Guidelines for the Management of Acne

Recommendations From a French Multidisciplinary Group

L. Le Cleach; B. Lebrun-Vignes; A. Bachelot; F. Beer; P. Berger; S. Brugére; M. Chastaing; G. Do-Pham; T. Ferry; J. Gand-Gavanou; B. Guigues; O. Join-Lambert; P. Henry; R. Khallouf; E. Lavie; A. Maruani; O. Romain; B. Sassolas; V.T. Tran; B. Guillot

Disclosures

The British Journal of Dermatology. 2017;177(4):908-913. 

In This Article

Specific Recommendations for Systemic Treatments

Antibiotics

In light of the low level of evidence of antibiotic efficacies and the risk of inducing bacterial resistance to those drugs, the indication of topical antibiotics has been limited (Figure 1). They must always be combined with a topical agent (benzoyl peroxide, retinoid or azelaic acid). Oral lymecycline or doxycycline prescriptions should always be limited to 3 months and combined with topical treatment. In light of the low level of evidence of oral erythromycin efficacy [no trial vs. placebo, four randomized controlled superiority trials vs. active comparator (doxycycline, n = 1, tetracycline, n = 3), of which none found a statistically significant difference between groups][13] and the high level of resistance of some bacterial species to it, use of this antibiotic must be limited to cases with profoundly affected quality of life, contraindication to cyclines and failure of well-administered topical treatment.

Other systemic antibiotics have no indication to treat acne.

Hormonal Therapy

When birth control is not required, combined oestrogen–progestin oral contraceptives are not indicated to treat acne. If a contraceptive method is needed, the prescription of combined oestrogen–progestin contraception should be assessed in terms of the risk/benefit ratio, notably the relative risk of thromboembolic events according to type of associated progestin.[14] A combined oestrogen–progestin contraceptive containing levonorgestrel is recommended as first-line therapy, with norgestimate as the second-line choice. If acne persists despite dermatological treatments (topical treatments or systemic antibiotics), other hormonal treatments, including cyproterone acetate/ethinylestradiol (2 mg/0·035 mg), should be considered as an alternative.

Patients must be given information regarding the risk of thromboembolic events and thromboembolism risk factors must be sought before starting treatment.

Isotretinoin

Isotretinoin is recommended as second-line treatment for moderate to severe acne and as first-line treatment for very severe acne (Figure 1). Regarding the risk of this treatment, a high level of evidence and concordant data support that isotretinoin does not increase the risk of inflammatory bowel disease. No available population-level data support that isotretinoin increases the risk of depression in, or suicide attempts by, patients suffering from acne; however, considering population and individual data, a rare individual risk could not be excluded. Before starting isotretinoin, the patient and his/her family circle must be informed of the potential risk of psychiatric disorders and the patient's treating physician must be notified of any mood or behaviour change. The Adolescent Depression Rating Scale can be used to help physicians detect mood changes in adolescents.[15] Informing the patient's primary-care physician of isotretinoin prescription and the potential risk of psychiatric disorders is recommended. General good practice recommendations for isotretinoin prescription, notably prevention of pregnancy, are mandatory.[16]

The WG consensus concluded that evidence was too weak to support sequential (1 week or 10 consecutive days per month) or low-dose isotretinoin [< 0·5 mg kg−1 (0·25–0·4 mg kg−1)].

Comparison With Other Current Guidelines

American Academy of Dermatology. Release date February 2016; same scope (except included complementary/alternative therapy); last search September 2014.[17]

Differences from French Guidelines:

  • Different grading system: mild, moderate and severe.

  • Topical dapsone (not available in France) is one of the options for second-line treatment for mild acne.

  • No restriction on the use of topical antibiotics.

  • Minocycline is one oral antibiotic treatment option.

  • Azithromycin is an option indicated in those who cannot use tetracyclines (i.e. pregnant women or children < 8 years of age).

  • Trimethoprim–sulfamethoxazole and trimethoprim are considered for patients unable to tolerate tetracyclines or those who are treatment-resistant.

  • Oral spironolactone is a second-line option for females with moderate or severe acne.

  • Low-dose isotretinoin (0·2–0·4 mg kg−1 daily) can be used to effectively treat acne and reduce the frequency and severity of medication-related side-effects.

European Dermatology Forum. Release date June 2016; same scope; last search July 2015.[18]

Differences from French Guidelines:

  • Different grading system: Comedonal acne; Mild–moderate papulopustular acne; Severe papulopustular acne, moderate nodular acne; Severe nodular acne, conglobate acne.

  • General recommendations not described as first-line and second-line therapy but as high strength of recommendation, medium strength of recommendation and low strength of recommendation.

  • Fixed-association adapalene or clindamycin and benzoyl peroxide are recommended for mild to moderate papulopustular acne (high strength of recommendation).

  • Minocycline is one of the systemic antibiotic options; however, doxycycline and lymecycline are preferred to minocycline and tetracycline.

  • In severe papulopustular, moderate nodular acne and severe nodular, conglobate acne a low dose of systemic isotretinoin (maximum 0·3 mg kg−1 daily) is one option for maintenance treatment (low strength of recommendation).

Evidence Supporting the Working Group's Decision on the Discrepancies Listed Above

  • Topical dapsone: we found no trial showing superiority or noninferiority over other topical treatments (treatment not marketed in France).

  • Minocycline: based on one Cochrane review that found no evidence of a superiority of minocycline over other cyclines in acne treatment and expressed concerns on safety, and a pharmacovigilance survey highlighting the higher risk of serious adverse events with minocycline compared with doxycycline, minocycline has an unfavourable benefit/risk balance and was not recommended.[3,19]

  • Azithromycin: we found eight RCTs comparing azithromycin to tetracycline, doxycycline or minocycline in patients with acne including one unpublished RCT (NCT 00392223). One noninferiority trial including 240 patients found that azithromycin was not inferior to doxycycline.[20] Five RCTs not designed as noninferiority trials were not able to demonstrate any superiority of azithromycin vs. cyclines, and one found a superiority of doxycycline vs. azithromycin.[21] The WG considered that these conflicting results and only one trial demonstrating noninferiority was of too low level of evidence to recommend azithromycin in acne treatment.

  • Trimethoprim–sulfamethoxazole: this drug was not assessed in our technical review.

  • Low-dose isotretinoin (0·25–0·4 mg kg−1 daily): we found one RCT comparing high doses (oral isotretinoin 1 mg kg−1 per day or every other day) to a low dose (20 mg every other day) during a 16-week trial. This trial was at high risk of bias due notably to the absence of blinding and absence of primary outcome.[22] One trial compared isotretinoin 5 mg with placebo in low-grade adult acne.[23] One negative RCT was not able to find a difference between isotretinoin 0·5–0·7 mg kg−1 daily and 0·25–0·4 mg kg−1 daily for the primary outcome (Global acne grading system score and number of lesions).[24] Other studies were not comparative or not randomized. The WG considered there was a too low level of evidence to recommend low-dose isotretinoin.

  • Oral spironolactone: acne secondary to hormonal diseases was not within the scope of these guidelines. One Cochrane review did not find any evidence of efficacy of spironolactone in acne treatment.[25] We did not find further RCTs published since the time of the search of the Cochrane review.

  • Fixed-association adapalene and benzoyl peroxide: we did not find a RCT comparing efficacies of and tolerances with the fixed-concentration adapalene 0·1%–benzoyl peroxide 2·5% vs. application of adapalene 0·1% and benzoyl peroxide 2·5% separately rather than as a fixed combination (e.g. adapalene in the morning and benzoyl peroxide in the evening), or demonstrating better adherence to the fixed combination.

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