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Systemic Lupus Erythematosus, An Issue of Rheumatic Disease Clinics, E-Book

Systemic Lupus Erythematosus, An Issue of Rheumatic Disease Clinics, E-Book

Ellen M. Ginzler

(2014)

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Book Details

Abstract

In only the last four years, there have been dramatic changes in the understanding of the immunology, genetic/epigenetic associations, and identification of new targets for therapy in Systemic Lupus Erythematosus. The editors have enlisted a superb group of authors to present articles detailing cutting-edge advances in these areas.

Table of Contents

Section Title Page Action Price
Front Cover Cover
Systemic Lupus Erythematosus\r i
Copyright\r ii
Contributors iii
CONSULTING EDITOR iii
EDITORS iii
AUTHORS iii
Contents vii
Foreword\r vii
Preface: Systemic Lupus Erythematosus\r vii
Environmental Influences on Systemic Lupus Erythematosus Expression\r vii
Clinical Perspectives on Lupus Genetics: Advances and Opportunities\r vii
Impact of Race and Ethnicity in the Course and Outcome of Systemic Lupus Erythematosus\r vii
The Immunopathology of Cutaneous Lupus Erythematosus\r viii
Pathogenesis and Treatment of Atherosclerosis in Lupus\r viii
Systemic Lupus Erythematosus and Malignancies: A Review Article\r viii
Post-marketing Experiences with Belimumab in the Treatment of SLE Patients\r viii
Recent Clinical Trials in Lupus Nephritis\r ix
The Kidney Biopsy in Lupus Nephritis: Is It Still Relevant?\r ix
Improving Participation in Clinical Trials of Novel Therapies: Going Back to Basics\r ix
RHEUMATIC DISEASE CLINICS\rOF NORTH AMERICA\x0B x
FORTHCOMING ISSUES x
November 2014 x
February 2015 x
RECENT ISSUES x
May 2014 x
February 2014 x
November 2013 x
Foreword xi
Preface: Systemic Lupus Erythematosus \r xiii
Environmental Influences on Systemic Lupus Erythematosus Expression 401
Key points 401
INTRODUCTION 401
INTERPLAY BETWEEN ENVIRONMENTAL FACTORS, GENETICS, AND EPIGENETICS 402
DIETARY INFLUENCES ON SLE 403
ESTABLISHED ENVIRONMENTAL RISK FACTORS FOR SLE 403
Silica Exposure and SLE 404
Cigarette Smoking and SLE 404
Smoking and the Role of Gene-Environment Interactions 405
EBV Exposure and SLE 405
INFLUENCE OF VITAMIN D STATUS ON SLE 405
LESS ESTABLISHED ENVIRONMENTAL RISK FACTORS 406
Metals and SLE 406
Pesticides, Persistent Organic Pollutants, and SLE 406
Other Environmental Agents and SLE 407
METHODOLOGICAL LIMITATIONS IN STUDIES OF ENVIRONMENTAL INFLUENCES 407
Defining the SLE Exposome 408
FUTURE CONSIDERATIONS AND SUMMARY 408
REFERENCES 409
Clinical Perspectives on Lupus Genetics 413
Key points 413
INTRODUCTION 413
Pathways Implicated by Lupus Genetics 414
Ubiquitination (nuclear factor kappa beta signaling) 414
DNA degradation (apoptosis/clearance of debris) 414
Innate immunity (Toll-like receptor pathways/interferon) 414
B-cell immunity (function/signaling) 418
T-cell immunity (function/signaling) 418
Neutrophil/monocyte immunity (function/signaling) 418
Lymphocyte development 418
Antigen presentation 419
Genetic Associations with Autoantibody Production 419
Association of Genes Within Select Lupus Clinical Subsets 419
Genetics of Nephritis and Renal Outcomes 420
ABIN1/TNIP1 420
APOL1 421
FcγRIIB 421
STAT4 421
TNFSF4 421
SLE Genetic Studies in Progress 421
FUTURE CONSIDERATIONS 422
Opportunities for Additional Clinically Important Genetic Studies 422
ACKNOWLEDGMENTS 424
REFERENCES 424
Impact of Race and Ethnicity in the Course and Outcome of Systemic Lupus Erythematosus 433
Key points 433
INTRODUCTION 433
DISEASE EXPRESSION 434
DISEASE ACTIVITY 435
DAMAGE ACCRUAL 438
WORK DISABILITY 439
MORTALITY 440
INFLUENCE OF ETHNICITY ON RESPONSE TO LUPUS THERAPY 442
MYCOPHENOLATE MOFETIL AND CYCLOPHOSPHAMIDE IN LN THERAPY IN MULTIETHNIC POPULATIONS 442
Induction Treatment 442
Maintenance Treatment 444
CELL-TARGETED BIOLOGICAL THERAPIES: B-CELL–TARGETED THERAPIES AND COSTIMULATION BLOCKER THERAPY 445
B-Cell–Targeted Therapies and Ethnicity 445
Costimulation Blocker Therapy (Abatacept) 445
ETHNIC DISPARITIES IN RENAL REPLACEMENT THERAPIES IN LN 446
SUMMARY 447
REFERENCES 447
The Immunopathology of Cutaneous Lupus Erythematosus 455
Key points 455
INTRODUCTION 455
Clinical Manifestations 455
PATHOGENESIS OVERVIEW 456
TRIGGERS 456
Genetics 456
UV Light 457
Infections 457
Drugs and Chemicals 458
Hormones 458
Apoptosis 458
Cytokines 458
IFNs 458
TNF-α 459
B-lymphocyte stimulator (BLyS) or BAFF 459
IL-6 459
IL-10 460
IL-17 460
Chemokines 460
ADAPTIVE IMMUNE SYSTEM 460
T Cells 460
B Cells 461
Autoantibodies 461
Complement 461
INNATE IMMUNE SYSTEM 461
DCs 461
Neutrophils 461
TLRs 462
THERAPEUTIC IMPLICATIONS 462
Photoprotection 462
Topical Therapy 462
Antimalarial Therapy 462
Immunosupressive and Immunomodulatory Therapy 463
SUMMARY 464
REFERENCES 466
Pathogenesis and Treatment of Atherosclerosis in Lupus 475
Key points 475
PATHOGENESIS OF ATH 476
High-Density Lipoprotein Prevents Oxidation and Inflammation 476
IDENTIFICATION OF PATIENTS WITH SLE AT RISK FOR CV EVENTS 477
Traditional and SLE-Specific Risk Factors for ATH in SLE 477
SLE-Specific Risk Factors 477
Disease activity, duration, and damage 477
POTENTIAL BIOMARKERS FOR ATH IN SLE 478
Antiphospholipid Antibodies 478
C-Reactive Protein 478
Proinflammatory HDL 478
Paraoxonase 479
Adipocytokines 479
Homocysteine 479
Biomarker Panels 482
SUBCLINICAL MEASURES OF ATH 482
MANAGEMENT STRATEGIES FOR PREVENTION OF CV COMPLICATIONS IN SLE 483
Minimizing Framingham Risk Factors 483
Hypertension: Antihypertensives 483
Dyslipidemia: Statin Use 484
THE IMPACT OF MODULATORS OF LUPUS DISEASE ACTIVITY ON CVD 485
Antimalarial Therapy 485
Azathioprine 485
Glucocorticoids 485
Mycophenolate Mofetil 485
CONSIDERATION FOR FUTURE CLINICAL TRIALS 486
REFERENCES 487
Systemic Lupus Erythematosus and Malignancies 497
Key points 497
INTRODUCTION 498
HEMATOLOGIC CANCERS 498
LUNG CANCERS 500
CERVICAL CANCERS AND DYSPLASIA 500
HEAD AND NECK CANCERS 501
DECREASED CANCER RISK IN SLE 501
SUMMARY 502
REFERENCES 503
Post-marketing Experiences with Belimumab in the Treatment of SLE Patients 507
Key points 507
INTRODUCTION 507
REGISTRATION STUDIES 508
METHOD 510
RESULTS 511
Post-approval Observational Results 511
Favorable clinical response to belimumab at 3 months 511
Twelve-month outcomes associated with belimumab in patients with systemic lupus erythematosus in clinical practice settings ... 513
Post-marketing experience with belimumab in US lupus centers: data from the Lupus Clinical Trials Consortium, Inc. (LCTC) n ... 513
DISCUSSION 514
SUMMARY AND FUTURE DIRECTIONS 515
REFERENCES 515
Recent Clinical Trials in Lupus Nephritis 519
Key points 519
INTRODUCTION 519
Course of Lupus Nephritis 520
Prognosis 520
Goals of Treatment 520
Traditional Treatment Approach 521
TRIALS OF ALTERNATIVE DOSING OF CYCLOPHOSPHAMIDE 521
Euro-Lupus Nephritis Trial 521
Myeloablative Regimen 523
Additional Trials 523
TRIALS OF AZATHIOPRINE, CYCLOSPORINE, OR TACROLIMUS AS ALTERNATIVES TO CYCLOPHOSPHAMIDE AS INDUCTION TREATMENT 523
Dutch Working Party Trial 523
Trials of Calcineurin Inhibitors 524
TRIALS OF MYCOPHENOLATE MOFETIL AS INDUCTION TREATMENT 524
Noninferiority Study 524
ALMS 527
TRIALS OF ALTERNATIVES TO PROLONGED TREATMENT WITH CYCLOPHOSPHAMIDE AS MAINTENANCE TREATMENTS 528
Miami Study 528
ALMS 528
MAINTAIN 530
Cyclosporine Versus Azathioprine 530
TRIAL OF RITUXIMAB 531
LUNAR 531
TRIALS IN MEMBRANOUS LUPUS NEPHRITIS 531
SYNTHESIS OF THE EVIDENCE 531
Cochrane Review 531
American College of Rheumatology Treatment Recommendations 532
SUMMARY 532
REFERENCES 532
The Kidney Biopsy in Lupus Nephritis 537
Key points 537
INTRODUCTION 537
WHEN AND HOW OFTEN DOES A PATIENT WITH LN NEED A KIDNEY BIOPSY? 538
BIOMARKERS OF KIDNEY DISORDERS 541
MOLECULAR DIAGNOSIS: THE FUTURE OF THE PERCUTANEOUS KIDNEY BIOPSY IN LN 546
SUMMARY 548
REFERENCES 549
Improving Participation in Clinical Trials of Novel Therapies 553
Key points 553
BACKGROUND 553
DETERMINANTS OF THE PHENOMENA 554
REVIEW OF LITERATURE ON MAXIMIZING ENROLLMENT/RETENTION 554
RECOMMENDATIONS 555
Keep It Simple 555
Communicate Using Plain English 556
Address the Factors Underlying Difficult Choices 556
Align “Ask” with Honest Emotion and Feelings 556
Minimize Time on Ineffective or Marginally Effective Treatments 557
Waste No Time 557
Learn from Refusals 557
SUMMARY 557
REFERENCES 558
Index 561