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Image courtesy of Chovatiya, R. (2021) and Thiboutot, D., Dreno, B., Abanmi, A., et al. (2018). It is available for download for patient education and bulk reprints at email reprints@jamanetowork.com

~8 minute read

Acne Pathogenesis

Our current understanding of acne is based on significant evidence that supports four areas of acne pathogenesis or the actions that cause acne:

- Androgen (testosterone and dihydrotestosterone) stimulated increased sebum production

- Hyperkeratinization of the hair follicle

- Growth of Cutibacterium acnes

- Inflammation

Our understanding of these mechanisms of actions have shaped the recommendations for treatment which can be found in the latest acne guidelines published by the American Academy of Dermatology (AAD) in 2016. The guidelines addressed a number of key areas, including:

- Topical therapies

- Systemic treatments

- Physical modalities

- Laser treatment

- Photodynamic therapy

- Acne grading and classification

- Microbiologic and endocrinologic testing

- The impact of diet

It does not address truncal acne, acne scarring or post-inflammatory dyschromia (hyperpigmentation and erythema). Furthermore, the studies evaluated to develop the 2016 Acne Guidelines did not include pregnant, lactating, or menopausal women; men; heavy smokers aged 35 and older; or those receiving hormone therapy (Baldwin et al., 2023).

Acne Management Consensus Roundtable

In 2022, an Acne Management Consensus Roundtable (group of dermatologists) convened to discuss the unmet needs of acne with emphasis on clascoterone, an anti-androgen approved by the Food and Drug Administration (FDA) in 2020 for patients 12 and older with moderate to severe acne. The group of dermatologists published a consensus statement in the Journal of Drugs in Dermatology titled, Unmet needs in the management of acne vulgaris: A consensus statement (Baldwin, Farberg, Frey, Hartman, Lain, Meltzer, & Draelos, 2023).This report is significant as there is an 85% incidence of acne in adulthood and it’s the number one diagnosis in dermatology globally. It's been well documented that acne is associated with reports of lower quality of life, poor self-esteem, and a higher risk of anxiety, depression, physical scarring, and suicidal ideation (Eichenfield, Sprague, & Eichenfield, 2021).

Adult Acne

While there is a misconception that acne is only associated with adolescence, there is a growing body of evidence and social media posts discussing the burden of the disease into adulthood. Acne is reported in more than 50% of adults aged 20 to 29 and more than 40% in adults aged 30 to 39. Some men (8%) and women (18%) develop acne for the first time after age 25 (Eichenfield et al., 2021).  I recently wrote about treatment recommendations for testosterone-induced acne in which I discussed an article that reported the persistence of mild acne in transgender men after ten years of testosterone therapy. This population is even more vulnerable to the psychodermatological impacts of acne and are at increased risk of hormone-induced acne due to treatment which may last decades.

I’m really inspired by the Acne Management Consensus Roundtable who continued to evaluate the latest evidence instead of simply relying on the latest guidelines. It reminds us of the importance of staying abreast and how a collective voice can be used to improve provider awareness and patient outcomes.

Hormonal Acne

We often associate acne on the forehead, nose, and chin (teenagers); lower portion of the face and jawline (adults); and that fluctuates with menstruation as hormonal acne. Additionally, people with medical conditions associated with higher levels of androgen, like polycystic ovary syndrome (PCOS) or who receive testosterone replacement are more prone to developing acne. However, based on acne pathogenesis as described above, we can see that all acne is hormonal, a point Baldwin et al. (2023) stated cannot be over emphasized. The mainstays of the traditional view of hormonal acne includes:

- Oral contraception

- Spironolactone (50-200 mg daily), used off label

- Isotretinoin

The Unment Needs of Acne

Unfortunately, none of these current options are preferred or appropriate for men, pregnant women, or transgender men. The wait time for an evaluation and to see desired outcomes is about 12 weeks (Baldwin et al., 2023). The general practice has been to start with topicals and add an oral medication for moderate to severe acne. However, when it came to the common treatment recommendations for hormonal acne, none of the topical options targeted all four areas of acne pathogenesis, including excess sebum production. While isotretinoin targets all 4 areas of pathogenesis, it is not safe during pregnancy or breastfeeding, nor recommended for men, heavy smokers aged 35 and older, or for those receiving testosterone (Baldwin et al., 2023).

Testosterone, Dihydrotestosterone (DHT), and Estrogen

Let’s take a close look at the mechanism of action of androgens. In people who have testes, testosterone and dihydrotestoerone (DHT) are produced by the testes, adrenal glands and in the pilosebaceous unit or hair follicle. In this case, the 5 alpha-reductase inhibitor (an enzyme which stimulates a reaction) converts testosterone into DHT. In people who have ovaries, testosterone and DHT is produced by the ovaries, adrenal glands, and pilosebaceous unit. The ovaries release estrogen, progesterone, and androstenedione. In this case, 5 alpha-reductase converts androstenedione into testosterone then to DHT. Both testosterone and DHT bind to androgen receptors in the pilosebaceous unit and trigger the expression of genes responsible for excess sebum production and inflammation (Baldwin et al., 2023).

Clascoterone (WINLEVI): A Topical Anti-Androgen

Now that we understand the action of androgens and how they contribute to the development of acne, we can see why certain medications are recommended. Clascoterone 1% (cream applied twice daily) is the first approved topical anti-androgen and it has a favorable profile:

- Targets all four areas of acne pathogenesis

- Can be used long-term in people aged 12 years and older with moderate to severe acne

- The most common side effects are itching, redness, scaling, and dryness (easily treated)

- No evidence of reduced libido or feminization in men

- The greatest concern is risk for suppression of the hypothalamic-pituitary-adrenal axis during or after treatment (an indication to stop application)

- Higher risk of systemic toxicity in pediatric patients

- No contraindications

Anti-androgen means the medication blocks testosterone and DHT from binding to the androgen receptor in the pilosebaceous unit which prevents excess sebum production and inflammation associated with the development of acne. It’s a wonderful treatment option for people seeking care, as most people who have mild acne tend to successfully treat it a home. Therefore, those seeking dermatology care tend to have moderate to severe acne. We always want to treat acne aggressively to avoid scarring and hyperpigmentation which take much longer to resolve and increase the risk for psychodermatologic concerns (anxiety, depression, suicidal ideation). It is an ideal option for those who do not want or cannot take oral medication. Most importantly, it is appropriate for the subset of the population previously untreated or under-treated for moderate to severe acne:

-Men

-Pregnant and breastfeeding

-Heavy smokers age 35 and older

-Receiving hormone replacement therapy

-Truncal acne

More research is needed to help answer questions about the mechanism of action as it relates to acne pathogenesis.

Journal of Drugs in Dermatology and Access to Information

The Journal of Drugs in Dermatology (JDD) is one of my favorite dermatology journals. Pharmacology is one of the most challenging aspects of being a nurse practitioner. In fact, I elected to center my DNP Project around pharmacology (specifically, antibiotic stewardship) to increase my knowledge base and confidence! At first, I thought JDD might publish boring studies I wouldn’t be interested in, but I was wrong. They have the most interesting articles and I often find my favorite topics on the front page: skin of color, diversity, and social media. It’s clear they have a mission to promote diversity and/or they have a diverse panel of authors. Either way, they are putting in the work! New articles are published daily to weekly. There’s so much valuable content, I can barely keep up.  

I love research, reading about the latest findings, and sharing them. It recently dawned on me that the Doctor of Nursing Practice degree was indeed the best option for me (as I once debated between the DNP and PhD). If you’re not familiar, there was a 17-year gap when it came to bringing the latest research findings to the patient. Meaning, if a researcher discovers new knowledge today that can improve acne, it would take another 17 years for products and information to be available for patient care. When it comes to research, all the requirements and regulations that have to be met prolonged advancing care and improving outcomes. Well, we all know that is not acceptable. Enter the Doctor of Nursing Practice (DNP) degree. Unlike the Doctor of Philosophy (PhD) where new knowledge is discovered, the DNP degree translates that new knowledge for the setting in which it is going to be implemented. The DNP gave me the language for what I love to do and the credentials to critically evaluate how the latest evidence can be used to improve nursing practice.

I recently discovered access to this information is not widely available to the general public, non-members, and those outside of academia. If it were not for databases like PubMed and publications like JDD, we would not have this opportunity. I will discuss this topic further and what is means to publish an Open Access article in the near future. In the meantime, visit JDD. They offer a complimentary subscription for nurse practitioners and physician associates practicing in dermatology! We love that and we love JDD. We always talk about access to care for patients, yet there remain barriers to access to knowledge for clinicians. I’m grateful to PubMed, Open Access publications, and the authors who make it possible for me to bring the latest evidence to you and translate the findings into information you can use today.

References

Baldwin, H., Farberg, A., Frey, C., Hartman, C., Lain, E., Meltzer, R. & Draelos, Z. (2023). Unmet needs in the management of acne vulgaris: A consensus statement. Journal of Drugs in Dermatology, 22(6), 582-587. https://doi.org/10.36849/JDD.7587

Chovatiya, R. (2021). Acne treatment. JAMA, 326(20), 2087. https://jamanetwork.com/journals/jama/fullarticle/2786498?resultClick=1

Eichenfield, D., Sprague, J., & Eichenfield, L. (2021). Management of acne vulgaris: A review. JAMA, 326(20), 2055-2067. https://doi.org.10.1001/jama.2021.17633

Madison, K. (2022). Antibiotic Stewardship for Asymptomatic Bacteriuria in Older Adults Residing in Long-Term Care at End-of-Life. , (). Retrieved from https://hsrc.himmelfarb.gwu.edu/son_dnp/109

Thiboutot, D., Dreno, B., Abanmi, A., et al. (2018). Practical management of acne for clinicians. J Am Acad Dermatol, 78(2 suppl 1):S1-S23. https://doi.org/10.1016/j.jaad.2017.09.078

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Kimberly Madison, DNP, AGPCNP-BC

Kimberly Madison is a doctorly prepared, dermatology nurse practitioner with a passion for writing, entrepreneurship, financial literacy, and mentorship. I created this blog to share my journey as I become a dermatology nurse practitioner and entrepreneur. Most importantly, I’m looking forward to helping nurse practitioners and aspiring students to better understand the business of dermatology and their role in improving access to care, providing culturally competent care, and advancing education.

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