Acne: What’s New and What’s to Come?

I still treat my acne twice daily with a whole cabinet full of various topicals. I’ve tried and failed doxycycline because it disrupts every single molecule of bacterial flora in my body. I’ve tried and failed spironolactone because I was the poster child for nearly all of its annoying and inconvenient side effects. I’ve tried and failed several OCPs because my body was a little too convinced by the estrogen and progesterone that it was actually pregnant, and decided to make me persistently sleepy and nauseous. I could put the 650-microsecond Nd:YAG that we have in clinic to use, but can’t bring myself to bother my co-rezzys (or myself) at the end of a long day seeing patients. And yes, I’ve already done a course of isotretinoin…two courses in fact. And no, I don’t have PCOS. So when I settled in to hear Dr. Andrew Alexis’s lecture on Acne: What’s new and what’s to come?, I was excited for some new strategies with which to help my patients, and myself. Dr. Alexis not only shared expert insights and strategies on how to optimize treatment for skin of color (SOC) patients with acne, but he also laid out an overview of some of the new and emerging acne treatments that we will presently be able to add to our armamentarium!

This article will provide an overview of the following:

-Understanding the unique presentation and needs of SOC patients with acne

-Sarecycline, a new tetracycline class antibiotic

-New topical acne medications in the pipeline

But first, let me share a few of the “A-ha” moments that I experienced during Dr. Alexis’s lecture, in the hope that they will entice you to read on…

-Subclinical inflammation is a driver of acne sequelae in SOC patients. Did you know about subclinical inflammation, because I surely did not!

-Don’t wait until the acne is controlled before you go after post-inflammatory hyperpigmentation (PIH). This notion rocked my world. Want to know how you can take down acne and PIH at the same time?? Read on…

-To the last point, do you have a SOC patient on isotretinoin who is clear of acne lesions but struggling with PIH? Stay with me to learn the secret cocktail Dr. Alexis uses for complexion blending…

-Have a FST III+ patient that you want to start on adapalene 0.3%-benzoyl peroxide 2.5% gel? I learned a pearl about anticipatory guidance that changed the way I counsel patients when starting this medication…

Understanding the unique presentation and needs of skin of color patients with acne

1 . Nip the acne in the bud!

Or as Dr. Alexis so eruditely explained, “early and effective treatment is the key to reducing long-term sequelae.” This is so important for a number of reasons. We know that moderate-to-severe truncal acne is at higher risk of progressing to hypertrophic scars and keloids, and once those fibroblasts and collagen are in place, they can be pesky and expensive to get rid of. (This is not to say they can’t be treated, and if you’d like to read about how, check out my recent post on Laser and Device Based Treatment of Scars. Additionally, subclinical inflammation—a completely new concept to me—may contribute to the formation of PIH. Subclinical inflammation is inflammation that is observed histologically, but not clinically, in the perilesional skin of SOC acne patients. Lending further credence to the quiet conflagration are studies that have found evidence of upregulated IL-1 and an increase in CD3+,CD4+ T-lymphocytes in clinically normal perifollicular skin compared to controls.1,2

The takeaway from all of this is that there is often more going on than meets the eye, and that an aggressive treatment approach is warranted to try to limit the extent to which patients with more richly pigmented skin are experiencing PIH as we try to get their acne under control. A multilayered approach is often required, and may consist of tetracycline antibiotics used alone or in combination with spironolactone, and a topical regimen that may variously consist of benzoyl peroxide, topical retinoids, topical dapsone, azelaic acid, and occasional intralesional triamcinolone (up to a concentration of 3.3 mg/mL).

2. Concurrently address hyperpigmentation.

This is a piece of teaching that has produced a huge paradigm shift in the way I treat acne. I had previously thought that it made more sense to try to get the acne under control first before chasing down PIH, but I now see that I am doing my SOC patients a disservice with this approach. And I am honestly surprised that I persisted with my erroneous ways for as long as I did—as a half-Korean woman with acne, I know that my red lesions become lingering brown spots that are a consistent, potent source of unhappiness and exasperation when my skin is acting up. Beyond my n of 1, there is a lot of data out there that attests to the fact that PIH is often more distressing to patients than the acne itself, particularly among patients with SOC. In a survey of 208 women between the ages of 25-45 who were struggling with acne, lesion clearance was found to be most important to white/Caucasian women, while 41.6% of non-white females reported PIH clearance to be the most important (vs. 8.4% of Caucasians).3

These findings make it necessary to both select agents that concurrently treat active acne and PIH, and to redefine the treatment endpoint as resolution of both PIH and acne. Though hydroquinone may be a reflexive choice when a patient complains of “dark spots,” we also know that it does nothing for acne, and applying it as a spot treatment to numerous PIH lesions is both laborious and impractical. Topical retinoids are effective in treating both acne and PIH, and are available in a wide variety of strengths and vehicles that can be customized to suit patient tolerability. Azelaic acid (AZA) is available as both a 20% cream and a 15% gel, and is known to be simultaneously antibacterial, anticomedonal, anti-inflammatory, and tyrosinase inhibitory. In a trial of 20 FST V-VI adults with acne and PIH, twice daily AZA 15% gel produced at least a 2-point improvement by the Investigator’s Global Assessment in acne in 100% of patients at week 16, while 31% of patients also had no PIH by this time.4 Patients should be specially counseled to apply these topicals to the entire face, given what we know about subclinical inflammation and its contribution to PIH.

Adjunctive therapies that can be easily and intermittently incorporated to boost treatment include salicylic acid, glycolic acid, and Jessner’s peels, at intervals of around 2 – 4 weeks. In this setting, 4% hydroquinone may be added to both enhance efficacy, and to prevent PIH from the peels themselves.

And as promised, for those patients whose skin has cleared a few months into isotretinoin, but who continue to be plagued by PIH, Dr. Alexis recommends a regimen consisting of topical vitamin C, mineral powder sunscreen, and azelaic acid compounded with a mild topical steroid to be used short term while regular use of a good moisturizer reconstitutes the skin’s barrier. Once that patient is no longer complaining of dryness, irritation, or stinging, and has reliably implemented a consistent moisturizing regimen that works for them, they can be transitioned to 20% azelaic acid cream, and can additionally start a topical niacinamide serum (which will impede melanosome transfer). Love it!

3. Avoid iatrogenic dyspigmentation by avoiding irritation.

 Treatment regimens must not only be aggressive enough to reduce inflammation and other pathogenic factors, but also well tolerated so that irritation is avoided. The tolerability of a topical regimen can be optimized by carefully considering the molecule, concentration, vehicle (favor aqueous gels, lotions, or creams), and dosing regimen of the medications that you are considering. Patients should furthermore be counseled to STOP potentially irritating toners, scrubs, astringents. So please drive the point home—no more rubbing alcohol or apricot scrub!!! And remind patients to apply a non-comedogenic moisturizer over their prescription topicals if dryness, stinging, burning, peeling, or other forms of irritation become an issue for them.

A relatively new addition to the topical acne armamentarium is tretinoin 0.05% lotion. Approved for the treatment of acne in patients 9 years old and older, this topical has many features to enhance both its cutaneous penetration and tolerability. This is a controlled release, micronized (10 microns, which is smaller than the size of the follicular orifice) form of tretinoin, that is formulated with moisturizing and hydrating ingredients such as hyaluronic acid, glycerin, hydrolyzed collagen, and water. In a recently published post hoc analysis of two multicenter, randomized, double-blind, vehicle-controlled phase 3 studies, Asian subjects aged 12 to 48 years were randomized (1:1) to receive tretinoin 0.05% lotion or vehicle once-daily for 12 weeks. At the treatment endpoint, there was a significant reduction in inflammatory and noninflammatory lesion counts with tretinoin 0.05% lotion compared with the vehicle, and only 5 subjects out of 69 reported mild transient scaling and burning that was present during the first 4-8 weeks of treatment.5

Another effective and well-tolerated topical that can concurrently treat both acne and PIH is adapalene 0.3%-benzoyl peroxide 2.5% (ABP) gel. In a study of once daily ABP gel in SOC patients (n = 50; 20 Asians, 17 black/African-Americans, and 13 Latin-Americans, most with FST IV (74%) or V (22%)) with moderate or severe facial acne, patients reported high satisfaction, good tolerability, treatment efficacy, and improvement in PIH.6 There were no adverse events leading to study discontinuation. Dr. Alexis has found that when using adapalene 0.3%-benzoyl peroxide 2.5% gel, side effects such as dryness and irritation peak at week 2, then taper off. He therefore emphasized the importance of arming patients with strategies to help them persevere through this initiation period, so that they can continue on a smooth course thereafter.

What’s new: Sarecycline

Sarecycline is a new, narrow-spectrum tetracycline antibiotic that preferentially inhibits P. acnes while having a minimal effect on gram-negative enteric flora. It is approved for the treatment of inflammatory lesions of non-nodular moderate to severe acne vulgaris in patients 9 years of age and older, and is recommended to be dosed at 1.5 mg/kg/day. Have you tried it yet with your patients?

What’s coming

Topical minocycline 2% gel and 4% foam, are currently in phase 2 and 3 trials, respectively.

A topical anti-androgen, clascoterone, is currently in phase 3 trials.

-The US FDA has accepted the new drug application for tazarotene 0.045% lotion. If approved, it will be the first tazarotene acne treatment available in lotion form.

Topical trifarotene, a unique retinoid receptor agonist that selectively targets retinoic acid receptor gamma, is in development for the treatment of both moderate facial and truncal acne.

So what are some of your tried and true regimens for acne in skin of color patients? Do you have any customized compounds that you like to use? What over the counter products do you like to recommend? Have you used sarecycline or tretinoin 0.05% lotion yet? What have your results been? Please share your comments at the end of this post, and on Instagram @nextstepsinderm!

Dr. Andrew Alexis is the Chair of the Department of Dermatology at Mount Sinai St. Luke’s and Mount Sinai West. He is also  Professor of Dermatology at the Icahn School of Medicine at Mount Sinai, where he is Director of the Skin of Color Center.

The above information was presented by Dr. Andrew Alexis at the 2019 Skin of Color Update held September 7-8 in New York City. The above highlights from his lecture were written and compiled by Dr Kimberly Huerth, Chief dermatology resident at Howard University in Washington DC.

Did you enjoy this post? Find more Skin of Color topics here. 

Purchase Skin of Color Update On-Demand:

Skin of Color Update On-Demand

 

 

 

References

  1. Jeremy AHT, Holland DB, Roberts SG, Thomson KF, Cunliffe WJ. Inflammatory events are involved in acne lesion initiation. J Invest Dermatol. 2003;121(1):20-27.
  2. Alexis AF. Acne in patients with skin of color. J Drugs Dermatol. 2011;10(6):13.
  3. Callender VD, Alexis AF, Daniels SR, et al. Racial differences in clinical characteristics, perceptions and behaviors, and psychosocial impact of adult female acne. J Clin Aesthet Dermatol. 2014;7(7):19-31.
  4. Kircik L. Efficacy and safety of azelaic acid (AzA) gel 15% in the treatment of post-inflammatory hyperpigmentation and acne: A 16-week, baseline-controlled study. J Drugs Dermatol. 2011;10(6):586-90.
  5. Han G, Armstrong AW, Desai SR, Guenin E. Novel tretinoin 0.05% lotion for the once-daily treatment of moderate-to-severe acne vulgaris in an asian population. J Drugs Dermatol. 2019;18(9):910-16.
  6. DuBois J, Ong G, Petkar G, et al. Patient-reported outcomes in acne patients with skin of color using adapalene 0.3%-benzoyl peroxide 2.5%: A prospective real-world study. J Drugs Dermatol. 2019;18(5):514-20.

Image Credits:

Main image courtesy of the Journal of Drugs in Dermatology

https://jddonline.com/articles/dermatology/S1545961618P0602X/6/

Please follow and like us:
error