by Nat Jones, RPh, FAPC, PCCA Clinical Compounding Pharmacist
Acne is the most common dermatologic disease, with a cumulative prevalence approaching 100 percent in males and females as they near puberty. In most cases, acne becomes less active as adolescence ends. However, the intensity and duration can vary among individuals — 20 percent will experience severe acne that can result in scarring.
The presence of acne may profoundly limit self-esteem and self-confidence, placing individuals at risk for developing depression and anxiety. Acne may also be associated with increased risk of self-injury and suicide attempts.1
Pathophysiology
Acne pathophysiology is multifactorial: sebum alteration, aberrant follicular keratinization and Cutibacterium acnes (C. acnes, formerly known as Propionibacterium acnes or P. acnes) combine to cause comedones that can lead to inflammation and acne lesions.
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Acne has multiple contributing factors, including hormones and neuropeptides, sebum production, the microbiome, as well as innate and adaptive immune functions. Androgens (dihydrotestosterone) stimulate sebocyte proliferation, which ultimately increases sebum production — a substrate for C. acnes growth — as well as lipid and triglyceride formation. Collectively, these factors induce the excessive shedding of skin cells, or hyperkeratinization, of the uppermost section of the hair follicle near the opening of pores, known as the follicular infrainfundibulum.
Diets comprised of high-glycemic-index foods, dairy and whey protein contribute to acne through stimulation of insulin-like growth factor-1 (IGF-1), while omega-3-fatty acids and low-glycemic-load diets are protective because they downregulate IGF-1. This suggests that increasing the ratio of monounsaturated to saturated fatty acids in sebum is proinflammatory and may promote acne.
Lesion Types & Treatment
Targeting inflammation is an important aspect of acne treatment. C. acnes stimulate inflammation via innate toll-like receptors (TLRs) and adaptive immunity (IL-17A and IFN-γ secretion from CD4+ T cells) and promote production of matrix metalloproteinases that contribute to scarring. C. acnes also form biofilms, which create a pro-inflammatory sebum concentration via increased lipase activity and promote resistance to treatment with antimicrobial agents.2 Because low-dose naltrexone (LDN) attenuates activation of TLRs in the skin, it can be used as an adjunct therapy to treat acne (and other inflammatory skin diseases) in resistant cases.3
There are different types of acne lesions: open comedones (blackheads), closed comedones (whiteheads), inflammatory lesions (where the follicular wall ruptures, releasing sebum, cells and bacteria into the surrounding tissue, causing inflammation and redness) and cystic lesions that can lead to atrophic scars (icepick and boxcar).
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Treatment of acne depends on severity (mild, moderate or severe), type of lesion and location. Acne lesions can appear on the face, forehead, chest, upper back and shoulders, or in combination of these areas, because these areas have the highest concentration of sebaceous glands. For a successful outcome, it is recommended that acne patients have a thorough regimen addressing all aspects of the disease.
Most regimens include:
- A cleansing routine (usually twice daily) with a cleanser that removes dirt but does not strip all the oils from the skin to allow for healthy barrier function, followed by a light non-comedogenic moisturizer (such as VersaBase® Cream).
- An exfoliation process 1-3 times a week, depending on severity.
- Active treatment of some single API or combination of an antibacterial and a keratolytic. If using nightly tretinoin, exfoliation may not be necessary.
In severe cases, isotretinoin may be considered with usual precautions for reproductive-age female patients.1 Compounding formulations (non-cosmetic), especially combinations, are very useful and often more convenient for patients who require more than one API in a single application. Compounding APIs include:
- Keratolytics
- Tretinoin
- Salicylic Acid
- Benzoyl Peroxide (also antibacterial)
- Antibacterial
- Clindamycin
- Erythromycin
- Minocycline
- Sulfacetamide
- Tea Tree Oil
- Sebostatic
- Niacinamide
- Azelaic Acid (also antibacterial)
- Miscellaneous
- Progesterone (5α-reductase inhibitor)
- Spironolactone (DHT receptor antagonist)
PCCA bases often used in acne formulations include VersaBase Cream, VersaBase Gel, Clarifying™, PracaSil®-Plus, Occlusaderm® and WO6® Anhydrous Topical Gel (sometimes with the addition of PermE8® Anhydrous Gel to modestly enhance penetration through the stratum corneum).
Therapy should always be tailored to the patients’ needs — sensitivities and exceptions are always the rule. Remember to let your patients know that you’re here to help and they are not alone combating acne! PCCA members may access formulations developed for compounded preparations on the Members-Only Website, including a new formulation that uses aminolevulinic acid* in a topical gel with PermE8 Anhydrous Gel and WO6 Anhydrous Topical Gel.
*Aminolevulinic acid (ALA) is a compound used in photodynamic therapy (PDT) to treat acne vulgaris. Although the mechanism of action of ALA with PDT is not fully understood, it is believed to reduce sebum excretion by suppression of the sebaceous gland function. ALA-PDT was shown to be effective for acne and did not exhibit severe side effects.4
Members with clinical services access may contact our Clinical Services team for help with acne preparations and other compounding concerns.
References
- Gupta, N., & Gupta, M. (2023). The Controversies Surrounding Acne and Suicide: Essential Knowledge for Clinicians. Cureus, 15(8), e43867. Accessed May 2024 at https://doi.org/10.7759/cureus.43867
- Cruz, S., Vecerek, N., & Elbuluk, N. (2023). Targeting Inflammation in Acne: Current Treatments and Future Prospects. American journal of clinical dermatology, 24(5), 681–694. Accessed May 2024 at https://doi.org/10.1007/s40257-023-00789-1
- Jaros, J., & Lio, P. (2019). Low Dose Naltrexone in Dermatology. Journal of drugs in dermatology: JDD, 18(3), 235–238. Accessed May 2024 at https://jddonline.com/articles/low-dose-naltrexone-in-dermatology-S1545961619P0235X/
- Asayama-Kosaka, S., Akilov, O. E., and Kawana, S. (2014). Photodynamic Therapy with 5% δ-Aminolevulinic Acid is Safe and Effective Treatment of Acne Vulgaris in Japanese Patients. Laser therapy, 23(2), 115–120. Accessed May 2024 at https://doi.org/10.5978/islsm.14-OR-09
These statements are provided for educational purposes only. They have not been evaluated by the Food and Drug Administration, and are not to be interpreted as a promise, guarantee or claim of therapeutic efficacy or safety. The information contained herein is not intended to replace or substitute for conventional medical care or encourage its abandonment.
