New Insights Into Systemic Drivers of Inflammation and Their Contributions to the Pathophysiology of Acne

February 2024 | Volume 23 | Issue 2 | 90 | Copyright © February 2024


Published online January 30, 2024

James Del Rosso DOa, Patricia K Farris MDb, Julie Harper MDc, Hilary Baldwin MDd, Adina Hazan PhDe, Isabelle Raymond PhDe

aJDR Dermatology Research/Thomas Dermatology, Las Vegas, NV; Advanced Dermatology and Cosmetic Surgery, Maitland, FL; Department of Dermatology, Touro University Nevada, Henderson, NV
bDepartment of Dermatology, Tulane University School of Medicine, New Orleans, LA
cThe Dermatology and Skin Care Center of Birmingham, Birmingham, AL
dThe Acne Treatment and Research Center, Brooklyn, NY; Department of Dermatology, Rutgers Robert Wood Johnson Medical School, Piscataway, NJ
eNutraceutical Wellness LLC, New York, NY

REFERENCES

  1. Graber EM. Treating acne with the tetracycline class of antibiotics: A review. Dermatological Reviews. 2021;2:321-330. doi:10.1002/der2.49 
  2. Preneau S, Dreno B. Female acne -- a different subtype of teenager acne? J Eur Acad Dermatol Venereol. 2012;26(3):277-282. doi: 10.1111/j.1468-3083.2011.04214.x 
  3. Fisk WA, Lev-Tov HA, Sivamani RK. Epidemiology and management of acne in adult women. Curr Dermatol Rep. 2014;3(1):29-39. doi:10.1007/s13671-014-0071-4 
  4. Holzmann R, Shakery K. Postadolescent acne in females. Skin Pharmacol Physiol. 2014;27 Suppl 1:3-8. doi:10.1159/000354887 
  5. Zaenglein AL, Pathy AL, Schlosser BJ, et al. Guidelines of care for the management of acne vulgaris. J Am Acad Dermatol. 2016;74(5):945-73 e33. doi:10.1016/j.jaad.2015.12.037 
  6. Dreno B, Amici JM, Demessant-Flavigny AL, et al. The impact of acne, atopic dermatitis, skin toxicities and scars on quality of life and the importance of a holistic treatment approach. Clin Cosmet Investig Dermatol. 2021;14:623-632. Published 2021 Jun 14. doi:10.2147/ccid.s315846 
  7. Eichenfield DZ, Sprague J, Eichenfield LF. Management of acne vulgaris: a review. JAMA. 2021;326(20):2055-2067. doi:10.1001/jama.2021.17633 
  8. Reid C, Griffiths CEM. Psoriasis and treatment: past, present and future aspects. Acta Derm Venereol. 2020;100(3):adv00032. doi:10.2340/00015555-3386 
  9. Mocanu M, Vata D, Alexa AI, et al. Atopic dermatitis-beyond the skin. Diagnostics (Basel). 2021;11(9):1553. doi:10.3390/diagnostics11091553 
  10. Sadick NS, Callender VD, Kircik LH, et al. New insight into the pathophysiology of hair loss triggers a paradigm shift in the treatment approach. J Drugs Dermatol. 2017;16(11):s135-s140. 
  11. Wang Y, Zhu M, Wu S, et al. Acne comorbidities. Clin Cosmet Investig Dermatol. 2022;15:2415-2420. doi:10.2147/CCID.S392165 
  12. Del Rosso JQ, Kircik LH. The sequence of inflammation, relevant biomarkers, and the pathogenesis of acne vulgaris: what does recent research show and what does it mean to the clinician? J Drugs Dermatol. 2013;12(8 Suppl):s109-s115. 
  13. Zhao J, Wang Y, Jiang L, et al. The application of skin care product in acne treatment. Dermatol Ther. 2020;33(6):e14287. doi:10.1111/dth.14287 
  14. Momin SB, Peterson A, Del Rosso JQ. A status report on drug-associated acne and acneiform eruptions. J Drugs Dermatol. 2010;9(6):627-636. 
  15. Baldwin H, Tan J. Effects of diet on acne and its response to treatment. Am J Clin Dermatol. 2021 Jan;22(1):55-65. doi:10.1007/s40257-020-00542-y 
  16. O'Neill AM, Gallo RL. Host-microbiome interactions and recent progress into understanding the biology of acne vulgaris. Microbiome. 2018;6(1):177. Published 2018 Oct 2. doi:10.1186/s40168-018- 0558-5 
  17. Sanchez-Pellicer P, Navarro-Moratalla L, Nunez-Delegido E, et al. Acne, microbiome, and probiotics: the gut-skin axis. Microorganisms. 2022;10(7):1303. doi:10.3390/microorganisms10071303 
  18. Tanghetti EA, Popp KF. A current review of topical benzoyl peroxide: new perspectives on formulation and utilization. Dermatol Clin. 2009;27(1):17-24. doi:10.1016/j.det.2008.07.001 
  19. Xu H, Li H. Acne, the skin microbiome, and antibiotic treatment. Am J Clin Dermatol. 2019;20(3):335- 344. doi:10.1007/s40257-018-00417-3 
  20. Del Rosso JQ, Webster GF, Rosen T, et al. Status Report from the Scientific Panel on Antibiotic Use in Dermatology of the American Acne and Rosacea Society: Part 1: Antibiotic Prescribing Patterns, Sources of Antibiotic Exposure, Antibiotic Consumption and Emergence of Antibiotic Resistance, Impact of Alterations in Antibiotic Prescribing, and Clinical Sequelae of Antibiotic Use. J Clin Aesthet Dermatol. 2016;9(4):18-24.
  21. Yosipovitch G, Tang M, Dawn A, et al. Study of psychological stress, sebum production and acne vulgaris in adolescents. Acta Dermato-Venereologica. 2007;87(2):135-139. doi:10.2340/00015555-0231 
  22. Chiu A, Chon SY, Kimball AB. The response of skin disease to stress: changes in the severity of acne vulgaris as affected by examination stress. Arch Dermatol. 2003;139(7):897-900. doi:10.1001/ archderm.139.7.897 
  23. Jovic A, Marinovic B, Kostovic K, et al. The impact of psychological stress on acne. Acta Dermatovenerol Croat. 2017;25(2):1133-1141.. 
  24. Zari S, Alrahmani D. The association between stress and acne among female medical students in Jeddah, Saudi Arabia. Clin Cosmet Investig Dermatol. 2017;10:503-506. Published 2017 Dec 5. doi:10.2147/CCID.S148499 
  25. Dreno B, Thiboutot D, Layton AM, et al. Large-scale international study enhances understanding of an emerging acne population: adult females. J Eur Acad Dermatol Venereol. 2015;29(6):1096-1106. doi:10.1111/jdv.12757 
  26. Del Rosso JQ, Harper JC, Graber EM, et al. Status report from the American Acne & Rosacea Society on medical management of acne in adult women, part 1: overview, clinical characteristics, and laboratory evaluation. Cutis. 2015;96(4):236-241. 
  27. Saric-Bosanac S, Clark AK, Sivamani RK, et al. The role of hypothalamus-pituitary-adrenal (HPA)-like axis in inflammatory pilosebaceous disorders. Dermatol Online J. 2020;26(2):13030/qt8949296f. Published 2020 Feb 15. 
  28. Antony B, Merina B, Iyer VS, et al. A pilot cross-over study to evaluate human oral bioavailability of BCM-95CG (Biocurcumax), a novel bioenhanced preparation of curcumin. Indian J Pharm Sci. 2008;70(4):445-449. doi:10.4103/0250-474X.44591 
  29. Ganceviciene R, Graziene V, Fimmel S, et al. Involvement of the corticotropin-releasing hormone system in the pathogenesis of acne vulgaris. Br J Dermatol. 2009;160(2):345-352. doi:10.1111/ j.1365-2133.2008.08959.x 
  30. Pondeljak N, Lugović-Mihić L. Stress-induced Interaction of Skin Immune Cells, Hormones, and Neurotransmitters. Clinical Therapeutics. 2020;42(5):757-770. doi:10.1016/j.clinthera.2020.03.008 
  31. Isard O, Knol AC, Castex-Rizzi N, et al. Cutaneous induction of corticotropin releasing hormone by Propionibacterium acnes extracts. Dermatoendocrinol. 2009;1(2):96-99. doi:10.4161/derm.1.2.8102 
  32. Toyoda M, Nakamura M, Makino T, et al. Sebaceous glands in acne patients express high levels of neutral endopeptidase. Exp Dermatol. 2002;11(3):241-247. doi:10.1034/j.1600-0625.2002.110307.x 
  33. Vileikyte L. Stress and wound healing. Clin Dermatol. 2007;25(1):49-55. doi:10.1016/j. clindermatol.2006.09.005 
  34. Kiecolt-Glaser JK, Marucha PT, et al. Slowing of wound healing by psychological stress. The Lancet. 1995;346(8984):1194-1196. doi:10.1016/s0140-6736(95)92899-5 
  35. Marucha PT, Kiecolt-Glaser JK, Favagehi M. Mucosal wound healing is impaired by examination stress. Psychosom Med. 1998;60(3):362-365. doi:10.1097/00006842-199805000-00025 
  36. Dunn JH, Koo J. Psychological stress and skin aging: a review of possible mechanisms and potential therapies. Dermatol Online J. 2013;19(6):18561. 
  37. Bowe WP, Joshi SS, Shalita AR. Diet and acne. J Am Acad Dermatol. 2010;63(1):124-141. doi:10.1016/j.jaad.2009.07.043 
  38. Smith RN, Mann NJ, Braue A, et al. The effect of a high-protein, low glycemic-load diet versus a conventional, high glycemic-load diet on biochemical parameters associated with acne vulgaris: a randomized, investigator-masked, controlled trial. J Am Acad Dermatol. 2007;57(2):247-256. doi:10.1016/j.jaad.2007.01.046 
  39. Emiroglu N, Cengiz FP, Kemeriz F. Insulin resistance in severe acne vulgaris. Postepy Dermatol Alergol. 2015;32(4):281-28. doi:10.5114/pdia.2015.53047 
  40. Wertheimer E, Trebicz M, Eldar T, et al. Differential roles of insulin receptor and insulin-like growth factor-1 receptor in differentiation of murine skin keratinocytes. J Invest Dermatol. 2000;115(1):24- 29. doi:10.1046/j.1523-1747.2000.00008.x 
  41. Aizawa H, Niimura M. Elevated serum insulin-like growth factor-1 (IGF-1) levels in women with postadolescent acne. J Dermatol. 1995;22(4):249-252. doi:10.1111/j.1346-8138.1995.tb03381.x 
  42. Melnik B. Dietary intervention in acne: Attenuation of increased mTORC1 signaling promoted by Western diet. Dermatoendocrinol. 2012;4(1):20-32. doi:10.4161/derm.19828 
  43. Thomas J. Role of zinc in acne: a study of 77 patients. Int J Re Dermatol. 2018;4(3). doi:10.18203/ issn.2455-4529.IntJResDermatol20182980 
  44. Michaelsson G. Decreased concentration of selenium in whole blood and plasma in acne vulgaris. Acta Derm Venereol. 1990;70(1):92. 
  45. Razavi M, Jamilian M, Kashan ZF, et al. Selenium supplementation and the effects on reproductive outcomes, biomarkers of inflammation, and oxidative stress in women with polycystic ovary syndrome. Horm Metab Res. 2016;48(3):185-190. doi:10.1055/s-0035-1559604 
  46. Lim S-K, Ha J-M, Lee Y-H, 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 
  47. Bowe WP, Patel N, Logan AC. Acne vulgaris: the role of oxidative stress and the potential therapeutic value of local and systemic antioxidants. J Drugs Dermatol. 2012;11(6):742-746. 
  48. Balta I, Ekiz O, Ozuguz P, et al. Nutritional anemia in reproductive age women with postadolescent acne. Cutan Ocul Toxicol. 2013;32(3):200-203. doi:10.3109/15569527.2012.751393 
  49. Jiang H, Li C, Wei B, Wang Q, et al. Serum homocysteine levels in acne patients. J Cosmet Dermatol. 2018;17(3):523-526. doi:10.1111/jocd.12456 
  50. Moshal KS, Sen U, Tyagi N, et al. Regulation of homocysteine-induced MMP-9 by ERK1/2 pathway. Am J Physiol Cell Physiol. 2006;290(3):C883-C891. doi:10.1152/ajpcell.00359.2005 
  51. Jablonska-Trypuc A, Matejczyk M, Rosochacki S. Matrix metalloproteinases (MMPs), the main extracellular matrix (ECM) enzymes in collagen degradation, as a target for anticancer drugs. J Enzyme Inhib Med Chem. 2016;31(sup1):177-183. doi:10.3109/14756366.2016.1161620 
  52. Jones P, Lucock M, Veysey M, et al. The vitamin D(-)folate hypothesis as an evolutionary model for skin pigmentation: an update and integration of current ideas. Nutrients. 2018;10(5):554. doi:10.3390/nu10050554 
  53. Dattola A, Silvestri M, Bennardo L, et al. Role of vitamins in skin health: a systematic review. Curr Nutr Rep. 2020;9(3):226-235. doi:10.1007/s13668-020-00322-4 
  54. Hartmann D, Bollag W. Historical aspects of the oral use of retinoids in acne. J Dermatol. 1993;20(11):674-678. doi:10.1111/j.1346-8138.1993.tb01362.x 
  55. Jo JH, Harkins CP, Schwardt NH, et al. Alterations of human skin microbiome and expansion of antimicrobial resistance after systemic antibiotics. Sci Transl Med. 2021;13(625):eabd8077. doi:10.1126/scitranslmed.abd8077 
  56. Armstrong AW, Hekmatjah J, Kircik LH. Oral Tetracyclines and Acne: A Systematic Review for Dermatologists. J Drugs Dermatol. 2020;19(11):s6-s13. 
  57. Platsidaki E, Dessinioti C. Recent advances in understanding Propionibacterium acnes (Cutibacterium acnes) in acne. F1000Res. 2018;7:F1000 Faculty Rev-1953. doi:10.12688/ f1000research.15659.1 
  58. Dreno 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 
  59. Li CX, You ZX, Lin YX, Liu HY, Su J. Skin microbiome differences relate to the grade of acne vulgaris. J Dermatol. 2019;46(9):787-790. doi:10.1111/1346-8138.14952 
  60. Firlej E, Kowalska W, Szymaszek K, et al. The Role of Skin Immune System in Acne. J Clin Med. 2019;46(9):787-790. doi:10.3390/jcm11061579 
  61. Deng Y, Wang H, Zhou J, et al. Patients with acne vulgaris have a distinct gut microbiota in comparison with healthy controls. Acta Derm Venereol. 2018;98(8):783-790. doi:10.2340/00015555- 2968 
  62. O'Neill AM, Liggins MC, Seidman JS, et al. Antimicrobial production by perifollicular dermal preadipocytes is essential to the pathophysiology of acne. Sci Transl Med. 2022;14(632):eabh1478. doi:10.1126/scitranslmed.abh1478 
  63. Maslowski KM, Mackay CR. Diet, gut microbiota and immune responses. Nat Immunol. 2011;12(1):5-9. doi:10.1038/ni0111-5 
  64. Wiertsema SP, van Bergenhenegouwen J, Garssen J, et al. The interplay between the gut microbiome and the immune system in the context of infectious diseases throughout life and the role of nutrition in optimizing treatment strategies. Nutrients. 2021;13(3):886. doi:10.3390/ nu13030886 
  65. Grice EA, Segre JA. The skin microbiome. Nat Rev Microbiol. 2011;9(4):244-253. doi:10.1038/ nrmicro2537 
  66. Yan HM, Zhao HJ, Guo DY, et al. Gut microbiota alterations in moderate to severe acne vulgaris patients. J Dermatol. 2018;45(10):1166-1171. doi:10.1111/1346-8138.14586 
  67. Del Rosso JQ, Kircik LH, Stein Gold L, et al. Androgens, androgen receptors, and the skin: from the laboratory to the clinic with emphasis on clinical and therapeutic implications. J Drugs Dermatol. 2020;19(3):30-35. 
  68. Mohiuddin M. A comprehensive review of acne vulgaris. Clinical Research in Dermatology: Open Access. 2019;6(2):1-34. doi: 10.15226/2378-1726/6/2/00186 
  69. Zouboulis CC. Acne and sebaceous gland function. Clin Dermatol. 2004;22(5):360-366. doi:10.1016/j. clindermatol.2004.03.004 
  70. Lucky AW, Biro FM, Huster GA, et al. Acne vulgaris in premenarchal girls. An early sign of puberty associated with rising levels of dehydroepiandrosterone. Arch Dermatol. 1994;130(3):308-314. doi:10.1001/archderm.130.3.308 
  71. Arora MK, Yadav A, Saini V. Role of hormones in acne vulgaris. Clin Biochem. 2011;44(13):1035-1040. doi:10.1016/j.clinbiochem.2011.06.984 
  72. Makrantonaki E, Ganceviciene R, Zouboulis C. An update on the role of the sebaceous gland in the pathogenesis of acne. Dermatoendocrinol. 2011;3(1):41-49. doi:10.4161/derm.3.1.13900 
  73. Lee WJ, Jung HD, Chi SG, et al. Effect of dihydrotestosterone on the upregulation of inflammatory cytokines in cultured sebocytes. Arch Dermatol Res. 2010;302(6):429-433. doi:10.1007/s00403-009-1019-6 
  74. Rao A, Douglas SC, Hall JM. Endocrine disrupting chemicals, hormone receptors, and acne vulgaris: a connecting hypothesis. Cells. 2021;10(6):1439. Published 2021 Jun 9. doi:10.3390/cells10061439 
  75. Carmina E, Dreno B, Lucky WA, et al. Female adult acne and androgen excess: a report from the multidisciplinary androgen excess and PCOS Committee. J Endocr Soc. 2022;6(3):bvac003. Published 2022 Feb 6. doi:10.1210/jendso/bvac003 
  76. Chen J, Liu Y, Zhao Z, Qiu J. Oxidative stress in the skin: Impact and related protection. Int J Cosmet Sci. 2021;43(5):495-509. doi:10.1111/ics.12728 
  77. Kardeh S, Moein SA, Namazi MR, et al. Evidence for the Important Role of Oxidative Stress in the Pathogenesis of Acne. Galen Med J. 2019;8:e1291. doi:10.31661/gmj.v0i0.1291 
  78. Sarici G, Cinar S, Armutcu F, et al. Oxidative stress in acne vulgaris. J Eur Acad Dermatol Venereol. 2010;24(7):763-767. doi:10.1111/j.1468-3083.2009.03505.x 
  79. Tochio T, Tanaka H, Nakata S, et al. Accumulation of lipid peroxide in the content of comedones may be involved in the progression of comedogenesis and inflammatory changes in comedones. J Cosmet Dermatol. 2009;8(2):152-158. doi:10.1111/j.1473-2165.2009.00437.x 
  80. Ayala A, Munoz MF, Arguelles S. Lipid peroxidation: production, metabolism, and signaling mechanisms of malondialdehyde and 4-hydroxy-2-nonenal. Oxid Med Cell Longev. 2014;2014:360438. doi:10.1155/2014/360438 
  81. Shindo Y, Witt E, Han D, et al. Dose-response effects of acute ultraviolet irradiation on antioxidants and molecular markers of oxidation in murine epidermis and dermis. J Invest Dermatol. 1994;102(4):470-475. doi:10.1111/1523-1747.ep12373027 
  82. Shindo Y, Witt E, Han D, et al. Enzymic and non-enzymic antioxidants in epidermis and dermis of human skin. J Invest Dermatol. 1994;102(1):122-124. doi:10.1111/1523-1747.ep12371744 
  83. Bouayed J, Bohn T. Exogenous antioxidants--Double-edged swords in cellular redox state: Health beneficial effects at physiologic doses versus deleterious effects at high doses. Oxid Med Cell Longev. 2010;3(4):228-237. doi:10.4161/oxim.3.4.12858 
  84. Trivedi NR, Cong Z, Nelson AM, et al. Peroxisome proliferator-activated receptors increase human sebum production. J Invest Dermatol. 2006;126(9):2002-2009. doi:10.1038/sj.jid.5700336 
  85. Tanghetti EA. The role of inflammation in the pathology of acne. J Clin Aesthet Dermatol. 2013;6(9):27-35. 
  86. Kang S, Cho S, Chung JH, et al. Inflammation and extracellular matrix degradation mediated by activated transcription factors nuclear factor-kappaB and activator protein-1 in inflammatory acne lesions in vivo. Am J Pathol. 2005;166(6):1691-1699. doi:10.1016/s0002-9440(10)62479-0 
  87. Burgess C, Gold M, Farris PK, et al. A novel systems-wide approach in addressing acne with a multi-targeting nutraceutical. J Drugs Dermatol. In Press. doi:10.36849/JDD.8138 

AUTHOR CORRESPONDENCE

Isabelle Raymond PhD Isabelle@nutrafol.com
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