Simon Murray, MD: AAD Recommendations for Acne Treatment

Acne vulgaris is the most common skin condition treated by dermatologists. Approximately 50 million people in the United States have acne vulgaris.

The AAD published evidence-based recommendations for treating physicians which aren’t guidelines, but rather the best evidence for treating acne. The recommendations are drawn from established literature. Additionally, several dermatologists presented at a session, “Translating Evidence into Practice: Acne Guidelines,” the 2019 Annual Meeting of the American Academy of Dermatology (AAD) in Washington, DC.

Drawn from the presentations and the AAD position paper, here are the recommendations for acne treatment with the following strategies. They are intended to advise but not mandate treatment options.

1. Dietary guidelines
2. Topical treatments
3. Systemic antibiotic therapy
4. Hormonal treatments
5. Isotretinoin

Dietary Guidelines

There are several food groups which may improve skin care but only 2 food groups are mentioned in the AAD recommendations. Evidence suggests that milk protein has a negative effect on acne. Skim milk has been shown to cause acne but not whole milk, cheese or not yogurt. A 2005 retrospective study of 47,000 women linked a history of drinking milk as a teenager to a diagnosis of acne. This trial has been widely criticized because it was retrospective, however the investigators conducted 2 prospective trials which indicated that there was an association between milk intake and acne, although only with skim milk. It is thought that the process of removing fat from the milk made the concentration of whey higher in the skim milk, which might be the actual pathologic agent. Restrictions of chocolate, oily foods, and iodized salt are no longer recommended to prevent acne.

The effect of high glycemic diets and acne has been studied in at least 3 clinical controlled trials which have shown that foods with high glycemic index predisposed to acne. At present it is prudent to recommend that people with acne avoid high glycemic foods. By extension it would be prudent to recommend a diet low in all refined sugar and simple carbohydrates.

There are some small preliminary studies examining the role of antioxidants including oral zinc, probiotics and fish oil to prevent acne, but the existing evidence is not strong enough to support any recommendations.

Topical Agents

There are several topical agents used to treat acne and they remain the first line choice either used alone or in combination with other agents. Topical agents include benzoyl peroxide (BP) in a variety of forms, topical antibiotics, topical retinoid, azelic acid, and topical Dapsone. There is little evidence to recommend compounds containing sulfur, nicotinamide, resorcinol, sodium sulfacetamide, or zinc in the treatment of acne.

Benzyl peroxide has antimicrobial activity against P acnes as well as comodolytic properties. Resistance to BP has never been demonstrated making it an ideal agent when used with antibiotics because it may reduce resistance to those agents. It comes in a variety of forms including washes, foams, cleansers, creams or gels. It ranges in strength from 2.5-10% with side effects increase as the strength of benzoyl peroxide increases. Benzyl peroxide can be combined with topical antibiotics or with systemic antibiotics. In mild cases it can be used as monotherapy. Side effects include dry, red skin, and contact dermatitis which may limit its use since side effects are dose dependent.

Topical retinoids are derivatives of Vitamin A. All are important in addressing the development of maintenance of acne and are recommended as monotherapy in primarily comedo dermal acne or in combination with topical or oral antimicrobials in patients with primarily inflammatory acne lesions.

Topical agents include tretinoin, adapalene, and tazarotene. They all come in a variety of formulations including lotions, gels, creams, and microsphere gels. If a person develops intolerance to a particular brand of retinoid, it is not unreasonable to change to another brand. It is also reasonable to start these drugs at the lowest doses and increase slowly. They can cause redness, dry skin, photosensitivity, and irritation if started at higher doses and some patients don’t tolerate them at all. Despite this they remain the mainstay of acne treatment.

Azelic acid 20% is mildly to moderately effective as a comodolytic, antibacterial, and anti-inflammatory agent. It is best used in patients with sensitive skin and can be used in patients who have post inflammatory dyspigmentation because of its lightening effect.

Dapsone 5% gel is available as an over the counter product, administered twice a day for acne vulgaris. It shows modest to moderate effect primarily in reducing inflammatory lesions. If it is applied with benzyl peroxide it may cause an orange-brown discoloration of the skin.

Salicylic acid is a comodolytic agent that is available OTC in a variety of strength for the treatment of acne. While it is well tolerated there are only limited trials attesting to its efficacy in acne.

Sulfur and resorcinol have been used for 50 years in the treatment of acne but there is no evidence to support that they are efficacious. Other agents which are used which have never been proven to be efficacious include topical zinc, topical nicotinamide, and topical aluminum chloride.

Topical antibiotics are effective treatment for acne and include topical erythromycin and clindamycin. Monotherapy with topical antibiotics is discouraged because of the antibiotic resistance so they should be used in combination with other agents like BP or retinoids. Clindamycin 1% gel is the preferred agent because it is less likely to produce resistance. Rare cases of C difficile infections have occurred with the use of topical clindamycin preparations for acne. Fixed Combinations of clindamycin and BP are available and improve compliance.

Systemic Antibiotics

The role of systemic antibiotics is changing in dermatology. Currently dermatologists are the largest prescriber of antibiotics of any physician specialty. Systemic antibiotics are indicated in the management of moderate to severe acne and forms of inflammatory acne that are resistant to topical treatments. Doxycycline and minocycline are more effective than tetracycline with minocycline being the most active.

Second line treatments include azithromycin, trimethoprim sulfa, and amoxicillin. Generally speaking erythromycin should be avoided because of the high rate of resistance. Trimethoprim sulfa and trimethoprim can be used in patients resistant to doxycycline. The current guidelines suggest shorter treatments rather than longer. Systemic antibiotics should be used for no longer than 90 days and if they do not show significant improvement should be discontinued. Secondly, they should be used in combination with topical agents because of growing resistance to systemic antibiotic therapy. A reasonable combination would be topical benzyl peroxide or topical retinoids and oral doxycycline.

Sarecycline is the newest agent for acne. It was approved in January 2019 for patients ages 9 and older, but carries the same warnings as tetracycline including teeth staining. Its once a day dosing and improved tolerability make it an attractive agent. It can show clinical benefit in as little as 3 weeks unlike other oral antibiotics which may take 3 months to work.

Hormonal Agents

The hormonal agents include combination oral contraceptives (COC) and Spironolactone which both exhibit anti-androgenic properties. COC’s exhibit activity against inflammation and comedal lesion counts after approximately 3 cycles. In women wishing to avoid pregnancy and treat acne they are ideal agents. Dozens of studies have confirmed their efficacy and safety. There are currently 4 oral estrogen containing combination agents approved to treat acne. Progesterone alone oral contraceptives are not effective. There are several concerns about the use of oral contraceptives including but not limited to:

1. Increased risk of breast cancer
2. Blood clotting diseases including phlebitis and pulmonary embolism
3. Increased risk for heart disease,
4. Worsening of migraine.

These are valid concerns; however, there are only a few absolute contraindications for the use of COCs. Contradictions to COC products include pregnancy, history of breast cancer, breast feeding, smokers older than 35 years, hypertension, history of deep vein thrombosis (VTE) or pulmonary embolism and other clotting disorder, migraine, prior stroke, uncompensated liver disease, or in patients with complicated diabetes.

Oral spironolactone is an effective anti-androgenic agent developed to treat blood pressure initially. Since it is an aldosterone receptor antagonist it also works for acne, although it is not FDA approved for this indication. Several trials have shown excellent results in doses of 50 to 200 mg per day. It may take 3 months to work but can be taken for indefinite periods of time without significant side effects. The use of spironolactone has tripled in recent years due to the growing acceptance of its safety and efficacy in acne. There is no recommendation to check potassium levels in spironolactone users except in certain situations.

Isotretinoin

Isotretinoin is indicated for severe nodular acne. It reduces sebum production, acne lesions, and scars. Doses are typically started low and increased as tolerated. However, there is a better effect and fewer relapses at higher doses. It is also appropriate in moderate acne that is producing scars or significant psychologic distress. Intermittent dosing is not appropriate. When using this medicine routine blood tests for liver functions, triglycerides, and cholesterol are appropriate. The one test that is most important is triglycerides because marked elevations have occurred. Many dermatologists report that when liver tests are abnormal it is often the result of another process, and not the medication. The medicine can cause birth defects so strict guidelines are in place in limit pregnant women from using this agent. All treated patients must adhere to the Ipledge monitoring program to reduce the risk of becoming pregnant while taking this medicine. This program requires the use of 2 methods to prevent pregnancy. The medicine can cause severe dryness of skin which may limit its use. In teenagers however, the dryness may be a welcome change from oily skin.

There is no proven link between the use of isotretinoin and inflammatory bowel disease. Changes in mood, depression, and suicide ideation have been reported, but to date there is no consensus of studies to prove this. Increased rates of staph infections have been reported to occur with isotrentoin and should be watched for. There is no proven risk of delayed bone epiphyseal closure or osteoporosis with isotretinoin and no monitoring for osteoporosis is indicated.

Conlusions

There are many controlled trials detailing the effectiveness and safety of the drugs used to treat acne. While acne is not a life-threatening disease, it can cause considerable psychological and physical scarring to the victims of the disease.

Evidence-based treatment recommendations allow physicians and patients the ability to make informed decisions on how best to treat this disease. It is very important that physicians recognize that the process of treating acne may be protracted and will often be trial and error and that relapses are common. None the less a significant number of patients will improve, which will improve the quality of their lives.