Abstract:

Acne vulgaris is a common chronic inflammatory disease of the pilosebaceous unit, which comprises the hair follicle, sebaceous gland, and arrector pili muscle. Acne can lead to significant physical and psychological morbidity, including scarring and reduced quality of life. For severe or treatment-resistant cases, systemic isotretinoin (13-cis-retinoic acid) is the gold standard treatment due to its ability to target multiple pathogenic factors, including sebum production, follicular hyperkeratinization, inflammation, and Cutibacterium acnes proliferation. A comprehensive literature search was conducted using databases such as PubMed, Google Scholar, ScienceDirect, and ResearchGate. The systemic effects of isotretinoin on hematological, inflammatory, and oxidative stress biomarkers highlight its broad impact on the body. While the drug’s anti-inflammatory properties are beneficial for acne treatment, its effects on oxidative stress and hematological parameters may pose risks, particularly in susceptible individuals. The observed reduction in neutrophil and RBC counts, along with elevated platelet counts and Hb levels, suggests that isotretinoin influences multiple hematological pathways. Similarly, the reduction in IL-8 and elevation in CRP levels underscore its complex role in modulating inflammation. The increase in MDA and decrease in TAS levels indicate that isotretinoin may disrupt the balance between oxidative stress and antioxidant defenses, potentially contributing to its adverse effects. Systemic isotretinoin therapy is highly effective for severe acne but is associated with significant systemic effects on hematological, inflammatory, and oxidative stress biomarkers. Future research should focus on elucidating the mechanisms underlying these changes and identifying strategies to mitigate adverse effects while preserving the drug’s therapeutic benefits.

References:

[1]. Mayslich, C., Grange, P. A., Dupin, N., 2021, Cutibacterium acnes as an opportunistic pathogen: an update of its virulence-associated factors. Microorganisms, 9(2), 303, doi:10.3390/microorganisms9020303.

[2]. Martel, J. L., Miao, J. H., Badri, T., Fakoya, A. O., 2024, Anatomy, hair follicle. In StatPearls [Internet]. StatPearls Publishing.

[3]. Alsohaimi, A. O., Alghamdi, A., Alghamdi, R. S., Alghamdi, A. H., Alkhathami, A. M., Alghamdi, M. A., Alghamdi, N. S., 2024, Prevalence of Acne Vulgaris in Adolescents and Young Adults in Al-Baha Region, Saudi Arabia. Cureus, 16(10), e71293. doi:10.7759/cureus.71293.

[4]. Vasam, M., Korutla, S., Bohara, R. A., 2023, Acne vulgaris: A review of the pathophysiology, treatment, and recent nanotechnology based advances. Biochemistry and Biophysics Reports, 36, 101578. doi:10.1016/j.bbrep.2023.101578.

[5]. Abd-Alkarem, M. H., Tawfeeq, E. N., 2022, Evaluation the levels of some oxidative stress parameters in iraqi patients with acne. Biochemical & Cellular Archives, 22(1). doi:103896.2022.22.733.

[6]. Hammill, C., Vaillancourt, T., 2023, Acne and its association with internalizing problems. Dermatological Reviews, 4(5), 228-238. doi:10.1002/der2.181.

[7]. dos Santos Marubayashi, B. A., Simoni, S. E., de Fariña, L. O., 2021, Topical treatments for acne: a bibliographic review. Brazilian Journal of Health Review, 4(1), 3910-3922. doi:10.34119/bjhrv4n1-310.

[8]. Măgerușan, Ș. E., Hancu, G., Rusu, A., 2023, A comprehensive bibliographic review concerning the efficacy of organic acids for chemical peels treating acne vulgaris. Molecules, 28(20), 7219, doi:10.3390/molecules28207219.

[9]. Li, Y., Hu, X., Dong, G., Wang, X., Liu, T., 2024, Acne treatment: research progress and new perspectives. Frontiers in Medicine, 11, 1425675, doi:10.3389/fmed.2024.1425675.

[10]. Daly, A. U., Baptista Gonçalves, R., Lau, E., Bowers, J., Hussaini, N., Charalambides, M., Layton, A. M., 2023, A systematic review of isotretinoin dosing in acne vulgaris. JEADV Clinical Practice, 2(3), 432-449, doi:10.1002/jvc2.154.

[11]. Puspita, F., Jusuf, N. K., Yosi, A., 2021, Plasma malondialdehyde levels related to acne vulgaris severity. Journal of General-Procedural Dermatology & Venereology Indonesia, 5(3), 3. doi:10.19100/jdvi.v5i3.262

[12]. Oğuz, I. D., Kulaklı, S., 2024, Effects of systemic isotretinoin treatment on hemogram, biochemical parameters, and inflammatory markers. Turkderm-Turkish Archives of Dermatology and Venereology, 58(1). doi:10.4274/turkderm.galenos.2024.44442.

[13]. Dr Diljeet Kaur, Assessing the serum levels of interleukins (IL-6,8,17, and 22) in subjects with acne vulgaris. International Research Journal of Pharmacy (IRJP). 2024 Jun 20;15(6):22–6.

[14]. Daye, M., Temiz, S. A., Öztürk, E. N. Y., Işık, B., 2022, Assessment of ELR, NLR, MPV, and CRP levels in patients with acne vulgaris. Assessment, 7(2), 241-244. doi: 10.4274/cjms.2021.2306.

[15]. Afroz, F., Afreen, H., Sultana, T., 2023, Isotretinoin's Impact on Liver Enzymes and Lipids in Acne Patients. Sch J App Med Sci, 6, 1109-1114. doi:10.36347/sjams.2023.v11i06.021.

[16]. Popa, G. L., Mitran, C. I., Mitran, M. I., Tampa, M., Matei, C., Popa, M. I., Georgescu, S. R., 2023, Markers of oxidative stress in patients with acne: A literature review. Life, 13(7), 1433. doi:10.3390/life13071433.

[17]. Wardani, E. M., Nugroho, R. F., 2024, Triglycerides and Acne: Assessing the Impact of Blood Lipid Levels on Acne Severity in Young Adults. Journal of Current Health Sciences, 4(2), 87-94. doi:10.47679/jchs.202469.

[18]. Del Rosso, J. Q., Kircik, L., 2024, The cutaneous effects of androgens and androgen-mediated sebum production and their pathophysiologic and therapeutic importance in acne vulgaris. Journal of Dermatological Treatment, 35(1), 2298878. doi:10.1080/09546634.2023.2298878.

[19]. Kurokawa, I., Layton, A. M., Ogawa, R., 2021, Updated treatment for acne: targeted therapy based on pathogenesis. Dermatology and therapy, 11(4), 1129-1139. doi:10.1007/s13555-021-00552-6.

[20]. Demirci Saadet, E., Sahin, U., 2023, Evaluation of hematological parameters in patients using systemic isotretinoin with diagnosis of acne vulgaris. Journal of Cosmetic Dermatology, 22(3), 1077-1082. doi:10.1111/jocd.15532.

[21]. Abdulwahab, M. H., sahib Jawad, A. A., 2022, The impact of isotretinoin on platelet and white blood cell count in patient with acne vulgaris. Karbala Journal of Medicine, 15(1).

[22]. Alrasheed, A. A., Alsadhan, K. F., Alfawzan, N. F., AbuDujain, N. M., Alnasser, A. H., Almousa, H., 2024, Impact of Isotretinoin on Blood Lipids and Liver Enzymes: A Retrospective Cohort Study in Saudi Arabia. Therapeutics and clinical risk management, 567-575. doi:10.2147/TCRM.S466113.

[23]. Al Dhafiri, M., Kaliyadan, F., Almukhaimar, S., Abdulrahman Alsultan, F., Al Hayim, E., Alnaim, R., Aldossari, A., 2024, Isotretinoin-Induced Dyslipidemia: a Single-Center Study in Saudi Arabia. Patient preference and adherence, 197-206. doi:10.2147/PPA.S445904.

[24]. Al Yaqoubi, W. S. A., Al Touby, S. S. J., Hossain, M. A., 2024, Laboratory investigations of liver function and lipid profiles tests before and after oral isotretinoin treatment among Acne valgaris clients at Ibri Polyclinic: A retrospective study. Toxicology Reports, 13, 101799. doi:10.1016/j.toxrep.2024.101799.

[25]. Mohamed, A. A., Hassnine, A., Elsayed, A., Montaser, M., Ismail, Y., El-Demery, A., Salah, E., 2021, Isotretinoin induced hyperlipidemia and impact of leptin gene rs 7799039 polymorphism in safety of acne patients. Pharmacogenomics and Personalized Medicine, 1679-1687. doi:10.2147/PGPM.S341723.

[26]. Sheriff, A., Kayser, S., Brunner, P., Vogt, B., 2021, C-reactive protein triggers cell death in ischemic cells. Frontiers in immunology, 12, 630430. doi:10.3389/fimmu.2021.630430.

[27]. Hareedy, M. S., Tawfik, K. M., 2022, Systemic isotretinoin has an impact on hemoglobin, ferritin, urea, ceruloplasmin, albumin, uric acid levels, and neutrophil to lymphocyte ratio in acne patients. Journal of Cosmetic Dermatology, 21(11), 6191-6198. doi:10.1111/jocd.15199.

[28]. Yavuz, C., 2021, Neutrophil-lymphocyte ratio and C-reactive protein levels in acne vulgaris patients treated with systemic isotretinoin. Journal of Contemporary Medicine, 11(6), 774-777. doi:10.16899/jcm.949763.

[29]. Monib, K. M. E. D., El‐fallah, A. A., Salem, R. M., 2022, Inflammatory markers in acne vulgaris: Saliva as a novel diagnostic fluid. Journal of Cosmetic Dermatology, 21(3), 1280-1285. doi:10.1111/jocd.14236.

[30]. Nauli, A., Putra, I. B., Jusuf, N. K., 2023, The correlation between interleukin-6 (IL-6) level and high sensitivity C-reactive protein (hs-CRP) level in acne vulgaris. Bali Medical Journal, 12(2), 1926-1929. doi:10.15562/bmj.v12i2.4239.

[31]. Huang, X. W., Pan, W., Zhong, M. Z., Chhonker, Y. S., Steele, A. D., Keohane, C. E., Mylonakis, E., 2023, Biological Evaluation of the Antibacterial Retinoid CD437 in Cutibacterium acnes Infection. Antimicrobial Agents and Chemotherapy, 67(4), e01679-22. doi:10.1128/aac.01679-22.

[32]. Singh, S., Khurana, A., Chitkara, A., 2023, Evaluation of serum levels of interleukins 6, 8, 17 and 22 in acne vulgaris: A cross-sectional study. Indian Journal of Dermatology, 68(2), 233. doi:10.4103/ijd.ijd_786_21.

[33]. Shubber, Z. I., Al-Shibly, I. K., 2021, Clinical and Immunological Evaluation of Isotretinoin in Patients with Acne Vulgaris. Indian Journal of Forensic Medicine and Toxicology, 15(3). doi:10.37506/ijfmt.v15i3.15531.

[34]. Saleh, H. M. A., Alzawahry, K. M. A., Gad, R. E. M., 2020, Assessment of Plasma Malondialdehyde in Acne Patients on Isotretinoin Therapy. QJM: An International Journal of Medicine, 113(Supplement_1), hcaa046-007. doi:10.1093/qjmed/hcaa046.007.

[35]. Alaqrawi, S., Balatay, A. A., 2023, Oxidative Stress in Patients with Acne Vulgaris under Isotretinoin Treatment in Duhok, KRG, Iraq: Effect Of Vitamin C. Journal of Pharmaceutical Negative Results, 2742-2748. doi:10.47750/pnr.2023.14.03.345.

[36]. Segmen, F., Aydemir, S., Küçük, O., Doğu, C., Dokuyucu, R., 2024, Comparison of Oxidative Stress Markers with Clinical Data in Patients Requiring Anesthesia in an Intensive Care Unit. Journal of Clinical Medicine, 13(22), 6979. doi:10.3390/jcm13226979.

[37]. Acer, E., Erdogan, H. K., Kocatürk, E., Ağaoğlu, E., Saracoglu, N., Bilgin, M., 2022, Evaluation of Total Oxidant and Total Antioxidant Status in Patients with Acne Vulgaris. Osmangazi Tıp Dergisi, 44(5), 654-658. doi:10.20515/otd.1054335.

[38]. Bremner, J. D., 2021, Isotretinoin and neuropsychiatric side effects: continued vigilance is needed. Journal of affective disorders reports, 6, 100230. doi:10.1016/j.jadr.2021.100230.

[39]. Ganesan, P., Shanmugham, R., Sekaran, S., Ganapathy, D., 2024, In vitro Anti-inflammatory and Antioxidant Activity of Ormocarpum cochinchinense. Texila International Journal of Public Health.12(4):1-13, doi: 10.21522/TIJPH.2013.12.04.Art011.