• 1

    Cavanagh PR, Lipsky BA, Bradbury AW, et al: Treatment for diabetic foot ulcers. Lancet 366: 1725, 2005.

  • 2

    Boulton AJ, Vileikyte L, Ragnarson-Tennvall G, et al: The global burden of diabetic foot disease. Lancet 366: 1719, 2005.

  • 3

    Singh N, Armstrong DG, Lipsky BA: Preventing foot ulcers in patients with diabetes. JAMA 293: 217, 2005.

  • 4

    Armstrong DG, Cohen K, Courric S, et al: Diabetic foot ulcers and vascular insufficiency: our population has changed, but our methods have not. J Diabetes Sci Technol 5: 1591, 2011.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 5

    Lipsky BA, Berendt AR, Cornia PB, et al: 2012 Infectious Diseases Society of America clinical practice guideline for the diagnosis and treatment of diabetic foot infections. Clin Infect Dis 54: e132, 2012.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 6

    Schaper NC, Apelqvist J, Bakker K: The international consensus and practical guidelines on the management and prevention of the diabetic foot. Curr Diab Rep 3: 475, 2003.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 7

    Armstrong DG, Wrobel J, Robbins JM: Are diabetes-related wounds and amputations worse than cancer? Int Wound J 4: 286, 2007.

  • 8

    Bus SA, Valk GD, Van Deursen, et al: The effectiveness of footwear and offloading interventions to prevent and heal foot ulcers and reduce plantar pressure in diabetes: a systematic review. Diabetes Metab Res Rev 24(suppl 1): S162, 2008.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 9

    Cohen S: Isolation of a mouse submaxillary gland protein accelerating incisor eruption and eyelid opening in the new-born animal. J Biol Chem 237: 1555, 1962.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 10

    Tsang MW, Wong WK, Hung CS, et al: Human epidermal growth factor enhances healing of diabetic foot ulcers. Diabetes Care 26: 1856, 2003.

  • 11

    Berlanga-Acosta J: Diabetic lower extremity wounds: the rationale for growth factors-based infiltration treatment. Int Wound J 8: 612, 2011.

  • 12

    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 8: 192, 2000.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 13

    Schaper NC: Diabetic foot ulcer classification system for research purposes: a progress report on criteria for including patients in research studies. Diabetes Metab Res Rev 20(suppl 1): S90, 2004.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 14

    Lipsky BA, Peters EJ, Senneville E, et al: Expert opinion on the management of infections in the diabetic foot. Diabetes Metab Res Rev 28(suppl 1): S163, 2012.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 15

    Fernandez-Montequin 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 6: 67, 2009.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 16

    Fernandez-Montequin JI, Infante-Cristia 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 4: 333, 2007.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 17

    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 14: 44, 2013.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 18

    Guillermo G, Calvagno M, Tolstano A, et al: Treatment of severe diabetic foot ulcers with recombinant epidermal growth factor (Heberprot-P): retrospective analysis of the obtained in Argentina [in Spanish]. Rev Argentina Cirugia Cardiovasc 10: 153, 2012.

    • Search Google Scholar
    • Export Citation
  • 19

    Valenzuela-Silva CM, Tuero-Iglesias AD, Garcia-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 36: 210, 2013.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 20

    Velazquez W, Vales A, Curbelo W: Impact of epidermal growth factor on the treatment of diabetic foot ulcers. Biotecnologia Aplicada 27: 136, 2010.

    • Search Google Scholar
    • Export Citation
  • 21

    Gonzalez-Acosta S, Calana-Gonzales-Posada B, Marrero-Rodriguez I, et al: Clinical evolution of diabetic foot treatment with Heberprot-P or with the conventional method [in Spanish]. Rev Cubana Angiol Cirugía Vascular 11: 11, 2011.

    • Search Google Scholar
    • Export Citation
  • 22

    García Herrera AL, Rodríguez Fernández R, Ruiz VM, et al: Reduction in the amputation rate with Heberprot P in the local treatment of diabetic foot [in Spanish]. Spanish J Surg Res XIV: 21, 2011.

    • Search Google Scholar
    • Export Citation
  • 23

    Blanes JI: Consensus document on treatment of infections in diabetic foot. Rev Esp Quimioter 24: 233, 2011.

  • 24

    Ertugrul BM, Oncul O, Tulek N, et al: A prospective, multi-center study: factors related to the management of diabetic foot infections. Eur J Clin Microbiol Infect Dis 31: 2345, 2012.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 25

    Ghanassia E, Villon L, Thuan DitDieudonne JF, et al: Long-term outcome and disability of diabetic patients hospitalized for diabetic foot ulcers: a 6.5-year follow-up study. Diabetes Care 31: 1288, 2008.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 26

    Winkley K, Stahl D, Chalder T, et al: Risk factors associated with adverse outcomes in a population-based prospective cohort study of people with their first diabetic foot ulcer. J Diabetes Complications 21: 341, 2007.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 27

    Lipsky BA: Medical treatment of diabetic foot infections. Clin Infect Dis 39 (suppl 2): S104, 2004.

  • 28

    Fernandez-Montequin JI, Valenzuela-Silva CM, Diaz OG, et al: Intra-lesional injections of recombinant human epidermal growth factor promote granulation and healing in advanced diabetic foot ulcers: multicenter, randomised, placebo-controlled, double-blind study. Int Wound J 6: 432, 2009.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 29

    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 22: 497, 2014.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation

An Assessment of Intralesional Epidermal Growth Factor for Treating Diabetic Foot Wounds

The First Experiences in Turkey

Bulent M. Ertugrul Department of Infectious Diseases and Clinical Microbiology, Adnan Menderes University School of Medicine, Aydin, Turkey.

Search for other papers by Bulent M. Ertugrul in
Current site
Google Scholar
PubMed
Close
 MD
,
Benjamin A. Lipsky University of Washington (Emeritus); Department of Medicine, University of Geneva; University of Oxford, Oxford, UK.

Search for other papers by Benjamin A. Lipsky in
Current site
Google Scholar
PubMed
Close
 MD
,
Ulas Guvenc Department of Dermatology, Tarsus Medical Park Hospital, Icel, Turkey.

Search for other papers by Ulas Guvenc in
Current site
Google Scholar
PubMed
Close
 MD
, and
the Turkish Intralesional Epidermal Growth Factor Study Group for Diabetic Foot Wounds
Restricted access

Background:

Intralesional epidermal growth factor (EGF) has been available as a medication in Turkey since 2012. We present the results of our experience using intralesional EGF in Turkey for patients with diabetic foot wounds.

Methods:

A total of 174 patients from 25 Turkish medical centers were evaluated for this retrospective study. We recorded the data on enrolled individuals on custom-designed patient follow-up forms. Patients received intralesional injections of 75 μg of EGF three times per week and were monitored daily for adverse reactions to treatment. Patients were followed up for varying periods after termination of EGF treatments.

Results:

Median treatment duration was 4 weeks, and median frequency of EGF administration was 12 doses. Complete response (granulation tissue >75% or wound closure) was observed in 116 patients (66.7%). Wounds closed with only EGF administration in 81 patients (46.6%) and in conjunction with various surgical interventions after EGF administration in 65 patients (37.3%). Overall, 146 of the wounds (83.9%) were closed at the end of therapy. Five patients (2.9%) required major amputation. Adverse effects were reported in 97 patients (55.7%).

Conclusions:

In patients with diabetic foot ulcer who received standard care, additional intralesional EGF application after infection control provided high healing rates with low amputation rates.

Full list of study group members available in JAPMA digital edition at www.japmaonline.org.

Corresponding author: Bulent M. Ertugrul, Department of Infectious Diseases and Clinical Microbiology, Adnan Menderes University School of Medicine, 09100 Aydin, Turkey. (E-mail: bulentertugrul@yahoo.com)