Vitiligo

Vitiligo has been, until recently, a rather neglected area in dermatology and medicine. Patients complain about this situation, which has offered avenues to quacks, and has led to the near orphan status of the disease. The apparently, simple and poorly symptomatic presentation of the disease has been a strong disadvantage to its study, as compared to other common chronic skin disorders such as psoriasis and atopic dermatitis. Vitiligo is still considered by doctors as a non disease, a simple aesthetic problem. A good skin-based angle of attack is also lacking because generalized vi- ligo is clearly epitomizing the view of skin diseases as simple targets of a systemic unknown dysregulation (diathesis), re? ecting the Hippocratic doctrine. This view has mostly restricted vitiligo to the manifestation of an auto-immune diathesis in the past 30 years. Thus, skin events, which are easily detected using skin biospies in most other situations, have not been precisely recorded, with the argument that a clinical diagnosis was suf? cient for the management (or most commonly absence of mana- ment) of the patient. This book is an international effort to summarize the information gathered about this disorder at the clinical, pathophysiological and therapeutic levels. Its primary aim is to bridge current knowledge at the clinical and investigative level, to point to the many unsolved issues, and to delineate future priorities for research. Vitiligo Title Page Copyright Page Preface Contents Contributors Part I: Defining the Disease Chapter 1 Historical Aspects 1.1.1 Before Vitiligo: Understanding Old Terms Meaning White Skin Spots 1.1.2 From Celsus to the Modern Period 1.1.3 Social Status of VitiligoPatients Across the Ages 1.1.4 Precursors to Phototherapy of Vitiligo 1.1.5 Modern History of Some Treatments of Vitiligo 1.1.6 Conclusions References 1.2 Clinical Overview Chapter 2 Epidemiology, Definitions and Classification 1.2.1.1 Introduction 1.2.1.2 Epidemiology 1.2.1.3 Vitiligo Vulgaris or Non-Segmental Vitiligo 1.2.1.4 Conditions to Exclude from the Definition of NSV 1.2.1.5 Segmental Vitiligo 1.2.1.6 Conditions to Exclude from the Definition of SV 1.2.1.7 Mixed Vitiligo 1.2.1.8 Classification Issues References Chapter 3 Histopathology 1.2.2.1 Introduction 1.2.2.2 Recommendations for a Proper Interpretation of Biopsies 1.2.2.3 Histo- and Immunohistochemistry Techniques for Studying Vitiligo 1.2.2.4 Pathological Findings Pathologic Stages Pigment Incontinence Findings in Perilesional and Distant Areas in Non-segmental vitiligo Nature of the Inflammatory Infi ltrate 1.2.2.5 Differential Diagnosis References 1.3 Clinical aspects Chapter 4 Generalized Vitiligo 1.3.1.1 Common Clinical Features 1.3.1.2 Distribution 1.3.1.3 Natural Course 1.3.1.4 Clinical Subtypes 1.3.1.5 Clinical Variants Inflammatory Vitiligo Multichrome Vitiligo Vitiligo Minor Blue Vitiligo References Chapter 5 Segmental Vitiligo 1.3.2.1 Epidemiology and Clinical Features Epidemiology and General Features Clinical Features Precipitating Factors References 1.3.2.2 Classification, Course and Prognosis Classification of Segmental Vitiligo on the Face (Hann) Classification of Segmental Vitiligo of the Face and Neck (Gauthier) Diagnosis, Course, and Special Locations Treatment Overview References Chapter 6 Vitiligo Universalis 1.3.3.1 Definition and Epidemiology 1.3.3.2 Clinical Features Precipitating Factors and Progression Infl uence of Previous Treatments Autoimmune Diseases Associated with Extensive Vitiligo and Application to VU 1.3.3.3 Diagnosis 1.3.3.4 Management Sun Protection Psychosocial Aspects 1.3.3.5 Conclusions References Chapter 7 Mucosal Vitiligo 1.3.4.1 Definition and Epidemiology 1.3.4.2 Oral Mucosa 1.3.4.3 Genital Mucosa 1.3.4.4 Management Principles References Chapter 8 Halo Nevi and Vitiligo 1.3.5.1 Definition 1.3.5.2 Clinical Features Epidemiology and Associated Disorders Pathogenesis, Histological, Immunological, and Genetic Data 1.3.5.3 Conclusions References Chapter 9 Hair Involvement in Vitiligo 1.3.6.1 Hair, Melanocytes, and Pigmentation Hair Follicles Hair Follicle Melanocytes, Melanocyte Reservoir, and Pigment Stem Cells 1.3.6.2 Pigmentation in the Hair Follicle 1.3.6.3 Hair Involvement in Vitiligo 1.3.6.4 Canities 1.3.6.5 Poliosis 1.3.6.6 Surgical Correction of Leukotrichia References Chapter 10 Non-Skin Melanocytes in Vitiligo 1.3.7.1 Introduction 1.3.7.2 Ocular Pigmentation 1.3.7.3 Otic Pigmentation 1.3.7.4 Leptomeningeal Pigmentation 1.3.7.5 Conclusions References Chapter 11 Autoimmune/Inflammatory and Other Diseases Associated with Vitiligo 1.3.8.1 A General Overviewof Association Studies 1.3.8.2 Autoinfl ammatory/Autoimmune DiseasesAssociated with Vitiligo: Clinical Analysis and Relevance of the Association Disorders with a Demonstrated or Possible Association with Vitiligo Disorders with No Clear Association with Vitiligo 1.3.8.3 Particular and Rare Associations Autoimmune Polyendocrine Syndrome and Multiple Autoimmune Disease Vogt–Koyanagi–Harada and Alezzandrini’s Syndrome Sarcoidosis 1.3.8.4 Other Reported Associations Lichen Planus; Lichen Sclerosus Urticaria Ichthyosis Malignant Melanoma Human Immunodefi ciency Virus Disease References Chapter 12 Vitiligo and Immunodeficiencies 1.3.9.1 General Background 1.3.9.2 Vitiligo and HIV Infection 1.3.9.3 Vitiligo and Idiopathic T-Cell Lymphocytopenia 1.3.9.4 Vitiligo and CVID 1.3.9.5 Complement Deficiencies and Vitiligo 1.3.9.6 Ultraviolet Irradiation and Vitiligo 1.3.9.7 Conclusions References Chapter 13 Inflammatory Vitiligo 1.3.10.1 Introduction 1.3.10.2 Isolated Clinically Inflammatory Vitiligo 1.3.10.3 Clinically Inflammatory Vitiligo Associated with Other Disorders 1.3.10.4 Differential Diagnosis 1.3.10.5 Histological Features of Clinically Inflammatory Vitiligo versus Common Clinically Non-Inflammatory Vitiligo 1.3.10.6 Summary and Concluding Remarks References Chapter 14 Rare Inherited Diseases and Vitiligo 1.3.11.1 The Interest of Studying Monogenic Disorders for the Understanding of Common NSV 1.3.11.2 Discussion of Some Selected Monogenic Disorders Autoimmune Polyendocrine Syndromes APS1/APECED Schmidt (APS2) Syndrome Immunodysregulation Polyendocrinopathy and Enteropathy X-Linked (IPEX; 304790) Mitochondrial Disorders MELAS (Myopathy, Encephalopathy, Lactic Acidosis, and Stroke-Like Episodes) and MERRF (Myoclonic Epilepsy Associated with Ragged-Red Fibers) Syndromes Breakage Disorders : Ataxia Telangiectasia and Nijmegen Breakage Syndrome Ataxia-Telangiectasia (AT) Nijmegen Breakage Syndrome (NBS) References Chapter 15 Vitiligo in Childhood 1.3.12.1 Introduction 1.3.12.2 Epidemiology 1.3.12.3 Classification 1.3.12.4 Familial Background 1.3.12.5 Clinical Characteristics 1.3.12.6 Disease Extent and Progression 1.3.12.7 Associated Skin Conditions 1.3.12.8 Associated Autoimmune diseases and Laboratory Investigations 1.3.12.9 Differential Diagnosis 1.3.12.10 Psychological Effects of Childhood Vitiligo 1.3.12.11 Summary of Therapeutic Issues References Chapter 16 Late-Onset Vitiligo 1.3.13.1 Introduction 1.3.13.2 Definition and Epidemiological Data 1.3.13.3 Significance of Late Onset Vitiligo 1.3.13.4 Therapeutic Considerations References Chapter 17 Evaluation, Assessment and Scoring 1.4.1 Introduction 1.4.2 Step by Step Evaluation 1.4.3 Associated Disorders and Laboratory Workup 1.4.4 Skin Biopsy 1.4.5 Scoring 1.4.6 Interobserver Variability 1.4.7 Correlations Between Assessment Variables 1.1.8 Subjective Items References Chapter 18 Quality of Life 1.5.1 Introduction and Historical Perspective 1.5.2 Modern Psychological Studies 1.5.3 Socio–Economic and Educational Consequences 1.5.4 Quality of Life Evaluation References Chapter 19 Natural History and Prognosis 1.6.1 Natural Course 1.6.2 Stability vs. Active Disease 1.6.3 Treatment Outcome and Stability of Repigmentation 1.6.4 Clinical Markers of Prognosis 1.6.5 Prognosis and Subtypes of Vitiligo References Chapter 20 Defining the Disease: Editor’s Synthesis 1.7.1 Clinical Assessment Is Important 1.7.2 Epidemiological Studies, Including Twin Studies, Are Needed 1.7.3 Variable Melanocytic Targets According to Clinical Subtypes 1.7.4 Lessons from Associated Diseases and Rare Syndromic Cases 1.7.5 Predictive Classifications of Facial Segmental Vitiligo? 1.7.6 Suboptimal Use of Pathology to Assess and Probably Understand Vitiligo 1.7.7 Summary References Part II: Understanding the Disease Chapter 21 Pathophysiology Overview 2.1.1 From Where to Start? A Good Hierarchy of Relevant Data Is Needed 2.1.2 Time for a Critical Reappraisal of the Convergence Theory 2.1.3 Melanocyte Loss: Survival Defect, True Destruction, or Multistep Process with Immune Acceleration? 2.1.4 The Genetics Angle: Unbiased and Productive? 2.1.5 Inflammation and Auto-Immunity.The Role of Stress 2.1.6 Identifying and Characterizing Skin and Non Skin Cellular Anomalies in Vitiligo 2.1.7 The Need for Translational Research 2.1.8 Conclusions and Scope of this Book Section References 2.2 Generalized Vitiligo Chapter 22 Genetics 2.2.1.1 Genetic Epidemiology 2.2.1.2 Identification of Vitiligo Susceptibility Genes The Candidate Gene Approach The Genome-Wide Approach The Gene Expression Approach 2.2.1.3 Concluding Remarks References Chapter 23 Environmental Factors 2.2.2.1 The Kobner’s Phenomenon Historical Aspects and Definition Clinical Features Aspect Incidence Identification of Factors Causing KP Pathomechanisms The KP in the Vitiligo Clinic Disease Activity Assessment Prediction of Vitiligo in at Risk Individuals Pathogenesis of Vitiligo Identifi cation of Disease Characteristics that Help Predicting the Outcome of Therapies Prevention of Onset of New Lesions and Improvement of Repigmentation Concluding Remarks References 2.2.2.2 Occupational Vitiligo Chemicals Triggering Occupational Vitiligo Clinical Observations Depigmentation Non-Cutaneous Effects Mode of Action of Phenols/Catechols Quinones and Link with Oxidative Damage Staging References Chapter 24 In Vivo Data 2.2.3.1 Non-Invasive Methodsfor Vitiligo Evaluation Introduction Defining the Extension of Vitiligo Objective Methods for the Assessment of Vitiligo Extent Skin Colour Measurements and Monitoring of Lesions Macroscopic Morphological Measurements Photography Wood’s Light Visible Light Photography Digital Photography Ultraviolet Light Photography Reflectance Spectroscopy Reflectance Tristimulus CIE Colourimetry Selected Spectral Bands and Narrow-BandRefl ectance Spectrophotometry Non-Invasive Micro-MorphologicalMeasurement: In Vivo-Refl ectanceConfocal Microscopy The Technology and Its Optical Principles Reflectance Confocal Microscopy and Vitiligo References 2.2.3.2 Electron Microscopy Ultrastructural Study of the Epidermis Depigmented Macules Melanocytes Keratinocytes Langerhans Cells Clinically Normal Appearing Skin Adjacentto Amelanotic Skin Melanocytes Keratinocytes Langerhans Cells Marginal Hyperpigmented Skin Melanocytes Keratinocytes Ultrastructural Studies of Infl ammatory Vitiligo Melanocytes Langerhans Cells Ultrastructural Study of the Basement Membrane Ultrastructural Study of Cultured Melanocytes from Vitiligo Patients Ultrastructural Study of the Dermis Concluding Remarks References Chapter 25 Animal Models 2.2.4.1 Animal Models of Autoimmune Vitiligo The Multifactorial Nature of Autoimmune Disorders: Application to Vitiligo Naturally Occurring Animal Models of Vitiligo Grey Horse The Sinclair Miniature Swine Water Buffalo The Vitiligo (C57Bl/J6-vit/vit) Mouse The Barred Plymouth Rock and White Leghorn Chickens 2.2.4.2 The Smyth Line Chicken Animal Model of Spontaneous Autoimmune Vitiligo The Genetics Basis of Smyth Line Autoimmune Vitiligo Inherent Melanocyte Defect in Smyth Line Autoimmune Vitiligo Immune System Involvement in Smyth Line Autoimmune Vitiligo Environmental Factors Involved in the Expression of Smyth Line Autoimmune Vitiligo Opportunities Provided by the Smyth Line Chicken Model for Autoimmune Vitiligo 2.2.4.3 Experimental Model of Induced Autoimmune Vitiligo: Mouse Model for the Role of Stress 2.2.4.4 Concluding Remarks References Chapter 26 In Vitro Approaches 2.2.5.1 Cell Isolation and Culture Isolation of Skin Melanocytes and Keratinocytes Isolation and Culture of Skin Fibroblasts Isolation and Culture of Hair Follicle Melanocytes and Keratinocytes Isolation and Freezing of Peripheral Blood Mononuclear cells (PBMC) 2.2.5.2 In Vitro Reconstructed Epidermis Preparation of Dead De-Epidermized Dermis Epidermal Reconstruction 2.2.5.3 Functional Studies of NSV Cells Using Monolayers: Melanocytes, Keratinocytes, and Fibroblasts 2.2.5.4 Functional Studies Using Reconstructed Epidermis 2.2.5.5 New Analytic Techniques Fluorescence-Based Assays Proteomic Metabolomic/Lipidomic Transcriptomic 2.2.5.6 Concluding Remarks References Chapter 27 Oxidative Stress 2.2.6.1 General Aspects 2.2.6.2 Catecholamine and Biopterin Metabolisms 2.2.6.3 Cellular Alterations Related to the Oxidative Stress 2.2.6.4 The Possible Genetic Background 2.2.6.5 The Systemic Oxidative Stress 2.2.6.6 Concluding Remarks References Chapter 28 Immune/Inflammatory Aspects 2.2.7.1 Introduction References 2.2.7.2 The Role of Innate Immunity in Vitiligo The Innate Immune System: An Overview The Skin Innate Immune System Cellular Components Soluble Components The Innate Immune System in Vitiligo Keratinocytes Dendritic Cells Macrophages Natural Killer Cells Pattern Recognition Receptors Antimicrobial Peptides Complement Concluding Remarks References 2.2.7.3 Humoral Immunity Melanocyte Antibodies in Vitiligo Correlations of Melanocyte Antibodies with Vitiligo Targets of Melanocyte Antibodies in Vitiligo The Origin of Melanocyte Antibodies in Vitiligo Pathogenic Effects of Melanocyte Antibodies Melanocyte Antibodies in Melanoma-Associated Hypopigmentation Other Antibodies in Vitiligo Interaction of Humoral and Cellular Immune Responses in Vitiligo Concluding Remarks References 2.2.7.4 Cell-Mediated Immunity Immune Infi ltrates in Vitiligo Skin T Cells and Depigmentation Homing of Immune Reactive T-Cells Vitiligo versus Melanoma T-Cell Responses CD4+ T Cells and Vitiligo Progression Melanocytes as Antigen-Presenting Cells Dendritic Cell Mediated Killing Additional Players in Cellular Immunity Heat Shock Proteinsin Immune Activation Concluding Remarks References Chapter 29 Cytokines and Growth Factors 2.2.8.1 Introduction: Melanocytic Homeostasis and Cytokines/Growth Factors References 2.2.8.2 An Overview of Epidermal Cytokines and Growth Factors in Vitiligo The Role of Melanogenic Cytokines The Role of Inflammatory Cytokines Summary: How the Epidermal Cytokine Network May Be Impaired in Vitiligo Skin References 2.2.8.3 In Vivo Studies of Melanogenic Cytokines and Receptors in Vitiligo Melanogenic Cytokines SCF and ET-1 in Lesional NSV Epidermis The Disruption of SCF-c-kit Interaction on Melanocyte Membranes as an Early Event in the Vitiligo Depigmenting Process Implication of MITF-M, the Melanocytic Master Transcription Factor Concluding Remarks: Possible Molecular Mechanisms in Vitiligo Melanocytes Dysfunction References Chapter 30 Proopiomelanocortin and Related Hormones 2.2.9.1 General Aspects of the Cutaneous Proopiomelanocortin System 2.2.9.2 Melanocortin Peptides: Potential Therapeutic Agents in Vitiligo? 2.2.9.3 POMC-Derived Peptides and Related Peptides in Peripheral Blood of Patients with Vitiligo 2.2.9.4 Genetic Abnormalities of POMC Components in Vitiligo 2.2.9.5 Expression of the Cutaneous POMC System in Vitiligo 2.2.9.6 Concluding Remarks References Chapter 31 Other Hypotheses 2.2.10.1 Introduction 2.2.10.2 The Early Melanocyte Aging Theory 2.2.10.3 The Melanocyte Detachment (“Melanocytorrhagic”) Theory 2.2.10.4 The Viral Hypotheses 2.2.10.5 Deficient Clearance of Apoptotic Fragments 2.2.10.6 The membrane Lipid Defect Mechanism References 2.3 Segmental Vitiligo: A Model to Understand Vitiligo? Introduction Chapter 32 2.3.1 Particular Clinical Characteristics of Segmental Vitiligo Clinical Observations and Hypotheses for SV Patterning Preferential Follicular Reservoir Involvement in SV References Chapter 33 2.3.2 The Concept of Mosaicism Applied to SV The Lines of Blaschko and Segmental Vitiligo The Association of SV and NSV Implications for Research of the Concept of Somatic Mosaicism Applied to Vitiligo References Chapter 34 2.3.3 The Neurogenic Hypothesis in Segmental Vitiligo Clinical Arguments Segmental Distribution Mixed Distribution Overlapping Several Dermatomes Localized Vitiligo or Leukodermas Following Nerve Damage Histological and Ultrastructural Arguments Experimental Findings in Animals Pathophysiological Arguments References Chapter 35 2.3.4 Segmental Vitiligo: A Model for Understanding the Recapitulation of Repigmentation Repigmentation of Segmental Vitiligo and Summary of Repigmentation Schemes Recapitulation of Vitiligo Repigmentation In Vitro and Clinical Relevance In Vivo Cells Involved in SV Repigmentation In Vitro Repigmentation Models Therapeutic Perspectives References Chapter 36 Editor’s Synthesis 2.4.1 Do All Supposed Mechanisms of Melanocyte Loss Occur In Vivo? 2.4.2 An Enlarged Vision of the Skin Melanogenic Unit May Apply to Vitiligo 2.4.3 Melanocyte Stemness and Vitiligo 2.4.4 The Somatic Mosaicism Hypothesis for SV and Deductions for NSV 2.4.5 Membrane Lipids as Possible Culprits 2.4.6 The Innate Immunity Hypothesis 2.4.7 Concluding Remarks References Part III: Therapy Chapter 37 Management Overview 3.1.1 Management-Oriented Evaluation 3.1.2 Treatment Overview UV Treatments Topical Therapies and Combined Therapies Surgery Camouflage and Depigmentation Other Therapies Counseling 3.1.3 Evidence-Based Guidelines References 3.2 Topical Therapies Chapter 38 Topical Corticosteroids 3.2.1.1 Introduction 3.2.1.2 Mode of Action and Rationale for Use in Vitiligo 3.2.1.3 Studies 3.2.1.4 Application Scheme 3.2.1.5 Side Effects 3.2.1.6 Safety Issues References Chapter 39 Calcineurin Inhibitors 3.2.2.1 Introduction 3.2.2.2 Mode of Action and Rationale for Use in Vitiligo 3.2.2.3 Studies 3.2.2.4 Tacrolimus and Pimecrolimus Monotherapy 3.2.2.5 Combination Therapy 3.2.2.6 Comparative Studies Between Tacrolimus and Pimecrolimus 3.2.2.7 General Outcome 3.2.2.8 Application Scheme 3.2.2.9 Side Effects 3.2.2.10 Safety Issues References Chapter 40 Vitamin D Analogues 3.2.3.1 Rationale for use 3.2.3.2 Studies References 3.3 Phototherapies Chapter 41 PUVA and Related Treatments 3.3.1.1 Introduction 3.3.1.2 Psoralens 3.3.1.3 Oral Photochemotherapy 3.3.1.4 Topical Photochemotherapy 3.3.1.5 Khellin + UV References Chapter 42 UVB Total Body and Targeted Phototherapies 3.3.2.1 Narrowband-UVB (NB-UVB) Phototherapy Introduction Pioneer Studies on NB UVB for Vitiligo Confirmative Studies on NB UVB for Vitiligo Efficacy of NB UVB vs. Other Phototherapeutic Modalities NB UVB in Combination with Topical Treatments NB UVB in Combination with Vitamins and Antioxidants Practical Aspects of NB-UVB Treatment 3.3.2.2 Targeted Phototherapy Lasers Excimer Laser 308 nm Helium–Neon NonLaser Light Sources Monochromatic Excimer Lamp or Light 308 nm (MEL 308 nm) Excimer Laser/Lamp vs. NB-UVB Mercury Arc Lamps Plasma Lamps Microphototherapy Edited by Torello Lotti, Francesca Prignano, and Gionata Buggiani) 3.3.2.3 Mechanism of Action of Phototherapies Narrow Band UVB Targeted Phototherapy 3.3.2.4 Side Effects of Phototherapies Narrowband UVB Targeted Phototherapy References Chapter 43 Vitamins and Antioxidants: Topical and Systemic 3.4.1 Introduction 3.4.2 Vitamin B 12 and folic acid, para-aminobenzoic acid 3.4.3 L-Phenylalanine 3.4.4 Antioxidants Background Studies Safety concerns References 3.5 Systemic Treatments Chapter 44 Corticosteroid Minipulses 3.5.1.1 Definition and Historical Background 3.5.1.2 Oral Corticosteroids Minipulses for Vitiligo 3.5.1.3 Personal Remarks References Chapter 45 Other Immunosuppressive Regimen 3.5.2.1 Rationale for the Use of Systemic Immunomodulators 3.5.2.2 Traditional Systemic Immunosuppressants 3.5.2.3 Anti-IFN-gamma Strategy 3.5.2.4 Targeting TNF-alpha by Antibodies 3.5.2.5 Effects of Efalizumab 3.5.2.6 Concluding Remarks References Chapter 46 Empirical, Traditional, and Alternative Treatments 3.6.1 Introduction 3.6.2 Chinese Traditional Products 3.6.3 Plant-Derived Extracts 3.6.4 Melagenin 3.6.5 Aspirn 3.6.6 Statins 3.6.7 Dermabrasion combined with 5-Fluorouracil 3.6.8 Others References 3.7 Surgical Therapies Chapter 47 Background and Techniques 3.7.1.1 Introduction 3.7.1.2 Selection of Patients 3.7.1.3 Surgical Methods Methods Based on Direct Transplantation of Unprocessed Tissue Methods Based on Transplantation of Processed Cells or Tissue 3.7.1.4 Preparation of the Recipient Area 3.7.1.5 A Guide to Advanced Methods for Vitiligo Surgery Basal Cell-Layer Suspension and Cultured Melanocyte Suspension Donor Tissue Release and Preparation of Free Cells Culturing of Melanocytes Premedication Anesthesia of the Recipient Site Transplantation and Aftercare Follow-Up Evaluation Ultra-Thin Grafting Calculation of Areas Premedication Anesthesia of Recipient Site Preparation of the Recipient Site (as Above) Donor Area Transplantation Phase Follow-Up Inspection Evaluation and Documentation References Chapter 48 The Outcomes: Lessons About Surgical Therapy for Vitiligo in the Past Two Decades 3.7.2.1 Introduction 3.7.2.2 Melanocytes Can Be Effectively and Safely Transplanted for Repigmentation of Depigmented Skin 3.7.2.3 Melanocyte Transplantation Is Mainly Successful in Stable Vitiligo 3.7.2.4 With Less Invasive Methods, Better Results Are Achieved 3.7.2.5 PUVA, NB-UVB, or Sunlight Exposure Enhance Repigmentation Rates 3.7.2.6 The Best Repigmentation Results Are Achieved in Segmental Vitiligo 3.7.2.7 Lasers Are Useful to Denude Recipient Sites 3.7.2.8 Frequent Failures with Surgery in Acral Vitiligo Are Seen 3.7.2.9 Surgical Repigmentation Is Similar to Medical Treatment 3.7.2.10 Surgical Repigmentation Is Permanent 3.7.2.11 Combination Therapy Is Useful to Enhance Repigmentation Rates 3.7.2.12 In Vitro Cultured Epidermal Sheets and Melanocyte Suspensions Are Important Options for Repigmenting Stable Vitiligo 3.7.2.13 Repigmentation of Leukotrichia May Be Achieved by Melanocyte Transplantation 3.7.2.14 What to Avoid when Performing Melanocyte Transplantation References Chapter 49 Combined Therapies for Vitiligo 3.8.1 Introduction 3.8.2 Combination of Surgical Therapies and Phototherapy 3.8.3 Combination of Surgical Therapies and Corticosteroids 3.8.4 Combination of Phototherapy and Topical Steroids 3.8.5 Combination of Phototherapy and Topical Calcineurin Inhibitors (TCI) 3.8.6 Combination of Phototherapy and Topical Vitamin D 3.8.7 Combination of Phototherapy and Antioxidants References Chapter 50 Camouflage 3.9.1 Introduction 3.9.2 Why Camouflage and Cosmetic Rehabilitation Are Needed 3.9.3 Camouflage as a Medical Intervention? 3.9.4 A Brief History of Camouflage 3.9.5 Camouflage Controlled Studies 3.9.6 Self-Tanning Creams, Lotions, and Sprays 3.9.7 Cover Creams, Foundations, Sticks 3.9.8 Vitiligo of the Lips 3.9.9 Leukotrichia 3.9.10 Permanent and Semi-Permanent Camouflage 3.9.11 Precautions of Use 3.9.12 Conclusion: Camouflage as a Balm for ‘Bruised’ Souls References Further Reading Chapter 51 Photoprotection Issues 3.10.1 Normal and Vitiligo Skin UV Sensitivity 3.10.2 Photoadaptation of Vitiliginous Skin to UV Irradiation 3.10.3 Vitiligo and Skin Cancer 3.10.4 Practical Photoprotection References Chapter 52 Depigmenting Agents 3.11.1 Introduction 3.11.2 Chemical Agents 3.11.3 Patient’s Selection 3.11.4 Protocol 3.11.5 Side Effects 3.11.6 Combinatory Chemical Approaches 3.11.7 Physical Approaches References Chapter 53 Therapy Adapted for Age, Gender, and Specific Locations 3.13.1 Age and Gender Issues Children Elderly Patients Gender Issues 3.12.2 Particular Locations Mucosae Hairs Hands References Chapter 54 Psychological Interventions 3.13.1 Why Psychological Support Is Important 3.13.2 Screening Patients in Need of Psychological Support 3.13.3 Psychological Interventions 3.13.4 Concluding Remarks References Chapter 55 The Patient Perspective 3.14.1 Introduction 3.14.2 Impact of the Disease on Patients and Families Adults Children Families 3.14.3 Role of Psychotherapy Stigma and Vitiligo Stress and Vitiligo Cognitive–Behavioural Therapy (CBT) 3.14.4 Patients’ Stories Maria, 55 years old Alfredo, 60 years old Robert, 11 years old Henrietta, 40 years old Gurdeep Lee 3.14.5 Patient Support Organisations 3.14.6 Inter-Organisational Cooperation 3.14.7 Other Issues Treatments Family doctors, Misdiagnosis, Early Diagnosis, and Treatment Internet and Alternative Treatments Research Involvement of Patients and Patient Support Organisations in Research Useful Websites References Chapter 56 Evidence-Based Medicine Perspective 3.15.1 History of EBM Approaches in Vitiligo 3.15.2 Meta-Analyses 3.15.3 Lim and Hexsel’s Algorithm 3.15.4 The 2007 German Evidence-Based Analysis 3.15.5 The 2008 Systematic Review of Natural Health Product Treatments 3.15.6 The British Guidelines for the Treatment of Vitiligo No Treatment Option Topical Treatment Phototherapy Systemic Therapy Surgical Treatments Psychological Treatments 3.15.7 The Indian Evidence-Based Practice Guidelines for Surgical Management of Vitiligo References Chapter 57 Editor’s Synthesis and Perspectives 3.16.1 From EBM Guidelines to Clinical Practice 3.16.2 Perspectives References Index