When to Move from Topical to Systematic Therapy for Acne, With Shanna Miranti, MPAS, PA-C

At the 2025 New Wave Dermatology meeting in Aventura, Florida, Shanna Miranti, MPAS, PA-C, a physician assistant at Riverchase Dermatology, presented on when to move from topical to systemic therapy for acne.

HCPLive sat down with Miranti during the meeting to discuss the 4 pillars of acne pathogenesis—excess sebum production, follicular hyperkeratinization, inflammation, and cutibacterium acne—and how to choose the best acne treatment regimen for your patient.

“What's most important is to make sure that we as providers are treating as many of these 4 pillars as possible,” Miranti said.

Isotretinoin, an oral retinoid, targets all 4 pillars of acne pathogenesis. This is currently the top acne treatment on the market, but new therapies are on the horizon.

The American Academy of Dermatology updated their 2016 acne guidelines in 2024, which now recommends limiting systemic antibiotic use to limit the development of resistance and to use concomitant benzoyl peroxide. The US Food and Drug Administration (FDA) approved many acne medications since 2019, including Aklief (trifarotene, a topical photostable retinoid), Amzeeq (topical minocycline), Arazlo (tazarotene 0.045%, a topical photostable retinoid), Seysara (saracycline, oral antibiotic), Winlevi (clascoterone, a topical anti-androgen), Twyneo (tretinoin 0.1%/ BPO 3%), and Cabtreo (Clindamycin 1.2%, Adapalene 0.15%, BPO 3.1%). With so many options available, Miranti said you should not just prescribe generic tretinoin.

When considering patient treatment options, Miranti recommended looking at each pillar individually. For instance, the only topical therapy that works for excessive sebum and oily skin is clascoterone, an androgen receptor blocker.

“If we can stop the sebum production and block those androgens, we will have a lot less acne in the future,” she said.

Systematic therapies for sebum production include isotretinoin, spironolactone (50 mg QD-BID), and oral contraceptive pills.

With the next pillar— follicular hyperkeratinization—retinoids work the best at opening the micromedone and a plugged follicle. Patients could use topical retinoids, such as tretinoin, adapalene, tazarotene, and trifarotene. However, due to potential irritation of retinoids, Miranti said dermatologists should counsel patients on protecting the skin barrier through moisturization.

Other than retinoids, patients could be prescribed azelaic acid or isotretinoin.

The next pillar is inflammation, managed by topical retinoids, topical antibiotics, topical dapsone, azelaic acid, and clascoterone. Systematic therapies for inflammation include isotretinoin, doxy, mino, sarecycline, spironolactone, and oral contraceptive pills.

“The earlier we can stop…inflammation, the better we can prevent scarring for our acne patients,” Miranti said.

The last pillar, cutibacterium acnes, can be treated with topical antibiotics (clindamycin with benzoyl peroxide, minocycline 4%), and systemic therapies of sarecycline, doxy, mino, and tetracycline, taken alongside benzoyl peroxide.

Miranti explained that patients will need to switch to systemic therapy if topical therapy does not control new active breakouts, breakouts are following a hormonal pattern, an acute situation such as stress or sports is causing a worsening of the inflammatory lesions, or when any scarring is present.

Treating the 4 pillars can help determine whether a patient needs to move from topical to systemic therapies.

“If we think of the four pillars of acne pathogenesis as four legs of a table, it makes sense that a table cannot stand up on one leg alone and a table would be very unbalanced on just 2 legs alone, 3 legs,” Miranti said. “Things do work on a tripod quite well, but of course, the 4 legs or 4 pillars are going to give you the most sturdy balance of a table. So, we really should try to choose medications or therapies for our patients that check all 4 boxes of the 4 pillars of acne pathogenesis, and we want to do that with the least amount of products possible.”

References

Miranti S. Acne: Moving Away from Topicals to Systemic Therapy. Presented at 2025 New Wave Dermatology from May 15 - 17, 2025 in Aventura, Florida.

Relevant disclosures for Miranti include Galderma Laboratories,Incyte Corporation, Verrica Pharmaceuticals, Ortho Dermatologics, a division of Bausch Health US, Almirall, and Arcutis Biotherapeutics.