Acne vulgaris

Published on 18/03/2015 by admin

Last modified 18/03/2015

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Acne vulgaris

Fragkiski Tsatsou and Christos C. Zouboulis

Evidence Levels: A Double-blind study B Clinical trial ≥ 20 subjects C Clinical trial < 20 subjects D Series ≥ 5 subjects E Anecdotal case reports

Acne vulgaris is a chronic inflammatory disorder of the pilosebaceous unit with a multifactorial pathogenesis and a highly variable morphology. Acne is one of the commonest dermatologic disorders encountered in everyday clinical practice with great impact on quality of life.

Management strategy

Treatment depends on the type and severity of acne lesions. Combination therapy is often appropriate to address the multifactorial pathophysiology. Treatment is addressed under the following headings: comedonal, mild papulopustular, moderate papulopustular acne without scarring, moderate papulopustular acne with scarring, nodulocystic and/or conglobate, acne fulminans. We also address post-acne scarring.

In mild forms of acne, topical therapy is most appropriate. Topical therapy is indicated in comedonal acne and mild to moderate papulopustular acne without scarring. Topical therapeutic agents also form a part of combination therapy with oral regimens or procedural therapies for treatment of more severe forms of acne. Topical agents include retinoids, antimicrobial and antibacterial agents, hormonal agents or herbal remedies. Four to 8 weeks should be allowed for most topical treatments to work before altering the regimen.

Treatment of choice for comedonal acne is monotherapy with topical retinoids as initiation therapy, due to its usually mild-to-moderate severity. Following successful treatment, topical retinoids are suitable for maintenance therapy. Topical retinoids act against comedones (macrocomedones) and microcomedones and have direct anti-inflammatory effects. Retinoids approved for topical acne treatment include tretinoin (all-trans-retinoic acid), isotretinoin (13-cis-retinoic acid), as well as the synthetic third-generation polyaromatic retinoids adapalene and tazarotene. Retinaldehyde is used in cosmetic preparations against acne. All topical retinoids are effective as single agents in mild-to-moderate acne but they differ in speed of efficacy and tolerability. Adverse events are local and include erythema, dryness, itching, and stinging. Adapalene is preferred to tretinoin and isotretinoin, since it shows the best tolerability/safety profile.

Treatment of choice for mild and moderate papulopustular acne without scarring is a combination of benzoyl peroxide (BPO) and topical retinoids, or BPO and topical antibiotics. Fixed-dose combination of clindamycin phosphate + BPO or fixed-dose combination of adapalene and BPO are both recommended as first-line treatment of both mild and moderate papulopustular acne without scarring.

For moderate papulopustular acne with scarring in males, oral antibiotics are the treatment of choice. Oral antibiotics improve inflammatory acne by inhibiting Propionibacterium acnes and/or inducing a genuine anti-inflammatory activity. Although there is no correlation between the number of P. acnes and the severity of acne, the occurrence of antibiotic-resistant P. acnes correlates with poor clinical response. Several antibiotics exhibit anti-inflammatory properties, assisting in the improvement of acne through decreased leukocyte chemotaxis and alteration of cytokine production. Tetracyclines, erythromycin and nadifloxacin reduce reactive oxygen species formation by neutrophils and, therefore, acne inflammation. New antibiotics for the treatment of acne include lymecycline, a second-generation tetracycline, and roxithromycin, a macrolide that exhibits anti-inflammatory and anti-androgenic activities.

Antibiotics with anti-inflammatory properties, such as tetracyclines (oxytetracycline, tetracycline chloride, doxycycline, minocycline, lymecycline) and macrolides (erythromycin, azithromycin), are the agents of choice for papulopustular acne. Second-generation tetracyclines (doxycycline, minocycline, lymecycline) have pharmacokinetic advantages over tetracycline. Doxycycline is used at 100 or 200 mg daily in two equal doses. Minocycline is not equally recommendable due to rare but potentially severe side effects and high cost. An initially higher dose of doxycycline or minocycline (4 weeks 100 mg daily, then 50 mg daily) is more effective than 50 mg daily over 12 weeks. Patients with strong seborrhea may require higher doses (doxycycline and minocycline up to 200 mg daily, lymecycline up to 600 mg daily). At such dosages increased side effects may be expected. Small daily doses with concomitant sub-inhibitory concentrations may promote resistance.

Systemic antibiotic therapy of moderate papulopustular acne should in general be continued for 3 months and should be combined with topical BPO (either continuously or at intervals) to prevent antibiotic resistance. Combination therapy with topical agents, especially retinoids, BPO or azelaic acid, also increases efficacy of treatment. It appears that antibiotic therapy longer than 3 to 6 months brings little additional effect but increases the risk of resistance. Treatment should be then switched to topical retinoids for maintenance therapy.

In nodulocystic or conglobate acne, oral isotretinoin is the treatment of choice. Systemic isotretinoin suppresses sebaceous gland activity, normalizes the pattern of keratinization within the pilosebaceous follicle, inhibits inflammation, and – in a secondary manner – reduces growth of P. acnes. It is the most effective anti-acne drug available, especially in the treatment of severe recalcitrant nodulocystic acne and in the prevention of acne scarring.

In most cases with severe acne, a 6- to 12-month course of isotretinoin 0.5 mg/kg/day is recommended. Higher doses are indicated particularly for severe involvement of the chest and back. Factors contributing to the need for longer treatment schedules include use of lower dose regimens, presence of severe acne, extrafacial involvement and prolonged history of the disease. The drug’s discontinuation may be followed by a disease relapse.

Isotretinoin treatment for acne can initially induce inflammatory flares of acne, occasionally leading to acne fulminans. This usually occurs 3 to 4 weeks after treatment initiation. Mild flares do not require modification of the oral dose and improve spontaneously. Severe episodes should be treated with addition of systemic prednisolone (30 mg/day), whereas dose reduction or discontinuation of isotretinoin may only be required in individual cases.

The adverse effect profile of oral isotretinoin includes characteristic dose-dependent mucocutaneous side effects (cheilitis, xerosis, dry mucosae, conjunctivitis, epistaxis), elevation of serum lipids, hyperostosis, extraskeletal calcification, arthralgia, and myalgia. Low-dose long-term regimens (0.1–0.2 mg/kg daily or intermittent use) and a micronized isotretinoin formulation with similar efficacy are associated with a lower risk of adverse events.

The teratogenic potential of isotretinoin with high rate of spontaneous abortions and life-threatening congenital malformations demands the use of secure contraception when it is prescribed for females of fertile age. Contraception is recommended 1 month before initiation of treatment, during the entire period of the drug administration, and over 3 months after discontinuation of the regimen. Oral isotretinoin is strictly contraindicated in pregnancy, during lactation, and in severe hepatic and renal dysfunction. Relative contraindications include hyperlipidemia, diabetes mellitus, and severe osteoporosis. Co-administration of vitamin A, tetracycline and high doses of aspirin is contraindicated. Liver enzymes and lipid levels in blood should be monitored.

For acne fulminans a combination of oral corticosteroid and isotretinoin is indicated. Infantile and pediatric acne may necessitate an alternative treatment. For patients with adrenal hyperandrogenism low-dose oral corticosteroid in combination with systemic retinoid is the treatment of choice.

Hormonal anti-androgen treatment is not a primary monotherapy and is largely reserved for female patients who present additional signs of peripheral hyperandrogenism or hyperandrogenemia. However, hormonal anti-androgens can be useful in females with acne tarda, persistent acne recalcitrant to other treatments, patients with an incidental need for contraception, and to provide contraceptive cover during systemic isotretinoin treatment.

Specific investigations

None are required routinely.

Consider microbiology to exclude Gram positive or Gram negative folliculitis

Consider endocrine work-up if hyperandrogenemia is suspected

First-line therapy

Comedonal acne
Topical retinoids	B
Dapsone gel with topical retinoid	B
Mild papulopustular acne
Benzoyl peroxide with topical retinoid	A
Benzoyl peroxide with topical antibiotic	A
Moderate papulopustular acne without scarring
Benzoyl peroxide with topical retinoid	A
Benzoyl peroxide with topical antibiotic	A
Moderate papulopustular acne with scarring
For males use oral antibiotics (tetracyclines, macrolides) with benzoyl peroxide or topical retinoid	A
For females use an oral anti-androgen contraceptive with benzoyl peroxide and topical antibiotic	A
Nodulocystic and/or conglobate acne
Oral isotretinoin*	A
Acne fulminans
Oral isotretinoin* with low-dose oral corticosteroids	C