The use of intralesional epidermal growth factor in the treatment of diabetic foot ulcers

Year 2023, , 607 - 612, 31.12.2023

Burhan Kurtuluş , Erbil Aydın

https://doi.org/10.47582/jompac.1350351

Abstract

Aims: The mitogenic and cell protective effects of epidemal growth factor (EGF) in wound healing stimulate the growth, re-covering the surface of the wound area. In this research we tried to elucidate the effectiveness of intradermal EGF application on wound healing in diabetic foot ulcers regarding the fact that EGF can accelerate the formation of skin cover layer on the infected surface, even in relatively ischemic cases.
Methods: The data of 68 patients who applied to our institution’s orthopedics and wound care outpatient clinic with the diagnosis of diabetic foot ulcer, who underwent wound care, debridement and follow-up were retrospectively analyzed. All of the patients included in this study were classified as Wagner Stage III and Stage IV diabetic foot ulcers and were followed up with standard wound care. EGF application was initiated if there was not enough bleeding on the wound borders and defect floor after debridement.
Results: The rate of patients with 50% or more granulation in the second week of treatment in the groups was 35.7% (n=10) in the standard treatment group, it was 60% (n=24) in the EGF group (p<0.05). Complete granulation rates at the fourth week of treatment in patients who did not show complete granulation in the second week of treatment was 30.8% (n=8) in the standard treatment and 61.1% (n=22) in the EGF treatment (p<0.05). Similarly, in patients who did not show complete granulation in the fourth week of treatment, complete granulation rates at the sixth week of treatment was found to be 44.4% (n=8) in standard treatment and 85.7% (n=12) in EGF treatment (p<0.05).
Conclusion: According to the results of this study, intradermal EGF application in diabetic foot ulcers may positively affect wound healing by accelerating the formation of a skin cover layer.

Keywords

Diabetic foot ulcer, EGF, epidermal growth factor, diabetic ulcer, wound care

Diyabetik ayak ülserlerinin tedavisinde intralezyonel epidermal büyüme faktörünün kullanımı

Abstract

Amaç: Epidemal büyüme faktörünün (EGF) yara iyileşmesindeki mitojenik ve hücre koruyucu etkileri büyümeyi uyararak yara bölgesinin yüzeyini yeniden kaplar. Bu araştırmada, EGF'nin nispeten iskemik vakalarda bile enfekte yüzeyde deri örtümü oluşumunu hızlandırabileceği gerçeğinden yola çıkarak diyabetik ayak ülserlerinde intradermal EGF uygulamasının yara iyileşmesi üzerindeki etkinliğini açıklamaya çalıştık.
Yöntemler: Kurumumuzun ortopedi ve yara bakım polikliniğine diyabetik ayak ülseri tanısıyla başvuran, yara bakımı, debridmanı ve takibi yapılan 68 hastanın verileri retrospektif olarak analiz edildi. Bu çalışmaya dahil edilen hastaların tamamı Wagner Evre III ve Evre IV diyabetik ayak ülseri olarak sınıflandırıldı ve standart yara bakımı ile takip edildi. Debridman sonrası yara kenarlarında ve defekt tabanında yeterli kanama olmaması durumunda EGF uygulamasına geçildi.
Bulgular: Tedavinin ikinci haftasında gruplarda %50 ve üzerinde granülasyon görülen hasta oranı standart tedavi grubunda %35,7 (n=10), EGF grubunda %60 (n=24) idi (p <0,05). Tedavinin ikinci haftasında tam granülasyon göstermeyen hastalarda tedavinin dördüncü haftasındaki tam granülasyon oranları standart tedavide %30,8 (n=8), EGF tedavisinde ise %61,1 (n=22) idi (p< 0.05). Benzer şekilde tedavinin dördüncü haftasında tam granülasyon göstermeyen hastalarda tedavinin altıncı haftasında tam granülasyon oranları standart tedavide %44,4 (n=8), EGF'de %85,7 (n=12) olarak belirlendi (p<0.05).
Sonuç: Bu çalışmanın sonuçlarına göre, diyabetik ayak ülserlerinde intradermal EGF uygulaması yara örtümünü hızlandırarak yara iyileşmesi üzerinde olumlu etki gösterebilir.

Keywords

Diyabetik Ayak Ülseri, EGF, Epidermal Büyüme Faktörü, Diyabetik Ülser, Yara Bakımı

References

• 1. Fernandez-Montequin JI, Valenzuela-Silva CM, Gonzalez Diaz O, et al. For the Cuban Diabetic Foot Study Group. Intralesional injections of recombinant human epidermal growth factor promote granulation and healing in advanced diabetic foot ulcers: multicenter, randomised, placebo-controlled, doubleblind study. Int Wound J. 2009;6:432-443.
• 2. Berlanga-Acosta J. Diabetic lower extremity wounds: the rationale for growth factors-based infiltration treatment. Int Wound J. 2011;8(6):612-620. doi:10.1111/j.1742-481X.2011.00840.x
• 3. Valenzuela-Silva CM, Tuero-Iglesias ÁD, García-Iglesias E, et al. Granulation response and partial wound closure predict healing in clinical trials on advanced diabetes foot ulcers treated with recombinant human epidermal growth factor. Diabetes Care. 2013;36(2):210-215. doi:10.2337/dc12-1323
• 4. Tsang MW, Wong WK, Hung CS, et al. Human epidermal growth factor enhances healing of diabetic foot ulcers. Diabetes Care. 2003;26(6):1856-1861. doi:10.2337/diacare.26.6.1856
• 5. Gomez-Villa R, Aguilar-Rebolledo F, Lozano-Platonoff A, et al. Efficacy of intralesional recombinant human epidermal growth factor in diabetic foot ulcers in Mexican patients: a randomized double-blinded controlled trial. Wound Repair Regen. 2014;22(4):497-503. doi:10.1111/wrr.12187
• 6. Singla S, Garg R, Kumar A, Gill C. Efficacy of topical application of beta urogastrone (recombinant human epidermal growth factor) in Wagner’s grade 1 and 2 diabetic foot ulcers: comparative analysis of 50 patients. J Nat Sci Biol Med. 2014;5(2):273-277. doi:10.4103/0976-9668.136160
• 7. Park KH, Han SH, Hong JP, et al. Topical epidermal growth factor spray for the treatment of chronic diabetic foot ulcers: a phase III multicenter, double-blind, randomized, placebo-controlled trial. Diabetes Res Clin Pract. 2018;142:335-344. doi:10.1016/j. diabres.2018.06.002
• 8. Yang S, Geng Z, Ma K, Sun X, Fu X. Efficacy of topical recombinant human epidermal growth factor for treatment of diabetic foot ulcer: a systematic review and meta-analysis. Int J Low Extrem Wounds. 2016;15(2):120-125. doi:10.1177/1534734616645444
• 9. Yang S, Geng Z, Ma K, Sun X, Fu X. Efficacy of topical recombinant human epidermal growth factor for treatment of diabetic foot ulcer: a systematic review and meta-analysis. Int J Low Extrem Wounds. 2016;15(2):120-125. doi:10.1177/1534734616645444
• 10. Basu S, Yoffe P, Hills N, Lustig RH. The relationship of sugar to population-level diabetes prevalence: an econometric analysis of repeated cross-sectional data. PLoS One. 2013;8(2):e57873. doi:10.1371/journal.pone.0057873
• 11. Singh N, Armstrong DG, Lipsky BA. Preventing foot ulcers in patients with diabetes. JAMA. 2005;293(2):217-228. doi:10.1001/ jama.293.2.217
• 12. Moxey PW, Gogalniceanu P, Hinchliffe RJ, et al. Lower extremity amputations--a review of global variability in incidence. Diabet Med. 2011;28(10):1144-1153. doi:10.1111/j.1464-5491.2011.03279.x
• 13. Bakker K, van Houtum WH, Riley PC. 2005: The International Diabetes Federation focuses on the diabetic foot. Curr Diab Rep. 2005;5(6):436-440. doi:10.1007/s11892-005-0051-y
• 14. Steed DL, Attinger C, Colaizzi T, et al. Guidelines for the treatment of diabetic ulcers. Wound Repair Regen. 2006;14(6):680-692. doi:10.1111/j.1524-475X.2006.00176.x
• 15. Buchberger B, Follmann M, Freyer D, Huppertz H, Ehm A, Wasem J. The evidence for the use of growth factors and active skin substitutes for the treatment of non-infected diabetic foot ulcers (DFU): a health technology assessment (HTA). Exp Clin Endocrinol Diabetes. 2011;119(8):472-479. doi:10.1055/s-0031-1279713
• 16. Agudelo-Suárez AA, Ruiz-Cantero MT, González-Zapata LI, Restrepo-Medrano JC, Ortiz-Barreda GM. The parliamentary political agenda: a tool for policy analysis of diabetes priorities in Spain. Gac Sanit. 2012;26(6):554-559. doi:10.1016/j. gaceta.2012.03.002
• 17. Whiting DR, Guariguata L, Weil C, Shaw J. IDF diabetes atlas: global estimates of the prevalence of diabetes for 2011 and 2030. Diabet Res Clin Pract. 2011;94(3):311-321.
• 18. Berlanga-Acosta J, Fernández-Montequín J, Valdés-Pérez C, et al. Diabetic foot ulcers and epidermal growth factor: revisiting the local delivery route for a successful outcome. Biomed Res Int. 2017;2017:2923759. doi:10.1155/2017/2923759
• 19. Singla S, Singla S, Kumar A, Singla M. Role of epidermal growth factor in healing of diabetic foot ulcers. Indian J Surg. 2012;74(6):451-455. doi:10.1007/s12262-012-0447-2
• 20. Fernández-Montequín JI, Infante-Cristiá E, Valenzuela-Silva C, et al. Intralesional injections of Citoprot-P (recombinant human epidermal growth factor) in advanced diabetic foot ulcers with risk of amputation. Int Wound J. 2007;4(4):333-343. doi:10.1111/ j.1742-481X.2007.00344.x
• 21. Fernández-Montequín JI, Betancourt BY, Leyva-Gonzalez G, et al. Intralesional administration of epidermal growth factorbased formulation (Heberprot-P) in chronic diabetic foot ulcer: treatment up to complete wound closure. Int Wound J. 2009;6(1):67-72. doi:10.1111/j.1742-481X.2008.00561.x
• 22. Velázquez W, Valles A, Curbelo W. Impacto del Heberprot-P en el tratamiento de las úlceras del pie diabético. Biotecnología Aplicada. 2010;27(2):136-141.
• 23. Yera-Alos IB, Alonso-Carbonell L, Valenzuela-Silva CM, et al. Active post-marketing surveillance of the intralesional administration of human recombinant epidermal growth factor in diabetic foot ulcers. BMC Pharmacol Toxicol. 2013;14:44. doi:10.1186/2050-6511-14-44
• 24. González Acosta S, Calaña González Posada B, Marrero Rodríguez I, López Fernández R. Evolución clínica del tratamiento en el pie diabético con Heberprot-P o con el método convencional. Rev Cubana Angiología y Cirugía Vascular. 2011;11(2):11.
• 25. Berlanga J, Fernández JI, López E, et al. Heberprot-P: a novel product for treating advanced diabetic foot ulcer. MEDICC Rev. 2013;15(1):11-15. doi:10.37757/MR2013V15.N1.4
• 26. Valenzuela-Silva CM, Tuero-Iglesias ÁD, García-Iglesias E, et al. Granulation response and partial wound closure predict healing in clinical trials on advanced diabetes foot ulcers treated with recombinant human epidermal growth factor. Diabetes Care. 2013;36(2):210-215. doi:10.2337/dc12-1323
• 27. Gomez-Villa R, Aguilar-Rebolledo F, Lozano-Platonoff A, et al. Efficacy of intralesional recombinant human epidermal growth factor in diabetic foot ulcers in Mexican patients: a randomized double-blinded controlled trial. Wound Repair Regen. 2014;22(4):497-503. doi:10.1111/wrr.12187
• 28. Acosta JB, Savigne W, Valdez C, et al. Epidermal growth factor intralesional infiltrations can prevent amputation in patients with advanced diabetic foot wounds. Int Wound J. 2006;3(3):232-239. doi:10.1111/j.1742-481X.2006.00237.x