5.

5 216 x 276 mm
mm

Wound Healing
Wound Healing, Second Edition
Annie Price, Specialist Registrar in Rehabilitation Medicine, Cardiff and Vale University Health Board, Cardiff, UK.
Joseph E. Grey, Consultant Physician, Cardiff and Vale University Health Board, Cardiff, UK.
Girish K. Patel, Consultant Dermatologist, Welsh Institute of Dermatology, Cardiff and Vale University Health Board,
Cardiff, UK and Honorary Professor, Cardiff University School of Biosciences, Cardiff University, UK.
Keith G. Harding CBE, Medical Director of the Welsh Wound Innovation Centre, Pontyclun, UK; Honorary
Consultant in Wound Healing, Cardiff and Vale University Health Board, Cardiff, UK; Professor of Wound Healing
Research, Cardiff University School of Medicine, Cardiff, UK; and Senior Clinical Research Director, Skin Research
Institute of Singapore, Singapore.

ABC of Wound Healing is a practical, highly illustrated guide to assessment, diagnosis and management of all

Wound Healing
common types of acute and chronic wounds. This concise yet comprehensive reference covers all essential
aspects of wound healing, including epidemiology, pathophysiology, assessment, treatment, long-term

SECOND EDITION
management, and prevention.
This revised second edition contains several new chapters on lymphoedema, nutrition, skin care, continence,
and scarring. Updated and expanded chapters cover a wider range of devices and therapies, and discuss
additional factors that impact wound healing processes, offering new clinical photographs as a visual guide.
Applying a multidisciplinary approach to the provision of wound care, ABC of Wound Healing:
• Covers common wounds including traumatic wounds, surgical wounds, diabetic foot ulcers, pressure
SECOND EDITION
injuries, and venous and arterial leg ulcers
• Emphasises the importance of reaching a diagnosis, the fundamental step in managing any wound
• Provides up-to-date information on medical, surgical and emerging treatments for patients with various
types of wounds
• Contains hundreds of full-colour illustrations and clinical photographs of wounds and treatments
Edited by Annie Price, Joseph E. Grey, Girish K. Patel,
ABC of Wound Healing, Second Edition, remains a must-have guide for junior doctors, specialist registrars in
medicine and surgery, specialist nurses, general practitioners and medical students.
and Keith G. Harding

Price I Grey I Patel I Harding

About the ABC series
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patient care, and remains an essential reference tool for GPs, junior doctors, medical students and
healthcare professionals.

Now offering over 80 titles, this extensive series provides you with a quick and dependable reference
on a range of topics in all the major specialties.

The ABC series is the essential and dependable source of up-to-date information for all practitioners
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www.wiley.com
Wound Healing
Wound Healing
Second Edition

EDITED BY

Annie Price
Cardiff and Vale University Health Board
Cardiff, UK

Joseph E. Grey
Cardiff and Vale University Health Board
Cardiff, UK

Girish K. Patel
Cardiff and Vale University Health Board
Cardiff, UK

Keith G. Harding CBE

Welsh Wound Innovation Centre
Pontyclun, UK
This edition first published 2022
© 2022 John Wiley & Sons Ltd

Edition History
Wiley-­Blackwell (1e, 2006)

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Library of Congress Cataloging-­in-­Publication Data

Names: Price, Annie (Of Welsh Wound Innovation (Organization)) editor. |
  Grey, Joseph E., editor. | Patel, Girish (Of Cardiff University) editor.
  | Harding, K. G. (Keith G.), editor.
Title: ABC of wound healing / edited by Annie Price, Joseph E. Grey, Girish
  Patel, Keith G. Harding.
Other titles: ABC series (Malden, Mass.)
Description: Second edition. | Hoboken, NJ : Wiley, 2022. | Series: ABC
 series
Identifiers: LCCN 2021028004 (print) | LCCN 2021028005 (ebook) | ISBN
  9780470658970 (paperback) | ISBN 9781118593844 (adobe pdf) | ISBN
  9781118593837 (epub)
Subjects: MESH: Wounds and Injuries–diagnosis | Wounds and
  Injuries–therapy | Ulcer–therapy | Wound Healing–physiology |
 Handbook
Classification: LCC RD93 (print) | LCC RD93 (ebook) | NLM WO 39 | DDC
 617.1–dc23
LC record available at https://lccn.loc.gov/2021028004
LC ebook record available at https://lccn.loc.gov/2021028005

Cover Design: Wiley

Cover Image: Courtesy of Professor Keith G. Harding

Set in 9.25/12pt Minion by Straive, Pondicherry, India

10 9 8 7 6 5 4 3 2 1
Contents

List of Contributors, vi
Foreword, viii
1 Wound Assessment, 1
Joseph E. Grey and Girish K. Patel
2 Traumatic Wounds, 9
Steven L.A. Jeffery and Stuart Enoch
3 Surgical Wounds and Surgical Site Infection, 14
Rhiannon L. Harries, Jared Torkington, and David Leaper
4 Burns, 20
Jonathan J. Cubitt and William A. Dickson
5 Diabetic Foot Ulcers, 26
Michael E. Edmonds and Annie Price
6 Venous and Arterial Leg Ulcers, 34
Joseph E. Grey and Girish K. Patel
7 Pressure Injuries, 41
Joseph E. Grey and Jacqui Fletcher
8 Uncommon Causes of Ulceration, 49
Girish K. Patel and Vincent Piguet
9 Infections, 56
Brendan Healy and Andrew Freedman
10 Lymphoedema and Wounds, 64
Christine Moffatt and Melanie Thomas
11 Nutrition, Skin Care and Continence, 71
Amy Ferris, Joseph E. Grey, and Girish K. Patel
12 Scars, 78
Paul Martin and Duncan A. McGrouther
13 Dressings and Devices, 85
Samantha Holloway, Stuart Enoch, and Joseph E. Grey
14 Drugs and Biological Approaches to Wound Healing, 94
Gregory Schultz and Girish K. Patel
Index, 102

v
 List of Contributors

Jonathan J. Cubitt Andrew Freedman

Consultant Burns and Plastic Surgeon Reader in Infectious Diseases
Welsh Centre for Burns and Plastic Surgery Cardiff University School of Medicine
Swansea Bay University Health Board Cardiff, UK
Swansea, UK Honorary Consultant Physician
(Chapter 4) Cardiff and Vale University Health Board
Cardiff, UK
(Chapter 9)
William A. Dickson MBE
Retired Consultant Burns and Plastic Surgeon
Welsh Centre for Burns and Plastic Surgery
Swansea Bay University Health Board Joseph E. Grey
Swansea, UK Consultant Physician
(Chapter 4) Department of Gerontology,
Cardiff and Vale University Health Board
Michael E. Edmonds Cardiff, UK
Consultant Physician (Chapters 1, 6, 7, 11, 13)
Diabetic Foot Clinic
King’s College Hospital
London, UK Rhiannon L. Harries
(Chapter 5) Consultant Colorectal Surgeon
Swansea Bay University Health Board
Stuart Enoch Swansea, UK
Professor, Higher Surgical Education (Chapter 3)
Directorate of Education and Research
Doctors Academy Group (Intl)
(Chapters 2, 13)
Brendan Healy
Consultant in Microbiology and Infectious Diseases
Amy Ferris Public Health Wales
Consultant Geriatrician Cardiff, UK
Cardiff and Vale University Health Board (Chapter 9)
Cardiff, UK
(Chapter 11)

Jacqui Fletcher OBE Samantha Holloway

Senior Clinical Advisor Reader
Stop the Pressure Programme Cardiff University School of Medicine
NHS England and NHS Improvement Cardiff, UK
(Chapter 7) (Chapter 13)

vi
 List of Contributors vii

Steven L.A. Jeffery Vincent Piguet

Consultant Burns and Plastic Surgeon Professor and Department Division Director
Royal Centre for Defence Medicine Dermatology, Department of Medicine
Birmingham, UK University of Toronto
Professor of Wound Study Toronto, Canada
Birmingham City University Division Head
Birmingham, UK Dermatology
Honorary Visiting Professor Women’s College Hospital
Cardiff University Toronto, Canada
Cardiff, UK (Chapter 8)
(Chapter 2)
Annie Price
David Leaper Specialist Registrar in Rehabilitation Medicine
Emeritus Professor of Surgery Cardiff and Vale University Health Board
University of Newcastle upon Tyne Cardiff, UK
Newcastle upon Tyne, UK (Chapter 5)
(Chapter 3)
Gregory Schultz
Paul Martin Emeritus Professor
Professor of Cell Biology University of Florida
Schools of Biochemistry and Physiology, Pharmacology & Neuroscience Gainesville, FL, USA
University of Bristol (Chapter 14)
Bristol, UK
(Chapter 12)
Melanie Thomas MBE
National Clinical Lead for Lymphoedema in Wales
Duncan A. McGrouther Lymphoedema Network Wales
Senior Consultant NHS Wales Health Collaborative, UK
Department of Hand and Reconstructive Microsurgery (Chapter 10)
SingHealth Duke-­NUS Academic Medical Centre
Singapore
(Chapter 12) Jared Torkington
Consultant Colorectal Surgeon
Christine Moffatt CBE Cardiff and Vale University Health Board
Cardiff, UK
International Professor of Clinical Nursing
(Chapter 3)
School of Social Sciences
Nottingham Trent University
Nottingham, UK
(Chapter 10)

Girish K. Patel
Consultant Dermatologist
Welsh Institute of Dermatology
Cardiff and Vale University Health Board
Cardiff, UK
Honorary Professor
Cardiff University School of Biosciences
Cardiff, UK
(Chapters 1, 6, 8, 11, 14)
 Foreword
The goal of treating wounds is to achieve healing and prevent sec-
ondary wound breakdown. Dressings have been used for thousands
of years and several notable medical advances have contributed to
better wound care. In the 1800s, Lister demonstrated the benefits of
antiseptic surgery in reducing infection risk and throughout the
18th and 19th centuries, debridement techniques were developed
and advanced by military surgeons. In the late 1800s, sterilised
gauze was mass-­ produced as ready-­ to-­
use surgical dressings.
George Winter’s observations in 1962, that wounds kept moist
healed faster than those kept dry, led to the development of many
new materials and advanced wound dressings. Over the past 60
years, there has been an explosion of treatments and current prac-
tice involves the use of dressings, devices, drugs, surgical interven-
tions and biologically based treatments to enhance wound healing.
Although a wide range of materials exists, the major benefits of
dressings are in managing exudate, minimising leakage and con-
trolling odour and pain. More recently, there has been a rapid
increase in the use of devices, from beds and mattresses that aim to
prevent and treat pressure injuries, to therapeutic footwear used in
diabetic foot disease and negative-­pressure devices for a range of
wound types. Drugs are often needed to assist in wound healing.
The most obvious example is the use of antibiotics for treating
wound infection. However, at a time when antimicrobial resistance
is seen as a global health challenge, greater understanding and
appropriate selection of agents to treat wound infection are urgently
needed. Surgery is an essential component for some wound healing
problems. This can range from simple draining of an abscess or
debridement of unhealthy tissue on the wound surface, through to
specialist vascular, orthopaedic or reconstructive procedures.
Advances in the understanding of wound healing biology have led
to an interest in biological therapies, from platelet concentrate to
stem cells.
While treatment advances are rapidly expanding the options for
wound care, recent studies have revealed that there are ongoing
viii
problems with wound assessment and diagnosis. Without
understanding the cause of the wound and appreciating factors that
contribute to delayed or non-­healing, successful treatment is less
likely. An emphasis on clinical assessment coupled with develop-
ments in wound diagnostics may help, but there is also a need for
greater engagement of medical specialties and their integration
with other members of a multidisciplinary team.
Complete healing of a wound is an obvious measure that should
be the goal of care when relevant. However, reduction in wound
size, pain, leakage and infection, or improvement in quality of life
could also be seen as measures of success in patients who do not
have the potential to heal their wounds. Similarly, prevention of
recurrence, avoidance of complications and provision of care in
dedicated settings should be seen as alternative measures of suc-
cess. There is a need to capture these factors when evaluating both
treatments and services.
Though scientific advances and enhancing the evidence base for
existing treatments are important, innovations in service provision
and education of healthcare professionals in the management of
wounds should not be underestimated. The future for individuals
with wound problems requires the ability to access a relevant and
capable multidisciplinary team that is appropriate for their needs.
Comprehensive, appropriate and patient-­centred wound care utilis-
ing evidence-­based treatments has the potential to benefit many. It
is only in recent years that the complexity of the wound healing
process and the wide range of factors that can influence healing
have been recognised. Greater funding and focus on this subject are
essential if the current situation is to be improved.
This new edition of the ABC of Wound Healing aims to take the
reader through these issues and provide a ready guide to the recog-
nition, investigation and management of a variety of wound types.
It is aimed at ensuring that individuals with wounds receive the
standard of care appropriate for modern-­day clinical practice.
Professor Keith G. Harding CBE
 CHAPTER 1

Wound Assessment
Joseph E. Grey1 and Girish K. Patel2,3
1
Department of Clinical Gerontology, Cardiff and Vale University Health Board, Cardiff, UK
2
Welsh Institute of Dermatology, Cardiff and Vale University Health Board, Cardiff, UK
3
Cardiff University School of Biosciences, Cardiff, UK

OVERVIEW
• Most wounds heal without difficulty, but all wounds have the
potential to become chronic.
• The key to successful wound management is diagnosis and
treatment of the underlying cause, which requires a detailed
history and assessment.
• Certain wound characteristics point to a specific diagnosis and
indicate the status of the wound, e.g. infected or clean, healing
or non-­healing.
• Many local and systemic factors may impede healing; these
should be identified and corrected where possible.
• Despite best practice, a small minority of wounds will never heal;
improving quality of life and preventing complications are the
treatment goals in these cases.
The majority of wounds, of whatever aetiology, heal without diffi-
culties (see Chapters  2–4). Some wounds, however, are subject to
factors that impede but do not prevent healing if managed appropri-
ately. In contrast, most common chronic wounds do not heal until
the underlying disease is adequately treated (see Chapters 5–8). A
minority of wounds do not heal despite best practice, where control
of symptoms and prevention of complications, rather than healing,
become the goals of treatment.
Complications of chronic wounds
• Sinus formation
• Fistula
• Unrecognised malignancy
• Malignant transformation in the ulcer bed (Marjolin ulcer)
• Osteomyelitis
• Contractures and deformity in surrounding joints
• Systemic amyloidosis
• Heterotopic calcification
• Colonisation by multiple drug-­resistant pathogens leading to
antibiotic resistance
• Anaemia
• Septicaemia
Approach to patients with wounds
In patients with wounds, it is important that the normal processes
of developing a diagnostic hypothesis are followed before attempt-
ing to treat the wound. A detailed clinical history should be taken,
along with an examination of the wound, surrounding skin and
(where relevant) the limb, and any appropriate investigations
should be performed. Seek to define the cause of the wound and
factors that might impede healing. In order to aid management,
regular wound assessments are used to monitor progress.
A systematic approach to wound assessment is helpful. The
­following factors should be considered as part of every wound
assessment.
Site of the wound
The site of the wound may aid diagnosis; diabetic foot ulcers often
arise in areas of abnormal pressure distribution caused by disor-
dered foot architecture. Venous ulcers mostly occur in the gaiter
area of the leg. Non-­healing ulcers, sometimes in unusual sites,
should prompt consideration of malignancy.
Size of the wound
This should be assessed at first presentation and regularly thereaf-
ter to monitor response to treatment and provide an indication of
healing. The simplest method is using a ruler to measure wound
dimensions (longest length and perpendicular width). Wound sur-
face area can be measured using an acetate tracing; the outline of
the wound margin is traced onto transparent acetate sheets marked
with 1 cm squares and the longest diameter in one plane is multi-
plied by the longest diameter in the perpendicular plane (for
approximately circular wounds) or the number of squares con-
tained within the wound outline are added together (for irregularly
shaped wounds). These methods are relatively subjective and can
be unreliable; accuracy is also affected by patient positioning, body
curvature or tapering of the limbs. More sophisticated methods
include using digitised area measurement software or laser tech-
niques, but these require training and specialist equipment. Clinical
photography should be carried out whenever possible.

ABC of Wound Healing, Second Edition. Edited by Annie Price, Joseph E. Grey, Girish K. Patel, and Keith G. Harding.
© 2022 John Wiley & Sons Ltd. Published 2022 by John Wiley & Sons Ltd.

1
2 ABC of Wound Healing

(a) (b)

(c) (d)

Common types of chronic wounds. (a) Venous leg ulcer. (b) Pressure injury. (c) Post-operative wound dehiscence. (d) Diabetic foot ulcer.

Causes of ulceration. Factors that impede wound healing.

• Vascular (venous, arterial, lymphatic, vasculitis) Local factors Systemic factors

• Neuropathic (e.g. diabetes, spina bifida, leprosy)
• Metabolic (e.g. diabetes, gout) • Inadequate blood supply • Advancing age and general immobility
• Connective tissue disease (e.g. rheumatoid arthritis, scleroderma, • Increased skin tension • Obesity
systemic lupus erythematosus) • Limited tissue mobility, e.g. • Smoking
• Pyoderma gangrenosum (often a reflection of systemic disorder) wound tethered by scarring • Malnutrition
• Haematological disease (red blood cell disorders, e.g. sickle cell disease; • Poor surgical apposition • Deficiency of vitamins and trace
white blood cell disorders, e.g. leukaemia; platelet disorders, e.g. • Wound dehiscence elements, e.g. scurvy
thrombocytosis) • Poor venous drainage • Systemic malignancy and terminal illness
• Dysproteinaemias (e.g. cryoglobulinaemia, amyloidosis) • Presence of foreign body and • Shock of any cause
• Immunodeficiency (e.g. HIV, immunosuppressive therapy) foreign body reactions • Chemotherapy
• Neoplastic (e.g. basal cell carcinoma, squamous cell carcinoma, • Continued presence of • Immunosuppressant medications, e.g.
metastatic disease) micro-­organisms and infection corticosteroids
• Infectious (bacterial, fungal, viral) • Excess local mobility, e.g. over • Inherited neutrophil disorders such as
• Panniculitis (e.g. necrobiosis lipoidica) a joint leucocyte adhesion deficiency
• Traumatic (e.g. pressure injury, radiation damage) • Previous radiotherapy • Impaired macrophage activity
• Iatrogenic (e.g. drugs) (malacoplakia)
• Dermatitis artefacta – self-­inflicted wounds
• Others (e.g. sarcoidosis)
the wound. Undermining of the edge of the wound must be identi-
fied by digital examination or use of a probe. The depth and extent
Depth of the wound of sinuses and fistulae should be identified. Undermining areas
Accurate methods for measuring wound depth are not practical or and sinuses should be packed with an appropriate dressing to
available in routine clinical practice. However, approximate meas- facilitate healing. Undermining wounds and sinuses with narrow
urements of greatest depth should be taken to assess the extent of necks that are difficult to dress can sometimes be laid open at the
 Wound Assessment 3

bedside to facilitate drainage and dressing. Wounds associated Laboratory investigations.

with multiple sinuses or fistulae should be referred for specialist
Investigation Rationale
surgical intervention.
Haemoglobin Anaemia may delay healing. May
also be an indicator of poor nutrition
Wound edge
(e.g. iron, B12 or folate deficiency)
Although not diagnostic, examination of the wound edge may help White cell count High count may indicate infection
to identify its aetiology in the context of the clinical history. All heal- Low count may reflect poor nutrition
ing wounds have a thin, shiny, tapered edge. Whereas venous leg Platelet count Thrombocytopenia may reflect bone
ulcers generally have gently sloping edges, arterial ulcers often appear marrow suppression and increased
risk of bleeding
well demarcated and ‘punched out’, and rolled or everted edges
Thrombocytosis may lead to
should raise the suspicion of malignancy. A biopsy should be taken increased small vessel thrombosis
from the edge of any suspicious wound. Erythrocyte sedimentation rate Non-­specific markers of infection/
(ESR); C-­reactive protein (CRP) inflammation. Useful in diagnosis
and monitoring treatment of
infectious/inflammatory ulceration
Clinical history Urea and creatinine High urea impairs wound healing.
Renal function important when
using antibiotics
• Ulcer duration
Albumin Protein loss delays healing
• Previous ulceration
Glucose, haemoglobin A1C Diabetes mellitus
• History of trauma Markers of autoimmune disease, Indicative of rheumatoid disease,
• Family history of ulceration e.g. rheumatoid factor, antinuclear systemic lupus erythematosus and
• Ulcer characteristics: antibodies, anticardiolipin other connective tissue disorders
◦◦ Site antibodies, lupus anticoagulant
◦◦ Pain Cryoglobulins, cryofibrinogens, Haematological disease
◦◦ Odour prothrombin time, partial
◦◦ Exudate/discharge thromboplastin time
Deficiency or defect of antithrombin Vascular thrombosis
• Underlying medical conditions including:
◦◦ Diabetes mellitus
III, protein C, protein S, factor V
Leiden
◦◦ Peripheral vascular disease
Haemoglobinopathy screen Sickle cell anaemia, thalassaemia
◦◦ Ischaemic heart disease, cerebrovascular accident
HIV status Kaposi sarcoma
◦◦ Neuropathy
Serum protein electrophoresis, Myeloma
◦◦ Connective tissue diseases, e.g. rheumatoid arthritis Bence-­Jones proteins
◦◦ Varicose veins Urinalysis Useful in connective tissue disease
◦◦ Deep venous thrombosis Wound swab Not routine. All ulcers colonised (not
• Previous venous or arterial surgery the same as infection). Swab only
• Smoking when clinical signs of infection
• Medications
HIV, human immunodeficiency virus.
• Allergies to drugs and dressings

with infection or non-­healing wounds. This can be treated by cau-

General principles of wound management
1 Diagnose and treat the underlying cause of the wound
2 Identify and correct factors that impede healing
3 Wash the wound (clean tap water for chronic wounds, sterile
water or saline for acute wounds)
4 Remove non-­viable tissue and debris
5 Choose a dressing appropriate for the level of wound exudate
(see Chapter 13)
Wound bed
Healthy granulation tissue is pink in colour and is an indicator of
healing. Unhealthy granulation tissue is dark red in colour, often
bleeds on contact and may indicate the presence of wound infec-
tion. Excess granulation or overgranulation may also be associated
tery with silver nitrate or topically applied steroid preparations. The
type of tissue at the base of the wound will provide useful informa-
tion relating to expectation of total healing time and the risk of
complications. For example, bone at the base of the wound may
suggest a protracted healing time and the possibility of underlying
osteomyelitis.
Necrotic tissue, slough and eschar
The wound bed may be covered with non-­viable, unhealthy tissue,
which can be classified as necrotic (dead) tissue, slough (immune
cells and debris, usually cream or yellow in colour) or eschar (dry,
black, hard necrotic tissue). The amount of necrosis and slough in
the wound is an indicator of the wound status. Necrotic tissue and
slough may be quantified as excessive (+++), moderate (++), mini-
mal (+) or absent (−). Since non-­viable tissue can harbour patho-
genic organisms and delay normal healing, it should be removed;
this is termed debridement.
4 ABC of Wound Healing

Surrounding skin
The surrounding skin may provide diagnostic clues as to the aetiol-
ogy of the wound; for example, the characteristic signs of chronic
venous insufficiency (see Chapter  6). Cellulitis associated with
wounds should be treated with systemic antibiotics. Eczematous
changes may need treatment with potent topical steroid prepara-
tions. Maceration of the surrounding skin is often a sign of the
inability of the dressing to control the wound exudate, which may
respond to more frequent dressing changes or change in dressing
type. Callus (hardened skin) surrounding and sometimes covering
neuropathic foot ulcers (e.g. in diabetes) must be debrided (see
Chapter 5).

Infection
All open wounds are colonised with bacteria. Bacteriological cul-
ture should be performed only if clinical signs of infection are pre-
sent or if there are issues of infection control to be considered (e.g.
methicillin-­resistant Staphylococcus aureus [MRSA], Panton
Valentine Leukocidin [PVL]-­secreting Staph. aureus). The classic
signs of infection are heat, redness, swelling and pain. Additional
Squamous cell carcinoma on the medial aspect of the knee – an unusual signs of wound infection include increased exudate, delayed heal-
location for a chronic leg ulcer. ing, contact bleeding and abnormal granulation tissue. Treatment
with antimicrobial therapy should be guided by microbiological
results and local resistance patterns (see Chapter 9).
Typical locations of some wound types.
Wound exudate
Site Type of ulcer
Loss of the epidermal barrier results in water loss presenting as exu-
Gaiter area of the leg Venous ulcer date. The quantity of exudate is usually classified as heavy (dressing
Sacrum, greater Pressure injury soaked; +++), medium (dressing wet; ++) or minimal (dressing
trochanter, heel dry; +). A moist (versus dry) wound environment promotes heal-
Dorsum of the foot Arterial ulcer, vasculitic ulcer
ing, but excessive exudate may be due to wound infection or
Shin Necrobiosis lipoidica diabeticorum, traumatic
ulcer oedema in the wound area and can delay healing. It can also macer-
Lateral malleolus Venous ulcer, arterial ulcer, pressure injury, ate the surrounding skin, leading to further breakdown. Exudate
hydroxyurea-­induced ulceration should be controlled using dressings appropriate for the level of
Plantar and lateral aspect Diabetic foot ulcer moisture, and any infection should be treated. Barrier films applied
of foot and toes
to the surrounding skin help prevent further maceration. The
Sun-­exposed areas Basal cell carcinoma, squamous cell carcinoma
oedematous leg should be elevated when seated.

(a) (b)

Methods of wound measurement. (a) Wound measurement using a ruler. (b) Wound measurement using acetate tracing.
 Wound Assessment 5

(a) (b)

The importance of probing a wound. (a) A small abdominal wound. (b) On examination with a probe, the wound is actually undermining by 2.5 cm in a cranial direction.

Wound edge characteristics.

Edges Type of ulcer

Transparent Epithelialising
White Macerated
Sloping Venous ulcer
Punched out Arterial/vasculitic ulcer
Rolled Basal cell carcinoma
Raised/thickened Squamous cell carcinoma
Undermining Pressure injury and ulceration, tuberculosis,
syphilis
Purple ± ragged edge Pyoderma gangrenosum or other inflammatory
disease (e.g. vasculitis)

Communication between pilonidal sinus wounds.

Odour
Malodour can be caused by infection, necrotic tissue and saturated
dressings. As well as treating the cause of malodour (e.g. debriding
necrotic tissue, treating infection), superabsorbent dressings or
charcoal dressings may be useful to control odour. Topical metroni-
dazole is useful for malodour associated with fungating tumours.

Pain
Pain is a characteristic feature of many healing and non-­healing
wounds. Pain can be caused by both nociceptive and neuropathic
stimuli. Intermittent pain is often related to dressing removal or
recent application of new dressings and may necessitate the use of
analgesia prior to dressing change. Constant pain may arise as a Healing edge of an abdominal wound. The size of the original wound is
result of the underlying condition, including ischaemia, neuropathy, evident by the amount of newly formed scar tissue present.
6 ABC of Wound Healing
tissue oedema, chronic tissue damage (e.g. lipodermatosclerosis),
infection or scarring (e.g. atrophie blanche). The nature and type of
pain should be identified and treated appropriately. Various pain
assessment tools are available to help assess the nature and severity
of pain. Patients with recalcitrant or difficult-­to-­control pain may
benefit from referral to a local pain team.
Non-­healing wounds
Non-­healing wounds have traditionally been defined as those that
fail to progress through an orderly sequence of repair in a timely
fashion. Such wounds are sometimes thought of as being caused by
neglect, incompetence, misdiagnosis or inappropriate treatment
Squamous cell carcinoma with raised edges.
(a)
Examination of the wound bed. (a) Healthy granulation tissue in a hidradenitis suppurativa excision. (b) Unhealthy granulation tissue in a diabetic foot ulcer.
strategies. However, it is important to appreciate and acknowledge
that some wounds are resistant to all efforts of treatment aimed at
healing and alternative endpoints should be considered. Measures
aimed at improving quality of life are paramount in these instances.
Quality of life
Several studies have shown that individuals with non-­ healing
wounds have a decreased quality of life. This is due to a multitude of
factors, including the frequency and regularity of dressing changes,
which cause disruption to daily routine, lack of sleep, restricted
mobility, pain, odour, wound infection and the physical and psycho-
logical effects of polypharmacy. The loss of independence associated
with functional decline can lead to changes, sometimes subtle, in
Dead tendon in the base of the wound (indicated by arrow).
(b)

(a)
(c)
Examination of the wound bed. (a) Necrotic tissue. (b) Slough. (c) Fibrin (scar tissue). (d) Eschar.
Types of wound debridement
1 Sharp – using a scalpel or curette at the bedside
2 Surgical – in the operating theatre using sharp or hydrosurgical
(high-­powered water jet) methods
3 Autolytic – facilitation of the body’s own mechanism of
debridement with moisture-­donating dressings
4 Biological – larval (maggot) therapy
5 Enzymatic – not widely used; paw-­paw or banana skin used in
developing countries
6 Mechanical – wet-­to-­dry dressings or debridement pads or wipes
7 Ultrasonic – low-­frequency ultrasound applied to wound bed
Wound Assessment 7
(b)
(d)
overall health and well-­being. These changes include altered eating
habits, depression, social isolation and a gradual reduction in activ-
ity levels. Many individuals with non-­healing wounds complain of
difficulties with emotions, finances, physical health, daily activities,
friendships and leisure pursuits.
Quality of life is not always related to ulcer healing. Patients’ con-
cerns and goals of treatment should be taken into consideration.
Control of odour, exudate and pain may improve an individual’s
quality of life. Additionally, optimisation of chronic wound manage-
ment will lead to a reduction in the frequency of dressing changes,
further enhancing quality of life. In a minority of instances, seem-
ingly drastic measures such as amputation in a person with chronic
leg ulceration may need to be considered where the quality of life is
severely affected by the non-­healing wound and its complications.
8 ABC of Wound Healing

(a) (b) (c)

(a) Pressure injury with extensive callus build-­up before debridement. (b) Sharp debridement using a ring curette at the bedside. (c) All callus has been removed
and healthy bleeding tissue is visible.

Larval debridement of a pressure injury. A non-­healing wound; this venous leg ulcer has been present for over
10 years and has not healed despite optimal treatment.

Common features of non-­healing wounds

• Absence of healthy granulation tissue

• Presence of necrotic and unhealthy tissue in the wound bed
• Excess exudate and slough
• Lack of adequate blood supply
• Failure of re-­epithelialisation
• Cyclical or persistent pain
• Recurrent wound breakdown
• Clinical or subclinical infection

Further reading
Falanga, V., Lindholm, C., Carson, P.A. et al. (eds.) (2012). Text Atlas of Wound
Management, 2e. London: Informa Healthcare.
Frykberg, R.G. and Banks, J. (2015). Challenges in the treatment of chronic
wounds. Advances in Wound Care 4 (9): 560–582.
Maceration of surrounding skin. Leaper, D.J., Schultz, G., Carville, K. et al. (2012). Extending the TIME con-
cept: what have we learned in the past 10 years? International Wound
Journal 9 (Suppl.2): 1–19.
Wounds UK (2018). Best Practice Statement: Improving Holistic Assessment of
Chronic Wounds. London: Wounds UK.
 CHAPTER 2
Traumatic Wounds
Steven L.A. Jeffery1,2,3 and Stuart Enoch4
1
Royal Centre for Defence Medicine, Birmingham, UK
2
Birmingham City University, Birmingham, UK
3
Cardiff University, Cardiff, UK
4
Directorate of Education and Research, Doctors Academy Group (Intl)
OVERVIEW
• Traumatic wounds are common and range from minor epithelial loss
that will heal spontaneously within a few days to extensive tissue
necrosis and degloving that require complex surgical treatment.
• Understanding the mechanism of injury helps guide wound
management.
• All traumatic wounds are contaminated to some degree; the risk
of infection is reduced by adequate cleaning and debridement.
• The reconstructive ladder is a useful framework for considering
methods of wound closure.
Since the evolution of our species, humans have been sustaining
traumatic injuries. In the fifth century BC, Hippocrates advocated
that wounds be bathed in water or wine, and that a suppurating
wound was a healing wound. In the early fourteenth century, Guy
de Chauliac proposed five wound management principles that have
stood the test of time.
Wound management principles
Removal of foreign bodies
Rejoining of severed tissues
Maintenance of tissue continuity
Preservation of organ substance
Prevention of complications
Mechanisms of injury
Traumatic wounds usually involve some loss or damage to an epi-
thelial surface (usually skin) but may also involve the underlying
connective tissue, with or without epithelial loss (e.g. contusion,
degloving or crush injury). Understanding the mechanism of injury
helps guide wound management. Traumatic wounds may be classi-
fied as superficial or deep, tidy or untidy, contaminated or not con-
taminated. They may be categorised as follows.
ABC of Wound Healing, Second Edition. Edited by Annie Price, Joseph E. Grey, Girish K. Patel, and Keith G. Harding.
© 2022 John Wiley & Sons Ltd. Published 2022 by John Wiley & Sons Ltd.
Abrasions are superficial epithelial wounds caused by frictional
scraping forces. When extensive, they may be associated with
fluid loss. Such wounds should be cleansed to minimise the risk
of infection and remove superficial foreign bodies (which can
result in unsightly ‘tattooing’). Abrasions can be covered with a
simple non-­adhesive dressing, if required, and are best left to
heal by re-­epithelialisation.
Lacerations occur when trauma exceeds the intrinsic tissue
strength, for example, when the skin is torn by blunt injury over
a bony prominence such as the elbow or the knee. The edges will
be irregular. Minimal tissue damage may be amenable to primary
suturing. Closure with adhesive strips (e.g. Steri-­Strips™) may be
appropriate in some circumstances, for example, simple linear
lacerations or a pretibial laceration. If post-injury oedema is
anticipated, primary suturing of the wound is not advisable since
this causes increased tissue tension and consequently risks
wound breakdown.
Penetrating trauma by a sharp point (e.g. a nail, bullet) may result in
minimal damage to skin and connective tissue but cause deeper
damage to vessels, nerves and/or internal organs. The visible skin
wound may be deceptive and hence a full exploration of the
wound is advisable. Penetration may carry dirty tissue deep into
the wound. In gunshot wounds, an exit wound may be present.
Contusions are caused by more extensive tissue trauma following
severe blunt or blast trauma. The overlying skin may appear to be
intact but later become non-­viable. Large haematomas under
skin or in muscle may be present. If superficial and fluctuant,
they can be evacuated with overlying necrotic tissues. Ultrasound
or magnetic resonance imaging scans may help to define a hae-
matoma amenable for evacuation. Extensive contusion risks
infection (antibiotic prophylaxis should be considered in open
wounds) and compartment syndrome (fasciotomy will be needed
to preserve the limb).
Bite wounds need special, urgent consideration because of the
degree of contamination and high risk of infection. The skin
injury could be a puncture wound, a laceration or an abrasion, or
a combination of these. There may also be deeper damage from a
crush injury. Humans and animals have high numbers of
9
10 ABC of Wound Healing
Pretibial laceration closed with adhesive strips.
Fasciotomy wound.
­ athogenic bacteria in their mouths and therefore human and
p residual defect.
animal bites carry a high risk of infection. Special attention
should be given to cleaning, irrigating and debriding these
wounds. Because of the risk of infection, there is concern about
when it is safe to primarily close these injuries and when they
should be left open. Nowadays it is thought to be relatively safe to
close bite wounds that are not deep, less than 24 hours old and
with little contamination. Human bites also carry the risk of viral
transmission, e.g. hepatitis B or C. Antibiotics should be pre-
scribed for 1 week. The tetanus status of the patient should be
determined and prophylaxis provided if needed.
Avulsion injuries and degloving: as with wounds from a blast injury,
these wounds are characterised by shearing of the skin and sub-
cutaneous tissues from the underlying fascia and muscle, with
disruption of the blood vessels where they perforate the fascia
before supplying the skin. The viability of the tissue should be
assessed, and non-­viable tissue excised. It is important not to
close these wounds under tension, as this will further reduce the
Management of bite wounds.
Safe to close Leave open after exploration and debridement
• <24 h old • >24 h old
• No signs of • Already showing signs of infection
infection • Deep puncture wound
• Superficial • Heavy contamination
• Light contamination • Crush injury
• Bites to the limbs, hands or feet
Degloving injury – avulsion of the skin from underlying tissue.
blood supply to the skin. Rather, such wounds should be left
open. Negative-­pressure wound therapy should be considered
(see Chapter 13).
Surgical incisions cause minimal tissue damage since they are usu-
ally made with precision and in an environment with appropriate
aseptic precautions. Controlled haemostasis and asepsis reduce
the risk of infection, leading to improved wound healing. Large
surgical wounds may be left open to heal by secondary intention
or with delayed skin grafting, depending on the extent of the
Management
Triage and resuscitation may be needed before definitive wound
management; this should be done according to the Advanced
Trauma Life Support® guidelines. Arterial bleeding is easy to recog-
nise (pulsatile and bright red) provided it is overt, but if it is hidden
from view, e.g. following penetrating injury to the aorta, it can lead
to profound unexpected haemorrhagic shock. Early exploration
and repair or ligation of blood vessels may be required. Venous
haemorrhage is flowing and dark red, and can usually be controlled
by adequate direct pressure. Capillary bleeding oozes and is bright
red; it can lead to shock if the injury is extensive and should not be
underestimated. All penetrating and traumatic wounds should be
explored if there is suspicion of blood vessel, nerve or organ dam-
age. Attention to fractures, debridement of devascularised tissue
and removal of foreign material may be required.

Contamination and debridement of traumatic
wounds
All traumatic wounds are contaminated and will contain a variable
amount of foreign material or dirt, depending on where and how
the wound was sustained. A knife wound may produce relatively
little wound contamination, whereas wounds sustained on the bat-
tlefield or in the farmyard will inevitably be heavily contaminated.
Patients with tetanus-­prone wounds should receive tetanus toxoid
vaccination +/– immunoglobulin. Patients with severely contami-
nated wounds should receive prophylactic broad-­spectrum antibi-
otics. Prior to wound debridement, all wounds should be cleaned of
particulate matter using soap and water.
The degree of debridement will depend on the extent of contami-
nation and the resources available. Large wounds should be assessed
and debrided under general anaesthetic. Photographs should be
taken in theatre to allow planning of further management without the
need for dressings to be taken down. 3D photography is particularly
Heavily contaminated traumatic wound.
Arm wound with tourniquet in place prior to debridement.
Traumatic Wounds 11
useful in recording complicated wounds. In limb wounds, tourniquet
control facilitates a bloodless field and effective excision of necrotic
and contaminating material.
Debridement should be performed systematically in layers: ‘Start
at the skin and work your way in’. The skin edges are best excised
using a scalpel. More mobile tissues, such as fat and muscle, are best
debrided using scissors. Debridement of material that is difficult to
pick up with forceps, such as sand or adventitial tissue, is best car-
ried out by hydrosurgical means.
Larger complex wounds are often uneven and contain numerous
pockets of foreign contaminated material, which may be forced
deep between tissue planes. Every such pocket must be explored
and included in the debridement. Once debridement is complete,
irrigation with at least 3 litres of warm saline should be performed,
prior to application of a dressing. High-­pressure irrigation is con-
traindicated as it further damages the tissues and drives foreign
material deeper.
12 ABC of Wound Healing

Dirt identified in bloodless field.

‘The solution to pollution is dilution’ – following debridement, wounds

should be irrigated thoroughly with warm saline.

Hydrosurgical debridement.

Wound closure
The ‘reconstructive ladder’ is a useful way of thinking about how to
close wounds. The simpler techniques are safest but may not give
the best result. Each rung of the ladder represents a more complex
type of wound closure. More complicated techniques may give a
better result, but the higher up the ladder, the worse the risk of fail-
ure. Decisions about wound management should take into account
local factors such as the location and size of the wound and mecha-
nism of injury, and patient factors such as comorbidities, expected
functional outcome, occupational circumstances and likely period
of time off work. Alternative treatments such as negative-­pressure
wound therapy and dermal matrices also have a role in reconstruct-
ing defects (see Chapter 14).
Timing of  wound closure  Clean, tidy wounds may be safely
closed within 6 hours of the injury. With the exception of the face,
hands and perineum, all other contaminated wounds should be left
open initially.
Debrided wound ready for dressing application.
Healing by secondary intention  Some wounds may be left
open to heal by secondary intention, i.e. by formation of granula-
tion tissue, re-­epithelialisation and wound contraction. Dressings
are used as a barrier and to optimise the environment for healing
(e.g. by absorbing excess exudate). This process is slow and can lead
to scarring and contractures.
Primary wound closure  Primary wound closure (approxima-
tion of wound edges) can be achieved by the following methods.
• Adhesive strips are useful in closing superficial wounds. They
allow for wound swelling and are associated with low infection
rates.
 Traumatic Wounds 13

are expensive but allow rapid closure of long wounds after pro-
Free tissue
transfers longed surgical procedures.
• Sutures are used to bring tissues together and to aid optimal
wound healing. The three important considerations for primary
Distant tissue
transfers
closure are the suture material, type of needle or appliance, and
the technique of closure (see Chapter 3). An adhesive polyure-
thane film dressing can be applied over sutured wounds to pro-
Local tissue transfers
vide a barrier to infection.

Skin graft Skin grafts  Where skin defects are too large for primary skin
apposition, and healing by secondary intention is inappropriate,
Direct tissue closure skin grafts may be used. Free skin grafts are taken from another
part of the body and rely on revascularisation from a healthy, well-­
Allow wound to heal by secondary intention
vascularised recipient wound bed. Split-­thickness skin grafts con-
sist of epidermis and a variable amount of dermis; the donor site is
The reconstructive ladder. left to heal by re-­epithelialisation. Full-­thickness skin grafts consist
of epidermis and dermis, with the donor site requiring primary clo-
sure, thereby limiting the size of graft that can be taken.

Skin flaps  Many wounds, such as fracture sites and exposed

bone or tendon, are not suitable for grafting, and techniques further
up the reconstructive ladder, such as a flap reconstruction must be
used. A flap is a unit of tissue that can be moved to cover a wound
while surviving on its own vascular supply. It may consist of differ-
ent tissue types, including skin, muscle, fat or bone. Local flaps are
moved (e.g. rotated or advanced) from an area adjacent to the
defect. Distant flaps can be pedicled (transferred whilst maintain-
ing its blood supply via one or more named blood vessels) or free
(detatched from its blood supply and reattached to vessels at the
recipient site using microsurgical techniques).
Both skin grafts and skin flaps require donor tissue, with the
additional risk of donor site complications such as infection, non-­
healing or scarring. Allografts (from cadaveric or living donors) or
xenografts (from animals, usually porcine) can be used when there
is not enough autologous tissue available, such as in severe burns.
These will usually be rejected by the host immune system but are
useful as a temporary cover.

Failed healing of donor site after harvesting of split-­thickness skin graft.

• Methacrylate ‘super-­glues’ are widely used for skin closure, par-
ticularly for the scalp. They can also be placed over the wound
edges following subcuticular suturing. They are usually contrain-
dicated in wounds with uneven edges, deep wounds and infected
wounds or bites.
• Metal clips and staples are alternatives to conventional suturing.
Despite their need for removal, they are associated with good
cosmetic results and low infection rates. Disposable applicators
Further reading
Clasper, J.C., Standley, D., Heppell, S. et al. (2009). Limb compartment syndrome
and fasciotomy. Journal of the Royal Army Medical Corps 155: 298–301.
Jeffery, S.L.A. (2009). Advanced wound therapies in the management of severe
military lower limb trauma: a new perspective. Eplasty 21: e28.
Jeffery, S.L.A. (2016). The management of combat wounds: the British mili-
tary experience. Advances in Wound Care 5 (10): 464–473.
Savage, J.M. and Jeffery, S.L.A. (2013). Use of 3D photography in complex-­
wound assessment. Journal of Wound Care 22 (3): 156–160.
Taylor, C.J. and Jeffery, S.L.A. (2009). Management of military wounds in the
modern era. Wounds UK 5 (4): 50–58.
 CHAPTER 3
Surgical Wounds and Surgical Site
Infection
Rhiannon L. Harries1, Jared Torkington2, and David Leaper3
1
Department of Colorectal Surgery, Swansea Bay University Health Board, Swansea, UK
2
Department of Colorectal Surgery, Cardiff and Vale University Health Board, Cardiff, UK
3
University of Newcastle upon Tyne, Newcastle upon Tyne, UK
OVERVIEW
• Surgical wounds are made in a sterile environment after
preparation of the skin using an antiseptic agent in order to
facilitate a surgical procedure.
• Varying methods of wound closure are available; there are many
factors to consider, including the site of the wound, the size of
the defect, the degree of contamination, etc.
• Surgical site infections (SSIs) are caused by many, often resistant,
organisms, usually derived from the patients themselves and
related to the site of surgery.
• Most SSIs are superficial but deeper infections can be life-­
threatening.
•  There is a focus on prevention of SSIs by identifying and
addressing risk factors.
A surgical wound is a cut or incision made to facilitate a surgical
procedure by using a cutting instrument such as a scalpel or dia‑
thermy. The size and location of the incision will be determined by
the source of the disease or injury being surgically treated, and con‑
sideration is given to the cosmetic outcome by favouring Langer’s
lines (corresponding to the natural orientation of collagen fibres in
the dermis), where possible.
Requirements for successful postoperative wound healing
Postoperative wound healing occurs only if certain principles are
followed:
• Absence of haematoma
• Absence of infection
• Accurate skin apposition
• Tension-­free apposition
ABC of Wound Healing, Second Edition. Edited by Annie Price, Joseph E. Grey, Girish K. Patel, and Keith G. Harding.
© 2022 John Wiley & Sons Ltd. Published 2022 by John Wiley & Sons Ltd.
14
Classification
Surgical incisions are made in a sterile environment after prepara‑
tion using an antiseptic agent (e.g. chlorhexidine, povidone‑iodine)
immediately prior to incision, in order to minimise infections.
Surgical wounds can be classified according to the degree of con‑
tamination, which helps predict the risk of subsequent infection
and its effect on wound healing.
Clean: clean surgical wounds with no evidence of inflammation or
infection. Also includes surgery involving the insertion of a pros‑
thesis. Examples include inguinal hernia repair, mastectomy,
cataract operation and thyroidectomy. Operations involving the
gastrointestinal, genitourinary and respiratory tracts are
excluded due to a higher risk of infection.
Clean-­contaminated: clean surgical wounds with a higher risk of
infection. These include operations involving controlled entry
into the gastrointestinal, genitourinary or respiratory tract (with‑
out spillage) and also aural or gynaecological surgery. Examples
include cholecystectomy (without spillage of bile), hysterectomy
and the insertion of grommets.
Contaminated: contaminated surgical wounds such as spillage from
the gastrointestinal tract or entrance into an infected genitouri‑
nary or biliary tract. Fresh traumatic wounds from a clean source
are included. Examples include colectomy and appendicectomy
for an inflamed appendix.
Dirty: dirty surgical wounds such as those with faecal contamination,
the presence of foreign bodies, devitalised tissue, bacterial inflam‑
mation or perforated viscus. Traumatic wounds either from a dirty
source or non-­ acute (>24 hours old) are included. Examples
include abscess drainage and laparotomy for faecal peritonitis.
The risk of wound infection varies from 0.5–2% for clean cases to
up to 40% for dirty cases. Prophylactic antibiotic administration is
recommended for contaminated and dirty cases. Antibiotic usage is
at the discretion of the surgeon for clean operations but it may be
indicated for certain cases, such as implant insertion. Antibiotics
must be administered 30 minutes prior to induction of anaesthesia
 Surgical Wounds and Surgical Site Infection 15

for maximal benefit. Antibiotic choice should be based on the

organism most likely to be the cause of a wound infection related to
the type of operation.

Wound closure
Surgical wounds can be closed by either primary or secondary
intention.
Primary intention: a wound closed by approximation of the wound
edges or by placement of a skin graft or flap in order to facilitate
the biological event of healing, by joining together the wound

Groin wound left open to heal by secondary intention.

Timings for removal of non-­absorbable sutures.

Site of sutures Number of days

Scalp and face 3–4

Upper limb 7
Lower limb 7–10
Over a joint 14
Primary closure using interrupted sutures. Trunk 10–14

edges and eliminating the dead space. Careful epidermal align‑
ment and eversion of the edges reduce scar formation. Primary
closure of a wound is suitable for acute (less than 24 hours dura‑
tion) clean wounds with tension-­free, well-­vascularised wound
edges.
Secondary intention: a wound left open to close via epithelialisation
and contraction. Secondary closure of a wound is advocated for
management of contaminated or infected wounds, or where
wound edges may be under tension if approximated.
A contaminated wound may be closed at 48 hours if there is no
ongoing evidence of infection (termed delayed primary closure).
Sutures
Primary closure is often performed using sutures, and can be
achieved by a variety of different suture materials and suturing
techniques. The ideal suture material needs a high breaking
strength, to be handled comfortably and to knot securely, with min‑
imal tissue reaction and bacterial growth. Suture choice is decided
based on both suture properties and patient factors.
Sutures can be either absorbable (e.g. polydioxane, polyglactin,
poliglecaprone) or non-­ absorbable (e.g. nylon, polypropylene).
Absorbable sutures provide temporary support and thereafter are
absorbed at varying rates. They are often used internally but do
have an advantage for skin closure in certain patients such as
children, as they do not require removal. Non-­absorbable sutures
require removal; the duration is dependent on the location of the
incision. While they do not absorb, some lose tensile strength over
time. Sutures should be removed using a method that prevents the
external part of the suture passing through the suture tracts to
avoid the introduction of infection.
Sutures are either monofilament or braided. Monofilament
sutures are made of a single strand, resist colonisation by micro-­
organisms and cause less tissue reaction compared to braided
sutures. Braided sutures are made of multiple strands braided or
twisted together and are easier to handle than monofilament
sutures. Antibacterial impregnated sutures are also commercially
available.
Size of suture thread is classified as a fraction of gauge 0.
Thinner sutures (e.g. 5/0) are used for skin closure on the face and
thicker sutures (e.g. 2/0) can be used for skin closure on the trunk.
Thinnest Thickest
8/0 6/0 4/0 2/0 0 2
Sizes of suture thread, classified as a fraction of gauge 0.
Needles are classified according to their type and shape, and their
choice is dependent on the tissue being sutured, gauge of needle
16 ABC of Wound Healing

Examples of suture materials.

Suture Material Synthetic/natural Braided/monofilament Absorbable/non-­absorbable

Monocryl® Poliglecaprone Synthetic Monofilament Absorption 90–120 d

Vicryl® Polyglactin 910 Synthetic Braided Absorption 56–70 d
PDS® Polydioxanone Synthetic Monofilament Absorption 180–210 d
Sofsilk™ Silkworm cocoons Natural Braided Absorption 2 yr
Surgipro™ Polypropylene Synthetic Monofilament Non-­absorbable
Ethilon® Nylon-­polyamide Synthetic Monofilament Non-­absorbable

Cross
section
Round bodled needles for
peritoneum, muscles, and fat
Cross Cross
section Cutting needles for aponeurosis
section
Cutting needles for stitching skin Needles used for suturing the Needles used for suturing the bowel
abdominal wall The threads are swaged into the needles

Types of needles used for different surgical procedures. Straight needles and hand needles are rarely used due to the added risk of needlestick injury. A cutting
needle has three edges with the cutting edge on the concave surface; it is suitable for tissue penetration and should be chosen for suturing skin. A reverse
cutting needle has the cutting edge on the inferior aspect of the needle. A round-­bodied, or tapercut, needle is shaped so the tip pierces and the needle then
separates the tissues and should be used for anastomosis. A blunt needle has a rounded end to avoid splitting tissues and is used for fascial closure.

1/4 circle 3/8 circle 1/2 circle

5/8 circle

Compound
J needle
curve

Straight
1/2 curved

Shapes of needles used in wound closure.

used, operative accessibility and surgeon preference. The needle
type is based on the cross-­sectional appearance.
A number of suturing techniques exist, and are dependent on
location of the incision, patient factors and surgeon choice. Knots
should be tied snug but not too tight as the skin is likely to swell as
a result of inflammation.
Other methods of primary closure
Primary closure may also be achieved by other methods includ‑
ing surgical staples, adhesive strips or adhesive glue. Surgical
staplers allow rapid closure of long wounds (e.g. laparotomy
incisions), but they require subsequent removal. Other forms of
surgical staples are also commonly used for bowel anastomosis
and gastric and lung resections. Skin adhesives (e.g. cyanoacr‑
ylate) are topically applied to easily approximated skin edges
where haemostasis is already achieved. The adhesive remains
liquid until exposed to water or water-­containing tissues, when
it polymerises and forms a bond. The skin adhesive acts as a
barrier to microbial penetration. Adhesive strips are useful for
closure of small superficial wounds and are applied across
the  wound in a manner that brings the skin on either side of
the  wound together. Durability of the adhesive strips can be
 Surgical Wounds and Surgical Site Infection 17

Interrupted
simple

Continuous
simple

Continuous
blanket (b)

Interrupted and
continuous
horizontal
mattress

Interrupted
longitudinal
mattress
(c)
Halsted’s stitch
(a) Suture techniques for closing skin. (b) Simple and mattress
closure. (c) Subcuticular closure.
(a)

A healed laparotomy wound closed with subcuticular sutures.

Dehiscence of an abdominal wound closed with staples.

compromised if they get wet. Skin adhesives or adhesive strips

may be an ideal choice for superficial lacerations, particularly in Some surgeons advocate the use of skin adhesives in place of a post‑
children. operative dressing.

Dressings
A postoperative dressing is chosen based on its ability to act as
an  effective barrier to bacterial contamination, allow gaseous
exchange, function as a waterproof barrier and allow wound moni‑
toring. It should be low-­adherent for easy non-­traumatic removal.
Surgical site infection
Surgical site infections (SSIs) are caused by many, often resistant
organisms usually derived from the patients themselves and related
to the site of surgery. Staphylococcus aureus is the most common
18 ABC of Wound Healing

organism causing SSI overall, whereas infections involving pros‑ Factors implicated in a higher risk of surgical site infection.
thetic materials, such as joint replacements or vascular grafts, are
Patient factors Demographics: age, sex
caused mainly by multiply resistant coagulase-­negative staphylo‑ Smoking
cocci. Exogenous pathogens from air-­borne microbes, the surgical Nutritional indices including obesity
team or suboptimal sterilisation of instruments can be infrequent Metabolic factors: diabetes, hepatorenal failure,
sources of contamination of the surgical site. low haemoglobin
Preoperative Nasal decontamination
At least 5% of patients undergoing open surgery develop an SSI.
factors Mechanical bowel preparation
They can range from a relatively trivial, short-­lived, wound dis‑ Skin preparation (surgical team’s hands, patient’s skin)
charge (e.g. after open hernia surgery) to being life-­threatening Operative factors Previous surgery
(e.g. mediastinitis and sternal wound dehiscence), and are associ‑ Antiseptic-­impregnated incise drapes
ated with over a third of postoperative related deaths. SSIs also Length and complexity of operation
Operating surgeon
increase the duration of hospital stay and can affect patients’ quality
Blood loss
of life, for example by causing cosmetically unacceptable scarring. Antimicrobial sutures
The costs to healthcare are large and have prompted many initia‑ Diathermy
tives, associated with extensive international media and political Postoperative Antiseptic lavage of wounds and cavities
campaigns, which aim to reduce the risk of SSI through attention to factors Antimicrobial dressings
Supplemental oxygen in recovery
risk factors.
Other factors Theatre environment
observed but Preoperative showering
Definitions of SSI with varying Theatre wear
The most widely used and most comprehensive definition is that levels of evidence Minimising movement in the operating theatre
proposed by the Centers for Disease Control and Prevention Banning jewellery and nail polish
Drapes and gowns
(CDC), but this only gives categorical data, which does not reflect
Wound drainage
the severity of an SSI. Broadly, there are three categories: superficial
incisional, infection in the skin or subcutaneous tissues; deep inci‑ The relevance of many of these factors needs revisiting with adequate trial
sional, where infection involves fascia or muscle; and deep/organ design.
space, with infection in, for example, the pleura after lung surgery
or the liver after hepatic resection. Most SSIs fall into the superficial
group and the less common deep/organ space infections are the
most serious or life-­threatening.
Surveillance is equally critical. The CDC requires that SSI sur‑
veillance should be undertaken for 30 days after soft tissue surgery
and up to a year after orthopaedic and vascular prosthetic opera‑
tions. The uptake of day case, fast track and enhanced recovery
after surgery has affected the accuracy of surveillance, which was
mostly based on inpatient data. The majority of SSIs have a mean Postoperative wound dehiscence caused by surgical site infection. The
time to presentation of 8–10 days and often present after the patient resulting wound is now clean and suitable for treatment with negative-­
has been discharged. pressure wound therapy (see Chapter 13).

Prevention of SSI – other evidence and risk
factors
Many other factors can potentially influence the incidence of SSI.
Being male or being elderly is associated with an increased risk of
SSI and obesity is an important, independent risk factor. Many
patient-­
related factors, including smoking, immunosuppressive,
nutritional, and metabolic factors, have a supportive experimental
base, which has not been proven in clinical trials.
Nasal decontamination (suppression) was introduced to reduce
the risk of methicillin-­resistant S. aureus (MRSA) and, although
not widely recommended, there is now evidence that this can
reduce SSIs. Mechanical bowel preparation has, controversially, not
been shown to reduce the risk of SSI, although there is evidence
that when combined with oral and systemic antibiotic prophylaxis,
it does reduce SSI after elective colon resection. Chlorhexidine in
2% alcohol has been shown to significantly reduce superficial and
deep SSIs after skin preparation.
In view of the continued rise of antibiotic resistance, the use of
antiseptic dressings and prophylactic antiseptic lavage of wounds
and cavities would benefit from reconsideration in future clinical
trials, as well as for treatment of established SSIs. Evidence that the
use of antimicrobial sutures can reduce SSIs is increasing; this has
been found in clean, prosthetic, abdominal and thoracic surgery.
Treatment of established SSI
The essentials of treating superficial and deep SSIs are to open the
area of infection and to drain pus. The open wound needs specific
wound care to allow healing by secondary intention, although
delayed primary or secondary closure may be feasible. Negative-­
pressure wound therapy may be useful in specific cases. Most
superficial and deep SSIs do not require antibiotics when drainage
and debridement are prompt. Antibiotics are warranted when
local cellulitis or wound necrosis is present. Organ/space infec‑
tions may require more aggressive measures with debridement,

and intra-­abdominal abscesses may require percutaneous drain‑
age procedures. Infected prostheses generally require removal,
although infections of vascular grafts, heart valves and prosthetic
joints pose special problems.
Further reading
Fry, D.E. (2002). The economic costs of surgical site infection. Surgical
Infections 3 (Suppl 1): S37–S43.
Horan, T.C., Gaynes, R.P., Martone, W.J. et al. (1992). CDC definitions of noso‑
comial surgical site infections, 1992 : a modification of CDC definitions of
Surgical Wounds and Surgical Site Infection 19
surgical wound infections. Infection Control and Hospital Epidemiology
13: 606–608.
Kirk, R.M. (2010). Basic Surgical Techniques, 6e. London: Churchill
Livingstone.
National Institute for Health and Care Excellence (NICE). (2008). Surgical site
infections: prevention and treatment. www.nice.org.uk/guidance/ng125
Scottish Intercollegiate Guidelines Network (SIGN). (2008). Antibiotic
prophylaxisinsurgery.www.sign.ac.uk/our-­guidelines/antibiotic-­prophylaxis-
­in-­surgery/
Smith, F., Dryburgh, N., Donaldson, J. et al. (2013). Debridement for surgical
wounds. Cochrane Database of Systematic Reviews 5 (9): CD006214.
 CHAPTER 4
Burns
Jonathan J. Cubitt and William A. Dickson
Welsh Centre for Burns and Plastic Surgery, Swansea Bay University Health Board, Swansea, UK
OVERVIEW
• Burns can occur from multiple sources; flame burns and scalds are
the most common mechanisms in adults and children respectively.
• The severity of a burn injury is related to the total body surface
area involved and the depth of the burn.
• Deeper burns usually require surgical intervention to reduce
healing time and prevent excessive scarring.
• Burn injuries can have systemic effects such as fluid loss and
infection.
• Strategies to reduce the incidence of burns are key.
A burn is an area of tissue necrosis caused by the transfer of energy
from a source to the tissue (thermal, electrical or radiation burns) or
due to the destructive properties of acids or alkalis (chemical burns).
Approximately 250 000 people are burnt in the UK each year. Of
these, 10% will require hospitalisation and 1% will be burnt enough
to threaten their life. About 200 people die each year from burns.
The current burns service in the UK is composed of burns facili-
ties, units and centres, with ability to deal with an increasing sever-
ity of all types of burns. The thresholds for transfer and the referral
guidelines are outlined on the British Burn Association website
(www.britishburnassociation.org/referral-­ guidance) with similar
guidelines in Australia and America (www.anzba.org.au; www.
ameriburn.org).
Mechanism of burn
Burns can occur from multiple sources.
Thermal injury
The depth of burn is related to the temperature of the source and
the duration of exposure.
Flames are very hot and cause deep/full-­thickness burns. They are
commonly associated with accelerants including petrol, lighter
fluid or gas.
ABC of Wound Healing, Second Edition. Edited by Annie Price, Joseph E. Grey, Girish K. Patel, and Keith G. Harding.
© 2022 John Wiley & Sons Ltd. Published 2022 by John Wiley & Sons Ltd.
20
Scald injuries, where the heat from hot fluids is dispersed very
quickly, often result in a partial-­thickness burn. Scalds account
for 60% of burns in children.
Contact burns often present as small burns on extremities, but
they can be serious in those not able to remove themselves from
the source of injury, e.g. children, elderly, disabled, those with
certain medical conditions or incapacitated by drugs or
alcohol.
Flash burns are caused by explosive ignition of a volatile substance
or flash from an electrical short circuit. The duration of exposure
to the high temperature is short and results in superficial burns
to unprotected areas such as the face and upper limbs. In addi-
tion, the flash may ignite clothing and cause flame burns.
Electrical injury
The pattern and extent of electrical injury are related to the
voltage.
Low voltage (household or industrial, 240–415 V) usually gives a
deep burn at the entry (contact) point and exit point of the elec-
tricity. The household alternating current may lead to cardiac
arrhythmias or cardiac arrest as it crosses the myocardium.
High voltage (>1000 V) is encountered in high-­tension transmis-
sion cables, substations or power stations. As the current travels
through the patient, it takes the route of least resistance and
can  cause unseen deeper tissue damage that may be life-­or
limb-­threatening.
Lightning is an ultra-­high-­tension, high-­amperage, short-­duration
discharge of electrical current that has an extremely high mortal-
ity with direct contact.
Chemical injury
Chemicals cause tissue necrosis by protein denaturation.
Acids cause a coagulative necrosis that forms a necrotic eschar that
limits the extent of the burn. These burns may be painful.
Copious irrigation with water is required as part of the first aid
for acid burns, to dilute and remove the chemical. Hydrofluoric
acid can cause systemic problems due to sequestration of calcium
 Burns 21

in the burn and needs to be treated with topical or systemic cal- cleaning products (e.g. drain unblocker) or cement are seen most
cium gluconate as soon as possible. commonly. Often the onset of pain is delayed, which may delay
Alkalis cause a liquefactive necrosis that allows the alkali to pene- first aid and cause more tissue damage. Similarly to acid burns,
trate deeper into the tissues. Alkali burns from caustic household copious irrigation is the first aid needed for alkali burns.

Burn aetiology by age. Radiation injury

Ionising radiation causes burns by the destruction of protein and
Adults Children the depth of tissue penetration and therefore the degree of damage
is proportional to the wavelength of the radiation and length of
Flame (48%) Scalds (60%)
Scalds (33%) Flame (25%)
exposure. Ultraviolet radiation causes sunburn and is the most
Contact (8%) Contact (10%) common example of radiation burn.
Electrical (5%) Electrical (2%)
Chemical (3%) Chemical (2%)
Friction (2%) Sunburn (1%) Burn assessment
Sunburn (1%)
The severity of burn injury is related to the total body surface area
Adapted from the manual for the “Emergency Management of Severe involved and the depth of the burn. The percentage body surface
Burns” course run by the British Burns Association. area is assessed using the Lund and Browder chart. The relative size

(a) (b)

(c) (d)

(a) Full thickness flame burn to lower limbs. (b) 'Pull over' scald (hot tea) to a toddler. (c) Contact burn to the palm of the hand. (d) Flash burn and erythema to
the face (note sparing of skin creases).
22 ABC of Wound Healing

of the head to the limbs varies with age, with children having pro-
portionally larger heads than adults. As the percentage total body
surface area of the burn increases, so do the general systemic effects
of the burn and the mortality rises.
The assessment of burn depth quantifies the amount of dermis
that remains and therefore the ability of the burn to heal with con-
servative management. Erythema represents epidermal damage
and is not included in the burn assessment. There are two broad
categories of burn depth: partial thickness and full thickness.
Partial-­thickness burns are further subdivided by the amount of
dermis that has been damaged. Superficial partial-­ thickness
burns (painful, blistered, pink) extend into the papillary dermis
and deep partial-­ thickness burns (blotchy red, less painful)
extend into the reticular dermis. Deeper burn injuries take
longer to heal without intervention and result in worse scarring.
Full-­thickness burns (leathery white or charred black) involve all
layers of the skin. These burns will not heal without intervention
unless they are very small.
Burns are not homogeneous and different depths can exist within
the same wound. Burn wounds are dynamic and due to the under-
lying pathophysiology, the depth may progress and therefore they
need to be assessed again at 48 hours.
Management of burn injuries
Immediate management and first aid
Remove the source of the burn; extinguish flames, switch off elec-
tricity, move the patient.
Assess the extent of injuries and treatment priorities using an
ABCDEF approach.
Reduce the temperature of the burn using cool running tap water
for 20 minutes (taking care to avoid hypothermia).
Cover the burn using a simple temporary dressing, polyvinyl chlo-
ride sheeting (‘cling film’) or sterile burn cooling gel.
Protocol for managing burn injuries

A = Airway and C Spine Control

B = Breathing
C = Circulation
D = Disability
E = Exposure and Environmental Control
F = Fluid Resuscitation

Wound management
Blisters should be deroofed, dead skin removed and burns cleaned
with mild soap and water, sterile saline or topical antiseptic solu-
tion. Superficial partial-­thickness burns should heal with dressings
alone. Deep partial-­thickness and full-­thickness burns generally
require surgery as they take a prolonged time to heal and do so with
Electrical burn. severe scarring.

(a) (b)

Chemical burns. (a) Acid burns to the hands. (b) Alkali burns to the knees.
 Burns 23

LUND AND BROWDER CHART

IGNORE
SIMPLE ERYTHEMA

A A
1
1

2 2 2 2
13 13 Superficial
Deep
112 112 112 112
REGION %

1 1
1 1
1 1 1 1 1 HEAD
2 2 2 2 2 2 2 1 2
1 NECK
ANT. TRUNK
B B B B POST. TRUNK
RIGHT ARM
LEFT ARM
BUTTOCKS
C C C C
GENITALIA
RIGHT LEG
3 3 3 3 LEFT LEG
14 14 14 14
TOTAL BURN

RELATIVE PERCENTAGE OF BODY SURFACE AREA AFFECTED BY GROWTH

AREA AGE 0 1 5 10 15 ADULT

A – ½ OF HEAD 9½ 8½ 6½ 5½ 4½ 3½
B – ½ OF ONE THIGH 2¾ 3¼ 4 4½ 4½ 4¾
C – ½ OF ONE LEG 2½ 2½ 2¾ 3 3¼ 3½

A Lund and Browder chart is useful for assessing the extent of burn injury (the relative proportions of body areas differ in children).

Dressings non-­adherent layers such as paraffin gauze (e.g. Jelonet®),
chlorhexidine-­impregnated gauze (e.g. Bactigras®), soft silicone
(e.g. Mepitel®) or soft polymer (e.g. UrgoTul®) are commonly used
with layers of gauze or gamgee to absorb exudate. Hydrocolloid
dressings (e.g. Duoderm®) absorb exudate and create a moist
environment to allow wound healing.
Alternative dressings, such as alginates, adhere to the wound and
separate off once the wound has healed. These dressings only adhere
to superficial partial-­ thickness burns and require a check at
24–48 hours to ensure that they have stuck, thereby confirming the
burn depth. Larger areas of superficial partial-­thickness burns can be
treated with synthetic epidermal substitutes (e.g. Biobrane®), which,
like the alginate dressings, adhere to the wound until it has healed.
Silver-­based products (e.g. Flamazine® or Flammacerium®) can
be applied to deeper burns to prevent infection whilst awaiting
surgery or if surgery is not appropriate. These dressings should
not be applied prior to review by a specialist burns team as they
complicate subsequent burn assessment.
Surgery at surgery, the burnt tissue is tangentially excised down
to healthy tissue. The resulting defect is reconstructed using
skin grafts taken from non-­burnt areas of the patient. If the
patient does not have adequate donor skin then cadaveric
a­ llograft skin or artificial skin substitutes can be used as a tem-
porary biological dressing. In the context of mixed depth
burns, particularly in important functional areas like the
hands, enzymatic debridement (e.g. Nexobrid®) can be utilised
to try to preserve as much viable dermis as possible and there-
fore improve the overall scarring.
Inhalational injury
The presence of an inhalational injury greatly increases the mortal-
ity of a burn. Facial burns, singeing of nasal hair and soot in the
oropharynx are indicators of possible inhalational injury and the
patient must be assessed by an anaesthetist prior to transfer to a
burns service, as early intubation may be required. Bronchoscopy
can be used to evaluate the severity of the inhalational injury and
enables the intensivist to wash out some of the soot and other prod-
ucts of combustion.
Circumferential full-­thickness burns
Full-­thickness burns are inelastic and may lead to respiratory dis-
tress on the chest or vascular compromise in the limbs. These
burns should be released with escharotomies to allow breathing or
24 ABC of Wound Healing

Superficial partial thickness Deep partial thickness Full thickness

Epidermis
le

land
follic

Nerve

Sweat g
Hair

Dermis

Blood vessels

Subcutaneous
tissue

Burn characteristics Pale pink Blotchy red White

Small blisters Possible blisters No blisters
Capillary refill No capillary refill No capillary refill
Painful Altered sensation No Sensation

Examples of different burn depths, correlating to the cross-­section of the skin.

perfusion of the limb. This may need to be carried out prior to
transfer for specialist care. Advice should be sought from the burns
service.
Fluid resuscitation
Burns greater than 15% total body surface area in adults and 10%
total body surface area in children require intravenous fluid
resuscitation to combat the systemic effects of the burn. The
Parkland Formula is used to calculate the volume of fluid needed;
50% is given in the first 8 hours following the burn and 50% is
given in the subsequent 16 hours.
The patient should be catheterised and the urine output should
be at least 0.5 mL/kg/h. The patient may require extra fluid to
ensure this urine output. Paediatric patients require maintenance

A Biobrane suit for a child with superficial partial-­thickness burns.

 Burns 25

(a)

A full thickness circumferential burn on the lower limb. An escharotomy has

been performed to maintain distal vascular supply.

(b)

(a) A full thickness torso burn which is restricting ventilation. (b) Chest
escharotomies being performed to release a shield of skin and allow ventilation.

fluids (4% glucose in 0.25% normal saline) in addition to the resus-

citation fluids to prevent hypoglycaemia.

Parkland formula

3–4 mL Hartmann solution/kg body weight/% total body surface area

Complications of burns
Early complications of burns include infection and, particularly in
children, toxic shock syndrome. Patients and parents should be
made aware of such risks if discharged, to ensure medical help is
quickly sought if these complications arise. All burns are tetanus-­
prone wounds and vaccination status should be ascertained and
updated as necessary.
Late complications of burns include hypertrophic scarring and
contractures, which may need further surgery in the future to
improve the functional and cosmetic outcome for the patient. Hypertrophic scarring.

Prevention of burns
Prevention of burns is key. The main improvement in reduction of
burns in the UK over the past 40 years has been the introduction of
legislation to reduce the flammability of clothing and furniture,
restrict the sales of fireworks and enforce the proper labelling of
flammable and hazardous materials.
Further reading
British Burn Association. (2012). National Burn Care Referral Guidance.
www.britishburnassociation.org/wp-­content/uploads/2018/02/National-­
Burn-­Care-­Referral-­Guidance-­2012.pdf
Herndon, D. (2017). Total Burn Care, 5e. Edinburgh: Elsevier Saunders.
Sood, R. and Achauer, B.M. (2006). Achauer and Sood’s Burn Surgery:
Reconstruction and Rehabilitation. Philadelphia: Elsevier Saunders.
 CHAPTER 5
Diabetic Foot Ulcers
Michael E. Edmonds1 and Annie Price2
1
Diabetic Foot Clinic, King’s College Hospital, London, UK
2
Cardiff and Vale University Health Board, Cardiff, UK
OVERVIEW
• Diabetic foot ulcers are common and associated with significant
morbidity and mortality.
• Diabetic foot ulcers can be classed as neuropathic or
neuroischaemic, depending on the vascular status of the limb.
• Debridement of callus is important to demonstrate the extent of
the ulcer and prevent further damage.
• Infection is common and ulcers that probe to bone are often
associated with underlying osteomyelitis.
• Successful treatment requires a multidisciplinary approach, but
recurrence is common.
Diabetic foot ulcers are associated with significant morbidity and
mortality, with high rates of infection and high risk of amputation.
Around 15–25% of people with diabetes will develop a foot ulcer in
their lifetime. Strategies aimed at prevention of foot ulcers are cru-
cial and require integrated care, regular monitoring and education
of the patient and their family.
Diabetic foot ulcers can be divided into two groups: those in
neuropathic feet, so-­called neuropathic ulcers, and those in feet
with ischaemia associated with neuropathy, so-­called neuroischaemic
ulcers. The crucial difference between the two types of feet is the
absence or presence of ischaemia due to peripheral artery disease.
Purely ischaemic ulcers are rare, usually painful and occur in the
critically ischaemic foot. Ischaemia may be confirmed by a low
pressure index (e.g. ankle-­brachial pressure index [ABPI] <0.9) (see
Chapter 6).
As many diabetic patients have medial arterial calcification, giv-
ing an artificially elevated ankle systolic pressure, it is also important
to examine the Doppler arterial waveform. The normal waveform is
pulsatile with a positive forward flow in systole followed by a short
reverse flow and a further forward flow in diastole (triphasic), but in
the presence of arterial narrowing the waveform shows a reduced
forward flow and is described as ‘dampened’. Toe pressures and
toe-­brachial pressure index (TBPI) measurements may also be
used when arterial calcification is suspected. Measurement of skin
ABC of Wound Healing, Second Edition. Edited by Annie Price, Joseph E. Grey, Girish K. Patel, and Keith G. Harding.
© 2022 John Wiley & Sons Ltd. Published 2022 by John Wiley & Sons Ltd.
26
­ erfusion pressure and transcutaneous oxygen pressure can help
p
identify which ulcers are more likely to heal in the presence of
peripheral arterial disease.
These bedside tests of arterial perfusion are associated with
intra-­and interuser variability and are not always able to accurately
rule out the presence of ischaemia. The results should be inter-
preted in the context of clinical features and progress of healing.
There is also some disagreement about the normal values, but it is
generally accepted that peripheral artery disease is unlikely if the
ABPI is 0.9–1.3, the TBPI is >0.75 and the Doppler waveform is
triphasic.
Neuropathic foot ulcer
The neuropathic foot is warm and well perfused with palpable pulses.
Sweating is diminished and the skin may be dry and prone to fissur-
ing. Neuropathic ulcers usually occur on the plantar aspect of the
foot under the metatarsal heads or on the plantar aspects of the toes.
The most frequent cause of ulceration is repetitive mechanical
forces of gait, which leads to callus, the most important preulcera-
tive lesion in the neuropathic foot. If allowed to become too thick,
the callus will press on the soft tissues underneath and cause ulcera-
tion. A layer of whitish, macerated, moist tissue found under the
surface of the callus indicates that the foot is close to ulceration and
urgent removal of callus is necessary. If callus is not removed,
inflammatory autolysis and haematomas develop under the callus.
This leads to tissue necrosis, resulting in a small cavity filled with
serous fluid, giving the appearance of a blister under the callus
which, when removed, reveals an ulcer.
Neuroischaemic foot ulcer
The neuroischaemic foot is typically a cool foot with diminished
pulse volume. The skin is thin, shiny and without hair. There is
atrophy of the subcutaneous tissue. The typical symptoms of ischae-
mia (e.g. intermittent claudication and rest pain) may be absent
because of neuropathy. Neuroischaemic ulcers are commonly seen
on the margins of the foot, especially on the medial surface of the

(a)
(a) Neuropathic diabetic foot ulcer. (b) Neuroischaemic diabetic foot ulcers.
Prevention of diabetic foot ulcers
Preventing diabetic foot ulcers requires the following key elements
1 Identification of the at-­risk foot – due to the presence of
neuropathy, many patients with preulcerative lesions or even
ulcers are asymptomatic. Risk factors include neuropathy,
peripheral arterial disease, foot deformity, end-­stage renal disease
and previous ulceration or amputation.
2 Regular examination of the at-­risk foot – this is usually done by a
podiatrist and involves screening for risk factors and checking
foot hygiene (e.g. toenail care).
3 Education of the patient, family and involved healthcare
professionals – the patient and/or their carers should understand
how to protect their feet, monitor for problems and seek help if
needed.
4 Review of footwear – is it appropriate and is special footwear
being worn regularly?
5 Treatment of risk factors – this includes removing callus, treating
ingrown nails and protecting blisters.
(adapted from Schaper et al. 2020).
first metatarsophalangeal joint and over the lateral aspect of the
fifth metatarsophalangeal joint. They may also develop on the tips
of the toes and beneath toenails if allowed to become overly thick.
The classic sign of preulceration in the neuroischaemic foot is a
red mark on the skin, often precipitated by tight shoes or a slip-­on
style shoe leading to frictional forces on the vulnerable margins of
the foot. The first sign of ischaemic ulceration is a superficial blister
usually secondary to friction. It then develops into a shallow ulcer
with a base of sparse pale granulation tissue or yellowish closely
adherent slough.
Principles of Management
Wound control
In the neuropathic foot, callus surrounding the ulcer is removed
with a scalpel together with slough and non-­viable tissue. The ulcer
should be probed to exclude undermining and the presence of a
Diabetic Foot Ulcers 27
(b)
sinus which, if extending to bone, may suggest underlying
­osteomyelitis. The ulcer should be cleansed and dressed with an
appropriate dressing.
In the neuroischaemic foot, slough and dried necrotic material
should be removed from the ulcer by sharp debridement. Cautious
debridement should be performed if the foot is very ischaemic
(ABPI <0.5). It is essential not to damage viable tissue. Some ischae-
mic ulcers develop a halo of thin glassy callus that dries out,
becomes hard and curls up. It is necessary to smooth off these areas
as they can catch on dressings and cause trauma to underlying tis-
sue. If a subungual ulcer is suspected, the nail should very gently be
cut back or layers of nail pared away, to expose and drain the ulcer.
Maggot therapy is sometimes used to debride diabetic foot ulcers,
especially those that are neuroischaemic.
Negative-­pressure wound therapy may be useful to aid healing in
postoperative wounds (i.e. those that have been surgically
debrided). A number of adjunctive treatments have been recom-
mended for use in non-­ infected ulcers that fail to heal after
4–6 weeks of optimal treatment. These include sucrose octasulfate
dressings, multilayered patches of autologous leucocytes, platelets
and fibrin, placental membrane allografts and topical oxygen ther-
apy. Hyperbaric oxygen may also be used for ischaemic ulcers that
do not heal following revascularisation.
Mechanical control
In the neuropathic foot, the overall aim is to redistribute plantar
pressures, while in the neuroischaemic foot it is to protect the vul-
nerable margins of the foot. Semi-­compressed adhesive felt padding
may be used to divert pressure especially from small ulcers in the
neuropathic foot. The most efficient way to redistribute plantar
pressure is to use either a total contact cast (treatment of choice for
indolent neuropathic ulcer) or a prefabricated cast such as an Aircast
or Scotchcast boot. If casting techniques are not available, tempo-
rary ready-­made shoes with a cushioning insole can be supplied.
When the neuropathic ulcer has healed, the patient should be fitted
with a cradled insole and bespoke shoes to prevent recurrence.
Occasionally, extra-­depth, ready-­made orthopaedic shoes with flat
cushioning insoles may suffice in the absence of very high-­pressure
areas. Some patients may benefit from surgical intervention to
28 ABC of Wound Healing

(a) (b)

(c)

Doppler waveforms. (a) Triphasic waveforms (normal). (b) Biphasic waveforms (usually normal). (c) Monophasic waveforms (abnormal, usually accompanied by
low pressure index unless arterial calcification is present). Source: Huntleigh.

(a) (b)

(a) Measurement of ankle pressure. (b) Measurement of toe pressure. Source: Huntleigh.

redistribute plantar pressures, such as resection of bony promi-
nences or tendon lengthening procedures.
As ulcers in neuroischaemic feet usually develop around the mar-
gins of the foot, a high-­street shoe that is sufficiently long, broad and
deep and fastens with a lace or strap high on the foot may be all that
is needed to accommodate the foot. Alternatively, a Scotchcast boot
or a ready-­made stock shoe that is wide-­fitting may be suitable.
All patients with neuropathic or neuroischaemic feet are at risk
of pressure ulcers, especially of the heel. Heel ulcers can be off-­
loaded by pressure-­relieving heel protectors or pressure relief ankle
foot orthoses (PRAFO). The heel protector has a built-­in pillow-­
style cushioning which provides a soft support surface. It reduces
foot rotation inside the boot.
Vascular control
Urgent vascular imaging by duplex ultrasound, computed tomog-
raphy (CT) angiography or magnetic resonance (MR) angiography
is required in the presence of severe ischaemia (ABPI <0.5 or toe

pressure <30 mmHg). However, it is important to proceed to imag-
ing for patients with mild or moderate ischaemia or even with nor-
mal bedside tests but where healing is not progressing despite
optimal treatment. This will identify the presence of stenoses or
occlusions and assess their suitability for angioplasty. If lesions are
too extensive for angioplasty, arterial bypass may be necessary.
Dry gangrene, especially of the digit, usually results from critical
ischaemia secondary to poor tissue perfusion and oxygenation
from atherosclerotic narrowing of the arteries of the leg. Ideally, the
ischaemic foot should be revascularised, either by angioplasty or
bypass graft or by a hybrid procedure often comprising angioplasty
above the knee and then a distal bypass below the knee, and the
digital necrosis should be surgically removed. However, when
revascularisation is not possible, the toes may be allowed to
autoamputate.
Areas of abnormal pressure distribution in the diabetic foot. Plantar ulcers
are most commonly seen under the hallux, on the first and fifth metatarsal
heads and under the heel.
(a)
(a) Ulcers seen on plantar aspect of foot following debridement of callus. (b) The amount of callus removed.
Diabetic Foot Ulcers 29
Microbiological control
Ulcers provide a portal of entry for invading bacteria. There is a
clinical spectrum ranging from local colonisation of the ulcer to
wet gangrene. In the presence of neuropathy and ischaemia, the
inflammatory response is impaired and early signs of infection may
be subtle. Only 50% of wound infection episodes are accompanied
by local clinical signs of infection.
Ulcers suspected to be infected should undergo sharp debride-
ment of surrounding callus and tissue debris, followed by deep
swab and tissue sampling (not of surface callus) for microbiological
culture immediately. Empirical broad-­spectrum antibiotics cover-
ing gram-­positive, gram-­negative and anaerobic bacteria should be
started. Narrow-­spectrum antibiotics should be given once the
organism and sensitivities are known. In addition, urgent surgical
intervention for the removal of infected necrotic tissue or the
drainage of pus in the foot with rapidly spreading infection may
be necessary.
Examination of an ulcer with a probe.
(b)
30 ABC of Wound Healing
(a)
Pressure redistribution. (a) Walking boot. (b) Custom made shoe. (c) Half shoe.
A below-­knee plaster cast with a frame that reduces forces through the foot.
Wet gangrene may complicate both neuropathic and neurois-
chaemic foot ulcers. This arises as a consequence of septic vasculitis
of the digital and small arteries of the foot as a result of infected
ulcers. The walls of these arteries are infiltrated by polymorphs
leading to occlusion of the lumen by septic thrombus. Wet gangrene
(b)
(c)
may need surgical intervention and sometimes amputation is
required. In the neuroischaemic foot, the contribution of athe­
rosclerotic occlusive disease may need to be addressed by
revascularisation.
Metabolic control
Wound healing and neutrophil function are impaired by hyper-
glycaemia; tight glycaemic control is therefore essential. Patients
with non-­ insulin-­
dependent diabetes suboptimally controlled
with oral hypoglycaemic therapy should be started on insulin.
Hyperlipidaemia and hypertension should be actively treated.
Patients should stop smoking. Those with neuroischaemic ulcers
should receive statin and antiplatelet therapy. Diabetic patients
with peripheral artery disease (in the absence of renal artery ste-
nosis) may also benefit from an angiotensin-­converting enzyme
(ACE) inhibitor to prevent further vascular episodes.
Education
Patients who have lost protective pain sensation need advice to
protect their feet from mechanical, thermal and chemical trauma.
Patients should be instructed on the principles of ulcer care,
stressing the importance of rest, footwear, regular dressings and
frequent observation for signs of infection. They should be taught
the four danger signs: swelling, pain, colour change and breaks in
the skin.

(a)
(a) A necrotic toe. (b) The necrotic toe has been amputated.
Local signs of wound infection
• Increased friability of granulation tissue
• Base of ulcer changes from healthy pink granulation tissue to
yellowish or grey tissue and becomes moist
• Discharge changes from clear to purulent
• Unpleasant odour
Overgranulation in a diabetic foot ulcer, which can be a sign of chronic
infection. There is an overgrowth of granulation tissue in the wound bed
and it appears spongy and red. It may bleed easily on contact.
Indications for urgent surgical intervention
• Large area of infected sloughy tissue
• Localised fluctuance and expression of pus
• Crepitus with gas in the soft tissues on x-­ray
• Purplish discolouration of the skin, indicating subcutaneous
necrosis
Diabetic Foot Ulcers 31
(b)
Osteomyelitis
• Osteomyelitis may complicate diabetic foot ulcers.
• The probe-­to-­bone test should be performed for all infected
diabetic foot ulcers; if bone is palpable in the base of the ulcer,
osteomyelitis is likely.
• Definitive diagnosis requires positive culture results from an
aseptically obtained bone biopsy (percutaneous or surgical), but
this is usually only performed when the diagnosis is unclear or
when identification of the causative organism is required.
• A combination of positive tests, such as probe-­to-­bone, elevated
inflammatory markers (particularly erythrocyte sedimentation rate
and C-­reactive protein) and typical x-­ray findings is most
suggestive of osteomyelitis.
• Magnetic resonance imaging (MRI) or nuclear imaging techniques
should be used if there is high clinical suspicion of osteomyelitis
but x-­rays are normal, or to help with operative planning should
surgery be required.
• Systemic antibiotics may be required for up to 6 weeks but if there
is no improvement during this time, bone cultures and/or surgical
intervention should be considered.
Organisation of care
Successful management of the diabetic foot requires the expertise of a
multidisciplinary team that provides rapid access, early diagnosis,
prompt treatment and integrated care. Patients need close follow-­up
for the rest of their lives. Such co-­ordinated care has led to a great
reduction in numbers of amputations as a result of diabetic foot ulcers.
Members of the multidisciplinary team
• Podiatrist • Radiologist
• Physician • Vascular surgeon
• Specialist nurse • Orthopaedic surgeon
• Orthotist • Microbiologist
• Dietitian
32 ABC of Wound Healing
Exposed bone (arrow) can suggest the presence of osteomyelitis.
Forefoot amputation due to wet gangrene.
Charcot osteoarthropathy (Charcot foot)
Charcot osteoarthropathy is a destructive process of weight-­bearing
joints often leading to disruption of the normal architecture of the
foot and severe deformity and instability. It is characterised by mul-
tiple fractures, bony destruction and bone resorption. Collapse of
the medial longitudinal arch is common, leading to a typical ‘rocker
A pin discovered in a neuropathic foot.
bottom’ foot deformity. However, early diagnosis and intervention
can prevent Charcot foot deformity.
Acute Charcot osteoarthropathy should be suspected in a neuro-
pathic patient who presents with a hot, erythematous and swollen
foot within days of a minor traumatic event, such as tripping.
However, often the patient may be unaware of any trauma.
Furthermore, the neuropathy may be a subtle small fibre neuropa-
thy and vibration sense and light touch may be intact in the foot.
X-­ray showing Charcot osteoarthropathy. There are multiple fractures and
destruction of the normal architecture of the mid-­foot. Previous amputations
can also be seen.

The presence of pain in the foot should not discourage the diagno-
sis of Charcot foot. It may be mistaken for cellulitis, gout or deep
vein thrombosis. The diagnosis can easily be missed because early
bone and joint damage may not be detectable on standard x-­ray. It
can be identified by radionuclide bone scan, preferably single-­
photon emission computed tomography (SPECT) together with
conventional CT or MRI.
Treatment is immediate immobilisation with a total contact cast
and limitation of activity to prevent further joint destruction. The
oedema and erythema of the affected joint may take 6–9 months of
immobilisation to recede. If deformity does develop, orthopaedic
reconstruction may be possible, although limited long-­term data
are available.
Acknowledgements
We would like to thank Huntleigh for providing us with images of
Doppler assessment and waveforms.
Diabetic Foot Ulcers 33
Reference
Schaper, N.C., van Netten, J.J., Apelqvist, J. et al. (2020). Practical guidelines
on the prevention and management of diabetic foot disease (IWDGF 2019
update). Diabetes/Metabolism Research and Reviews 36 (S1): e3266.
Further reading
Edmonds, M. and Foster, A.V.M. (2014). Managing the Diabetic Foot, 3e.
Oxford: Wiley-­Blackwell.
Hinchliffe, R.J., Forsythe, R.O., Apelqvist, J. et al. (2020). Guidelines on diag-
nosis, prognosis and management of peripheral artery disease in patients
with foot ulcers and diabetes (IWDGF 2019 update). Diabetes/Metabolism
Research and Reviews 36 (S1): e3276.
Lipsky, B.A., Senneville, E., Abbas, Z.G. et al. (2020). Guidelines on the diag-
nosis and treatment of foot infection in persons with diabetes (IWDGF
2019 update). Diabetes/Metabolism Research and Reviews 36 (S1): e3280.
Rogers, L.C., Frykberg, R.G., Armstrong, D.G. et al. (2011). The Charcot foot
in diabetes. Diabetes Care 34 (9): 2123–2129.
 CHAPTER 6
Venous and Arterial Leg Ulcers
Joseph E. Grey1 and Girish K. Patel2,3
1
Department of Clinical Gerontology, Cardiff and Vale University Health Board, Cardiff, UK
2
Welsh Institute of Dermatology, Cardiff and Vale University Health Board, Cardiff, UK
3
Cardiff University School of Biosciences, Cardiff, UK
OVERVIEW
• There are multiple causes of lower leg ulcers; venous leg
ulceration is the most common.
• Dual or multiple aetiologies may coexist, especially in elderly
patients.
• All patients with lower leg ulcers should be evaluated for
peripheral arterial disease, which can be undertaken routinely by
measuring the ankle brachial pressure index (ABPI).
• Compression is the mainstay of treatment for all venous leg
ulcers; some patients may also benefit from venous surgery.
• Revascularisation should be considered for all patients with
arterial disease.
Leg ulcers affect around 1% of the adult population, rising to 3.6%
among those over 65 years of age. Most are caused by chronic
venous insufficiency (45–80%) or peripheral arterial disease
(5–20%). Up to 20% of leg ulcers in elderly patients are caused by
a combination of venous and arterial disease, so-­called mixed
ulcers.
Venous ulceration
Venous leg ulcers arise as a result of sustained venous hypertension
caused by chronic venous insufficiency. In the normal venous sys-
tem, pressure decreases with exercise as a result of the action of the
calf muscle pump to 20–30 mmHg, from a standing pressure of
around 100 mmHg. When the muscles relax, the valves in the per-
forating veins connecting the superficial venous circulation to
the deep venous circulation prevent reflux and the pressure in the
superficial veins remains low. When the valves are incompetent, the
superficial venous pressure remains high. Up to 10% of the popula-
tion in Europe and North America has valvular incompetence,
which is either congenital or secondary to deep vein thrombosis,
with 0.2% developing venous ulceration. Forty to fifty percent of
venous ulcers are due to superficial venous insufficiency and/or
perforating vein incompetence, with a normal deep venous system.
ABC of Wound Healing, Second Edition. Edited by Annie Price, Joseph E. Grey, Girish K. Patel, and Keith G. Harding.
© 2022 John Wiley & Sons Ltd. Published 2022 by John Wiley & Sons Ltd.
34
Clinical features
There are many risk factors for venous ulceration. Recurrent venous
ulceration occurs in up to 70% of those at risk. Many venous ulcers
are painful, which is typically helped by leg elevation (in contrast to
peripheral arterial disease, where pain is typically worse on leg
elevation).
Ninety-­five percent of venous ulcers are located in the gaiter
area of the leg, characteristically occurring around the malleoli.
Ulceration may be discrete or circumferential. The ulcer bed is
often covered with a fibrinous layer mixed with granulation tis-
sue, surrounded by an irregular, gently sloping edge. Ulcers
occurring above the mid-­calf or on the foot are likely to have
other causes.
Pitting oedema is often present and may predate the ulcer. It is
typically worse towards the end of the day. Extravasation of eryth-
rocytes into the skin occurs, resulting in the deposition of haemosi-
derin that manifests as brown skin pigmentation.
Prolonged venous insufficiency leads to additional skin changes,
with the dermis and subcutaneous tissue becoming indurated and
fibrosed, so that the peripheral oedema is no longer pitting.
Progressive fibrosis leads to a more fragile and atrophic skin sur-
face, with loss of sweat glands and hair follicles, termed lipoderma-
tosclerosis. Severe lipodermatosclerosis may be associated with
atrophie blanche – areas of white angular scar tissue with low blood
flow due to occlusion of small vessels in the dermis, with a propen-
sity to ulcerate.
As a result of these changes in the leg, a rigid woody hardness
often develops which, at its worst, may have the appearance of an
inverted champagne bottle. Fibrotic entrapment of the calf muscle
pump may lead to progressive contraction of the Achilles tendon,
which further hinders venous return, worsening venous insuffi-
ciency. Venous (gravitational) eczema (erythema, scaling, weep-
ing and itching) is also common and is distinct from cellulitis. In
addition to venous eczema, irritant and allergic contact dermatitis
of the surrounding skin are common due to the effects of exudate
or sensitisation to allergens in topically applied products and
dressings.
 Venous and Arterial Leg Ulcers 35

Typical venous ulcer with an irregular border and sloping edges located in
the gaiter area of the lower limb.

Assessment
The diagnosis of venous ulcers is mostly based on the clinical fea-
tures described above. All patients with leg or foot ulcers should
undergo an assessment to determine the vascular status of the limb
(for example, ABPI) prior to commencing any form of compres-
sion. This aids diagnosis by ruling out an arterial component and
Typical arterial ulcer with exposed tendon and well-­defined edges.
indicates that compression is safe. Duplex scanning of the venous
system demonstrates the presence of venous disease and can be
used to identify superficial, deep or perforator vein incompetence. ­ alignancy or if the ulcer fails to heal following 3 months of ade-
m
A biopsy should be considered if there is any suspicion of quate treatment; this will require referral to a specialist.

Features of venous and arterial ulcers.

Venous Arterial

History History of varicose veins, deep vein thrombosis, venous insufficiency History suggestive of peripheral arterial disease, intermittent
or venous incompetence claudication and/or rest pain
Classic site Over the medial gaiter region of the leg Usually over the toes, foot and ankle
Edges Sloping Punched-­out
Wound bed Often covered with slough Often covered with varying degrees of slough and necrotic tissue
Exudate level Usually high Usually low
Pain Pain is not severe unless associated with excessive oedema or infection Pain a feature even in the absence of infection
Oedema Usually associated with limb oedema Oedema not common
Associated Venous eczema, lipodermatosclerosis, atrophie blanche, Trophic changes, gangrene may be present
features haemosiderosis
Treatment Compression is the mainstay Revascularisation

Risk factors for venous ulceration. Management

Direct risk factors
Varicose veins
Deep vein thrombosis
Chronic venous insufficiency
Poor calf muscle function
Arteriovenous fistulae
Obesity
History of leg fracture
Indirect risk factors
All risk factors leading to deep vein
thrombosis including protein C, protein S
and antithrombin III deficiency
Family history of varicose veins
A history of minor trauma prior to the
development of ulceration may also be
identified
Compression  Compression is the mainstay of venous ulcer
management. Graded compression, with greatest pressure at the
ankle (approximately 40 mmHg) tapering off to lower pressure
below the knee (approximately 18 mmHg), increases limb hydro-
static pressure and concomitantly reduces superficial venous pres-
sure. Various compression bandage systems are used and may be
elastic or inelastic, single or multi-­layer. Unna’s boot, a wet zinc
oxide bandage applied from toes to knee covered with elastic com-
pression bandage, is widely used in the United States. Compression
36 ABC of Wound Healing

Brown skin pigmentation caused by haemosiderin deposition. Severe eczema.

Venous surgery  Some patients may benefit from surgery to treat

venous incompetence. There are various methods available to treat
superficial venous incompetence, including vein ligation and strip-
ping, thermal or radiofrequency ablation or sclerotherapy. Surgical
repair of damaged valves can be used to treat incompetence of the
deep venous system, although currently the evidence for this is lim-
ited and it is not widely available in the UK.

Drugs  Oral pentoxifylline can be used as an adjunct to compres-

sion or in patients who cannot tolerate compression, though it
commonly causes gastrointestinal upset. The risks of polyphar-
macy in elderly patients should also be considered. Analgesia may
be needed, particularly for dressing changes. Antibiotics should
only be used to treat infection but do not improve healing when
Atrophie blanche. used routinely.

Wound and  skin care  At each dressing change, the ulcer and
Features of venous eczema and cellulitis.
surrounding skin should be cleaned using potable water to remove
debris, dry skin and dressing material. Low-­adherent dressings are
Venous eczema Cellulitis suitable for most venous ulcers. A moist, but not wet, wound envi-
ronment can improve healing and dressing choice should reflect
Common features Red, warm, painful and tender to touch
this (see Chapter 13).
Distinguishing Usually chronic Insidious: usually 24–72 h
features Diffuse and poorly Usually well demarcated Sharp debridement of non-­viable tissue may expedite venous
demarcated ulcer healing and can be carried out at the bedside. Shave therapy
Increase in exudate No increase in exudate (excision of the whole ulcer) followed by skin grafting or skin graft-
Itchy Not itchy ing alone may be useful in patients in whom other treatment
Scaly Not scaly
modalities have failed.
Treated with topical Treated with systemic
steroids antibiotics Venous ulcers commonly become infected (see Chapter  9
for  signs of infection). The most frequent organisms include
Staphylococcus aureus, Pseudomonas aeruginosa and β-­
haemolytic streptococci. Topical antiseptics and antimicrobials
kits (two-­layer hosiery) and wraps are also a­vailable and many (e.g. silver, iodine or honey-­based products) should be used to
patients can apply these themselves, reducing the frequency of treat localised infection, whereas systemic antibiotics (e.g. peni-
nurse visits. Compression using pneumatic devices (e.g. Flowtron™) cillin or macrolide) are required for spreading cellulitis or sys-
has been used to promote healing of venous ulcers in patients with temic infection.
oedematous legs. Patients should be warned to look out for any Emollients should be used on the surrounding skin to prevent
side-­effects of compression (such as numbness, tingling, pain, drying. Associated venous eczema should be treated with ointment-­
dusky toes), remove the compression should any symptoms arise based topical steroids and emollients. Eczema can become second-
and seek advice. arily infected and require systemic antibiotic therapy.
 Venous and Arterial Leg Ulcers 37

SEVERE ECZEMA

Very potent corticosteroid for 3–4 weeks, e,g. clobetasol

propionate (Dermovate®). Also use an emollient*

Step-up Step-down

INFECTED ECZEMA MILD ECZEMA ‘WEEPING’ ECZEMA

Combination of a very Moderately potent Combination of a very

potent corticosteroid, an
antiseptic and astringent
agent such as potassium
permanganate (1 in 10,000),
and oral antibiotics
corticosteroid for 3–4 weeks, potent corticosteroid, and an
e.g. clobetasone butyrate antiseptic and astringent
(Eumovate®). Also use an agent such as potassium
emollient such as 50/50 permanganate (1 in 10,000)

Step-up Step-down

NO ECZEMA

*e,g. aqueous cream; liquid Daily emollient*

and white soft paraffin (50/50)

Treatment algorithm for venous eczema.

Lifestyle advice  The leg should always be elevated when seated
but patients should be encouraged to remain active, provided
they are wearing some form of compression system. Skin care
and hygiene are also important, as are general health and well-­
being (e.g. weight management, adequate nutrition, smoking
cessation).
Once the venous ulcer has healed, it is essential that patients fol-
low simple advice aimed at preventing recurrence. This includes
compression stockings for life, skin care, leg elevation, calf exercises
and a healthy diet. The reported annual venous ulcer recurrence
rate of 20% is strongly influenced by patient adherence.
Organisations such as leg clubs may help reduce this figure.
Arterial ulceration
Arterial ulceration arises as a result of reduced arterial blood supply
to the lower limb. The most common cause is atherosclerotic dis-
ease of the medium and large arteries. Other causes include diabe-
tes (which may accelerate atherosclerosis and thus present at an
earlier age), thromboangiitis, vasculitis and sickle cell disease, some
of which may predispose to the formation of atheroma. Further
damage to the arterial system occurs with concurrent hypertension
through damage of the intimal layer of the artery. A reduced arte-
rial blood supply causes tissue hypoxia and tissue damage.
Thrombotic and atheroembolic episodes may also play a part in
tissue damage and ulcer formation. Ulceration frequently occurs
after seemingly trivial trauma or as the result of localised pressure.
Clinical features
Peripheral arterial disease is most common in men older than 45
and women older than 55. A familial history of premature athero-
sclerotic disease may be present. Modifiable risk factors for
peripheral arterial disease include smoking, hyperlipidaemia,
hypertension, diabetes and obesity with associated decreased
activity. There may also be a history of generalised vascular prob-
lems such as myocardial infarction, angina, stroke, renal impair-
ment and intermittent claudication. Rest pain may be present and
may be alleviated by hanging the foot over the side of the bed or
sleeping in a chair. Pain usually begins distal to the obstruction,
moving proximally as ischaemia progresses. The ulcer itself is
often painful.
Arterial ulcers typically occur over the toes, heels and bony
prominences of the foot. The ulcer appears ‘punched out’, with well-­
demarcated edges and a pale, non-­granulating, often necrotic base.
The surrounding skin may exhibit dusky erythema, be cool to
touch, hairless, thin and brittle with a shiny texture. The toenails
thicken, become opaque and may eventually be lost. Gangrene of
the extremities may also occur.
Examination of the arterial system may reveal decreased or
absent dorsalis pedis and posterior tibial pulses. There may be
bruits in the proximal leg arteries indicating the presence of athero-
sclerosis or, rarely, arterial aneurysm. The capillary refill time is
often reduced. Buerger’s test (a delay of greater than 10–15 seconds
in return of colour after raising an ischaemic leg to 45° for 1 min-
ute) may be positive.
38 ABC of Wound Healing

(a)

(c)

(b)

Types of compression. (a) Single-­layer elastic bandage. (b) Two-­layer hosiery kit. (c) Compression wrap.

(a) (b)

Sharp debridement at the bedside. (a) Before debridement. (b) After debridement.
 Venous and Arterial Leg Ulcers 39

Compression stockings.

Pressure at
Class ankle (mmHg) Indication

I 14–17 Varicose veins

II 18–24 Prevention of recurrence of venous ulcers on small
(narrow) legs and slim patients and for mild oedema
III 25–35 Chronic venous insufficiency and oedema and large
heavy legs

An angiogram showing multilevel arterial disease. The arrow indicates a

stenosis in the right superficial femoral artery.

Arterial ulcers with typical skin changes (hairless, shiny and thin).

most likely to have an impact on healing of arterial ulceration.

Assessment
The ABPI is helpful in the identification of peripheral vascular dis-
ease. However, intimal calcification can cause incompressible vessels
that result in an abnormally high ABPI recording, as frequently
occurs in diabetes and with advancing age. A duplex ultrasound pro-
vides more information on arterial occlusion, stenosis and areas of
diffuse and continuous atheromatous disease. Angiography is the
gold standard investigation and is required for preoperative planning,
allowing direct assessment of the lower limb vascular anatomy.
Management
Surgery  If arterial disease is suspected, urgent referral to a vascu-
lar surgeon is required. Increasing the peripheral blood flow
(revascularisation) by, for example, a bypass graft (for diffuse
disease) or angioplasty (for localised stenosis) is the intervention
Operative indications for chronic ischaemia include non-­healing
ulceration, gangrene, rest pain and progression of disabling clau-
dication. In some cases, there are no revascularisation options
and limb amputation may be required. Revascularisation is not
always successful and is not guaranteed to restore blood supply
adequately for healing. Conservative treatment is preferred by
some patients and may be appropriate in those unfit for surgical
intervention.
Drugs  Pain from arterial insufficiency can be severe, requiring
­opioid analgesia. Statins and antiplatelets are recommended,
provided there are no contraindications. Vasoconstrictive drugs
such as non-­selective β-­blockers should be avoided. Infection
can cause rapid deterioration in an arterial ulcer and treatment
with systemic antibiotics (along the lines for venous ulceration
outlined above) should be commenced.

Interpretation of ankle brachial pressure index.

Index Signs and symptoms Severity of disease Action

≥0.7–1 Mild intermittent claudication, or
no symptoms
0.7–0.5 Varying degrees of intermittent
claudication
0.5–0.3 Severe intermittent claudication
and rest pain
≤0.3 or ankle systolic Critical ischaemia (rest pain >
pressure < 50 mmHg 2 weeks) with or without tissue
loss (ulcer, gangrene)
Mild arterial disease
Mild to moderate arterial
disease
Severe arterial disease
Severe arterial disease,
risk of losing limb
Reduce risk factors and change lifestyle: stop smoking, maintain
weight, exercise regularly, consider antiplatelet agent
As for index ≥0.7–1, plus referral to outpatient vascular specialist
and possible arterial imaging (duplex scan and/or angiogram)
As for index ≥0.7–1, plus urgent referral to vascular specialist and
possible arterial imaging (duplex scan and/or angiogram)
Urgent referral to vascular emergency on-­call team and possible
surgical or radiological intervention

An index of 1 to 1.1 is considered to be normal. The data in the table should be used as an adjunct to the clinical findings. Erroneous readings may be the
result of incompressible arteries secondary to the presence of calcification or tissue oedema. Patients may present with an arterial ulcer even with a normal
index. Acute limb ischaemia may occur either due to an embolus or a thrombus (“acute on chronic” ischaemia) and should be referred as an emergency to a
vascular specialist or emergency department for urgent intervention to prevent imminent limb loss.
40 ABC of Wound Healing
Wound care  Choice of wound dressings will be dictated by the
nature of the wound. It is not always appropriate to debride arte-
rial ulcers as this may promote further ischaemia and lead to the
formation of a larger ulcer.
Lifestyle advice  Patients with arterial insufficiency should stop
smoking and follow simple advice on foot and leg care. Control
of diabetes, hypertension and hyperlipidaemia should be opti-
mised. Walking is beneficial and should be encouraged.
Mixed ulcers
Ulceration of mixed aetiology is not uncommon; patients may suf-
fer from combinations of venous and arterial disease resulting in
ulcers of mixed aetiologies, which will limit the degree of compres-
sion (if any) that can be used. The coexistence of other pathology
that can contribute to delayed healing is also common, for example
lymphoedema, diabetes and rheumatoid arthritis.
Further reading
Barwell, J.R., Davies, C.E., Deacon, J. et al. (2004). Comparison of surgery and
compression with compression alone in chronic venous ulceration (ESCHAR
study): randomised controlled trial. Lancet 363 (9424): 1854–1859.
Nelson, E.A., Bell‐Syer, S.E.M. (2014). Compression for preventing recurrence
of venous ulcers. Cochrane Database of Systematic Reviews 9: CD002303.
Patient guidelines for the protection of lower limbs and feet
• Examine the feet daily for broken skin, blisters, swelling or
redness.
• Report worsening symptoms, e.g. decreasing walking distance,
pain at rest, pain at night, skin colour changes.
• Keep the skin moist with, e.g. 50/50 white soft paraffin and liquid
paraffin mix.
• Never walk around barefoot.
• Ensure shoes are well fitting and free of friction and pressure
points. Check for foreign objects (stones, etc.) before wearing
them. Avoid open-­toed sandals and pointed shoes.
• Give up smoking.
• Exercise regularly within the limits of pain and tolerance.
O’Meara, S., Cullum, N., Nelson, E.A., and Dumville, J.C. (2012). Compression
for venous leg ulcers. Cochrane Database of Systematic Reviews 11:
CD000265.
SIGN (Scottish Intercollegiate Guidelines Network). (2010). Management of
chronic venous leg ulcers. www.sign.ac.uk/our-­guidelines/management-­of-­
chronic-­venous-­leg-­ulcers/
Singer, A.J., Tassiopoulos, A., and Kirsner, R.S. (2017). Evaluation and man-
agement of lower-­extremity ulcers. New England Journal of Medicine 377:
1559–1567.
 CHAPTER 7
Pressure Injuries
Joseph E. Grey1 and Jacqui Fletcher2
1
Department of Clinical Gerontology, Cardiff and Vale University Health Board, Cardiff, UK
2
Stop the Pressure Programme, NHS England and NHS Improvement, UK
OVERVIEW
• Most pressure injuries are avoidable.
• Focus on prevention by identifying individuals at risk of pressure
damage and instituting measures to reduce risks.
• Regular and systematic skin inspection is vital to identify at-­risk
skin or early pressure damage.
• Pressure injuries have a serious impact on quality of life and result
in significant costs to healthcare providers.
• Manage pressure injuries through pressure
redistribution – regular change of position of the individual and/
or use of specialist equipment.
The term pressure injury is used to describe the spectrum of damage
related to pressure or pressure in combination with shear. Other
terms used to describe this phenomenon include pressure ulcers,
pressure sores, bed sores and decubitus ulcers. There is ongoing
debate about the correct terminology and all of these terms remain in
use. The term ulcer implies full-­thickness skin loss. However, it is
possible for pressure damage to result in a soft tissue injury without a
break in the skin. In this chapter, therefore, the term pressure injury
will be used.
Pressure injury advisory panels
Many of the guidelines and consensus documents on pressure
injuries were developed by collaborative advisory panels, such as
the National Pressure Injury Advisory Panel (NPIAP) for the USA, the
European Pressure Ulcer Advisory Panel (EPUAP) for Europe, and
the Pan Pacific Pressure Injury Alliance (PPPIA) for Australia,
New Zealand, Hong Kong and Singapore.
Pressure injuries are caused by a local breakdown of tissue as a
result of deformation of the tissue due to mechanical loading forces.
The risk of developing a pressure injury depends on the mechanical
load applied to the tissue and the tolerance of the t­issue to the
­loading forces applied. The mechanical load may be in the form of
ABC of Wound Healing, Second Edition. Edited by Annie Price, Joseph E. Grey, Girish K. Patel, and Keith G. Harding.
© 2022 John Wiley & Sons Ltd. Published 2022 by John Wiley & Sons Ltd.
Definition of a pressure injury
‘A pressure injury is defined as localised damage to the skin and/or
underlying tissue, as a result of pressure or pressure in combination
with shear. Pressure injuries occur over a bony prominence but may
also be related to a medical device or other object.’
(EPUAP/NPIAP/PPPIA 2019)
direct pressure or shear caused by the individual’s own body weight
or by a medical device or other object, such as tubing trapped
between the body and support surface. An individual’s tolerance to
the forces applied is determined by anatomy (e.g. presence of
deformities that increase the prominence of bony structures), tissue
properties (e.g. strength, stiffness, blood supply) and capacity for
tissue repair. All patients are potentially at risk of developing a pres-
sure injury but they are more likely to occur in certain populations,
for example, those who are older, have a serious illness, spinal cord
injury, chronic neurological condition, hip fracture or those who
reside in a long-­term care facility. While it is generally accepted that
most pressure injuries are avoidable, some occur despite following
best practice guidelines, or in situations where optimal preventive
measures could not be implemented.
Examples of situations where implementation of optimal
preventive measures may not be possible or appropriate.
• Critical illness (haemodynamic or spinal instability) that prevents
repositioning.
• Terminal illness, where patient comfort may take priority over
pressure injury prevention or where skin failure occurs as a
consequence of severe systemic illness.
• Acute event affecting mobility without immediate medical attention,
e.g. a fall or loss of consciousness due to collapse or intoxication.
• Patients with capacity who refuse repositioning or other
pressure-­redistributing measures.
• Patients who have not previously been seen by a healthcare
professional.
41
42 ABC of Wound Healing

(a) (b)

Examples of common pressure injury sites. (a) Pressure injury over elbow joint. (b) Pressure injury on heel.

Supine position

Heels Sacrum Eibows Scapulae Back of

head

Prone position

Toes Knees Genitalia Breasts Acromion Cheek

(men) (women) process and ear

Lateral position

Medial and Greater Acromion

Malleous Ribs Ear
lateral condoyle trochanter process

Potential sites for pressure injury development in those at risk. The most commonly affected sites are the sacrum, heel, ischium, ankle, elbow and hip.
 Pressure Injuries 43

The precise frequency of pressure injury occurrence is unknown,

with wide variation in the reported rates of both prevalence and
incidence. Rates vary considerably when studied by speciality
(orthopaedics, palliative care, etc.) and care setting (acute, commu-
nity, nursing home, etc.). Furthermore, there is little if any consist-
ency in the way data are both collected and analysed.
What is known is that pressure injuries are costly to both the
patient and healthcare provider. The cost of treating pressure inju-
ries has been estimated to range from £2000 (Category/Stage I) to
£20 000 (Category/Stage IV) (2016/17 figures), with increases in
the cost relating to both increased length of hospital stay and
increased frequency of complications. Costs to the patient include Shear force, e.g. from sliding down a bed.

increased length of hospitalisation, pain, reduction in overall qual-

ity of life and increased risk of morbidity and mortality. There is
also a significant burden placed on family and carers.

Pathogenesis
Mechanical loading by direct pressure or shear forces will lead to defor-
mation of the tissues. This deformation may cause damage to cell
structures and impair transport processes such as blood and lymphatic
flow. Resulting cell death triggers an inflammatory response leading to
localised oedema and increased interstitial pressures, further increas-
ing the mechanical load present and perpetuating the damage.
Sustained tissue deformation is the key process that characterises pres-
sure injuries. The level of mechanical load that leads to a pressure
injury depends on a number of factors, including tissue tolerance to
loading forces. This is influenced by age, disease states, temperature,
perfusion, tissue type and ­composition of the soft tissues.
Key definitions in pressure injury pathogenesis.
Term Description
Mechanical load Any type of force applied to the tissues by contact
between the skin and a solid surface
Normal force Type of external mechanical load that is perpendicular to
the skin surface
Shear force Type of external mechanical load that is parallel to the skin
surface
Friction Contact force parallel to the skin surface caused by an
individual’s body weight or medical device. Can be
static (no relative movement between the two interfaces)
or dynamic (relative movement occurs between the two
interfaces)
Friction is a complex force. Static friction, the inability of two
surfaces to move across each other, causes high points of shear as
cells and tissues deform in an attempt to move with gravity. Once
the movement is sufficient to overcome static friction, dynamic
friction occurs where the two surfaces move in opposing direc-
tions. Frictional forces may lead to epidermal stripping and the for-
mation of intraepidermal blisters, which in turn lead to superficial
skin erosions. Loss of skin barrier function may increase the risk of
pressure injury. Such forces may occur, for example, when a patient
is repositioned in bed without the use of a slide sheet or as a result
of ill-­fitting prosthetic devices or footwear.
Friction forces, e.g. repositioning a patient on a bed sheet.
An excessively moist environment, caused, for example, by perspi-
ration, urinary or faecal incontinence or excessive wound drainage,
enhances the deleterious effects of pressure and friction. It also causes
maceration of the skin, which compounds these factors.
Classification
Many different classification tools are available. The most widely
used tool is the international classification system developed jointly
by the NPIAP, EPUAP and PPPIA in 2014. The numerical categories/
stages (I–IV) are based on the deepest tissue type exposed, i.e. seen in
the wound base or directly palpated. It is important to remember that
anatomical location will affect the tissue type exposed. For example,
the bridge of the nose, the pinna of the ear and malleolus have very
little subcutaneous tissue and so more advanced pressure injuries
may actually present as shallow ulcers. In some cases the depth of the
injury cannot be determined. These injuries are termed unstageable
or suspected deep tissue injuries, depending on the clinical features.
The numerical system is not intended to imply progression or heal-
ing. Pressure injuries should not be downstaged despite observation
of healing. However, deep tissue injuries and unstageable injuries can
be reclassified once the depth of injury becomes evident.
There has been much discussion about the allocation of this
numerical category or stage as research in this area suggests that
clinicians are unable to classify pressure injuries reliably. Newer
guidance is suggesting the adoption of only two categories: superficial
pressure injuries – those that only affect the skin – and deep pres-
sure injuries – those that are deeper than the skin. Biomechanical
research is beginning to uncover a clearer picture of how deforma-
tion in the deep tissues results in Category/Stage III and IV ­pressure
injuries, whilst Category/Stage I and II are more related to
superficial forces and the element of shear (and therefore
­
­deformation) plays a smaller part.
44 ABC of Wound Healing

Category/Stage I: Non-blanchable redness of intact skin

Intact skin with non-blanchable redness of a localised area usually over a bony
prominence. Darkly pigmented skin may not have visible blanching; its colour may
differ from the surrounding area. The area may be painful, firm, soft, warmer or cooler
compared to adjacent tissue. Category/Stage I may be difficult to detect in individuals
with dark skin tones. May indicate ‘at-risk’ individuals (a heralding sign of risk).

Category/Stage II: Partial-thickness skin loss or blister

Partial-thickness loss of dermis presenting as a shallow open ulcer with a red/pink
wound bed, without slough. May also present as an intact or open/ruptured
serum-filled blister. Presents as a shiny or dry shallow ulcer without slough or bruising.
* This category/stage should not be used to describe skin tears, tape burns, perineal
dermatitis, maceration or excoriation.
*Bruising indicates suspected deep tissue injury.

Category/Stage III: Full-thickness skin loss (fat visible)

Full-thickness tissue loss. Subcutaneous fat may be visible but bone, tendon or muscle
is not exposed. Slough may be present but does not obscure the depth of tissue loss.
May include undermining and tunnelling. The depth of a Category/ Stage III pressure
ulcer varies by anatomical location. The bridge of the nose, ear, occiput and malleolus
do not have subcutaneous tissue and Category/Stage III ulcers in these areas can be
shallow. In contrast, areas of significant adiposity can develop extremely deep Catego-
ry/Stage III pressure ulcers. Bone/tendon is not visible or directly palpable.

Category/Stage IV: Full-thickness tissue loss (muscle/bone visible)

Full-thickness tissue loss with exposed bone, tendon or muscle. Slough or eschar may
be present on some parts of the wound bed. Often includes undermining and
tunnelling. The depth of a Category/Stage IV pressure ulcer varies by anatomical
location. The bridge of the nose, ear, occiput and malleolus do not have subcutaneous
tissue and these ulcers can be shallow. Category/Stage IV ulcers can extend into muscle
and/or supporting structures (e.g. fascia, tendon or joint capsule), making osteomyelitis
possible.

Definition of Category/Stage I to IV pressure injuries from the International NPIAP/EPUAP Pressure Ulcer Classification System (2014).

Unstageable: Depth unknown

Full-thickness tissue loss in which the base of the ulcer is covered by slough (yellow, tan, grey, green or brown) and/or eschar (tan, brown or black)
in the wound bed. Until enough slough and/or eschar is removed to expose the base of the wound, the true depth, and therefore category/stage,
cannot be determined. Stable (dry, adherent, intact without erythema or fluctuance) eschar on the heels serves as the body's natural (biological)
cover and should not be removed.
Definition of unstageable pressure injuries from the International NPIAP/EPUAP Pressure Ulcer Classification System (2014).
 Pressure Injuries 45

Suspected Deep Tissue Injury: Depth unknown

Purple or maroon localised area of discoloured intact skin or blood-filled blister due to
damage of underlying soft tissue from pressure and/or shear. The area may be
preceded by tissue that is painful, firm, mushy, boggy, warmer or cooler compared to
adjacent tissue. Deep tissue injury may be difficult to detect in individuals with dark
skin tones. Evolution may include a thin blister over a dark wound bed. The wound
may evolve further and become covered by thin eschar. Evolution may be rapid,
exposing additional layers of tissue even with optimal treatment.

Definition of suspected deep tissue injury, from the International NPIAP/EPUAP Pressure Ulcer Classification System (2014).

Prevention and treatment or enteral (via a nasogastric or percutaneous endoscopic gas-

Many countries, including the UK and USA, are now following the
‘Bundle’ approach to pressure injury prevention and management.
This focuses on a small number of key activities which, if p
­ erformed
correctly and consistently, will help prevent pressure injuries
occurring.
Bundle approach.
The aSSKINg bundle (used in the UK) includes:
• Assessment of risk
• Skin assessment and management
• Surface selection and use
• Keeping the patient moving
• Incontinence and moisture assessment and management
• Nutrition and hydration
• Giving of information
Source: NHS England’s National Stop the Pressure programme.
https://nhs.stopthepressure.co.uk/index.html
Assessment of risk
The purpose of risk assessment is to identify individuals who are
susceptible to pressure injury in order to implement strategies
aimed at reducing risk. Although many factors have been described
as contributing to the risk of developing pressure injuries,
immobility has been identified as being the most important.
Consideration should be paid to the duration of immobility, i.e. is it
temporary (sedation/limb fracture) or permanent (spinal cord
injury, chronic neurological condition)? Other important factors
include the following.
Nutritional and hydration status: there is a correlation between
the degree of malnutrition and the extent and severity of pres-
sure injury. Malnutrition also impairs healing. Measures of
nutritional status predictive of pressure injury formation
include decreased body weight, decreased triceps skinfold
thickness and lymphopenia. Serum albumin is a commonly
used surrogate marker but its relatively long half-­life makes it
inaccurate; serum prealbumin and transferrin are more relia-
ble. Attention to nutrition is critical in the prevention and
management of pressure injuries. Patients at high risk and
those with established ulceration should be assessed and
reviewed by a dietitian. Supplementary feeding, either assisted
trostomy [PEG] tube), may be necessary. Vitamins and trace
element supplementation should also be provided. Adequate
hydration is essential.
Factors affecting perfusion and oxygenation (e.g. pulmonary disease,
peripheral arterial disease, cardiac disease, low blood pressure):
care should be exercised on the use of drugs such as sedatives,
analgesics and those that alter blood flow, such as antihyperten-
sives. Patients requiring inotropes are particularly susceptible.
Patients with diabetes may have both altered sensation (due to
peripheral neuropathy) and reduced tissue perfusion (due to car-
diovascular disease) and so may be at higher risk of pressure
damage.
Skin hydration: both dry skin and excessive skin moisture are risk
factors. Emollients may be needed to rehydrate skin and barrier
preparations can be used to protect skin from excess moisture.
Skin status: the presence of a Category/Stage I pressure injury indi-
cates that the individual is at risk of developing a deeper pressure
injury. Repositioning for the management of a pressure injury
can put other areas at risk.
Advanced age: while advanced age alone is not a risk factor, it is asso-
ciated with comorbidities that increase the risk of immobilisation
and pressure injury, e.g. fractures, faecal and urinary inconti-
nence, dry skin, multiple comorbidities with the associated poly-
pharmacy due to chronic systemic conditions (e.g. diabetes),
altered sensation (e.g. stroke, sedation) and terminal illness.
The effects of all risk factors should be minimised through
­optimal management.
Risk assessment tools
A systematic evaluation of risk factors will help identify individuals
at risk of pressure injury. Many risk assessment tools (RATs) have
been developed. All at-­risk individuals should be assessed at ­regular
intervals and the RATs should be used as an adjunct to, not a
­substitute for, clinical judgement. The Waterlow Score, Braden
Scale and PURPOSE T tool are the most widely used in the UK.
Skin assessment
Inspection of the skin should be carried out at every opportunity,
ensuring bony prominences and any other at-­risk areas are checked.
If needed, equipment such as masks, catheters and cannulae should
be moved to visualise the underlying skin. Any clothing or devices
such as antiembolic or compression stockings should also be removed
to visualise the heels. Consideration should be given to the level of
46 ABC of Wound Healing

Components of three risk assessment scales.

PURPOSE-­T Waterlow Braden

Mobility Yes Yes Yes

Sensation Yes Yes Yes
Skin status Yes Yes No
Previous history of pressure damage Yes No No
Age No Yes No
Gender No Yes No
Specific predisposing diseases Yes Yes No
Nutritional status Yes Yes Yes
Skin moisture (e.g. incontinence) Yes Yes Yes
Prolonged pressure (e.g. on operating table) No Yes No
Friction and shear No No Yes
Medical device Yes No No

No one assessment scale assesses all possible risk factors.

sensation the patient has in the lower extremities and simple exami-
nation tools can be used to identify peripheral neuropathy.

Surface selection
Redistributing pressure from high-­risk areas aims to prevent pres-
sure damage. Once a pressure injury has occurred, pressure redis-
tribution is key to prevent further damage and to allow healing to
occur.

(a)

(a)

(b)

Types of support surface. (a) Mattress made from pressure-­redistributing

(b) foam, a type of reactive support surface. (b) An active support surface; note
the pump at the end of the bed. When the pump is activated, air cells within
Reactive support surfaces. (a) An inflatable cushion. (b) An inflatable boot. the mattress allow alternating inflating and deflating to redistribute pressure.
 Pressure Injuries 47

(a) (b)

(a) Large unstageable pressure injury (covered in eschar) on the lower back. (b) Almost complete healing following surgical debridement and negative pressure
wound therapy.

A wide range of equipment exists for patients managed in a bed

or chair, such as mattresses and overlays, cushions and heel protec-
tors. A reactive support surface changes load distribution when a
person lies or sits on it. An active support surface requires a power
supply and changes load distribution with or without a person sit-
ting or lying on it. The type of equipment used depends on the
patient’s needs and the level of risk from pressure damage; expert
advice should be sought. In the hospital setting, the majority of bed
spaces now have electronic bed frames that assist in both moving
and handling the patient and also redistributing the patient’s
weight. Manual repositioning is still required even when patients
have sophisticated support surfaces as this not only allows the skin
to be checked but also serves to prevent other complications such as
urinary and chest infections. While regular turning is recom-
mended, placing the patient on their back or side should be avoided,
as this places them directly on a large bone. Use of positions such as
the 30° tilt avoids positioning the patient on a large bone and sup-
ports their weight on large muscles such as the buttocks.
Additional specialist equipment may be required to float the
heels off a surface when heels are considered to be particularly vul-
nerable. Specialist products exist to help redistribute pressure in Category/Stage IV pressure injury with necrotic muscle and bone in the
difficult areas of the body where devices may cause abnormally wound base. The bone may feel irregular or crumbly to touch, highly
high pressure, for example over the bridge of the nose or beneath a suggestive of osteomyelitis.
catheter, and should be initiated before damage occurs.

Wound care
Basic wound care, for example cleansing and use of appropriate
dressings, is vital to aid healing once pressure injuries have
occurred. Care should be taken to ensure that the dressing does not
increase the pressure over the injured area or damage the surround-
ing skin. Debridement should also be performed to remove any
non-­viable tissue (e.g. slough or eschar); however, necrotic tissue at
the heel may be left in situ and allowed to self-­ debride.
­Negative-­pressure wound therapy may be useful in the manage-
ment of excess exudate and aiding healing after debridement of
non-­viable tissue. Pain relief may be required, especially prior to
dressing changes.
Safeguarding
Pressure injuries may occur as a result of neglect or maltreatment of
children or adults. When this is suspected, local procedures for raising
concerns should be followed to ensure appropriate investigation and
future prevention. Documentation and photographs are important in
all cases but especially when there are safeguarding concerns.
48 ABC of Wound Healing
Surgery
Surgical debridement may be necessary for extensive Category/
Stage III–IV pressure injuries and flap reconstruction may be
required to close the defect. However, it is still vital to ensure that
any contributing factors (i.e. ongoing pressure damage, nutritional
status, smoking status, etc.) are addressed as recurrence rates are
high. While surgical treatment may be appropriate in a small subset
of patients with pressure injuries, many patients will not have access
to this or be declined surgical intervention by appropriately trained
professionals due to the risks of surgery and/or the high risk of
recurrence. Larval debridement may be useful in patients unfit for
surgery. Other surgical procedures, for example defunctioning
colostomy, may be useful to prevent faecal contamination of open
wounds on the sacrum/buttocks in incontinent patients.
Complications
Infection is a common complication of pressure injuries; this ranges
from localised wound infection to systemic sepsis. When bone is
exposed, there is a risk of developing osteomyelitis, which may
require treatment with a prolonged course of antibiotics and/or
surgical debridement. Amputation may be required for severe pres-
sure damage to the limbs. Rarely, amyloidosis or malignancy may
arise as a result of chronic ulceration.
References
European Pressure Ulcer Advisory Panel, National Pressure Injury
Advisory Panel and Pan Pacific Pressure Injury Alliance. Prevention
and Treatment of Pressure Ulcers/Injuries: Quick Reference Guide.
Emily Haesler (Ed.). EPUAP/NPIAP/PPPIA: 2019.
National Pressure Ulcer Advisory Panel, European Pressure Ulcer Advisory
Panel and Pan Pacific Pressure Injury Alliance. Prevention and
Treatment of Pressure Ulcers: Clinical Practice Guideline. Emily Haesler
(Ed.). Cambridge Media: Osborne Park, Western Australia; 2014.
Further reading
Dealey, C., Posnett, J., and Walker, A. (2012). The cost of pressure ulcers in the
United Kingdom. Journal of Wound Care 21 (6): 261–266.
Gillespie, B.M., Chaboyer, W.P., McInnes, E. et al. (2014). Repositioning for
pressure ulcer prevention in adults. Cochrane Database of Systematic
Reviews 4: CD009958.
McInnes, E., Jammali-­ Blasi, A., Bell-­
Syer, S.E.M., and Leung, V. (2018).
Support surfaces for treating pressure ulcers. Cochrane Database of
Systematic Reviews 10: CD009490.
National Institute for Health and Care Excellence (NICE). (2014). Pressure
ulcers: prevention and management (CG179). www.nice.org.uk/guidance/
CG179.
 CHAPTER 8
Uncommon Causes of Ulceration
Girish K. Patel1,2 and Vincent Piguet3,4
1
Welsh Institute of Dermatology, Cardiff and Vale University Health Board, Cardiff, UK
2
Cardiff University School of Biosciences, Cardiff, UK
3
Dermatology, Department of Medicine, University of Toronto, Toronto, Canada
4
Dermatology, Women’s College Hospital, Toronto, Canada
OVERVIEW
•  Ulceration has many causes; rarer pathologies should be
suspected when ulcers present in atypical locations, without the
classic features of more common pathologies, or fail to respond
as expected to treatment.
•  Histopathological analysis (biopsy) is often helpful to establish a
diagnosis.
•  In systemic diseases, the pathological process itself can lead to
skin ulceration, but drug treatments (e.g. immunosuppression)
and other complications (e.g. anaemia) can contribute to
non-­healing.
•  Treatment may require specialist advice and input from secondary
care specialties such as rheumatology, dermatology and renal
medicine.
This chapter describes some of the many rarer causes of ulceration.
Pathologies that are more common in certain parts of the world,
such as leprosy, fungal infections, Buruli ulcer and ulceration
resulting from Kaposi sarcoma, are not covered here.
Inflammatory disorders
Connective tissue diseases
Skin ulceration is a feature of many connective tissue diseases. For
example, ulceration develops in up to 10% of patients with rheuma-
toid arthritis. In addition to the underlying disease process, healing
can also be impaired by complications such as anaemia, skin atro-
phy, dependent oedema, deformity, neuropathy, microvascular dis-
ease, local factors and the toxic effects of drugs used in disease
treatment.
Ulceration associated with connective tissue disease is usually of
rapid onset or enlargement, associated with pain (not relieved by
raising or lowering the leg), fever, malaise, arthralgia and myalgia.
The ulcer may have an atypical location, tender margin and/or a
violaceous or erythematous inflammatory border. Occasionally
ABC of Wound Healing, Second Edition. Edited by Annie Price, Joseph E. Grey, Girish K. Patel, and Keith G. Harding.
© 2022 John Wiley & Sons Ltd. Published 2022 by John Wiley & Sons Ltd.
multiple skin ulcers occur. Treatment may require immunosup-
pressants, including steroids and/or cytotoxic agents.
Pyoderma gangrenosum
This is an uncommon ulcerating lesion that may be associated with
pathergy  – the appearance of lesions at the site of trauma (e.g.
venepuncture). Surgical debridement of pyoderma gangrenosum
often leads to worsening of the ulceration. The diagnosis of pyo-
derma gangrenosum is primarily clinical but may be associated
with specific features on histology. Other causes, such as vasculitis,
infection or malignancy, should be excluded. There is usually a his-
tory of a painful sterile pustule/nodule with surrounding erythema,
which eventually ruptures and ulcerates.
The predominant features are pain and rapid expansion of the
ulcer, which has a characteristic erythematous or violaceous
overhanging edge. The wound bed is often purulent and may
extend to muscle. The most commonly affected area is the lower
leg, but pyoderma gangrenosum can occur anywhere on the
body. It may also occur around stoma sites (termed peristomal
pyoderma gangrenosum). The underlying aetiology is unknown,
but at least 50% of cases are associated with underlying active
or quiescent systemic disease such as inflammatory bowel dis-
ease, seronegative rheumatoid arthritis and lymphoproliferative
disorders.
Treatment is usually with immunosuppressants, which may be
topical or systemic.
Necrobiosis lipoidica diabeticorum
This usually presents as a pretibial yellowish atrophic plaque. It is
frequently associated with diabetes mellitus and has a propensity to
ulcerate, usually as a result of minor trauma. Typically, such ulcera-
tion is slow to heal, painful and frequently complicated by infec-
tion. In most cases, the ulceration will heal with appropriate wound
care and the use of potent topical corticosteroids to the surround-
ing skin. Topical PUVA (psoralen and ultraviolet A) therapy may
also have a role.
49
50 ABC of Wound Healing

Cutaneous necrosis
Blood flow
Vessel intima
Blood constituents

Common causes
Inflammatory disorders
Venous hypertension
Ulceration Connective tissue disease
Peripheral arterial disease
Skin disease
Diabetic foot ulceration

Neuropathic Malignancy Metabolic Infection latrogenic

disease Dermatitis
artefacta

Uncommon causes of ulceration.

(b)

(a) (c)

Examples of uncommon causes of ulceration. (a) Acroangiodermatitis or pseudo-­Kaposi sarcoma, a rare angioproliferative disorder in this case associated with
paralysed limbs. (b) Martorell hypertensive ulcers, caused by poorly controlled blood pressure. (c) Ulceration due to tophaceous gout; gouty tophi are palpable
in the wound and surrounding skin.
 Uncommon Causes of Ulceration 51

Connective tissue disorders that can cause and/or exacerbate chronic

ulceration.

Rheumatoid arthritis
Systemic lupus erythematosus
Dermatomyositis
Systemic sclerosis
Sjogren syndrome
Behçet disease

Peristomal pyoderma gangrenosum.

An ulcer caused by rheumatoid arthritis. The deformity of the foot also

contributes to delayed healing.

Necrobiosis lipoidica diabeticorum.

Change in blood flow

Change in the vessel Change in blood

intima constituents

Virchow’s triad of thrombosis.

Pyoderma gangrenosum. The wound bed is purulent and the edge is blood constituents. This provides a useful framework within which
inflamed/violaceous. to consider the causes of cutaneous necrosis.

Cutaneous necrosis due to a change in blood flow

Cutaneous necrosis
Cutaneous necrosis is a manifestation of tissue death that occurs as
a consequence of rapid ischaemia, often as the result of vessel occlu-
sion. The pattern and extent of necrosis are a manifestation of the
size of the affected vessels. In the 1860s, Rudolf Virchow proposed
that thrombus formation was attributable to three components: a
change in blood flow, a change in the vessel intima and a change in
Rapid reduction in local blood flow that may arise from an embolic
event, severe perniosis (chilblains) or Raynaud phenomenon can
present with dramatic digital necrosis. Raynaud phenomenon can be
primary (Raynaud disease) or secondary, related to a variety of con-
ditions such as connective tissue diseases. All patients with Raynaud
phenomenon should be advised to avoid the cold, refrain from smok-
ing and reduce caffeine intake. Long-­acting calcium channel antagonists
52 ABC of Wound Healing

such as nifedipine are often helpful. Topical vasodilators, for example
glyceryl trinitrate, may also be of benefit. In severe chronic disease,
cervical sympathectomy can be undertaken while in severe acute
necrotising disease, infusions with prostaglandin E1 or prostacyclin
(prostaglandin I2) can save digits.
Cutaneous necrosis due to a change in the vessel
intima
There are many causes of cutaneous necrosis attributable to changes
in the vessel intima.
Calciphylaxis is characterised by painful, haemorrhagic skin necro-
sis with a reticulated edge. Skin histology shows vessel intramural
hyperplasia, intravascular calcification and thrombosis. Calciphylaxis
most often occurs in patients with renal failure undergoing dialysis
but it can occur in patients with normal renal function (termed non-­
uraemic calciphylaxis), where it may be associated with hyperparathy-
roidism or may be idiopathic. Treatment consists of analgesia, removal
of calcium deposits at the site of any ulceration and control of predis-
posing factors.
Almost all types of vasculitis can present with skin necrosis.
Some types, such as Wegener granulomatosis and classic polyarte-
ritis nodosa, can cause chronic ulceration. The vasculitides are
classified according to the size of vessel affected. The medium-­
sized vessel vasculitides present with painful nodules that may
ulcerate. Small vessel vasculitis typically presents with palpable
purpura.

Cutaneous necrosis due to a change in blood

Sclerodactyly caused by systemic sclerosis. The patient also suffers from
Raynaud phenomenon.
constituents
A number of coagulation factors have now been identified in asso-
ciation with cutaneous necrosis, due to either genetic or acquired
alteration in function. In addition, there are a number of syndromes
associated with hypercoagulability.
Antiphospholipid syndrome is a heterogeneous group of dis-
orders characterised by the presence of autoantibodies against
various phospholipids, including lupus anticoagulant and anti-
cardiolipin. It mostly affects females and may be associated
with systemic lupus erythematosus. Antiphospholipid syn-
drome may present with multiple arterial and venous throm-
botic episodes, recurrent spontaneous miscarriage and the
presence of livedo reticularis (mottled discolouration of the

(a) (b)

(a) Cutaneous calcinosis (calcium deposits in the skin). (b) Calciphylaxis (calcification of the small vessels in the skin and subcutaneous fat).

Causes of vasculitis classified according to the size of vessel affected (Chapel Hill Consensus Conference, 1992).

Large vessels Medium-­sized vessels Small vessels

Giant cell (temporal) arteritis Classic polyarteritis nodosa Wegener granulomatosis

Takayasu arteritis Kawasaki disease Churg–Strauss syndrome
Microscopic polyangiitis
Henoch–Schönlein purpura
Essential cryoglobulinaemic vasculitis
Cutaneous leucocytoclastic vasculitis

Adapted from Jennette et al. 1994.


(a)
(a) Purpuric rash associated with cutaneous vasculitis. (b) Cutaneous leucocytoclastic vasculitis.
skin). Antiphospholipid syndrome is a cause of livedoid
vasculopathy, a disorder characterised by painful ulceration in
association with livedo reticularis and atrophie blanche.
Livedoid vasculopathy has also been described in association
with factor V Leiden mutation. Treatment for this progressive,
painful and debilitating condition requires anticoagulation, in
addition to therapies to treat the underlying disease.
Warfarin necrosis is an uncommon transient phenomenon
which occurs at the initiation of warfarin therapy in the absence of
heparin. Females are more commonly affected and individuals are
usually in the sixth or seventh decade of life. Warfarin necrosis
typically involves sites abundant in subcutaneous fat, such as
breasts, hip, buttock and thigh. The administration of warfarin
results in a transient decrease of vitamin K-­sensitive factors, includ-
ing protein C, resulting in a temporary hypercoagulable state that
spontaneously corrects itself. Warfarin therapy should therefore be
continued.
Heparin necrosis is rare and may be caused by both unfrac-
tionated and low molecular weight heparin. It is associated
with the formation of antibodies that lead to platelet clumping.
The continued use of heparin leads to greater platelet clump-
ing and emboli affecting both cutaneous and internal organs.
Cutaneous necrosis occurs at injection and distant sites.
Continuation of heparin therapy aggravates the condition,
with potentially fatal consequences, and it should be stopped
immediately.
Purpura fulminans includes three different syndromes: neonatal,
associated with sepsis and postinfective (including COVID-­19).
Widespread capillary and venule thrombosis occurs, causing pur-
pura and skin necrosis. Characteristically, skin necrosis favours the
extremities and in particular the digits. Purpura fulminans is a
complication of either hereditary or acquired protein C or protein S
deficiency.
Uncommon Causes of Ulceration 53
(b)
Coagulation factor abnormalities associated with cutaneous necrosis.
Protein C deficiency
Protein S deficiency
Antithrombin III deficiency
Heparin cofactor II deficiency
Homocystinaemia
Raised prothrombin concentrations
Factor XII deficiency
Factor V Leiden mutation
Infection
Staphylococcus aureus and beta-­haemolytic Streptococcus pyogenes
are responsible for many of the infections that can complicate exist-
ing ulceration. They may also, in certain circumstances, be the
cause of ulceration. Beta-­haemolytic Streptococcus may lead to ery-
sipelas, bullous cellulitis, punched-­out ulceration (ecthyma) and
necrotising fasciitis. Where there is a history of foreign travel,
Leishmania, atypical Mycobacterium and deep mycotic infection
should also be considered as causes of ulceration. In patients with
AIDS or other immunosuppressive states, ulceration may be a
manifestation of infection with syphilis, tuberculosis, bacillary
angiomatosis, herpes simplex and cytomegalovirus infection.
Malignancy
Many types of cancers, including metastases, present with skin
ulceration, including the most common forms of skin cancer,
basal cell carcinoma and squamous cell carcinoma. Although the
incidence of squamous cell carcinoma increases with age, it may
present in younger individuals with a genetic predisposition, a
history of excessive ultraviolet light exposure or a history of organ
54 ABC of Wound Healing
transplantation (requiring immunosuppression). Squamous cell
carcinoma may also develop within long-­standing chronic ulcera-
tion associated with burns, scalds, radiotherapy or venous disease
(Marjolin ulcer). Features of malignancy include rapid enlargement
of the lesion despite conventional treatment, pain, bleeding and
often a rolled edge. Squamous cell carcinoma arising in long-­
standing chronic ulcers can exhibit a more aggressive phenotype,
with a greater potential to metastasise.
In most cases of skin cancer, the preferred treatment is surgical
excision. However, when there is significant comorbidity or dis-
seminated metastatic disease, palliative treatment in the form of
radiotherapy and local wound care may be more appropriate.
(a)
(c)
Skin malignancies. (a) Basal cell carcinoma. (b) Squamous cell carcinoma. (c) Cutaneous lymphoma. (d) Malignant melanoma.
Drug and iatrogenic causes
Hydroxyurea, used to treat myeloproliferative diseases, may cause a
painful, shallow, lower leg ulcer, usually over the medial malleolus,
up to 15 years after commencement of therapy. Healing is normally
only achieved when hydroxyurea is discontinued.
Radiotherapy, used to treat benign and malignant diseases, is
associated with an endarteritis that may result in ulceration and
impair wound healing. Furthermore, after radiotherapy, the skin is
at increased risk of ulceration as a result of chronic radiation der-
matitis, allergic contact dermatitis, squamous cell carcinoma and
angiosarcoma.
(b)
(d)

Punch biopsy taken from a chronic leg ulcer for histopathological analysis.
The wound edge and bed should be included in the sample to allow
comparison between the wound and the normal skin.
A non-­healing surgical wound due to radiotherapy damage to the
surrounding skin.
Dermatitis artefacta
Also known as factitious wounding, dermatitis artefacta describes
the creation of skin lesions by the patient themselves, usually due to
an underlying psychological problem. It is different from deliberate
self-­harm, as patients try to conceal the cause of the wound. There
may be a history that is incongruent with the appearance of the
wound, and the wound may be in an atypical location. Further clues
Uncommon Causes of Ulceration 55
Dermatitis artefacta. Note the unusual location on the thigh and healthy
surrounding skin.
can be gained from the pattern of the lesion and skin biopsy to
exclude pathology and identify the presence of foreign material.
Occasionally admission to hospital is necessary to verify the diag-
nosis. Direct confrontation of the patient is unhelpful. Ideally, these
cases should be managed by a multidisciplinary team involving a
psychologist or psychiatrist, but patients often refuse to engage
with mental health services. Complications can arise from these
wounds, for example infection and scarring, and therefore ongoing
supportive management is important.
Reference
Jennette J.C., Falk R.J., Andrassy K., et al. Nomenclature of systemic vascu-
litides. Proposal of an International Consensus Conference. Arthritis
Rheum 1994;37:187–192.
Further reading
Cohen, P.R. (2009). Neutrophilic dermatoses: a review of current treatment
options. American Journal of Clinical Dermatology 10 (5): 301–312.
Enoch, S., Miller, D.R., Harding, K.G., and Price, P.E. (2004). Early diagnosis
is vital in the management of squamous cell carcinomas associated with
chronic non-­healing ulcers: a case series and review of the literature.
International Wound Journal 1 (3): 165–175.
Nigwekar, S.U., Thadhani, R., and Brandenburg, V.M. (2018). Calciphylaxis.
New England Journal of Medicine 378: 1704–1714.
Panuncialman, J. and Falanga, V. (2010). Unusual causes of cutaneous ulcera-
tion. Surgical Clinics of North America 90 (6): 1161–1180.
Rawlings, C.R., Fremlin, G.A., Nash, J., and Harding, K. (2016). A
rheumatology perspective on cutaneous vasculitis: assessment and
investigation for the non-­rheumatologist. International Wound Journal
13 (1): 17–21.
 CHAPTER 9

Infections
Brendan Healy1 and Andrew Freedman2,3
1
Microbiology Department, Public Health Wales, Cardiff, UK
2
Cardiff University School of Medicine, Cardiff, UK
3
Cardiff and Vale University Health Board, Cardiff, UK

OVERVIEW Signs of wound infection

•  Infection is a major cause of delayed healing in both chronic and

• Redness
acute wounds.
• Heat
•  Management of all wounds requires inspection of the wound.
• Pain
Wounds cannot be managed without visible inspection.
• Swelling
•  Wound infections are diagnosed clinically based on the patient’s
• Exudate (purulent, serous or serosanguinous)
symptoms and characteristics of the wound and surrounding skin.
• Odour
•  Most wound infections are superficial, but deeper or systemic
• Poor healing
infections can occur.
• Contact bleeding
•  Pus or tissue specimens are preferred to wound swabs.
• Epithelial bridging
•  Microbiological results of wound specimens do not diagnose
• Tissue breakdown
wound infections but are useful to guide antibiotic therapy in
• Presence of unhealthy granulation tissue
clinically infected wounds.
• Systemic illness in the absence of other focus of infection

Despite optimal treatment, some wounds are slow to heal. In
chronic wounds, infection perpetuates the abnormal inflammatory
response, contributing to delayed healing. The challenge clinically
and microbiologically is to identify those wounds in which healing
is impaired as a result of infection and in which systemic or topical
antimicrobial treatment will be of benefit. Whilst most infections
are superficial, involving the wound and surrounding skin, more
severe infections can occur, including systemic sepsis, abscess for-
mation, osteomyelitis and necrotising fasciitis. In addition, inade-
quate control of localised wound infection can lead to cellulitis,
lymphangitis, bacteraemia, systemic inflammatory response syn-
drome, multiorgan failure and death.
Infection in acute wounds usually presents with the classic
signs of redness, swelling, heat and pain. In chronic wounds, how-
ever, infection can be more difficult to diagnose. The host
response is often affected by the presence of underlying disease,
such as diabetes, chronic venous insufficiency or peripheral arte-
rial disease, and the signs of infection may be more subtle.
Currently, there is no diagnostic test available that can confirm or
refute the presence of infection, although several point-­of-­care
tests are being developed.
Staphylococci and streptococci are the most commonly encoun-
tered pathogenic organisms in community-­ acquired superficial
wounds. More unusual organisms may be found in bite wounds,
reflecting the oral flora of the biting animal. Pathogenic organisms
causing surgical wound infections vary according to the anatomical
site of surgery and source of the organism and reflect the endogenous
and local/hospital flora (e.g. more antibiotic-­resistant organisms,
including methicillin-­resistant Staphylococcus aureus [MRSA]).
Management of bite wounds
• Carry out meticulous surgical debridement and cleansing of wound.
• Send deep tissue specimens for microbiology testing.
• Consider empirical treatment with antibiotics.
• Consider tetanus prophylaxis.
• Seek microbiological advice if bite was by exotic animal.
All chronic wounds are colonised by bacteria. Bioburden
(the  number of bacteria present) is described as a continuum,

ABC of Wound Healing, Second Edition. Edited by Annie Price, Joseph E. Grey, Girish K. Patel, and Keith G. Harding.
© 2022 John Wiley & Sons Ltd. Published 2022 by John Wiley & Sons Ltd.

56
 Infections 57

Severity of clinical signs

Local Systemic
Contamination Colonisation
infection infection

Contamination: Presence of non-replicating micro-organisms in the wound – these

are rapidly cleared by host defences

Colonisation: Presence of replicating organisms adherent to wound bed

without causing cellular damage to host

Local infection: Classic signs of infection (redness (erythema), warmth,

swelling, and pain) may be present with or without surrounding cellulitis. Often
microbiologically described as bacterial burden of >150 organisms/mm3

Systemic infection: Increasing bacterial burden in the wound. If untreated, this

will result in systemic dissemination resulting in sepsis; progression may lead
to multiorgan failure and even death

Spectrum of bioburden in chronic wounds.

(a) (b)

(c) (d)

(a) A clean, healing wound. (b) A leg ulcer with heavy slough, likely colonised with bacteria - this should be debrided to aid healing. (c) A leg ulcer with necrotic
and unhealthy tissue, which can suggest localised infection - often treated with debridement plus topical antimicrobials e.g. silver dressings. (d) An ulcer with
surrounding cellulitis - this requires systemic antibiotics.

from ­contamination, to colonisation, to localised and systemic ­ otoriously difficult to recognise and treat. A combination of
n
infection. The organisms present are often polymicrobial and regular debridement to disrupt the biofilm, cleansing with
can form biofilms – communities of microbes that are resistant antiseptics and use of topical antimicrobial dressings is
­
to antimicrobials and evade host defences. Biofilms are recommended.
58 ABC of Wound Healing

Sampling wounds Types of sample

Superficial wound swabs  The ease of obtaining and processing
When to sample
superficial wound swabs, combined with their relatively low cost
It is inappropriate to sample all wounds. Samples for culture should be
and non-­invasive nature, make them the most appropriate method
taken only from overtly infected wounds and from wounds that are
for wound sampling in most instances. Organisms cultured from a
deteriorating, increasing in size or failing to make satisfactory progress
superficial swab may, however, simply reflect the colonising bacte-
despite an optimal environment for wound healing. Indicators of
rial flora and are not always representative of the pathogenic organ-
wound infection include redness, swelling, purulent exudate, smell,
isms invading deeper tissue. This is particularly relevant to deep
pain and systemic illness in the absence of other foci. Subtle signs of
surgical and deep penetrating wounds.
local wound infection include unhealthy ‘foamy’ granulation tissue,
contact bleeding, tissue breakdown and epithelial bridging. Wound
Tissue and pus  Tissue or pus, or both, should be collected when-
sampling may also be indicated for surveillance of drug-­ resistant
ever possible, as growth from these samples is more representative
organisms (depending on local protocol) and prior to certain surgical
of pathogenic flora. They are also amenable to quantitative
procedures, such as skin grafting.
­microbiological analysis and other techniques used to improve the

(a) (b)

Change in exudate can indicate wound infection. (a) Purulent exudate. (b) Green exudate (typical of Pseudomonas infection).

(a) (b)

Changes in the wound bed can indicate wound infection. (a) Unhealthy granulation tissue in a diabetic foot ulcer. (b) Necrotic tissue with surrounding skin
erythema.
 Infections 59

Charcoal swab used to perform a superficial wound swab.

Quantitative analysis  Bacterial load greater than 100 000 organ-

How to take a superficial wound swab
• Removal of superficial debris followed by swabbing of the wound
bed is considered the best way to obtain a superficial wound
swab.
• Swabs containing transport media and charcoal should be used as
they help to preserve bacteria before laboratory analysis.
• Timely delivery of the swab to the microbiology laboratory is
essential.
diagnostic yield (e.g. broth culture). Tissue sampling should always
be performed when therapeutic debridement of the wound is
­carried out, and when superficial sampling methods have been
ineffective. It is also preferable to sample bone prior to starting
­antibiotic treatment in cases of osteomyelitis.
Less invasive techniques  Methods such as dermabrasion and
various absorbent pads exist. A wide range of products are availa-
ble, but none are currently in routine use.
Microbiological analysis
Semi-­quantitative analysis  Most laboratories will perform a
semi-­quantitative analysis on wound swabs. This entails grading
bacterial growth as scanty, light, moderate or heavy. Semi-­
quantitative analysis introduces a bias towards motile and fast-­
growing organisms. Fastidious organisms such as anaerobes may be
under-­represented. Semi-­quantitative counts have been shown to
correlate with quantitative tissue counts in both burn wounds and
diabetic foot ulcers.
isms or colony-­forming units per gram of tissue is a predictor of
wound infection. However, some wounds that are more heavily colo-
nised will heal spontaneously and, conversely, some organisms are
able to cause severe infection at much lower levels of colonisation.
Infection depends on the pathogenicity of the organism, the type of
wound and the host response.
Interpretation of results  Most wound swabs will yield bacterial
growth. Growth of bacteria from wounds is not synonymous with
infection, and treatment based on microbiological results alone is
not warranted. Wound infection is determined by the clinical pic-
ture, not by microbiological results. Growth of organisms from
wound samples is used to guide antibiotic therapy in clinically
infected wounds.
Treatment
Wound infections in association with systemic illness, deep inva-
sion or cellulitis require empirical systemic antibiotic treatment
while culture results are awaited. Choice of treatment will depend
on factors such as the type and site of the wound, previous micro-
biological results and host factors such as drug allergies and comor-
bidities. Local antimicrobial prescribing guidelines should be used
to select the most appropriate empirical antibiotics and expert
advice should be sought where necessary.
Selecting the most appropriate treatment modality for locally infected
wounds is more challenging. Treatment with topical antiseptics such as
silver compounds or iodine will be sufficient in many wounds and
should be instituted first line wherever possible. Topical treatment
avoids the potential side-­ effects of systemic antibiotics, such as

Microbiological analysis.

Type of analysis Suitable samples Advantages Disadvantages

Gram stain Tissue, pus or dry swab transported
immediately to laboratory
Quantitative culture Tissue, pus, dermabrasion specimens,
absorbent pad specimens
Semi-­quantitative culture All specimens
Instant results, good correlation with
quantitative counts
Counts >105 organisms or colony-­forming
units per gram of tissue predict wound
infection
Practical, can be carried out on swab
specimens, some correlation with quantitative
analysis
Poor sensitivity; no antibiotic sensitivity
pattern
Invasive, labour intensive, costly,
impractical for all samples
Imprecise, bias towards motile/
fast-­growing organisms
60 ABC of Wound Healing

Clostridium difficile diarrhoea, anaphylaxis, gastrointestinal upset and
selection of resistant organisms. However, topical treatments some-
times produce local irritant effects, which can, paradoxically, lead to
delay in wound healing. Systemic treatment may be indicated if topical
medication has been unsuccessful. Local guidelines should be followed
in conjunction with microbiology results and expert advice where
appropriate.
disproportionate to clinical signs, anaesthesia over the infected area
and systemic illness.
Osteomyelitis associated with wound infection
Osteomyelitis may develop after direct inoculation of bone from a
contiguous focus of infection. This can be a devastating complica-
tion of wound infection, requiring specialist intervention and
management.

Topical antimicrobial preparations Diagnosis  The diagnosis of osteomyelitis should be considered

• Iodine-­releasing agents (povidone‑iodine preparations,
cadexomer‑iodine preparations)
• Potassium permanganate solution
• Acetic acid solution (particularly effective against Pseudomonas)
• Silver-­releasing agents (composite silver dressings, silver
sulfadiazine)
• Topical antibiotics (e.g. metronidazole)
in any chronic wound that does not heal despite optimal treat-
ment or in any wound (especially in those with diabetes) that can
be probed to bone. Plain x-­rays of the affected area should be the
first line of investigation. Radiographic changes, however, can lag
behind the evolution of infection by at least 2  weeks; a single,
negative plain x-­ray film does not therefore exclude osteomyelitis.
Magnetic resonance imaging is more sensitive than plain radiog-
raphy. Nuclear scintigraphy, either a technetium bone scan or a

In general, topical antibiotics are not recommended. Reasons for

this include inadequate penetration for deep skin infections, devel- Clinical features of necrotising fasciitis.
opment of antibiotic resistance, hypersensitivity reactions, systemic
absorption when applied to large wounds and local irritant effects. Early presentation Late presentation
Short courses of topical antibiotics can be useful in certain circum-
• Pain (may be disproportionate • Severe pain
stances (e.g. topical metronidazole for malodorous wounds).
to clinical signs) • Skin discolouration (purple or black)
• Cellulitis • Blistering
Specific infections • Swelling of affected region • Haemorrhagic bullae
• Induration • Crepitus
Necrotising fasciitis • Skin anaesthesia • Discharge of ‘dishwater’ fluid
Clinicians must always be alert to the possibility of necrotising • Fever • Severe sepsis or systemic inflammatory
• Tachycardia response syndrome
­fasciitis. A high level of suspicion followed by prompt aggressive
• Multiorgan failure
surgical debridement of devitalised necrotic tissue is essential if
the  patient is to survive. Important clinical markers include pain Based on Hasham et al. (2005).

(a) (b) (c)

Surgery for necrotising fasciitis. (a) Necrotising fasciitis of the groin - the appearance at the time of diagnosis. (b) Extensive wound following emergency surgical
debridement. (c) Healing wound during treatment with negative pressure wound therapy.
 Infections
Chronic osteomyelitis of the tibia associated with multiple wounds on the
anterior lower leg.
labelled white cell scan, may also be helpful but requires careful
interpretation. It can be difficult to differentiate osteomyelitis
from chronic soft tissue infection irrespective of the modality
used.
X-­ray showing osteomyelitis of the fourth metatarsal, associated with a
diabetic foot ulcer. There has been a previous transmetatarsal forefoot
amputation.
61
Management  Antibiotics penetrate poorly into devitalised
bone, and long courses of antibiotics may be required. It is there-
fore important to define the infecting organism(s) from the outset
so that antibiotic treatment can be targeted. Ideally, in the absence
of systemic illness, microbiological sampling of the infected bone
should precede antibiotic therapy. Surgery followed by prolonged
systemic antibiotic treatment (generally a minimum of 6 weeks),
may be indicated in selected patients. Surgery enables debride-
ment of all necrotic bone and tissue and provides deep samples
for microbiological analysis. In some patients, surgery is not pos-
sible either because of the site of the wound or because of the
patient’s comorbidities. Under these circumstances, a prolonged
course of antibiotics may be warranted.
Choice of treatment is dependent on the antibiotic sensitivity
pattern of the infecting organism(s) along with antibiotic proper-
ties, such as bone penetration, and host factors, such as drug allergy.
Combination therapy is often used to gain maximal effect.
Inflammatory markers (C-­reactive protein) and radiological images
can be used to monitor response, but radiological improvement will
often lag behind clinical improvement by up to 6 weeks.
In chronic osteomyelitis, long-­term suppressive therapy or
periodic antibiotic treatment at times of wound deterioration
or wound-­associated systemic illness may be appropriate.
Methicillin-­resistant Staphylococcus aureus
Topical antimicrobial agents, such as iodine and silver compounds,
have activity against MRSA and may be used in localised wound
infection when there is no evidence of invasion, cellulitis or sys-
temic upset.
In a systemically unwell individual, glycopeptides (vancomycin
or teicoplanin) are still often used first line. Daptomycin is an alter-
native option. In all cases of MRSA osteomyelitis and in some
MRSA wound infections, a second antistaphylococcal agent with
good penetration to bone and superficial skin sites is often added,
for example fusidic acid or rifampicin. Both rifampicin and fusidic
acid can cause hepatitis and regular monitoring of liver function is
required.
Oral options for MRSA infections include oxazolidinones (line-
zolid, tedizolid), clindamycin, doxycycline and co-­ trimoxazole.
Rifampicin or fusidic acid are often used as partner drugs. Neither
rifampicin nor fusidic acid should be used as monotherapy as
resistance can develop on treatment. The combination of rifampicin
with fusidic acid is generally avoided because of the perceived risk
of hepatotoxicity.
Oxazolidinones have excellent bioavailability, can be adminis-
tered orally and have good skin and bone penetration. They are
generally well tolerated in short courses (under 2  weeks).
Oxazolidinone use is currently limited by their side-­effect profile,
which includes bone marrow suppression and optic nerve disor-
ders. Linezolid is licensed for use for a maximum of 28 days.
Pseudomonas wound infection
Pseudomonas can cause particular problems when managing
wounds. It often colonises ‘wet’ wounds such as venous ulcers and
burns. When Pseudomonas is present, the wound can have a dis-
tinctive odour and green colour and it will often produce copious
62 ABC of Wound Healing

Osteomyelitis suspected or can probe to bone

Is the patient systemically unwell?

Yes No

Swab wound and Plain x ray

start empirical
antibiotic treatment

Is osteomyelitis proved?

Yes No

Consider further Discuss with radiologist

imaging to identify and consider other imaging
extent of infection (eg. MRI, bone scan)

Is ostemyelitis proved?

Yes No

Is Surgery indicated?

Yes No

Empirical antibiotic regime

started at induction, surgical
specimens to microbiology

Four to six Consider Treat as soft tissue

week course of prolonged course infection. Consider
antibiotics guided of antibiotic imaging again after
by microbiology treatment two to four weeks

Algorithm for management of suspected osteomyelitis.

amounts of exudate. As such, it is often possible to diagnose the
presence of Pseudomonas clinically. Topical acetic acid (concentra-
tion 1–5%) is extremely effective at treating wounds that are colo-
nised/infected with Pseudomonas and should be used first line
wherever possible.
Care must be taken when treating Pseudomonas infections with
systemic antibiotics. There are a very limited number of options
and only one oral option (quinolones, e.g. ciprofloxacin). In addi-
tion, Pseudomonas can readily develop resistance to antibiotics dur-
ing treatment. As such, systemic treatment should be used
judiciously. If therapy is given unnecessarily and resistance devel-
ops, future treatment is made more difficult. Dual therapy is a strat-
egy that is sometimes employed to reduce the risk of resistance
developing. In the opinion of the authors, systemic therapy should
 Infections
Chest sinuses caused by chronic mediastinitis following cardiac surgery.
also always be combined with topical therapy (e.g. acetic acid) to
help reduce the burden of infection on the surface and in an attempt
to reduce development of resistance.
Before starting systemic antibiotics, the wound should be care-
fully assessed. Topical treatment should be applied first wherever
possible. Systemic therapy should be reserved for those patients
who are systemically unwell, those who do not respond to topical
treatment and those with clear evidence of infection in the wound
base or surrounding tissues. Treating the underlying cause of the
wound is also important to reduce the risk of recurrence.
Pseudomonas will not thrive in a dry wound.
63
Infections that cause chronic wounds
Occasionally, chronic wounds can be caused by deep infections, for
example chronically infected implants. Sinus formation from the
site of infection to the skin can result in wounds that have high
exudate levels. Unless surgical intervention or antibiotics can treat
the underlying infection, the wound will not heal. In cases where
these treatment options are not possible, long-­term antibiotic sup-
pressive therapy may keep the infection under control and appro-
priate dressing regimes should be used to relieve the patient’s
symptoms.
Some specific types of infective organisms can cause skin changes
and/or wounds, for example tuberculosis, cutaneous leishmaniasis
and melioidosis. Such infections are rare in the UK, but should be
considered in returning travellers or immigrants from endemic
areas. Whenever suspected, discussion with the local microbiology
department is required as specialist tests and treatment will be
needed.
Reference
Hasham, S., Matteucci, P., Stanley, P.R., and Hart, N.B. (2005). Necrotising
fasciitis. BMJ 330: 830–833.
Further reading
International Wound Infection Institute (IWII) (2016). Wound Infection in
Clinical Practice. London: Wounds International.
Lipsky, B.A., Senneville, E., Abbas, Z.G. et al. (2020). Guidelines on the
diagnosis and treatment of foot infection in persons with diabetes
(IWDGF 2019 update). Diabetes/Metabolism Research and Reviews 36
(S1): e3280.
Lipsky, B.A., Dryden, M., Gottrup, F. et al. (2016). Antimicrobial stewardship
in wound care: a position paper from the British Society for Antimicrobial
Chemotherapy and European Wound Management Association. Journal of
Antimicrobial Chemotherapy 71: 3026–3035.
 CHAPTER 10

Lymphoedema and Wounds
Christine Moffatt1 and Melanie Thomas2
1
School of Social Sciences, Nottingham Trent University, Nottingham, UK
2
Lymphoedema Network Wales, NHS Wales Health Collaborative, UK

Lymphoedema is a chronic condition and can have a major impact

OVERVIEW
•  Lymphoedema is common, with over 250 million people affected
worldwide.
•  Lymphoedema is often intermingled with the term chronic
oedema; both occur as a result of failure of the lymphatic system.
•  There are many causes; primary lymphoedema is due to a
developmental abnormality of the lymphatic system whereas
secondary lymphoedema is caused by acquired damage to the
lymphatic system.
•  Lymphoedema can result in a number of skin changes, including
cellulitis and skin ulceration.
•  Reduction of swelling, through skin care, massage, exercise and
compression, is the mainstay of treatment.
In many healthcare systems, the care of patients with lymphoedema
or chronic oedema occurs in separate services to those treating
patients with wounds. This lack of integration contributes to poor
outcomes, with wounds failing to heal in the presence of oedema
and chronic wounds contributing to oedema formation. In recent
years, however, there has been a growing appreciation of the need
to define the epidemiology and natural history of this problem in
order to improve outcomes and standardise care delivery.
There is considerable misunderstanding about who is affected by
lymphoedema throughout the world. In developing countries, it is
most commonly associated with lymphatic filariasis, a tropical dis-
ease caused by parasitic infection that is transmitted by mosquitoes.
In the West, it is usually thought of as a consequence of cancer and
its treatment, with particular emphasis placed on the breast cancer
population (of whom a quarter develop the condition). In fact, only
a third of the patients treated for lymphoedema have a cancer diag-
nosis; approximately 10% suffer with primary lymphoedema and
over 60% have secondary lymphoedema, associated with condi-
tions such as venous disease, immobility and comorbidities such as
heart failure and obesity. Estimates of world prevalence range from
140 to 250 million and indicate how imprecise our understanding
of the problem remains.
on patients’ quality of life. Increased limb size can affect mobility
and body image, as well as causing pain and discomfort. Skin
problems including recurrent cellulitis are common and may
­
require long-­term antibiotics and frequent hospitalisations.
Defining lymphoedema
Lymphoedema is oedema that has been present for 3 months or
more. Lymphoedema is often intermingled with the term chronic
oedema; both occur as a result of failure of the lymphatic system.
The lymphatic system is a network of vessels and nodes that trans-
ports interstitial fluid from the tissues to the bloodstream. It is
also involved in immune defence, transporting lymphocytes,
­bacteria, proteins and cell debris. Abnormalities or damage to the
lymphatic system can lead to swelling of one or more limbs as well
as the corresponding quadrant of the trunk. It can also cause
swelling of the head, neck, breast or genitalia, and even affect the
internal organs.
Causes of lymphoedema
Primary lymphoedema is caused by a congenital disease or devel-
opmental abnormality of the lymphatics and can present at birth,
early or late in life. Secondary lymphoedema occurs due to damage
of the lymphatic system, caused by cancer treatment (e.g. lymph
node dissection or radiation treatment), trauma, immobility,
­obesity and venous disease.
Types of primary lymphoedema
• Congenital lymphoedema – present at birth or in early infancy
• Lymphoedema praecox – onset between 2 and 35 years of age
(most commonly during puberty)
• Lymphoedema tarda – onset after 35 years of age

ABC of Wound Healing, Second Edition. Edited by Annie Price, Joseph E. Grey, Girish K. Patel, and Keith G. Harding.
© 2022 John Wiley & Sons Ltd. Published 2022 by John Wiley & Sons Ltd.

64
 Lymphoedema and Wounds 65

(a) (b)

Lymphoedema resulting from cancer treatment. (a) Unilateral upper limb lymphoedema. (b) Unilateral lower limb lymphoedema.

(a) (b)

(a) Lymphoedema caused by trauma to the lower limb. (b) Lymphovenous oedema.

Structural and functional abnormalities of the lymphatics fre-
quently coexist. Low output failure, i.e. reduced lymphatic trans-
port, results from aplasia/hypoplasia, obstruction, valvular
incompetence and loss of contractibility (e.g. due to loss of move-
ment). High output failure occurs due to overloading of the lymph
transport capacity, such as in liver cirrhosis, nephrotic syndrome,
cardiac failure or venous insufficiency. Long-­standing high output
failure can result in a damaged lymphatic system, perpetuating the
problem.
Whatever the underlying cause, lymph stagnates, with the accu-
mulation of protein, macromolecules, hyaluronan, fat, water and
cell debris in the interstitium. Secondary degenerative changes in
the tissue and chronic inflammation develop due to impaired
lymph transport of immune cells. The accumulated fluid is also a
rich culture medium for bacteria, and these factors together can
lead to a cycle of recurrent episodes of cellulitis, often accompanied
by wounds that further damage the lymphatics, leading to worsen-
ing oedema and tissue changes such as fibrosis and adipose tissue
deposition.
Complications of lymphoedema
• Skin changes and chronic wounds
• Recurrent cellulitis
• Lymphangiosarcoma (Stewart–Treves syndrome)
66 ABC of Wound Healing

Primary lymphoedema.

Staging Effects of lymphoedema on the skin

Progression of disease has been described using a number of
staging systems. The most commonly used classification system
was developed by the International Society of Lymphology and
it defines progression according to changes in the tissues. All
classifications in use have their limitations and are not empiri-
cally ­validated. It is often difficult in practice to assess tissue
changes and objective methods to assess fibrosis are not widely
available. However, the progression of tissue changes is thought
to be important in predicting response to treatment such as
compression therapy.
Lymphoedema causes many disturbances in the skin that can lead
to the development of chronic wounds. Common skin changes seen
in patients with lymphoedema are described below.
Hyperkeratosis
Thickening of the skin with excess levels of keratin, resulting in
brown/grey patches. It is often exacerbated by mechanical trauma
such as low-­grade friction from footwear and compression devices.
It should not be confused with acanthosis nigricans (hyperpigmen-
tation of the skin associated with obesity and endocrine disorders).

Papillomatosis
Firm, raised projections of the skin due to dilation of lymphatic
Stages of lymphoedema. vessels and fibrosis, often accompanied by hyperkeratosis.

Stage Description Lymphangiectasia

Soft fluid-­filled projections or cysts caused by dilation of lymphatic
Stage 0 Latent or subclinical condition where swelling is not
clinically evident despite impaired lymph transport and the vessels. They frequently rupture with minor trauma, leading to
risk of developing lymphoedema is noted. Stage 0 can exist lymphorrhoea.
for many years
Stage 1 Early accumulation of fluid that is high in protein. Swelling can
temporarily reduce with elevation. Tissues are soft and often
pitting oedema is present. Excess volume between limbs of
<20%
Stage 2 Accumulation of fluid with pitting/non-­pitting oedema that
does not reduce on elevation. At later stages, skin changes
such as fibrosis may be present. Excess volume between limbs
of 20–40%
Stage 3 Non-­pitting swelling with skin changes including
hyperkeratosis, papillamatosis, recurrent cellulitis and an excess
limb volume of >40%

International Society of Lymphology (2016). Hyperkeratosis.

 Lymphoedema and Wounds 67

Examples of wounds associated with lymphoedema and chronic oedema.

Wound types

Venous ulceration Associated with varicose veins, deep vein thrombosis, obesity and reduced mobility
Infection Manifestation of cellulitis
Necrotising fasciitis/panniculitis
Fungal infection
Trauma Orthopaedic surgery
Compression damage from inappropriate padding during bandaging
Pressure damage often associated with neuropathy
Neuropathic Pressure damage following inappropriate application of compression therapy
Pressure ulceration
Tumour Wounds due to treatment such as surgery or radiotherapy
Invasive tumours causing fungating wounds
Skin tumours such as basal cell carcinoma, squamous cell carcinoma and melanoma
Dermatological Venous eczema
Allergic contact dermatitis/irritant dermatitis
Erosive pustular dermatitis
Stewart–Treves syndrome (lymphangiosarcoma) – a rare complication of lymphoedema
Pemphigus/pemphigoid – may occur due to friction or insufficient padding under compression
Morbid obesity Wounds occur due to a combination of factors, for example pressure ulceration, mycotic infection,
immobility and decreased function, poor skin care
Congestive cardiac failure Wounds in the gaiter region are common in severe heart failure
Self-­inflicted A rare problem. Secretan syndrome occurs when patients use a tourniquet to artificially induce an
obstructive oedema
’Wet legs’ Superficial wounds as a result of lymphorrhoea which causes skin to become macerated

Papillomatosis.

Lymphorrhoea where it can lead to cellulitis. Other causes of folliculitis include

Beads of lymph fluid that seep from oedematous tissues when
breaks appear in the skin. Lymphorrhoea often causes ‘wet legs’,
increasing the risk of superficial wounds, ulceration and cellulitis.
Folliculitis
Inflammation of the hair follicles, usually due to bacterial or fungal
infection, leads to a rash with small pustules within a localised area.
It can occur anywhere but is particularly common on the trunk,
buttocks and limbs. Use of emollients may cause a non-­infective
folliculitis as cream embeds within the hair follicle. Staphylococcus
aureus is the most common organism associated with folliculitis,
fungal infections such as Candida, which usually affects moist areas
such as skinfolds.
Cellulitis
Cellulitis occurs in over 50% of patients with lymphoedema due to
their impaired immune response. In many patients, recurrent epi-
sodes of cellulitis occur and often result in hospitalisation for intra-
venous antibiotics. Group A streptococcal and S. aureus infections
are the main cause, but the causative organism is not always identi-
fied. Clinical features include pain, swelling, warmth, redness, lym-
phangitis and blistering. More severe cases result in systemic upset.
68 ABC of Wound Healing
Cellulitis – the right lower limb is swollen and erythematous.
In rare cases, cellulitis may lead to sepsis, necrotising fasciitis and
panniculitis, particularly in immunocompromised patients.
Infection may occur due to tinea pedis, venous eczema, ulceration,
damaged toe nails or trauma from pets, plants or insects. Acute
cellulitis further damages the lymphatics, worsening oedema.
Guidelines from the British Lymphology Society are available on
the management of cellulitis in lymphoedema, and some patients
require long-­term prophylactic antibiotics.
Contact dermatitis
Localised skin irritation caused by exposure to an irritant or aller-
gen causes redness, blistering and itching/pain. It is common in
patients with oedema, especially those with venous ulceration due
to loss of the barrier function of the skin and regular, prolonged use
of topical treatments and dressings. Patch testing is useful to iden-
tify allergens. Exacerbating factors include incontinence, poor
hygiene and failure to control the oedema.
Innervation
Peripheral neuropathy may directly and indirectly influence blood
and lymphatic flow, the formation of the protective mantle and
recognition and response to noxious stimuli. Paralysed limbs
develop chronic oedema through the combined effects of hyperae-
mia, gravity, loss of the lymphovenous pump and immobility.
Wounds in patients with lymphoedema and peripheral neuropathy
are usually caused by unrecognised trauma from shoes, compres-
sion therapy, wheelchairs or injury.
Ulceration
Chronic inflammation, susceptibility to infection and reduced
­tissue perfusion due to the presence of oedema increase the risk of
Ulceration caused by compression bandaging.
skin ulceration and will also impair healing. Ulceration rarely
occurs in patients with primary lymphoedema except as a compli-
cation of cellulitis or venous disease. Venous ulceration occurs as
consequence of ambulatory venous hypertension and may occur
following minor trauma or associated venous eczema. A propor-
tion of patients report that ulceration occurs spontaneously with no
evident trigger but the formation of oedema is a known risk factor
for recurrence. Some patients have coexisting conditions, for exam-
ple lymphoedema and peripheral arterial disease, therefore holistic
assessment and consideration of other causes of ulceration are
important.
Management of lymphoedema
The International Consensus Best Practice Document
(Lymphoedema Framework  2006) outlines the management of
lymphoedema. Management requires a holistic, multidisciplinary
approach to deliver decongestive lymphatic therapy that includes
the following:
• Exercise and movement to enhance lymphatic and venous flow.
• Swelling reduction and maintenance to reduce the limb size/­
volume and improve tissue consistency through compression
and manual lymphatic drainage.
• Skin care to optimise the condition of the skin, treat any compli-
cations and minimise the risk of cellulitis.
• Risk reduction to avoid factors that may exacerbate
lymphoedema.
• Pain and psychological management to enhance self-­management
and self-­efficacy.
Although the evidence base for decongestive therapy is growing,
there are still many unanswered questions about this multimodal

Lower limb ulcers caused by lymphoedema.
treatment and how it is used in the heterogeneous population.
Currently, treatment is considered in the following two stages:
Intensive treatment: the aim of this stage is to provide intensive
treatment to reduce the oedema, reshape the limb and improve
skin conditions such as lymphorrhoea. Treatment consists of the
application of multilayer compression bandages with skin care,
exercise and manual lymphatic drainage. Intensive treatment is
carried out over a number of weeks (usually 1–4) although most
oedema reduction occurs within the first week. Bandages are
applied and removed daily or a few times a week to support
oedema reduction.
Long-­term management/maintenance therapy: this phase focuses
on limiting further deterioration of swelling, enhancing limb
function and gaining long-­ term control of the swelling.
Compression is mainly provided through compression gar-
ments, wraps and compression devices although some patients
may choose to self-­bandage, particularly at night. Support,
education and encouragement are key to helping patients
adjust to living with a chronic condition and maximising their
ability to self-­manage and achieve a sense of control. When
there is a failure of the initial treatment or a deterioration of
swelling, the patient may undergo a further period of inten-
sive treatment.
Palliative management
In patients with a poor prognosis or terminal illness, the period
of intensive treatment is adapted with the focus on relief of symp-
toms, prevention of complications and maximising quality of life.
Compression bandaging or lower compression garments are
often effective at reducing congestion in these situations. Specific
Lymphoedema and Wounds 69
palliative lower compression garments are available along with
padded night-­time support.
Other treatment options
Surgery may be appropriate for selected cases, for example if there
is severe disability due to swelling or following failure of conserva-
tive treatment. This can involve debulking of excess subcutaneous
tissue and skin, or liposuction to remove excess adipose tissue.
Long-­term maintenance compression therapy is required postop-
eratively. Lymphovenous bypass and lymph node transplant surger-
ies have also gained evidence in restoring lymphatic function, but
these procedures are not readily available to all lymphoedema
patients.
Although commonly used, diuretics are not recommended for
the treatment of lymphoedema and should be reserved for patients
with specific comorbidities such as congestive cardiac failure.
Wound management
Successful management of patients with lymphoedema and wounds
depends on establishing the correct diagnosis and identifying coex-
isting and contributory factors in order to develop an individual-
ised plan of treatment. Principles of effective wound management
are essential, with exudate control being a high priority and highly
dependent on control of the oedema through compression therapy.
Effective wound healing requires the control of lymphoedema and
where possible the eradication of complications such as cellulitis.
Approaches combining expertise from the wound healing and lym-
phoedema communities are showing improvement in health out-
comes such as reduced episodes of cellulitis and improvements in
quality of life and function.
70 ABC of Wound Healing
Acknowledgements
We would like to thank Lymphoedema Network Wales for provid-
ing us with the clinical images in this chapter.
References
International Society of Lymphology (ISL) (2016). The diagnosis and treat-
ment of peripheral lymphoedema: 2016 consensus document of the
International Society of Lymphology. Lymphology 49: 170–184.
Lymphoedema Framework (2006). Best Practice for the Management of
Lymphoedema: International Consensus. London: MEP Ltd.
Further reading
British Lymphology Society. (2016). Consensus Document on the
Management of Cellulitis in Lymphoedema. Lichfield: British Lymphology
Society.
Moffatt, C.J., Keeley, V., Franks, P.J. et al. (2017). Chronic oedema: a prevalent
health care problem for UK health services. International Wound Journal
14 (5): 772–781.
Olszewski, W.L. (2003). Pathophysiological aspects of lymphoedema of
human limbs: 1. Lymph protein composition. Lymphatic Research and
Biology 1 (3): 235–243.
 CHAPTER 11
Nutrition, Skin Care and Continence
Amy Ferris1, Joseph E. Grey1, and Girish K. Patel2,3
1
 Department of Clinical Gerontology, Cardiff and Vale University Health Board, Cardiff, UK
2
 Welsh Institute of Dermatology, Cardiff and Vale University Health Board, Cardiff, UK
3
 Cardiff University School of Biosciences, Cardiff, UK
OVERVIEW
•  Malnutrition can impair wound healing processes; a balanced
diet, including adequate intake of carbohydrates, proteins, fats,
vitamins and trace elements, is important.
•  Further assessment by a dietitian to ensure adequate intake may
be required in those who are malnourished, those with poor
nutrition or those with large, complex wounds including burns
and pressure injuries.
•  Surrounding skin complications including dryness, maceration,
allergy and eczema are common and may lead to delayed healing
of existing wounds or development of new skin breakdown.
•  Faecal and urinary incontinence may lead to excess moisture and
change in pH, resulting in skin breakdown.
•  Management of incontinence includes practical measures to
manage symptoms and treatments to address the underlying
cause.
Nutrition
Both under-­and overnutrition can have a negative effect on
wound healing and tissue integrity. Energy requirements
increase during wound healing, initially to counteract the cata-
bolic response to trauma and then to match the anabolic drive
of the proliferative phase of wound healing. Restoration of the
extracellular matrix and cellular proliferation requires energy
from adequate nutrition (carbohydrates, fats and occasionally
proteins), protein synthesis and degradation (amino acids) and
cofactors in the form of vitamins and trace elements. Nutritional
support should strive to minimise the effects of catabolism and
meet the needs of the anabolic phase, preferably through the
most effective enteral route.
Maintenance of a healthy weight is important for all patients.
Obesity has many implications for health and is also associated
with delayed wound healing, an increased risk of developing
peripheral vascular disease, deep vein thrombosis and
decreased mobility (which can all contribute to lower limb
wound formation).
ABC of Wound Healing, Second Edition. Edited by Annie Price, Joseph E. Grey, Girish K. Patel, and Keith G. Harding.
© 2022 John Wiley & Sons Ltd. Published 2022 by John Wiley & Sons Ltd.
Carbohydrates and fats
The main energy requirement in simple wounds is for collagen syn-
thesis. A reduced calorie intake may have detrimental effects on
collagen synthesis, configuration, deposition and remodelling and
may lead to breakdown of proteins to supplement energy when car-
bohydrate and fat availability is limited. Only large complicated
wounds, in the presence of a catabolic state (e.g. burn injury or sep-
ticaemia), are likely to have a direct metabolic impact on total
energy requirements, which is estimated in most adults at
30–35 kcal/kg of body weight per day.
Sugars are not the only sources of energy. Fatty acids produce six
times more energy than glucose and are also crucial constituents of
the mediators of inflammation and the cell membrane. Glycolipids
and glycoproteins (sugars, proteins and lipids covalently linked
together) are also crucial components of the cell membrane as well
as an energy source.
Proteins
One-­ third of the body’s protein is collagen and almost three-­
quarters of the protein in the skin is collagen. Collagen imparts
both tensile strength and flexibility to the skin, hence deficiencies
or defects in collagen dramatically impair wound healing. Proteins
are a crucial component of a functioning immune system and defi-
ciency may lead to an increased risk of wound infection. Protein
requirement can increase from 1.25 g/kg body weight up to 2 g/kg
body weight for patients with very deep wounds, such as Category
III or IV pressure injuries. Up to 100 g of protein can be lost per day
through wound exudate, which needs to be factored into patients’
nutritional plans.
While essential amino acid deficiency is uncommon, supraphysio-
logical doses of two specific amino acids have been reported to
enhance wound healing. Levels of arginine, a precursor for proline
during collagen synthesis, decrease after injury. Arginine is important
in maintaining a positive nitrogen balance, stimulating T-­lymphocyte
function, release of growth factors and generation of nitric oxide.
There is some evidence that arginine supplementation along with oral
nutritional supplements may promote wound healing in adults.
71
72 ABC of Wound Healing
Glutamine is important in gluconeogenesis and is a precursor for the
synthesis of nucleotides. Glutamine may enhance neutrophil killing
and stimulate the release of growth hormones and is a potent antioxi-
dant (in the glutathione form). Supplemental glutamine has been
advocated for the treatment of wounds but the true benefit of this
remains to be established.
Vitamins
Vitamins are fundamental compounds that cannot be synthesised
de novo by humans. Most cases of vitamin-­associated poor wound
healing arise in the context of malnutrition, when multiple nutri-
ents are deficient. The importance of vitamin C in wound healing is
well documented and a significant role for vitamins A and E has
also been identified.
Historical perspective of the importance of vitamin C
in wound healing
• In 1498, the Portuguese sailor Vasco da Gama, while travelling
around the tip of Africa, gave an account of scurvy among his
sailors and observed the rapid disappearance of symptoms after
the ship reached shore and the crew were able to consume fruits.
• Sir James Lancaster took bottles of lemon juice during his voyage
to the East Indies in 1601 to prevent scurvy.
• In 1747, the Scottish physician James Lind conducted the first
clinical trial among patients with scurvy and observed the rapid
and dramatic effects of citrus fruit. Lind concluded that citrus
fruits were the ‘most effectual remedies for distemper at sea’.
• In 1795, another Scottish physician, Sir Gilbert Blane, persuaded
the Lords of the Admiralty to approve the taking of citrus fruits
for long sea voyages.
• The incidence of scurvy declined dramatically, with occasional
prominence, such as during the Great Potato Famine and the First
World War.
• Attempts to reproduce the disease in an animal model were
successful in 1907, when Axel Holst and Theodor Frölich
developed the guinea pig model and showed that scurvy was a
disorder of dietary deficiency.
• In 1927, the Hungarian scientist Albert Szent-­Györgyi isolated
vitamin C from oranges and cabbages and reported its effective-
ness in preventing scurvy in the guinea pig model.
• In 1939, Dr John Crandon investigated the effects of vitamin C
deficiency on wound healing on himself. After 182 days
abstaining from vitamin C, an old appendicectomy scar began to
disintegrate and a newly formed wound failed to heal, confirming
the importance of vitamin C deficiency in wound healing.
• It is now known that vitamin C is a specific cosubstrate for the
enzymes 4-­hydroxylase and lysyl hydroxylase, which are important
in collagen biosynthesis.
The retinoic acid form of vitamin A is necessary for normal
growth and stratification of the skin. Supplemental vitamin A has
been shown to improve wound healing in dietary deficiency. It may
also moderate the adverse effects of corticosteroids, cyclophospha-
mide, γ-­irradiation and diabetes. Administration of vitamin A has
been associated with an increase in collagen deposition, mac-
rophage influx and activation.
Vitamin E maintains and stabilises membrane integrity. It also
protects against oxidative stress, which may be beneficial for the
management of inflammatory lower leg ulcers, such as pyoderma
gangrenosum.
Vitamin K is a vital nutrient for the production of clotting factors
II, VII, IX and X, essential in thrombus formation and the preven-
tion of bleeding.
Trace elements
A number of inorganic compounds are essential for maintaining
skin integrity and also have therapeutic potential in wound healing.
Zinc deficiency is associated with delayed wound healing. However,
while the potential medicinal value of zinc was described in
Egyptian papyri over 3000 years ago, there are few robust data to
confirm the effect of zinc supplementation on wound healing in the
clinical setting.
Magnesium is a cofactor for many enzymatic reactions, includ-
ing collagen synthesis, and is required for normal wound healing.
Copper, a cofactor in protein synthesis, is also essential for wound
healing. Iron is required for hydroxylation of proline and lysine,
both of which are essential for collagen synthesis. It is likely that
many other trace elements are also involved in wound healing and
further research on their role is needed. It remains to be determined
whether supraphysiological doses of these elements provide any
clinical benefit in wound healing.
Assessment of nutritional status
If nutritional screening suggests that a patient has poor nutrition,
referral to a dietitian for expert assessment and management is
advised. The nutritional status of all individuals with wounds needs
to be assessed carefully. Many patients with, for example, pressure
injuries may be malnourished as a result of their primary disease,
difficulty in preparing or eating food or lack of appetite. There are
a number of methods available to make an initial assessment of the
nutritional status.
Assessment of nutritional status.
Non-­invasive Invasive
History of weight loss Serum creatinine/height index
Weight as a percentage of ideal body Serum albumin
weight Serum prealbumin
Anthropometric measurements (e.g. Serum transferrin
triceps skinfold thickness) Serum total iron binding capacity
Lymphocyte count (<1.8 × 109/L)
Urinary nitrogen assessment
Administering nutrition
Nutritional support can improve the rate of wound healing, either
enterally (nutritional supplements by mouth, nasogastric tube or
percutaneous endoscopic gastrostomy [PEG]) or parenterally.
Generally, a ‘food first’ approach is preferred, which may include
high-­energy, high-­protein food options as well as fortification of
foods to increase the nutritional value of meals. This is generally
tolerated well by patients but can be inadequate if they are not able
to eat the quantity of food needed to meet their requirements. Oral

(a)
(a) A standard adult nasogastric tube. (b) A nasogatric tube inserted through the nostril to the stomach.
nutritional supplements may be useful, in the forms of drinks,
yoghurts, shots or mousses, to provide concentrated calories and
nutrition in small volumes.
If patients are unable to swallow due to a mechanical problem or
are unconscious, nasogastric or PEG feeding enables access to the
enteral route for delivery of nutrition. PEG insertion carries a sig-
nificant risk of complications and should only be performed after
careful consideration of alternative options. Nasogastric feeding is
less invasive but there is marked variability in how well it is toler-
ated and repeated problems with tube positioning may prevent
adequate feeding. Nasogastric feeding may also be used to supple-
ment an oral diet in patients who are mechanically able to eat but
are not meeting their dietary requirements.
Total parenteral nutrition, where all nutritional needs are adminis-
tered through the intravenous route, is reserved for a very select group
(a)
(a) Hyperkeratosis in a patient with chronic venous leg ulcers. (b) Severe skin maceration in a patient with chronic lymphoedema.
Nutrition, Skin Care and Continence 73
(b)
of patients in whom either the enteral route is not accessible (e.g.
bowel obstruction or fistulae) or where absorption is significantly
impaired (e.g. short gut syndrome). This specialist intervention car-
ries a significant risk of complications and is generally used as a last
resort when all the other options have been exhausted.
Skin care
In all patients with wounds, care of the surrounding skin is vital to
aid the healing process and to prevent new areas of skin breakdown.
Particularly in leg ulcers, the combination of exudate, irritation and
pressure from occlusive dressings commonly causes skin problems
such as dermatitis, maceration and hyperkeratosis.
Regular skin cleansing, ideally by showering or bathing, use of
non-­perfumed emollients and selection of appropriate dressings
(b)
74 ABC of Wound Healing

(a) (b)

(a) Irritation caused by an adhesive dressing; note the redness is in the distribution of the adhesive borders of the dressing. (b) Eczema of the lower leg and foot.

Common skin problems associated with chronic wounds.

Skin problem Clinical findings Management strategies

Dry skin Scaling and flaking, crust formation, splitting and Wash the area with soap substitutes and apply emollient
fissures regularly to maintain hydration
Maceration Wet skin surface, white tinged tissues, initially feels Add extra padding on top of wound contact layer to contain
soft and boggy then becomes thickened, fibrous exudate, switch to a more absorbent dressing, increase
and stiff frequency of dressing changes. Barrier creams can help protect
vulnerable tissue. Consider compression and elevation to control
oedema if this is a contributing factor. If maceration is already
established, it may require debridement of devitalised tissue to
allow healing
Hyperkeratosis Scaly build-­up of skin cells in small ‘plaque’-­like Wash surrounding skin in soap substitute to encourage the
patches hyperkeratotic plaques to slough off. Consider use of
monofilament debridement pads. Sharp debridement can also
be used to remove hyperkeratotic plaques.
Salicyclic acid preparations may help by softening keratin
Allergy and contact dermatitis Redness, warmth and itching of skin, in the Remove the allergen (patch testing may be needed for
distribution of contact with the allergen. Classically identification). Short-­term topical steroids to treat inflammation
seen as a well-­demarcated patch corresponding to the
shape of the dressing causing sensitivity
Eczema Itching, scaling, erythema, excoriation marks, oozing Ensure regular emollient use and washing with soap substitute.
and weeping with some crusting of exudate Short-­term use of topical steroids.
Wean down steroid use once eczema is controlled as sudden
withdrawal can cause a rebound flare
Incontinence-­associated dermatitis/ Initial erythema progressing to superficial tissue loss, Investigate and where appropriate treat the underlying cause of
moisture lesions usually widespread and uneven over the area of incontinence. Increase the frequency of pad changes if these are
contact and can demonstrate ‘copy’ or ‘kissing’ lesions used. Cleanse the area regularly. Use a water-­based barrier
mirrored either side of a skinfold. Tissue can also cream to protect the skin from further damage. Sometimes
appear macerated or excoriated. In the natal cleft urinary catheters, faecal management systems or even stomas
often presents as a vertical split in the skin can be used to reduce further skin damage from urine and
faeces, but these should be considered a last resort due to their
associated risk

that are changed regularly can prevent or treat these complications.
Until the surrounding skin is in good condition, it is unlikely that a
wound will heal and once healed, it is crucial that good skin care be
maintained both to reduce the risk of scarring and to help prevent
future tissue breakdown.
Continence
Faecal and urinary incontinence may lead to skin breakdown or
exacerbate existing wounds such as pressure injuries. Incontinence
is more prevalent in populations at risk of developing chronic
 Nutrition, Skin Care and Continence 75

wounds, for example older age groups and those with neurological Management of incontinence
disorders. The management of incontinence is key to protect the This may be divided into practical measures to manage symptoms
skin and aid wound healing. and treatments to address the underlying cause. A variety of prod-
Continence is dependent on an integrated system of neuro- ucts and devices are available to help manage urinary and faecal
logical and muscular functions. It requires synchronisation of incontinence, including pads, bottles, urisheaths and bladder cath-
the autonomic muscular contractions of the bladder or bowel eters, faecal management systems, commodes and bladder alarms.
with the higher functions of conscious relaxation of external These strategies are not without potential problems and require
sphincters at an appropriate time and place. A compromise of careful consideration before use. Indwelling urinary catheters
any of these systems may lead to incontinence. Urinary or faecal increase the risk of urinary tract infections and urosepsis, while
incontinence may have a significant impact on patients’ quality pads, if not changed frequently enough when wet, may contribute
of life and their ability to live independently, and may cause to skin damage.
strain for carers. While incontinence is not an inevitable part of The mainstay of treatment for stress incontinence is to strengthen
ageing, its prevalence rises with age and it is recognised as a the pelvic floor. This may be done through a range of means,
‘frailty syndrome’, which can often be improved through careful including pelvic floor exercises, surgical or pessary management of
management. prolapses, and surgery such as urethral sling insertion. Overactive
bladder symptoms may sometimes respond well to bladder retraining,
Causes of incontinence
Urinary incontinence may be categorised as stress, urge, overflow,
functional, or be of mixed aetiology.
Stress incontinence occurs when the urethral sphincter valve is
damaged or inappropriately relaxes and can no longer over-
come an increase in intra-­abdominal pressure (for example,
straining or coughing), leading to uncontrolled release of urine.
It is more commonly seen in patients who have had pelvic sur-
gery, multiple pregnancies or obesity, which increases pressure
on the sphincter. It may also be associated with neurological
conditions such as multiple sclerosis or spinal cord injury,
which lead to inappropriate relaxation and contraction of the
sphincter.
Urge incontinence (also known as overactive bladder or detrusor
instability) occurs when the detrusor muscle of the bladder
contracts spontaneously and forcefully at inappropriate times,
causing frequent, unpredictable and powerful urges to pass
urine, which cannot be overcome. Urisheaths – an option for managing urinary incontinence in men.
Overflow incontinence is seen when the outflow from the blad- The sheath is placed over the penis and connected to a collecting bag.
der is obstructed (e.g. by prostatic enlargement, a gynaeco- Source: Great Bear Healthcare.
logical or bowel mass or even a very full rectum), preventing
effective voiding. As the residual urinary volume increases,
the intravesicular pressure increases, eventually overcoming
the sphincter valve and allowing urine to leak out.
Functional incontinence relates to problems not directly involving
the bladder but rather with the process of accessing the toilet.
Patients may become incontinent because they are unable to
mobilise to the toilet in time, do not have access to the assistance
they need or lack the dexterity to be able to adjust their clothing.
Cognitive impairment may also be associated with continence
problems due to an inability to recognise the biofeedback sensa-
tions associated with maintaining continence.
Faecal incontinence is most commonly associated with condi-
tions affecting the integrity of the internal and external anal sphinc-
ters or their nerve supply. It may also occur when peristalsis is so
powerful that it overcomes the closed sphincter. Other associated
conditions include gastrointestinal malignancies, prolapse,
inflammatory bowel conditions, neurological conditions and
­
Erosion of the urethra caused by an indwelling urethral catheter – a rare but
postoperative complications. Severe constipation may cause
­ serious complication of long-­term urethral catheterisation. Source: Great
­overflow incontinence from the distended rectum. Bear Healthcare.
76 ABC of Wound Healing

Incontinence

Urinary Faecal

Stress Overactive bladder Overflow Functional

Conservative management options

• Pelvic floor exercises • Reduce caffeine
• Pessaries (females • Modify fluid intake
only) • Bladder retraining
exercises
• Optimise bowel regime • Mobility aids
• Double voiding • Commode
• Urinary catheter • Carer support
(intermittent self • Consider personal care aids
catheterisation vs indwelling • Regular toileting schedule
urethral vs suprapubic) • Optimise cognition
• Manage delirium
• Adjust diet to optimise
stool consistency
• Physiotherapy with
biofeedback training
• Faecal management
system

Generic management options: containment devices, review diuretic medications, adjust fluid intake, manage urinary tract infections, optimise BMI

Medical management options

• Anticholinergic • Alpha-blocker (males only) • Manage stool

agent • 5-alpha reductase inhibitor consistency with
• Beta-3 adrenergic (males only) loperamide, laxatives,
agonist suppositories, enemas

Surgical management options

• Pelvic floor repairs • Intravesicular botulinum • Transurethral resection of prostate • Perineal prolapse repair
(females only) toxin injections (males only) • Stoma
• Sacral nerve stimulation • Resection of obstructing uterine
fibroids (females only)

Options for managing incontinence.

but many patients will also require the use of an antimuscarinic

agent or a β3-­adrenergic agonist to relax the detrusor contractions.
Botulinum toxin injections to the bladder or sacral nerve stimula-
tion may also be beneficial.
Bladder outflow obstruction may be managed by the insertion of
a urinary catheter. Pharmacological interventions in men with out-
flow obstruction due to prostatic hypertrophy include treatment
with an α-­blocker, to relax the smooth muscle of the prostate, or a
5α-­reductase inhibitor, to reduce the size of the prostate. For some
men, surgery in the form of a transurethral resection of the prostate
may be necessary.
Improvement in urinary incontinence may also be achieved by
adjusting fluid intake during the day, maintaining a healthy weight,
reviewing medications that may be making symptoms worse (e.g.
diuretics) and ensuring a regular bowel. These measures should be Moisture lesions on the buttock.
trialled prior to considering medical or surgical treatments.

Effects of incontinence on the skin

Individuals suffering with urinary and faecal incontinence are at
significant risk of skin breakdown. Moisture causes skin macera-
tion which, in combination with the pH change caused by the
alkaline properties of urine and faecal proteases, may further
compromise skin integrity. Subsequent loss of skin barrier
f­ unction leads to colonisation by potentially pathogenic bacteria
from perineal and gut flora, most commonly Escherichia coli and
anaerobes (e.g. Clostridium difficile). These bacteria are common
causes of wound bed infection in pressure injuries. Dressing
wounds in the perianal area can be challenging in the presence of

incontinence. The dressings often become soiled, needing more
frequent changes, which may disrupt the wound bed. Dressings
can also become dislodged during personal care, increasing the
risk of infection.
In addition to managing the incontinence itself, the affected skin
also needs to be treated in order to restore its barrier function. This
may take many months even in the absence of further insults. The
skin should be cleansed with an emollient wash, gently dried and
then supported to recover through the application of a water-­
resistant barrier cream. Barrier creams protect against excessive
moisture and reduce degradation of the skin by faecal proteases.
They may also reduce the risk of shear forces, which can easily tear
already macerated skin. Moist skin is often colonised by commen-
sal microbes that may become pathogenic in this environment. In
the absence of overt infection, they should be targeted by changing
their environment. Preparations containing topical antifungals and
antibiotics should be avoided unless there is proven infection, since
they predispose to the development of resistant microbes and aller-
gic contact dermatitis.
Nutrition, Skin Care and Continence 77
Acknowledgements
We would like to thank Great Bear Healthcare for providing us with
the images of urisheaths and urethral erosion.
Further reading
Barber, G.A., Weller, C.D., and Gibson, S.J. (2017). Effects and associations of
nutrition in patients with venous leg ulcers: a systematic review. Journal of
Advanced Nursing 74 (4): 774–787.
Beeckman, D. (2017). A decade of research on incontinence-­associated der-
matitis (IAD): evidence, knowledge gaps and next steps. Journal of Tissue
Viability 26 (1): 47–56.
Clark, M., Schols, J., Benati, G. et al. (2004). Pressure ulcers and nutrition: a
new European guideline. Journal of Wound Care 13 (7): 267–272.
Langemo, D., Anderson, J., Hanson, D. et al. (2006). Nutritional consid-
erations in wound care. Advances in Skin & Wound Care 19 (6):
297–303.
National Institute for Health and Care Excellence (NICE). (2019). Guideline
123. Urinary incontinence and pelvic organ prolapse in women: manage-
ment. www.nice.org.uk/guidance/ng123
 CHAPTER 12

Scars
Paul Martin1 and Duncan A. McGrouther2
1
Schools of Biochemistry and Physiology, Pharmacology & Neuroscience, University of Bristol, Bristol, UK
2
Department of Hand and Reconstructive Microsurgery, Singhealth Duke-­NUS Academic Medical Centre, Singapore

and any functional disability. Once a scar is formed, however, it is a

OVERVIEW
permanent characteristic that may be modified but cannot be
•  Scarring is the residual consequence of the healing process removed. Even surgical excision to “revise” the scar may improve
following wounding or tissue injury. the appearance but will, of course, result in a further scar.
•  The appearance of a scar depends on many factors, including
age, tissue type, genetic profile, type and size of injury, and
treatment received.
•  The extent of scarring can be limited by careful wound Camouflage
management.
•  Scars undergo a period of maturation over months or years by In some patients, the cosmetic effects of scarring can have a
which they become less prominent, although they generally profound impact on quality of life. Camouflage using specialist
remain as permanent features. cover products may be a good option, and in the UK specialist
•  A variety of techniques are available to alter the appearance of a camouflage services and prescribed products are available.
scar, for example surgical revision, but there is the potential to
make the scar worse.

Wound healing has been traditionally classified as comprising

A scar is the visible, palpable mark remaining after a wound has
healed. Scars are most familiar to us after skin healing, but it should
be appreciated that all tissue injuries in adult mammals heal by
fibrotic reactive mechanisms. Taken together, the problems that
arise from this healing process represent an extensive range of
fibrotic pathologies with the potential to limit organ function and
mobility, and cause disfigurement.
Focusing on the body surface, the typical scarring reaction fol-
lowing injury is the consequence of a temporal sequence of cellular
and matrix changes which are reflected by characteristic clinical
appearances. Depending upon a wide number of determining fac-
tors, including age of the patient, genetic profile, type and size of
injury, and treatment, the scar tissue ultimately reaches a stable
morphology. For example, for an incisional surgical lesion, this
typically appears as a white line with hardened deeper tissues, as
well as a failure to re-­establish appendages and frequently an altera-
tion in the pigment pattern of that region of skin.
Therapeutic interventions are possible at various stages in scar
development with the aim of minimising the obvious appearance
three phases: inflammation, proliferation and remodelling/resolu-
tion. There is considerable overlap across these phases and also a
preceding phase of bleeding and fibrin deposition, which is critical
to initiation of the repair process and to eventual scar morphology.
This simplistic classification presents a useful framework for the
description of scarring. Under each heading, we will discuss clinical
features, biology and therapeutic options.
Inflammation
Clinical
A very significant contributor to the extent of final scarring will be
the initial causative wound. Very small wounds such as needle
punctures or superficial wounds such as abrasions or tattoos may
not leave a visible scar. There appears to be a critical depth of skin
injury at which scarring will result and this seems to be associated
with the initiation of a certain degree of inflammatory stimulus.
Sharp incised wounds such as glass lacerations or surgical incisions

ABC of Wound Healing, Second Edition. Edited by Annie Price, Joseph E. Grey, Girish K. Patel, and Keith G. Harding.
© 2022 John Wiley & Sons Ltd. Published 2022 by John Wiley & Sons Ltd.

78
 Scars 79

(a) (b)

(c) (d)

Examples of skin scarring. (a) Laparotomy wound healed by primary intention. (b) Post-operative axillary wound healed by secondary intention. (c) Scarring
following surgical treatment for necrotising fasciitis. (d) Scarring following post-operative wound dehiscence.

(a) (b)

Abnormal scarring caused by skin diseases. (a) Hidradenitis suppurativa. (b) Wrinkled paper scar, typically associated with healed pyoderma gangrenosum.
80 ABC of Wound Healing
are not associated with tissue loss and as the injury is localised,
there is little initial damage to the wound marginal tissues. The
main challenge to the organism is therefore to bridge a very mini-
mal gap by the generation of a fibrin clot which is then invaded by
fibroblastic cells that replace the fibrin by a collagenous link. This
process is driven by inflammatory mediators and is not confined to
the infill area but is associated with varying degrees of change in the
wound margins, including collagenolysis, angiogenesis and subse-
quent fibroplasia. Where there is tissue loss (as in abrasion or avul-
sion injuries) or severe cellular damage (blunt injuries or burns),
the body must endeavour to not only bridge the defect but to
replace damaged cells and matrix. Ischaemic tissue that has been
devascularised will become intensively scarred without there being
any obvious or visible tissue defect.
Cellular and molecular processes
Our current understanding is limited but early studies showed that
inflammation, the influx of neutrophils and macrophages that
combat infection and clear cell and matrix debris, might also be, in
part, causal of fibrosis because embryos, which exhibit a very
reduced inflammatory response, can heal without a scar. More
recent studies indicate that several inflammation-­ dependent
cytokines released at the wound site are profibrotic and there is
experimental evidence to suggest that reducing levels of two of
these, transforming growth factor-­β1 (TGF-­β1) and osteopontin,
may reduce scarring. Recent studies have shown that mechanical
signals may drive fibrosis, possibly also through regulation of the
degree of inflammation, thus explaining the clinical observation
that a single continuous wound may scar differently along its length
depending on differing mechanical forces.
Management options
It is possible to limit the amount of scar formation by careful
wound management aimed at preventing infection and minimis-
ing additional tissue trauma. The incised wound requires only
cleaning by irrigation with physiological fluid followed by surgical
closure in a sterile environment using the least traumatic surgical
techniques. There should be minimal handling of wound margins
and wherever possible interrupted sutures should be avoided. To
prevent scar stretching, the wound can be splinted internally by
using subcutaneous and intracutaneous (‘subcuticular’) sutures,
which can either be absorbable or a material such as monofilament
nylon that can be left in situ for 2 weeks or longer. The wound can
then be splinted externally by adherent skin tapes, often attached
by additional adhesive (e.g. Dermabond®); such tapes must not be
applied under tension or they will blister the skin due to traction.
The use of such techniques can contribute to the prevention of scar
stretching which is a major determinant of the final morphology.
If the wound has been contaminated, antibiotic prophylaxis may
be added.
In addition to careful wound management, there are currently no
clear, science-­led, clinical measures that have been shown to be
beneficial in modifying scar formation but there is promise that a
better understanding of the profibrotic signals released by inflam-
matory cells, as described above, may reveal potential therapeutic
targets.
Proliferation
Clinical
The term proliferation has been used to describe a visible increase
in the volume of the scar which projects above the surface. The
clinical term hypertrophic is the usual description and it is an almost
invariable event in every scar. A more extreme increase in scar vol-
ume is exhibited in some patients who respond to tissue damage by
developing a keloid scar.
The term keloid is often misapplied to any unsatisfactory scar but
it should be reserved for a scar that invades surrounding dermis
and persists for many years, perhaps indefinitely. The tendency to
develop keloid scars is genetically determined, although it is an
individual tendency and many siblings of keloid patients form scars
that mature normally. It is possible for keloid scars to occur in all
skin types but they are more common in people with dark skin.
They can be painful, itchy, disfiguring and distressing. The most
common sites are earlobes (particularly after piercings), shoulders
and the characteristic midline presternal area where they form a
butterfly morphology, apparently in response to tension. They can
occur after very minor skin trauma, for example after acne or
chickenpox, but can also be spontaneous. There is considerable
variability and most keloid formers have normal scars at other sites.
Cellular and molecular changes
To replace tissues lost at the time of wounding, considerable cell
proliferation must occur in the advancing epidermal front and
other cell types including fibroblasts and vascular endothelial cells.
On histological examination, hypertrophic scars exhibit consider-
able cellularity and matrix deposition but proliferation may not be
the only source of this increased cellularity, which may involve con-
tributions of mesenchymal stem cells from bone marrow together
with cells from tissue niches such as in hair follicles. Keloid scars are
initially highly cellular but later the central areas become acellular.
Management
Hypertrophic scars will eventually become flat and pale. The clini-
cal descriptive term is mature. Pressure will expedite this process
and can be applied by pressure garments for large areas or simple
adhesive tape for smaller areas. Silicon may be beneficial although
the mechanism(s) underpinning this therapy are not clear. This can
be applied as sheets or ointment.
Keloid scars may respond to these measures also, at least by
reduction of pain and itch. Earlobe keloids can be treated by pres-
sure clips. Steroid injection may reduce the keloid volume. This is
generally administered on several occasions at intervals of 4 weeks,
but can cause loss of pigment or atrophy of subcutaneous fat. Such
complications generally resolve spontaneously after a few months.
Remodelling
Clinical
The remodelling phase of a scar continues for months or years;
scars in childhood generally appear to grow as the patient grows.
However, there are few precise data and some small scars can
remain much the same size. Once a scar has developed, it is a
 Scars 81

(a) (b)

(c) (d)

Surgical revision of a stretched scar. (a) The anterior end of the scar (arrows) from a 3-year old sharp injury to the cheek has been revised by excision,
re-suture and taping to prevent stretching. This segment of the scar is the best outcome that revision can achieve- a thin pale linear scar. The central and
posterior parts of the scar have been revised by excision and re-suture but without tape support 6 months ago. The scar in these areas has stretched again.
(b) The scar has been re-excised and sutured with a subcuticular suture and tape is being applied. (c) Two layers of tape are applied to provide mechanical
support and the wound will be supported by tape for several weeks. (d) At 3 months post-operatively, further stretching has been prevented and the
erythema is beginning to resolve posteriorly.

permanent feature although with the passage of time, it may
become less obvious as the initial redness fades completely.
Areas of scar such as those following burns may go through a
phase of hypertrophy with gradual resolution and eventual thin-
ning to the point of atrophy over a period of several years.
However, such scars remain obvious due to permanent differ-
ences in texture, pigmentation and surface reflectance.
Cellular and molecular changes
As scar tissue remodels, it becomes less vascular, less cellular and
the collagenous matrix demonstrates orientation along dominant
lines of tension. Remodelling changes can be considered as the
usual pattern of events (we hesitate to use the term normal), but
there are a number of aberrant events that may occur, listed below.
Scar contracture  To some extent, all scars contract although
this may not have a clinical effect if the wound is on a flat surface.
However, if the wound crosses a concavity, such as the hollow in
front of the elbow, the wound contraction may leave a tight scar,
often described as a bridle scar. Scars that result from burns or
scalds are particularly likely to result in joint contractures. Such
shortened contractures may respond to splinting but generally
require surgical release and possibly skin grafts or skin flaps.
Pigmentation changes  Scar tissue is initially depigmented but
may gradually acquire the pigmentation of surrounding skin which
is slow, variable and patchy. More obvious changes may occur in the
wound margins with either hyperpigmentation or depigmentation
or a mixture of both. Such pigmentary changes are most obvious in
patients with more pigmented skin. Patients should avoid strong
sun exposure during wound healing and minor changes may
improve spontaneously but once established, there is no reliable
way of correcting the problem. Small areas may be excised and cell
therapies have been tried with variable outcomes. It is believed that
wound hyperpigmentation, like scarring, may also be a conse-
quence of the wound inflammatory response.
82 ABC of Wound Healing
(a)
(b)
(c)
Early changes in scar morphology – hypertrophy. (a) One month after wound
closure. The scar tissue is essentially a line of closure with little tendency to
stretching and little wound margin reaction. (b) Two months after wound
closure. The scar has raised (the term hypertrophic is used). Multiple parallel
blood vessels indicate that matrix is laid down along lines of maximum skin
tension and blood vessels follow the matrix scaffold. There are erythema and
pigment changes in the wound margins. (c) Seven months after wound
closure. The scar is flattening, becoming more stretched with less distinct
margins and gradually becoming more pale (mature). Full maturation can
take 2 years or more.
Permanent erythema  Some scars remain permanently red
and this seems more likely in patients with a ‘rosy complexion’
(this is difficult to measure or define but skin tends to have
prominent microcirculation). There seems to be prominent
­ est line possible rather than altering orientation.
A keloid scar following ear piercing.
a­ ngiogenesis in not just the scar tissue but also the wound mar-
gins. Such scars may respond to laser therapy.
Scar stretching  This is perhaps the most common scar prob-
lem where a linear scar widens, with studies showing the greatest
stretch in the first 3 weeks but a widening tendency continuing for
at least 3 months. The forces promoting this are the skin’s inherent
elasticity combined with the movement of underlying joints and
muscles. Traditional wound closure by interrupted sutures
removed at 5 days offers little mechanical support. Layered wound
closure and taping as described above can minimise stretch.
However, if scar stretching is established, consideration can be
given to scar revision. This is essentially excision of scar tissue
and resuturing of the wound. Experience and judgement are
required for advising on such treatments, considering whether
the original wound management techniques and wound environ-
ment (location, infection, etc.) can actually be improved.
Contour problems  These can arise from tissue displacement or
scar contractures, as scar tissue contracts not just longitudinally but
vertically as well, producing indentation. Such problems require
surgical revision and closure in layers but indentation is difficult to
correct. The linear orientation of a scar can be altered by proce-
dures such as a Z-­plasty or W-­plasty, which convert a linear scar to
a zig-­zag pattern. Although widely illustrated in textbooks, great
judgement is required in advocating such techniques, as there is a
potential to make the scar worse rather than better. In most situa-
tions where surgery is done, it is best to aim to achieve the narrow-
 Scars 83

(a) (b)

Hypertrophy or keloid? (a) A lesion has been excised from the left shoulder and sutured with interrupted sutures, which were removed at 5 days. The scar has
several unsatisfactory features; it is stretched and raised (hypertrophic) with prominent suture marks. The apparent growth of the scar is due to stretching
rather than invasion as occurs in a keloid scar. This scar is already flattening in the centre and will eventually mature. (b) A keloid scar following vaccination that
is growing by invasion of surrounding dermis in the direction of dominant lines of skin tension, giving a ‘propeller’ shape.

(a) (b)

Later changes – scar maturation. (a) A facial wound has been sutured but due to infection, the sutures had to be removed and the wound was allowed to heal
by secondary intention. (b) Five years later, the scar is mature with some flattening of the scar tissue (atrophy) and pigmentary and texture changes.
84 ABC of Wound Healing
Further reading
Eming, S.A., Wynn, T.A., and Martin, P. (2017). Inflammation and metabo-
lism in tissue repair and regeneration. Science 356: 1026–1030.
Martin, P. and Nunan, R. (2015). Cellular and molecular mechanisms of
repair in acute and chronic wound healing. British Journal of Dermatology
173 (2): 370–378.
Mori, R., Shaw, T.J., and Martin, P. (2008). Molecular mechanisms link-
ing wound inflammation and fibrosis: knockdown of osteopontin
leads to rapid repair and reduced scarring. Journal of Experimental
Medicine 205 (1): 43–51.
Shah, M., Foreman, D.M., and Ferguson, M.W. (1992). Control of scarring in
adult wounds by neutralising antibody to transforming growth factor beta.
Lancet 339 (8787): 213–214.
Shaw, T.J. and Martin, P. (2009). Wound repair at a glance. Journal of Cell
Science 122 (18): 3209–3213.
 CHAPTER 13
Dressings and Devices
Samantha Holloway1, Stuart Enoch2, and Joseph E. Grey3
1
Cardiff University School of Medicine, Cardiff, UK
2
Directorate of Education and Research, Doctors Academy Group (Intl)
3
Department of Clinical Gerontology, Cardiff and Vale University Health Board, Cardiff, UK
OVERVIEW
•  Dressings protect the wound bed and optimise conditions for
wound healing; a moist wound environment accelerates healing.
•  An understanding of the underlying pathology is key to achieving
healing in chronic wounds.
•  Selection of the most appropriate dressing requires consideration
of level of exudate, condition of the wound bed, stage of healing,
underlying cause, symptoms of the patient and cost.
•  Potential adverse effects of dressings include damage to
surrounding skin by pooling of exudate, allergy or adhesive
elements causing trauma on removal.
•  Various devices, generally requiring specialist knowledge and
equipment, may be used as adjunctive therapies to aid healing.
As a general principle, dressings that promote moist wound healing
are required for the treatment of the majority of wounds. In addi-
tion, adjuvant therapies or devices may be required to optimise
conditions for wound healing. A wide range of dressings and
devices is currently available; choosing the most appropriate treat-
ment should be based on a fundamental understanding of the phys-
iology of wound healing, the aetiology of the wound and
consideration of treatment options. Some of these are principles
that have been addressed in previous chapters and are essential
requirements if a successful outcome is to be achieved.
Dressings
Types of dressings
Wound dressings currently available in the UK are based on mate-
rial types rather than dressing properties. The product names pro-
vided in the following generic categories are examples only and not
an exhaustive list. The specific products available often depend on
local formularies, which vary throughout the country. Dressings
may be further classified as basic (dressings that cover the wound
bed) and advanced (designed to optimise the wound environment
for healing, for example by controlling the levels of moisture at the
wound surface).
ABC of Wound Healing, Second Edition. Edited by Annie Price, Joseph E. Grey, Girish K. Patel, and Keith G. Harding.
© 2022 John Wiley & Sons Ltd. Published 2022 by John Wiley & Sons Ltd.
Principles of wound management
The choice of dressing and/or device will depend on a number of
factors, including:
• Wound aetiology and stage of healing
• Treatment objective/expected outcome (which might not be
healing in the first instance), i.e. reduction in pain or odour,
eradication of infection or promotion of granulation tissue
• Practitioner knowledge of the range and mechanism of action of
the interventions available to maximise their effect
• Manufacturers’ recommendations for the use of a dressing or
device and availability of the dressing or device
• Patient-­centred rather than product-­centred decision-­making
processes.
Characteristics of the ideal dressing
• Capable of maintaining a high humidity at the wound site while
removing excess exudate
• Free of particles and toxic wound contaminants
• Non-­toxic and non-­allergenic
• Capable of protecting the wound from further trauma
• Can be removed without causing trauma to the wound
• Impermeable to bacteria
• Thermally insulating
• Will allow gaseous exchange
• Comfortable and conformable
• Require only infrequent changes
• Cost-­effective
• Long shelf-­life
Basic dressings
Low adherent dressings  Cheap and widely available, the major
function of basic dressings is to allow exudate to pass through into
a secondary dressing while maintaining a moist wound bed. The
two categories of dressings in this group are tulle and knitted
viscose. They are particularly useful for clean, granulating wounds
85
86 ABC of Wound Healing
with low levels of exudate. They are not suitable for wounds with
necrotic tissue. They require careful removal as they can adhere to
and damage the newly formed granulation tissue.
Absorbent dressings  These dressings were designed to
supersede the use of gauze as a primary dressing. They can be
helpful in managing exudate but can adhere to the wound bed.
They are available with and without adhesive borders. More
advanced forms have been developed, for example, with regard to
sequestering bacteria.
Advanced dressings
Non-­adherent dressings  While these may be considered as
simple dressings, recent developments in wound contact layers
have meant that the limitations of low adherent dressings have been
overcome with the introduction of materials such as silicone and
knitted polyester. These advances are more closely aligned to the
principles of moist wound healing. They are indicated for use in
clean granulating wounds, with the advantage that some products
Low/non-adherent and absorbent dressings Uses
Paraffin gauze (tulle gras) Flat, shallow wounds
Cuticell Classic, Jelonet, Neotulle, Paragauze with low exudate and
granulation tissue
Absorbents Acute and chronic
Advadraw, Alione, Alldress, Askina Pad, Cerdak wounds that are
Aerocloth, Cosmopor E, Cutiplast, Cutisorb LA, exuding
Drisorb, Interpose, Kerramax, Medipore + Pad,
Pharmapore-­PU, PremierPad, Release, Skintact,
Softpore, Solvaline N, Sterifix, Telfa, Vacutex
Non-­adherent/wound contact layers Wound contact layer for
Adaptic, Askina SilNet, Atrauman, Cestra Primary, clean granulating
Curity Non-­Adhering Dressing, Mepilex Transfer, wounds where
Mepitel, N-­A Dressing, N-­A Ultra, Physiotulle, adherence needs to be
Silflex, Silon TSR, Tegaderm Contact, Telfa Clear, avoided
Tricotex, Urgotul, Vacunet
Note: Many of the products listed in the table are dressing types protected
by trademarks/names. It should be recognised that these refer to specific
products and are not generic names.
A clean, granulating postoperative wound suitable for covering with a low
adherent dressing.
can be left on for 4–5 days and only require the secondary dressing
to be changed. This reduces the risk of disturbing any newly formed
tissue.
Semi-­permeable films  Semi-­permeable (or vapour-­permeable)
films were one of the first major advances in wound management
and heralded a major change in the way wounds were managed.
They consist of sterile plastic sheets of polyurethane coated with
hypoallergenic acrylic adhesive. They are used mainly as a
transparent primary wound cover. Impermeable to fluids and
bacteria, they are permeable to air and water vapour, the control of
which is dependent on the moisture-­vapour transmission rate,
which varies depending on the brand. It is through this mechanism
that this type of dressing creates a moist wound environment. Films
are very flexible and are good for wounds in ‘difficult’ anatomical
sites, for example over joints. They are mainly indicated for
superficial wounds but can also be used as secondary dressings.
Some brands have an absorbent ‘island’ of low adherent material
but generally they are unable to cope with moderate to large
amounts of exudate and may cause maceration of the surrounding
skin. In addition, they need to be removed carefully to avoid
damage and/or pain.
Semi-­permeable films Uses
ActivHeal Film, Askina Derm, Bioclusive, • Flat, shallow wounds with
Blisterfilm, C-­View, Episil, Hydrofilm, low-­medium exudate
Leukomed T, Mepore Film, Opsite Flexifix, • Promote moist environment
PolyskinII, ProtectFilm, Suprasorb F, • Protect against contamination
Tegaderm Film, Vacuskin and trauma
• Adhere to healthy skin but
not to wound, therefore
caution is required in patients
with fragile skin
• Allow visual checks
• May be left in place for
several days
• Useful as secondary dressing
• Not suitable for infected or
heavily exuding wounds
Note: Many of the products listed in the table are dressing types protected
by trademarks/names. It should be recognised that these refer to specific
products and are not generic names.
Hydrocolloids  Sodium carboxymethylcellulose, gelatin, pectin,
elastomers and adhesives are bonded to a carrier of semi-­
permeable film or a foam sheet to produce a flat, occlusive,
adhesive dressing that forms a gel on the wound surface,
promoting moist wound healing. Cross-­linkage of the materials
influences the viscosity of the gel under the dressing and also the
transparency of the product. This gel, which may be yellow and
malodorous, may be mistaken for infection. Hydrocolloids are
virtually impermeable to water vapour and air, and can be used to
rehydrate dry, necrotic tissue and promote autolytic debridement.
They are reported to reduce wound pain and their barrier
 Dressings and Devices 87

properties allow the patient to bathe or shower and continue with
normal daily activities without disturbing or risking contaminating
the wound. They can be left in place for up to 7 days but generally
wear time is approximately 3–5 days. Caution should be exercised
when using hydrocolloids in wounds that require frequent
inspection, for example diabetic foot ulcers.
Hydrocolloid fibres are now available in the form of hydrophilic,
non-­woven flat sheets, referred to as hydrofiber dressings. On
­contact with exudate, fibres are converted from a dry dressing to a
Hydrocolloid and hydrofiber
dressings Uses
soft coherent gel sheet, making them suitable for wounds with a
large amount of exudate. They are often used on wounds where,
traditionally, alginates have been used. Both forms of hydrocolloid
dressing are now available with impregnated silver.
Hydrogels  Hydrogels consist of a matrix of insoluble polymers
with up to 96% water content, enabling them to donate water
molecules to the wound surface and maintain a moist environment
in the wound bed. As the polymers are only partially hydrated,
hydrogels have the ability to absorb a degree of wound exudate,
the amount varying between different brands. They transmit
moisture vapour and oxygen but their bacterial and fluid

Hydrocolloid • Cavity or flat shallow wounds

ActivHeal Hydrocolloid, Askina Biofilm
Transparent; there are also ranges in the
following, Comfeel Plus, DuoDerm,
Granuflex, Hydrocoll, NU-­DERM,
Tegaderm, Ultec
Hydrofiber
Aquacela, Versivab
with low-­medium exudate
• Absorb some exudate but not
rapidly
• Conformable
• Good in ‘difficult areas’ – heel,
elbow, sacrum
• May be left in place for several days
• Aid autolytic debridement
• May cause maceration if
changed too infrequently
• Useful in flat wounds, cavities,
sinuses, undermining wounds
• Highly absorbent
• Non-­adherent
• May be left in place for several
days
• Need secondary dressing

Note: Many of the products listed in the table are dressing types protected
by trademarks/names. It should be recognised that these refer to specific
products and are not generic names.
a
 May also be classified as protease-­modulating or ‘specialised’ dressings. A wound with high exudate levels (seen dripping down the leg) suitable for
b
 Also classified as a foam dressing but has hydrofiber technology. a hydrofiber dressing.

(a) (b)

(a) A dry, necrotic wound. (b) A wound with adherent, thick slough. Rehydration with a hydrocolloid or hydrogel dressing may promote autolytic debridement
and remove the unhealthy tissue in both wounds.
88 ABC of Wound Healing

permeability is dependent on the type of secondary dressing used.
Hydrogels promote wound debridement by rehydration of non-­
viable tissue, facilitating the process of natural autolysis.
Amorphous hydrogels are most commonly used and are presented
as a thick, viscous gel. Hydrogel sheets are now also available
although their fluid handling ability is more limited. Considered
to be a standard form of management for sloughy or necrotic
wounds, they are not indicated for wounds producing high levels
of exudate, or where there is evidence of gangrene, which should
be kept dry in order to reduce the risk of infection. Caution is also
required if larval therapy is to be used as hydrogels with propylene
glycol can cause the larvae to suffocate.
or used in sinus and cavity wounds, where a secondary dressing
will be required.
Foam dressings  Foam dressings are manufactured as either
polyurethane or silicone foam. They transmit moisture vapour and
oxygen and provide thermal insulation to the wound bed.
Polyurethane foams consist of two or three layers, including a
hydrophilic wound contact surface and a hydrophobic backing,
making them highly absorbent. They facilitate uniform disper-
sion of exudate throughout the absorbent layer and prevent
strike-­through due to the presence of a semi-­permeable backing,
although the fluid-­ handling capacity varies across the range.

Alginate dressings  These dressings are produced from the

naturally occurring calcium and sodium salts of alginic acid found in Alginates Uses
a family of brown seaweed (Phaeophyceae). Alginates are generally of
two kinds: those containing 100% calcium alginate or a combination Calcium alginates • Useful in cavities, sinuses and
Algisite M, Curasorba, Melgisorb, undermining wounds
of calcium with sodium alginate, usually in a ratio of 80:20. Alginates Sorbalgona, Sorbsana, Suprasorb A, • All wound types with moderate-­
are either rich in mannuronic or guluronic acid; the relative amount of Tegaderm Alginate high exudate
each influences the amount of exudate absorbed and the shape the • Highly absorbent
dressing will retain. Alginates partly dissolve on contact with wound • Need secondary dressing
fluid to form a hydrophilic gel due to the exchange of sodium ions in • Need to be changed once
saturated (often daily)
wound fluid for calcium ions in the dressing. Alginates can absorb
15–20 times their weight of fluid, making them suitable for highly Calcium‑sodium alginate • As above but also have
exuding wounds. ActivHeal Alginate, Kaltostat haemostatic properties

Generally, dressings are left in place until saturated with exu- Combination – alginate and • Moderate to heavy exudate
date. They should not be used on wounds with little or no exu- hydrocolloid • Can aid autolytic debridement
date since they will adhere to the healing wound surface, causing SeaSorb Soft, Urgosorbb
pain and damaging healthy tissue on removal. Blood clots can
Note: Many of the products listed in the table are dressing types protected
also cause adherence of the dressing. Their ion exchange prop- by trademarks/names. It should be recognised that these refer to specific
erties make some alginates useful haemostatic agents and they products and are not generic names.
are often used for postoperative wound packing. They are avail- a
 Available as a range of dressings.
able in sheet or rope form that can be layered into deep wounds
b
 Also has haemostatic properties.

Hydrogels Uses

Hydrogel-­impregnated dressings • Donate moisture to

Askina Transorbent rehydrate wound bed

Amorphous hydrogels • Facilitate autolysis so useful

ActivHeal Hydrogel, AquaForm Hydrogel,
Askina Gel, Cutimed Gel, GranuGEL,
Intrasite Conformable, Intrasite Gel,
NU-­GEL, Purilon
Hyiodinea, Octenilinb, Prontosan
Wound Gelc
for sloughy/necrotic wounds
• Useful in flat wounds,
cavities and sinuses
• May be left in place for
several days
• Need secondary dressing

Hydrogel sheets • May cause maceration so

ActiFormCool, Aquaflo, Geliperm, careful monitoring of
Hydrosorb, Novogel surrounding skin is required

Note: Many of the products listed in the table are dressing types protected
by trademarks/names. It should be recognised that these refer to specific
products and are not generic names.
a
 Contains hyaluronic acid, iodine and potassium iodide.
b
 Contains octenidine.
c
 Contains polyhexamethalyene biguanide. A cavity wound suitable for packing with an alginate dressing.
 Dressings and Devices 89

They are available in adhesive and non-­adhesive forms, the choice cadexomer iodine can absorb up to 7 mL of fluid. As fluid is
of which will depend on the condition of the patient’s surround- absorbed, iodine is slowly released, reducing the bacterial load and
ing skin. They are also available in different shapes for particular also debriding the wound of debris. This mode of action facilitates
areas of the body.
Silicone foams consist of a polymer of silicone elastomer, derived
from two liquids that when mixed together form a foam while Foam/hydrocellular dressings Uses
expanding to fit the wound shape, resulting in a soft open-­cell foam
ActivHeala, Advasorba, Allevynb, Askinaa, Biatainc, • Flat, shallow wounds
dressing. Cutimeda, Kendalla, Kerraboot, Kerraheel, • Requires at least
The major advantage of foam is the ability to contain exudate and Lyofoama, Mepilexa, Permafoama, Polymema, some exudate to
protect the periwound area. They are available in various thick- Tegaderm Foama, Tiellea, Transorbent, Trufoama, avoid drying the
nesses and are suitable for a wide range of wound types. UrgoCell TLC, Versiva XCd wound out
• Controls exudate
according to type
Antimicrobial dressings  Antimicrobial dressings can help • Degree of cushioning
reduce the bioburden at the wound surface and are useful for and protection for
treating localised wound infection. Some dressings release an bony areas
antimicrobial agent into the wound whereas others absorb the • May be left in place
bacteria and then act upon it. Examples of antimicrobial agents for 2–3 days
• Available in adhesive
used in dressings are described below. and non-­adhesive
forms as well as a
Silver  In ionic or nanocrystalline form, silver has, for many years, range of shapes
been used as an antimicrobial agent, particularly in the treatment of Cavity wounds • Granulating cavity
burns (in the form of silver sulfadiazine cream). A wide range of Cavi-­Care, Allevyn cavity wounds with
dressings impregnated with silver is available that can be used for low-­medium exudate
different wound types. Silver dressings should only be used when • Can stay in place for
infection is suspected (based on the presence of clinical signs and 5–7 days

symptoms); however, there is continued debate about its efficacy Note: Many of the products listed in the table are dressing types protected
and cost-­effectiveness. by trademarks/names. It should be recognised that these refer to specific
products and are not generic names.
Iodine  Available as povidone‑iodine, an iodophor (a compound of a
 Available in a range, i.e. adhesive/non-­adhesive.
iodine linked to a non-­ionic surfactant) produced as an impregnated
b
 Range of sheet, rope and cavity dressings available.
c
 Available in a range which includes items impregnated with ibuprofen.
tulle or cadexomer‑iodine, a three-­ dimensional starch lattice d
 Hydrofiber technology.
containing 0.9% iodine. It has good absorptive properties; 1 g of

Some alginates have haemostatic properties so are useful for wounds that
are bleeding. A granulating abdominal wound suitable for a foam dressing.
90 ABC of Wound Healing
the delivery of iodine over a prolonged period of time, thus, in
theory, maintaining a constant level of iodine in the wound bed.
Caution should be exercised in patients with thyroid disease due to
possible systemic uptake of iodine and thyroid function should be
monitored in patients, particularly those with large wounds, who
are treated with iodine dressings. They should be avoided during
pregnancy and lactation.
Honey  Honey of the pasture and manuka varieties has some
antibacterial action, inhibits excessive inflammatory response and
promotes autolytic debridement. It is available as an impregnated
dressing or a gel. Interest in the use of honey has increased and
in  vitro work has suggested that it is effective against organisms
An infected wound (indicated by presence of purulent exudate and dark,
unhealthy granulation tissue) suitable for an antimicrobial dressing.
Antimicrobial dressings
Silver
Acticoat range, Actisorb Silver 220, Algisite Ag, Allevyn Ag range, Aquacel Ag,
Atrauman Ag, Biatain Ag range, Contreet Hydrocolloid, Flamazine, Melgisorb Ag
range, Mepilex Ag, Physiotulle Ag, Polymem range, SeaSorb Ag, Silvercel Non-­
Adherent, Sorbsan range, Suprasorb A+AG, Tegaderm Alginate Ag, UrgoCell range
Iodine
Inadine, Iodoflex, Iodosorb
Honey (available as ointments and dressings)
Actibalm, Actilite (low adherent), Activon range, Algivon (calcium alginate), Medihoney • Can aid debridement
range (alginate, non-­adherent tulle, tube), Melladerm range, Mesitran range
Polyhexamethylene biguanide (PHMB)
Kendall AMD range, Kerlix AMD, Suprasorb X+PHMB, Telfa AMD
Chlorhexidine
Bactigras, Biopatch, chlorhexidine gauze dressing
DACC (dialkylcarbamoyl chloride)
Cutimed Sorbact range
Note: Many of the products listed in the table are dressing types protected by trademarks/names. It should be recognised that these refer to specific products
and are not generic names.
such as methicillin-­resistant Staphylococcus aureus (MRSA). It can
be used on a variety of wounds but caution is required in patients
with extreme sensitivity to bee stings and products. Patients with
diabetes should also be monitored closely.
Polyhexamethylene biguanide (PHMB) This has been used as a
disinfectant in industry for many years. Initially available as a
wound cleanser, it has now been incorporated into several dressing
types, and is therefore suitable for use on a variety of wounds.
Prolonged use of silver dressings can cause staining of the skin and the
wound bed.
Uses
• All locally infected wound types
• Can be left on for up to 7 days depending on type
• Available with composite materials for non-­adherence and absorbency
• Some are shaped for awkward areas
• Management of local wound infection
• Can aid wound debridement
• Infected acute and chronic wounds
• May help with wound malodour
• Caution with known sensitivity to bee products
• Useful for a range of exudate levels
• Wound contact layer with antimicrobial activity
• Absorb exudate and bind bacteria
• Available in sheets and rope so can be used on flat and cavity
wounds/sinuses
 Dressings and Devices 91

Many other natural products including yoghurt, tea tree oil and
potato peelings have been used in various parts of the world to treat
ulcers with varying degrees of success; controlled studies, however,
are lacking.
Odour absorbent dressings
The underlying cause of wound malodour should be established as
it is an adverse sign (for example, indicates infection). Strategies
such as debridement, treatment with topical antiseptics, and
increased frequency of dressing changes are key. Dressings contain-
ing activated charcoal help reduce odour. Topical metronidazole gel
can also be helpful for malodorous wounds, particularly fungating
malignant wounds where it can be used alone or as an adjunct to
other dressings.
Specialised dressings
The production and activity of several proteases, including matrix
metalloproteinases, serine proteases and neutrophil elastases,
which are tightly regulated in the normal acute response to wound
healing, may be altered in chronic wounds. Raised levels of such
proteases can be detrimental to wound healing, and products aimed
at counteracting their effect have been developed. The actions
of protease-­modulating matrix dressings include inactivation of
Odour absorbent dressings Uses
Anabacta, Askina Carbosorb, • Fungating, malodorous wounds
Carboflex, Carbonet, Carbopad • Degrees of absorbency help to manage
VC, Clinisorb, Lyofoam C, exudate
Sorbsan Plus Carbonb • Exudate reduces dressing effectiveness
• May adhere to the wound bed so
caution required on removal
• Some can be cut to size
• Can be used in combination with other
primary dressings
proteases by binding them into the dressing. Other preparations act
to lower the wound pH, thus producing a weak acidic environment
to promote healing. Such products may be useful in the treatment
of chronic wounds refractory to conventional treatments with
advanced wound dressings.
Unwanted effects of dressings
Maceration of the skin surrounding a wound may occur if a dress-
ing with a low absorptive capacity is used on a heavily exuding
wound. If the dressing is highly absorptive then more frequent
dressing changes may be needed, in addition to investigation and
management of the cause of the excessive exudate (such as infec-
tion). The skin surrounding a highly exuding wound may be fur-
ther protected through the use of emollients (such as 50/50 mix of
white soft paraffin and liquid paraffin) or the application of barrier
films. Conversely, use of a highly absorptive dressing on a dry
wound may lead to disruption of healthy tissue and pain on
removal.
Allergic reactions to dressings are not uncommon. When sus-
pected, the dressing should be avoided and the surrounding skin
may require treatment with topical steroids. Patch testing (usu-
ally requiring referral to a dermatologist) is helpful to establish
potential allergens, particularly in patients with long-­standing
ulcers that have been exposed to many different dressings and
topical treatments. Tapes used to keep dressings in place are
another common cause of allergy. Adhesives may also lead to
trauma of fragile surrounding skin and ideally should be avoided
in chronic lower limb wounds and in elderly patients.
Many dressings require secondary dressings, for example pad-
ding on highly exuding wounds, which may make them bulky.
Secondary dressings should not be too tight, especially in patients
with peripheral arterial disease.

Note: Many of the products listed in the table are dressing types protected
by trademarks/names. It should be recognised that these refer to specific
products and are not generic names.
a
 Contains metronidazole gel.
b
 Calcium alginate and charcoal.

Specialised dressings Uses

ActivHeal Aquafiber, Aquacel, • Non-­healing, chronic wounds

Cadesorb, Curea P1, Cutisorb Ultra,
DryMax Extra, Flaminal range,
Flivasorb, Iodozymea, MelMax,
Oxyzymea, Promogran range, Sorbion
range, Suprasorb C, Tegaderm Matrix,
Urgostart range
• May require a secondary dressing
• Dressing change frequency
determined by volume of
exudate
• Can be used on infected wounds
as they sequester bacteria

Note: Many of the products listed in the table are dressing types protected
by trademarks/names. It should be recognised that these refer to specific
products and are not generic names. Failure to adequately control exudate levels may result in maceration of the
a
 Contains an enzyme that produces iodine. surrounding skin.
92 ABC of Wound Healing

Devices device, and anxiety around device malfunction. There is also a risk of
damaging the surrounding skin as adhesive dressings are essential to
Certain wound types require treatment with specific devices that form an air-­tight seal.
target the underlying pathophysiology, for example, compression
therapy (bandages and/or hosiery) for venous leg ulcers or offload- Oxygen therapy
ing devices for pressure injuries (discussed in the relevant chap- Oxygen is required in all stages of wound healing, and local tissue
ters). The following are examples of devices that, in the right hypoxia is a common factor in many chronic wounds. Increasing
circumstances, may be used as adjunctive therapies to aid healing. the availability of oxygen, through either systemic or topical oxygen
The evidence for their effectiveness is variable and not all are used therapy, corrects the imbalance between oxygen supply and demand
routinely in clinical practice. to promote healing processes such as angiogenesis, collagen syn-
thesis and granulation tissue formation. Topical oxygen therapy
Negative-­pressure wound therapy (also known involves the application of pure oxygen directly to the wound area.
as vacuum-­assisted closure and topical
Examples of available devices include cannulas or tubing under-
negative-­pressure therapy)
neath occlusive dressings to deliver oxygen extracted from the air
Although there is limited evidence that negative pressure wound
therapy (NPWT) improves healing rates, it is commonly used in
the treatment of chronic wounds, for example diabetic foot ulcers.
It can also be used in acute wounds such as large surgical wounds
where healing by secondary intention is indicated. More recently, it
has been used in wounds healing by primary intention in order to
reduce the risk of surgical site infection.
Foam or gauze dressings are applied to the wound surface and
covered with an occlusive film to form an air-­tight seal. Continuous
or intermittent subatmospheric pressure is then applied (usually at
−50 to −125 mmHg) via suction tubing that connects the dressing
to a vacuum pump and waste collector. Various systems are availa-
ble, including small portable devices that can be used for wounds
with low exudate levels and devices that also provide wound irriga-
tion and instillation of antimicrobial treatments.
Negative-­pressure wound therapy is thought to aid healing by
enhancing wound retraction, reducing interstitial oedema and
improving blood supply, stimulating granulation tissue formation
and continuously removing debris and excess exudate. As it involves
the use of a closed system and requires less frequent dressing changes,
it may provide some protection against infection. Due to the applica-
tion of pressure, NPWT can be painful and additional analgesia may Occasionally, even the most absorptive dressings cannot control exudate
be required. Some patients have described a negative effect on quality levels and creative solutions, such as using stoma bags to collect fluid, are
of life and sleep disturbance due to being continuously attached to a required.

Allergy should be suspected when there is skin inflammation in the distribution of the dressing, as shown.

Negative-­pressure wound therapy. Gauze covered by an occlusive film forms
a seal and a vacuum pump is attached via tubing to provide suction.
Contraindications to the use of NPWT
• Untreated osteomyelitis
• Presence of malignant tissue
• Exposed organs, vessels or vascular anastomoses
• Bleeding/high risk of bleeding
• Presence of necrotic tissue
using a portable oxygen generator, and plastic chambers or boots
that can be placed around an extremity that allow delivery of
­oxygen under pressure. Oxygen can also be embedded in dressings
and gels.
Hyperbaric oxygen therapy involves breathing 100% oxygen
under pressure, which hyperoxygenates the blood. Multiple treat-
ments are administered in a specialised chamber for 1–2 hours at a
time over a period of weeks. It may be useful for diabetic foot ulcers
and ischaemic ulcers and there is some evidence that it reduces the
risk of major amputations.
Electrical stimulation
Intact skin has an electrical potential, and damage to the epithelial
layer creates an electrical field that helps guide epithelial cell migra-
tion during healing. Devices that provide electrical stimulation to
Dressings and Devices 93
Topical oxygen therapy. A circular device is placed directly on the wound
bed, allowing continuous delivery of oxygen from an oxygen generator
device around the size of a mobile phone. Secondary dressings are applied
to protect the wound and to absorb exudate.
the wound area through electrodes placed on the skin or wound
surface, as well as bioelectric dressings containing small batteries,
have been developed. Electrical stimulation may reduce bioburden,
increase local perfusion and accelerate healing, but evidence for its
effectiveness is limited and it is not used in routine clinical
practice.
Further reading
Apelqvist, J., Willy, C., Fagerdahl, A.M. et al. (2017). EWMA document: nega-
tive pressure wound therapy. Journal of Wound Care 1 (26): S1–S154.
Bryant, R.A. and Nix, D. (2016). Principles of wound healing and topical man-
agement. In: Acute and Chronic Wounds: Nursing Management, 5e (eds.
R.A. Bryant and D. Nix), 306–324. St Louis: Elsevier.
Rajendran, S. (2019). Advanced Textiles for Wound Care, 2e. Cambridge:
Woodhead Publishing, Elsevier.
Thomas, S. (2010). Surgical Dressings and Wound Management. Cardiff:
Medetec Publishing.
Vowden, K. and Vowden, P. (2017). Wound dressings: principles and practice.
Surgery 35 (9): 489–494.
 CHAPTER 14

Drugs and Biological Approaches

to Wound Healing
Gregory Schultz1 and Girish K. Patel2,3
1
University of Florida, Gainesville, FL, USA
2
Welsh Institute of Dermatology, Cardiff and Vale University Health Board, Cardiff, UK
3
Cardiff University School of Biosciences, Cardiff, UK

An improved understanding of wound healing biology has led to

OVERVIEW
•  Drug therapies may be used to improve healing in certain wound
types, for example vasodilators for ischaemic ulcers or immune
modulators for inflammatory ulcers.
•  Certain drugs are known to impair healing and should be stopped
whenever possible (a consideration of risk vs benefit is required).
•  An improved understanding of wound biology has led to the
development of so-­called biological therapies, including recombi-
nant growth factors and tissue engineered skin substitutes.
•  The efficacy of these treatments, particularly for chronic wounds,
has been variable in clinical trials.
•  Success often depends on adequate wound bed preparation, i.e.
removal of barriers to healing.
The healing of acute wounds involves a complex and dynamic
series of events leading to the repair of injured tissues. These events,
triggered by tissue injury, involve four overlapping but well-­defined
phases: haemostasis, inflammation, proliferation and remodelling.
Haemostasis is secured by platelet aggregation and clot formation.
The inflammatory phase begins with the arrival of phagocytic neu-
trophils and, later, macrophages at the wound site; they are impor-
tant sources of and substrates for growth factors. The proliferative
phase is characterised by the formation of new blood vessels (angi-
ogenesis) and synthesis of extracellular matrix components such as
collagen, granulation tissue formation and re-­epithelialisation. The
extracellular matrix is continually remodelled during the final
phase; an avascular scar is the end-­result of the healing process.
Chronic wounds may be arrested in any of the four phases; com-
monly, however, disruption occurs in the inflammatory or prolif-
erative phases. Many mediators, including inflammatory cells,
growth factors, proteases such as matrix metalloproteinases
(MMPs) and cellular and extracellular elements, play important
roles in different stages of the healing process. Alterations in one or
more of these components may account for the impaired healing
observed in chronic wounds.
the development of newer treatments targeting these specific
abnormalities. The discipline of regenerative medicine defines
three main therapeutic approaches: (i) tissue replacement by
induced regeneration, (ii) creation of three-­dimensional organs/tis-
sues using bio-­artificial scaffolds, and (iii) cell transplantation.
These are considered below, but combining all three techniques
may achieve maximal benefit.
Regeneration versus repair
Regeneration is defined as restoration of damaged tissue to its
normal state, i.e. the replacement of like with like. Humans
have a limited capacity to regenerate tissues; examples of
tissues that can regenerate include the oral mucosa and the
epithelial layer of the skin; injury leads to healing without scar
tissue formation.
Repair describes the process of healing by fibrosis and scar
tissue formation. In humans, any skin injury that is deeper than
the basal layer of the epidermis triggers healing by scar
formation.
Regenerative medicine uses advanced technologies and therapies
such as tissue engineering, biomaterials, stem cells and growth
factors with the aim of repairing, replacing or regenerating cells
and/or tissues to restore function.
Induced regeneration
Many drugs are currently used routinely to promote wound heal-
ing, while some such as growth factors are still undergoing clinical
trials. These drugs support existing wound management approaches
and may turn out to benefit other forms of tissue regeneration.
Some drugs actively block healing and merely stopping these drugs
may be sufficient to restore and promote healing.

ABC of Wound Healing, Second Edition. Edited by Annie Price, Joseph E. Grey, Girish K. Patel, and Keith G. Harding.
© 2022 John Wiley & Sons Ltd. Published 2022 by John Wiley & Sons Ltd.

94
 Drugs and Biological Approaches to Wound Healing 95

Maximum response
Inflammatory phase Proliferative phase Epithelialisation
and remodelling

Growth factors

Haemostatic phase
Early Late

Macrophages
• Epithelialisation
• Fibroblast • Extracellular matrix
Phagocytosis proliferation remodelling
and removal of • Collagen synthesis • Increase in tensile
foreign bodies • Extracellular matrix strength of wound
reorganisation • Scar maturation
• Angiogenesis
• Granulation tissue
Neutrophils formation
• Epithelialisation
0.1 0.3 1 3 10 30 100 300
Days after wounding (log scale)

A simplified diagram showing the overlapping phases of wound healing. Inflammatory cells and growth factors are involved in all phases. Source: Adapted
from Clark (1991).

Drugs that can impair wound healing.

Drug class Name of drug Effects on wound healing

Anti-­inflammatories Non-­steroidal anti-­inflammatory drugs • Affect inflammatory phase by inhibiting cyclo‑oxygenase production
• Reduce tensile strength of wound

Colchicine • Affects inflammatory phase

• Affects proliferative phase by decreasing fibroblast proliferation
• Affects remodelling phase by degrading the newly formed extracellular matrix

Corticosteroids Prednisolone • Affects haemostatic phase by decreasing platelet adhesion

• Affects inflammatory phase by affecting phagocytosis
• Affects remodelling phase by reducing fibroblast activity and inhibiting collagen
synthesis

Immunosuppressants Ciclosporine, • Impair inflammatory phase

mycophenolate, • Increase the risk of wound infection
tacrolimus,
rapamycin

Antiplatelets Aspirin • Affects haemostatic phase by inhibiting platelet aggregation

• Inhibits inflammation mediated by arachidonic acid metabolites

Anticoagulants Heparin • Affects haemostatic phase by its effect on fibrin formation

• Can lead to thrombus formation by causing thrombocytopenia (white clot
syndrome)

Warfarin • Affects haemostatic phase by its effect on fibrin formation

• Can cause tissue necrosis and gangrene by the release of atheromatous plaque
emboli in the form of microcholesterol crystals, so-­called ‘blue toe syndrome’

Vasoconstrictors Nicotine, cocaine, epinephrine, norepinephrine, • Affect proliferative phase by inhibiting neovascularisation and decreasing
ergotamine granulation tissue formation
• Impair microcirculation and increase graft rejection and ulcer necrosis

Anticancer drugs Azathioprine, cyclophosphamide, methotrexate, • Affect inflammatory phase by reducing numbers of inflammatory cells and thus
5-­fluorouracil, fludarabine, vincristine, cisplatin increasing the risk of wound infection
• Affect proliferative phase by decreasing cell proliferation

Growth factor inhibitors (bevacizumab, gefitinib, • Affect proliferative phase by inhibiting re-­epithelialisation, neovascularisation and
Iressa®, zelboraf, sorafenib) decreasing granulation tissue formation

Others Nicorandil and hydroxyurea • These drugs may induce painful ulceration
96 ABC of Wound Healing

Perianal ulceration caused by nicorandil. An ischaemic ulcer caused by systemic sclerosis and peripheral arterial
disease, suitable for treatment with iloprost.

Vasodilator drugs used in wound healing.

Drug class Name of drug Actions Uses

Prostacyclin analogue Iloprost • Vasodilation • Intermittent claudication

• Inhibits platelet aggregation
• Severe limb ischaemia
• Prevention of imminent gangrene
• Reduce pain and clinical symptoms
associated with Raynaud disease
• May be useful for arterial ulcers
including those due to scleroderma

Methylxanthine Pentoxifylline • Improves perfusion of • Treatment of intermittent claudication in

peripheral vascular beds
• Reduces blood viscosity and
platelet aggregation
• May reduce inflammation by
inhibiting tumour necrosis
factor-­α (TNF-­α)
peripheral arterial disease
• Venous leg ulcers – for patients who
cannot tolerate compression or as an
adjunctive therapy
• May be useful in sickle cell ulcers,
livedoid vasculitis and necrobiosis
lipoidica

Calcium antagonists Diltiazem, • Vasodilation • Vasculitic ulcers

amilodipine and • Raynaud disease
nifedipine

Nitrates Glyceryl trinitrate (GTN) – applied • Vasodilation • Established treatment for chronic anal
topically as 0.2% or 0.4% ointment fissures
• May have a role in treatment of vasculitic
ulcers

Inhibitors of cyclic guanosine Sildenafil • Vasodilation • Established treatment for erectile

monophosphate-­specific dysfunction and pulmonary artery
phosphodiesterase type 5 hypertension
• May have a role in treatment of vasculitic
ulcers and Raynaud disease

Vasodilators in wound healing Immune modulators

Many wounds result from circulatory problems (chronic venous
insufficiency or peripheral arterial disease), which may be the pri-
mary cause of the disease or a confounding factor. Drug therapy is
often used to compliment conventional approaches (e.g. revascu-
larisation procedures for arterial disease) or when surgical inter-
vention is not an option.
Wounds that are a consequence of an underlying inflammatory dis-
ease, e.g. vasculitis or pyoderma gangrenosum, usually will not heal
until the inflammatory process has been controlled by immune
modulators. In pyoderma gangrenosum, for example, additional
trauma to the wound, e.g. wound debridement, often worsens the
condition. Immune modulators are therefore an essential adjunct
 Drugs and Biological Approaches to Wound Healing 97

A recalcitrant venous ulcer that has failed to heal despite compression Sickle cell ulcers. Vasodilator drugs may reduce pain and aid healing.
therapy, suitable for treatment with pentoxifylline.

Immune-­modulating drugs used in wound healing.

Drug class Name of drug Actions Uses

Glucocorticoids Prednisolone or topical • Attenuate excessive inflammatory response • Ulcers caused by connective tissue diseases,
corticosteroids • Long-­term use can have detrimental effect on healing e.g. rheumatoid arthritis
• Vasculitic ulcers
• Pyoderma gangrenosum

Calcineurin Ciclosporine • Immunosuppressant • Inflammatory ulcers, e.g. pyoderma

inhibitors Tacrolimus – topical and gangrenosum
systemic
preparations

Other immune modulators Many immune modulators are available and being developed, including those that specifically target
inflammatory molecules such as TNF-­α, CD20 and IL-­12. Their use in wound healing depends on the
primary cause of the wound and they may be beneficial for inflammatory disorders such as pyoderma
gangrenosum

to facilitate healing of affected tissues. Immunosuppressants are
also essential for the maintenance of allogeneic tissue grafts
(discussed later).
Drugs that reduce matrix degradation
Non-­ healing chronic wounds typically demonstrate excessive
inflammation with elevated MMP levels, leading to matrix degra-
dation and subsequent impairment of healing. A wound diagnostic
that measures wound bed MMP levels has recently been developed
and commercialised, and is said to detect harmful MMP levels in
chronic wounds. In addition to advanced wound dressings, tetracy-
cline antibiotics, such as doxycycline, are able to inactivate MMPs
and so promote chronic wound healing. Phenytoin can inhibit col-
lagenases (reducing collagen breakdown), but its use is limited due
to toxicity.
Growth factors
Growth factors are key molecular regulators of normal wound heal-
ing. Different growth factors function in all four sequential phases
of normal healing of skin wounds. As their names indicate, a major
physiological effect of most growth factors is to stimulate prolifera-
tion of cells. However, different growth factors generally target dif-
ferent types of cells.
With the development of recombinant protein expression
techniques in the early 1980s, large amounts of pure human
sequence growth factors became available. One of their first
clinical applications was in wound healing, leading to enhanced
healing of partial-­thickness skin graft donor sites in patients
undergoing skin grafting. Since that time, multiple recombinant
human growth factors have been tested in a variety of wound
healing studies. Treatment of impaired wounds with various
exogenous growth factors can stimulate key processes of heal-
ing, including angiogenesis (granulation tissue formation),
extracellular matrix formation (scar matrix), contraction of scar
tissue and epithelialisation.
The first growth factor to receive FDA clearance with the claim
of enhanced wound healing was rhPDGF-­BB – recombinant human
platelet-­derived growth factor-­BB (Regranex®). The pivotal phase
III clinical trial showed that topical rhPDGF-­ BB significantly
enhanced both the rate and percentage of chronic diabetic foot
ulcers that healed. However, phase IV postmarket approval analysis
of clinical data led the FDA to issue a ‘black box’ warning that treat-
ment of patients with more than three tubes of the product
increased the risk of dying from cancer. Although not in itself car-
cinogenic, it should be avoided in patients with known malignancy.
The rhPDGF-­BB story continues to impact the field of wound care.
98 ABC of Wound Healing

Pyoderma gangrenosum being treated with corticosteroids.

Cutaneous Crohn’s disease causing ulceration and inflammation in the natal

cleft, managed with targeted anti-­TNF-­α therapy.

Keratinocyte growth factor (KGF, Kepivance™) received FDA

approval in 2004 for the treatment of severe oral mucositis following
treatment for haematological malignancies with high doses of
chemotherapy and radiation therapy followed by stem cell rescue.
Subsequently, injections of recombinant human epidermal growth
factor (rhEGF) into diabetic foot ulcers have been reported by inves-
tigators for many years to stimulate healing. A large randomised
controlled trial of topical recombinant human fibroblast growth fac-
tor (rhFGF) reported a significant acceleration of epithelial healing
Rheumatoid ulcer requiring treatment with immune-­modulating therapies
such as corticosteroids.
of deep partial-­thickness burns and skin graft donor sites. Other
growth factors, including GM-­CSF and growth ­hormone, have also
been associated with improved healing in a variety of acute and
chronic wounds.
 Drugs and Biological Approaches to Wound Healing 99

Wound bed preparation Gene therapy

Wound bed preparation is the concept of identifying and removing
abnormalities that could be impairing wound healing in order to
accelerate the normal healing processes or facilitate the effective-
ness of wound healing therapies. Examples include treating
infection, removing non-­viable tissue and ensuring adequate tissue
oxygenation.
Proteases present in chronic wounds are likely to limit the effective-
ness of exogenous growth factors. Gene therapy (insertion of a
gene into recipient cells) has been explored as an alternative, with
the aim of increasing production of endogenous growth factors.

Bio-­artificial scaffolds including

Growth factors are key molecular regulators of normal wound
healing, and disruption of their actions on target cells impairs heal-
ing and typically leads to stalled or chronic wounds. However,
growth factors must be used within the context of a wound bed that
has been properly prepared (e.g. by debridement of unhealthy or
infected tissue) to reduce inflammation and protease activities. In
the absence of appropriate wound bed preparation, treatment with
exogenous growth factors has minimal effects on healing.
the creation of three-­dimensional tissues
Repair of damaged tissues like the skin or internal organs typically
requires the generation of a three-­ dimensional matrix that is
­populated by cell types that maintain their differentiated functions.
This has c­ reated a major challenge for the emerging field of tissue
engineering to construct functional three-­dimensional bio-­artificial
tissues. The design of the extracellular matrix is crucial to achieving
the final functional tissue construct. The extracellular matrix

Major growth factors that play important roles in normal wound healing.

Growth factor Cell source Actions

Transforming growth factor (TGF): Platelets TGF-­β1 and TGF-­β2:

• TGF-­β1 Fibroblasts Chemotactic for fibroblasts
• TGF-­β2 Macrophages Promote extracellular matrix (ECM) formation:
• TGF-­β3 • ↑ collagen and TIMP synthesis
• ↓ MMP synthesis
TGF-­β3 reduces scarring by:
• ↓ collagen
• ↓ fibronectin

Platelet-­derived growth factor (PDGF) Platelets Activate immune cells and fibroblasts
Macrophages Promote ECM formation by:
Endothelial cells • ↑ collagen and TIMP synthesis
• ↓ MMP synthesis

Vascular endothelial growth factor (VEGF) Endothelial cells ↑ Angiogenesis

Fibroblast growth factor (FGF) Macrophages ↑ Angiogenesis

Endothelial cells ↑ Keratinocyte proliferation and migration
Fibroblasts ↑ ECM deposition

Keratinocyte growth factor (KGF) Fibroblasts ↑ Keratinocyte proliferation and migration

Insulin-­like growth factor (IGF) Liver ↑ Keratinocyte and fibroblast proliferation

Skeletal muscle ↑ Angiogenesis
Fibroblasts ↑ Collagen synthesis
Macrophages ↑ ECM formation
Neutrophils ↑ Cell metabolism

Epidermal growth factor (EGF) Keratinocytes ↑ Keratinocyte proliferation and migration

Macrophages ↑ ECM formation

Connective tissue growth factor (CTGF) Fibroblasts ↑ Collagen synthesis

Endothelial cells Mediates action of TGF-­βs on collagen synthesis
Epithelial cells

Colony-­stimulating factors: Stromal cells G-­CSF – stimulates granulocyte (white blood cell) proliferation
• Granulocyte colony-­stimulating factor (G-­CSF) Fibroblasts GM-­CSF – stimulates proliferation of granulocytes and
• Granulocyte macrophage colony-­stimulating Endothelial cells macrophages
factor (GM-­CSF) Lymphocytes

MMP-matrix metalloproteinase; TIMP-tissue inhibitor of metalloproteinase.

100 ABC of Wound Healing

­ aterial must contain the correct molecules that ‘signal’ stem cells
m dressings that must be frequently removed from the wound bed.
(described below) seeded into the tissue to proliferate and differen-
tiate into the correct phenotype. In addition, the generated tissue
construct must be sufficiently durable to enable handling during
manufacturing and by a surgeon during application onto (or into) a
patient.
Fortunately, material engineers have decades of experience and a
wide range of natural molecules and synthetic polymers can be
used alone or, more frequently, in combination to achieve the
required performance specifications. These include intact fibrillar
collagens (type I and III), basement membrane collagen (type IV),
large polymers of hyaluronic acid, multidomain adhesion proteins
like fibronectin and laminin, and minimally processed tissues
including amniotic membrane, porcine small intestine submucosa
and sheep fore-­stomach submucosa.
Tissue engineered skin substitutes consist of skin cells or a scaf-
fold (to replace the extracellular matrix) or both, which form a tem-
porary or permanent functional skin replacement. Acellular skin
substitutes have the advantage of being readily available and pro-
vide a temporary barrier function, often requiring skin grafting
later on. Cultured cells take time to produce but may offer permanent
coverage.
New clinical needs and applications are constantly emerging.
One area that appears promising is the use of an implantable
matrix with negative-­ pressure wound therapy (NPWT).
Currently, NPWT uses open cell polyurethane foam or gauze
However, an engineered three-­dimensional matrix that serves as
a scaffold to accelerate vascularisation and remains in the wound
bed should provide a better and more rapid clinical outcome.
Combining these natural or artificial tissue constructs with
growth factors (or preserving the endogenous growth factors
found in the starting biological tissues) enhances the effects of
these bio-­scaffold products.
Cell-­based therapies
The cells in our bodies are constantly renewing at an astonishing
rate; we lose over 50 billion cells each day. Cell numbers in many
tissues are replenished and maintained by a hierarchical system
from adult tissue-­specific stem cells. The aim of cell-­based thera-
pies is therefore to replace lost or exhausted adult tissue stem cell
Sources of cells
Autologous: cells harvested from one area of the body and
transplanted to a different area in the same individual.
Allogeneic: cells harvested from one individual and transplanted into
a genetically different individual from the same species.
Xenogeneic: cells harvested from one individual and transplanted
into an individual from a different species.

Examples of tissue engineered skin substitutes.

Product Description Uses/advantages Disadvantages

Acellular skin substitutes

Biobrane® Nylon fibres embedded in silicon and combined Temporary cover for partial-­ Risk of infection
with porcine collagen thickness wounds, e.g. burns or
donor sites

Integra® Bovine collagen and chondroitin-­6-­sulfate Immediate coverage for Requires 2nd operation 3–4 weeks later to
glycosaminoglycan (dermal substitute) combined surgically excised full-­thickness remove silicon membrane and replace with
with silicon membrane (epidermal substitute) burns autologous skin graft
Requires healthy wound base

Alloderm® Acellular cadaveric dermis Full-­thickness burns and deep No epidermal layer – may require
ulcers autologous skin graft

Cellular allogenic skin substitutes

Transcyte® Fibroblasts from neonatal foreskin embedded in Partial-­or full-­thickness burns May require autologous skin graft after
nylon mesh 2–3 weeks

Dermagraft® Neonatal fibroblasts cultured on a biodegradable Non-­healing diabetic foot Not suitable for infected wounds or those
mesh ulcers and venous leg ulcers with exposed tendon or bone

Apligraf® Combination of neonatal keratinocytes, neonatal Non-­healing diabetic foot Not suitable for infected wounds
fibroblasts and bovine collagen – a composite ulcers and venous leg ulcers
skin graft with living epidermis and dermis

Cellular autologous skin substitutes

Cultured epidermal Autologous keratinocytes (from a skin biopsy) Partial-­thickness burns No dermal replacement therefore may not
autograft, e.g. EpicelTM, are cultured in the laboratory and applied using Much smaller donor site be helpful in full-­thickness wounds/burns.
CellMistTM a carrier system, e.g. a sheet or spray compared to autologous skin Variable take – transplanted keratinocytes
grafting can be digested by proteases in the wound

numbers, to restore tissue viability. This may be simply achieved by
skin grafts, taking redundant skin from a donor site and placing it
onto the wound. In the absence of redundant tissue, cells in the
form of allogeneic grafts can be transplanted from donor individu-
als. This approach necessitates immunosuppression to prevent
graft-­versus-­host disease, but is still favourable for transplantation
of vital organs.
Expansion of adult tissue stem cells
This approach was first employed successfully in the expansion of
human skin stem cells to treat burn injuries and more recently
adapted to expand human corneal epithelia from limbal stem cells for
the treatment of corneal scarring. A small sample of intact limbal
stem cells from the unaffected eye is collected and the stem cells are
then expanded to form a new cornea which is then transplanted onto
the affected eye. Since mostly this is an autologous approach, it avoids
the need for immunosuppression. The enrichment of stem cells in
tissue culture has also facilitated gene therapy, since inserted genes
are introduced into long-­lived adult tissue stem cells, for the treat-
ment of skin blistering disease with prominent wounding.
Stem cells
• Stem cells can differentiate into other cell types (termed potency)
and also have the capacity for self-­renewal.
• Embryonic stem cells, derived from the blastocyst (early stage
embryo), are pluripotent, i.e. they can divide into cell types from
all three germ layers (endoderm, mesoderm and ectoderm).
• Multipotent adult or somatic stem cells are found in bone
marrow, adipose tissue and blood and can differentiate into
closely related cell types.
• Induced pluripotent stem cells are adult cells that have been
genetically altered to become pluripotent.
• The skin also contains stem cells; epidermal stem cells are located
in the basal layer and can regenerate the epidermis (making them
unipotent). Multipotent stem cells are found in the hair follicle
bulge and can differentiate into epidermal and skin appendage
cell types.
Expansion of other cell types
Allograft neonatal skin cells that have diminished capacity to
induce an immune response have been expanded in tissue culture
and then placed into a collagen matrix, producing a skin substitute.
Two products have been developed commercially and are currently
available in many countries: Dermagraft® (neonatal fibroblasts
alone) and Apligraf® (neonatal keratinocytes and fibroblasts).
Although the cells from these products, when applied onto
Drugs and Biological Approaches to Wound Healing 101
i­mmunocompetent skin, are eventually lost, during the first few
weeks the cells are able to sense their environment and produce
­factors that promote healing. Clinical trials in venous leg ulceration
and diabetic foot ulceration show these products to be beneficial in
patients with otherwise recalcitrant ulcers.
The ability to expand cells in defined tissue culture conditions
has been used to expand other cell types, most notably mesenchy-
mal stem cells, which are found in adult bone marrow and adipose
tissue and possess the capacity to differentiate into other cell types
(e.g. bone and cartilage). Mesenchymal stem cells also appear to
facilitate healing after significant injury and clinical studies using
mesenchymal stem cells for wound healing are ongoing. Similarly,
the ability to differentiate embryonic stem cells and more recently
induced pluripotent stem cells has led to interest in their potential
use in wound healing.
Concerns about biological treatments
Despite often promising results in laboratory studies and preclini-
cal trials, biological therapies have not always translated well to
real-­life patients. This may be due to the abnormalities seen in the
chronic wound environment that limit the effectiveness of treat-
ments such as recombinant growth factors. The use of stem cells,
particularly embryonic stem cells, remains controversial due to
ethical concerns and legal restrictions. Stem cells are also associated
with a potential risk of malignancy. The use of allogeneic or xeno-
geneic donor tissues or cells carries the risk of rejection by the host
immune system and possible transmission of diseases. Production
and cost are also concerns; specialist technology and knowledge are
required for the production of these advanced therapies, which may
limit widespread use.
Reference
Clark RA. In: Goldsmith LA (ed.) Physiology, Biochemistry and Molecular
Biology of the Skin. 2nd edn. Vol 1. New York: Oxford University Press,
1991: 577.
Further reading
Jull, A., Waters, J., and Arroll, B. (2002). Pentoxifylline for treatment of venous
leg ulcers: a systematic review. Lancet 359 (9317): 1550–1554.
Karukonda, S.R., Flynn, T.C., Boh, E.E. et al. (2000). The effects of drugs on
wound healing – part II. Specific classes of drugs and their effect on healing
wounds. International Journal of Dermatology 39 (5): 321–333.
Pang, C., Ibrahim, A., Bulstrode, N.W., and Ferretti, P. (2017). An overview of
the therapeutic potential of regenerative medicine in cutaneous wound
healing. International Wound Journal 4 (3): 450–459.
Schultz, G.S., Sibbald, G., Falanga, V. et al. (2003). Wound bed preparation:
a  systematic approach to wound management. Wound Repair and
Regeneration 11: S1–S28.
 Index

ABPI see ankle‐brachial pressure index calcification  26, 28, 39, 52 DACC see dialkylcarbamoyl chloride
abrasions 9 callus  4, 8, 26–29 debridement
absorbent dressings  86 camouflage 78 diabetic foot ulcers  26–27, 29
acid burns  20–22 cancers  53–54, 64–65, 95, 97 infection 56–61
acroangiodermatitis 50 carbohydrates 71 pressure injuries  48
adherent dressings  85–86 casts  27–28, 30 traumatic wounds  11–12
adhesive strips  12, 16–17 cavity wounds  87–90 venous leg ulcers  36, 38
adult tissue stem cells  101 cell‐based therapies  100–101 wound assessments  7–8
advanced dressings  86–91 cell sources  100 degloving 10
alginate dressings  88–89 cellular processes, scars  80–83 depth of wound  2–3, 22, 24, 43, 44
alkali burns  21 cellulitis 64–69 dermatitis artefacta  54–55
allogenic cells  100–101 charcoal swabs  58, 59 diabetic foot ulcers  26–33, 57, 59
allograft neonatal skin cells  101 Charcot osteoarthropathy (Charcot foot)  diagnosis, infections  60–61
amputations  26–32, 39, 48, 61, 93 32–33 dialkylcarbamoyl chloride (DACC)  90
angiosarcoma 54–55 chemical injuries  20–22 diuretics 69
ankle‐brachial pressure index [ABPI]  26–29, chronic oedema  64, 67 Doppler arterial waveforms  26, 28
34–35, 39 chronic wounds dressings 85–93
antibacterial impregnated sutures  15–16 assessments 1–4 burns 22–25
antibiotics  9–11, 14, 15, 18, 29, 36–37, complications  1, 3 infection 57
56–63 continence 74–75 skin care  73–74
antimicrobial dressings  89–91 dressings and devices  85–86, 90–92 surgical wounds  17
antiphospholipid syndrome  52–53 drugs and biological therapies  94–101 drugs 94–101
antiseptics  14, 18, 22, 37, 57, 59 infection  56–57, 60–63 ulcers  36, 40, 54–55, 94–98, 100–101
arterial calcification  26, 28 lymphoedema 64–69
arterial disease  34–35, 37–40, 45, circumferential full‐thickness burns  23–24 edges of wounds  3, 5–6
91–92, 96 clean‐contaminated surgical wounds  14 education, diabetic foot ulcers  30, 32
arterial leg ulcers  34–35, 37–40 clean surgical wounds  14 electrical injuries  20, 22
assessments see wound assessments clinical history  1, 3 electrical stimulation  93
autologous cells  100 clips 13 embryonic stem cells  101
avulsion wounds  10 closure  9, 12–18, 80–82, 92 epidermal substitutes  23–24
compression devices  34–40, 66–69 erythema  21–23, 82
basal cell carcinomas  53–54 connective tissue diseases  49, 51 eschar  3, 7–8, 41–48
basic dressings  85–86 contact burns  20–21 Escherichia coli 76–77
bio‐artificial scaffolds  99–100 contact dermatitis  34, 54–55, 68, 74 expansion of cell types  101
Biobrane suits  23–24 contamination exudate  4, 58, 62–63, 85–93
biological therapies  29–32, 94–101 surgical site infections  17–19
biopsies  3, 31, 35, 49, 55 surgical wounds  14 faecal incontinence  74, 75–77
bite wounds  9–10, 56 traumatic wounds  11–12 fats, nutrition  71
blisters  22, 24 continence 74–77 flame injuries  20–21
blood constituents  52–53 contracture, scars  81 flaps  13–15, 48
body surface area charts  21–23 contusions 9 flash burns  20–21
boots/footwear  27–28, 30 corticosteroids  95, 97, 98 fluid resuscitation  24, 25
Braden scale  45 Crohn’s disease  98 foam dressings  88–89
burns 20–25 cutaneous necrosis  51–53 folliculitis 67

ABC of Wound Healing, Second Edition. Edited by Annie Price, Joseph E. Grey, Girish K. Patel, and Keith G. Harding.
© 2022 John Wiley & Sons Ltd. Published 2022 by John Wiley & Sons Ltd.

102
 Index 103

footwear  27, 30 localised infections  56–61 pressure injuries  41–48

friction 43 low adherent dressings  85–86
full‐thickness injuries  22–25, 44 lower leg ulcers  34–40
low voltage injuries  20
gangrene  29–30, 39, 49, 51, 72, 78–79, 95–98 Lund and Browder charts  21–23
gauze dressings  86, 92–93 lymphoedema 64–70
gene therapy  99 lymphorrhoea 66
grafts  13, 15, 18–19, 23, 58, 81, 95–101
granulation tissue  3, 6, 58, 86, 90–92 maceration  4, 8, 43, 44, 73–76, 86–88, 91
growth factors  94–101 malignancy  1–3, 53–55, 97–98
malnutrition  45, 71–72
heparin necrosis  53 malodour see odour
hidradenitis suppurativa  78–79 management see wound management
high voltage injuries  20 Martorell hypertensive ulcers  50
honey 90 materials, sutures  15–16
hosiery  36, 38 matrix metalloproteinases (MMP)  94
hydration  45, 85–86 measurements, wound assessments  1–2, 4–5
hydrocellular dressings  89 mechanical loading, pressure injuries  43
hydrocolloid dressings  86–87 medical management, incontinence  75–76
hydrofiber dressings  87 melanoma 54
hydrogel dressings  87–88 methicillin‐resistant Staphylococcus aureus
hydroxyurea 54 (MRSA)  4, 18, 56, 61, 90
hyperkeratosis  66–67, 73–74 mixed leg ulcers  34, 40
hypertrophic scarring  25, 80–83 MMP see matrix metalloproteinases
moisture lesions  76–77
iatrogenic causes, ulceration  54–55 molecular processes, scars  80–83
imaging  28–33, 39, 60–62 morphology, scarring  80, 82
immediate burn management  22, 24 MRSA see methicillin‐resistant
immune modulating drugs  96–98 Staphylococcus aureus
impaired healing Mycobacterium 53
drug effects  54, 94, 95, 99
infections 56 necrobiosis lipoidica diabeticorum  49, 51
lymphoedema 67 necrotic tissue  3, 7–8, 27, 57, 59–60
metabolic control  30 necrotising fasciitis  60, 78–79
nutrition  45, 71 needles 15–16
incision wounds  10, 14–19, 78 negative pressure wound therapy
incontinence 74–77 (NPWT)  18, 27, 47, 92–93, 100
induced regeneration  94 neuroischaemic foot ulcers  26–30
infections 56–63 neuropathic foot ulcers  26–32
diabetic foot ulcers  26–31, 58, 59 non‐adherent dressings  86
osteomyelitis 60–62 NPWT see negative pressure wound therapy
scars 80–83 nutrition  45, 71–74
surgical incisions  14–19
uncommon ulceration causes  53 obesity 71
wound assessments  4 odour, wound assessments  5
inflammation odour absorbent dressings  91
lymphoedema 64–67 oedema 64–70
nutrition 71–72 osteomyelitis  27, 29, 31–32, 60–62
scars 78–81 overflow incontinence  75
ulceration causes  49–51 oxygenation 45
inhalation injuries  23 oxygen therapy  92–93
injuries, pressure injuries  41–48
iodine preparations  89–90 pain 5–6
ionising radiation  21 papillomatosis  66, 67
ischaemia  26–30, 94, 96 Parkland formula  24, 25
partial‐thickness injuries  22, 24, 44
Kaposi sarcomas  49–50 penetrating trauma  9
keloid scars  80, 82–83 perfusion  45, 68
Keratinocyte growth factor (KGF), Kepivance®  98 perianal ulceration  96
peripheral arterial disease  34–35, 37–40, 45,
laboratory investigations  1, 3, 59–60, 100–101 91–92, 94, 96
lacerations 9–10 peristomal pyoderma gangrenosum  49, 51
larval debridement  8 pigmentation 81
leg ulcers  34–40, 57, 68–69, 73–75 polyhexamethylene biguanide (PHMB)  90
Leishmania 53 postoperative abdominal wounds  78
lightning injuries  20, 22 postoperative wound healing  14
pressure redistribution  46–47
prevention
burns 25
diabetic foot ulcers  26–27
leg ulcers  37, 48
pressure injuries  41–48
surgical site infections  18
primary intention  15–17
primary lymphoedema  64, 66, 68
primary wound closure  12–17
proliferation, scars  80, 82–83
proteins, nutrition  71–72
pseudo‐Kaposi sarcoma  50
Pseudomonas infections  36, 60–63
PURPOSE‐T assessments  45
purpura fulminans  53
pyoderma gangrenosum  49, 51, 79, 96–98
quality of life  6–8, 43, 64, 69, 75, 92
quantitative analysis  58
radiation injury  21
radiotherapy 54–55
Raynaud phenomenon  51–52
recombinant human epidermal growth factor
(rhEGF) 98
recombinant human platelet‐derived growth
factor‐BB (Regranex®)  97
reconstructive ladder  12–13
redistributing pressure  46–47
remodelling scars  80–83
resuscitation  10, 24, 25
revascularisation  34–35, 39–40
rhEGF see recombinant human epidermal
growth factor
rheumatoid arthritis  49, 51
rheumatoid ulcers  96, 98
risk factors
pressure injuries  41–48
risk assessments  45
surgical site infections  18
venous leg ulcers  34–35
safeguarding, pressure injuries  47
sampling wounds  58–59
scald injuries  20–21
scar contracture  81
scars  25, 78–84
sclerosis 51–52
secondary dressings  85–86, 88, 91–92
secondary intention  12, 15, 18
secondary lymphoedema  64–65
semi‐permeable films  86
semi‐quantitative analysis  59
sickle cell ulcers, drugs  94, 97
silver antimicrobial dressings  89–90
silver‐based burn products  23
skin care, leg ulcers  36–39, 73–74
skin flaps  13–15, 48
skin grafts  13–14, 18–19, 23, 57, 81, 97–101
skin hydration  45, 86
slough  3, 7–8, 44, 47, 57
specialised dressings  91
squamous cell carcinomas  2, 4, 6, 53–55
SSI see surgical site infections
104 Index

Staphylococcus aureus toe pressures  26, 28–29 warfarin necrosis  53

leg ulcers  36 tophaceous gout  50 Waterlow scale  45
lymphoedema 66–67 trace elements  72 wound assessments
MRSA  4, 18, 56, 61, 90 traumatic wounds  9–13 burns 21–22
surgical site infections  17–18 treatment general 1–8
uncommon ulceration causes  53 diabetic foot ulcers  26–33 leg ulcers  35–36, 39
staples  13, 16–17 infections 56–63 nutritional status  72
stem cells  100–101 leg ulcers  34–40 wound bed  3, 6–7, 98–99
Streptococcus  37, 53 lymphoedema 64–70 wound closure  9, 12–18, 80–82, 92
stress incontinence  75 pressure injuries  45–48 wound management
superficial wounds  56–61, 67, 78, 86 surgical site infections  18–19 biological therapies  99–101
super‐glues 13 burns 22–25
surgery ulceration/ulcers debridement 8
burns 23 causes  1–2, 49–55 devices 92–93
incontinence 75–76 diabetic foot ulcers  26–33 diabetic foot ulcers  26–33
leg ulcers  34, 36, 39–40 drugs  36, 40, 54–55, 94–98, 100–101 dressings 85–86
lymphoedema 69 leg ulcers  34–40 drugs 94–98
pressure injuries  48 lymphoedema  64, 66–69 infections  58, 61–63
scarring 78–82 pressure injuries  41, 43–48 leg ulcers  36–40
surgical incisions  10, 14–19 uncommon causes  49–55 lymphoedema 67–70
surgical site infections (SSI)  14, 17–19 wound assessments  1–8 pressure injuries  41, 44–48
surgical wounds  14–19 urisheaths 75 principles  1, 3
surrounding skin, wound assessments  4, 8 urethra erosion  75–76 surgery 12–13
sutures  13, 15–17 urge incontinence  75 surgical wounds  14–17
swabs 58–59 urinary incontinence  74–77 traumatic wounds  10–13
synthetic epidermal substitutes  23–24 wound sampling  58–59
systemic infections  56–62 vacuum‐assisted closure  92 wrinkled paper scaring  78–79
vapour‐permeable films  86
thermal injuries  20–21 vasodilators 96 xenogeneic cells  100–101
tissue necrosis  3, 7–8, 26 venous leg ulcers  34–37, 39–40, 96, 97
tissue sampling  59 vitamins 72
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