About the Book
• The first textbook entirely devoted to systemic vasculitis (SV) edited by multinational team of contributors.
• Divided into six sections, the first section deal with epidemiology, genetics and classification of vasculitis syndrome.
• The second section deals with basic sciences and the role of neutrophils, antineutrophil cytoplasmic antibodies along with the details on skin, nerves and brain, lungs and kidney pathology.
• Contains innumerable illustrative microphotographs of various pathological changes in different organs.
• The third section deals with imaging modalities significant in diagnosing and assessing disease activity.
• The fourth section deals with the clinical manifestations based upon organ system.
• The fifth section contains chapters detailing the approach to children and adult with vasculitis, assessing disease activity and damage.
• The last section deals with individual vasculitis syndromes.
• Essential reading for practicing and academic rheumatologists, pathologists, internists and other clinicians involved in the management of patient with systemic vasculitides.
About the Author
Aman Sharma MD MAMS FIACM FICP FRCP (London)
Table of Contents:
SECTION 1 Introduction
1. Epidemiology of Systemic Vasculitis 3
David GI Scott, Paul Bacon
Large-Vessel Vasculitis 3
Medium-Vessel Vasculitis 5
Small-Vessel Vasculitis ANCA-associated Vasculitis 6
Small-Vessel Vasculitis-Immune Complex 8
2. Genetics of Vasculitis 10
John Mathew, Ramya J
Large-Vessel Vasculitis 10
Medium-Vessel Vasculitis 12
Small-Vessel Vasculitis 12
3. Classification of Vasculitis 16
Aman Sharma, Richard Watts
American College of Rheumatology Criteria 17
Chapel Hill Consensus Conference
Nomenclature System 17
European Medical Agency Algorithm 18
Classification of Childhood Vasculitis 18
SECTION 2 Basic Sciences
4. Neutrophils in
ANCA-associated Vasculitis 23
Véronique Witko-Sarsat, Arnaud Roccabianca,
Luc Mouthon
The ANCA Antigens PR3 and MPO:
Keys in the Pathophysiology of
ANCA-Associated Vasculitides 23
Neutrophil Activation in ANCA-Associated
Vasculitides: Role of ANCA 26
5. Antineutrophil Cytoplasmic Antibodies 29
Ashish Aggarwal, Aman Sharma, Wolfgang L Gross
Antineutrophil Cytoplasmic Antibodies 29
Antineutrophil Cytoplasmic
Antibody-Associated Vasculitis 29
Production of ANCA 29
Interaction between ANCAs and
their Target Antigens 30
Pathophysiology of AAV 30
Genetic Association of AAV 30
Environmental Factors 30
Pathogenic B-Cell Response
and Production of ANCA 30
Aberrant T-Cell Response
and Granuloma Formation 31
Monocyte Activation and AAV 31
ANCA-Mediated Interaction between
Neutrophils and Endothelial Cells 31
ANCA in the Diagnosis of Vasculitis 31
Should ANCA Titers may be Used for
the Management of ANCA-Vasculitis? 32
6. Animal Models of ANCA Vasculitis 35
Mark Little, Alice Coughlan
Passive Transfer Model 36
Bone Marrow Transplant Model 36
Mouse Model of Autoimmune Vasculitis 36
Rat Model of Experimental
Autoimmune Vasculitis 36
Rodent Models of PR3-ANCA Disease 37
Insights from Animal Models 37
7. Pathogenesis of Vasculitis 40
Durga Prasanna Misra, Anupam Wakhlu,
Vikas Agarwal
Classification and Nomenclature 40
Pathogenesis of Large-Vessel Vasculitis 40
Pathogenesis of Medium-Vessel Vasculitis 42
Pathogenesis of Immune-Complex-Mediated
Small-Vessel Vasculitis 43
ANCA-Associated Small Vessel Vasculitis 44
8. Pathology of Cutaneous Vasculitis 49
BD Radotra
Large-Vessel Vasculitis 49
Medium-Vessel Vasculitis 50
Small-Vessel Vasculitis 50
9. Pathology of Pulmonary Vasculitis 54
Amanjit Kaur, Ashim Das
Primary Vasculitides 54
Secondary Vasculitides 60
10. Pathology of Renal Vasculitis 64
Ritambhra Nada, Manish Rathi,
Aman Sharma, J Charles Jennette
Small-Vessel Vasculitis 64
Medium-Vessel Vasculitis 75
Large-Vessel Vasculitis 79
11. Pathology of Central Nervous
System and Peripheral Nerves 85
BD Radotra, RK Vasishta
Noninfectious Central
Nervous System Vasculitides 85
Primary Angiitis of Central
Nervous System (PACNS) 87
Central Nervous System
Vasculitis due to Infections 90
SECTION 3 Imaging Modalities
12. Imaging in Vasculitis 95
Chirag Ahuja, NK Khandelwal
Ultrasonography 95
Computed Tomography 95
Magnetic Resonance Imaging 96
Digital Subtraction Angiography 96
Imaging: What to Look for? 96
Large-Vessel Vasculitis 97
Medium-Vessel Vasculitis 99
Kawasaki Disease 101
Small-Vessel Vasculitis 101
Variable-Vessel Vasculitis 102
Single-Organ Vasculitis 103
Vasculitis Associated with Systemic Disease 103
Infection-Related Vasculitis 103
13. Positron Emission
Tomography and Vasculitides 106
Enrico Tombetti, Justin C Mason
Principles of PET Imaging 106
18F-FDG PET/CT in Vasculitides 107
Future Promising Technical Improvements 113
SECTION 4 Clinical Manifestations According
to Organ Involvement
14. Cutaneous Vasculitis 121
Sunil Dogra, Vinay Keshavamurthy
Epidemiology 121
Classification and Nomenclature of Vasculitis 121
Pathogenesis 122
Approach to a Patient with Vasculitis 124
Cutaneous Leukocytoclastic Angiitis (CLA) 126
IgA Vasculitis 126
Urticarial Vasculitis 127
Cryoglobulinemic Vasculitis 127
ANCA-Associated Vasculitis 128
Polyarteritis Nodosa and Cutaneous Arteritis 129
Treatment 129
15. Retinal Vasculitis 132
Reema Bansal, Mohit Dogra, Amod Gupta
Clinical Features 133
Diagnostic Work-Up 133
Tuberculosis 135
Herpes Viruses 135
Cytomegalovirus 136
Toxoplasmosis 137
Syphilis 137
Behçet’s Disease 138
Sarcoidosis 138
Systemic Vasculitis Granulomatosis with
Polyangiitis (Wegener’s Granulomatosis),
Polyarteritis Nodosa, and Takayasu’s Arteritis 138
Frosted Branch Angiitis 140
16. Cardiac Manifestations 142
Rajesh Vijayvergiya, Saujatya Chakraborty
Pathogenesis 142
Specific Vasculitis 143
Polyarteritis Nodosa 143
Granulomatosis with Polyangiitis (Wegener’s) 143
Eosinophilic Granulomatosis with Polyangiitis
(Churg-Strauss Syndrome) 143
Microscopic Polyangiitis 144
Cryoglobulinemic Vasculitis 144
Kawasaki’s Disease 144
Takayasu Arteritis 144
Behçet’s Disease 145
17. Pulmonary Manifestations 149
SK Jindal
Clinical Manifestations 149
Granulomatosis with Polyangiitis (Wegener’s) 151
Behçet’s Disease 152
Eosinophilic Granulomatosis with Polyangiitis
(Churg–Strauss Syndrome) 153
Connective Tissue Disorders 153
Miscellaneous Vasculitides with
Pulmonary Manifestations 153
Pulmonary Renal Syndrome 154
Management of Pulmonary Vasculitis 154
18. Renal Manifestations 157
Manish Rathi, Aman Sharma, Ritambhra Nada
Large-Vessel Vasculitis 157
Medium-Vessel Vasculitis 158
Small-Vessel Vasculitis 158
Other Vasculitis 161
19. Neurological Manifestations 164
Manish Modi, Manoj Goyal
Central Nervous System Syndromes 164
Peripheral Nervous System Syndromes 167
20. Vasculitic Neuropathy 173
Manoj Goyal, Manish Modi
Classification 173
Epidemiology 174
Pathogenesis and Pathology 175
Clinical Features 176
Types of Vasculitic Neuropathies 176
Diagnosis 180
Differential Diagnosis 181
Management 181
21. Gastrointestinal Manifestations 190
Saroj K Sinha, Raghavendra Prasada,
Rakesh Kochhar
Gastrointestinal Tract Involvement
in Large-Vessel Vasculitis 190
Gastrointestinal Tract Involvement in
Medium-Vessel Vasculitis 190
Gastrointestinal Tract Involvement in
Small-Vessel Vasculitis 193
IgA Vasculitis (Henoch-Schönlein Purpura) 194
Vasculitis Associated with Systemic Disease 197
Behçet’s Disease Vasculitis 200
Localized Vasculitis of Gastrointestinal Tract 201
22. Head and Neck Manifestations 205
Naresh K Panda, Roshan K Verma
Otolaryngologist Perspective 205
Head and Neck Manifestations in GPA 206
Otologic Manifestation 206
Rhinologic Manifestations 206
Otolaryngologist’s Role 207
Laryngeal and Tracheal Manifestation 208
Oral Manifestations 208
Differential Diagnosis 208
Eosinophilic Granulomatosis with Polyangiitis
(Churg-Strauss Vasculitis) 208
Kawasaki Disease 209
Polyarteritis Nodosa 209
Giant Cell Arteritis 210
Head and Neck Manifestations 210
SECTION 5 Principles of Management
23. Approach to Childhood Vasculitis 217
Amita Aggarwal, Anuj Shukla
Prevalence 217
Clinical Features 217
Case Vignette 218
Henoch-Schönlein Purpura 219
Behçet’s Syndrome 220
Classical Polyarteritis Nodosa 220
Takayasu’s Arteritis 221
24. Approach to Adult with
Systemic Vasculitis 225
Pradeep Bambery, Vinay Sagar, Aman Sharma
25. Assessment of Disease
Activity and Damage 232
Aman Sharma, Ram Nath Misra
Tools for Assessment 232
Radiological Assessment 232
Computerized Tomography 233
Ultrasonography 233
Positron Emission Tomography 233
Serological Markers in Disease Assessment 233
Clinical Indices of Disease Assessment 234
Disease Activity 234
Instruments for Assessing Disease Activity 234
Birmingham Vasculitis Activity Score 235
Indian Takayasu Clinical Activity Score 235
Vasculitis Damage Index 235
Quality of Life Assessment 235
Patient Reported Outcomes 235
26. Newer and Future
Treatment of Vasculitis 238
David Jayne
Current Outcomes 238
Newer Therapies 239
Other Forms of Vasculitis 240
Future Therapies for Vasculitis 241
Disclosures 243
SECTION 6 Individual Vasculitis Syndromes
27. Giant Cell Arteritis and
Polymyalgia Rheumatica 247
Tanaz A Kermani
Case Vignette 247
Epidemiology 248
Diagnosis 249
Clinical Features 249
Investigations 250
Diagnostic Approach 252
Management 253
28. Takayasu’s Arteritis 258
Aravind G Hegde, Ruchika Goel,
George Joseph, Debashish Danda
Case Vignette 258
History 259
Epidemiology 259
Classification Criteria and Diagnosis 259
Pathology 260
Pathogenesis 261
Clinical Features 262
Diagnosis 263
Imaging 263
Differential Diagnosis 264
Treatment 264
Corticosteroids 264
Conventional Immunosuppressives 265
Definition of Refractory Disease in TA 265
Biologic Agents 265
Endovascular and Surgical Interventions 266
Disease Activity Assessment and Monitoring 267
Future Directions 268
29. Kawasaki Disease 272
S Madhusudan, Surjit Singh
Case Vignette 272
Epidemiology 272
Etiopathogenesis 273
Clinical Features 273
Clinical Criteria for the Diagnosis of KD 274
Investigations 274
Incomplete and Atypical KD 274
Differential Diagnosis 274
Treatment 275
30. Polyarteritis Nodosa 277
Loïc Guillevin
Case Vignette 277
Classification Criteria and Diagnosis 278
Epidemiology 278
Etiology and Precipitating Factors 278
Histology 280
Clinical Features 281
Laboratory Tests 284
Angiography 284
Outcome and Prognosis of PAN 284
Treatment of PAN 285
How should PAN be Treated? 285
31. Granulomatosis with Polyangiitis
(Wegener’s Granulomatosis) 289
Aman Sharma, Pradeep Bambery
Case Vignette 289
Classification and Nomenclature 289
Epidemiology 290
Pathogenesis 290
Clinical Features 290
Upper Airways and Nose 291
Oral Manifestations 292
Pulmonary Involvement 292
Renal Manifestations 292
Fiberoptic Endoscopy and Bronchoscopy 294
Measurement of Disease Activity 294
Treatment 295
Morbidity 296
32. Microscopic Polyangiitis 300
Chetan Mukhtyar, P Sharma
Case Vignette 300
Epidemiology 301
Diagnosis 301
Clinical Features 301
Investigations 301
Diagnostic Approach 302
Management 302
Prognosis 303
33. Eosinophilic Granulomatosis with
Polyangiitis (Churg-Strauss Syndrome) 306
Christian Pagnoux, Corisande Baldwin
Case Vignette 306
Epidemiology 308
Pathogenesis 308
Diagnosis 309
Clinical Features 309
Management 314
34. Immunoglobulin A Vasculitis 320
Deepti Suri, Vikas Suri
Case Vignette 320
35. Primary Angiitis of
Central Nervous System 325
Atul Khasnis, Leonard Calabrese
Case Vignette 325
Imaging 325
Biopsy and Pathology 326
Mimics 326
Diagnosing PACNS 327
Treatment 327
36. Behçet’s Disease 329
Fatma Alibaz-Oner, Haner Direskeneli
Case Vignette 329
Epidemiology 329
Diagnosis 330
Clinical Features 330
Investigations 333
Diagnostic Approach 333
Management 333
37. Cryoglobulinemic Vasculitis 337
Cloé Comarmond, Patrice Cacoub
Case Vignette 337
Epidemiology 337
Diagnosis 338
Clinical Features 339
Diagnostic Approach 340
Management 340
Therapeutic Guidelines for HCV-MC 341
38. Relapsing Polychondritis 344
Aman Sharma, Arjun D Law,
Kusum Sharma, Rohini Handa
Epidemiology 344
Etiopathogenesis 344
Clinical Features 345
Auricular and Vestibular Involvement 345
Joint Involvement 345
Nasal Involvement 345
Respiratory Tract Involvement 346
Cardiovascular Involvement 346
Ocular Involvement 347
Neurologic Involvement 347
Renal Involvement 347
Dermatological Involvement 347
Other Symptoms 347
Prognosis 348
Associated Conditions 348
Diagnostic Criteria 348
Differential Diagnosis 348
Investigations 348
Assessment of Disease Activity 349
Management 349
Management of Complications
and Sequelae 350
39. IgG4 Disease 355
M Vishnu Vardhan Reddy
Epidemiology 356
Pathogenesis 356
Diagnosis 357
Histopathological Features
of IgG4-Related Disease 358
Quantitative Assessment
of the IgG4 Stain 358
Image Characteristics Suggestive of
IgG4-Related Disease on 18F-Fdg PET/CT 359
Pancreas 360
Aortitis 363
Peripheral Nerves 363
40. Infection-associated Vasculitis 365
Neha Garg, Ajay Wanchu
Viral Infections and Vasculitis 365
HIV-associated Vasculitis 365
Parvovirus B19 Associated Vasculitis 367
Cytomegalovirus 367
Epstein-Barr Virus 367
Varicella-Zoster Virus 368
Bacterial Infections and Vasculitis 368
41. Vasculitis Mimics 372
Subramanian Ramaswamy, Vinod Ravindran
Case Vignette 372
When to Suspect Vasculitic Mimics? 373
Infections 373
Disorders of the Connective Tissue Matrix 374
Drug-induced Vasculitis 374
Malignancy-associated Vasculitis 375
Atherothrombotic Vascular Disorders 375
Miscellaneous 375
Diagnostic Approach and Management 376
42. Secondary Vasculitis 378
Varun Dhir
Rheumatoid Vasculitis 378
Lupus Vasculitis 381
Paraneoplastic Vasculitis 383
Infection-associated Vasculitis 384
43. Cogan’s Syndrome 388
Tommy CY Chan, Vishal Jhanji
Epidemiology 388
Clinical Features 388
Ocular Manifestations 389
Audiovestibular Manifestations 389
Systemic Manifestations 389
Diagnostic Approach and Investigations 389
Treatment 390
44. Malignancy-associated Vasculitis 392
Narendra Kumar, Pankaj Kumar,
Rupali Agarwal, Shabab Lalit Angurana
Association of Vasculitis and Malignancy 392
Risk Factors and Pathogenesis of
Malignancy-associated Vasculitis 393
Clinical Presentation and Prognosis 394
Specific Malignancy-associated Vasculitis 395
ANCA-associated Vasculitis and Malignancy 397
When and How to Rule
Out Underlying Malignancy
in a Patient of Vasculitis? 398
45. Pregnancy and Vasculitis 401
Shankar Naidu, Susmita Sharma,
Aman Sharma, Surjit Singh
Fertility Concerns 401
Conception and Preconception
Counseling 402
Pregnancy Outcomes 402
Large-Vessel Vasculitis 402
Medium-Vessel Vasculitis 403
Small-Vessel Vasculitis 403
Variable-Vessel Vasculitis 404
46. Prevention and Management of Infections 407
Gaurav Prakash, Subhash Varma,
Pankaj Malhotra
Defining Immunocompromised Host 407
Common Medications in the Treatment of
Vasculitis that Cause Immunosuppression 408
Prevention of Infections in
the Patient Treated for Vasculitis 408
Treatment of Vasculitis in Specific Infections 410
Clinical Features and Evaluation of Infections in
An Immunocompromised Host 410
Management 411
Index 413
