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Guideline on the treatment of acne

Clinical features and variants

Comedonal acne

  • Comedones/non-inflamed lesions:
    • open comedones (blackheads)
    • closed comedones (whiteheads)
  • Comedones frequently have a mid-facial distribution in childhood and, when evident early in the course of the disease, this pattern is indicative of poor prognosis

Papulopustular acne

  • Mixture of non-inflammatory and inflammatory lesions
  • Superficial inflammatory lesions include papules and pustules (5 mm or less in diameter). These may evolve into deep pustules or nodules in more severe disease. Inflammatory macules represent regressing lesions that may persist for many weeks and contribute markedly to the general inflammatory appearance

Nodular/conglobate acne

  • Small nodules are defined as firm, inflamed lesions >5 mm in diameter, painful by palpation. Nodules are defined as larger than 5 mm, and large nodules are >1 cm in size. They may extend deeply and over large areas, frequently resulting in painful lesions, exudative sinus tracts, and tissue destruction
  • Conglobate acne:
    • a rare but severe form of acne found most commonly in adult males with few or no systemic symptoms
    • characterised by multiple grouped comedones amidst inflammatory papules, tender, suppurative nodules, which commonly coalesce to form sinus tracts
    • lesions usually occur on the trunk and upper limbs and frequently extend to the buttocks. In contrast to ordinary acne, facial lesions are less common
    • often presents in the second to third decade of life and may persist into the sixth decade

Other acne variants

  • These guidelines do not cover other acne variants, such as acne fulminans, gram-negative folliculitis, rosacea fulminans, vasculitis, mechanical acne, oil/tar acne, chloracne, acne in neonates and infants, and late-onset, persistent acne

Acne grading

  • There are inherent difficulties in objectively measuring acne. Over 25 different methods have been described, but there is no consensus as to which should be used
  • This guideline uses the following classification:
  • comedonal acne
  • mild to moderate papulopustular acne
  • severe papulopustular acne, moderate nodular acne
  • severe nodular acne, conglobate acne

Therapeutic options

  • Click here for a summary of therapeutic recommendations
  • Limitations can apply that may necessitate the use of a treatment with a lower strength of recommendation as a first-line therapy (e.g. financial resources/reimbursement limitations, legal restrictions, availability, drug licensing)
  • In cases with more widespread disease/moderate severity, initiation of a systemic treatment can be recommended
  • In cases of severe nodular/conglobate acne, an additional short term systemic treatment with corticosteroids can be considered

Choice of type of topical retinoid

  • Adapalene should be selected in preference to tretinoin and isotretinoin

Choice of type of systemic antibiotics

  • Doxycycline and lymecycline should be selected in preference to minocycline and tetracycline

Considerations on isotretinoin and dosage

  • For severe papulopustular acne/moderate nodular acne, a dosage of systemic isotretinoin of 0.3–0.5 mg/kg can be recommended
  • For conglobate acne, a dosage of systemic isotretinoin of ≥0.5 mg/kg can be recommended
  • The duration of the therapy should be at least 6 months. In cases where an insufficient response is seen, the treatment period can be prolonged

Oral isotretinoin considerations with respect to EMEA directive

  • The current European Directive for prescribing oral isotretinoin differs from the recommendations given in this guideline, with respect to indication
  • The EU directive states: ‘oral isotretinoin should only be used in severe acne, nodular and conglobate acne, that has or is not responding to appropriate antibiotics and topical therapy’. The inference of this being that it should now not be used at all as first-line therapy. After almost three decades of experience with oral isotretinoin, the published data and opinion of many experts, including the authors of the EU Acne Guidelines, support systemic isotretinoin being considered as the first-choice treatment for severe papulopustular, moderate nodular, and severe nodular/ conglobate acne. Theoretically, in EU countries clinicians are free to prescribe drugs, such as oral isotretinoin, according to their professional experience. However, in the event of any medical problems, they could be deemed liable if they have failed to follow recommended prescribing practice

Consideration on isotretinoin and the risk of depression

  • It is reported that rates of depression among isotretinoin users ranged from 1–11 % across trials, with similar rates in oral antibiotic control groups
  • Overall, trials comparing depression before and after treatment did not show a statistically significant increase in depression diagnoses or depressive symptoms
  • The available data on suicidal behaviour during isotretinoin treatment are insufficient to establish a meaningful causative association
  • As part of a medical history, patients should be assessed for prior symptoms of depression before the initiation of isotretinoin, and during the course of the treatment. Patients should be informed about a possible risk of depression and suicidal behaviour

Antibiotic resistance

  • The use of topical and systemic antibiotics should be optimised by using appropriate combinations for a predefined duration, in order to reduce the development of antibiotic resistance
  • Because of the risk of the development of antibiotic resistance, topical monotherapy with antibiotics is generally not recommended
  • Use of topical antibiotics can lead to resistance largely confined to the skin of treated sites, whereas oral antibiotics can lead to resistance in commensal flora at all body sites
  • Resistance is more common in patients with moderate-to-severe acne and in countries with high outpatient antibiotic sales. Resistance is disseminated primarily by person-to-person contact, and so the spread of resistant strains by the treating physicians and by family and friends occurs frequently
  • The use of systemic antibiotics should be limited (both indication and duration) and topical antibiotic monotherapy should be avoided. Other recommendations include stricter cross-infection control measures when assessing acne in the clinic, and combining any topical/systemic antibiotic therapy with broad-spectrum antibacterial agents, such as benzoyl peroxide

Maintenance therapy

  • The strategy for treating acne includes an induction phase followed by a maintenance phase, and is further supported by adjunctive treatments and/or cosmetic treatments
  • Maintenance therapy can be defined as the regular use of appropriate therapeutic agents to ensure that acne remains in remission
  • In order to minimise antibiotic resistance, long-term therapy with antibiotics is not recommended as an alternative to topical retinoids. If an antimicrobial effect is desired, the addition of benzoyl peroxide to topical retinoid therapy is preferred
  • For successful long-term treatment, any acne maintenance therapy must be tolerable, appropriate for the patient’s lifestyle, and convenient to use
  • The natural history of acne suggests that maintenance therapy should continue over a period of months to years depending upon the patient’s age

Patient education

  • Education about the pathophysiology of acne can enhance patient adherence to maintenance therapy. However, the psychosocial benefits of clearer skin may be the most compelling reason for consistent maintenance therapy
  • It may also be helpful to explain to patients that acne is often a chronic disease, which requires both acute and maintenance therapy for sustained remission
Summary of therapeutic recommendations
Comedonal acneMild-to-moderate papulopustular acneSevere papulopustular/moderate nodular acneSevere nodular/conglobate acne
High strength of recommendation
  • Adapalene + BPO (fc) or
  • BPO + clindamycin (fc)
  • Isotretinoin
  • Isotretinoin
Medium strength of recommendation
  • Topical retinoid
  • Azelaic acid or
  • BPO or
  • Topical retinoid or
  • Systemic antibiotics + adapalene*
  • Systemic antibiotics + adapalene*or
  • Systemic antibiotics + azelaic acidor
  • Systemic antibiotics + adapalene + BPO (fc)
  • Systemic antibiotics + azelaic acid
Low strength of recommendation
  • Azelaic acid or
  • BPO
  • Blue light or
  • Oral zinc or
  • Topical erythromycin + isotretinoin (fc) or
  • Topical erythromycin + tretinoin (fc) or
  • Systemic antibiotics + BPOor
  • Systemic antibiotics + azelaic acidor
  • Systemic antibiotics, + adapalene + BPO§ (fc)
  • Systemic antibiotics + BPO
  • Systemic antibiotics + BPOor
  • Systemic antibiotics + adapalene*,§or
  • Systemic antibiotics + adapalene + BPO§ (fc)
Alternatives for females—Low strength of recommendation
  • Hormonal antiandrogens + topical treatment or
  • Hormonal antiandrogens + systemic antibiotics
  • Hormonal antiandrogens + systemic antibiotics
* only studies found on systemic antibiotics + adapalene. Isotretinoin and tretinoin can be considered for combination treatment based on expert opinion
† indirect evidence from nodular and conglobate acne and expert opinion
‡ indirect evidence from a study also including chlorhexidine, recommendation additionally based on expert opinion
§ indirect evidence from severe papularpustular acne
BPO=benzoyl peroxide; fc=fixed combination.

full guidelines available from…
European Dermatology Forum.

European Dermatology Forum. Guideline on the treatment of acne. September 2011.
First included: February 2012.