Skin in Systemic Autoimmune Diseases (eBook)

Cover 1
Contents 16
Preface 6
Series Editor 8
Volume Editors 10
List of Contributors 12
The Skin and the Immune System 18
The Skin as an Immunologic Organ 20
Introduction: the skin as an organ of defence 20
Evolving concepts of the skin as an immunological organ 21
The skin immune system 22
Immune responses in skin 24
Conclusions 25
Key points 25
References 26
T Cells and Dendritic Cells in Immuno-Mediated Skin Pathology 28
Introduction 28
Self-reactive T cell subsets 28
Dendritic cells—key regulators of immune responses 32
Dendritic cells in mixed connective tissue disease 35
Dendritic cells in Sjögren’s syndrome 35
Dendritic cells induce psoriasis 35
Acknowledgments 35
References 35
D6 as a Decoy and Scavenger Receptor for Inflammatory CC Chemokines in the Skin 40
Introduction 40
Expression and ligand recognition by the D6 chemokine decoy receptor 41
In vitro properties 41
D6 as a decoy in the skin 42
Concluding remarks 44
Key points 44
References 44
Autoantibodies and Skin Involvement in Systemic Autoimmune Diseases 46
Introduction 46
Autoantibodies in Systemic Sclerosis (SSc) 47
Pathogenic autoantibodies 47
Anti-fibroblast antibodies 47
Anti-endothelial antibodies 47
Anti-matrix metalloproteinase (MMP) antibodies 48
Prognostic autoantibodies 48
Pathogenic autoantibodies in systemic lupus erythematosus: the anti-Ro/SSA model 49
Clinical and pathogenic associations 49
Prognostic autoantibodies in other systemic autoimmune diseases 50
Dermatomyositis (DM) 50
Other myositis 50
Rheumatoid arthritis (RA) 50
Key points 51
References 51
Skin Involvement in Systemic Autoimmune Diseases 54
Photosensitivity in Lupus Erythematosus 56
Introduction 56
Pathophysiology of photosensitivity in LE 57
Clinical photosensitivity and phototesting 58
References 63
Cutaneous Manifestations of Lupus Erythematosus 66
Introduction 66
Specific cutaneous manifestations of lupus erythematosus 67
Acute cutaneous lupus erythematosus 67
Subacute cutaneous lupus erythematosus 68
Chronic cutaneous lupus erythematosus 69
Discoid lupus erythematosus 69
Chilblain lupus erythematosus 71
Lupus erythematosus profundus 71
Intermittent cutaneous lupus erythematosus 72
Lupus erythematosus tumidus 72
Non-specific cutaneous manifestations of lupus erythematosus 73
Bullous skin lesions in lupus erythematosus 74
Urticarial Vasculitis 74
Papulonodular mucinosis 75
Annular erythema 76
Conclusions 76
Acknowledgements 76
Key points 77
References 77
Subacute Cutaneous Lupus Erythematosus: A Quarter Century’s Perspective 82
Introduction and historical perspective 82
Epidemiology 83
Incidence and prevalence 83
Demographics 83
Environmental influences 84
Etiology/pathogenesis 85
Clinical manifestations 87
Clinical features 87
Association with other forms of cutaneous LE and LE nonspecific skin disease 89
Association with SLE 89
Association with other autoimmune diseases 90
SCLE as a paraneoplastic phenomenon 90
Diagnostic investigations 90
Serology/immunology 90
Other laboratory features 91
Differential diagnosis 91
Treatment 93
Protection from ultraviolet light 93
Physical protection 93
Chemical sunscreens 93
Local corticosteroids 94
Antimalarials 94
Dapsone 95
Retinoids 96
Thalidomide 96
Gold 96
Clofazimine 96
Other agents 97
Systemic corticosteroids and other immunosuppressive agents 97
Combination therapy 97
Experimental therapy 98
UVA-1 phototherapy 98
Recombinant biologic response modifiers 98
Prognosis 98
Acknowledgements 100
Key points 100
References 100
Differential Diagnosis of LE-specific Skin Lesions 104
Introduction 104
Acute cutaneous lupus erythematosus 104
Dermatologic features 104
Clinical background 104
Differential diagnosis of localized ACLE 104
Acne rosacea vs ACLE 105
Contact dermatitis vs ACLE 105
Photodermatitis vs ACLE 105
Seborrheic dermatitis vs ACLE 106
Dermatomyositis vs ACLE 106
Erysipelas vs ACLE 106
Delusion of lupus vs ACLE 107
Differential diagnosis of generalized ACLE 107
Morbilliform drug reactions vs generalized ACLE 107
Erythema multiforme vs generalized ACLE 107
Subacute cutaneous lupus erythematosus 108
Dermatologic features 108
Clinical background 109
Differential diagnosis of papulosquamous SCLE 109
Psoriasis vs papulosquamous SCLE 109
Polymorphic light eruption vs papulosquamous SCLE 109
Differential diagnosis of annular-polycyclic SCLE 110
Superficial gyrate erythema vs annular-polycyclic SCLE 110
Tinea corporis vs annular-polycyclic SCLE 111
Chronic cutaneous lupus erythematosus 111
Dermatologic features 111
Clinical background 111
Differential diagnosis of early CCLE, non-scaling pattern 111
Polymorphic light eruption vs early CCLE, non-scaling pattern 112
Jessner’s benign lymphocytic infiltration of the skin vs early CCLE, non-scaling pattern 112
Lymphocytoma cutis vs early CCLE, non-scaling pattern 112
Granuloma faciale vs early CCLE, non-scaling pattern 113
Pernio vs early CCLE, non-scaling pattern 113
Lupus pernio vs early CCLE, non-scaling pattern 114
Differential diagnosis of early CCLE, scaling pattern 114
Actinic keratoses vs early CCLE, scaling pattern 114
Seborrheic dermatitis vs early CCLE, scaling pattern 115
Psoriasis vs early CCLE, scaling pattern 115
Tinea faciei vs early CCLE, scaling pattern 115
Lichen ruber planus vs early CCLE, scaling pattern 115
Differential diagnosis of fully developed CCLE lesions 116
Differential diagnosis of late CCLE lesions 116
Lichen ruber planus vs late CCLE 116
Lupus vulgaris vs late CCLE 117
Other infectious granulomatous diseases vs late CCLE 117
Key points 117
References 118
Dermatologic aspects of Antiphospholipid Antibody Syndrome 120
Introduction 120
Prevalence 120
Clinical manifestations 121
Livedo reticularis 121
Skin ulcerations 121
Digital gangrene 122
Multiple subungual splinter hemorrhages 123
Superficial venous thrombosis 123
Thrombocytopenic purpura 124
Pseudovasculitis manifestations 124
Extensive cutaneous necrosis 125
Primary anetoderma 125
Melanoderma 126
Histologic features 126
Relationship between skin lesions and other manifestations of aps 127
Detection of antiphospholipid antibodies (aPL) in dermatology 128
Skin manifestations 128
Tests for detection of aPL 128
Treatment 129
Conclusions 131
Key points 131
References 131
The Skin in Systemic Scleroderma 136
Introduction 136
Prevalence/epidemiology 136
Etiology/pathogenesis of skin fibrosis 137
Clinical manifestations 139
Diagnostic investigations 142
Histology 144
Differential diagnosis 144
Treatment 146
Key points 148
References 149
Dermatomyositis 152
Introduction 152
Epidemiology/Prevalence 152
Etiology 152
Overlap syndromes 152
Viruses 152
Cancer 153
Myotoxic drugs 153
Pathogenesis 153
Presence of autoantibodies 153
Immunopathology of muscle and skin 153
Muscle 153
Skin 154
Clinical manifestations 156
Extramuscular manifestations 156
Diagnostic investigations 157
Serum muscle enzymes 157
Electromyography 157
Muscle biopsy 157
Differential diagnosis 157
Prognosis and complications 158
Management 158
Corticosteroids 159
Prednisone failures and nonsteroidal immunosuppressive therapies 159
References 160
Mucocutaneous Manifestations of Sjogren’s Syndrome 164
Introduction 164
Prevalence 165
Epidemiology 165
Aetiology/Pathogenesis 166
Aetiology: genetic predisposition 166
Aetiology: hormones 166
Aetiology: exogenous agents 167
Aetiology: microchimerism 167
Pathogenesis: autoimmune epithelitis 168
Pathogenesis: interaction of immune and neurosecretory functions 168
Clinical manifestations 169
Mucosal involvement: dry eyes 169
Mucosal involvement: dry mouth 169
Cutaneous involvement 170
Cutaneous involvement: xerosis 170
Cutaneous involvement: vascular lesions 171
Cutaneous involvement: miscellaneous 173
Diagnostic investigations 173
Laboratory tests 173
Tests used for the evaluation of xerophthalmia 173
Tests used for the evaluation of xerostomia 173
Differential diagnosis 174
Treatment 174
Treatment of ocular- and oral involvement 174
Treatment of extraglandular manifestations 174
Key points 175
References 175
Rheumatoid Arthritis and the Skin 178
Introduction 178
Epidemiology/Prevalence 178
Aetiology 178
Genetic factors 178
Environmental factors 179
Viruses 179
Bacteria 179
Sex hormones 179
Pathogenesis 179
Diagnosis and clinical features 180
Imaging 182
Laboratory abnormalities 182
Rheumatoid factor 182
Other autoantibodies in RA 183
Acute phase reactants 183
Synovial fluid analysis 183
Assessment 183
Disease activity measures 183
Functional disability 183
Radiographic assessment 184
Indices 184
Treatment 184
Management of early and established active inflammatory disease 184
Management of end-stage disease 185
Non-steroidal anti-inflammatory drugs 185
Corticosteroids 185
Disease-modifying anti-rheumatics drugs 185
Biological agents 186
anti-TNF-a monoclonal antibody therapy 186
Anakinra 186
Anti-B-cell therapy 186
Cutaneous manifestations 186
Rheumatoid nodules 187
Cutaneous vasculitis 188
Histological characteristics 189
Leg ulcers 190
Felty’s syndrome 191
Neutrophilic dermatoses 191
Pyoderma gangrenosum 191
Rheumatoid neutrophilic dermatosis 191
Cutaneous atrophy with stellate scarring 192
Adverse skin reactions to drugs 192
Non-steroid anti-inflammatory drugs 192
Disease-modifying anti-rheumatics drugs 192
Biologic agents 194
Anti-TNF-a monoclonal antibody therapy 194
Anakinra 195
Conclusion 195
Key points 195
References 196
Behçet’s Syndrome 202
Introduction 202
Prevalence 202
Epidemiology 203
Etiology/Pathogenesis 203
Clinical manifestations 205
Oral ulcers 205
Genital ulcerations 206
Acneiform and papulopustular lesions 207
Nodular lesions 207
Sweet syndrome 209
The pathergy reaction 210
Other cutaneous manifestations 211
Extragenital ulcers 212
Dermographism and atopy 212
Eye involvement 212
Musculoskeletal involvement 212
Vascular involvement 213
Neurologic manifestations of Behçet’s syndrome 213
Gastrointestinal involvement 213
Behçet’s syndrome in children 214
Diagnosis 214
Differential diagnosis 214
Differential diagnosis of oral and mucocutaneous disease 214
Differential diagnosis of oral genital and ocular mucocutaneous disease 214
Prognosis and treatment 215
Treatment of mucocutaneous manifestations 216
Treatment of systemic manifestations 217
Key points 218
References 218
Outcome Measures in Cutaneous Autoimmune Disease: Dermatomyositis and Lupus Erythematosus 224
Introduction to outcome measures in cutaneous autoimmune disease 224
Disease activity measurements for skin disease 224
The validation process 225
What does the score mean? What is its clinical utility? 226
Assessors 227
Dermatomyositis 227
Disease activity measurement for cutaneous DM 228
The Dermatomyositis Skin Severity Index (DSSI) 229
Lupus 230
Disease activity measurement for CLE 230
Choice of CLE measures 231
Erythema 231
Area 232
Separate measurements of disease activity and damage 232
Associated symptoms 233
The Cutaneous LE Activity and Severity Index (CLASI) 233
Validation of the CLASI 233
Conclusion 235
Key points 235
Acknowledgement 235
References 235
Capillaroscopy: Which is Its Role in the Diagnosis of Connective Tissue Diseases? 238
Microvascular involvement 238
Raynaud’s phenomenon 238
The role of capillaroscopy in the early diagnosis of secondary RP 240
Giant capillaries 240
Angiogenesis 240
Architectural derangement of the nailfold microvascular network 241
Loss of capillaries and/or avascular areas 241
The most common capillaroscopic patterns and the connective tissue diseases 242
Scleroderma and scleroderma-like 242
Systemic lupus erythematosus 244
Antiphospholipid syndrome 244
The most common capillaroscopic patterns for the diagnosis of secondary Raynaud: the scleroderma pattern 245
Key points 247
References 247
Skin Manifestations in Vasculitides 250
Cutaneous Small Vessel Vasculitis including Urticarial Vasculitis 252
Cutaneous small vessel vasculitis 252
Introduction 252
Epidemiology 252
Etiology 253
Pathogenesis 254
Clinical manifestations 255
Diagnostic investigations 256
Differential diagnosis 257
Treatment 258
Urticarial vasculitis 260
Introduction 260
Prevalence 260
Epidemiology 260
Etiology/pathogenesis 260
Clinical manifestations 261
Diagnostic investigations 261
Differential diagnosis 262
Treatment 262
Key points for CSVV 262
Key points for UV 262
References 262
Henoch-Schönlein Purpura 266
Introduction 266
Prevalence, Distribution, Age and Sex 266
Etiology/Pathogenesis 266
Histological findings 266
Skin 266
Kidney 267
Digestive tract 267
IgA immunological abnormalities 267
Plasma IgA 267
IgA synthesis 268
IgA complexes 268
IgA complexes clearance 268
Complement 268
Immunogenetic factors 268
Coagulation 269
Mucosal permeability 269
Allergy 269
Pathophysiological hypothesis 269
Clinical Features 270
Skin involvement 270
Renal involvement 270
Gastro-intestinal involvement 271
Joints involvement 272
Involvement of other organs 272
Secondary forms of HSP 272
Diagnosis 272
Treatment 273
Key points 274
References 274
Mixed Cryoglobulinemia 278
Introduction 278
Prevalence 279
Epidemiology 279
Etiopathogenesis 279
Clinical manifestations 283
Diagnostic investigations 285
Differential diagnosis 286
Treatment 286
Key points 288
References 289
Skin Involvement in Small, Medium-sized Vessel and Granulomatous Vasculitides 292
Introduction 292
Definitions and classification of systemic vasculitides 292
Pathogenesis 294
Dermatologic manifestations of small, medium-sized vessel and granulomatous vasculitides 294
Main clinical cutaneous manifestations 294
Histopathology 296
Polyarteritis Nodosa 298
Churg-Strauss syndrome 299
Wegener’s granulomatosis 299
Microscopic polyangiitis 301
Other dermatologic manifestations associated with systemic vasculitides 301
Extravascular necrotizing granuloma (Winkelmann’s granuloma) 301
Panniculitis 302
Pyoderma gangrenosum 302
Granuloma 303
Superficial thrombophlebitis 303
Gangrene 303
Raynaud’s phenomenon 303
Diagnostic investigations and differential diagnoses 303
Prognosis 305
Treatment 306
Principles of treatment for primary systemic vasculitides 306
Corticosteroids 306
Immunosuppressants 306
Other therapies 306
Treatment of dermatologic manifestations 307
Key points 307
References 307
Kawasaki Disease 312
Introduction 312
Prevalence 312
Epidemiology 312
Etiopathogenesis 313
Clinical manifestations 313
Diagnostic criteria 313
Atypical-incomplete kawasaki disease 315
Acute cardiac complications 316
Long term cardiac complications 317
Diagnostic investigations 318
Laboratory 318
Cardiac imaging 318
Echocardiography 318
Cardiac stress testing 318
Coronary angiography 318
Magnetic resonance angiography (MRA) 319
Differential diagnosis 319
Treatment 319
Initial treatment 319
Aspirin 319
Intravenous immunoglobulins 320
Management of refractory Kawasaki disease 320
Experimental treatments 321
Medical treatment of coronary artery abnormalities 321
Surgical and catheter coronary interventions 321
Catheter coronary interventions 321
Coronary surgery 322
Key points 322
References 322
New Insight in the Treatment of the Skin Manifestations in Systemic Autoimmune Diseases 328
Skin Targets for New Biological Agents in Systemic Autoimmune Diseases 330
Introduction 330
Nonspecific biological agents 330
High-dose intravenous immunoglobulins 330
Specific biological agents 331
Agents targeting T-cells 331
Agents targeting B-cells 332
Agents targeting proinflammatory or immunomodulatory cytokines 332
Anti-tumour necrosis factor-a 332
Interleukin-1 receptor antagonist 334
Cytokines causing immunodeviation 334
Agents targeting T-cell/antigen-presenting cell interaction 335
Other biological compounds 336
Conclusion and outlook 337
Key points 337
References 337
New Trends in Topical and Systemic Immunosuppressive Treatment 342
Immunosuppressive agents licensed for other indications 342
Ciclosporin A 343
Calcineurin inhibitors 343
Tacrolimus (FK506) 343
Pimecrolimus (ASM-981) 344
Methotrexate 344
Leflunomide 344
Mycophenolate mofetil 345
15-deoxyspergualin 345
Anti-B cell therapy 345
CD20 346
CD22 346
B lymphocyte stimulator 346
Costimulation 347
CTL4-Ig 347
(Anti-) Cytokines 347
Tumor necrosis factor alpha 347
Interleukin 10 347
Interferon alpha 348
Interleukin 6 348
Hormone therapy 348
Dehydroepiandrosterone 348
LE-specific immunomodulation 348
LJP394 349
Heteropolymer ETI-104 349
Anti id16/6-Peptides 349
Complement-inhibition 349
Conclusion 350
Key points 350
Acknowledgements 350
References 350
Index 354