Acne clinical guideline

Disease burden

• Acne is very common among adolescents and young adults, but can persist into adulthood

• Nearly 85% of teenagers are affected by acne at some point during their teenage years

• In total, more than 50 million people have acne in the United States

• Permanent scarring, poor self-image, depression, and anxiety can result from acne

• The direct cost of acne is estimated to exceed $3 billion annually

Pathogenesis

Understanding of acne pathogenesis is evolving, but may involve a combination of the following factors:

• Follicular hyperkeratinization

• Microbial colonization with P. acnes

• Sebum production

• Complex inflammatory mechanisms

• Neuroendocrine regulatory mechanisms

• Diet

• Genetic factors

• Non-genetic factors

An acne grading system may be helpful in patient care, but at present there is no universal system for grading and assessing severity of acne.

To facilitate therapeutic decisions and assess treatment response, clinicians can use a consistent method of grading and classifying acne using the following characteristics:

• Number of acne lesions

• Type of acne lesions

• Disease severity

• Anatomical sites

• Scarring

• Quality of Life (QOL)

Microbiologic testing

Routine testing is NOT recommended, though patients exhibiting acne-like lesions suggestive of gram negative folliculitis may benefit from microbiologic testing.

Endocrinologic testing

Routine testing is NOT recommended, though laboratory evaluation of acne patients with additional signs of androgen excess is recommended.

Recommendations

• Benzoyl peroxide alone or in combination with topical antibiotics for mild acne

• Benzoyl peroxide in combination with topical retinoids or systemic antibiotic therapy for moderate to severe acne

• Retinoids as monotherapy in primarily comedonal acne or in combination with topical or oral antimicrobials in mixed/primarily inflammatory acne

• Topical dapsone 5% gel for inflammatory acne, particularly in adult females

• Azelaic acid for post-inflammatory dyspigmentation

Other points of note

• Benzoyl peroxide does not confer bacterial resistance

• Topical antibiotics are NOT recommended as monotherapy due to risk of bacterial resistance

• Combination therapy should be used in the majority of acne patients to target different aspects of acne pathogenesis

• Patients should be counseled on pregnancy risks when starting a retinoid or if a female patient desires pregnancy

• The topical therapy of acne in children under the age of 12 years with FDA-approved products has expanded

  • Benzoyl peroxide 2.5%/adapalene 1% gel – ages 9 and up

  • Tretinoin 0.05% micronized gel – ages 10 and up

• The use of topical maintenance regimens after oral antibiotic therapy cannot be overemphasized

• Topical therapies can accomplish continued efficacy months after discontinuation of systemic antibiotics

Systemic antibiotics are recommended for use in moderate to severe inflammatory acne that are resistant to topical therapies. They should be used in combination with a topical retinoid and benzoyl peroxide. Limiting antibiotic use to minimize antibiotic resistance is suggested.

Recommendations

Oral tetracycline, doxycycline, minocycline, erythromycin, azithromycin, trimethoprim/sulfamethoxazole (TMP/SMX), trimethoprim and cephalexin have been shown to be effective in the treatment of moderate and severe acne, and forms of inflammatory acne that are resistant to topical treatments.

Other points of note

• Tetracyclines (tetracycline, doxycycline, minocycline) are the preferred systemic antibiotics

• Oral erythromycin and azithromycin use should be limited to those who cannot use tetracyclines:

  • Pregnant women

  • Children under 8 years of age

• Trimethoprim-sulfamethoxazole and trimethoprim use should be restricted to patients unable to tolerate tetracyclines or in treatment-resistant patients

• Use of all other systemic antibiotics is discouraged

• Monotherapy with systemic antibiotics is NOT recommended

• When prescribing systemic antibiotics, the issue of bacterial resistance remains a major concern

• The Centers for Disease Control (CDC) has stressed antibiotic stewardship

  • Limit antibiotic use to the shortest possible duration, typically three months, to minimize the development of bacterial resistance.

  • Concomitant topical therapy with benzoyl peroxide and/or a retinoid should be used with systemic antibiotics, as well as for maintenance after completion of systemic antibiotic therapy

• Limiting systemic antibiotic use is urged due to reported associations of inflammatory bowel disease, pharyngitis, Clostridium difficile infection, and induction of Candida vulvovaginitis.

Oral contraceptives may improve acne for many women. They could be used alone or in combination with other acne treatments.

Recommendations

• Estrogen-containing combined oral contraceptives for inflammatory acne in females

• Currently four FDA-approved combined oral contraceptives for the treatment of acne

• Acne reduction with these agents can take time

Other points of note

• Spironolactone can be useful in the treatment of acne in select females, though evidence of its efficacy is limited

• Oral corticosteroid therapy can be of temporary benefit in patients who have severe inflammatory acne while starting standard acne treatment

• Long-term adverse effects of corticosteroids prohibit use as a primary therapy for acne

Recommendations

Oral isotretinoin is recommended for the treatment of severe nodular acne.

Other points of note

• Oral isotretinoin is appropriate for the treatment of moderate acne that is treatment-resistant or for the management of acne that is producing physical scarring and/or psychosocial distress

• Low-dose isotretinoin can be used to effectively treat acne and reduce the frequency and severity of medication-related side effects

• Intermittent dosing of isotretinoin is NOT recommended

• Routine monitoring of liver function tests, serum cholesterol and triglycerides at baseline and again until response to treatment is established is recommended

• Routine monitoring of complete blood count is NOT recommended

• Every woman of child-bearing potential taking isotretinoin should be carefully counseled regarding various contraceptive methods that are available and the specific requirements of the iPLEDGE system at each clinic visit

• Patient-independent forms of birth control, including long acting reversible contraceptives, should be considered whenever appropriate

• Prescribing physicians also should monitor their patients for any indication of inflammatory bowel disease and depressive symptoms and educate their patients about the potential risks with isotretinoin

There is limited evidence to recommend the use and benefit of physical modalities for the routine treatment of acne including:

• Comedo removal

• Pulsed dye laser

• Potassium titanyl phosphate (KTP) laser

• Fractionated and non-fractionated infrared lasers

• Fractionated CO2 laser

• Photodynamic therapy (PDT)

• Glycolic acid peels

• Salicylic acid peels

Intralesional corticosteroid injections are effective in the treatment of larger individual acne nodules.

Herbal and alternative therapies have been reported to have value in treating acne:

• Tea tree oil

• Topical and oral ayurvedic compounds

• Oral barberry extract

• Gluconolactone solution

Although most of these products appear to be well tolerated, very limited data exist regarding the safety and efficacy of these agents to recommend their use in acne.

• No specific dietary changes are recommended in the management of acne

• Emerging data suggests that high glycemic index (GI) diets may be associated with acne

• Limited evidence suggests that some dairy, particularly skim milk, may influence acne