Approach

Combination therapy is the mainstay of treatment.[36]​ It is generally agreed that topical retinoids should be considered for inclusion in combination treatments for most patients; these can prevent and improve hyperpigmentation associated with inflammatory acne lesions, particularly in patients with darker skin.

Topical or oral antibiotics should not be used as monotherapy because of the risk of developing resistance.​[34][35][36]

A review of the patient’s skin care routine is important for all types of acne. In general, patients should be encouraged to:[19][34]​​​

  • Use only noncomedogenic products on skin (including makeup)

  • Use nonalkaline (skin pH neutral or slightly acidic) synthetic detergent to cleanse skin twice daily

  • Avoid using scrubs, astringents, fragranced products, or other irritants

  • Avoid picking, squeezing, or scratching acne lesions, and

  • Avoid getting hair products on the face.

Severity assessment

Baseline evaluation prior to treatment should include an assessment of the severity of the patient’s acne as this will determine the initial and ongoing approaches to treatment.[36] An objective measure of severity should be made using one of the validated assessment tools.[36] See Diagnostic criteria.

Patient satisfaction with appearance, the extent of scarring/dark marks, treatment satisfaction, long-term acne control, and the impact on quality of life should also be assessed.[36] 

Mild acne

Patients with mild acne (i.e., grade 2 mild severity acne; some noninflammatory lesions with no more than a few inflammatory lesions [papules/pustules only, no nodular lesions]), should be treated with multimodal topical therapy combining multiple mechanisms of action.[36]

Recommended fixed-dose topical combinations include:​[34][36]​​

  • Topical antibiotic with benzoyl peroxide

  • Topical retinoid with benzoyl peroxide

  • Topical retinoid with an antibiotic, plus concomitant use of benzoyl peroxide to prevent the development of antibiotic resistance

Clascoterone, salicylic acid, or azelaic acid may also be considered to treat patients with mild acne. These agents may be used in addition to combination therapy, or as monotherapy as an alternative to combination therapy.[36]

A consensus statement from the Global Alliance to Improve Outcomes in Acne suggests that topical antibiotics may be tapered and discontinued once there is improvement, though chronic treatment is often needed. If no improvement is noted within 6-8 weeks, topical antibiotics should be discontinued and an alternative therapy considered.[45] Topical retinoids should be continued until the acne is completely clear.[45]

The use of benzoyl peroxide may be associated with cutaneous irritation, such as erythema, pruritus, and skin burning.[46] [ Cochrane Clinical Answers logo ]

Comedonal acne is especially responsive to topical retinoids (e.g., tretinoin, adapalene, tazarotene, and trifarotene).[47][48][49]​​​​​ In mild, primarily comedonal acne, some guidance suggests that topical retinoids may be used as monotherapy.[35][45]​​​​​​​​ Topical adapalene appears to be associated with a lower rate of toxicity than topical tretinoin. In one systematic review, 62% of patients using topical tretinoin experienced adverse events; the comparable figures for adapalene 0.1% and adapalene 0.3% were 19% and 40%, respectively.[50]​ Patients should be started with a lower potency retinoid, increasing to a higher potency if skin irritation is minimal. Topical adapalene is less likely to cause irritation than tretinoin.[51]

Clascoterone, a topical androgen receptor inhibitor, is indicated for the treatment of acne vulgaris in patients ≥12 years of age. In phase 3 vehicle-controlled randomized trials of 12 weeks duration, clascoterone resulted in a significant reduction in absolute noninflammatory lesions from baseline.[52]​ Adverse events were mostly mild; the predominant local skin reaction was trace or mild erythema.

Azelaic acid, an antimicrobial with mild comedolytic and anti-inflammatory properties, may be considered as an adjunct therapy for the treatment of postinflammatory dyspigmentation.[36][53]

Salicylic acid has been used for years for its keratolytic properties, but few well-designed trials of its safety and efficacy are available.[54][55]​​​​ It is considered a less effective comedolytic agent than topical retinoids.

Moderate to severe acne or acne that is resistant to standard treatment

Treatment for patients with moderate to severe acne (i.e., grade 3: moderate severity; up to many noninflammatory lesions and may have some inflammatory lesions, but no more than one small nodular lesion to grade 4: severe severity; many noninflammatory and inflammatory lesions, but no more than a few nodular lesions) includes systemic antibiotics with concomitant benzoyl peroxide, hormonal therapy, or isotretinoin.[34][36]

Intralesional corticosteroids can be considered as an adjunct treatment for patients with larger acne papules or nodules at risk of acne scarring or for rapid improvement in inflammation or pain.[34][36]

Systemic antibiotics

If patients are treated with systemic antibiotics, exposure should be limited due to the possible development of antibiotic resistance and other antibiotic associated adverse effects, such as inflammatory bowel disease or clostridium difficile infection.[36] When systemic antibiotics need to be used for longer than 3 months (some people require indefinite antibiotic therapy), topical benzoyl peroxide should always be used in conjunction with the antibiotic.[45][56][57]​​​​​ The most commonly used systemic antibiotics include tetracyclines (e.g., doxycycline, minocycline, tetracycline, sarecycline) and erythromycin. Other alternative options may include azithromycin, amoxicillin, or a cephalosporin.[58]​ A guideline from the US conditionally recommends that doxycycline should be given in preference to azithromycin.[36]

To limit the use of systemic antibiotics to reduce the development of antibiotic resistance and other antibiotic associated complications the addition of other beneficial topical therapies are recommended.[36] 

Hormonal therapy

Hormonal therapy may be used in women who experience acne flares associated with menstrual periods. It can also be helpful in women with established ovarian or adrenal hyperandrogenism and in those with polycystic ovary syndrome.

Treatment options include combined oral contraceptives or antiandrogenic drugs such as spironolactone.[59][60][61][62]

Combined oral contraceptives treat acne through their antiandrogenic properties, which decrease ovarian androgen production, increase sex hormone-binding globulin, and reduce free testosterone that would otherwise activate the androgen receptor.[36] However, it should be noted that progestin-only oral contraceptives, intramuscular injections, intrauterine devices, or subcutaneous implants may worsen acne.[36]

In the US, four combined oral contraceptives are recommended for the treatment of acne in women who require oral contraception:[36]

  • Norgestimate/ethinyl estradiol

  • Norethindrone/ethinyl estradiol

  • Drospirenone/ethinyl estradiol

  • Drospirenone/ethinyl estradiol/levomefolate

Evidence has demonstrated that treatment with combined oral contraceptives reduced lesion counts in both inflammatory and noninflammatory acne compared with vehicle at 6 months.[36] Treatment is not limited to patients with acne affecting the jawline or with premenstrual flares, hirsutism, or hyperandrogenism.[36]

Spironolactone is an aldosterone antagonist that decreases testosterone production and competitively inhibits testosterone and dihydrotestosterone binding to androgen receptors in the skin. Spironolactone may also inhibit 5-alpha reductase and increase steroid-hormone-binding globulin.[36] In combination with topical benzoyl peroxide, spironolactone has been demonstrated to reduce the severity of acne compared with placebo and benzoyl peroxide at 12 weeks.[63] As monotherapy, compared with placebo, spironolactone improved acne scores at 12 and 24 weeks.[62][64]​​​​​ Some evidence suggests that spironolactone may have similar clinical effectiveness to that of oral tetracycline-class antibiotics for the treatment of acne.[61]​ Spironolactone is not approved for the treatment of acne, but off-label use for the treatment of acne is common in practice.

Intralesional corticosteroids

Although there is limited evidence, intralesional corticosteroid injections are used as an adjuvant treatment for acne. One small trial of nine patients reported that lesions injected with triamcinolone resolved within 3-7 days, much faster than those injected with saline solution.[65] There is an extremely low risk of localized skin atrophy, systemic absorption of the corticosteroid, and possible adrenal suppression, but adverse effects are long lasting when they do occur.[66]

Isotretinoin

For patients with moderate to severe acne, or acne unresponsive to other treatments, a course of oral isotretinoin for 15-20 weeks is the recommended treatment of choice.[35][36][67]​​​​​​[68]​​​​ [ Cochrane Clinical Answers logo ] [Evidence C]​​​​​​​ In practice, treatment is started at the recommended dose and then uptitrated based on adverse effects. Treatment should continue until the patient is acne free for 2-3 months (usually about 5-8 months total), as this appears to be a better predictor of relapse than daily or cumulative dose and allows for individualized treatment regimens.[69][70] Some patients may require a repeat course of isotretinoin.

Adverse effects can be severe, and regular monitoring during treatment with isotretinoin is required. Severe headaches, decreased night vision, significant liver enzyme or lipid elevations, or signs of adverse psychiatric events necessitate prompt discontinuation. Elevated serum cholesterol, triglycerides, and transaminases have been reported in some patients taking oral isotretinoin. Laboratory monitoring during isotretinoin treatment should include liver function tests, and a fasting lipid panel, but complete blood count monitoring is not required.[36]

Isotretinoin is teratogenic; all women should have a pregnancy test before starting the drug and subsequently monthly while taking it.[36] In the US, isotretinoin can only be prescribed through the iPledge risk management program. iPledge system (for isotretinoin prescribing) Opens in new window

Results from studies investigating whether isotretinoin increases the incidence of depression and/or suicidal ideation are conflicting; signs and symptoms of depression should be monitored during and after treatment.[36][71][72]​​​​ Depressive symptoms often improve after treatment with isotretinoin, as well as with other therapies, as the acne symptoms improve.[73][74]

Lidose and micronized formulations of isotretinoin improve oral bioavailability, pharmacologic bioactivity, and increase efficacy in patients who are unwilling/unable to take regular isotretinoin with a high fat/calorie meal.[75]

Pregnant women

In pregnant women with acne, only a few topical agents are considered safe to use during pregnancy, including clindamycin, erythromycin, and azelaic acid.[36] Some evidence suggests that salicylic acid can be used in pregnancy if the area of exposure and duration of therapy is limited, it is not recommended for use in large areas or under occlusion due to the potential for systemic absorption.[36]

Data from a UK population based cohort study indicate that prescribing an oral macrolide antibiotic in any trimester is associated with an increased risk of genital malformations. Therefore, oral erythromycin should not be prescribed for the treatment of acne in women who are pregnant.[76]

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