a case report illustrating the management of a complex neuropathic

Vowden K, D’Arcy A*, Vowden P.
Dept. of Vascular Surgery and *Podiatry, Bradford Royal Infirmary, Bradford,
The foot without a protective response is always at risk of significant trauma or
continuous low grade injury. When ulceration occurs in this situation management
can be challenging and may require the use of a number of advanced wound care
products used in conjunction with offloading, which in this case involved ambulatory
pressure relief.
Case study
A 42 year old Asian male patient with a 37 year history of chronic foot ulceration
secondary to a peripheral neuropathy initially thought, although not confirmed, to be
due to leprosy was referred to the combined diabetic and vascular foot clinic in
August 2000. The patient reported that he had previously had 24 attempts at skin
grafting including amputation of the great toe with transfer of the skin to the ulcerated
area on the sole of the foot. The last skin graft was performed in 1984 and following
failure of these procedures he was offered below knee amputation but declined this
radical form of treatment, preferring to continue with self-treatment, community and
plastic surgical dressings and periodic courses of antibiotics. More recently he had
required these three monthly.
On referral to the combined foot clinic, there were two plantar ulcers, one across the
metatarsal heads with a further ulcer towards the heal (Figure 1). Despite intensive
conventional management which included offloading with an Aircast® (Aircast
Incorporated) boot, debridement and a variety of protective dressings these areas
coalesced into a single ulcer measuring 23.6cm2 (Figure 2).
Having concluded that this ulcer was unlikely to heal with either further dressings and
offloading or another autologous skin graft we elected to treat the ulcer with a
bioengineered skin product, Apligraf® (Organogenesis, Canton, MA and Novartis
Pharmaceuticals, East Hanover, NJ). Following further wound bed preparation, which
on this occasion including the use of Hyaluronic acid, Hyalofill® (ConvaTec Ltd)
(Figure 3) we considered the ulcer ready for grafting. The Apligraf was airfreighted
from the USA in environmentally stabilised packaging which provides a shelf-life of
five days (Figure 4). We placed two of the 7.5cm diameter Apligrafs, fenestrated to
allow drainage of exudate, onto the wound (Figure 5). The grafts were held in place
by a combination of Mepital® (Mölnlycke), Lyofoam® (Seton) and orthopaedic wool
covered with a retention crepe bandage. Initially the patient was managed as an
outpatient with complete off-loading, returning to the Aircast® and limited
mobilisation after four weeks.
At the first major dressing change on day 5 there was already an improvement in the
wound with evidence of an advancing healing edge (Figure 6). At 4 weeks (Figure 7)
there had been a marked reduction in the ulcer size (>50%) and the remainder of the
wound appeared healthy with a reduction in hyperkeratinosis and exudate. Rapid
healing continued as shown by the images at 6 weeks (Figure 8), 7 weeks (Figure 9)
and 8 weeks (Figure 10). The ulcer has now healed (Figure 11) and other than one
minor ulcer recurrence six month after healing the ulcer remains healed and the
patient has returned to full mobility in custom made footwear.
It would appear that the use of Apligraf has achieved what the patients own skin
failed to do, namely the resolution of this chronic foot ulcer. Apligraf®
(Organogenesis, Canton, MA and Novartis Pharmaceuticals, East Hanover, NJ) is a
living human skin equivalents (HSEs) consisting of a tissue engineered bi-layered
skin equivalent having both an epidermis and a dermis [1, 2]. It consists of
keratinocytes and fibroblasts derived from neonatal foreskin and bovine collagen.
Apligraf has been demonstrated to produces a great number of cytokines and growth
factors and is immunologically well tolerated. Although the exact mode of action of
HSE’s are not known they appear to act by both filling the wound defect with an
extracellular matrix and by producing bio-active chemicals which enhance healing
and which are produced by normal skin during the healing process. The value of this
product in the management of diabetic neuropathic foot ulceration has recently been
published [3-5]. It has been suggested that the neonatal origin of cells used in the
production of Apligraf may provide the product with an advantage over other skin
products and possibly even over autografts. Certainly in this case where management
by conventional grafting techniques had failed repeatedly the healing of this ulcer
following a single application of Apligraf has been remarkable.
This case illustrates the importance of good wound bed preparation (WBP) before the
application of either skin or biosynthetic skin substitutes if effective use of a scares or
expensive resources is to be used effectively. The aspects of good wound care as they
relate to WBP have recently been discussed in an article published in this journal [6].
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Pham, H.T., B.I. Rosenblum, T.E. Lyons, J.M. Giurini, J.S. Chrzan, G.M.
Habershaw, and A. Veves, Evaluation of a human skin equivalent for the
treatment of diabetic foot ulcers in a prospective, randomised, clinical trial.
Wounds, 1999. 11(4): p. 79-86.
Brem, H., J. Balledux, T. Bloom, M.D. Kerstein, and L. Hollier, Healing of
diabetic foot ulcers and pressure ulcers with human skin equivalent: a new
paradigm in wound healing. Arch Surg, 2000. 135(6): p. 627-34.
Veves, A., V. Falanga, D.G. Armstrong, and M.L. Sabolinski, Graftskin, a
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Vowden, P. and Vowden, K. (2002). Wound Bed Preparation (WBP). World
Wide Wounds. Available: Internet Journal www.worldwidewounds.com,
Version: Revision 1. Accessed on: April 2002.