EVALUATION OF THE EFFECTS OF ISOTRETINOIN TREATMENT ON SERUM URIC ACID AND MEAN PLATELET VOLUME IN PATIENTS WITH ACNE VULGARIS

Abstract

Objective Oral isotretinoin is an effective treatment used for years in the treatment of acne vulgaris. Many side effects of it have been reported, and new ones appear day by day. In this study, it was aimed to investigate whether isotretinoin causes changes in serum uric acid and MPV levels, which are markers that can be evaluated in many diseases. Material and Methods 78 patients who were admitted to Dermatology Outpatient Clinic of our hospital and were diagnosed with mild to moderate or severe acne vulgaris and to whom isotretinoin treatment was started at least three months ago, were included in this study. Hemogram parameters, lipid levels, monocyte / HDL ratio, MPV and uric acid levels were examined before treatment and at the third month of treatment in patients who started isotretinoin at a dose of approximately 0.5 mg / kg / day as a standard. Results While there was no significant change between the hemogram parameters, MPV and uric acid levels of the patients before and in the third month of treatment (p> 0.005); there were significant differences between lipid levels (triglyceride, total cholesterol, LDL) (p <0.005). When the patients were grouped as mild-moderate and severe acne according to the global acne scoring, no significant difference was found between the MPV and uric acid levels measured before the treatment and in the third month of treatment (p=0.43, p=0.23, p=0.31, p=0.14, respectively). Conclusion There are studies showing that uric acid and MPV may be associated with atherosclerosis in the literature. There are contradictory studies and case reports in terms of the effects of isotretinoin treatment on cardiovascular system, also on MPV or uric acid levels. There had been no previous study evaluating both parameters. In this study, we found that systemic isotretinoin treatment did not affect hematological parameters, MPV and serum uric acid parameters, which were shown to be associated with many inflammatory conditions including atherosclerosis. We think that isotretinoin treatment used in the treatment of acne vulgaris can be used safely in individuals without any underlying cardiovascular system or hematological disease.

Keywords

• Acne
• isotretinoin
• uric acid
• MPV

AKNE VULGARİS HASTALARINDA İSOTRETİNOİN TEDAVİSİNİN SERUM ÜRİK ASİT VE ORTALAMA TROMBOSİT HACMİ (MPV) ÜZERİNE OLAN ETKİLERİNİN ARAŞTIRILMASI

Abstract

Amaç Sistemik oral isotretinoin, orta-şiddetli akne vulgaris ve tedaviye dirençli hafif akne vulgaris tedavisinde yıllardır kullanılan etkin bir tedavidir. İsotretinoin tedavisinin birçok yan etkisi bildirilmiş olup, gün geçtikçe yeni yan etkileri de ortaya çıkmaktadır. Bu çalışmada, isotretinoin tedavisinin birçok hastalıkla ilişkili değerlendirilebilen belirteçler olan serum ürik asit ve MPV düzeylerinde değişime neden olup olmadığının araştırılması amaçlandı. Gereç ve Yöntem Hastanemiz Dermatoloji Polikliniğine başvuran, en az üç ay önce isotretinoin tedavisi başlanmış olan ve kontrollerini aksatmayan, hafif-orta veya şiddetli akne vulgaris tanısı almış 78 hasta çalışmaya alındı. Standart olarak yaklaşık 0,5 mg/kg/gün dozda isotretinoin tedavisi başlanan hastaların tedavi öncesi ve tedavinin 3. ayındaki hemogram parametreleri, lipit düzeyleri, monosit/HDL oranı ve MPV ile ürik asit düzeyleri incelendi. Bulgular Hastaların tedavi öncesi ve tedavinin 3. ayında bakılan hemogram parametreleri, MPV ve ürik asit düzeyleri arasında herhangi bir anlamlı değişiklik saptanmamışken (p>0,05); lipit düzeyleri arasında (trigliserit, total kolesterol, LDL) anlamlı farklılıklar mevcuttu (p<0,05). Hastalar, global akne skorlamasına göre hafif-orta ve şiddetli aknesi olanlar şeklinde gruplandırıldığında tedavi öncesi ve tedavinin 3. ayında bakılan MPV ile ürik asit düzeyleri arasında da herhangi bir anlamlı değişiklik saptanmadı (sırasıyla p=0.43, p=0.23; p=0.31, p=0.14). Sonuç Literatürde ürik asit ve MPV’nin ateroskleroz dahil birçok inflamatuvar durumla ilişkili olabileceğini gösteren çalışmalar mevcuttur. İsotretinoin tedavisinin de kardiyovasküler sistem ve kemik iliği üzerine etkileri açısından çelişkili sonuçların bildirildiği araştırmalar ve olgu sunumları bulunmaktadır. İsotretinoin tedavisinin MPV üzerine veya ürik asit seviyeleri üzerine olan etkilerinin ayrı ayrı yapılmış çalışmaları mevcut olup, bu çalışmalar çelişen sonuçlara sahiptirler. Literatürde, daha önceden her iki parametrenin aynı anda değerlendirildiği bir çalışma bulunmamaktadır. Bu çalışmamızda, sistemik isotretinoin tedavisinin, ateroskleroz dahil birçok inflamatuvar durumla ilişkili olabileceği gösterilmiş olan parametrelerden MPV ve serum ürik asit üzerine ve hematolojik diğer parametreler üzerine bir etkisi olmadığını saptadık. Akne vulgaris tedavisinde kullanılan isotretinoin tedavisinin, altta yatan herhangi bir kardiyovasküler sistem veya hematolojik hastalığı olmayan kişilerde güvenli bir şekilde kullanılabileceğini düşünmekteyiz.

Keywords

• Akne
• İsotretinoin
• ürik asit
• ortalama trombosit hacmi

References

1. 1. Zaenglein AL, Thiboutot DM. Acne vulgaris. In: Bolognia JL, Jorizza JL, Rapini RP, editors. Dermatology. (2nd ed.) Spain: Mosby Elsevier Inc 2008; 495-508.
2. 2. Rigopoulos D, Larios G, Katsambas AD. The role of isotretinoin in acne therapy: why not as first-line therapy? Facts and controversies. Clin Dermatol. 2010;28:24–30.
3. 3. Jiang H, Li C. Common Pathogenesis of Acne Vulgaris and Atherosclerosis. Inflammation. 2019; 42(1):1-5.
4. 4. Zouboulis, C.C., E. Jourdan, M. Picardo. Acne is an inflammatory disease and alterations of sebum composition initiate acne lesions. Journal of the European Academy of Dermatology & Venereology. 2013; 28 (5): 527–32.
5. 5. Jeremy, A.H., D.B. Holland, S.G. Roberts, K.F. Thomson, W.J. Cunliffe. Inflammatory events are involved in acne lesion initiation. Journal of Investigative Dermatology.2003; 121 (1): 20–27.
6. 6. Yuan, Y., P. Li, J. Ye. Lipid homeostasis and the formation of macrophage-derived foam cells in atherosclerosis. Protein & Cell 3. 2012; (3): 173–81.
7. 7. Ndrepepa G. Uric acid and cardiovascular disease. Clin Chim Acta. 2018 ;484:150-63.
8. 8. Kanbay M, Solak Y, Dogan E, Lanaspa MA, Covic A. Uric acid in hypertension and renal disease: the chicken or the egg? Blood Purif. 2010;30(4):288-95.

9. 9. Ishizaka Y, Yamakado M, Toda A, Tani M, Ishizaka N. Relationship between serum uric acid and serum oxidative stress markers in the Japanese general population. Nephron Clin Pract. 2014;128(1-2):49-56.
10. 10. Lei Z, Cai J, Hong H, Wang Y. Serum Uric Acid Level and Outcome of Patients With Ischemic Stroke: A Systematic Review and Meta-Analysis. Neurologist. 2019; 24(4):121-31.
11. 11. Waring WS. Uric acid: An important antioxidant in acute ischaemic stroke. QJM. 2002; 95:691–3.
12. 12. Yousefi M, Rahimi H, Barikbin B, Toossi P, Lotfi S, Hedayati M, et al. Uric Acid: a new antioxidant in patients with pemphigus vulgaris. Indian J Dermatol. 2011;56(3):278-81.
13. 13. Chu SG, Becker RC, Berger PB, Bhatt DL, Eikelboom JW, Konkle B, et al. Mean platelet volume as a predictor of cardiovascular risk: a systematic review and meta-analysis. J Thromb Haemost. 2010 ;8(1):148-56.
14. 14. Milovanovic M, Nilsson E, Järemo P. Relationships between platelets and inflammatory markers in rheumatoid arthritis. Clin Chim Acta. 2004;343:237-40.
15. 15. Canpolat F, Akpinar H, Eskioglu F. Mean platelet volume in psoriasis and psoriatic arthritis. Clin Rheumatol 2010;29:325-8.
16. 16. Lowenstein EB, Lowenstein EJ. Isotretinoin systemic therapy and the shadow cast upon dermatology's downtrodden hero. Clin Dermatol. 2011;29:652–61.
17. 17. Elnady B, Elkhouly T, Dawoud NM, Desouky DE, Kewan HH, Dawoud DM, et al. New onset of axial spondyloarthropathy in patients treated with isotretinoin for acne vulgaris: incidence, follow- up, and MRI findings. Clin Rheumatol. 2020;39(6):1829-38.
18. 18. Scheinfeld N, Bangalore S. Facial edema induced by isotretinoin use: a case and a review of the side effects of isotretinoin. J Drugs Dermatol. 2006 ;5(5):467-8.
19. 19. Akçay M, Yüksel S. Isotretinoin-associated possible Kounis syndrome: A case report and a review of other cardiovascular side effects reported in the literature. Turk Kardiyol Dern Ars. 2019;47(4):324-328.
20. 20. Karadağ AS, Çalka Ö, Akdeniz N. Evaluation of Side Effects of Isotretinoin in 150 Patients with Acne Vulgaris. Turkderm j. 2011; 45(1): 37-42.
21. 21. Cemil BC, Ayvaz HH, Ozturk G, Ergin C, Akıs HK, Gonul M, Arzuhal E. Effects of isotretinoin on body mass index, serum adiponectin, leptin, and ghrelin levels in acne vulgaris patients. Postepy Dermatol Alergol. 2016;33(4):294-9.
22. 22. Bérard A, Azoulay L, Nakhai-Pour HR, Moussally K. Isotretinoin and the risk of cardiovascular, cerebrovascular and thromboembolic disorders. Dermatology. 2011;223(1):45-51.
23. 23. Lorenzo N, Antuña P, Dominguez L, Rivero F, Bastante T, Alfonso F. Acute myocardial infarction in a young woman on isotretinoin treatment. Int J Cardiol. 2015; 15;181:39-41.
24. 24. Roodsari MR, Akbari MR, Sarrafi-rad N, Saeedi M, Gheisari M, Kavand S. The effect of isotretinoin treatment on plasma homocysteine levels in acne vulgaris. Clin Exp Dermatol. 2010;35(6):624-6.
25. 25. Hasdemir C, Sagcan A, Sekuri C, Ildizli M, Ulucan C, Ceylan C. Isotretinoin (13-cis-retinoic acid) associated atrial tachycardia. Pacing Clin Electrophysiol. 2005;28(4):348-9.
26. 26. Seçkin HY, Baş Y, Takçı Z, Kalkan G. Effects of isotretinoin on the inflammatory markers and the platelet counts the platelet counts in patients with acne vulgaris. Cutan Ocul Toxicol 2016; 35: 89-91.
27. 27. Tamer F, Yuksel ME, Avcı E. Is mean platelet volume an inflammatory marker in acne patients treated with isotretinoin? Acta Dermatovenerol Alp Pannonica Adriat. 2019;28(2):65-9.
28. 28. Johnson TM, Rapini RP. Isotretinoin-induced thrombocytopenia. J Am Acad Dermatol 1987; 17:838-9.
29. 29. Schmutz JL, Barbaud A, Trechot P. Thrombocytosis induced by low-dose isotretinoin. Ann Dermatol Venereol 2002;129:355.
30. 30. Hansen TJ, Lucking S, Miller JJ, Kirby JS, Thiboutot DM, Zaenglein AL. Standardized laboratory monitoring with use of isotretinoin in acne. J Am Acad Dermatol 2016;75:323-8.
31. 31. Gencoglan G, Inanir I, Miskioglu M, Gunduz K. Evaluation of sequential effect of isotretinoin on the haematological parameters in patients with acne vulgaris. Cutan Ocul Toxicol. 2018;37(2):139-42.
32. 32. Ataseven A, Ugur Bilgin A. Effects of isotretinoin on the platelet counts and the mean platelet volume in patients with acne vulgaris. ScientificWorldJournal. 2014;2014:156464.
33. 33. Kutlu Ö. Effect of isotretinoin treatment on the inflammatory markers in patients with acne vulgaris: can monocyte/HDL be a new indicator for inflammatory activity of isotretinoin treatment? Cutan Ocul Toxicol. 2019; 17:1-4.
34. 34. Solak B, Erdem T, Solak Y. Isotretinoin use for acne vulgaris is associated with increased serum uric acid levels. J Dermatolog Treat. 2017;28(1):82-5.
35. 35. Choi WJ, Ford ES, Curhan G, Rankin JI, Choi HK. Independent association of serum retinol and β-carotene levels with hyperuricemia: A national population study. Arthritis Care Res (Hoboken). 2012;64(3):389-96.