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First, determine the types of lesions they have. “Do they have comedones, papules/pustules, and nodules present?” she asked during the virtual Pediatric Dermatology 2020: Best Practices and Innovations Conference. Second, quantify the number of lesions that they have. Is it few? Several? Many? Third, determine the extent of their acne. “Is it limited to half the face, or is it generalized to the face, back, chest, and shoulders?” added Dr. Zaenglein, professor of dermatology and pediatrics at Penn State University, Hershey.
Fourth, identify postinflammatory changes such as erythema, hyperpigmentation, and scarring “because that’s going to influence your management,” she said. “Finally, you want to give a quick investigative global assessment of the acne severity where you quantify them as being clear, almost clear, mild, moderate, or severe. You want to do this with each patient at every visit so you can determine what their initial treatment’s going to be and what their management going forward is going to be.”
According to Dr. Zaenglein, the best acne treatments are based on the pathogenesis of the skin condition and trying to target as many pathogenic factors as possible. The four main pathogenic factors in acne include hyperkeratinization, increased sebum production, cutibacterium, and inflammation. “This is not a stepwise process; there’s an interplay between all of those factors,” she said. “All acne is inflammatory, but each of the treatments we have target specific factors. Retinoids target hyperkeratinization and inflammation, whereas the hormonal therapies will address decreased sebum production. Antimicrobial agents like benzoyl peroxide and antibiotics will work to decrease cutibacterium acnes. All of these are influenced by the exposome. This includes your genetics, external factors like pollution or changes in seasons that can affect your skin and the severity of your acne.” A state of hyperandrogenism, she added, “can definitely increase acne” and is seen in patients with polycystic ovary syndrome (PCOS).
For patients with mild acne, initial treatment should consist of a topical retinoid and, almost always, benzoyl peroxide, “unless it’s a pure comedonal form of acne,” Dr. Zaenglein said. She recommended using the combination of a topical retinoid and benzoyl peroxide, noting that while it used to be difficult to find benzoyl peroxide, “nowadays there are numerous manufacturers and different formulations of benzoyl peroxide. We also have over-the-counter adapalene now, which is great. So now we have a complete routine for patients with adapalene and benzoyl peroxide that you can combine together in a cost-effective way.”
If the initial regimen fails to improve the patient’s mild acne, a second-line treatment would be to change the retinoid and continue on the existing benzoyl peroxide formulation or to add dapsone gel if the patient is experiencing skin irritation. The four retinoids currently available include adapalene, tretinoin, tazarotene, and trifarotene. “These normalize keratinocyte differentiation, reduce keratinocyte proliferation, and decrease expression of inflammatory markers,” Dr. Zaenglein noted. “They also prevent scarring. Adapalene is considered to be the most tolerable, whereas tazarotene may have an edge on efficacy. There’s a lot of overlap; head-to-head studies may not always match them up exactly, but generally this is how it’s considered. Picking the right retinoid for your patient based on efficacy and tolerability is most important.”
The newest topical retinoid, trifarotene 50 mcg/g cream, is a fourth-generation retinoid which is retinoic acid receptor gamma selective. Pivotal trials were conducted in patients aged 9 years and older with moderate facial and truncal acne. With monotherapy there was a success rate of 36% at 12 weeks and 60% at 52 weeks based on the Investigator’s Global Assessment. Another newcomer, tazarotene 0.045% lotion, is a third-generation retinoid which is retinoic acid receptor alpha beta gamma selective. It’s approved for moderate to severe facial acne in patients 9 years and older.
To optimize tolerance to retinoids, Dr. Zaenglein asks patients about their typical skin care regimen. “I ask them what they’re washing their face with,” she said. “Are they using apricot scrubs or harsh cleansers? Make sure they’re applying it to the entire face and not spot-treating. You get less irritation when it’s applied to dry skin, so you can recommend that. Make sure that they use a bland unscented moisturizer in the morning and apply it over top of their retinoid. I always warn them that irritation usually peaks at about 2 weeks. If they can power through, the irritation will improve with continued use.”
Dr. Andrea L. Zaenglein
To optimize adherence to retinoids, she asks patients how many nights per week that they apply it. If they are using it all seven nights, “they’re good at using it,” she said. “If they say three nights, then they need to work on getting it on more frequently.”
Topical dapsone gel (5% and 7.5%) is mainly used for patients with papular-pustular acne. “Its mechanism of action for acne is not known, but presumptively it’s anti-inflammatory,” Dr. Zaenglein said. “It doesn’t require G6PD [glucose-6-phosphate dehydrogenase] testing. It can cause some orange discoloration of your skin or fabrics if you use it with benzoyl peroxide, so you want to apply them at different times of the day. It’s well tolerated. I tend to use it in patients who have problems tolerating any topical retinoid or any benzoyl peroxide but have mild to moderate acne.”
For patients with moderate acne, consider combination therapy to target as many pathogenic factors as possible. “Use a topical retinoid plus benzoyl peroxide with or without a systemic antibiotic,” Dr. Zaenglein advised. “I may give them an oral antibiotic if their acne is not responsive to the routine. But you wouldn’t want to combine the systemic antibiotic with a topical antibiotic, like clindamycin with doxycycline, because you don’t need two antibiotics. Make sure that you treat aggressively up front. It can take up to 3 months to see improvement. I counsel my patients that we’ll rescue with the antibiotic and then we maintain, but we’re going to stop that antibiotic after 3 months.”
Systemic antibiotic options for acne include tetracyclines, doxycycline, minocycline, and sarecycline. “Tetracycline itself we don’t use too much because you have to take it on an empty stomach, and availability is sometimes an issue,” she said. “Primarily, we use doxycycline. You can take it with food, so that helps. The main side effects are gastrointestinal upset and photosensitivity. Alternately, you can use minocycline, which is also okay to take with food. It does have more potentially worrisome side effects, including pseudotumor cerebri, blue pigmentation, autoimmune hepatitis, and DRESS [drug reaction with eosinophilia and systemic symptoms].”
Sarecycline is the first narrow spectrum tetracycline for acne, with fewer vestibular and phototoxic side effects, compared with other tetracyclines. “It also has less effect on the GI flora,” Dr. Zaenglein said. “It’s a good alternative but it can be costly, so make sure to check the pricing for your patients.” She does not use other antibiotics such as TMP/SMX, penicillins, or cephalosporins for acne patients. “The reason is, the tetracyclines are not only antibacterial, but they’re anti-inflammatory,” she explained. “They also are lipophilic, so they will penetrate into the sebaceous unit where the heart of the acne is.”
For patients who don’t want to take an oral antibiotic, consider minocycline 4% foam, which was studied in moderate to severe acne in patients aged 9 years and older. The pooled results from the three studies showed a 47% mean improvement in inflammatory acne, compared with 37% among those in the vehicle arm. “You wouldn’t use this as monotherapy; you’d use this in combination with the topical retinoid and the benzoyl peroxide,” Dr. Zaenglein said.
Most primary care providers do not prescribe isotretinoin for patients with severe acne, but they can start patients on triple therapy with a topical retinoid, benzoyl peroxide, and a systemic antibiotic at its full dose. “The efficacy of triple therapy in patients you would typically deem as isotretinoin worthy is actually pretty good,” she said. “There have been several studies looking at this, and about 70%-80% of patients will respond to triple therapy, where they are no longer deemed isotretinoin candidates. They still may need to move on to isotretinoin, but they will be improved.”
Dr. Zaenglein disclosed that she is a consultant for Cassiopea, Novartis, and Pfizer. She has also received grants or research support from AbbVie, Incyte, and Pfizer.