Vitiligo (eBook)

Preface 5
Contents 7
Contributors 12
Part I: Defining the Disease 17
Chapter 1 18
Historical Aspects 18
1.1.1 Before Vitiligo: Understanding Old Terms Meaning White Skin Spots 18
1.1.2 From Celsus to the Modern Period 20
1.1.3 Social Status of VitiligoPatients Across the Ages 20
1.1.4 Precursors to Phototherapy of Vitiligo 21
1.1.5 Modern History of Some Treatments of Vitiligo 22
1.1.6 Conclusions 23
References 23
1.2 Clinical Overview 25
Chapter 2 26
Epidemiology, Definitions and Classification 26
1.2.1.1 Introduction 26
1.2.1.2 Epidemiology 27
1.2.1.3 Vitiligo Vulgaris or Non-Segmental Vitiligo 27
1.2.1.4 Conditions to Exclude from the Definition of NSV 27
1.2.1.5 Segmental Vitiligo 34
1.2.1.6 Conditions to Exclude from the Definition of SV 34
1.2.1.7 Mixed Vitiligo 35
1.2.1.8 Classification Issues 35
References 36
Chapter 3 38
Histopathology 38
1.2.2.1 Introduction 38
1.2.2.2 Recommendations for a Proper Interpretation of Biopsies 39
1.2.2.3 Histo- and Immunohistochemistry Techniques for Studying Vitiligo 40
1.2.2.4 Pathological Findings 40
Pathologic Stages 40
Pigment Incontinence 41
Findings in Perilesional and Distant Areas in Non-segmental vitiligo 41
Nature of the Inflammatory Infi ltrate 42
1.2.2.5 Differential Diagnosis 43
References 44
1.3 Clinical aspects 46
Chapter 4 47
Generalized Vitiligo 47
1.3.1.1 Common Clinical Features 47
1.3.1.2 Distribution 48
1.3.1.3 Natural Course 49
1.3.1.4 Clinical Subtypes 49
1.3.1.5 Clinical Variants 49
Inflammatory Vitiligo 49
Multichrome Vitiligo 50
Vitiligo Minor 50
Blue Vitiligo 50
References 50
Chapter 5 52
Segmental Vitiligo 52
1.3.2.1 Epidemiology and Clinical Features 53
Epidemiology and General Features 53
Clinical Features 53
Precipitating Factors 54
References 54
1.3.2.2 Classification, Course and Prognosis 55
Classification of Segmental Vitiligo on the Face (Hann) 55
Classification of Segmental Vitiligo of the Face and Neck (Gauthier) 56
Diagnosis, Course, and Special Locations 56
Treatment Overview 58
References 59
Chapter 6 61
Vitiligo Universalis 61
1.3.3.1 Definition and Epidemiology 61
1.3.3.2 Clinical Features 62
Precipitating Factors and Progression 62
Infl uence of Previous Treatments 64
Autoimmune Diseases Associated with Extensive Vitiligo and Application to VU 64
1.3.3.3 Diagnosis 64
1.3.3.4 Management 64
Sun Protection 65
Psychosocial Aspects 65
1.3.3.5 Conclusions 65
References 66
Chapter 7 67
Mucosal Vitiligo 67
1.3.4.1 Definition and Epidemiology 67
1.3.4.2 Oral Mucosa 67
1.3.4.3 Genital Mucosa 68
1.3.4.4 Management Principles 69
References 69
Chapter 8 70
Halo Nevi and Vitiligo 70
1.3.5.1 Definition 70
1.3.5.2 Clinical Features 71
Epidemiology and Associated Disorders 71
Pathogenesis, Histological, Immunological, and Genetic Data 72
1.3.5.3 Conclusions 73
References 73
Chapter 9 74
Hair Involvement in Vitiligo 74
1.3.6.1 Hair, Melanocytes, and Pigmentation 74
Hair Follicles 74
Hair Follicle Melanocytes, Melanocyte Reservoir, and Pigment Stem Cells 75
1.3.6.2 Pigmentation in the Hair Follicle 75
1.3.6.3 Hair Involvement in Vitiligo 76
1.3.6.4 Canities 78
1.3.6.5 Poliosis 78
1.3.6.6 Surgical Correction of Leukotrichia 79
References 80
Chapter 10 81
Non-Skin Melanocytes in Vitiligo 81
1.3.7.1 Introduction 81
1.3.7.2 Ocular Pigmentation 82
1.3.7.3 Otic Pigmentation 83
1.3.7.4 Leptomeningeal Pigmentation 85
1.3.7.5 Conclusions 85
References 85
Chapter 11 87
Autoimmune/Inflammatory and Other Diseases Associated with Vitiligo 87
1.3.8.1 A General Overviewof Association Studies 87
1.3.8.2 Autoinfl ammatory/Autoimmune DiseasesAssociated with Vitiligo: Clinical Analysis and Relevance of the Association 90
Disorders with a Demonstrated or Possible Association with Vitiligo 90
Disorders with No Clear Association with Vitiligo 92
1.3.8.3 Particular and Rare Associations 94
Autoimmune Polyendocrine Syndrome and Multiple Autoimmune Disease 94
Vogt–Koyanagi–Harada and Alezzandrini’s Syndrome 94
Sarcoidosis 95
1.3.8.4 Other Reported Associations 95
Lichen Planus Lichen Sclerosus95
Urticaria 95
Ichthyosis 95
Malignant Melanoma 96
Human Immunodefi ciency Virus Disease 96
References 87
Chapter 12 99
Vitiligo and Immunodeficiencies 99
1.3.9.1 General Background 99
1.3.9.2 Vitiligo and HIV Infection 100
1.3.9.3 Vitiligo and Idiopathic T-Cell Lymphocytopenia 102
1.3.9.4 Vitiligo and CVID 103
1.3.9.5 Complement Deficiencies and Vitiligo 103
1.3.9.6 Ultraviolet Irradiation and Vitiligo 103
1.3.9.7 Conclusions 104
References 104
Chapter 13 106
Inflammatory Vitiligo 106
1.3.10.1 Introduction 106
1.3.10.2 Isolated Clinically Inflammatory Vitiligo 107
1.3.10.3 Clinically Inflammatory Vitiligo Associated with Other Disorders 107
1.3.10.4 Differential Diagnosis 108
1.3.10.5 Histological Features of Clinically Inflammatory Vitiligo versus Common Clinically Non-Inflammatory Vitiligo 109
1.3.10.6 Summary and Concluding Remarks 109
References 111
Chapter 14 113
Rare Inherited Diseases and Vitiligo 113
1.3.11.1 The Interest of Studying Monogenic Disorders for the Understanding of Common NSV 113
1.3.11.2 Discussion of Some Selected Monogenic Disorders 116
Autoimmune Polyendocrine Syndromes 116
APS1/APECED 116
Schmidt (APS2) Syndrome 117
Immunodysregulation Polyendocrinopathy and Enteropathy X-Linked (IPEX 304790)
MELAS (Myopathy, Encephalopathy, Lactic Acidosis, and Stroke-Like Episodes) and MERRF (Myoclonic Epilepsy Associated with Ragged-Red Fibers) Syndromes 117
Breakage Disorders : Ataxia Telangiectasia and Nijmegen Breakage Syndrome 118
Ataxia-Telangiectasia (AT) 118
Nijmegen Breakage Syndrome (NBS) 120
References 120
Chapter 15 122
Vitiligo in Childhood 122
1.3.12.1 Introduction 122
1.3.12.2 Epidemiology 123
1.3.12.3 Classification 123
1.3.12.4 Familial Background 123
1.3.12.5 Clinical Characteristics 124
1.3.12.6 Disease Extent and Progression 125
1.3.12.7 Associated Skin Conditions 125
1.3.12.8 Associated Autoimmune diseases and Laboratory Investigations 126
1.3.12.9 Differential Diagnosis 126
1.3.12.10 Psychological Effects of Childhood Vitiligo 126
1.3.12.11 Summary of Therapeutic Issues 126
References 127
Chapter 16 128
Late-Onset Vitiligo 128
1.3.13.1 Introduction 128
1.3.13.2 Definition and Epidemiological Data 129
1.3.13.3 Significance of Late Onset Vitiligo 129
1.3.13.4 Therapeutic Considerations 130
References 130
Chapter 17 131
Evaluation, Assessment and Scoring 131
1.4.1 Introduction 131
1.4.2 Step by Step Evaluation 132
1.4.3 Associated Disorders and Laboratory Workup 134
1.4.4 Skin Biopsy 134
1.4.5 Scoring 134
1.4.6 Interobserver Variability 134
1.4.7 Correlations Between Assessment Variables 137
1.1.8 Subjective Items 137
References 137
Chapter 18 139
Quality of Life 139
1.5.1 Introduction and Historical Perspective 139
1.5.2 Modern Psychological Studies 140
1.5.3 Socio–Economic and Educational Consequences 140
1.5.4 Quality of Life Evaluation 141
References 141
Chapter 19 142
Natural History and Prognosis 142
1.6.1 Natural Course 143
1.6.2 Stability vs. Active Disease 143
1.6.3 Treatment Outcome and Stability of Repigmentation 143
1.6.4 Clinical Markers of Prognosis 144
1.6.5 Prognosis and Subtypes of Vitiligo 144
References 144
Chapter 20 146
Defining the Disease: Editor’s Synthesis 146
1.7.1 Clinical Assessment Is Important 146
1.7.2 Epidemiological Studies, Including Twin Studies, Are Needed 147
1.7.3 Variable Melanocytic Targets According to Clinical Subtypes 147
1.7.4 Lessons from Associated Diseases and Rare Syndromic Cases 147
1.7.5 Predictive Classifications of Facial Segmental Vitiligo? 147
1.7.6 Suboptimal Use of Pathology to Assess and Probably Understand Vitiligo 148
1.7.7 Summary 148
References 149
Part II: Understanding the Disease 150
Chapter 21 151
Pathophysiology Overview 151
2.1.1 From Where to Start? A Good Hierarchy of Relevant Data Is Needed 151
2.1.2 Time for a Critical Reappraisal of the Convergence Theory 152
2.1.3 Melanocyte Loss: Survival Defect, True Destruction, or Multistep Process with Immune Acceleration? 152
2.1.4 The Genetics Angle: Unbiased and Productive? 152
2.1.5 Inflammation and Auto-Immunity.The Role of Stress 153
2.1.6 Identifying and Characterizing Skin and Non Skin Cellular Anomalies in Vitiligo 153
2.1.7 The Need for Translational Research 153
2.1.8 Conclusions and Scope of this Book Section 154
References 154
2.2 Generalized Vitiligo 155
Chapter 22 156
Genetics 156
2.2.1.1 Genetic Epidemiology 156
2.2.1.2 Identification of Vitiligo Susceptibility Genes 158
The Candidate Gene Approach 158
The Genome-Wide Approach 160
The Gene Expression Approach 161
2.2.1.3 Concluding Remarks 162
References 162
Chapter 23 165
Environmental Factors 165
2.2.2.1 The Kobner’s Phenomenon 166
Historical Aspects and Definition 166
Clinical Features 168
Aspect 168
Incidence 168
Identification of Factors Causing KP 168
Pathomechanisms 169
The KP in the Vitiligo Clinic 170
Disease Activity Assessment 170
Prediction of Vitiligo in at Risk Individuals 170
Pathogenesis of Vitiligo 170
Identifi cation of Disease Characteristics that Help Predicting the Outcome of Therapies 170
Prevention of Onset of New Lesions and Improvement of Repigmentation 170
Concluding Remarks 171
References 171
2.2.2.2 Occupational Vitiligo 173
Chemicals Triggering Occupational Vitiligo 173
Clinical Observations 174
Depigmentation 174
Non-Cutaneous Effects 175
Mode of Action of Phenols/Catechols 176
Quinones and Link with Oxidative Damage 176
Staging 176
References 177
Chapter 24 179
In Vivo Data 179
2.2.3.1 Non-Invasive Methodsfor Vitiligo Evaluation 180
Introduction 180
Defining the Extension of Vitiligo 181
Objective Methods for the Assessment of Vitiligo Extent 181
Skin Colour Measurements and Monitoring of Lesions 182
Macroscopic Morphological Measurements 182
Photography 182
Wood’s Light 182
Visible Light Photography 184
Digital Photography 185
Ultraviolet Light Photography 185
Reflectance Spectroscopy 185
Reflectance Tristimulus CIE Colourimetry 186
Selected Spectral Bands and Narrow-BandRefl ectance Spectrophotometry 187
Non-Invasive Micro-MorphologicalMeasurement: In Vivo-Refl ectanceConfocal Microscopy 187
The Technology and Its Optical Principles 187
Reflectance Confocal Microscopy and Vitiligo 188
References 190
2.2.3.2 Electron Microscopy 193
Ultrastructural Study of the Epidermis 193
Depigmented Macules 193
Melanocytes 193
Keratinocytes 194
Langerhans Cells 194
Clinically Normal Appearing Skin Adjacentto Amelanotic Skin 194
Melanocytes 194
Keratinocytes 195
Langerhans Cells 195
Marginal Hyperpigmented Skin 195
Melanocytes 195
Keratinocytes 196
Ultrastructural Studies of Infl ammatory Vitiligo 196
Melanocytes 196
Langerhans Cells 196
Ultrastructural Study of the Basement Membrane 196
Ultrastructural Study of Cultured Melanocytes from Vitiligo Patients 196
Ultrastructural Study of the Dermis 197
Concluding Remarks 198
References 198
Chapter 25 200
Animal Models 200
2.2.4.1 Animal Models of Autoimmune Vitiligo 200
The Multifactorial Nature of Autoimmune Disorders: Application to Vitiligo 200
Naturally Occurring Animal Models of Vitiligo 201
Grey Horse 201
The Sinclair Miniature Swine 202
Water Buffalo 203
The Vitiligo (C57Bl/J6-vit/vit) Mouse 203
The Barred Plymouth Rock and White Leghorn Chickens 204
2.2.4.2 The Smyth Line Chicken Animal Model of Spontaneous Autoimmune Vitiligo 205
The Genetics Basis of Smyth Line Autoimmune Vitiligo 207
Inherent Melanocyte Defect in Smyth Line Autoimmune Vitiligo 207
Immune System Involvement in Smyth Line Autoimmune Vitiligo 208
Environmental Factors Involved in the Expression of Smyth Line Autoimmune Vitiligo 208
Opportunities Provided by the Smyth Line Chicken Model for Autoimmune Vitiligo 209
2.2.4.3 Experimental Model of Induced Autoimmune Vitiligo: Mouse Model for the Role of Stress 210
2.2.4.4 Concluding Remarks 210
References 211
Chapter 26 214
In Vitro Approaches 214
2.2.5.1 Cell Isolation and Culture 214
Isolation of Skin Melanocytes and Keratinocytes 215
Isolation and Culture of Skin Fibroblasts 215
Isolation and Culture of Hair Follicle Melanocytes and Keratinocytes 215
Isolation and Freezing of Peripheral Blood Mononuclear cells (PBMC) 216
2.2.5.2 In Vitro Reconstructed Epidermis 216
Preparation of Dead De-Epidermized Dermis 216
Epidermal Reconstruction 216
2.2.5.3 Functional Studies of NSV Cells Using Monolayers: Melanocytes, Keratinocytes, and Fibroblasts 217
2.2.5.4 Functional Studies Using Reconstructed Epidermis 218
2.2.5.5 New Analytic Techniques 220
Fluorescence-Based Assays 220
Proteomic 223
Metabolomic/Lipidomic 223
Transcriptomic 223
2.2.5.6 Concluding Remarks 223
References 223
Chapter 27 226
Oxidative Stress 226
2.2.6.1 General Aspects 226
2.2.6.2 Catecholamine and Biopterin Metabolisms 227
2.2.6.3 Cellular Alterations Related to the Oxidative Stress 227
2.2.6.4 The Possible Genetic Background 229
2.2.6.5 The Systemic Oxidative Stress 230
2.2.6.6 Concluding Remarks 231
References 231
Chapter 28 233
Immune/Inflammatory Aspects 233
2.2.7.1 Introduction 233
References 234
2.2.7.2 The Role of Innate Immunity in Vitiligo 234
The Innate Immune System: An Overview 234
The Skin Innate Immune System 235
Cellular Components 235
Soluble Components 236
The Innate Immune System in Vitiligo 237
Keratinocytes 237
Dendritic Cells 237
Macrophages 238
Natural Killer Cells 238
Pattern Recognition Receptors 238
Antimicrobial Peptides 238
Complement 239
Concluding Remarks 239
References 239
2.2.7.3 Humoral Immunity 242
Melanocyte Antibodies in Vitiligo 242
Correlations of Melanocyte Antibodies with Vitiligo 242
Targets of Melanocyte Antibodies in Vitiligo 243
The Origin of Melanocyte Antibodies in Vitiligo 245
Pathogenic Effects of Melanocyte Antibodies 245
Melanocyte Antibodies in Melanoma-Associated Hypopigmentation 246
Other Antibodies in Vitiligo 247
Interaction of Humoral and Cellular Immune Responses in Vitiligo 247
Concluding Remarks 248
References 248
2.2.7.4 Cell-Mediated Immunity 250
Immune Infi ltrates in Vitiligo Skin 251
T Cells and Depigmentation 251
Homing of Immune Reactive T-Cells 253
Vitiligo versus Melanoma T-Cell Responses 254
CD4+ T Cells and Vitiligo Progression 255
Melanocytes as Antigen-Presenting Cells 255
Dendritic Cell Mediated Killing 256
Additional Players in Cellular Immunity 256
Heat Shock Proteinsin Immune Activation 257
Concluding Remarks 258
References 258
Chapter 29 262
Cytokines and Growth Factors 262
2.2.8.1 Introduction: Melanocytic Homeostasis and Cytokines/Growth Factors 263
References 264
2.2.8.2 An Overview of Epidermal Cytokines and Growth Factors in Vitiligo 265
The Role of Melanogenic Cytokines 265
The Role of Inflammatory Cytokines 265
Summary: How the Epidermal Cytokine Network May Be Impaired in Vitiligo Skin 266
References 266
2.2.8.3 In Vivo Studies of Melanogenic Cytokines and Receptors in Vitiligo 267
Melanogenic Cytokines SCF and ET-1 in Lesional NSV Epidermis 268
The Disruption of SCF-c-kit Interaction on Melanocyte Membranes as an Early Event in the Vitiligo Depigmenting Process 268
Implication of MITF-M, the Melanocytic Master Transcription Factor 271
Concluding Remarks: Possible Molecular Mechanisms in Vitiligo Melanocytes Dysfunction 273
References 275
Chapter 30 276
Proopiomelanocortin and Related Hormones 276
2.2.9.1 General Aspects of the Cutaneous Proopiomelanocortin System 276
2.2.9.2 Melanocortin Peptides: Potential Therapeutic Agents in Vitiligo? 278
2.2.9.3 POMC-Derived Peptides and Related Peptides in Peripheral Blood of Patients with Vitiligo 278
2.2.9.4 Genetic Abnormalities of POMC Components in Vitiligo 279
2.2.9.5 Expression of the Cutaneous POMC System in Vitiligo 280
2.2.9.6 Concluding Remarks 281
References 282
Chapter 31 284
Other Hypotheses 284
2.2.10.1 Introduction 284
2.2.10.2 The Early Melanocyte Aging Theory 284
2.2.10.3 The Melanocyte Detachment (“Melanocytorrhagic”) Theory 285
2.2.10.4 The Viral Hypotheses 285
2.2.10.5 Deficient Clearance of Apoptotic Fragments 286
2.2.10.6 The membrane Lipid Defect Mechanism 286
References 286
2.3 Segmental Vitiligo: A Model to Understand Vitiligo? 287
Introduction 287
Chapter 32 288
2.3.1 Particular Clinical Characteristics of Segmental Vitiligo 288
Clinical Observations and Hypotheses for SV Patterning 288
Preferential Follicular Reservoir Involvement in SV 289
References 290
Chapter 33 290
2.3.2 The Concept of Mosaicism Applied to SV 290
The Lines of Blaschko and Segmental Vitiligo 290
The Association of SV and NSV 291
Implications for Research of the Concept of Somatic Mosaicism Applied to Vitiligo 292
References 293
Chapter 34 294
2.3.3 The Neurogenic Hypothesis in Segmental Vitiligo 294
Clinical Arguments 294
Segmental Distribution 294
Mixed Distribution Overlapping Several Dermatomes 294
Localized Vitiligo or Leukodermas Following Nerve Damage 295
Histological and Ultrastructural Arguments 295
Experimental Findings in Animals 296
Pathophysiological Arguments 296
References 297
Chapter 35 298
2.3.4 Segmental Vitiligo: A Model for Understanding the Recapitulation of Repigmentation 298
Repigmentation of Segmental Vitiligo and Summary of Repigmentation Schemes 298
Recapitulation of Vitiligo Repigmentation In Vitro and Clinical Relevance In Vivo 298
Cells Involved in SV Repigmentation 298
In Vitro Repigmentation Models 299
Therapeutic Perspectives 300
References 301
Chapter 36 303
Editor’s Synthesis 303
2.4.1 Do All Supposed Mechanisms of Melanocyte Loss Occur In Vivo? 304
2.4.2 An Enlarged Vision of the Skin Melanogenic Unit May Apply to Vitiligo 305
2.4.3 Melanocyte Stemness and Vitiligo 305
2.4.4 The Somatic Mosaicism Hypothesis for SV and Deductions for NSV 306
2.4.5 Membrane Lipids as Possible Culprits 306
2.4.6 The Innate Immunity Hypothesis 306
2.4.7 Concluding Remarks 306
References 307
Part III: Therapy 308
Chapter 37 309
Management Overview 309
3.1.1 Management-Oriented Evaluation 309
3.1.2 Treatment Overview 310
UV Treatments 310
Topical Therapies and Combined Therapies 310
Surgery 311
Camouflage and Depigmentation 311
Other Therapies 311
Counseling 311
3.1.3 Evidence-Based Guidelines 312
References 312
3.2 Topical Therapies 314
Chapter 38 315
Topical Corticosteroids 315
3.2.1.1 Introduction 315
3.2.1.2 Mode of Action and Rationale for Use in Vitiligo 315
3.2.1.3 Studies 316
3.2.1.4 Application Scheme 317
3.2.1.5 Side Effects 317
3.2.1.6 Safety Issues 317
References 317
Chapter 39 319
Calcineurin Inhibitors 319
3.2.2.1 Introduction 319
3.2.2.2 Mode of Action and Rationale for Use in Vitiligo 319
3.2.2.3 Studies 320
3.2.2.4 Tacrolimus and Pimecrolimus Monotherapy 320
3.2.2.5 Combination Therapy 320
3.2.2.6 Comparative Studies Between Tacrolimus and Pimecrolimus 320
3.2.2.7 General Outcome 322
3.2.2.8 Application Scheme 322
3.2.2.9 Side Effects 324
3.2.2.10 Safety Issues 324
References 325
Chapter 40 327
Vitamin D Analogues 327
3.2.3.1 Rationale for use 327
3.2.3.2 Studies 328
References 329
3.3 Phototherapies 331
Chapter 41 332
PUVA and Related Treatments 332
3.3.1.1 Introduction 332
3.3.1.2 Psoralens 333
3.3.1.3 Oral Photochemotherapy 334
3.3.1.4 Topical Photochemotherapy 336
3.3.1.5 Khellin + UV 337
References 338
Chapter 42 340
UVB Total Body and Targeted Phototherapies 340
3.3.2.1 Narrowband-UVB (NB-UVB) Phototherapy 340
Introduction 340
Pioneer Studies on NB UVB for Vitiligo 340
Confirmative Studies on NB UVB for Vitiligo 341
Efficacy of NB UVB vs. Other Phototherapeutic Modalities 342
NB UVB in Combination with Topical Treatments 343
NB UVB in Combination with Vitamins and Antioxidants 344
Practical Aspects of NB-UVB Treatment 344
3.3.2.2 Targeted Phototherapy 346
Lasers 346
Excimer Laser 308 nm 346
Helium–Neon 348
NonLaser Light Sources 348
Monochromatic Excimer Lamp or Light 308 nm (MEL 308 nm) 348
Excimer Laser/Lamp vs. NB-UVB 348
Mercury Arc Lamps 349
Plasma Lamps 349
Microphototherapy 349
Edited by Torello Lotti, Francesca Prignano, and Gionata Buggiani) 349
3.3.2.3 Mechanism of Action of Phototherapies 350
Narrow Band UVB 350
Targeted Phototherapy 351
3.3.2.4 Side Effects of Phototherapies 351
Narrowband UVB 351
Targeted Phototherapy 352
References 352
Chapter 43 356
Vitamins and Antioxidants: Topical and Systemic 356
3.4.1 Introduction 356
3.4.2 Vitamin B 12 and folic acid, para-aminobenzoic acid 356
3.4.3 L-Phenylalanine 357
3.4.4 Antioxidants 357
Background 357
Studies 357
Safety concerns 359
References 360
3.5 Systemic Treatments 362
Chapter 44 363
Corticosteroid Minipulses 363
3.5.1.1 Definition and Historical Background 363
3.5.1.2 Oral Corticosteroids Minipulses for Vitiligo 364
3.5.1.3 Personal Remarks 364
References 365
Chapter 45 366
Other Immunosuppressive Regimen 366
3.5.2.1 Rationale for the Use of Systemic Immunomodulators 366
3.5.2.2 Traditional Systemic Immunosuppressants 366
3.5.2.3 Anti-IFN-gamma Strategy 367
3.5.2.4 Targeting TNF-alpha by Antibodies 368
3.5.2.5 Effects of Efalizumab 368
3.5.2.6 Concluding Remarks 369
References 369
Chapter 46 371
Empirical, Traditional, and Alternative Treatments 371
3.6.1 Introduction 371
3.6.2 Chinese Traditional Products 371
3.6.3 Plant-Derived Extracts 372
3.6.4 Melagenin 372
3.6.5 Aspirn 372
3.6.6 Statins 372
3.6.7 Dermabrasion combined with 5-Fluorouracil 373
3.6.8 Others 373
References 375
3.7 Surgical Therapies 376
Chapter 47 377
Background and Techniques 377
3.7.1.1 Introduction 377
3.7.1.2 Selection of Patients 378
3.7.1.3 Surgical Methods 379
Methods Based on Direct Transplantation of Unprocessed Tissue 379
Methods Based on Transplantation of Processed Cells or Tissue 379
3.7.1.4 Preparation of the Recipient Area 380
3.7.1.5 A Guide to Advanced Methods for Vitiligo Surgery 381
Basal Cell-Layer Suspension and Cultured Melanocyte Suspension 381
Donor Tissue 381
Release and Preparation of Free Cells 382
Culturing of Melanocytes 383
Premedication 383
Anesthesia of the Recipient Site 384
Transplantation and Aftercare 384
Follow-Up Evaluation 385
Ultra-Thin Grafting 385
Calculation of Areas 387
Premedication 387
Anesthesia of Recipient Site 387
Preparation of the Recipient Site (as Above) 387
Donor Area 387
Transplantation Phase 387
Follow-Up Inspection 388
Evaluation and Documentation 388
References 389
Chapter 48 390
The Outcomes: Lessons About Surgical Therapy for Vitiligo in the Past Two Decades 390
3.7.2.1 Introduction 390
3.7.2.2 Melanocytes Can Be Effectively and Safely Transplanted for Repigmentation of Depigmented Skin 390
3.7.2.3 Melanocyte Transplantation Is Mainly Successful in Stable Vitiligo 391
3.7.2.4 With Less Invasive Methods, Better Results Are Achieved 391
3.7.2.5 PUVA, NB-UVB, or Sunlight Exposure Enhance Repigmentation Rates 391
3.7.2.6 The Best Repigmentation Results Are Achieved in Segmental Vitiligo 391
3.7.2.7 Lasers Are Useful to Denude Recipient Sites 393
3.7.2.8 Frequent Failures with Surgery in Acral Vitiligo Are Seen 393
3.7.2.9 Surgical Repigmentation Is Similar to Medical Treatment 393
3.7.2.10 Surgical Repigmentation Is Permanent 393
3.7.2.11 Combination Therapy Is Useful to Enhance Repigmentation Rates 394
3.7.2.12 In Vitro Cultured Epidermal Sheets and Melanocyte Suspensions Are Important Options for Repigmenting Stable Vitiligo 394
3.7.2.13 Repigmentation of Leukotrichia May Be Achieved by Melanocyte Transplantation 395
3.7.2.14 What to Avoid when Performing Melanocyte Transplantation 395
References 395
Chapter 49 397
Combined Therapies for Vitiligo 397
3.8.1 Introduction 397
3.8.2 Combination of Surgical Therapies and Phototherapy 397
3.8.3 Combination of Surgical Therapies and Corticosteroids 398
3.8.4 Combination of Phototherapy and Topical Steroids 398
3.8.5 Combination of Phototherapy and Topical Calcineurin Inhibitors (TCI) 399
3.8.6 Combination of Phototherapy and Topical Vitamin D 399
3.8.7 Combination of Phototherapy and Antioxidants 399
References 400
Chapter 50 402
Camouflage 402
3.9.1 Introduction 402
3.9.2 Why Camouflage and Cosmetic Rehabilitation Are Needed 402
3.9.3 Camouflage as a Medical Intervention? 403
3.9.4 A Brief History of Camouflage 403
3.9.5 Camouflage Controlled Studies 405
3.9.6 Self-Tanning Creams, Lotions, and Sprays 405
3.9.7 Cover Creams, Foundations, Sticks 406
3.9.8 Vitiligo of the Lips 407
3.9.9 Leukotrichia 407
3.9.10 Permanent and Semi-Permanent Camouflage 407
3.9.11 Precautions of Use 407
3.9.12 Conclusion: Camouflage as a Balm for ‘Bruised’ Souls 407
References 408
Further Reading 408
Chapter 51 409
Photoprotection Issues 409
3.10.1 Normal and Vitiligo Skin UV Sensitivity 409
3.10.2 Photoadaptation of Vitiliginous Skin to UV Irradiation 410
3.10.3 Vitiligo and Skin Cancer 411
3.10.4 Practical Photoprotection 412
References 414
Chapter 52 416
Depigmenting Agents 416
3.11.1 Introduction 416
3.11.2 Chemical Agents 417
3.11.3 Patient’s Selection 417
3.11.4 Protocol 417
3.11.5 Side Effects 418
3.11.6 Combinatory Chemical Approaches 418
3.11.7 Physical Approaches 418
References 419
Chapter 53 420
Therapy Adapted for Age, Gender, and Specific Locations 420
3.13.1 Age and Gender Issues 420
Children 420
Elderly Patients 421
Gender Issues 421
3.12.2 Particular Locations 421
Mucosae 421
Hairs 422
Hands 422
References 423
Chapter 54 424
Psychological Interventions 424
3.13.1 Why Psychological Support Is Important 424
3.13.2 Screening Patients in Need of Psychological Support 425
3.13.3 Psychological Interventions 425
3.13.4 Concluding Remarks 426
References 426
Chapter 55 427
The Patient Perspective 427
3.14.1 Introduction 427
3.14.2 Impact of the Disease on Patients and Families 427
Adults 427
Children 428
Families 428
3.14.3 Role of Psychotherapy 428
Stigma and Vitiligo 429
Stress and Vitiligo 429
Cognitive–Behavioural Therapy (CBT) 429
3.14.4 Patients’ Stories 429
Maria, 55 years old 429
Alfredo, 60 years old 430
Robert, 11 years old 430
Henrietta, 40 years old 430
Gurdeep 430
Lee 430
3.14.5 Patient Support Organisations 431
3.14.6 Inter-Organisational Cooperation 431
3.14.7 Other Issues 431
Treatments 431
Family doctors, Misdiagnosis, Early Diagnosis, and Treatment 431
Internet and Alternative Treatments 433
Research 433
Involvement of Patients and Patient Support Organisations in Research 434
Useful Websites 435
References 435
Chapter 56 436
Evidence-Based Medicine Perspective 436
3.15.1 History of EBM Approaches in Vitiligo 436
3.15.2 Meta-Analyses 436
3.15.3 Lim and Hexsel’s Algorithm 438
3.15.4 The 2007 German Evidence-Based Analysis 439
3.15.5 The 2008 Systematic Review of Natural Health Product Treatments 440
3.15.6 The British Guidelines for the Treatment of Vitiligo 440
No Treatment Option 440
Topical Treatment 440
Phototherapy 440
Systemic Therapy 441
Surgical Treatments 441
Psychological Treatments 441
3.15.7 The Indian Evidence-Based Practice Guidelines for Surgical Management of Vitiligo 442
References 444
Chapter 57 445
Editor’s Synthesis and Perspectives 445
3.16.1 From EBM Guidelines to Clinical Practice 445
3.16.2 Perspectives 446
References 447
Index 448