Primary Immunodeficiency Diseases

by Rezaei, Nima; Aghamohammadi, Asghar; Notarangelo, Luigi D.

• ISBN13: 9783540785378
• ISBN10: 354078537X
• Format: Paperback
• Copyright: 2008-09-03
• Publisher: Springer Verlag

Summary

Primary immunodeficiency diseases (PID) are a group of disorders involving defects in one or more components of the immune system, and are characterized by an increased incidence of infections, autoimmunity, and malignancies. Although PID seem to be rare, the number of patients diagnosed has increased in recent years, and more than 150 different forms of PID have been identified. Nevertheless, because of inadequate medical awareness, a significant number of patients with PID are either not recognized as having a PID or are not diagnosed as early as they should be. Such delays lead to a substantial increase in morbidity and mortality among affected individuals.Our understanding of PID is improving rapidly, which will hopefully lead to more accurate diagnosis and efficient disease management. This book contains the most recent advances in the field, as well as a concise and structured review of previously identified PID. Although the book's primary focus is on practical diagnosis and management, the pathophysiology of PID is also discussed.This book is a comprehensive yet manageable resource for physicians and nurses wishing to learn more about PID, as well as a useful tool for both doctors-in-training and specialists in clinical decision-making and treatment planning.

Table of Contents

An Introduction to Primary Immunodeficiency Diseases	p. 1
Definition	p. 1
Background	p. 1
History	p. 2
Registries	p. 2
Etiology	p. 2
Classification	p. 2
Genetic Defects	p. 11
Pathophysiology	p. 12
Clinical Manifestations	p. 14
Infections	p. 14
Autoimmunity	p. 15
Malignancies	p. 19
Other Manifestations	p. 19
Diagnosis	p. 20
Warning Signs and Symptoms	p. 20
Diagnostic Approach	p. 21
Laboratory Tests	p. 24
Management	p. 25
General Considerations	p. 25
Vaccination	p. 26
Antibiotics	p. 27
Immunoglobulin Replacement Therapy	p. 28
Transplantation	p. 28
Gene Therapy	p. 29
Adjunct Therapies	p. 29
Combined T and B Cell Immunodeficiencies	p. 39
Introduction	p. 39
T-B+ Severe Combined Immunodeficiency (¿c Deficiency, JAK3 Deficiency, IL7-R¿ Deficiency, CD45 Deficiency, CD3¿/CD3¿/CD3¿/CD3¿ Deficiencies)	p. 42
Definition	p. 42
Etiology	p. 42
Clinical Manifestations	p. 44
Diagnosis	p. 45
Management	p. 46
T-B- Severe Combined Immunodeficiency(RAG1/2 Deficiencies, Artemis Deficiency, ADA Deficiency)	p. 48
Definition	p. 48
Etiology	p. 49
Clinical Manifestations	p. 52
Diagnosis	p. 52
Management	p. 52
Omenn Syndrome	p. 53
Definition	p. 53
Etiology	p. 53
Clinical Manifestations	p. 53
Diagnosis	p. 53
Management	p. 54
DNA Ligase IV Deficiency	p. 54
Definition	p. 54
Etiology	p. 54
Clinical Manifestations	p. 54
Diagnosis	p. 55
Management	p. 55
Cernunnos Deficiency	p. 55
Definition	p. 55
Etiology	p. 55
Clinical Manifestations	p. 55
Diagnosis	p. 55
Management	p. 56
Purine Nucleoside Phosphorylase (PNP) Deficiency	p. 56
Definition	p. 56
Etiology	p. 56
Clinical Manifestations	p. 57
Diagnosis	p. 58
Management	p. 58
Immunoglobulin Class Switch Recombination Deficiencies (affecting CD40-CD40L) (CD40 ligand Deficiency, CD40 Deficiency)	p. 59
Definition	p. 59
Etiology	p. 59
Clinical Manifestations	p. 60
Diagnosis	p. 61
Management	p. 61
MHC Class II Deficiency (CIITA Deficiency, RFX5 Deficiency, RFXAP Deficiency, RFXANK Deficiency)	p. 62
Definition	p. 62
Etiology	p. 62
Clinical Manifestations	p. 63
Diagnosis	p. 64
Management	p. 64
MHC Class I Deficiency (TAP1/2 Deficiencies, Tapasin Deficiency)	p. 65
Definition	p. 65
Etiology	p. 65
Clinical Manifestations	p. 66
Diagnosis	p. 67
Management	p. 67
CD8 Deficiency (CD8¿ Chain Defect, ZAP-70 Deficiency)	p. 68
Definition	p. 68
Etiology	p. 68
Clinical Manifestations	p. 69
Diagnosis	p. 69
Management	p. 70
CD4 Deficiency (p56lck Deficiency, Idiopathic CD4 Lymphopenia)	p. 70
Definition	p. 70
Etiology	p. 70
Clinical Manifestations	p. 71
Diagnosis	p. 71
Management	p. 71
CRAC Deficiency	p. 72
Definition	p. 72
Etiology	p. 72
Clinical Manifestations	p. 72
Diagnosis	p. 72
Management	p. 73
Winged-Helix-Nude (WHN) Deficiency	p. 73
Definition	p. 73
Etiology	p. 73
Clinical Manifestations	p. 73
Diagnosis	p. 73
Management	p. 74
CD25 Deficiency	p. 74
Definition	p. 74
Etiology	p. 74
Clinical Manifestations	p. 75
Diagnosis	p. 75
Management	p. 76
STAT5B Deficiency	p. 76
Definition	p. 76
Etiology	p. 76
Clinical Manifestations	p. 77
Diagnosis	p. 77
Management	p. 78
Predominantly Antibody Deficiencies	p. 97
Introduction	p. 97
Agammaglobulinemia with Absent B Cells (Btk Deficiency, ¿ Heavy Chain Deficiency, ¿5/14.1 Deficiency, Ig¿ Deficiency, Igß Deficiency, BLNK Deficiency, LRRC8 Deficiency, Other Forms of Agammaglobulinemia)	p. 99
Definition	p. 99
Etiology	p. 99
Clinical Manifestations	p. 101
Diagnosis	p. 104
Management	p. 104
Hypogammaglobulinemia with Normal/Low Number of B Cells (Common Variable Immunodeficiency, ICOS Deficiency, TACI Deficiency, CD19 Deficiency, Other Forms of Hypogammaglobulinemia)	p. 105
Definition	p. 105
Etiology	p. 105
Clinical Manifestations	p. 108
Diagnosis	p. 110
Management	p. 110
Immunoglobulin Class Switch Recombination Deficiencies (Due to Intrinsic B Cell Defects)(AID Deficiency, UNG Deficiency, Other CSR Selective Deficiencies)	p. 111
Definition	p. 111
Etiology	p. 111
Clinical Manifestations	p. 113
Diagnosis	p. 113
Management	p. 113
Selective IgA Deficiency	p. 113
Definition	p. 113
Etiology	p. 114
Clinical Manifestations	p. 114
Diagnosis	p. 115
Management	p. 115
Other Immunoglobulin Isotypes or Light Chain Deficiencies (Isolated IgG Subclass Deficiency, IgA with IgG Subclass Deficiency, Ig Heavy Chain Deletions, ¿ Light Chain Deficiency)	p. 116
Definition	p. 116
Etiology	p. 116
Clinical Manifestations	p. 116
Diagnosis	p. 117
Management	p. 117
Specific Antibody Deficiency with Normal Immunoglobulin Concentrations	p. 117
Definition	p. 117
Etiology	p. 117
Clinical Manifestations	p. 118
Diagnosis	p. 118
Management	p. 118
Transient Hypogammaglobulinemia of Infancy	p. 118
Definition	p. 118
Etiology	p. 118
Clinical Manifestations	p. 118
Diagnosis	p. 119
Management	p. 119
Phagocytes Defects	p. 131
Introduction	p. 131
Severe Congenital Neutropenias (ELA2 Deficiency, GFI1 Deficiency, HAX1 Deficiency, CSF3R Deficiency, Neutropenia with Myelodysplasia)	p. 131
Definition	p. 131
Etiology	p. 132
Clinical Manifestations	p. 134
Diagnosis	p. 134
Management	p. 134
Cyclic Neutropenia	p. 135
Definition	p. 135
Etiology	p. 135
Clinical Manifestations	p. 136
Diagnosis	p. 136
Management	p. 136
Leukocyte Adhesion Deficiency (LAD Types 1-3)	p. 136
Definition	p. 136
Etiology	p. 137
Clinical Manifestations	p. 137
Diagnosis	p. 139
Management	p. 139
RAC-2 Deficiency	p. 141
Definition	p. 141
Etiology	p. 141
Clinical Manifestations	p. 141
Diagnosis	p. 141
Management	p. 141
ß-Actin Deficiency	p. 141
Definition	p. 141
Etiology	p. 141
Clinical Manifestations	p. 142
Diagnosis	p. 143
Management	p. 143
Chronic Granulomatous Disease (CGD) (gp91 phox Deficiency, p22 phoxDeficiency, p47 phox Deficiency, p67 phox Deficiency)	p. 143
Definition	p. 143
Etiology	p. 143
Clinical Manifestations	p. 144
Diagnosis	p. 148
Management	p. 149
Neutrophil G-6PD Deficiency	p. 152
Definition	p. 152
Etiology	p. 153
Clinical Manifestations	p. 153
Diagnosis	p. 153
Management	p. 153
Myeloperoxidase Deficiency	p. 153
Definition	p. 153
Etiology	p. 153
Clinical Manifestations	p. 153
Diagnosis	p. 154
Management	p. 154
Specific Granule Deficiency	p. 154
Definition	p. 154
Etiology	p. 154
Clinical Manifestations	p. 154
Diagnosis	p. 154
Management	p. 155
Shwachman-Diamond Syndrome	p. 155
Definition	p. 155
Etiology	p. 155
Clinical Manifestations	p. 156
Diagnosis	p. 156
Management	p. 157
Localised Juvenile Periodontitis	p. 158
Definition	p. 158
Etiology	p. 158
Clinical Manifestations	p. 158
Diagnosis	p. 158
Management	p. 158
Papillon-Lefèvre Syndrome	p. 158
Definition	p. 158
Etiology	p. 158
Clinical Manifestations	p. 159
Diagnosis	p. 159
Management	p. 159
Genetic Disorders of Immune Regulation	p. 167
Introduction	p. 167
Familial Hemophagocytic Lymphohistiocytosis (Perforin Deficiency, MUNC13-4 Deficiency, Syntaxin 11 Deficiency)	p. 168
Definition	p. 168
Etiology	p. 168
Clinical Manifestations	p. 169
Diagnosis	p. 169
Management	p. 171
Immunodeficiency with Hypopigmentation (Chediak-Higashi Syndrome, Griscelli Syndrome, Type II, Hermansky-Pudlak Syndrome, Type II, p14 Deficiency)	p. 172
Definition	p. 172
Etiology	p. 172
Clinical Manifestations	p. 173
Diagnosis	p. 173
Management	p. 174
X-Linked Lymphoproliferative Syndrome (XLP) (SAP Deficiency, XIAP Deficiency)	p. 175
Definition	p. 175
Etiology	p. 175
Clinical Manifestations	p. 176
Diagnosis	p. 177
Management	p. 178
Autoimmune Lymphoproliferative Syndrome (ALPS) (ALPS Ia, Ib, IIa, IIb, III)	p. 178
Definition	p. 178
Etiology	p. 178
Clinical Manifestations	p. 180
Diagnosis	p. 180
Management	p. 181
Autoimmune Polyendocrinopathy with Candidiasis and Ectodermal Dystrophy (APECED)	p. 182
Definition	p. 182
Etiology	p. 182
Clinical Manifestations	p. 182
Diagnosis	p. 183
Management	p. 184
Immunodysregulation, Polyendocrinopathy, Enteropathy, X-Linked (IPEX)	p. 184
Definition	p. 184
Etiology	p. 184
Clinical Manifestations	p. 185
Diagnosis	p. 186
Management	p. 186
Defects in Innate Immunity: Receptors and Signaling Components	p. 195
Introduction	p. 195
Defective Toll-Like Receptor (TLR) Signaling Without Ectodermal Dysplasia (IRAK-4 Deficiency, TLR3 Deficiency, UNC-93B Deficiency)	p. 196
Definition	p. 196
Etiology	p. 198
Clinical Manifestations	p. 198
Diagnosis	p. 198
Management	p. 199
Defective Toll-Like Receptor (TLR)Signaling with Ectodermal Dysplasia(XL- and AD-Anhidrotic Ectodermal Dysplasias with Immunodeficiency)	p. 199
Definition	p. 199
Etiology	p. 199
Clinical Manifestations	p. 200
Diagnosis	p. 201
Management	p. 201
Mendelian Susceptibility to Mycobacterial Diseases (IFN-¿ Receptor 1/2 Deficiencies, IL-12/23Receptor ß1 Chain Deficiency, IL-12p40 Deficiency, STAT1 Deficiency, LZ-NEMO Deficiency)	p. 201
Definition	p. 201
Etiology	p. 202
Clinical Manifestations	p. 203
Diagnosis	p. 203
Management	p. 204
Warts, Hypogammaglobulinemia, Infections, Myelokathexis (WHIM) Syndrome	p. 205
Definition	p. 205
Etiology	p. 205
Clinical Manifestations	p. 205
Diagnosis	p. 206
Management	p. 206
Epidermodysplasia Verruciformis (EV Types 1,2)	p. 207
Definition	p. 207
Etiology	p. 207
Clinical Manifestations	p. 207
Diagnosis	p. 208
Management	p. 208
Autoinflammatory Disorders	p. 215
Introduction	p. 215
Familial Mediterranean Fever (FMF)	p. 217
Definition	p. 217
Etiology	p. 218
Clinical Manifestations	p. 218
Diagnosis	p. 219
Management	p. 219
Mevalonate Kinase Deficiency (MKD) (Hyperimmunoglobulinemia D and Periodic Fever Syndrome, Mevalonic aciduria)	p. 220
Definition	p. 220
Etiology	p. 220
Clinical Manifestations	p. 220
Diagnosis	p. 221
Management	p. 221
Tumor Necrosis Factor Receptor-Associated Periodic Syndrome (TRAPS)	p. 221
Definition	p. 221
Etiology	p. 222
Clinical Manifestations	p. 222
Diagnosis	p. 222
Management	p. 223
Cryopyrin-Associated Periodic Syndrome(CAPS) (Chronic Infantile Neurological Cutaneous Articular Syndrome, Muckle-Wells Syndrome, Familial Cold Autoinflammatory Syndrome)	p. 223
Definition	p. 223
Etiology	p. 223
Clinical Manifestations	p. 223
Diagnosis	p. 224
Management	p. 224
Blau Syndrome	p. 224
Definition	p. 224
Etiology	p. 224
Clinical Manifestations	p. 225
Diagnosis	p. 225
Management	p. 225
Pyogenic Arthritis, Pyoderma Gangrenosum and Acne Syndrome (PAPA)	p. 225
Definition	p. 225
Etiology	p. 225
Clinical Manifestations	p. 225
Diagnosis	p. 226
Management	p. 226
Multifactorial/Polygenic Autoinflammatory Diseases	p. 226
Periodic Fever, Aphtous Stomatitis, Pharyngitis and Cervical Adenitis (PFAPA)	p. 226
Systemic Onset Juvenile Idiopathic Arthritis (SoJIA)	p. 227
Adult-Onset Still's Disease (AOSD)	p. 227
Chronic Recurrent Multifocal Osteomyelitis (CRMO)	p. 227
Crohn's Disease (CD)	p. 227
Behçet's Disease (BD)	p. 227
""Undifferentiated""	p. 228
Complement Deficiencies	p. 235
Introduction	p. 235
Deficiencies of Classical Pathway Components (C1q/C1r/C1s Deficiencies, C4 Deficiency, C2 Deficiency)	p. 238
Definition	p. 238
Etiology	p. 238
Clinical Manifestations	p. 239
Diagnosis	p. 239
Management	p. 239
Deficiencies of Lectin Pathway Components (MBL Deficiency, MASP2 Deficiency)	p. 239
Definition	p. 239
Etiology	p. 240
Clinical Manifestations	p. 240
Diagnosis	p. 240
Management	p. 240
Deficiencies of Alternative Pathway Components (Factor D Deficiency, Properdin Deficiency)	p. 240
Definition	p. 240
Etiology	p. 241
Clinical Manifestations	p. 241
Diagnosis	p. 241
Management	p. 241
Deficiency of Complement Component C3	p. 241
Definition	p. 241
Etiology	p. 242
Clinical Manifestations	p. 242
Diagnosis	p. 242
Management	p. 242
Deficiencies of Terminal Pathway Components (C5-9 Deficiencies)	p. 242
Definition	p. 242
Etiology	p. 242
Clinical Manifestations	p. 242
Diagnosis	p. 242
Management	p. 243
Deficiencies of Complement Regulatory Proteins (C1 Inhibitor Deficiency, Factor I Deficiency, Factor H Deficiency, CD46 Deficiency, CD55 Deficiency, CD59 Deficiency)	p. 243
Definition	p. 243
Etiology	p. 243
Clinical Manifestations	p. 244
Diagnosis	p. 245
Management	p. 246
Other Well-Defined Immunodeficiencies	p. 251
Introduction	p. 251
Other Syndromes Associated with Defective DNA Repair (Ataxia-Telangiectasia, Ataxia-Like Syndrome, Nijmegen Breakage Syndrome, Bloom's Syndrome, ICF Syndrome)	p. 252
Definition	p. 252
Etiology	p. 253
Clinical Manifestations	p. 254
Diagnosis	p. 257
Management	p. 257
Di George Syndrome	p. 258
Definition	p. 258
Etiology	p. 258
Clinical Manifestations	p. 259
Diagnosis	p. 261
Management	p. 261
Wiskott-Aldrich Syndrome	p. 262
Definition	p. 262
Etiology	p. 262
Clinical Manifestations	p. 264
Diagnosis	p. 265
Management	p. 266
Hyper-IgE Syndrome (Stat3Deficiency, Tyk2 Deficiency, HIES with Unknown Origin)	p. 267
Definition	p. 267
Etiology	p. 267
Clinical Manifestations	p. 267
Diagnosis	p. 268
Management	p. 269
Immuno-Osseous Dysplasias (Schimke Syndrome, Cartilage Hair Hypoplasia)	p. 269
Definition	p. 269
Etiology	p. 270
Clinical Manifestations	p. 271
Diagnosis	p. 272
Management	p. 272
Chronic Mucocutaneous Candidiasis	p. 272
Definition	p. 272
Etiology	p. 273
Clinical Manifestations	p. 273
Diagnosis	p. 274
Management	p. 274
Netherton Syndrome	p. 274
Definition	p. 274
Etiology	p. 275
Clinical Manifestations	p. 275
Diagnosis	p. 276
Management	p. 276
Dyskeratosis Congenita and Høyeraal-Hreidarsson Syndrome	p. 276
Definition	p. 276
Etiology	p. 276
Clinical Manifestations	p. 277
Diagnosis	p. 278
Management	p. 278
Syndromic Immunodeficiencies	p. 291
Introduction	p. 291
Syndromes Associated with Growth Deficiency	p. 293
Cartilage Hair Hypoplasia	p. 294
Schimke Immuno-osseous Dysplasia	p. 294
Short-Limb Skeletal Dysplasia with Combined Immunodeficiency	p. 294
Roifman Syndrome (Roifman Syndrome 1)	p. 294
Roifman-Costa Syndrome (Roifman Syndrome 2)	p. 294
Spondyloenchondrodysplasia	p. 295
Growth Hormone Pathway Defects	p. 295
Kabuki Syndrome	p. 295
CHARGE Association	p. 295
Rubinstein-Taybi Syndrome	p. 295
Mulvihill-Smith Syndrome	p. 296
Syndromes Associated with Gastrointestinal Dysfunction	p. 296
Shwachman-Diamond Syndrome	p. 298
Familial Intestinal Polyatresia	p. 298
Trichohepatoenteric Syndrome	p. 298
Syndromes Associated with Cutaneous Abnormalities	p. 298
Wiskott-Aldrich Syndrome	p. 298
Chediak-Higashi Syndrome	p. 298
Griscelli Syndrome, Type II	p. 298
Omenn Syndrome	p. 298
WHN Deficiency	p. 299
Papillon-Lefèvre Syndrome	p. 299
WHIM Syndrome	p. 299
Hypohidrotic/Anhidrotic Ectodermal Dysplasia	p. 299
Incontinentia Pigmenti	p. 299
OLEDAID Syndrome	p. 299
Dyskeratosis Congenita	p. 300
Hermansky-Pudlak Syndrome, Type II	p. 300
Poikiloderma with Neutropenia	p. 300
Acrodermatitis Enteropathica	p. 300
Netherton Syndrome	p. 300
p14 Deficiency	p. 300
Syndromes Associated with Neurologic Dysfunction	p. 300
Myotonic Dystrophy	p. 300
Høyeraal-Hreidarsson Syndrome	p. 301
Cohen Syndrome	p. 301
Inborn Errors of Metabolism Associated with Immunodeficiency	p. 301
Adenosine Deaminase Deficiency	p. 301
Purine Nucleoside Phosphorylase Deficiency	p. 301
Leukocyte Adhesion Deficiency, Type 2	p. 301
Congenital Disorders of Glycosylation, Type I	p. 302
Glycogen Storage Disease Ib/Ic	p. 303
Barth Syndrome	p. 303
Galactosemia	p. 303
Branched-Chain Amino Acidurias	p. 303
Lysinuric Protein Intolerance	p. 303
Syndromes with Chromosome Instability and/or Defective DNA Repair Associated with Immunodeficiency	p. 303
Nijmegen Breakage Syndrome	p. 303
Bloom Syndrome	p. 304
Ataxia-Telangiectasia	p. 304
DNA Ligase IV Deficiency	p. 305
ICF Syndrome	p. 305
Fanconi Pancytopenia	p. 305
Syndromes Associated with Chromosomal Abnormalities of Number or Structure	p. 305
Deletions of 22q11 and 10p13-p14	p. 305
Trisomy 21	p. 305
Partial Deletions of Chromosome 4p	p. 306
Turner Syndrome	p. 306
Treatment of Primary Immunodeficiency Diseases	p. 315
Introduction	p. 315
Therapy for Combined T and B Cell Immunodeficiencies	p. 315
Severe Combined Immunodeficiency	p. 315
Immunoglobulin Class Switch Recombination Deficiencies (Affecting CD40-CD40L)	p. 317
MHC Class II Deficiency	p. 318
Therapy for Predominantly Antibody Deficiencies	p. 318
Agammaglobulinemia with Absent B Cells	p. 318
Hypogammaglobulinemia with Normal/Low Number of B Cells	p. 319
Immunoglobulin Class Switch Recombination Deficiencies (Due to Intrinsic B Cell Defects)	p. 319
Selective IgA Deficiency	p. 320
Isolated IgG Subclass Deficiency	p. 321
Specific Antibody Deficiency with Normal Immunoglobulin Concentrations	p. 321
Transient Hypogammaglobulinemia of Infancy	p. 321
Therapy for Phagocytes Defects	p. 321
Severe Congenital Neutropenias/Cyclic Neutropenia	p. 321
Leukocyte Adhesion Deficiency	p. 323
Chronic Granulomatous Disease	p. 323
Therapy for Genetic Disorders of Immune Regulation	p. 323
Chediak-Higashi Syndrome	p. 323
Griscelli Syndrome, Type II	p. 324
X-Linked Lymphoproliferative Syndrome	p. 324
Therapy for Defects in Innate Immunity: Receptors and Signaling Components	p. 325
IRAK-4 Deficiency	p. 325
Mendelian Susceptibility to Mycobacterial Diseases	p. 325
Warts, Hypogammaglobulinemia, Infections, Myelokathexis(WHIM) Syndrome	p. 325
Therapy for Autoinflammatory Disorders	p. 325
Familial Mediterranean Fever	p. 325
Other Autoinflammatory Disorders	p. 326
Therapy for Complement Deficiencies	p. 326
Deficiencies of Classical, Lectin and Alternative Pathways Components	p. 326
Deficiencies of Terminal Pathway Components	p. 326
C1 Inhibitor Deficiency	p. 326
Therapy for Other Well-Defined Immunodeficiencies	p. 326
Ataxia-Telangiectasia	p. 326
Di George Syndrome	p. 327
Wiskott-Aldrich Syndrome	p. 328
Hyper-IgE Syndrome	p. 328
Chronic Mucocutaneous Candidiasis	p. 328
Index	p. 335
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