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Article

Acne pathogenesis

Author(s):

The pathogenesis of acne is not entirely understood, but new insights may yield new therapeutic targets in the near future. As research into the pathogenesis of acne continues, the spectrum of available therapies will continue to expand.

The pathogenesis of acne is not entirely understood, but new insights may yield new therapeutic targets in the near future.

"We now know that there are some other factors involved that had not been previously described," says Rachel Reynolds M.D., FAAD, an attending dermatologist at Beth Israel Deaconess Medical Center and Residency Training Director of the Harvard Combined Dermatology Residency Program, discussing the disease at AAD 2015.

READ: Acne in skin of color

One of the recent insights about acne pathogenesis is that inflammation actually precedes comedogenesis. "We used to think that comedones preceded inflammation, but we now know that inflammation is involved in the development of comedones," said Dr. Reynolds.

Via IL1-alpha, inflammation is recognized as preceding hyperkeratinization in comedone formation, and increased levels of IL1-alpha are found in open comedones, explained Dr. Reynolds.

NEXT: Insights into the sebaceous gland

 

New insights into the sebaceous gland reveal that melanocortin-1 receptor is higher in sebaceous glands of acne patients. In a study of 33 patients, investigators sought to study, through immunohistochemistry, if changes of melanocortin-1 receptor expression are produced in acne lesions compared to skin from patients without acne. They observed seboctyes and keratinocytes of the ductus seboglandularis of acne-involved skin demonstrated very high melanocortin-1 receptor expressed compared to normal skin.1

"We now know sebaceous glands have receptors for melanocortin," said Dr. Reynolds. "Animal studies have looked at topical melanocortin inhibitors as potential therapies for acne."

READ: Gold microparticles zap sebaceous follicles

An appreciation of the role of sebum lipids is coming to the fore. "We understand that they are pro-inflammatory," said Dr. Reynolds.

Decreased linoleic acid not only can impair the skin barrier and make it more permeable, but its depletion has been linked to the pathogenesis of acne, noted Dr. Reynolds.

Research has also identified the significance of toll-like receptor 2 in the pathogenesis of acne, according to Dr. Reynolds. Specifically, investigators found toll-like receptor 2 activation and secretion of IL-1alpha from keratinocytes may potentially be triggering comedogenesis, making toll-like receptor 2 essential to the development of acne.2

READ: Alternative treatment options for acne

"P. acnes bind to toll-like receptor 2 and trigger inflammatory pathways and antimicrobial pathways," said Dr. Reynolds. "Theoretically, if you could block toll-like receptor 2, you could have an impact on the development of inflammatory acne."

There is also a greater understanding of retinoid mechanisms, and the anti-inflammatory impacts of retinoids, noted Dr. Reynolds. Among their actions, retinoids induce CD209+ macrophages that attack P. acnes. In addition, isotretinoin decreases matrix metalloproteinases in sebum.

NEXT: The role of androgens and their contribution to pathogenesis of acne

 

The role of androgens and their contribution to the pathogenesis of acne continue to be explored. It is recognized that skin that is prone to acne has greater androgen receptor density as well as greater 5alpha-reductase activity, noted Dr. Reynolds. Patients with conditions like polycystic ovary syndrome, congenital adrenal hyperplasia, and androgen-secreting tumors have elevated rates of acne.

READ: Acne ingredients to embrace or avoid

Biofilm may also be a factor in acne, according to Dr. Reynolds. P. acnes biofilms adhere to the follicular lining, thereby contributing to the follicular plug that heralds comedone formation. P. acnes biofilms also play a role in the development of resistance to antibiotic therapy.

Recent in situ studies have demonstrated IL-17 expressing cells were found in skin biopsies of acne patients and were not detectable in skin biopsies of healthy donors and isotype controls. Investigators have also demonstrated Vitamin A and Vitamin D inhibited Th17 differentiation induced by P. acnes.3

As research into the pathogenesis of acne continues, the spectrum of available therapies will continue to expand. 

More on acne

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Acne-fighting collection aims to clear problem skin

Pre-adolescent acne 

NEXT: References

 

 

Dr. Reynolds had no relevant disclosures.

1. Ganceviciene R, Graziene V, Bohm M, Zouboulis CC. Increased in situ expression of melanocortin-1 receptor in sebaceous glands of lesional skin of patients with acne vulgaris. Exp Dermatol. 2007 Jul;16(7):547-52.           

2. Selway JL, Kurcab T, Kealey T, Langlands K. Toll-like receptor 2 activation and comedogenesis: implications for the pathogenesis of acne.  BMC Dermatol. 2013;13:10.

3. Agak GW et al. Propionibacterium acnes Induces an IL-17 Response in Acne Vulgaris that is Regulated by Vitamin A and D. J Invest Dermatol. 2014;134(2):366-73.

 

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