Table Of ContentLuc Téot
Thomas A. Mustoe
Esther Middelkoop
Gerd G. Gauglitz
Editors
Textbook on Scar
Management
State of the Art Management
and Emerging Technologies
123
Textbook on Scar Management
Luc Téot • Thomas A. Mustoe • Esther Middelkoop
Gerd G. Gauglitz
Editors
Textbook on Scar
Management
State of the Art Management and Emerging Technologies
Editors Thomas A. Mustoe
Luc Téot Division of Plastic and Reconstructive
Department of Burns, Wound Healing and Surgery
Reconstructive Surgery Northwestern University School of Medicine
Montpellier University Hospital Chicago, Illinois, USA
Montpellier, France
Gerd G. Gauglitz
Esther Middelkoop Department of Dermatology and Allergy
Amsterdam UMC, Vrije Universiteit Ludwig Maximilian University Munich
Amsterdam, Department of Plastic, Munich, Germany
Reconstructive and Hand Surgery,
Amsterdam Movement Sciences, Amsterdam,
The Netherlands Association of Dutch Burn
Centers, Red Cross Hospital
Beverwijk, The Netherlands
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V
Foreword
The interest in wound healing goes back to the beginning of history and has not dimin-
ished throughout the centuries also because practical implications of wound healing
studies have remained very relevant for public health. During the last century, much
progress has been made in the understanding of basic mechanisms of skin wound heal-
ing, and it has been realized that healing processes evolve similarly in various organs. It
has been established that fibrotic diseases are regulated by analogous mechanisms,
albeit less controlled, compared to those regulating wound healing. Moreover, many
advances, such as the use of antiseptics and, later, of antibiotics, as well as the intro-
duction of skin transplants have facilitated the treatment of wounds. It has been shown
that wound healing evolution depends on several factors including the type of injury
causing the damage, the tissue and/or organ affected, and the genetic or epigenetic
background of the patient.
This Compendium has the merit of discussing a broad spectrum of topics, including
the general biology of wound healing, modern diagnostic approaches, and therapeutic
tools, applied to many different clinical situations. It should be of interest to teachers,
students, and clinicians working in different aspects of wound healing biology and
pathology. I am sure that it will rapidly become an important reference book in these
fields.
Giulio Gabbiani
Emeritus Professor of Pathology
University of Geneva
Geneva, Switzerland
Preface
Scars represent the indelible cutaneous signature of aggression, surgery, traumas, and
other events occurring during life. Most of them cause no problem, but some of them
become sources of social exclusion, especially in a world where beauty is glorified. The
psychosocial aspects surrounding culture, religion, and uses may be determinant. Even
a transient redness may become source of suffering. Paradoxically, major keloids or
massive contractures cause definitive loss of function or social problems leading to
exclusion in developing countries, whereas simultaneously, we assist a rapid extension
of laser technology indications for minor scar problems in the same countries. When
we founded the Scar Club in 2006 together with Prof. Tom Mustoe, the aim was and
still is the diffusion of knowledge and the development of all types of mechanical
devices and antiscarring drugs.
Important financial support for researches in the field of growth factors and antis-
carring agents was recruited, aiming at controlling cell proliferation and secretion using
chemical compounds, but the results were modest. Mechanical control of keloids or
hypertrophic scars is proposed and reimbursed in some countries, applying medical
devices capable to exert forces over the suture during the post-operative period or over
post-burn scars.
This small group formed the Scar Club, composed of passionate colleagues who
attracted surgeons and dermatologists, researchers, and physiotherapists, becoming an
upmost scientific biannual rendezvous attracting colleagues from all over the world.
The Scar Club group is built like a club, focusing on researches, new organizations and
collaborations, new strategies, and development of guidelines.
The need for a larger educational initiative appeared since 2015 and the GScarS was
founded in 2016. In October 2018, the first GScarS meeting was held in Shanghai with
a successful event, grouping more than 600 colleagues. The idea came from the Board
to provide an educational book free of charge, open source, and downloadable from
anywhere. Patients and caregivers suffer most of the time from an insufficient profes-
sional training, and scar science is poorly represented in teaching courses at universi-
ties. Most of the proposed treatments are still based on cultural or anecdotal medicine.
It is time to propose a structuration of the scar knowledge based on evidence-based
medicine, consensus, guidelines, and key opinion leaders’ expertise.
This Compendium on scar management proposes a synthesis of the basic principles
in scar management, including the large armamentarium of medical devices having
proven efficacy and considered as the standards of care, and also the most recent tech-
niques accessible in scar management, provided by the most prominent specialists com-
ing from all over the world. It will be completed by a series of illustrations, schematic
strategies, and clinical cases accessible on the Springer website.
Luc Téot
Montpellier, France
VII
Contents
I Biology and Scar Formation
1 Fetal Wound Healing ............................................................ 3
Magda M. W. Ulrich
1.1 Background ........................................................................ 4
1.2 Inflammation ....................................................................... 4
1.3 Extracellular Matrix ................................................................. 5
1.4 Angiogenesis ....................................................................... 5
1.5 Keratinocytes....................................................................... 6
1.6 Fibroblasts.......................................................................... 7
1.7 Mechanical Forces .................................................................. 7
1.8 Remodeling ........................................................................ 8
1.9 Skin Appendix Formation ........................................................... 8
1.10 Conclusions......................................................................... 8
References.......................................................................... 9
2 Mechanobiology of Cutaneous Scarring....................................... 11
Rei Ogawa
2.1 Background ........................................................................ 12
2.2 Role of Mechanobiology in Cutaneous Scarring ...................................... 12
2.3 Cellular and Tissue Responses to Mechanical Forces .................................. 12
2.4 Role of Mechanobiology in the Development of Pathological Scars.................... 13
2.5 A Pathological Scar Animal Model that Is Based on Mechanotransduction ............. 16
2.6 Mechanotherapy for Scar Prevention and Treatment.................................. 16
2.7 Conclusion.......................................................................... 17
References.......................................................................... 17
3 Scar Formation: Cellular Mechanisms.......................................... 19
Ian A. Darby and Alexis Desmoulière
3.1 Background ........................................................................ 20
3.2 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20
3.3 General Mechanisms of Scar Formation .............................................. 20
3.4 Morphological and Biochemical Characteristics of Myofibroblast Phenotype .......... 21
3.5 Cellular Origins of Myofibroblasts.................................................... 21
3.6 Regulation of Myofibroblast Phenotype.............................................. 22
3.7 Role of Myofibroblasts in Pathological Scarring and Fibrosis .......................... 22
3.8 The Role of Mechanical Tension...................................................... 23
3.9 Role of Innervation in Skin Healing .................................................. 24
3.10 Therapeutic Options ................................................................ 25
3.11 Conclusion.......................................................................... 25
References.......................................................................... 26
II Epidemiology of Scars and Their Consequences
4 The Epidemiology of Keloids.................................................... 29
Chenyu Huang, Zhaozhao Wu, Yanan Du, and Rei Ogawa
4.1 Background ........................................................................ 30
4.2 Demographic Risk Factors That Shape Keloid Rates................................... 30
4.3 Genetic Risk Factors That Shape Keloid Rates......................................... 32
4.4 Environmental Risk Factors That Shape Keloid Rates.................................. 32
V III Contents
4.5 Conclusion.......................................................................... 34
References.......................................................................... 34
5 Epidemiology of Scars and Their Consequences: Burn Scars................. 37
Margriet E. van Baar
5.1 Burn Injuries and Their Treatment.................................................... 38
5.2 Prevalence of Burn Scars and Their Consequences . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 39
5.3 Factors Predicting Scar Outcome After Burns......................................... 41
5.4 Clinical Relevance................................................................... 42
5.5 Conclusion.......................................................................... 42
References.......................................................................... 43
6 Scar Epidemiology and Consequences......................................... 45
M. El Kinani and F. Duteille
6.1 Introduction and Background ....................................................... 46
6.2 Reminder of the Spectrum of Scars .................................................. 46
6.3 Hypertrophic Scars.................................................................. 46
6.4 Basic Epidemiology ................................................................. 46
6.5 Keloid Scars......................................................................... 47
6.6 Specific Situation: The Burnt Patient Healing ......................................... 47
6.7 Impact of Scars ..................................................................... 48
6.8 Conclusion.......................................................................... 48
References.......................................................................... 48
7 Other Scar Types: Optimal Functional and Aesthetic
Outcome of Scarring in Cleft Patients.......................................... 51
Wouter B. van der Sluis, Nirvana S. S. Kornmann, Robin A. Tan,
and Johan P. W. Don Griot
7.1 Background ........................................................................ 52
7.2 Objectives of Cleft Lip Surgery....................................................... 52
7.3 Treatment Protocol.................................................................. 52
7.4 Cleft Lip Reconstruction: Surgical Techniques ........................................ 52
7.5 Secondary Cleft Lip Reconstruction.................................................. 55
7.6 Evaluation of Aesthetic Outcome .................................................... 55
7.7 Conclusion.......................................................................... 56
Further Reading .................................................................... 57
III Hypertrophic and Keloid Scar: Genetics
and Proteomic Studies
8 Genetics of Keloid Scarring ..................................................... 61
Alia Sadiq, Nonhlanhla P. Khumalo, and Ardeshir Bayat
8.1 Background ........................................................................ 62
8.2 HLA Immunogenetics ............................................................... 62
8.3 Linkage............................................................................. 63
8.4 Large-Scale Population Single-Nucleotide Polymorphism (SNP)....................... 64
8.5 Gene Expression .................................................................... 65
8.6 MicroRNAs (miRNA) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 65
8.7 Long noncoding RNA (lncRNA)....................................................... 65
8.8 Small Interfering RNA (siRNA)........................................................ 65
8.9 Microarray Analysis ................................................................. 70
8.10 Epigenetics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 71
8.11 Mutations .......................................................................... 72
8.12 Copy Number Variation ............................................................. 72
IX
Contents
8.13 FISH (Fluorescence In Situ Hybridization)............................................. 72
8.14 Conclusions......................................................................... 72
Further Readings/Additional Resources.............................................. 73
IV International Scar Classifications
9 International Scar Classification in 2019....................................... 79
Thomas A. Mustoe
9.1 Immature Scar ...................................................................... 80
9.2 Mature Scar......................................................................... 80
9.3 Atrophic Scar ....................................................................... 82
9.4 Linear Hypertrophic Scar............................................................ 82
9.5 Widespread Hypertrophic Scar ...................................................... 82
9.6 Keloid .............................................................................. 83
Bibliography........................................................................ 84
V Scar Symptoms
10 Scar Symptoms: Pruritus and Pain.............................................. 87
Osama Farrukh and Ioannis Goutos
10.1 Pain: Definition and Subtypes ....................................................... 88
10.2 Pain Pathway ....................................................................... 88
10.3 Conclusion.......................................................................... 97
References.......................................................................... 98
11 Scar Symptom: Erythema and Thickness....................................... 103
Yating Yang, Xiaoli Wu, and Wei Liu
11.1 Mechanisms of Erythema in Scar..................................................... 104
11.2 Contributions of Erythema to Scar Development and Associated Clinical Symptoms ... 105
11.3 Scar Erythema and Scar Thickness ................................................... 105
11.4 Clinical Measurement of Scar Redness and Thickness ................................. 105
11.5 Clinical Relevance................................................................... 106
11.6 Clinical Treatment for Thick Scar ..................................................... 107
11.7 Conclusion.......................................................................... 107
References.......................................................................... 107
12 Scar Symptoms: Pigmentation Disorders...................................... 109
A. Pijpe, K. L. M. Gardien, R. E. van Meijeren-Hoogendoorn, E. Middelkoop,
and Paul P. M. van Zuijlen
12.1 Pathophysiology and Epidemiology ................................................. 110
12.2 Measurement Techniques ........................................................... 111
12.3 Therapies........................................................................... 112
12.4 Conclusion.......................................................................... 115
References.......................................................................... 115
13 Scar Contractures................................................................ 117
Marguerite Guillot Masanovic and Luc Téot
13.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 118
13.2 General Features.................................................................... 118
13.3 Contractures of the Neck ............................................................ 118
13.4 Axillar Contractures................................................................. 119
13.5 Hand Contractures.................................................................. 119
X Contents
13.6 Other Anatomical Sites of Scar Contractures.......................................... 120
13.7 Rehabilitation Programs............................................................. 120
13.8 Surgical Strategies .................................................................. 121
13.9 Z Plasties ........................................................................... 121
13.10 Skin Grafts.......................................................................... 121
13.11 Dermal Substitutes.................................................................. 121
13.12 Flaps ............................................................................... 121
13.13 Conclusion.......................................................................... 122
References.......................................................................... 122
VI Scar Assessment Scales
14 Scar Assessment Scales.......................................................... 125
Michelle E. Carrière, Annekatrien L. van de Kar, and Paul P. M. van Zuijlen
14.1 Background ........................................................................ 126
14.2 Domains............................................................................ 126
14.3 Scar Assessment Scales.............................................................. 126
14.4 Measurement Properties/Clinimetrics................................................ 127
14.5 Conclusion.......................................................................... 131
References.......................................................................... 131
15 Japan Scar Workshop (JSW) Scar Scale (JSS) for Assessing Keloids
and Hypertrophic Scars ......................................................... 133
Rei Ogawa
15.1 Background ........................................................................ 134
15.2 JSW Scar Scale (JSS) 2015............................................................ 1 34
15.3 Classification Table.................................................................. 134
15.4 Evaluation Table .................................................................... 134
15.5 Clinical Suitability and Usefulness of the JSS ......................................... 136
15.6 Conclusion.......................................................................... 136
References.......................................................................... 140
VII Objective Assessment Technologies (Cutometer, Laser
Doppler, 3D Imaging, Stereophotogrammetry)
16 Objective Assessment Technologies: General Guidelines
for Scar Assessment ............................................................. 143
Julian Poetschke and Gerd G. Gauglitz
16.1 Background ........................................................................ 144
16.2 Choosing the Right Tools for Each Scar . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 144
16.3 Optimizing the Measurement Process................................................ 144
16.4 Interpreting Therapeutic Success with Objective Scar Assessment Technologies ....... 146
16.5 Conclusion.......................................................................... 146
References.......................................................................... 147
17 Objective Assessment Tools: Physical Parameters in Scar Assessment...... 149
M. E. H. Jaspers and P. Moortgat
17.1 Clinimetrics......................................................................... 150
17.2 Color ............................................................................... 151
17.3 Elasticity............................................................................ 153
17.4 Perfusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 156
17.5 Conclusion.......................................................................... 157
References.......................................................................... 157