Epidermal growth factor intralesional infiltrations can prevent amputation in patients with advanced diabetic foot wounds

Abstract

This study examined if a series of epidermal growth factor (EGF) local infiltrations can enhance the healing process of complicated diabetic wounds. Twenty-nine in-hospital patients with diabetic neuropathic or ischaemic lesions with high risk of amputation were treated in a non controlled pilot study conducted at the National Institute of Angiology, Havana. Lesions, classified as Wagner's grade 3 or 4, included ulcers > or = 20 cm2 for > or = 25 days or amputation residual bases > or = 30 cm2 for > or = 15 days, healing refractory despite comprehensive wound care. EGF (25 microg) intralesional infiltrations (approximately 250 microl of a 25 microg/ml solution/injection point) were performed thrice weekly up to the eighth week. Wound closure was monitored during the treatment and recurrence examined for a year following discharge from hospital. Eighty-six per cent of the patients treated showed a productive granulation at infiltration session 8. Histological examination at this point indicated a substantial wound matrix transformation, granulation tissue cell repopulation and angiogenesis. Of the 29 patients treated, amputation was prevented in 17 (58.6%) of them who completed 24 infiltration sessions. They averaged 71.1 +/- 18.3% of reepithelisation during a mean in-hospital period of 66.5 +/- 4.9 days. Wound recurrence after 1 year of follow-up appeared in only one patient. Preliminary evidences suggest that EGF intralesional infiltrations may be effective in reducing diabetic lower limb amputation.

Figure 1

Schematic of patients’ outcome.

Figure 2

Histological aspects representative of ischaemic and neuropathic lesions before and after epidermal growth factor (EGF) local infiltrations. Representative images of the normal appearance of ischaemic (A, B) and neuropathic (C, D) lesions. Samples were collected just before the first EGF infiltration (A, C) and during the third week of treatment, eighth infiltration session (B, D). (Hematoxylin/eosin staining, magnification ×10.) (A) Ischaemic lesion before treatment. Wound matrix and its cellularity appear disorganised, with unfunctional small vessels exhibiting prominent endothelial nuclei (indicated by arrows). Irreversible nuclear changes (pyknosis) are abundant. (B) Ischaemic lesion at the eighth infiltration session. The wound matrix appears consolidated and organised, and with a number of well‐shaped vessels showing luminal blood (indicated by arrows). (C) Neuropathic lesion before treatment. It is characteristic of the lesion the absence of collagen bundles and the spider web image of the matrix. The reduced number of fibroblastic cells is remarkable. (D) Neuropathic lesion at the eighth infiltration session. The matrix appears dense, consolidated and indurated by compact collagen material. The presence of fibroblastic cells appears largely increased.