Therapy of Skin Diseases (eBook)

Preface 5
Acknowledgements 7
Contents 8
Contributors 13
Part I: Introduction 22
Chapter 1.1 23
Biology of the Skin 23
1.1.1 Cellular Composition of the Epidermis 23
1.1.2 Cellular and Structural Composition of the Dermis 25
1.1.3 Basement Membranes 27
1.1.4 Cell–Matrix and Cell–Cell Adhesion in the Skin 27
1.1.5 Molecular Basis of the Epidermal Barrier 30
1.1.6 Cellular Communication Within the Skin 31
1.1.7 Concluding Remarks 31
References 32
Chapter 1.2 35
Immune Mechanisms 35
Abbreviations 35
1.2.1 Innate Immunity 35
1.2.2 Activation of Innate Responses via Toll-Like Receptors 35
1.2.3 Protection from Cutaneous Infection by Antimicrobial Peptides 36
1.2.4 Monocytes/Macrophages 36
1.2.5 Adaptive Immunity 36
1.2.6 Antigen-Presenting Cellsof the Epidermis 36
1.2.7 Contact Allergy 37
1.2.8 Keratinocytes are Important Regulators of Skin Immunity 38
References 39
Chapter 1.3 41
General Pharmacology 41
1.3.1 Basic Principles and Definitions 41
1.3.2 Pharmacokinetics: Absorption 42
1.3.3 Bioavailability of Orally Administered Drugs 42
1.3.4 Percutaneous Absorption 42
1.3.5 Pharmacokinetics: Distribution 43
1.3.6 Pharmacokinetics: Metabolism 43
1.3.7 Half-Life 43
1.3.8 Area Under the Curve (AUC) 44
1.3.9 Clearance 44
1.3.10 Pharmacokinetics: Excretion 45
1.3.11 Drug Transporters 45
1.3.12 Pro-Drugs 46
1.3.13 Pharmacogenetics 46
1.3.14 Pharmacogenetics and Adverse Drug Reactions 46
References 47
Chapter 1.4 48
Immunomodulation in Dermatology 48
1.4.1 Introduction 48
1.4.2 B Cell Targeting 48
1.4.2.1 Rituximab 48
1.4.2.2 Mycophenolate Mofetil 49
1.4.3 T Cell Targeting 50
1.4.3.1 Alefacept 50
1.4.3.2 Efalizumab 50
1.4.3.3 Cyclosporin 50
1.4.3.4 Tacrolimus 51
1.4.4 Tumor Necrosis Factor- alpha Targeting 51
1.4.4.1 Infliximab 52
1.4.4.2 Etanercept 52
1.4.4.3 Adalimumab 52
1.4.5 Other Targeting Pathways 53
1.4.5.1 Abatacept 53
1.4.5.2 CTLA4 Targeting 53
1.4.5.3 IL-12/23 p40 Targeting 54
1.4.5.4 Intravenous Immunoglobulin 54
1.4.6 Prophylaxis and Precautions 55
References 55
Chapter 1.5 58
Basic Principles of Geneticsand Gene Therapy 58
1.5.1 Principles of Genetics 58
1.5.2 Basics of Genetics 59
1.5.3 Overview of Genetic Disease 59
1.5.4 Overview of Mendelian Genetics 60
1.5.5 Autosomal Dominant Inheritance 63
1.5.6 Autosomal Recessive Inheritance 63
1.5.7 X-Linked Dominant Inheritance 64
1.5.8 X-Linked Recessive Inheritance 64
1.5.9 Incomplete Penetrance, Delayed Onset Diseases, Variable Expression, De Novo Mutations, Segmental and Germline Mosaicism 65
1.5.9.1 Incomplete Penetrance and Delayed Onset Disease 65
1.5.9.2 Variable Expression 65
1.5.9.3 De Novo Mutationsand Germline Mosaicism 65
1.5.10 Chromosomal Abnormalities 66
1.5.11 Polygenic Diseases 67
1.5.12 Gene Therapy 68
1.5.13 Naturally Occurring Gene Therapy: Revertant Mosaicism 69
References 70
Chapter 1.6 75
Percutaneous Absorption and Principles of Corneotherapy/Skin Care 75
Abbreviations 75
1.6.1 The Stratum Corneum (SC) as Skin Barrier 75
1.6.2 The Structure of the SC as Skin Barrier 76
1.6.3 In Vivo Evaluation of the SC Barrier Function 76
1.6.4 Percutaneous Absorption (or Percutaneous Penetration) 77
1.6.5 Appendageal Penetration 77
1.6.6 Occlusion 77
1.6.7 Influence of Vascularization 78
1.6.8 Water-Binding Capacity of the SC 78
1.6.9 Skin Care Products 78
1.6.10 In Vivo Assessment of Skin Surface Hydration 78
1.6.11 Corneotherapy 78
References 79
Chapter 1.7 81
Principles of Systemic Therapy 81
1.7.1 Introduction 81
1.7.2 Pharmacologic Principles of Systemic Therapy 81
1.7.3 General Principles of Systemic Drug Therapy 82
1.7.3.1 When to Consider Systemic Therapy 83
1.7.3.2 Know the Patient 83
1.7.3.3 Know the Skin Disease 84
1.7.3.4 Know the Medication Under Consideration 84
1.7.3.4.1 Identify Absolute and Relative Contraindications to Systemic Drug Therapy 84
1.7.3.4.2 Identify Polymorphisms in Drug Metabolism 86
1.7.3.4.3 Cytochrome P450 (CYP) 86
1.7.3.4.4 N -Acetyltransferase (NAT) 87
1.7.3.4.5 Thiopurine S -Methyltransferase (TPMT) 87
1.7.3.4.6 Glucose-6-Phosphate Dehydrogenase (G6PD) 88
1.7.3.4.7 Know the Adverse Effect Profi le of the Medication Under Consideration 88
1.7.3.4.8 Minimize Potential Drug Interactions 88
1.7.3.4.9 Monitor for Toxicity During Therapy 91
1.7.3.4.10 Make Adjustments to the Treatment Regimen to Decrease Toxicity or Increase Clinical Response 92
1.7.3.4.11 Enlist Help of Outside Specialists 92
1.7.5 Global Variations 93
References 93
Chapter 1.8 95
Retinoid Pharmacology 95
1.8.1 Physiological Role and Distribution of Retinoids in Human Skin 95
1.8.2 General Therapeutic Outline 96
1.8.3 Current Established Therapies 96
1.8.4 Retinol and Retinaldehyde 97
1.8.4.1 Tretinoin 97
1.8.4.2 Isotretinoin 97
1.8.4.3 Alitretinoin 98
1.8.4.4 Acitretin and Etretinate 98
1.8.4.5 Adapalene 99
1.8.4.6 Tazarotene 99
1.8.4.7 Bexarotene 100
1.8.5 Experimental Approaches 100
1.8.6 Complication to Avoid 101
1.8.7 Global Variations 101
References 101
Chapter 1.9 104
Ultraviolet (UV) A and (UV) B Phototherapy 104
1.9.1 UVB phototherapy 104
1.9.2 Mechanisms of Action of Ultraviolet Phototherapy 104
1.9.2.1 Action Spectrum of UVB Phototherapy 104
1.9.2.2 The Mechanisms of Action of UVB Phototherapy: Apoptosis and Immune Suppression 104
1.9.2.3 Clinical Efficacy of Narrow-Band UVB for Psoriasis and Atopic Dermatitis 105
1.9.2.4 Excimer Light/Laser 105
1.9.3 Complications to Avoid 106
1.9.4 Global Variations 106
1.9.5 UVA1 Phototherapy 106
1.9.6 Mechanism of Action of Ultraviolet A-1 (UVA1) Phototherapy 106
1.9.7 Clinical Efficacy 106
1.9.7.1 Atopic Dermatitis 106
1.9.7.2 Localized and Systemic Scleroderma 107
1.9.8 Complications to Avoid 107
1.9.9 Global Variations 107
References 108
Chapter 1.10 109
Laser Therapy 109
1.10.1 Background 109
1.10.2 Characteristics 110
1.10.3 Aminolevulinic Acid 111
1.10.3.1 Methyl Ethyl Aminolevulinic Acid 111
1.10.4 General Therapeutic Outline 111
1.10.4.1 Ablative Technologies 111
1.10.4.1.1 Carbon Dioxide (CO 2 ) Lasers 111
1.10.4.1.2 Erbium:YAG Laser 112
1.10.4.1.3 Plasma Skin Resurfacing 113
1.10.5 Nonablative Technologies 113
1.10.5.1 Vascular Lasers and Light Sources 114
1.10.5.1.1 Appropriate Wavelength 114
1.10.6 Treatment Issues 114
1.10.6.1 Q-switched and Long-Pulsed Laser Systems 115
1.10.6.2 Yellow and Green Light Lasers 115
1.10.6.3 Nonlaser Light Sources 116
1.10.6.4 Infrared Lasers and Light Sources 116
1.10.7 Currently Available Technologies 117
1.10.7.1 1,064 nm Nd:YAG Laser 117
1.10.7.2 1,320 nm Nd:YAG Laser 117
1.10.7.3 1,450 nm Diode Laser 117
1.10.7.4 1,540 nm Erbium: Glass Laser 118
1.10.7.5 Fractional Photothermolysis 118
1.10.8 Complications to Avoid 118
1.10.9 Global Variations 119
References 119
Chapter 1.11 121
Photodynamic Therapy 121
1.11.1 History and General Concept 121
1.11.2 Systemic PDT 122
1.11.2.1 History and Current Status 122
1.11.2.2 Complications to Avoid 122
1.11.3 Topical PDT 122
1.11.3.1 History and Current Status 122
1.11.3.2 Application to Nonmelanoma Skin Cancers 122
1.11.3.3 Approaches to Inflammatory Skin Disorders and Photorejuvenation 123
1.11.3.4 New Modalities 124
1.11.3.5 Complications to Avoid 124
1.11.3.6 Photodynamic Diagnosis with Topical Application of ALA 124
1.11.4 Mechanisms of PDT 124
1.11.4.1 Photodynamic Action: Induction of Apoptosis of Tumor Cells 124
1.11.4.2 Effects on Tumor Stroma 125
1.11.4.3 Induction of Infl ammation and Antitumor Immunity 125
1.11.4.4 Susceptibility of Cells to PDT 125
1.11.5 Global Variations and Operative Procedure 125
References 126
Chapter 1.12 128
Dermatologic Surgery 128
1.12.1 Etiology and Pathogenesis 128
1.12.2 Clinical Characteristics and Diagnosis 129
1.12.3 General Therapeutic Outline 130
1.12.4 Current Established Therapies 130
1.12.4.1 Skin Biopsy 130
1.12.4.2 Elliptical Excision 131
1.12.4.3 Mohs Surgery 132
1.12.4.4 Reconstructive Surgery 132
1.12.4.5 Surgery in Children 133
1.12.5 Experimental Approaches 133
1.12.6 Complications to Avoid 133
1.12.7 Global Variations 133
Further Reading 133
Chapter 1.13 135
Neurophysiology of Itch 135
1.13.1 Neuronal Pathways for Itch: From Skin to Brain (Fig. 1.13.1 ) 135
1.13.2 Interactions Between Itch and Pain 136
1.13.3 Peripheral and Central Neuronal Sensitization 137
1.13.4 Pruritogens 137
1.13.5 Pruritus of Origins Other Than Skin 138
1.13.6 Therapeutic Targets 138
1.13.7 Global Variations 139
References 139
Part II: Intectious Diseases 141
Chapter 2.1 142
Bacterial and Mycobacterial Infections 142
2.1.1 Impetigo and Ecthyma 142
2.1.1.1 Etiology and Pathophysiology 142
2.1.1.2 Clinical Characteristics and Diagnosis 142
2.1.1.3 General Therapeutic Outline 142
2.1.1.4 Current Established Therapies 143
2.1.1.5 Experimental Approaches 143
2.1.1.6 Complications to Avoid 143
2.1.1.7 Global Variations 143
2.1.2 Folliculitis, Furuncles, and Carbuncles 143
2.1.2.1 Etiology and Pathophysiology 143
2.1.2.2 Clinical Characteristics and Diagnosis 144
2.1.2.3 General Therapeutic Outline 144
2.1.2.4 Current Established Therapies 144
2.1.2.5 Experimental Approaches 144
2.1.2.6 Complications to Avoid 144
2.1.3 Erysipelas 145
2.1.3.1 Etiology and Pathophysiology 145
2.1.3.2 Clinical Characteristics and Diagnosis 145
2.1.3.3 General Therapeutic Outline 145
2.1.3.4 Current Established Therapies 145
2.1.3.5 Experimental Approaches 145
2.1.3.6 Complications to Avoid 145
2.1.4 Cellulitis 145
2.1.4.1 Etiology and Pathophysiology 146
2.1.4.2 Clinical Characteristics and Diagnosis 146
2.1.4.3 General Therapeutic Outline 146
2.1.4.4 Current Established Therapies 146
2.1.4.5 Experimental Approaches 146
2.1.4.6 Complications to Avoid 146
2.1.4.7 Global Variations 147
2.1.5 Necrotizing Fasciitis 147
2.1.5.1 Etiology and Pathophysiology 147
2.1.5.2 Clinical Characteristics and Diagnosis 147
2.1.5.3 General Therapeutic Outline 147
2.1.5.4 Current Established Therapies 147
2.1.5.5 Experimental Approaches 148
2.1.5.6 Complications to Avoid 148
2.1.5.7 Global Variations 148
2.1.6 Staphylococcal Scalded Skin Syndrome 148
2.1.6.1 Etiology and Pathophysiology 149
2.1.6.2 Clinical Characteristics and Diagnosis 149
2.1.6.3 General Therapeutic Outline 149
2.1.6.4 Current Established Therapies 149
2.1.6.5 Experimental Approaches 149
2.1.6.6 Complications to Avoid 149
2.1.6.7 Global Variations 150
2.1.7 Cutaneous Anthrax 150
2.1.7.1 Etiology and Pathophysiology 150
2.1.7.2 Clinical Characteristics and Diagnosis 150
2.1.7.3 General Therapeutic Outline 150
2.1.7.4 Current Established Therapies [33] 150
2.1.7.5 Experimental Approaches 151
2.1.7.6 Complications to Avoid 151
2.1.7.7 Global Variations 151
2.1.8 Leprosy 151
2.1.8.1 Etiology and Pathophysiology 151
2.1.8.2 Clinical Characteristics and Diagnosis 152
2.1.8.3 General Therapeutic Outline 152
2.1.8.4 Current Established Therapies 152
2.1.8.5 Experimental Approaches 153
2.1.8.6 Complications to Avoid 153
2.1.8.7 Global Variations 153
2.1.9 Cutaneous Tuberculosis 153
2.1.9.1 Etiology and Pathophysiology 153
2.1.9.2 Clinical Characteristics and Diagnosis 154
2.1.9.3 General Therapeutic Outline 154
2.1.9.4 Current Established Therapies 154
2.1.9.5 Experimental Approaches 155
2.1.9.6 Complications to Avoid 155
2.1.9.7 Global Variations 155
2.1.10 Bartonella Infections 155
2.1.10.1 Etiology and Pathophysiology 155
2.1.10.2 Clinical Characteristics and Diagnosis 156
2.1.10.3 Diagnosis 156
2.1.10.4 General Therapeutic Outline 156
2.1.10.5 Current Established Therapies 156
2.1.10.6 Experimental Approaches 156
2.1.10.7 Complications to Avoid 157
2.1.10.8 Global Variations 157
2.1.11 Tularemia 157
2.1.11.1 Etiology and Pathophysiology 157
2.1.11.2 Clinical Characteristics and Diagnosis 157
2.1.11.3 General Therapeutic Outline 158
2.1.11.4 Current Established Therapies 158
2.1.11.5 Experimental Approaches 158
2.1.11.6 Complications to Avoid 158
2.1.11.7 Global Variations 158
References 159
Chapter 2.2 162
Fungal Infection 162
2.2.1 Superficial Fungal Infection 162
2.2.1.1 Dermatophytosis 162
2.2.1.1.1 Etiology and Pathophysiology 162
2.2.1.1.2 Clinical Features 162
2.2.1.1.3 Diagnosis 163
2.2.1.1.4 General Therapeutic Outlines 163
2.2.1.1.5 Current Established Therapies 163
2.2.1.1.6 Complications to Avoid 164
2.2.1.1.7 Global Variations 164
2.2.1.2 Candidiasis 164
2.2.1.2.1 Etiology and Pathophysiology 164
2.2.1.2.2 Clinical Features and Diagnosis 164
2.2.1.2.3 General Therapeutic Outlines 165
2.2.1.2.4 Current Established Therapies 165
2.2.1.2.5 Complications to Avoid 165
2.2.1.2.6 Global Variation 165
2.2.1.3 Tinea Versicolor 165
2.2.1.3.1 Etiology and Pathophysiology 165
2.2.1.3.2 Clinical Features and Diagnosis 165
2.2.1.3.3 General Therapeutic Outlines 165
2.2.1.3.4 Current Established Therapies 166
2.2.1.3.5 Complications to Avoid 166
2.2.2 Subcutaneous Fungal Infection 166
2.2.2.1 Sporotrichosis 166
2.2.2.1.1 Etiology and Pathophysiology 166
2.2.2.1.2 Clinical Features and Diagnosis 167
2.2.2.1.3 General Therapeutic Outlines 167
2.2.2.1.4 Current Established Therapies 167
2.2.2.1.5 Complications to Avoid 167
2.2.2.1.6 Global Variation 167
2.2.2.2 Dematiaceous (Brown-Pigmented) Fungal Infections 167
2.2.2.2.1 Etiology and Pathophysiology 167
2.2.2.2.2 Clinical Features and Diagnosis 167
2.2.2.2.3 General Therapeutic Outlines 168
2.2.2.2.4 Current Established Therapies 168
2.2.2.2.5 Complications to Avoid 168
2.2.2.2.6 Global Variation 168
2.2.2.3 Cryptococcosis 168
2.2.2.3.1 Etiology and Pathophysiology 168
2.2.2.3.2 Clinical Features and Diagnosis 168
2.2.2.3.3 General Therapeutic Outlines 168
2.2.2.3.4 Current Established Therapies 169
2.2.2.3.5 Complications to Avoid 169
References 169
Chapter 2.3 170
Viral Infections 170
2.3.1 Herpes Simplex 170
2.3.1.1 Etiology and Pathophysiology 170
2.3.1.2 Clinical Characteristics and Diagnosis 170
2.3.1.3 Current Established Therapies 171
2.3.1.4 Experimental Approaches 171
2.3.2 Varicella and Zoster 171
2.3.2.1 Etiology and Pathophysiology 171
2.3.2.2 Clinical Characteristics and Diagnosis 172
2.3.2.3 Current Established Therapies 172
2.3.3 Human Papillomavirus 173
2.3.3.1 Etiology and Pathophysiology 173
2.3.3.2 Clinical Characteristics and Diagnosis 173
2.3.3.3 Current Established Therapies 173
2.3.4 Molluscum Contagiosum 173
2.3.4.1 Etiology and Pathophysiology 173
2.3.4.2 Clinical Characteristics and Diagnosis 174
2.3.4.3 Current Established Therapies 174
2.3.5 Hand, Foot, and Mouth Disease 174
2.3.5.1 Etiology and Pathophysiology 174
2.3.5.2 Clinical Characteristics and Diagnosis 175
2.3.5.3 Current Established Therapies 175
2.3.5.4 Complications to Avoid 175
2.3.5.5 Global Variations 175
References 175
Chapter 2.4 177
Sexually Transmitted Diseases (STDs) 177
2.4.1 Syphilis 177
2.4.1.1 Epidemiology and Pathophysiology 177
2.4.1.2 Clinical Characteristics and Diagnosis 177
2.4.1.3 Therapeutic Outline 178
2.4.1.4 Current Established Therapy 178
2.4.1.5 Complications 178
2.4.1.6 Global Variations 178
2.4.2 Gonorrhea 179
2.4.2.1 Epidemiology and Pathophysiology 179
2.4.2.2 Clinical Characteristics and Diagnosis 179
2.4.2.3 Therapy 179
2.4.2.4 Complications 179
2.4.3 Trachomatis 179
2.4.3.1 Epidemiology and Pathophysiology 179
2.4.3.2 Clinical Characteristics and Diagnosis 180
2.4.3.3 Therapy 180
2.4.4 Lymphogranuloma Inguinalis 180
2.4.4.1 Etiology and Pathophysiology 180
2.4.4.2 Clinical Characteristics and Diagnosis 180
2.4.4.3 Therapy 180
2.4.4.4 Complications 181
2.4.5 Chancroid (Ulcus molle) 181
2.4.5.1 Epidemiology and Pathophysiology 181
2.4.5.2 Clinical Characteristics and Diagnosis 181
2.4.5.3 Therapy 181
2.4.5.4 Complications 181
2.4.6 Granuloma Inguinale (Donovanosis) 181
2.4.6.1 Ethiology and Pathophysiology 181
2.4.6.2 Clinical Characteristics and Diagnosis 181
2.4.6.3 Complication 182
2.4.6.4 Therapy 182
2.4.7 Other Sexually Transmitted Diseases 182
References 182
Chapter 2.5 184
Human Immunodeficiency Virus (HIV) 184
2.5.1 Etiology and Pathophysiology 184
2.5.2 Clinical Characteristics 185
2.5.2.1 HIV and Pregnancy 185
2.5.2.2 HIV and Tumors 185
2.5.2.3 Diagnosis 185
2.5.3 Antiretroviral Therapy 186
2.5.4 Experimental Approaches 187
2.5.5 Complications 189
2.5.5.1 Immune Reconstitution Syndrome 189
2.5.5.2 Resistance 189
2.5.5.3 Drug Monitoring and Drug Interaction 189
2.5.5.4 Side Effects of Antiretroviral Therapy 190
2.5.6 Global Variations 190
References 190
Chapter 2.6 192
Ectoparasitic and Protozoan Diseases 192
2.6.1 Ectoparasitic Infestations 192
2.6.1.1 Pediculosis 192
2.6.1.1.1 Etiology and Pathophysiology 192
2.6.1.1.2 Clinical Characteristics and Diagnosis 192
2.6.1.1.3 General Therapeutic Outline 192
2.6.1.1.4 Current Established Therapies 192
2.6.1.1.5 Experimental Approaches 193
2.6.1.1.6 Complications to Avoid 193
2.6.1.1.7 Global Variations 194
2.6.1.2 Scabies 194
2.6.1.2.1 Etiology and Pathophysiology 194
2.6.1.2.2 Clinical Characteristics and Diagnosis 194
2.6.1.2.3 General Therapeutic Outline 194
2.6.1.2.4 Current Established Therapies 194
2.6.1.2.5 Experimental Approaches 194
2.6.1.2.6 Complications to Avoid 195
2.6.1.2.7 Global Variations 195
2.6.2 Protozoan Infections 195
2.6.2.1 Amoebic Infection 195
2.6.2.1.1 Etiology and Pathophysiology 195
2.6.2.1.2 Clinical Characteristics and Diagnosis 196
2.6.2.1.3 General Therapeutic Outline 196
2.6.2.1.4 Current Established Therapies 196
2.6.2.1.5 Experimental Approaches 196
2.6.2.1.6 Complications to Avoid 196
2.6.2.1.7 Global Variations 196
2.6.2.2 Leishmaniasis and trypanosomiasis 196
2.6.2.2.1 Etiology and Pathophysiology 197
2.6.2.2.2 Clinical Characteristics and Diagnosis 197
2.6.2.2.3 General Therapeutic Outline 197
Current Established Therapies 197
2.6.2.2.4 Experimental Approaches 197
2.6.2.2.5 Complications to Avoid 198
2.6.2.2.6 Global Variations 198
References 199
Part III: Papulosquamous Dermatoses 201
Chapter 3.1 202
Psoriasis 202
3.1.1 Etiology and Pathophysiology 202
3.1.2 Clinical Characteristics and Diagnosis 202
3.1.3 General Therapeutic Outline 203
3.1.3.1 Quality of Life and Patient Satisfaction Rate for Treatments 204
3.1.3.2 Evaluation of Biologic Agents 204
3.1.3.3 Pathophysiological Rationale of Psoriasis Therapy 204
3.1.4 Current Established Therapies 205
3.1.4.1 Topical Agents 205
3.1.4.1.1 Topical Corticosteroids 205
3.1.4.1.2 Active Vitamin D3 Analogs 206
3.1.4.1.3 Topical Sequential Therapy of Psoriasis (Koo) 206
3.1.4.1.4 Anthralin (Dithranol) 206
3.1.4.1.5 Tazarotene 206
3.1.4.1.6 Tar 206
3.1.4.2 UV Phototherapy 207
3.1.4.2.1 Goeckerman Treatment and Broadband UVB 207
3.1.4.2.2 PUVA (8-Methoxypsoralen (8-MOP) and UVA) Therapy 207
Oral PUVA Therapy 207
Topical PUVA Therapy 207
Bath PUVA Therapy 207
Adverse Reactions of PUVA Therapy 207
3.1.4.2.3 Narrowband UVB Therapy 207
3.1.4.2.4 Balneophototherapy 208
3.1.4.3 Systemic Therapy 208
3.1.4.3.1 Retinoids 208
3.1.4.3.2 Ciclosporin 208
3.1.4.3.3 Methotrexate 208
3.1.4.3.4 Fumaric Acid Esters 209
3.1.4.3.5 Hydroxyurea 209
3.1.4.4 Biologics 209
3.1.4.4.1 Alefacept 209
3.1.4.4.2 Efalizumab 209
3.1.4.4.3 Etanercept 210
3.1.4.4.4 Infliximab 210
3.1.4.4.5 Adalimumab 210
3.1.5 Experimental Approaches 210
3.1.6 Complications to Avoid 210
3.1.7 Global Variations 211
References 211
Chapter 3.2 215
Parapsoriasis and Related Disorders 215
3.2.1 Etiology and Pathophysiology 215
3.2.2 Clinical Characteristics and Diagnosis 216
3.2.3 General Therapeutic Outline 217
3.2.4 Modes of Action 217
3.2.4.1 Current Established Treatments 217
3.2.4.2 Topical Corticosteroids 217
3.2.4.3 Coal Tar Products 217
3.2.4.4 Photo(chemo)therapy 218
3.2.4.5 Methotrexate 218
3.2.5 Experimental Approaches 218
3.2.6 Global Variation 218
3.2.7 In Conclusion 218
References 218
Chapter 3.3 220
Lichen Planus 220
3.3.1 Clinical Features 220
3.3.2 Histology 222
3.3.3 Pathogenesis 222
3.3.4 LP as a Manifestation of Chronic Graft-Vs.-Host Disease (GVHD) 223
3.3.5 Treatment 224
3.3.5.1 Conventional Therapies and Their Complication 224
3.3.5.2 Immunosuppressant Agents and Their Complications 225
3.3.5.3 Phototherapy and Its Complication 226
3.3.5.4 Biologics and Its Complication 226
3.3.6 Global Variations 227
3.3.7 Complications to Avoid 227
3.3.8 Conclusions 227
References 228
Part IV: Atopic Dermatitis and Related Diseases 230
Chapter 4.1 231
Atopic Dermatitis 231
4.1.1 Definition 231
4.1.2 Etiology and Pathophysiology 231
4.1.2.1 Epidemiology 231
4.1.2.2 Genetics 232
4.1.2.3 Immunological Mechanisms 232
4.1.2.4 Autoallergens 233
4.1.3 Clinical Characteristics and Diagnosis 233
4.1.4 General Therapeutic Outline 234
4.1.5 Current Established Therapies 234
4.1.6 Experimental Approaches 236
4.1.7 Complications to Avoid 236
4.1.8 Global Variations 237
References 237
Chapter 4.2 240
Pruritus 240
4.2.1 Etiology and Pathophysiology 240
4.2.2 Clinical Characteristics and Diagnosis 241
4.2.3 General Therapeutic Outline 241
4.2.4 Current Established Therapies and Neurobiological Basis 241
4.2.4.1 Targeting Pruritus Elicitation in the Skin 241
4.2.4.1.1 The Vanilloid Capsaicin 244
4.2.4.1.2 The Cannabinoid N -Palmitoylethanolamine (PEA) 244
4.2.4.1.3 Cold, Menthol, Icilin 244
4.2.4.1.4 Calcineurin Inhibitors 245
4.2.4.1.5 H1-Antihistamines 245
4.2.4.1.6 H2-Blockers 245
4.2.4.1.7 Leukotrien Receptor Antagonists 245
4.2.4.1.8 Immunosuppressant Cyclosporin A 246
4.2.4.2 Targeting Pruritus Elicitation in Central Nervous System 246
4.2.4.2.1 Anticonvulsants: Gabapentin and Pregabalin 246
4.2.4.2.2 Mu-Opioid Receptor Antagonists: Naltrexone, Nalmefene, Naloxone 247
4.2.4.2.3 Antidepressants 247
4.2.5 Experimental Approaches 247
4.2.6 Complications to Avoid 248
4.2.7 Global Variations 248
References 248
Chapter 4.3 251
Urticaria 251
4.3.1 Etiology and Pathophysiology 251
4.3.1.1 Mechanisms of Wheal Formation 251
4.3.1.2 Mechanisms of Mast Cell Degranulation 252
4.3.1.2.1 Activation of Fc e RI 252
4.3.1.2.2 Complement 253
4.3.1.2.3 Neuropeptides 253
4.3.1.2.4 Osmolality 254
4.3.1.2.5 Others (Opioids and Proteases) 254
4.3.1.3 Causes of Urticaria 254
4.3.1.3.1 Direct Stimuli for Wheal Formation 254
4.3.1.3.2 Urticaria Aggravating Factors 254
4.3.2 Clinical Characteristics and Diagnosis 255
4.3.2.1 Idiopathic Urticarias (Ordinary Urticarias) (Acute and Chronic Urticarias) 256
4.3.2.2 Physical Urticarias 257
4.3.2.2.1 Mechanical Urticaria (Symptomatic Dermographism) 257
4.3.2.2.2 Cold Urticaria 258
4.3.2.2.3 Solar Urticaria 258
4.3.2.2.4 Delayed Pressure Urticaria 258
4.3.2.2.5 Other Physical Urticarias 258
4.3.2.3 Cholinergic Urticaria 258
4.3.2.4 Urticaria Induced by Exogenous Antigen via Allergic Mechanism 258
4.3.2.5 Urticaria Induced by Exogenous Substance via Nonallergic Mechanism 259
4.3.2.6 Angioedema 259
4.3.2.7 Other Types of Urticaria 259
4.3.2.8 Diagnosis 259
4.3.3 General Therapeutic Outline 260
4.3.4 Current Established Therapies 260
4.3.4.1 Idiopathic Urticaria 260
4.3.4.1.1 Acute Urticaria 260
4.3.4.1.2 Chronic Urticaria 261
4.3.4.2 Urticaria with Symptoms Induced by Specific Factors 261
4.3.4.3 Angioedema 261
4.3.5 Experimental Approaches 263
4.3.5.1 Idiopathic Urticaria 263
4.3.5.2 Urticaria in Cryopirin-Associated Diseases 263
4.3.5.3 Urticaria Mediated by IgE/Fc e RI 263
4.3.6 Complications to Avoid 263
4.3.7 Global Variations 264
4.3.7.1 Classification 264
4.3.7.2 Clinical Characteristics 264
4.3.7.3 Etiology 264
4.3.7.4 Therapies for Idiopathic Urticaria Nonresponsive to Single Doses of Antihistamines 264
References 265
Chapter 4.4 267
Mastocytosis 267
4.4.1 Etiology and Pathophysiology 267
4.4.2 Clinical Characteristics and Diagnosis 269
4.4.2.1 Skin Manifestation 269
4.4.2.2 Systemic Involvement 270
4.4.2.3 Histopathology 271
4.4.2.4 Blood Count and MC Mediators 271
4.4.3 General Therapeutic Outline 271
4.4.4 Current Established Therapies 272
4.4.4.1 Antihistamines 272
4.4.4.2 Cromolyn Sodium and Anti-Inflammatory Agents 272
4.4.4.3 Ultraviolet Irradiation 272
4.4.4.4 Treatment of Mastocytomas and Bullae 272
4.4.4.5 Immunomodulatory Agents and Chemotherapy 272
4.4.5 Experimental Approaches 273
4.4.5.1 Imatinib Mesylate 273
4.4.5.2 AMN107 273
4.4.5.3 Dasatinib 273
4.4.5.4 PKC412 273
4.4.5.5 Other Small-Molecule Kit Tyrosine Kinase Inhibitors 274
4.4.5.6 Other Signaling Inhibitors 274
4.4.6 Complications to Avoid 274
4.4.7 Global Variations 275
References 275
Part V: Allergic Reactions and Hypersensitive Diseases 277
Chapter 5.1 278
Allergic Contact Dermatitis 278
5.1.1 Etiology and Pathophysiology 278
5.1.2 Immunology 278
5.1.2.1 Sensitization 278
5.1.2.2 Elicitation 279
5.1.3 Pathology 279
5.1.4 Contact Allergens 279
5.1.5 Skin Prerequisites 279
5.1.6 Clinical Characteristics and Diagnosis 280
5.1.7 General Therapeutic Outline 282
5.1.7.1 Prevention 282
5.1.7.1.1 Secondary Prevention and Tertiary Prevention 282
5.1.7.1.2 Why Secondary Prevention Often Does Not Work Sufficiently 282
5.1.8 Current Established Therapies 283
5.1.9 Experimental Approaches 283
5.1.9.1 Identifying a Substance 283
5.1.9.2 In Vivo Testing in Humans 283
5.1.9.2.1 Serial Dilution Test 283
5.1.9.2.2 Repeated Open Application Test (ROAT) 283
5.1.10 Complications to Avoid 284
5.1.11 Global Variations 284
References 285
Chapter 5.2 287
Photosensitivity Diseases 287
5.2.1 Principles of Photosensitivity Diseases 287
5.2.2 Evaluation of Photosensitive Patients 287
5.2.3 Phototesting 288
5.2.3.1 Light Source 288
5.2.3.2 UVA Irradiation 288
5.2.3.3 UVB Irradiation 289
5.2.3.4 Visible Light Irradiation 289
5.2.4 Photopatch Testing 289
5.2.4.1 Indication 289
5.2.4.2 Procedure 289
5.2.4.3 Evaluation 289
5.2.5 Drug Phototesting 289
5.2.6 Solar Urticaria 290
5.2.6.1 Etiology and Pathophysiology 290
5.2.6.2 Clinical Characteristics and Diagnosis 291
5.2.6.3 General Therapeutic Outline 291
5.2.6.4 Current Established Therapies 292
5.2.6.5 Experimental Approaches 292
5.2.6.6 Complications to Avoid 293
5.2.6.7 Global Variations 293
5.2.7 Polymorphous Light Eruption 293
5.2.7.1 Etiology and Pathophysiology 293
5.2.7.2 Clinical Characteristics and Diagnosis 293
5.2.7.3 General Therapeutic Outline 294
5.2.7.4 Current Established Therapies 294
5.2.7.5 Experimental Approaches 294
5.2.7.6 Global Variations 294
5.2.8 Chronic Actinic Dermatitis 294
5.2.8.1 Etiology and Pathophysiology 294
5.2.8.2 Clinical Characteristics and Diagnosis 295
5.2.8.3 General Therapeutic Outline 295
5.2.8.4 Current Established Therapies 295
5.2.8.5 Experimental Approaches 295
5.2.8.6 Global Variations 296
5.2.9 Drug-Induced Photosensitivity 296
5.2.9.1 Etiology and Pathophysiology 296
5.2.9.2 Clinical Characteristics and Diagnosis 296
5.2.9.3 General Therapeutic Outline 297
5.2.9.4 Current Established Therapies 297
References 297
Chapter 5.3 299
Drug Reactions 299
5.3.1 Introduction 299
5.3.2 Epidemiology 300
5.3.3 Etiology and Pathophysiology 300
5.3.3.1 Immediate Hypersensitivity: Allergic Anaphylaxis 300
5.3.3.1.1 Pseudoallergic Reactions 301
5.3.3.1.2 Angioedema Without Urticaria 301
5.3.3.2 Jarisch-Herxheimer-Reaction 302
5.3.3.3 Drug-Induced Autoimmune Reactions 302
5.3.3.4 Delayed-Type Hypersensitivity Reaction and Late-Type Allergy 303
5.3.3.4.1 Allergic Contact Dermatitis 303
5.3.3.4.2 Maculopapulous Drug-Induced Exanthema 303
5.3.3.4.3 Bullous Allergic Drug Reactions 303
Fixed Drug Reaction 303
Erythema Multiforme-Like Drug Reaction 304
Stevens-Johnson Syndrome (SJS) 304
Toxic Epidermal Necrolysis 304
Drug-Induced Hypersensitivity Syndrome 305
Acute Generalized Eruptive Pustulosis 306
5.3.3.5 Photoallergic and Phototoxic Reactions 307
5.3.4 Clinical Characteristics and Diagnostics 307
5.3.4.1 Skin Tests 308
5.3.4.2 In Vitro Test 311
5.3.4.3 Serological Testing Systems 311
5.3.4.4 Cellular Testing Systems 312
5.3.4.4.1 Basophile Activation Test 312
5.3.4.5 Lymphocyte Transformation Test (LTT) 312
5.3.4.6 Allergy Card 312
5.3.5 Role of Drug Metabolism 312
5.3.6 General Therapeutic Outline 312
5.3.7 Current Established Therapies 313
5.3.8 Experimental Approaches 314
5.3.9 Complications to Avoid 316
5.3.11 Global Variations (For the Therapy) 316
References 316
Further Reading 320
Chapter 5.4 322
Hypersensitivity Syndrome Reaction 322
Synonyms 322
5.4.1 Clinical Characteristics and Diagnosis 322
5.4.2 Etiology and Pathophysiology 323
5.4.3 Differential Diagnosis 325
5.4.4 Management 325
References 326
Chapter 5.5 328
Eosinophilic Dermatoses 328
5.5.1 Etiology and Pathophysiology 328
5.5.2 Clinical Characteristics and Diagnosis 328
5.5.2.1 Atopic Dermatitis 329
5.5.2.2 Prurigo 330
5.5.2.3 Bullous Pemphigoid 330
5.5.2.4 Ofuji Disease (Eosinophilic Pustular Folliculitis) 331
5.5.2.5 Hypereosinophilic Syndrome 331
5.5.3 General Therapeutic Outline 331
5.5.3.1 Glucocorticoid 331
5.5.3.2 Antihistamine 333
5.5.3.3 Immuno Suppressants 333
5.5.4 Current Established Therapy 333
5.5.4.1 Th2 Cytokine Modulator 333
5.5.4.2 Thromboxane A2 (TXA2) Inhibitors 333
5.5.4.3 Topical Vitamin D3 333
5.5.5 Experimental Approaches 334
5.5.5.1 Anti IL5 Antibody 334
5.5.5.2 STAT6 Decoy 334
5.5.6 Complications to Avoid 335
5.5.7 Global Variations 335
References 335
Chapter 5.6 337
Neutrophilic Dermatoses 337
5.6.1 Pyoderma Gangrenosum 337
5.6.1.1 Etiology and Pathophysiology 337
5.6.1.2 Clinical Characteristics and Diagnosis 337
5.6.1.2.1 Classic PG 337
5.6.1.2.2 Peristomal PG 338
5.6.1.2.3 Pustular PG 338
5.6.1.2.4 Bullous PG 338
5.6.1.2.5 Vegetative PG 338
5.6.1.3 General Therapeutic Outline 338
5.6.1.4 Current Established Therapies 338
5.6.1.4.1 Topical Treatments 338
5.6.1.4.2 Systemic Corticosteroids 339
5.6.1.4.3 Cyclosporine 339
5.6.1.4.4 Other Immunosuppressants 339
5.6.1.4.5 Antitumor Necrosis Factor Agents 339
5.6.1.5 Experimental Approaches 339
5.6.1.6 Complications to Avoid 339
5.6.1.7 Global Variation 339
5.6.2 Sweet’s Syndrome 340
5.6.2.1 Etiology and Pathophysiology 340
5.6.2.2 Clinical Characteristics and Diagnosis 340
5.6.2.2.1 Classical, Nonpustular Lesions 340
5.6.2.2.2 Superfi cial or Pustular Lesions 340
5.6.2.2.3 Subcutaneous Lesions 341
5.6.2.3 General Therapeutic Outline 341
5.6.2.4 Current Established Therapies 341
5.6.2.4.1 Systemic Corticosteroids 341
5.6.2.4.2 Topical Corticosteroids 341
5.6.2.4.3 Potassium Iodide and Colchicine 341
5.6.2.5 Experimental Approaches 341
5.6.2.6 Complications to Avoid 342
5.6.2.7 Global Variation 342
5.6.3 Erythema Elevatum Diutinum 342
5.6.3.1 Etiology and Pathophysiology 342
5.6.3.2 Clinical Characteristics and Diagnosis 342
5.6.3.3 General Therapeutic Outline 343
5.6.3.4 Current Established Therapies 343
5.6.3.5 Experimental Approaches 343
5.6.3.6 Complications to Avoid 343
5.6.3.7 Global Variation 343
5.6.4 Subcorneal Pustular Dermatosis (Sneddon-Wilkinson’s Disease) 343
5.6.4.1 Etiology and Pathophysiology 343
5.6.4.2 Clinical Characteristics and Diagnosis 343
5.6.4.3 General Therapeutic Outline 344
5.6.4.4 Current Established Therapies 344
5.6.4.5 Experimental Approaches 344
5.6.4.6 Complications to Avoid 344
5.6.4.7 Global Variation 344
5.6.5 Rheumatoid Neutrophilic Dermatosis 344
5.6.5.1 Etiology and Pathophysiology 344
5.6.5.2 Clinical Characteristics and Diagnosis 344
5.6.5.3 General Therapeutic Outline 345
5.6.5.4 Current Established Therapies 345
5.6.5.5 Experimental Approaches 345
5.6.5.6 Complications to Avoid 345
5.6.5.7 Global Variation 345
5.6.6 Neutrophilic EccrineHidradenitis (NEH) 345
5.6.6.1 Etiology and Pathophysiology 345
5.6.6.2 Clinical Characteristics and Diagnosis 345
5.6.6.3 General Therapeutic Outline 346
5.6.6.4 Current Established Therapies 346
5.6.6.5 Experimental Approaches 346
5.6.6.6 Global Variation 346
5.6.6.7 Pyodermatitis-Pyostomatitis Vegetans 346
5.6.6.8 Etiology and Pathophysiology 346
5.6.6.8 Clinical Characteristics and Diagnosis 346
5.6.6.10 General Therapeutic Outline 346
5.6.6.11 Current Established Therapies 346
5.6.6.12 Experimental Approaches 347
5.6.6.13 Complications to Avoid 347
5.6.6.14 Global Variation 347
References 347
Chapter 5.7 349
Skin Manifestations in Rheumatologic Disorders 349
5.7.1 Adult-Onset Still Disease 349
5.7.1.1 Etiology and Pathophysiology 349
5.7.1.2 Clinical Characteristicsand Diagnosis 350
5.7.1.3 General Therapeutic Outline 350
5.7.1.4 Current Established Therapies 350
5.7.1.5 Experimental Approaches 351
5.7.1.6 Complications to Avoid 351
5.7.1.7 Global Variations 351
5.7.2 Relapsing Polychondritis 351
5.7.2.1 Etiology and Pathophysiology 351
5.7.2.2 Clinical Characteristics and Diagnosis 352
5.7.2.3 General Therapeutic Outline 352
5.7.2.4 Current Established Therapies 353
5.7.2.5 Experimental Approaches 353
5.7.2.6 Complications to Avoid 353
5.7.2.7 Global Variations 353
5.7.3 Reiter Syndrome 353
5.7.3.1 Etiology and Pathophysiology 353
5.7.3.2 Clinical Characteristics and Diagnosis 354
5.7.3.3 General Therapeutic Outline 354
5.7.3.4 Current Established Therapies 354
5.7.3.5 Experimental Approaches 354
5.7.3.6 Complications to Avoid 354
5.7.3.7 Global Variations 355
References 355
Part VI: Acne and Rosacea 357
Acne and Its Variants 358
6.1.1 Introduction 358
6.1.2 Etiology and Pathophysiology 358
6.1.3 Clinical Characteristics and Diagnosis 359
6.1.4 Acne Variants and Syndromes 360
6.1.5 General Therapeutic Outlines 362
6.1.6 Currently Established Therapies 362
6.1.7 Systemic Treatments 365
6.1.8 Complications to Avoid 367
6.1.9 Acneiform Dermatoses 367
6.1.10 Experimental Approaches 368
6.1.11 Global Variation 369
References 369
Rosacea and Related Diseases 373
6.2.1 Introduction 373
6.2.2 Etiology and Pathophysiology 373
6.2.3 Clinical Characteristics and Diagnosis 374
6.2.3.1 Erythematotelangiectatic Subtype 375
6.2.3.2 Papulopustular Rosacea Subtype 376
6.2.3.3 Phymatous Rosacea Subtype 376
6.2.3.4 Ocular Rosacea Subtype 376
6.2.3.5 Granulomatous Rosacea Variant 376
6.2.4 General Therapeutic Outlines 377
6.2.5 Currently Established Therapies 379
6.2.5.1 Phymatous Rosacea (Subtype III, Stage 4) 380
6.2.5.2 Ocular Rosacea (Subtype IV) 380
6.2.5.3 Granulomatous Variant 381
6.2.5.4 Rosacea Conglobata 381
6.2.6 Rosacea-Related Disorders 381
6.2.6.1 Rosacea Fulminans 381
6.2.6.2 Steroid-Induced Acneiform Eruption 381
6.2.6.3 Perioral Dermatitis 381
6.2.6.4 Persistant Edema in Rosacea (Morbihan’s Disease) 381
6.2.7 Complications to Avoid 382
6.2.8 Experimental Approaches 382
6.2.9 Global Variation 382
References 383
Part VII: Autoimmune Diseases 385
Chapter 7.1 386
Acquired Bullous Disease 386
7.1.1 Etiology and Pathophysiology 386
7.1.1.1 Pemphigus Group 386
7.1.1.2 Bullous Pemphigoid 387
7.1.2 Clinical Characteristics and Diagnosis 388
7.1.2.1 Clinical Characteristics 388
7.1.2.1.1 Pemphigus Vulgaris 388
7.1.2.1.2 Pemphigus Foliaceus 388
7.1.2.1.3 Paraneoplastic Pemphigus 389
7.1.2.1.4 Bullous Pemphigoid 390
7.1.2.1.5 Epidermolysis Bullosa Acquisita 390
7.1.2.2 Diagnosis 390
7.1.3 General Therapeutic Outline 391
7.1.4 Current Established Therapies 391
7.1.4.1 Systemic Treatment 391
7.1.4.2 Topical Treatment 396
7.1.5 Experimental Approaches 396
7.1.6 Complications to Avoid 397
7.1.7 Global Variation 399
7.1.7.1 Choice of Adjuvant Therapy 399
7.1.7.2 Corticosteroids Alone or In Combination with Immunosuppressants 399
References 399
Chapter 7.2 403
Connective Tissue Diseases 403
7.2.1 Systemic Lupus Erythematosus 403
7.2.2 Etiology and Pathophysiology 403
7.2.3 Clinical Characteristics and Diagnosis 404
7.2.3.1 Clinical Features 404
7.2.3.2 Skin Lesion 404
7.2.3.3 Laboratory Findings 405
7.2.4 General Therapeutic Outline 406
7.2.5 Current Established Therapies 406
7.2.5.1 Topical Therapy of the Skin 406
7.2.5.2 Nonsteroidal Systemic Therapy 406
7.2.5.3 Systemic Corticosteroids 406
7.2.5.4 Immunosuppressive Agents 406
7.2.5.5 Other Therapies 407
7.2.6 Experimental Approaches 407
7.2.7 Complications to Avoid 407
7.2.8 Global Variations 407
7.2.9 Systemic Sclerosis 408
7.2.10 Etiology and Pathophysiology 408
7.2.11 Clinical Characteristics and Diagnosis 408
7.2.11.1 Diagnosis 408
7.2.11.2 Classification 409
7.2.11.3 Autoantibody 410
7.2.11.4 Clinical Parameters 410
7.2.12 General Therapeutic Outline 410
7.2.13 Current Established Therapies 410
7.2.13.1 Vascular Injury 410
7.2.13.2 Tissue Fibrosis 411
7.2.13.3 Other Features 411
7.2.14 Experimental Approaches 411
7.2.15 Complications to Avoid 411
7.2.16 Global Variations 412
7.2.17 Dermatomyositis 412
7.2.18 Etiology and Pathophysiology 412
7.2.19 Clinical Characteristics and Diagnosis 412
7.2.19.1 Diagnostics and Classification 412
7.2.19.2 Clinical Features 413
7.2.19.3 Autoantibodies 414
7.2.20 General Therapeutic Outline 415
7.2.21 Current Established Therapies [73] 415
7.2.22 Experimental Approaches 415
7.2.23 Complications to Avoid 416
7.2.24 Global Variations 416
7.2.25 Polyarteritis Nodosa 416
7.2.26 Etiology and Pathophysiology 416
7.2.27 Clinical Characteristics and Diagnosis 417
7.2.27.1 Epidemiology 417
7.2.27.2 Classification 417
7.2.27.3 Clinical Features 417
7.2.28 General Therapeutic Outline 419
7.2.29 Current Established Therapies 419
7.2.30 Experimental Approaches 419
7.2.31 Complications to Avoid 419
7.2.32 Global Variations 420
References 420
Chapter 7.3 423
Cutaneous Vasculitis 423
7.3.1 Etiology and Pathophysiology 423
7.3.2 Clinical Characteristics and Diagnosis 423
7.3.3 General Therapeutic Outline 425
7.3.4 Current Established Therapy 425
7.3.5 Experimental Approaches 426
7.3.6 Global Variations 427
References 427
Chapter 7.4 429
Graft-Versus-Host Disease 429
7.4.1 Etiology and Pathophysiology 429
7.4.1.1 Acute GVHD (aGVHD) 429
7.4.1.2 Chronic GVHD (cGVHD) 430
7.4.2 Clinical Characteristics Diagnosis and Grading 430
7.4.2.1 aGVHD 430
7.4.2.1.1 Clinical Characteristics 430
7.4.2.1.2 Diagnosis 430
7.4.2.1.3 Grading of aGVHD 430
7.4.2.2 cGvHD 430
7.4.2.2.1 Clinical Characteristics 430
7.4.2.2.2 Diagnosis 431
7.4.2.2.3 Grading of cGVHD 431
7.4.3 General Therapeutic Outline 431
7.4.3.1 aGVHD 431
7.4.3.2 cGVHD 432
7.4.4 Current Established Prophylactic and Therapeutic Modalities 432
7.4.4.1 aGVHD 432
7.4.4.1.1 T-Cell Depletion 432
7.4.4.1.2 Posttransplant Prophylaxis 432
7.4.4.1.3 First-Line Therapy of Established aGVHD 432
7.4.4.2 cGVHD 433
7.4.4.2.1 T-Cell Depletion 433
7.4.4.2.2 First-Line Therapy for cGVHD 433
7.4.5 Second-Line Therapies and Experimental Approaches 433
7.4.5.1 Experimental Approaches to Prophylaxis 433
7.4.5.2 Second-Line Therapies and Experimental Approaches to Therapy 433
7.4.5.2.1 Strategies for Steroid-Refractory aGVHD 433
7.4.5.2.2 Strategies for Steroid-Refractory cGVHD 434
7.4.6 Complications to Avoid 434
7.4.6.1 Overtreatment 434
7.4.6.2 Infectious Complications 435
7.4.6.2.1 Infectious Complications of aGVHD 435
7.4.6.2.2 Infectious Complications of cGVHD 435
7.4.6.3 Drug Toxicity and Interactions 435
7.4.7 Global Variations 435
References 435
Chapter 7.5 438
Vitiligo 438
7.5.1 Etiology and Pathophysiology 438
7.5.2 Clinical Characteristics and Diagnosis 438
7.5.3 General Therapeutic Outline 438
7.5.4 Medical Repigmentation Therapies 439
7.5.4.1 Conventional Therapeutic Approaches 439
7.5.4.1.1 Psoralens and Ultraviolet Light (PUVA) 439
Oral PUVA 439
PUVASOL 440
Topical PUVA 441
Other Forms of Photo(Chemo)therapy 441
7.5.4.1.2 Steroids 441
Topical Steroids 441
Intralesional Steroids 441
Systemic Steroids 441
7.5.4.2 Recent Therapeutic Approaches 442
7.5.4.2.1 Recent Phototherapies 442
Narrow-Band UVB Phototherapy (NB-UVB) 442
Targeted Phototherapies 442
308 nm Excimer Laser 442
308-nm Monochromatic Excimer Light 442
7.5.4.2.2 Recent Topical Agents 443
Topical Calcineurin Inhibitors (Tacrolimus, Pimecrolimus) 443
Topical Vitamin D Derivatives (Calcipotriene, Tacalcitol) 443
7.5.4.2.3 Combination Therapies 443
7.5.4.3 Antioxidant Therapies 443
7.5.4.3.1 Pseudocatalase 443
7.5.4.3.2 Ginko Biloba 444
7.5.5 Surgical Repigmentation Therapies 444
7.5.5.1 Tissue Grafts 444
7.5.5.1.1 Full-Thickness Punch Grafting (“Minigrafting”) 444
7.5.5.1.2 Split-Thickness Grafting 444
7.5.5.1.3 Suction Blister Grafting 444
7.5.5.1.4 Comparison of Tissue Grafting Techniques 444
7.5.5.2 Cellular Grafts 444
7.5.5.2.1 Transplantation of Noncultured Autologous Epidermal Cell Suspensions 445
7.5.5.2.2 Transplantation of In Vitro-Cultured Pure Melanocytes 445
7.5.5.2.3 Transplantation of In Vitro-Cultured Autologous Epidermis 445
7.5.5.2.4 Comparison of Cell Grafting Techniques 445
7.5.5.3 Choice of A Surgical Technique 445
7.5.6 Other Therapies 445
7.5.6.1 Depigmentation 445
7.5.6.1.1 Bleaching Agents 445
7.5.6.1.2 Laser Therapy 447
7.5.6.2 Micropigmentation 447
7.5.6.3 Camouflage 447
7.5.6.4 Sun Protection 447
7.5.6.5 Counseling 447
7.5.7 Future Directions 447
7.5.8 Global Variations 448
References 448
Chapter 7.6 453
Therapy of Noninfectious Granulomatous Diseases 453
7.6.1 Sarcoidosis 453
7.6.1.1 Etiology and Pathophysiology 453
7.6.1.2 Clinical Characteristics and Diagnosis 453
7.6.1.3 General Therapeutic Outline 454
7.6.1.4 Current Established Therapies 454
7.6.1.5 Experimental Approaches 454
7.6.1.6 Complications to Avoid 455
7.6.2 Granuloma Annulare 455
7.6.2.1 Etiology and Pathophysiology 455
7.6.2.2 Clinical Characteristics and Diagnosis 455
7.6.2.3 General Therapeutic Outline 455
7.6.2.4 Current Established Therapies 455
7.6.2.5 Experimental Approaches 456
7.6.2.6 Complications to Avoid 456
7.6.3 Necrobiosis Lipoidica 456
7.6.3.1 Etiology and Pathophysiology 456
7.6.3.2 Clinical Characteristics and Diagnosis 456
7.6.3.3 General Therapeutic Outline 456
7.6.3.4 Current Established Therapies 456
7.6.3.5 Experimental Approaches 457
7.6.3.6 Complications to Avoid 457
7.6.4 Necrobiotic Xathogranuloma 457
7.6.4.1 Etiology and Pathophysiology 457
7.6.4.2 Clinical Characteristics and Diagnosis 457
7.6.4.3 General Therapeutic Outline 457
7.6.4.4 Current Established Therapies 458
7.6.4.5 Experimental Approaches 458
7.6.4.6 Complications to Avoid 458
7.6.5 Miscellanea 458
7.6.5.1 Rheumatoid Nodule 458
7.6.5.2 Elastolytic Granuloma 458
7.6.5.3 Metastatic Crohn’s Disease 458
7.6.5.4 Granulomatous Rosacea and Perioral Dermatitis 458
7.6.5.5 Lupus Miliaris Disseminatus Faciei 459
7.6.5.6 Foreign Body Granulomas 459
7.6.5.7 Cutaneous Granulomas Associated with Primary Immunodeficiency Disorders and Lymphomas 459
7.6.5.8 Interstitial granulomatous dermatitis 459
7.6.5.9 Global Variations 459
References 459
Part VIII: Metabolic Diseases 461
The Porphyrias 462
8.1.1 Etiology and Pathophysiology 462
8.1.1.1 Enzymatic and Molecular Defects Underlying the Porphyrias 462
8.1.1.1.1 Porphyria Cutanea Tarda (PCT) 462
8.1.1.1.2 Erythropoietic Protoporphyria (EPP) 463
8.1.1.1.3 Congenital Erythropoietic Porphyria (CEP) 463
8.1.1.1.4 Hepatoerythropoietic Porphyria (HEP) 464
8.1.1.1.5 Acute Intermittent Porphyria (AIP) 464
8.1.1.1.6 Variegate Porphyria (VP) 464
8.1.1.1.7 Hereditary Coproporphyria (HCP) 464
8.1.1.1.8 d - Aminolevulinic Acid Dehydratase (ALAD) Deficiency Porphyria 464
8.1.1.2 Etiopathology of the Cutaneous Symptoms 465
8.1.1.3 Etiopathology of the Acute Porphyric Attack 465
8.1.2 Clinical Characteristics and Diagnosis 465
8.1.2.1 Classifi cation 465
8.1.2.2 Clinic of the Nonacute Porphyrias 466
8.1.2.2.1 Porphyria Cutanea Tarda 466
8.1.2.2.2 Erythropoietic Protoporphyria 467
8.1.2.2.3 Congenital Erythropoietic Porphyria 467
8.1.2.2.4 Hepatoerythropoietic Porphyria 469
8.1.2.3 Clinic of the Acute Porphyrias 469
8.1.2.4 Diagnostic Tests 470
8.1.3 General Therapeutic Outline 472
8.1.4 Current Established Therapies 472
8.1.4.1 Therapy of the Nonacute Porphyrias 472
8.1.4.2 Therapy of the Acute Porphyrias 473
8.1.4.2.1 Therapy of the Cutaneous Symptoms 473
8.1.4.2.2 Therapy of an Acute Porphyric Attack 473
8.1.5 Experimental Approaches 473
8.1.5.1 Bone Marrow Transplantation 473
8.1.5.2 Liver Transplantation 475
8.1.5.3 Combined Liver and Bone Marrow Transplantation 475
8.1.5.4 Therapy with [Nle4, D-Phe7]-Alpha-Melanocyte Stimulating Hormone 475
8.1.5.5 Enzyme Replacement Therapy 476
8.1.5.6 Gene Therapy 476
8.1.6 Complications to Avoid 477
References 477
Chapter 8.2 480
Deposition Diseases 480
8.2.1 Amyloidosis 480
8.2.1.1 Etiology and Pathophysiology 480
8.2.1.2 Clinical Characteristics and Diagnosis 480
8.2.1.3 General Therapeutic Outline 481
8.2.1.4 Current Established Therapies 481
8.2.1.5 Complications to Avoid 481
8.2.1.7 Global Variations 482
8.2.2 Xanthoma 482
8.2.2.1 Etiology and Pathophysiology 482
8.2.2.2 Clinical Characteristics and Diagnosis 482
8.2.2.3 General Therapeutic Outline 483
8.2.2.4 Current Established Therapies 483
8.2.3 Fabry Disease 483
8.2.3.1 Etiology and Pathophysiology 483
8.2.3.2 Clinical Characteristics and Diagnosis 484
8.2.3.3 General Therapeutic Outline 484
8.2.3.4 Current Established Therapies 484
8.2.3.5 Experimental Approach 484
8.2.4 Calcinosis Cutis 484
8.2.4.1 Etiology and Pathophysiology 485
8.2.4.2 Clinical Characteristics and Diagnosis 485
8.2.4.3 General Therapeutic Outline 485
8.2.4.4 Current Established Therapies 485
8.2.4.5 Experimental Approaches 485
8.2.4.6 Complications to Avoid 486
8.2.5 Hemochromatosis 486
8.2.5.1 Etiology and Pathophysiology 486
8.2.5.2 Clinical Characteristics and Diagnosis 487
8.2.5.3 General Therapeutic Outline 487
8.2.5.4 Current Established Therapies 487
8.2.5.5 Experimental Approach 487
8.2.5.6 Complications to Avoid 487
8.2.5.7 Global Variations 487
References 487
Part IX: Cosmetic Dermatology 489
Chapter 9.1 490
Hair Diseases (Alopecia Areata and Androgenetic Alopecia) 490
9.1.1 Alopecia Areata 490
9.1.1.1 Etiology and Pathophysiology 490
9.1.1.2 Clinical Characteristics and Diagnosis 491
9.1.1.3 General Therapeutic Outline 491
9.1.1.4 Current Established Therapies 491
9.1.1.4.1 Topical Corticosteroids 491
9.1.1.4.2 Intralesional Corticosteroids 491
9.1.1.4.3 Systemic Corticosteroids 491
9.1.1.4.4 Topical Immunotherapy 491
9.1.1.4.5 Minoxidil 492
9.1.1.4.6 Dithranol (Anthralin) 492
9.1.1.4.7 Photochemotherapy 492
9.1.1.4.8 Wigs 492
9.1.1.5 Experimental Approaches 492
9.1.1.5.1 Steroid Pulse Therapy 492
9.1.1.5.2 Ciclosporin 492
9.1.1.5.3 Aromatherapy 493
9.1.1.5.4 Biologic Immunomodulators 493
9.1.1.6 Complications to Avoid 493
9.1.1.7 Global Variations 493
9.1.2 Androgenetic Alopecia 493
9.1.2.1 Etiology and Pathophysiology 493
9.1.2.2 Clinical Characteristics and Diagnosis 494
9.1.2.3 General Therapeutic Outline 494
9.1.2.4 Current Established Therapies 494
9.1.2.4.1 Finasteride 494
9.1.2.4.2 Minoxidil 494
9.1.2.4.3 Other Agents for FAGA 495
9.1.2.4.4 Hair Transplantation 495
9.1.2.5 Experimental Approaches 496
9.1.2.5.1 Ketoconazole Lotion 496
9.1.2.5.2 Finasteride for FAGA 496
9.1.2.6 Complications to Avoid 496
9.1.2.7 Global Variations 496
References 496
Chapter 9.2 499
Nail Diseases 499
9.2.1 Nail Psoriasis 499
9.2.1.1 Etiology and Pathophysiology 499
9.2.1.2 Clinical Characteristics and Diagnosis 499
9.2.1.3 General Therapeutic Outline 500
9.2.1.4 Current Established Therapies 500
9.2.1.4.1 Topical Therapy 500
9.2.1.4.2 Intralesional Therapy 501
9.2.1.4.3 Systemic Therapy 501
9.2.1.5 Biologic Approaches 501
9.2.1.6 Complications to Avoid 501
9.2.2 Onychomycosis 502
9.2.2.1 Etiology and Pathophysiology 502
9.2.2.2 Clinical Characteristics and Diagnosis 502
9.2.2.3 General Therapeutic Outline 503
9.2.2.4 Current Established Therapies 503
9.2.2.4.1 Topical Therapy 503
9.2.2.5 Systemic Therapy 503
9.2.2.5.1 Combination Therapy 503
9.2.2.5.2 Other Therapies 503
9.2.2.6 Experimental Approaches 504
9.2.2.6.1 Boosted Therapy 504
9.2.2.6.2 New Antifungals 504
9.2.2.7 Complications to Avoid 504
9.2.2.8 Global Variations 504
References 504
Chapter 9.4 506
Hyperhidrosis 506
9.3.1 Etiology and Pathophysiology 506
9.3.1.1 Introduction 506
9.3.1.2 Background 506
9.3.1.3 Histopathology 506
9.3.1.4 Pathophysiology 507
9.3.1.5 Etiology 507
9.3.2 Clinical Characteristics and Diagnosis 508
9.3.2.1 Primary Hyperhidrosis 508
9.3.2.2 Secondary Hyperhidrosis 508
9.3.3 General Therapeutic Outline 508
9.3.4.1 Topical Therapy 508
9.3.4.2 Systemic Therapy 508
9.3.4.3 Iontophoresis 509
9.3.4.4 Botulinum Toxin 509
9.3.4.5 Surgical Treatment 510
9.3.4.5.1 Sympathectomy 510
9.3.4.5.2 Surgical Removal of Eccrine Glands 510
9.3.5 Experimental Approaches 510
9.3.6 Complications to Avoid 510
9.3.7 Global Variations 511
References 511
Chapter 9.4 514
Disorders of Pigmentation 514
9.4.1 Melasma 514
9.4.1.1 Etiology and Pathophysiology 514
9.4.1.2 Clinical Characteristics and Diagnosis 514
9.4.1.3 General Therapeutic Outline 515
9.4.1.4 Current Established Therapies 515
9.4.1.5 Complications to Avoid 515
9.4.1.6 Global Variations 515
9.4.2 Solar Lentigo 515
9.4.2.1 Etiology and Pathophysiology 515
9.4.2.2 Clinical Characteristics and Diagnosis 515
9.4.2.3 General Therapeutic Outline 516
9.4.2.4 Current Established Therapies 516
9.4.2.5 Experimental Approaches 516
9.4.2.6 Complications to Avoid 516
9.4.2.7 Global Variations 516
9.4.3 Ephelides (Freckles) 517
9.4.3.1 Etiology and Pathophysiology 517
9.4.3.2 Clinical Characteristics and Diagnosis 517
9.4.3.3 General Therapeutic Outline 517
9.4.3.4 Current Established Therapies 517
9.4.3.5 Experimental Approaches 517
9.4.3.6 Complications to Avoid 517
9.4.3.7 Global Variations 518
9.4.4 Nevus Spilus (Speckled Lentiginous Nevus) 518
9.4.4.1 Etiology and Pathophysiology 518
9.4.4.2 Clinical Characteristics and Diagnosis 518
9.4.4.3 General Therapeutic Outline 518
9.4.4.4 Current Established Therapies 518
9.4.4.5 Experimental Approaches 519
9.4.4.6 Complications to Avoid 519
9.4.4.7 Global Variations 519
9.4.5 Postinfl ammatory Hyperpigmentation 519
9.4.5.1 Etiology and Pathophysiology 519
9.4.5.2 Clinical Characteristics and Diagnosis 519
9.4.5.3 General Therapeutic Outline 519
9.4.5.4 Current Established Therapies 519
9.4.5.5 Complications to Avoid 520
9.4.5.6 Global Variations 520
9.4.6 Acquired Bilateral Nevus of Ota-Like Macules (ABNOM) 520
9.4.6.1 Etiology and Pathophysiology 520
9.4.6.2 Clinical Characteristics and Diagnosis 520
9.4.6.3 General Therapeutic Outline 521
9.4.6.4 Current Established Therapies 521
9.4.6.5 Experimental Approaches 521
9.4.6.6 Complications to Avoid 521
9.4.6.7 Global Variations 521
9.4.7 Nevus of Ota 521
9.4.7.1 Etiology and Pathophysiology 521
9.4.7.2 Clinical Characteristics and Diagnosis 521
9.4.7.3 General Therapeutic Outline 521
9.4.7.4 Current Established Therapies 522
9.4.7.5 Complications to Avoid 522
9.4.7.6 Global Variations 522
9.4.8 Vitiligo 522
9.4.8.1 Etiology and Pathophysiology 522
9.4.8.2 Clinical Characteristics and Diagnosis 522
9.4.8.3 General Therapeutic Outline 523
9.4.8.4 Current Established Therapies 523
9.4.8.5 Experimental Approaches 523
9.4.8.6 Complications to Avoid 524
9.4.8.7 Global Variations 524
References 524
Chapter 9.5 527
Cosmetic Surgery 527
9.5.1 Etiology and Pathophysiology 527
9.5.2 Clinical Characteristics and Diagnosis 528
9.5.3 General Therapeutic Outline 528
9.5.4 Current Established Therapies 529
9.5.4.1 Q-Switched Lasers 529
9.5.4.2 Electrodessication and Curettage, Cryotherapy, or Scissor Excision 529
9.5.4.3 Pulsed-Dye Laser, KTP Laser, and Intense Pulsed Light Devices 529
9.5.4.4 Prepackaged Injectable Soft-Tissue Augmentation Materials 530
9.5.4.5 Ablative and Fractional Facial Resurfacing 530
9.5.4.6 Rytidectomy, Blepharoplasty, and Brow Lifting 531
9.5.4.7 Liposuction 531
9.5.4.8 Treatment of Leg Veins 531
9.5.5 Experimental Approaches 531
9.5.6 Complications to Avoid 532
9.5.7 Global Variations 532
Further Reading 532
Part X: Inherited Diseases 534
Chapter 10.1 535
Inherited Bullous Diseases 535
10.1.1 Etiology and Pathophysiology 535
10.1.2 Clinical Characteristicsand Diagnosis 536
10.1.2.1 Epidermolysis Bullosa Simplex 536
10.1.2.2 EB Simplex with MuscularDystrophy 536
10.1.2.3 EB Simplex with Pyloric Atresia 539
10.1.2.4 Junctional Epidermolysis Bullosa 539
10.1.2.4.1 Junctional EB Herlitz 539
10.1.2.4.2 Junctional EB Non-Herlitz 539
10.1.2.4.3 Junctional EB with Pyloric Atresia 539
10.1.2.5 Dystrophic EpidermolysisBullosa 540
10.1.2.5.1 Dominant Dystrophic EB 540
10.1.2.5.2 Non-Hallopeau-SiemensRecessive Dystrophic EB 540
10.1.2.5.3 Hallopeau-Siemens RecessiveDystrophic EB 540
10.1.2.5.4 Lethal AcantolythicEpidermolysis Bullosa 540
10.1.2.5.5 Kindler Syndrome 540
10.1.3 General Therapeutic Outline 541
10.1.4 Current Established Therapies 541
10.1.4.1 Topical Medication 541
10.1.4.2 Systemic Therapy 541
10.1.4.3 Surgery 542
10.1.4.4 Skin Cancer Screening 542
10.1.4.5 Nutrition 542
10.1.4.6 Dental Care 542
10.1.4.7 Physical Therapy 542
10.1.4.8 Psychological Support 542
10.1.4.9 Genetic Counseling 542
10.1.5 Experimental Approaches 543
10.1.6 Complications to Avoid 543
10.1.7 Global Variations 544
References 544
Chapter 10.2 546
Inherited Keratinocyte Diseases (Ichthyosis and Related Disorders) 546
10.2.1 Ichthyosis Vulgaris 546
10.2.1.1 Etiology and Pathophysiology 546
10.2.1.2 Clinical Characteristicsand Diagnosis 546
10.2.1.3 General Therapeutic Outline 546
10.2.1.4 Current Established Therapies 547
10.2.1.5 Complications to Avoid 547
10.2.1.6 Global Variations 547
10.2.2 X-linked Recessive Ichthyosis 547
10.2.2.1 Etiology and Pathophysiology 547
10.2.2.2 Clinical Characteristicsand Diagnosis 547
10.2.2.3 General Therapeutic Outline 547
10.2.2.4 Current Established Therapies 547
10.2.2.5 Experimental Approaches 548
10.2.2.6 Complications to Avoid 548
10.2.2.7 Global Variations 548
10.2.3 Autosomal Recessive Ichthyosis (Lamellar Ichthyosis, Nonbullous Congenital Ichthyosiform Erythroderma, and Harlequin Ichthyosis) 548
10.2.3.1 Etiology and Pathophysiology 548
10.2.3.2 Clinical Characteristicsand Diagnosis 548
10.2.3.3 General Therapeutic Outline 548
10.2.3.4 Current Established Therapies 548
10.2.3.5 Experimental Approaches 549
10.2.3.6 Complications to Avoid 549
10.2.3.7 Global Variations 549
10.2.4 Bullous CongenitalIchthyosiform Erythroderma 549
10.2.4.1 Etiology and Pathophysiology 549
10.2.4.2 Clinical Characteristicsand Diagnosis 550
10.2.4.3 General Therapeutic Outline 550
10.2.4.4 Current Established Therapies 550
10.2.4.5 Experimental Approaches 550
10.2.4.6 Complications to Avoid 550
10.2.4.7 Global Variations 550
10.2.5 Netherton’s Syndrome 550
10.2.5.1 Etiology and Pathophysiology 550
10.2.5.2 Clinical Characteristicsand Diagnosis 551
10.2.5.3 General Therapeutic Outline 551
10.2.5.4 Current Established Therapies 551
10.2.5.5 Experimental Approaches 551
10.2.5.6 Complications to Avoid 551
10.2.5.7 Global Variations 551
10.2.6 Sjögren-Larsson syndrome 551
10.2.6.1 Etiology and Pathophysiology 551
10.2.6.2 Clinical Characteristicsand Diagnosis 551
10.2.6.3 General Therapeutic Outline 552
10.2.6.4 Current EstablishedTherapies 552
10.2.6.5 Experimental Approaches 552
10.2.6.6 Complications to Avoid 552
10.2.6.7 Global Variations 552
10.2.7 Darier’s Disease 552
10.2.7.1 Etiology and Pathophysiology 552
10.2.7.2 Clinical Characteristicsand Diagnosis 552
10.2.7.3 General Therapeutic Outline 553
10.2.7.4 Current Established Therapies 553
10.2.7.5 Complications to Avoid 553
10.2.7.6 Global Variations 553
10.2.8 Palmoplanter Keratoderma 553
10.2.8.1 Etiology and Pathophysiology 553
10.2.8.2 Clinical Characteristicsand Diagnosis 553
10.2.8.3 General Therapeutic Outline 553
10.2.8.4 Current Established Therapies 553
10.2.8.5 Complications to Avoid 557
10.2.8.6 Global Variations 557
References 557
Chapter 10.3 559
Immunodefi ciency Disorders 559
10.3.1 Chronic Mucocutaneous Candidiasis (CMC) 559
10.3.1.1 Etiology and Pathophysiology 559
10.3.1.2 Clinical Characteristics and Diagnosis 559
10.3.1.3 General Therapeutic Outline 559
10.3.1.4 Current Established Therapies 559
10.3.1.5 Experimental Approaches 559
10.3.1.6 Complications to Avoid 560
10.3.1.7 Global Variations 560
10.3.2 Cartilage-Hair Hypoplasia Syndrome (CHHS) 560
10.3.2.1 Etiology and Pathophysiology 560
10.3.2.2 Clinical Characteristics and Diagnosis 560
10.3.2.3 General Therapeutic Outline 560
10.3.2.4 Experimental Approaches 560
10.3.2.5 Global Variations 560
10.3.3 Severe Combined Immunodefi ciency 561
10.3.3.1 Etiology and Pathophysiology 561
10.3.3.2 Clinical Characteristics and Diagnosis 561
10.3.3.3 Current Established Therapies 561
10.3.3.4 Experimental Approaches 561
10.3.3.5 Complications to Avoid 561
10.3.3.6 Global Variations 561
10.3.4 Hypohidrotic Ectodermal Dysplasia with Immunodeficiency (HED-ID) 561
10.3.4.1 Etiology and Pathophysiology 562
10.3.4.2 Clinical Characteristics and Diagnosis 562
10.3.4.3 Current Established Therapies 562
10.3.4.4 Complications to Avoid 562
10.3.4.5 Global Variations 562
10.3.5 Ataxia-Telangiectasia (AT) 562
10.3.5.1 Etiology and Pathophysiology 562
10.3.5.2 Clinical Characteristics and Diagnosis 562
10.3.5.3 Current Established Therapies 562
10.3.5.4 Experimental Approaches 563
10.3.5.5 Complications to Avoid 563
10.3.5.6 Global Variations 563
10.3.6 Antibody Defi ciencies Disorders 563
10.3.6.1 Etiology and Pathophysiology 563
10.3.6.2 Clinical Characteristics and Diagnosis 563
10.3.6.3 Current Established Therapies 564
10.3.6.4 Experimental Approaches 564
10.3.6.5 Complications to Avoid 564
10.3.6.6 Global Variations 564
10.3.7 Wiskott-Aldrich Syndrome (WAS) 564
10.3.7.1 Etiology and Pathophysiology 564
10.3.7.2 Clinical Characteristicsand Diagnosis 564
10.3.7.3 General Therapeutic Outline 565
10.3.7.4 Current Established Therapies 565
10.3.7.5 Experimental Approaches 565
10.3.7.6 Global Variations 565
10.3.8 Complement Disorders 565
10.3.8.1 Etiology and Pathophysiology 565
10.3.8.2 Clinical Characteristics and Diagnosis 565
10.3.8.3 Current Established Therapies 566
10.3.8.4 Experimental Approaches 566
10.3.8.5 Complications to Avoid 566
10.3.8.6 Global Variations 566
10.3.9 Chronic Granulomatous Disease (CGD) 567
10.3.9.1 Etiology and Pathophysiology 567
10.3.9.2 Clinical Characteristics and Diagnosis 567
10.3.9.3 Current Established Therapies 567
10.3.9.4 Experimental Approaches 567
10.3.9.5 Complications to Avoid 567
10.3.9.6 Global Variations 568
10.3.10 Leukocyte Adhesion Deficiency (LAD) 568
10.3.10.1 Etiology and Pathophysiology 568
10.3.10.2 Clinical Characteristics and Diagnosis 568
10.3.10.3 Current Established Therapies 568
10.3.10.4 Experimental Approaches 568
10.3.10.5 Global Variations 568
10.3.11 Hyperimmunoglobulinemia E Syndrome (HIES) 569
10.3.11.1 Etiology and Pathophysiology 569
10.3.11.2 Clinical Characteristics and Diagnosis 569
10.3.11.3 Current Established Therapies 569
10.3.11.4 Experimental Approaches 569
10.3.11.5 Complications to Avoid 569
10.3.11.6 Global Variations 569
10.3.12 Silvery Hair Syndromes 570
10.3.12.1 Etiology and Pathophysiology 570
10.3.12.2 Clinical Characteristics and Diagnosis 570
10.3.12.3 Current Established Therapies 570
10.3.12.4 Experimental Approaches 570
10.3.12.5 Global Variations 571
References 571
Chapter 10.4 573
Disorders of DNA repair 573
10.4.1 What is DNA repair? 573
10.4.2 Clinical Characteristicsand Diagnosis of DisordersRelated to DNA Repair Defi ciency 574
10.4.2.1 XP 574
10.4.2.2 CS 575
10.4.2.3 TTD 575
10.4.3 Management of Patientswith XP, CS or TTD andTherapeutic Outline 575
10.4.4 Experimental Approaches 576
10.4.5 Global Variations 578
References 578
Part XI: Benign and Malignant Tumors 580
Chapter 11.1 581
Nonmelanoma Skin Cancer 581
11.1.1 BCC 582
11.1.1.1 Etiology and Pathophysiology 582
11.1.2 Clinical Characteristics and Diagnosis 583
11.1.3 General Therapeutic Outline 585
11.1.4 Current Established Therapies 587
11.1.5 Experimental Approaches 589
11.1.6 SCC 590
11.1.6.1 Etiology and Pathophysiology 590
11.1.6.2 Clinical Characteristics and Diagnosis 591
11.1.6.2.1 Actinic Keratosis 591
11.1.6.2.2 SCC In situ (Bowen’s Disease) 592
11.1.6.2.3 Invasive SCC 592
11.1.6.3 General Therapeutic Outline 593
11.1.6.4 Current Established Therapies 595
11.1.6.4.1 Preventive Treatments 595
11.1.6.4.2 Topical Treatment of SCCsor Precurs or Lesions 595
11.1.6.5 Experimental Approaches 597
11.1.6.6 Complications to Avoid 597
11.1.7 Global Variations 598
References 598
Chapter 11.2 603
Malignant Melanoma 603
11.2.1 Epidemiology, Etiology and Pathogenesis 603
11.2.2 Classifi cation and Diagnosis 604
11.2.2.1 Classifi cation 604
11.2.2.2 Clinical Diagnosis and Dermoscopy 605
11.2.2.2.1 Clinical Diagnosis and Criteria 605
11.2.2.2.2 Diagnosis with Dermoscopy 606
11.2.2.3 Histopathologic and Genetic Diagnosis 606
11.2.3 General Therapeutic Outline 607
11.2.3.1 Staging and Prognosis 607
11.2.3.2 Clinical Guidelines for Management of Cutaneous Melanoma 608
11.2.4 Current Therapies and Management 608
11.2.4.1 Surgical Treatment of Primary Lesions 608
11.2.4.2 Sentinel Lymph Node Biopsy 608
11.2.4.3 Adjuvant Therapy for High-Risk Patients 609
11.2.4.4 Management of Metastatic Lesions 609
11.2.5 Experimental Approaches 610
11.2.5.1 Immunotherapy 610
11.2.5.2 Gene Therapy and Molecular Targeting Therapy 610
11.2.6 Complications to Avoid 610
11.2.7 Global Variations 611
References 612
Chapter 11.3 615
Treatment of Cutaneous Lymphomas 615
11.3.1 Introduction 615
11.3.2 General Aspects 616
11.3.3 Treatment of Cutaneous T-Cell Lymphoma 616
11.3.3.1 Patch/Plaque Disease 617
11.3.3.1.1 Phototherapies 618
11.3.3.1.2 Total-Skin Topical Chemotherapy 618
11.3.3.1.3 Total-Skin Radiation Therapy 618
11.3.3.2 Erythroderma 619
11.3.3.2.1 Retinoid Therapy 619
11.3.3.2.2 Extracorporeal Photophoresis 619
11.3.3.2.3 a -Interferon 620
11.3.3.3 Cytotoxic Chemotherapy 620
11.3.3.4 Novel Approved Treatment Modalities for CTCL 620
11.3.3.4.1 DAB 389 IL-2 620
11.3.3.4.2 Alemtuzumab 621
11.3.3.4.3 Histone Deacetylase Inhibitors 621
11.3.4 Treatment of Primary Cutaneous B Cell Lymphoma 622
11.3.4.1 Rituximab 622
References 622
Chapter 11.4 624
Vascular Malformations 624
11.4.1 Etiology and Pathogenesis 624
11.4.1.1 Capillary Malformations 624
11.4.1.2 Venous Malformations 626
11.4.1.3 Lymphatic Malformations 626
11.4.1.4 Arteriovenous Malformations 627
11.4.2 Clinical Characteristics and Diagnosis 628
11.4.2.1 Capillary Malformations 628
11.4.3.2 Venous Malformations 630
11.4.2.3 Lymphatic Malformations 631
11.4.2.4 Arteriovenous Malformations 631
11.4.3 General Therapeutic Outline 632
11.4.4 Current Established Therapies of Capillary Malformations 632
11.4.5 Current Established Therapies of Venous and Lymphatic Malformations 633
11.4.6 Current Established Therapies of Arteriovenous Malformations 635
References 637
Chapter 11.5 640
Rare Malignancies of the Skin 640
11.5.1 Introduction 640
11.5.2 Sarcomas with Fibrocytic Differentiation: Dermatofibrosarcoma Protuberans 641
11.5.2.1 Etiology and Pathophysiology 641
11.5.2.2 Clinical Characteristics and Diagnosis 641
11.5.2.3 General Therapeutic Outline 642
11.5.2.4 Current Established Therapies 642
11.5.2.5 Experimental Approaches 642
11.5.2.6 Complications to Avoid 642
11.5.2.7 Global Variations 642
11.5.3 Sarcomas with Myogenic Differentiation: Leiomyosarcoma 642
11.5.3.1 Etiology and Pathophysiology 644
11.5.3.2 Clinical Characteristics and Diagnosis 644
11.5.3.3 General Therapeutic Outline 644
11.5.3.4 Current Established Therapies 644
11.5.3.5 Experimental Approaches 644
11.5.3.6 Complications to Avoid 644
11.5.3.7 Global Variations 644
11.5.4 Sarcomas with Lipogenic Differentiation: Liposarcoma 645
11.5.4.1 Etiology and Pathophysiology 645
11.5.4.2 Clinical Characteristics and Diagnosis 645
11.5.4.3 General Therapeutic Outline 646
11.5.4.4 Current Established Therapies 646
11.5.4.5 Experimental Approaches 646
11.5.4.6 Complications to Avoid 646
11.5.4.7 Global Variations 646
11.5.5 Sarcomas with Vascular Differentiation: Angiosarcoma 646
11.5.5.1 Etiology and Pathophysiology 646
11.5.5.2 Clinical Characteristics and Diagnosis 646
11.5.5.3 General Therapeutic Outline 647
11.5.5.4 Current Established Therapies 647
11.5.5.5 Experimental Approaches 647
11.5.5.6 Complications to Avoid 647
11.5.5.7 Global Variations 649
11.5.6 Sarcomas with Neural Differentiation: Malignant Peripheral Nerve Sheath Tumor 649
11.5.6.1 Etiology and Pathophysiology 649
11.5.6.2 Clinical Characteristics and Diagnosis 649
11.5.6.3 General Therapeutic Outline 649
11.5.6.4 Current Established Therapies 649
11.5.6.5 Experimental Approaches 650
11.5.6.6 Complications to Avoid 650
11.5.6.7 Global Variations 650
11.5.7 Sarcomas of UncertainDifferentiation 650
11.5.7.1 Atypical Fibroxanthoma 650
11.5.7.2 Epithelioid Sarcoma 651
11.5.7.3 Clear Cell Sarcoma 651
11.5.8 NeuroendocrineCarcinoma 651
11.5.8.1 Etiology and Pathophysiology 651
11.5.8.2 Clinical Characteristics and Diagnosis 651
11.5.8.3 General Therapeutic Outline 652
11.5.8.4 Current Established Therapies 652
11.5.8.5 Experimental Approaches 652
11.5.8.6 Complications to Avoid 652
11.5.8.7 Global Variations 652
11.5.9 General Therapeutic Guidelines 652
11.5.9.1 Adjuvant Chemotherapy 652
11.5.9.2 Palliative Chemotherapy 653
11.5.9.3 Experimental Approaches 654
References 654
Part XII: Miscellaneous Disorders 656
Chapter 12.1 657
Diseases of Pregnancy and Their Management 657
12.1.1 Atopic Dermatitis 657
12.1.1.1 Etiology and Pathophysiology 657
12.1.1.2 Clinical Characteristics and Diagnosis 658
12.1.1.3 General Therapeutic Outline 658
12.1.1.4 Current Established Therapies 658
12.1.1.5 Complications to Avoid 658
12.1.1.6 Global Variations 658
12.1.2 Pruritus in Pregnancy 659
12.1.2.1 Intrahepatic Cholestasis of Pregnancy 659
12.1.2.1.1 Etiology and Pathophysiology 659
12.1.2.1.2 Clinical Characteristics and Diagnosis 659
12.1.2.1.3 General Therapeutic Outline 660
12.1.2.1.4 Current Established Therapies 660
12.1.2.1.5 Complications to Avoid 660
12.1.2.1.6 Global Variations 662
12.1.3 Specifi c Dermatoses of Pregnancy 662
12.1.3.1 Herpes (Pemphigoid) Gestationis 662
12.1.3.1.1 Etiology and Pathophysiology 662
12.1.3.1.2 Clinical Characteristics and Diagnosis 662
12.1.3.1.3 General Therapeutic Outline 664
12.1.3.1.4 Current Established Therapies 664
12.1.3.1.5 Complications to Avoid 664
12.1.3.1.6 Global Variations 665
12.1.3.2 Pruritic Urticarial Papules and Plaques of Pregnancy (PUPPP) 665
12.1.3.2.1 Etiology and Pathophysiology 665
12.1.3.2.2 Clinical Characteristics and Diagnosis 665
12.1.3.2.3 General Therapeutic Outline 666
12.1.3.2.4 Current Established Therapies 666
12.1.3.2.5 Complications to Avoid 666
12.1.3.2.6 Global Variations 667
12.1.3.3 Prurigo of Pregnancy 667
12.1.3.3.1 Etiology and Pathophysiology 667
12.1.3.3.2 Clinical Characteristics and Diagnosis 667
12.1.3.3.3 General Therapeutic Outline 667
12.1.3.3.4 Current Established Therapies 667
12.1.3.3.5 Complications to Avoid 667
12.1.3.3.6 Global Variations 668
12.1.3.4 Pruritic Folliculitis of Pregnancy 668
12.1.3.4.1 Etiology and Pathophysiology 668
12.1.3.4.2 Clinical Characteristics and Diagnosis 668
12.1.3.4.3 General Therapeutic Outline 668
12.1.3.4.4 Current Established Therapies 669
12.1.3.4.5 Complications to Avoid 669
12.1.3.4.6 Global Variations 669
References 669
Chapter 12.2 672
Pediatric Dermatology 672
12.2.1 Pediatric Dermatology Therapy: Scope, Specifi c Challenges, and Worldwide Variations/Priorities 672
12.2.2 Highlights of Some Important Disorders in Pediatric Dermatology 674
12.2.2.1 Scabies 674
12.2.2.1.1 Etiology and Pathophysiology (See Chap. ELSTON) 674
12.2.2.1.2 Clinical Characteristics and Diagnosis 674
12.2.2.1.3 General Therapeutic Outline 675
12.2.2.1.4 Current Established Therapies 675
12.2.2.1.5 Experimental Approaches 675
12.2.2.1.6 Complications to Avoid 675
12.2.2.1.7 Global Variations 675
12.2.2.2 Kawasaki Disease 675
12.2.2.2.1 Etiology and Pathophysiology 675
12.2.2.2.2 Clinical Characteristics and Diagnosis 676
12.2.2.2.3 General Therapeutic Outline 676
12.2.2.2.4 Current Established Therapies 676
12.2.2.2.5 Experimental Approaches 676
12.2.2.2.6 Complications to Avoid 676
12.2.2.2.7 Global Variations 677
12.2.2.3 Alarming Hemangiomas 677
12.2.2.3.1 Etiology and Pathophysiology 677
12.2.2.3.2 Clinical Characteristics and Diagnosis 677
12.2.2.3.3 General Therapeutic Outline 677
12.2.2.3.4 Current Established Therapies 677
12.2.2.3.5 Experimental Therapies 678
12.2.2.3.6 Complications to Avoid 678
12.2.2.3.7 Global Variations 678
12.2.2.4 Condylomata Acuminata 678
12.2.2.4.1 Etiology and Pathophysiology 678
12.2.2.4.2 Clinical Characteristics and Diagnosis 678
12.2.2.4.3 General Therapeutic Outline 679
12.2.2.4.4 Current Established Therapies 679
12.2.2.4.5 Experimental Therapies 679
12.2.2.4.6 Complications to Avoid 679
12.2.2.4.7 Global Variations 679
12.2.2.5 Langerhans Cell Histiocytosis 679
12.2.2.5.1 Etiology 679
12.2.2.5.2 Clinical Characteristics and Diagnosis 680
12.2.2.5.3 General Therapeutic Outline 680
12.2.2.5.4 Current Established Therapies 680
12.2.2.5.5 Experimental Therapies 680
12.2.2.5.6 Complications to Avoid 681
12.2.2.5.7 Global Variations 681
12.2.3 General Therapeutic Principles in Pediatric Dermatology 681
12.2.3.1 Age Versus Severity in Therapy of Skin Disorders 681
12.2.3.2 The Need of a Management Plan to Communicate Efficiently with the Parents 681
12.2.3.3 Specialized Facilities Are Needed to Manage the Child with a Serious Skin Disorder 682
References 682
Chapter 12.3 684
Aging and Photoaging of the Skin 684
12.3.1 Etiology and Pathophysiology of Skin Aging 684
12.3.1.1 Mechanisms Leading to Aging of the Skin 684
12.3.1.1.1 Reactive Oxygen Species Initiate the Aging Process 685
12.3.1.1.2 Extracellular Matrix Alterations Maintain the Aged Phenotype of the Skin 686
12.1.2.2 Functional Changes Related to Skin Aging 687
12.3.2 Clinical Characteristics 687
12.3.3 General Therapeutic Outline 688
12.3.4 Current Established Therapies 688
12.3.4.1 Topical Treatments 688
12.3.4.1.1 Retinoids 688
12.3.4.1.2 Vitamin C 689
12.3.4.2 Injectables 689
12.3.4.2.1 Botox 689
12.3.4.2.2 Dermal Fillers 690
Temporary Fillers 690
Permanent Fillers 690
Mechanisms of action 690
12.3.4.3 Resurfacing Procedures 691
12.3.5 Experimental Approaches 691
12.3.6 Complications to Avoid 692
12.3.6.1 Complications to Skin Aging 692
12.3.6.2 Complications to Therapy 692
References 693
Chapter 12.4 696
Occupational Dermatoses 696
12.4.1 Introduction 696
12.4.2 Contact Dermatitis 696
12.4.2.1 Chemical Burns 696
Key Features 696
12.4.2.1.1 Etiology and Pathophysiology 696
12.4.2.1.2 Clinical Characteristics and Diagnosis 697
12.4.2.1.3 General Therapeutic Outline 697
12.4.2.1.4 Current Established Therapies 698
12.4.2.1.5 Complications to Avoid 699
Take Home Message 699
12.4.2.1.6 Global Variations 699
12.4.2.2 Irritant Contact Dermatitis 699
Key Features 699
12.4.2.2.1 Etiology and Pathophysiology 700
12.4.2.2.2 Clinical Characteristics and Diagnosis 700
12.4.2.2.3 General Therapeutic Outline 700
12.4.2.2.4 Current Established Therapies 701
Prevention 701
12.4.2.2.5 Experimental Approaches 702
12.4.2.2.6 Complications to Avoid 702
Take Home Message 702
12.4.2.2.7 Global Variations 702
12.4.2.3 Allergic Contact Dermatitis 702
12.4.3 Contact Urticaria and Protein Contact Dermatitis 703
Key Features 703
12.4.3.1 Etiology and Pathophysiology 703
12.4.3.2 Clinical Characteristics and Diagnosis 703
12.4.3.3 General Therapeutic Outline 704
12.4.3.4 Current Established Therapies 704
12.4.3.4.1 Prevention 704
12.4.3.5 Experimental Approaches 704
12.4.3.6 Complications to Avoid 705
Take Home Message 705
12.4.3.7 Global Variations 705
12.4.4 Chemically Induced Acne 705
12.4.4.1 Chloracne 705
Key Features 705
12.4.4.1.1 Etiology and Pathophysiology 705
12.4.4.1.2 Clinical Characteristics and Diagnosis 706
12.4.4.1.3 General Therapeutic Outline 706
12.4.4.1.4 Current Established Therapies 706
12.4.4.1.5 Experimental Approaches 706
12.4.4.1.6 Complications to Avoid 707
Take Home Message 707
12.4.4.1.7 Global Variations 707
Other causes 707
12.4.5 Hand-Arm Vibration Syndrome Vibration White Finger
Key Features 707
12.4.5.1 Etiology and Pathophysiology 707
12.4.5.2 Clinical Characteristics and Diagnosis 707
12.4.5.3 General Therapeutic Outline 708
12.4.5.3.1 Prevention 708
12.4.5.4 Current Established Therapies 709
12.4.5.5 Experimental Approaches 709
12.4.5.6 Complications to Avoid 709
Take Home Message 709
12.4.5.7 Global Variations 709
12.4.6 Scleroderma-Like Disorders 709
12.4.7 Pigmentary Disorders 709
12.4.8 Skin Cancer 711
12.4.9 Infection 712
References 712
Chapter 12.5 714
Wound Healing 714
12.5.1 Etiology and Pathophysiology 714
12.5.2 Clinical Characteristics and Diagnosis 715
12.5.2.1 Impaired Healing Associated with Vascular Disease 716
12.5.2.2 Impaired Healing Associated with Increased Pressure 718
12.5.2.3 Impaired Healing Associated with an Altered Immune Response 719
12.5.3.4 Additional Differential Diagnosis 720
12.5.3 General Therapeutic Outline 721
12.5.4 Current Established Therapies 722
12.5.4.1 Treatment of Systemic Disease 722
12.5.4.1.1 Restoration of Functional Vascular System 722
12.5.4.1.2 Correction of Metabolic State 722
12.5.4.1.3 Normalization of Immune Response 722
12.5.4.2 Local Treatment 723
12.5.4.2.1 Debridement 723
12.5.4.2.2 Induction of Granulation Tissue 724
Wound dressings 724
Growth Factors 725
Cell-Based Treatments 725
Negative Pressure Wound Therapy (NPWT) 727
12.5.4.2.3 Induction of Reepithelialization 727
12.5.5 Experimental Approaches 727
12.5.6 Complications to Avoid 728
12.5.7 Global Variations 728
References 729
Index 731