increased sun sensitivity

When tazarotene is started, apparent worsening of acne, with improvement possibly taking 3 to 4 wk to occur

Requires use of protective clothing and sunscreen

Should be avoided during pregnancy

Adapalene 0.1% gel, cream, lotion; 0.3% gel)

Some redness, burning, and increased sun sensitivity

As effective as tretinoin but less irritating

Requires use of protective clothing and sunscreen

Azelaic acid 20% cream

Possible lightening of skin

Minimally irritating

May be used by itself or with tretinoin

Should be used cautiously in people with darker skin because of skin-lightening effects

Glycolic acid 5–10%

Stinging

Mild irritation

OTC product in cream, lotion, or solution; adjunct therapy

Oral antibiotics

Tetracycline 250–500 mg bid

Increased sun sensitivity

Inexpensive and safe, but must be taken on an empty stomach

Requires use of protective clothing and sunscreen

Doxycycline 50–100 mg bid

Increased sun sensitivity

Good first-line drug in terms of efficacy and cost

Requires use of protective clothing and sunscreen

Minocycline 50–100 mg bid

Headache

Dizziness

Skin discoloration

Most effective antibiotic but is expensive

Erythromycin 250–500 mg bid

Stomach upset

Frequent development of bacterial resistance

Oral retinoid

Isotretinoin 1–2 mg/kg once/day for 16–20 wk

Possible harm to a developing fetus

Possible effect on blood cells, the liver, and fat (triglyceride and cholesterol) levels

Dry eyes, chapped lips, drying of mucous membranes

Pain or stiffness of large joints and lower back with high dosages

Associated with depression, suicidal thoughts, attempted suicide, and (rarely) completed suicide

Unclear whether associated with new or worsened inflammatory bowel disease (Crohn disease and ulcerative colitis)

For sexually active women, requires a pregnancy test before the start of therapy with isotretinoin and at monthly intervals during use of the drug plus use of 2 forms of contraception or sexual abstinence, beginning 1 mo before the drug is started, continued during drug use, and for 1 mo after stopping the drug

Requires periodic CBC, liver function tests, fasting glucose, and lipid profile

Mild acne

Treatment of mild acne should be continued for 6 wk or until lesions respond. Maintenance treatment may be necessary to maintain control.

Single-agent therapy is generally sufficient for comedonal acne. A mainstay of treatment for comedones is daily topical tretinoin as tolerated. Daily adapalene gel, tazarotene cream or gel, azelaic acid cream, and glycolic or salicylic acid are alternatives for patients who cannot tolerate topical tretinoin. Adverse effects include erythema, burning, stinging, and peeling. Adapalene and tazarotene are retinoids; like tretinoin, they tend to be somewhat irritating and photosensitizing. Azelaic acid has comedolytic and antibacterial properties by an unrelated mechanism and may be synergistic with retinoids.

Dual therapy (eg, a combination of tretinoin with benzoyl peroxide, a topical antibiotic, or both) should be used to treat mild papulopustular (inflammatory) acne. The topical antibiotic is usually erythromycin or clindamycin. Combining benzoyl peroxide with these antibiotics may help limit development of resistance. Glycolic acid may be used instead of or in addition to tretinoin. Treatments have no significant adverse effects other than drying and irritation (and rare allergic reactions to benzoyl peroxide).

Physical extraction of comedones using a comedone extractor is an option for patients unresponsive to topical treatment. Comedone extraction may be done by a physician, nurse, or physician assistant. One end of the comedone extractor is like a blade or bayonet that punctures the closed comedone. The other end exerts pressure to extract the comedone.

Oral antibiotics (eg, tetracycline, minocycline, doxycycline, erythromycin) can be used when wide distribution of lesions makes topical therapy impractical.

Moderate acne

Oral systemic therapy with antibiotics is the best way to treat moderate acne. Antibiotics effective for acne include tetracycline, minocycline, erythromycin, and doxycycline. Full benefit takes 12 wk.

Topical therapy as for mild acne is usually used concomitantly with oral antibiotics.

Doxycycline and minocycline are first-line drugs; both can be taken with food. Tetracycline is also a good first choice, but it cannot be taken with food and may have lower efficacy than doxycycline and minocycline. Doxycycline and minocycline dosage is 50 to 100 mg po bid. Doxycycline may cause photosensitivity, and minocycline may have more adverse effects with chronic use, including drug-induced lupus and hyperpigmentation. Tetracycline dosage is 250 or 500 mg po bid between meals. To reduce the development of antibiotic resistance after control is achieved (usually 2 to 3 mo), the dose is tapered as much as possible to maintain control. Antibiotics may be discontinued if topical therapy maintains control.

Erythromycin is another option, but it can cause GI adverse effects and antibiotic resistance develops more often.

Long-term use of antibiotics may cause a gram-negative pustular folliculitis around the nose and in the center of the face. This uncommon superinfection may be difficult to clear and is best treated with oral isotretinoin after discontinuing the oral antibiotic. Ampicillin is an alternative treatment for gram-negative folliculitis. In women, prolonged antibiotic use can cause candidal vaginitis; if local and systemic therapy does not eradicate this problem, antibiotic therapy for acne must be stopped.

If the patient is female and unresponsive to oral antibiotics, a trial of oral antiandrogens (oral contraceptives and/or spironolactone) may be considered.

Severe acne

Oral isotretinoin is the best treatment for patients with moderate acne in whom antibiotics are unsuccessful and for those with severe inflammatory acne. Dosage of isotretinoin is usually 1 mg/kg once/day for 16 to 20 wk, but the dosage may be increased to 2 mg/kg once/day. If adverse effects make this dosage intolerable, it may be reduced to 0.5 mg/kg once/day. After therapy, acne may continue to improve. Most patients do not require a 2nd course of treatment; when needed, it should be resumed only after the drug has been stopped for 4 mo. Retreatment is required more often if the initial dosage is low (0.5 mg/kg). With this dosage (which is very popular in Europe), fewer adverse effects occur, but prolonged therapy is usually required. Cumulative dosing has gained support; a total dosage of 120 to 150 mg/kg resulted in lower recurrence rates.

Isotretinoin is nearly always effective, but use is limited by adverse effects, including dryness of conjunctivae and mucosae of the genitals, chapped lips, arthralgias, depression, elevated lipid levels, and the risk of birth defects if treatment occurs during pregnancy. Hydration with water followed by petrolatum application usually alleviates mucosal and cutaneous dryness. Arthralgias (mostly of large joints or the lower back) occur in about 15% of patients. Increased risk of depression and suicide is much publicized but probably rare. It is not clear whether risk of new or worsened inflammatory bowel disease (Crohn disease and ulcerative colitis) is increased.

CBC, liver function, and fasting glucose, triglyceride, and cholesterol levels should be determined before treatment. Each should be reassessed at 4 wk and, unless abnormalities are noted, need not be repeated until the end of treatment. Triglycerides rarely increase to a level at which the drug should be stopped. Liver function is seldom affected. Because isotretinoin is teratogenic, women of childbearing age are told that they are required to use 2 methods of contraception for 1 mo before treatment, during treatment, and for at least 1 mo after stopping treatment. Pregnancy tests should be done before beginning therapy and monthly until 1 mo after therapy stops.

Cystic acne

Intralesional injection of 0.1 mL triamcinolone acetonide suspension 2.5 mg/mL (the 10 mg/mL suspension must be diluted) is indicated for patients with firm (cystic) acne who seek quick clinical improvement with reduced scarring. Local atrophy may occur but is usually transient. For isolated, very boggy lesions, incision and drainage are often beneficial but may result in residual scarring.

Other forms of acne

Pyoderma faciale is treated with oral corticosteroids and isotretinoin.

Acne fulminans is treated with oral corticosteroids and systemic antibiotics.

Acne conglobata is treated with oral isotretinoin if systemic antibiotics fail.

For acne caused by endocrine abnormalities (eg, polycystic ovary syndrome, virilizing adrenal tumors in females), antiandrogens are indicated. Spironolactone, which has some antiandrogen effects, is sometimes prescribed to treat acne at a dose of 50 to 100 mg po once/day. Cyproterone acetate is used in Europe. When other measures fail, an estrogen/progesterone–containing contraceptive may be tried; therapy 6 mo is needed to evaluate effect.

Scarring

Small scars can be treated with chemical peels, laser resurfacing, or dermabrasion. Deeper, discrete scars can be excised. Wide, shallow depressions can be treated with subcision or injection of collagen or another filler. Fillers, including collagen, hyaluronic acid, and polymethylmethacrylate, are temporary and must be repeated periodically.

More Information

Key Points

  • If noninflammatory, acne is characterized by comedones and, if inflammatory, by papules, pustules, nodules, and cysts.

  • Mild and moderate acne usually heals without scarring by the mid 20s.

  • Recommend that patients avoid triggers (eg, occlusive cosmetics and clothing, cleansers, lotions, high humidity, some drugs and chemicals, possibly a high intake of milk or a high-glycemic diet).

  • Consider the psychologic as well as the physical effects of acne.

  • Prescribe a topical comedolytic (eg, tretinoin) plus, for inflammatory acne, benzoyl peroxide, a topical antibiotic, or both.

  • Prescribe an oral antibiotic for moderate acne and oral isotretinoin for severe acne.

  • Treat cystic acne with intralesional triamcinolone.

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