Long-term Follow-up of treatment of chronic foot wounds with recombinant human epidermal growth factor in patients with different complications of diabetes mellitus
https://doi.org/10.14341/DM12701
Abstract
BACKGROUND: Diabetic foot ulcer (DFU) is a dangerous complication of diabetes mellitus (DM), which can lead to the development of chronic wounds and amputations. Recombinant human epidermal growth factor (rhEGF) can be used as an adjuvant treatment for chronic wounds resistant to standard treatment. Studies have demonstrated its clinical efficacy, however, there is insufficient information on the long-term results of treatment, its safety and the effect on the progression of diabetes complications, adverse cardiovascular events and the development of cancer.
AIM: To assess the long-term results of rhEGF therapy for trophic foot ulcers in individuals with multiple complications of diabetes.
METHODS: The study included 20 patients with type 1 and type 2 diabetes and various forms of DFS without critical ischemia, who had previously been treated with DFS using rhEGF in order to assess the general condition, progression of microand macrovascular complications of diabetes, adverse cardiovascular events, the development of cancer and the quality of life.
RESULTS: There was a statistically significant difference between the area of wound defects, the percentage of granulation tissue that filled the wound defect, before the start of rhEGF treatment and at the time of discharge from the hospital (p <0.05). During treatment with rhEGF, mild adverse events were observed in 35%. Complete epithelialization of wounds in most patients occurred in 3 [2; 4] months. In 11.76%, the wound was not completely epithelialized. Relapse occurred in 5.8% due to non-compliance with limb unloading. Minor amputation was performed in 1 patient. Progression of diabetic retinoand nephropathy was revealed in 23.5%. 11.76% suffered myocardial infarction of unknown age, 1 patient (5.88%) suffered acute cerebrovascular accident. Serious adverse events in the form of PE with a fatal outcome and critical ischemia of the lower limb were recorded in 5.8%.
CONCLUSIONS: As a result of the study of long-term results of rhEGF treatment of chronic foot wounds, a low percentage of relapses and small amputations, the absence of high amputations and oncological diseases, the development of serious adverse events in 2 patients, the progression of diabetic retinoand nephropathy in 4 patients, the development of IM of unknown age in 2 patients was recorded. and stroke in 1 patient after rhEGF therapy.
About the Authors
E. L. ZaitsevaRussian Federation
Ekaterina L. Zaitseva, MD, PhD, senior research associate; eLibrary SPIN: 1075-3022
11 Dm. Ulyanova street, 117036 Moscow
V. M. Zhilyaev
Russian Federation
Viktor M. Zhilyaev, clinical residence; eLibrary SPIN: 7728-9212
Moscow
G. R. Galstyan
Russian Federation
Gagik R. Galstyan, MD, PhD, Professor; eLibrary SPIN: 9815-7509
Moscow
References
1. IDF atlas (9th edition). [Internet]. Brussels, Belgium. International Diabetes Federation; 2019. Available from: http://www.diabetesatlas.org.
2. Standards of specialized diabetes care. Edited by Dedov II, Shestakova MV, Mayorov AYu. 9th edition. Diabetes mellitus. 2019;22(151):1-144. (In Russ.). https://doi.org/10.14341/DM221S1
3. Singh N. Preventing Foot Ulcers in Patients With Diabetes. JAMA. 2005;293(2):217. https://doi.org/10.1001/jama.293.2.217
4. Pemayun TGD, Naibaho RM, Novitasari D, Amin N, Minuljo TT. Risk factors for lower extremity amputation in patients with diabetic foot ulcers: a hospital-based case–control study. Diabet Foot Ankle. 2015;6(1):29629. https://doi.org/10.3402/dfa.v6.29629
5. Ramsey SD, Newton K, Blough D, et al. Incidence, outcomes, and cost of foot ulcers in patients with diabetes. Diabetes Care. 1999;22(3):382-387. https://doi.org/10.2337/diacare.22.3.382
6. Jakosz N. Book review – IWGDF Guidelines on the Prevention and Management of Diabetic Foot Disease. Wound Pract Res. 2019;27(3):144. https://doi.org/10.33235/wpr.27.3.144
7. Cohen S. Isolation of a Mouse Submaxillary Gland Protein Accelerating Incisor Eruption and Eyelid Opening in the New-born Animal. J Biol Chem. 1962;237(5):1555-1562. https://doi.org/10.1016/S0021-9258(19)83739-0
8. Berlanga-Acosta J. Diabetic lower extremity wounds: the rationale for growth factors-based infiltration treatment. Int Wound J. 2011;8(6):612-620. https://doi.org/10.1111/j.1742-481X.2011.00840.x
9. Gibbs S, Silva Pinto AN, Murli S, et al. Epidermal growth factor and keratinocyte growth factor differentially regulate epidermal migration, growth, and differentiation. Wound Repair Regen. 2000;8(3):192-203. https://doi.org/10.1046/j.1524-475x.2000.00192.x
10. Falanga V. Growth Factors and Chronic Wounds: The Need to Understand the Microenvironment. J Dermatol. 1992;19(11):667-672. https://doi.org/10.1111/j.1346-8138.1992.tb03756.x
11. Mast BA, Schultz GS. Interactions of cytokines, growth factors, and proteases in acute and chronic wounds. Wound Repair Regen. 1996;4(4):411-420. https://doi.org/10.1046/j.1524-475X.1996.40404.x
12. Tsang MW, Wong WKR, Hung CS, et al. Human Epidermal Growth Factor Enhances Healing of Diabetic Foot Ulcers. Diabetes Care. 2003;26(6):1856-1861. https://doi.org/10.2337/diacare.26.6.1856
13. Montequin JF, Bonachea LS, Acosta JB, et al. Intralesional and perilesional application of an epidermal growth factor (Heberprot-P®) in diabetic foot ulcers. Part one. Angiology and Vascular Surgery. 2018;24(4):33-42.
14. 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. https://doi.org/10.1111/j.1742-481X.2006.00237.x
15. 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. October 2007;4(4):333-343. https://doi.org/10.1111/j.1742-481X.2007.00344.x
16. Fernández-Montequín JI, Valenzuela-Silva CM, González-Díaz O, et al. Intra-lesional injections of recombinant human epidermal growth factor promote granulation and healing in advanced diabetic foot ulcers: multicenter, randomised, placebocontrolled, double-blind study. Int Wound J. 2009;6(6):432-443. https://doi.org/10.1111/j.1742-481X.2009.00641.x
17. Fernández-Montequín JI, Betancourt BY, Leyva-Gonzalez G, et al. Intralesional administration of epidermal growth factor-based formulation (Heberprot-P) in chronic diabetic foot ulcer: treatment up to complete wound closure. Int Wound J. 2009;6(1):67-72. https://doi.org/10.1111/j.1742-481X.2008.00561.x
18. Ertugrul BM, Lipsky BA, Guvenc U. An Assessment of Intralesional Epidermal Growth Factor for Treating Diabetic Foot Wounds. J Am Podiatr Med Assoc. 2017;107(1):17-29. https://doi.org/10.7547/15-056
19. Kahraman M, Misir A, Kizkapan TB, et al. The Long-Term Outcomes Following the Application of Intralesional Epidermal Growth Factor in Patients With Diabetic Foot Ulcers. J Foot Ankle Surg. 2019;58(2):282-287. https://doi.org/10.1053/j.jfas.2018.08.041
20. Grant MB, Afzal A, Spoerri P, et al. The role of growth factors in the pathogenesis of diabetic retinopathy. Expert Opin Investig Drugs. 2004;13(10):1275-1293. https://doi.org/10.1517/13543784.13.10.1275
21. Khan ZA, Chakrabarti S. Growth Factors in Proliferative Diabetic Retinopathy. Exp Diabesity Res. 2003;4(4):287-301. https://doi.org/10.1155/EDR.2003.287
22. Ware JE, Snow KK, Kosinski M, Gandek B. SF-36 Health Survey Manual and Interpretation Guide. Bost New Engl Med Cent. 1993.
23. Amirdjanova VN, Goryachev DV, Korshunov NI, et al. SF-36 questionnaire population quality of life indices Objective. Rheumatol Sci Pract. 2008;122(1):36-48 (In Russ.). https://doi.org/10.14412/1995-4484-2008-852
24. Wilson KJ, Gilmore JL, Foley J, et al. Functional selectivity of EGF family peptide growth factors: Implications for cancer. Pharmacol Ther. 2009;122(1):1-8. https://doi.org/10.1016/j.pharmthera.2008.11.008
Review
For citations:
Zaitseva E.L., Zhilyaev V.M., Galstyan G.R. Long-term Follow-up of treatment of chronic foot wounds with recombinant human epidermal growth factor in patients with different complications of diabetes mellitus. Diabetes mellitus. 2020;23(6):532-540. (In Russ.) https://doi.org/10.14341/DM12701

This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND 4.0).