Acne Treatment Protocol

Acne Treatment Protocol

Definition and Pathophysiology

Acne vulgaris is an inflammatory disease of the skin that affects those areas which contain sebaceous glands, including the nose, central forehead, medial cheeks, medial chin, back, and trunk. [1]

Acne lesions are generally more severe and prevalent in males, but more persistent in females. Acne may appear in neonates and infants, but mostly occurs during adolescence (an estimated 90% of teens are affected) [1], and typically resolves by age 30. It can lead to significant distress and loss of self-esteem.

Acne vulgaris is influenced by multiple factors. The condition arises from the interaction of four main elements [2]:

  • Inflammatory mediators released into the skin
  • Follicular hyperkeratinisation (increased keratinocyte proliferation and decreased desquamation) causing follicle blockage
  • Colonisation by Cutibacterium acnes (formerly Propionibacterium acnes)
  • Excessive sebum production

Inflammation usually precedes hyperkeratinisation, with cytokines from T cells and macrophages activating endothelial cells to increase inflammatory mediators around hair follicles.

Hyperkeratinisation leads to sebum and keratin filled microcomedones. Colonisation of Cutibacterium acnes promotes further inflammation.

Excess sebum production may arise due to hormonal changes, particularly an increase in androgens.

Other factors, such as growth hormone, insulin-like growth factor, and peroxisome proliferator-activated receptors, also influence the sebaceous gland and may contribute to acne. The sebaceous gland acts as a neuroendocrine-inflammatory organ, responding to stress via corticotrophin-releasing hormones.

Patient signs and symptoms

  • Open comedones (blackheads): Dark, non-inflammatory spots with easily expressed material.
  • Closed comedones (whiteheads): Small, white papules (1-2 mm) with material that is not easily expressed.
  • Inflamed lesions: Papules, pustules, or nodules.
  • Large cysts and nodules: May drain and leave scars.
  • Scarring: Varies by skin type and acne severity, including:
  • Small pits or “ice-pick” scars
  • Atrophic or depressed scars
  • Hypertrophic scars (more common in darker skin tones)

Risk Factors

  • High Insulin Levels: Linked to insulin resistance, stimulating epithelial cell proliferation and androgen production, increasing sebum.[1]
  • Hormonal Fluctuations: Common during adolescence, menstruation, and pregnancy.[1]
  • Low Zinc Levels: Some acne patients have been found to have lower serum, hair, and nail zinc levels.[1]
  • Dysbiosis: Dysbiosis of the skin and gut microbiome is another contributing factor to acne, with overgrowth of C. acnes contributing to increased inflammation in the skin.[3]
  • Medications: Includes corticosteroids, anabolic steroids, oral contraceptives, lithium, isoniazid, phenytoin, phenobarbitone, and high iodine levels.[1]
  • Topical Products: Cosmetic or hair products with vegetable or animal fats.[1]
  • Environmental Irritants: Industrial oils, tar, wood preservatives, sealing compounds, and pollutants.[1]
  • Friction and Sweating: From headbands, backpacks, helmets, or tight collars.[1]
  • Squeezing and Picking: Can worsen acne.[1]
  • Genetics: There is a genetic component to severe acne and scarring, although specific genes have not been identified. [1]

Red Flags

Younger than 12 years: Patients should be referred to a doctor if diagnosis is unclear, patient is younger than 12.[4]

Signs of androgen excess: Such as excess hirsutism, androgenetic alopecia, menstrual irregularities. Endocrine evaluation is indicated if signs of androgen excess are present.[4]

Therapeutic goals

The following therapeutic goals can assist in the management of acne[6-10]:

  • Support epidermal barrier and reduce skin barrier dysfunction.
  • Address nutrient deficiencies (e.g., omega 3, vitamin A, zinc, vitamin D).
  • Support wound healing to help prevent scar formation.
  • Address skin inflammation and limit oxidative damage.
  • Support the gut microbiome.
  • Consider underlying hormonal factors (i.e. elevated androgens, low SHBG)

Screening and Investigations

Pathology Testing

Rationale

Diet and exercise record

Helps assess patient's dietary habits, glycemic load and overall diet quality.

Vitamin D

Vitamin D is inversely associated with severity of acne. Improvement in inflammatory lesions was noted after supplementation (p<0.05).[11]
LH:FSH ratio

The ratio is usually close to 1:1, but if the LH is higher, it is one possible indication of PCOS. Evaluate LH:FSH ratio in early follicular phase between day 2 to 6 of menstrual cycle.

Testosterone and sex-hormone binding globulin (SHBG)

Recommended to use calculated free testosterone along with calculated free androgen index and SHBG for superior specificity and sensitivity and functional hormone dynamic.

Treatment recommendations

Core Treatment:

VERISOL® Collagen and Sodium Hyaluronate for Skin Health

Dose: Take 3 tablets daily.

An innovative formula with hyaluronic acid and VERISOL® collagen peptides to support collagen formation, skin elasticity, hydration, and dermal repair.

  • Collagen peptides[12] and vitamin C[13] support wound healing, collagen supports skin barrier integrity, and nicotinamide (vitamin B3) has potent anti-inflammatory effects[14] and enhances skin barrier function.[15]

AND

BCM-95™ Curcumin, Grape Seed Extract and Burdock for Skin Inflammation and Lymphatic System Support

Dose: 1 tablet twice daily with food

  • Arctium lappa (burdock) root is traditionally used for treating boils and skin eruptions. Its effectiveness is attributed to its anti-inflammatory and antimicrobial properties, particularly against gram-positive bacteria like C. acnes.[16]
  • Curcuma longa (turmeric) has been shown to reduce acne lesions due to its anti-inflammatory and antimicrobial effects. Curcumin, a component of turmeric, inhibits C. acnes. A clinical trial indicated that turmeric might enhance skin barrier integrity in individuals with high sebum production.[17-19]
  • Grape seed extract is known for its antioxidant and anti-inflammatory activities.[20]

To support nutritional health for skin integrity and wound healing:

High Bioavailability Zinc with Vitamin C

Dose: Adults and teenagers: Acute: Add 1/2 metric teaspoon (1.9g) to 200ml of water twice daily with food. Drink immediately. Maintenance: Add ½ metric teaspoon (1.9g) to 200ml of water once daily with food. Drink immediately.

  • Zinc and vitamin C are amongst the most critical nutrients in healthy immunity and skin function, involved in wound healing, immune balance and resistance to infection.
  • A systematic review and meta-analysis found that zinc is effective for the treatment of acne, particularly at decreasing the number of inflammatory papules.[21]

AND

High Purity, Low Reflux, Concentrated Fish Oil

Dose: 2 capsules daily with food

A sustainably sourced, highly purified and high-strength

  • EPA and DHA modulate the production of inflammatory prostaglandins, eicosanoids, leukotrienes and thromboxane. Omega 3 essential fatty acids also support healthy immune signalling and support skin health.[22]

AND

If vitamin D levels are <75 nmol/L:
Vitamin D3
Dosage: Take 1 capsule daily with food.

  • Vitamin D is inversely associated with severity of acne. Improvement in inflammatory lesions was noted after supplementation (p<0.05).[11]

If with chronic gut issues, antibiotic over use and dysbiosis

Strain Specific Probiotics for Gut Microbiota Restoration and Support

Dosage: Take 1 capsule twice daily.

Probiotic strains to protect commensal groups and encourage gut microbiota restoration in SIBO, displace potential pathogens and enhance gastrointestinal mucosal integrity.

  • Saccharomyces cerevisiae (boulardii) [SB], Lactobacillus rhamnosus (LGG®), and Bifidobacterium animalis ssp lactis (BB-12®) help restore a healthy gut microbiome.[23,24]
  • In 20 adults, 3 billion CFU/d LGG® for 12 weeks improved acne lesions. Skin biopsies showed improvement in markers of skin health such as insulin-like growth factor 1 (p<0.001).[25]
  • In 96 adults, 14 billion CFU/d of LGG® for 4 weeks improved transepidermal water loss, indicating improved skin barrier function. Self-reported pimples/breakouts were reduced (p<0.01).[26]

Additional considerations

If with PCOS-related skin issue with elevated LH:FSH ratio and high androgens

Inositol, Peony & Liquorice to Clear Testosterone

Acute dose: 2 tablets twice daily Maintenance:2 tablets once daily

  • Peony and licorice shown to inhibit androgen and testosterone synthesis.[27,28] Inositol enhances insulin sensitivity whilst supporting FSH and aromatase activity.[29,30]

Diet and Lifestyle

Diet:

  • A high Glycaemic Index (GI) diet can cause a persistent rise in serum insulin levels. Elevated insulin is known to trigger epithelial cell proliferation and increased sebum production, both of which are risk factors for acne.
  • Adopting a low GI diet can significantly improve the incidence and severity of acne in adolescents.
  • A diet rich in soluble fiber, antioxidants, phytonutrients, and essential fatty acids from nuts and fish, along with plenty of fluids, is generally recommended.[4]
  • Reducing intake of sugar, white flour, refined and processed oils, trans fatty acids, and dairy products is also advised.[4]

Lifestyle:

  • Apply topical treatments to the entire affected area.[4]
  • Wash affected areas gently, avoiding scrubbing and abrasive cleansers, which may cause more inflammation and make acne worse.[4]
  • Avoid using toners and oil-based moisturisers.[4]
  • Not to squeeze or pick the acne lesions, as this increases the risk of scarring.[4]

Pharmaceutical Treatments

Topical retinoids: First-line treatment in mild to moderate acne.[4]
Benzoyl peroxide: First-line treatment in mild to moderate acne.[4]
Antibiotics (topical or oral): For moderate to severe acne.[4]
Oral contraceptives: For females with moderate to severe acne.[4]
Isotreinoin: For severe acne or moderate acne unresponsive to other treatments.[4]

References

  1. Santer M, Burden-Teh E, Ravenscroft J. Managing acne vulgaris: an update. Drug Ther Bull. 2023;62(1):6-10. Published 2023 Dec 27. doi:10.1136/dtb.2023.000051
  2. Jaggi Rao. Medscape. Acne Vulgaris Practice Essentials. Aug 2020.Leung AK, Barankin B, Lam JM, Leong KF, Hon KL. Dermatology: how to manage acne vulgaris. Drugs Context. 2021;10:1-18. doi:10.7573/dic.2021-8-6
  3. Chilicka K, Dzieńdziora-Urbińska I, Szyguła R, Asanova B, Nowicka D. Microbiome and probiotics in acne vulgaris—a narrative review. Life. 2022;12(3):422. doi:10.3390/life12030422
  4. Australian Medicines Handbook Pty Ltd. Acne. In: Australian Medicines Handbook. Updated January 2024. Accessed January 30, 2024. https://amhonline.amh.net.au/chapters/dermatological-drugs/drugs-acne/acne https://emedicine.medscape.com/article/1069804-overview
  5. Lee YB, Byun EJ, Kim HS. Potential role of the microbiome in acne: a comprehensive review. J Clin Medicine. 2019;8(7):987. doi:10.3390/jcm8070987
  6. Dréno B, Dagnelie MA, Khammari A, Corvec S. The skin microbiome: a new actor in inflammatory acne. Am J Clin Dermatol. 2020;21(Suppl 1):18-24. doi:10.1007/s40257-020-00531-1
  7. Thiboutot D, Rosso JQD. Acne vulgaris and the epidermal barrier: is acne vulgaris associated with inherent epidermal abnormalities that cause impairment of barrier functions? Do any topical acne therapies alter the structural and/or functional integrity of the epidermal barrier? J Clin Aesthetic Dermatology. 2013;6(2):18-24.
  8. Pfisterer K, Shaw LE, Symmank D, Weninger W. The extracellular matrix in skin inflammation and infection. Frontiers Cell Dev Biology. 2021;9:682414. doi:10.3389/fcell.2021.682414
  9. Firlej E, Kowalska W, Szymaszek K, Roliński J, Bartosińska J. The role of skin immune system in acne. J Clin Medicine. 2022;11(6):1579. doi:10.3390/jcm11061579
  10. Adams JA, Adams AJ, Klepser ME. Pharmacist prescriptive authority for acne: an evidence-based approach to policy. Innov Pharm. 2021;12(2):10.24926/iip.v12i2.3897. doi:10.24926/iip.v12i2.3897
  11. Lim S-K, Ha J-M, Lee Y-H, Lee Y, Seo Y-J, Kim C-D, et al. Comparison of vitamin D levels in patients with and without acne: a case-control study combined with a randomized controlled trial. PLoS ONE. 2016;11(8): e0161162. doi:10.1371/journal.pone.0161162
  12. Choi FD, Sung CT, Juhasz MLW, Mesinkovsk NA. Oral collagen supplementation: a systematic review of dermatological applications. J Drugs Dermatology Jdd. 2019;18(1):9-16.
  13. Pullar JM, Carr AC, Vissers MCM. The roles of vitamin C in skin health. Nutrients. 2017;9(8):866. doi:10.3390/nu9080866
  14. Walocko FM, Eber AE, Keri JE, AL‐Harbi MA, Nouri K. The role of nicotinamide in acne treatment. Dermatol Ther. 2017;30(5):e12481. doi:10.1111/dth.12481
  15. Snaidr VA, Damian DL, Halliday GM. Nicotinamide for photoprotection and skin cancer chemoprevention: a review of efficacy and safety. Exp Dermatol. 2019;28:15-22. doi:10.1111/exd.13819
  16. Miazga-Karska M, Michalak K, Ginalska G. Anti-acne action of peptides isolated from burdock root—preliminary studies and pilot testing. Molecules. 2020;25(9):2027. doi:10.3390/molecules25092027
  17. Vaughn. Effects of turmeric (Curcuma longa) on skin health: a systematic review of the clinical evidence. Phytother Res. 2016;30(8):1243-1264. doi:10.1002/ptr.5640
  18. Liu CH, Huang HY. In vitro anti-propionibacterium activity by curcumin containing vesicle system. Chem Pharm Bulletin. 2013;61(4):419-425. doi:10.1248/cpb.c12-01043
  19. Vaughn AR, Clark AK, Notay M, Sivamani RK. Randomized controlled pilot study of dietary supplementation with turmeric or herbal combination tablets on skin barrier function in healthy subjects. J Med Food. 2018;21(12):1260-1265. doi:10.1089/jmf.2018.0015
  20. Sochorova L, Prusova B, Cebova M, et al. Health effects of grape seed and skin extracts and their influence on biochemical markers. Molecules. 2020;25(22):5311. doi:10.3390/molecules25225311
  21. Yee BE, Richards P, Sui JY, Marsch AF. Serum zinc levels and efficacy of zinc treatment in acne vulgaris: A systematic review and meta-analysis. Dermatol Ther. 2020;33(6):e14252. doi:10.1111/dth.14252
  22. Khayef G, Young J, Burns-Whitmore B, Spalding T. Effects of fish oil supplementation on inflammatory acne. Lipids Health Dis. 2012;11:165. Published 2012 Dec 3. doi:10.1186/1476-511X-11-165
  23. Collignon A, Sandré C, Barc MC. Saccharomyces boulardii modulates dendritic cell properties and intestinal microbiota disruption after antibiotic treatment. Gastroenterol Clin Biol. 2010 Sep;34 Suppl 1:S71-8.
  24. Barc MC, Charrin-Sarnel C, Rochet V, Bourlioux F, Sandré C, Boureau H, et al. Molecular analysis of the digestive microbiota in a gnotobiotic mouse model during antibiotic treatment: Influence of Saccharomyces boulardii. Anaerobe. 2008 Oct;14(4):229-33. doi: 10.1016/j.anaerobe.2008.04.003.
  25. Fabbrocini G, Bertona M, Picazo Ó, Pareja-Galeano H, Monfrecola G, Emanuele E. Supplementation with Lactobacillus rhamnosus SP1 normalises skin expression of genes implicated in insulin signalling and improves adult acne. Benef Microbes. 2016;7(5):625-630. doi:10.3920/BM2016.0089
  26. Miyazawa K, Harata G, Yoda K, Yamazaki K, He F, Hiramatsu M. Effects of intake of Lactobacillus rhamnosus GG on intestinal environment and skin condition in healthy adults: a randomized, double-blind, placebo-controlled study. Int J Probiotic Prebiotic. 2018;13(1):11-8.
  27. Sakamoto K, Wakabayashi K.Inhibitory Effect of Glycyrrhetinic Acid on Testosterone Production in Rat Gonads. Endocrinol Japon. 1988;35(2):333-342. doi:10.1507/endocrj1954.35.333
  28. Ong M, Cheng J, Jin X, et al. Paeoniflorin extract reverses dexamethasone-induced testosterone over-secretion through downregulation of cytochrome P450 17A1 expression in primary murine theca cells. J Ethnopharmacol. 2019;229:97-103. doi:10.1016/j.jep.2018.09.006
  29. DiNicolantonio JJ, O’Keefe JH. Myo-inositol for insulin resistance, metabolic syndrome, polycystic ovary syndrome and gestational diabetes. Open Hear. 2022;9(1):e001989. doi:10.1136/openhrt-2022-001989
  30. Greff D, Juhász AE, Váncsa S, et al. Inositol is an effective and safe treatment in polycystic ovary syndrome: a systematic review and meta-analysis of randomized controlled trials. Reprod Biol Endocrinol. 2023;21(1):10. doi:10.1186/s12958-023-01055-z
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