Behcet's Syndrome (eBook)

Behçet’s Syndrome 1
Dedication 7
Preface 9
Contents 11
Contributors 13
Chapter 1: Introduction: Dedicated Mondays and an Acquaintance-Based View of Behçet’s Syndrome 17
References 20
Chapter 2: History and Diagnosis 22
Introduction 22
Early Descriptions of the Syndrome 23
Development of the Full Clinical Description of the Syndrome 24
Aphthous Ulceration 24
Eye Manifestations [30–33] 25
Skin Lesions 26
Pathergy Test 26
Joints 27
Vasculitis/Vasculopathy 27
Pulmonary and Neurological Lesions 28
Gastrointestinal System 29
Family History, Epidemiology and Geographical Differences in Prevalence 29
Aetiopathogenesis 30
Diagnosis 31
Treatment 36
Disease or Syndrome? 36
International Liaison 39
References 41
Chapter 3: Epidemiology of Behçet’s Syndrome and Regional Differences in Disease Expression 49
Epidemiology of Behçet’s Syndrome in Turkey 49
Epidemiology of Behçet’s Syndrome in the World 57
Asia (Table 3.2) 57
Europe 58
Africa 59
America 59
Australia 60
Differing Disease Expression in Behçet’s Syndrome 60
Gastrointestinal Involvement 60
Pathergy Test 61
HLA-B5(51) Association 61
Conclusions 62
References 62
Chapter 4: The Mucocutaneous Manifestations and Pathergy Reaction in Behçet’s Disease 67
Recurrent Aphthous Stomatitis 67
Genital Ulcers 69
Cutaneous Lesions 70
Erythema Nodosum-Like Lesions 71
Superficial Thrombophlebitis 72
Papulopustular Lesions, Pseudofolliculitis, and Acneiform Lesions 72
Other Cutaneous Lesions 75
Skin Pathergy Reaction 75
Differential Diagnosis 78
Local Treatment of Mucocutaneous Lesions (See Chap. 19 for Systemic Treatment) 80
References 81
Chapter 5: Eye Disease in Behçet’s Syndrome 87
Epidemiology 87
Clinical Symptoms and Findings 88
Anterior Chamber Findings Reflecting an Acute Attack 89
Anterior Chamber Findings Reflecting Permanent Damage 90
Posterior Segment and Retinal Findings Reflecting an Acute Attack 92
Posterior Chamber and Retinal Findings Reflecting Permanent Damage 95
Fluorescein Angiography and Indocyanine Green Angiograpy 95
Immunohistopathologic Evaluation 97
Clinical Course and Prognosis (See Also Chap. 17) 97
Disease Assessment 98
Management 100
Systemic Therapy 101
Local Therapy 103
Surgical Procedures 104
Peripheral Iridectomy 104
Cataract Surgery 104
Vitrectomy 104
References 104
Chapter 6: Behçet’s Syndrome and the Nervous System 109
Introduction 109
Diagnosis of NBS 110
Epidemiology of NBS 111
Extra-axial NBS 111
Intra-axial NBS 112
Classification of Intra-axial NBS 112
Arterial-NBS 113
Headache in BS 113
Neuro-Psycho-Behçet’s Syndrome 113
Cognitive Changes Observed in Patients with NBS 113
Neuromuscular Disease in BS 114
Subclinical NBS 115
Neuropathology of NBS 115
Neuroimmunology of NBS 116
Diagnostic Studies in NBS 117
Neuroimaging 117
Cerebrospinal Fluid 119
Differential Diagnosis 119
Differential Diagnosis of Intra-axial (Parenchymal) NBS 119
Prognosis 122
Treatment 122
Intra-axial NBS: Acute Episodes 122
Intra-axial NBS: Long-term Treatments 122
Treatment of CVST in NBS 123
EULAR (European League Against Rheumatism) Recommendations for the Treatment of NBS 123
References 124
Chapter 7: Vascular Disease in Behçet’s Syndrome 128
Arterial Involvement 128
Clinical Picture 129
Pathology 130
Radiology 131
Management 131
Pulmonary Artery Involvement 132
Clinical Picture 133
Radiology 134
Differential Diagnosis 134
Pathology 135
Management 136
Venous Thrombosis 137
Deep Vein Thrombosis of Lower Extremities 137
Vena Caval Thrombosis 138
Budd–Chiari Syndrome 139
Cerebral Venous Thrombosis (Also See Chap. 6) 139
Cardiac Involvement (See Also Chap. 8) 141
Intracardiac Thrombosis 141
References 142
Chapter 8: Endothelial Dysfunction and Atherosclerosis in Behçet’s Syndrome 147
Endothelium 147
Endothelial Cell Dysfunction: What Is It and How Is It Measured? 148
Endothelial Cell Dysfunction in Various Diseases 148
Endothelial Cell Dysfunction in Behçet’s Syndrome 149
Atherosclerosis in Behçet’s Syndrome 151
Cardiovascular Diseases and Its Associated Mortality 151
Cardiac Involvement and Cardiac Functions in BS 152
Subclinical Atherosclerosis 153
Lipid Abnormalities in BS 153
Why Is Atherosclerosis Not Overtly Accelerated in BS? 155
References 155
Chapter 9: Locomotor System Disease in Behçet’s Syndrome 161
Joint Involvement 161
Joints Involved 162
Enthesopathy 163
Number of Joints Involved 164
Symmetry 165
Duration 165
Morning Stiffness 165
Subcutaneous Nodules 166
Pseudothrombophlebitis (Baker’s Cyst Rupture) and Pseudoseptic Arthritis 166
Laboratory Findings 167
Synovial Fluid 167
Radiological Changes 167
Synovial Histology 168
Fibromyalgia 169
Myositis 169
Osteonecrosis 170
Functional Outcome Measures in Locomotor System Disease 170
Treatment (See Also Chap. 19) 170
References 171
Chapter 10: Behçet’s Disease: Gastrointestinal Involvement 176
Introduction 176
Epidemiology 176
Clinical Manifestations 178
GI Manifestations 178
Extraintestinal Manifestations 180
Laboratory Findings 180
Endoscopic and Radiologic Findings 181
Pathogenesis 183
Immune Abnormalities 183
Genetics 184
Environment 185
Intestinal Permeability 185
Diagnosis 185
Differential Diagnosis 186
Inflammatory Bowel Disease 186
Intestinal Tuberculosis 187
NSAID (Nonsteroidal Antiinflammatory Drugs) Enterocolitis 188
Simple Ulcer Syndrome 188
Malignancy 188
Other Enterocolitides 189
Disease Activity Index/Inflammatory Bowel Disease Questionnaire 189
Pathology (See Chap. 13) 189
Treatment (See Also Chap. 19) 189
Medical Management 189
5-ASA or Sulfasalazine 189
Glucocorticoids 190
Immunomodulators 190
Thalidomide 190
Biological Agents 190
Autologous Hematopoietic Stem Cell Transplantation 191
Endoscopic Therapy 191
Surgical Treatment 191
Prognosis 192
Summary 192
References 193
Chapter 11: Miscellaneous Manifestations of Behçet’s Disease 200
Introduction 200
Hematologic Associations of Behçet’s Disease 200
Auditory and Vestibular Dysfunction in Behçet’s Disease 202
Renal Involvement and Amyloidosis 204
Glomerulonephritis 206
Renal Vascular Disease 206
End-Stage Renal Failure and BS 207
Urologic Manifestations of Behçet’s Disease 207
References 211
Chapter 12: Juvenile Behçet’s Syndrome 216
Epidemiology 216
Familial Aggregation 218
Age at Disease Onset and Mode of Onset 218
Puberty 218
Skin Mucosa Lesions and Arthritis 219
Eye Disease 221
Vascular Involvement 221
Neurological Involvement 222
Intestinal Involvement 222
Mortality and Outcome 222
Management 223
References 223
Chapter 13: Behçet’s Disease: Pathology 226
Mucocutaneous Lesions 226
Oral Ulcers 226
Genital Ulcers 227
Papulopustular and Acneiform Lesions 227
EN-Like Nodular Lesions 228
Superficial Thrombophlebitis 229
Sweet’s Syndrome-Like Lesions 229
Pathergy Reaction (See Also Chap. 4) 229
Ocular Involvement 230
Cardiovascular Manifestations 230
Pulmonary Manifestations (See Also Chap. 7) 233
Neurologic Involvement (See Also Chap. 6) 237
Parenchymal CNS Involvement 237
Nonparenchymal CNS Involvement (Neuro-Vasculo-BD (NvB)) 238
Gastrointestinal Manifestations 239
Pharyngeal Involvement 239
Esophageal and Gastric Involvement 239
Intestinal Involvement 240
References 246
Chapter 14: Disease Mechanisms 253
Introduction 253
Infectious Etiology 254
Herpes Simplex Virus 254
Innate Immunity 255
Neutrophil Activation 255
gd T Cells in BD 255
NK and Cytotoxic T Cells 256
Autoinflammation and BD 257
Adaptive Immunity in BD 258
Cellular Immunity 258
Regulatory Activity in BD 259
Autoimmunity and B Cell Activity 259
Pathways from Innate to Adaptive Responses 261
Pathogenesis of Vascular Involvement 263
Coagulation and Fibrinolytic Pathway Abnormalities 263
Severity and Gender 264
Behçet’s Disease or Syndrome: Observations from the Clinic: Different Antigenic Stimuli or Inflammatory Milieu for Different 264
Conclusions 265
References 266
Chapter 15: Genetics of Behçet’s Disease 275
Familial Aggregation 275
Geographic Distribution 276
HLA-B51 and Other MHC Associations 276
Other MHC Associations 279
Non-HLA Genes and Behçet’s Disease 280
References 281
Chapter 16: Animal Models of Behçet’s Disease 287
Introduction 287
Environmental Pollution Model 287
Infectious Models 288
Bacterial Infectious Models 288
Viral Infectious Models 288
Autoimmune Models 289
Heat Shock Proteins 289
S-Ag-Induced Uveitis 289
Tropomyosin 290
Transgenic Model 290
Comments (Summarized in Table 16.1) 291
References 293
Chapter 17: Prognosis in Behçet’s Syndrome 295
Introduction 295
Mortality 296
Skin-Mucosa Lesions and Arthritis 298
Eye Disease 298
Vascular Disease 301
Neurological Disease 303
Development of De Novo Major Organ Complications During Follow-Up 305
Cancer 305
References 306
Chapter 18: Disease Assessment in Behçet’s Disease 309
Principles of Measurement 310
ICF Model of Disease 310
An Example 311
Choosing a Measure 311
Rasch Analysis 312
Individual Tests and Assessment in BD 312
Disease Activity: The Whole Person Assessments 312
The Behçet’s Disease Current Activity Form 314
The Behçet’s Syndrome Activity Scale (BSAS) 314
The Iranian BD Dynamic Measure 318
Biological Markers in Disease Activity 318
Measurement of Visual Activity 318
Mouth Ulcers 319
A Composite Index for Oral Ulcer Activity in Behçet’s Disease 319
Assessment of Oral Health Related QoL in Clinical Practice 320
Oral Ulcer Treatment Modalities and OHQoL 320
Nervous System 321
Joint Involvement 321
Disability and Participation Measures 322
QoL Assessments 322
BD-Specific QoL Measure 323
Conclusions 323
References 323
Chapter 19: Medical Management of Behçet’s Syndrome 326
Colchicine 327
Azathioprine 331
Cyclosporin A 332
Thalidomide 333
Corticosteroids 333
Cyclophosphamide 334
Other Immunosuppressives 334
Antibiotics 335
Anticoagulants 335
Miscellaneous 335
Biologic Agents and Stem Cell Transplantation Used for the Treatment of BS 336
Interferon Alpha 336
TNF-Antagonists 338
Other Biologic Agents 339
Alemtuzumab (Campath 1-H) 339
Daclizumab 339
Rituximab 340
Il-1-Receptor Antagonist (Anakinra) 340
Stem Cell Transplantation 340
References 341
Index 348