Comparative Efficacy of Topical N-Acetylcysteine-Doxycycline versus Benzoyl Peroxide-Doxycycline in Moderate Acne Vulgaris: Add-on Double-Blind Randomized Controlled Trial
Keywords:
Acne vulgaris, Benzoyl peroxide, N-acetyl cysteine, Skin DiseasesAbstract
Introduction: Acne vulgaris is a prevalent skin disorder affecting approximately 85% of adolescents. While topical retinoid and benzoyl peroxide (BPO) are standard treatments, their side effects often decrease patient adherence. Objectives: Due to the potential side effects of these drugs, we decided to explore the efficacy and safety of topical N-acetylcysteine (NAC) plus doxycycline compared to BPO-doxycycline in moderate acne vulgaris. Method: In this double-blind, randomized clinical trial, 40 patients were divided into two groups: Group A received 100 mg/day doxycycline+5% NAC, while Group B received 100 mg/day doxycycline +5% BPO. Patients were assessed over three months using Total Lesion Count (TLC), Investigator Global Assessment (IGA), Global Acne Grading System (GAGS), and Cardiff Acne Disability Index (CADI). Statistical analysis was performed using STATA 14.2, with p < 0.05 considered significant. Results: The NAC group showed a significantly greater reduction in CADI scores (MD=-3.60, 95% CI: -4.26 to -2.95, p < 0.001), GAGS scores (MD = -9.76, 95% CI: -11.84 to -7.68, p < 0.001), and TLC (MD = -4.29, 95% CI: -6.38 to -2.19, p = 0.002) compared to BPO. IGA scores also improved more significantly in the NAC group (MD = -0.85, 95% CI: -1.12 to -0.58, p < 0.001). Only one patient reported mild scaling with NAC, suggesting better tolerability. Conclusion: Topical NAC combined with doxycycline was significantly more effective than BPO-doxycycline in reducing acne severity and lesion count, with minimal adverse effects. NAC may serve as a more efficacious alternative for treating moderate acne vulgaris.
References
Yan HM, Zhao HJ, Guo DY, Zhu PQ, Zhang CL, Jiang W. Gut microbiota alterations in moderate to severe acne vulgaris patients. J Dermatol. 2018;45(10):1166-71. DOI: 10.1111/1346-8138.14586. PMID: 30101990.
Purdy S, de Berker D. Acne vulgaris. BMJ Clin Evid. 2011;1714. PMID: 21477388.
Dréno B. What is new in the pathophysiology of acne, an overview. J Eur Acad Dermatol Venereol. 2017;31:8-12. DOI: 10.1111/jdv.14374. PMID: 28805938.
Li X, He C, Chen Z, Zhou C, Gan Y, Jia Y. A review of the role of sebum in the mechanism of acne pathogenesis. J Cosmet Dermatol. 2017;16(2):168-73. DOI: 10.1111/jocd.12345. PMID: 28556292.
Liu Y, Sun Q, Xu H, Ma G, Wu P. Serum level changes of inflammatory cytokines in patients with moderate to severe acne vulgaris treated with dual-wavelength laser. Chinese Journal of Plastic and Reconstructive Surgery. 2023;5(2):47-52. DOI: 10.1016/j.cjprs.2023.05.001.
Eichenfield DZ, Sprague J, Eichenfield LF. Management of acne vulgaris: a review. JAMA. 2021;326(20):2055-67. DOI: 10.1001/jama.2021.17633. PMID: 34812859.
Samuels DV, Rosenthal R, Lin R, Chaudhari S, Natsuaki MN. Acne vulgaris and risk of depression and anxiety: a meta-analytic review. J Am Acad Dermatol. 2020;83(2):532-41. DOI: 10.1016/j.jaad.2020.02.040. PMID: 32088269.
Sood S, Jafferany M, Vinaya Kumar S. Depression, psychiatric comorbidities, and psychosocial implications associated with acne vulgaris. J Cosmet Dermatol. 2020;19(12):3177-82. DOI: 10.1111/jocd.13753. PMID: 33006820.
Mohsin N, Hernandez LE, Martin MR, Does AV, Nouri K. Acne treatment review and future perspectives. Dermatol Ther. 2022;35(9):e15719. DOI: 10.1111/dth.15719. PMID: 35841269.
Tobiasz A, Nowicka D, Szepietowski JC. Acne vulgaris—Novel treatment options and factors affecting therapy adherence: A narrative review. J Clin Med. 2022;11(24):7535. DOI: 10.3390/jcm11247535. PMID: 36556150.
Baldwin H. Oral antibiotic treatment options for acne vulgaris. J Clin Aesthet Dermatol. 2020;13(9):26. PMID: 33133338.
Kircik LH. Doxycycline and minocycline for the management of acne: a review of efficacy and safety with emphasis on clinical implications. J Drugs Dermatol. 2010;9(11):1407-11. PMID: 21061764.
Narsa AC, Suhandi C, Afidika J, Ghaliya S, Elamin KM, Wathoni N. A Comprehensive Review of the Strategies to Reduce Retinoid-Induced Skin Irritation in Topical Formulation. Dermatol Res Pract. 2024;2024:5551774. DOI: 10.1155/2024/5551774. PMID: 39184919.
Pei Y, Liu H, Yang Y, et al. Biological activities and potential oral applications of N‐acetylcysteine: progress and prospects. Oxid Med Cell Longev. 2018;2018(1):2835787. DOI: 10.1155/2018/2835787. PMID: 29849877.
Alsulaimani H, Kokandi A, Khawandanh S, Hamad R. Severity of Acne Vulgaris: Comparison of Two Assessment Methods. Clin Cosmet Investig Dermatol. 2020;13:711-6. DOI: 10.2147/CCID.S266320. PMID: 33061511.
Bae IH, Kwak JH, Na CH, Kim MS, Shin BS, Choi H. A Comprehensive Review of the Acne Grading Scale in 2023. Ann Dermatol. 2024;36(2):65-73. DOI: 10.5021/ad.23.094. PMID: 38576244.
Aghaei S, Mazharinia N, Jafari P, Abbasfard Z. The Persian version of the Cardiff Acne Disability Index. Reliability and validity study. Saudi Med J. 2006;27(1):80-2. PMID: 16432599.
Mardani N, Mozafarpoor S, Goodarzi A, Nikkhah F. A systematic review of N‐acetylcysteine for treatment of acne vulgaris and acne‐related associations and consequences: Focus on clinical studies. Dermatol Ther. 2021;34(3):e14915. DOI: 10.1111/dth.14915. PMID: 33629414.
Fox L, Csongradi C, Aucamp M, Du Plessis J, Gerber M. Treatment modalities for acne. Molecules. 2016;21(8):1063. DOI: 10.3390/molecules21081063. PMID: 27529209.
Del Rosso JQ. Oral Doxycycline in the Management of Acne Vulgaris: Current Perspectives on Clinical Use and Recent Findings with a New Double-scored Small Tablet Formulation. J Clin Aesthet Dermatol. 2015;8(5):19-26. PMCID: PMC4445892.
Han JJ, Faletsky A, Barbieri JS, Mostaghimi A. New acne therapies and updates on use of spironolactone and isotretinoin: a narrative review. Dermatol Ther (Heidelb). 2021;11:79-91. DOI: 10.1007/s13555-020-00481-w. PMID: 33409936.
Naik PP. Trifarotene: a novel therapeutic option for acne. Dermatol Res Pract. 2022;2022(1):1504303. DOI: 10.1155/2022/1504303. PMID: 35668721.
Hebert A, Thiboutot D, Gold LS, et al. Efficacy and safety of topical clascoterone cream, 1%, for treatment in patients with facial acne: two phase 3 randomized clinical trials. JAMA Dermatol. 2020;156(6):621-30. DOI: 10.1001/jamadermatol.2020.0465. PMID: 32320027.
Janeczek M, Moy L, Riopelle A, et al. The potential uses of N-acetylcysteine in dermatology: a review. J Clin Aesthet Dermatol. 2019;12(5):20. PMCID: PMC6561714.
Nakai K, Yoneda K, Murakami Y, et al. Effects of Topical N-Acetylcysteine on Skin Hydration/Transepidermal Water Loss in Healthy Volunteers and Atopic Dermatitis Patients. Ann Dermatol. 2015;27(4):450-1. DOI: 10.5021/ad.2015.27.4.450. PMID: 26273165.
Rosato E, Borghese F, Pisarri S, Salsano F. The treatment with N-acetylcysteine of Raynaud's phenomenon and ischemic ulcers therapy in sclerodermic patients: a prospective observational study of 50 patients. Clin Rheumatol. 2009;28(12):1379-84. DOI: 10.1007/s10067-009-1251-7. PMID: 19690939.
Grant JE, Chamberlain SR, Redden SA, Leppink EW, Odlaug BL, Kim SW. N-Acetylcysteine in the Treatment of Excoriation Disorder: A Randomized Clinical Trial. JAMA Psychiatry. 2016;73(5):490-6. DOI: 10.1001/jamapsychiatry.2016.0060. PMID: 27007062.
AlAnbari H, Sahib A, Raghif A. Effects of silymarin, N-acetylcysteine and selenium in the treatment of papulopustular acne. Oxid Antioxid Med Sci. 2012;1:201-7. DOI: 10.5455/oams.290912.or.019
Sahib A, Al-Anbari H, Salih M, Abdullah F. Effects of oral antioxidants on lesion counts associated with oxidative stress and inflammation in patients with papulopustular acne. J Clin Exp Dermatol Res. 2012;3(163):2. DOI: 10.4172/2155-9554.1000163.
Thakker D, Raval A, Patel I, Walia R. N‐acetylcysteine for polycystic ovary syndrome: a systematic review and meta‐analysis of randomized controlled clinical trials. Obstet Gynecol Int. 2015;2015(1):817849. DOI: 10.1155/2015/817849. PMID: 25653680.
Montes LF, Wilborn WH, Montes CM. Topical acne treatment with acetylcysteine: clinical and experimental effects. Skinmed. 2012;10(6):348-51. PMID: 23346662.
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