Dubois' Lupus Erythematosus and Related Syndromes

Daniel J Wallace MD, FACP, MACR is a board-certified internist and rheumatologist. A Clinical Professor of Medicine at the David Geffen School of Medicine at UCLA, he is the Associate Director of the Rheumatology Fellowship Program at Cedars-Sinai Medical Center, where he also serves on the Board of Governors. Dr. Wallace has authored nearly 450 peer reviewed manuscripts, 30 book chapters, eight textbooks (on lupus, osteoarthritis, Sjogren's syndrome and fibromyalgia) and his practice includes caring for 2,000 lupus patients, the largest lupus cohort in the United States. Dr Wallace is co-chair of the Lupus Industry Council of the Lupus Research Alliance, past chair of the Lupus Foundation of America, and has served on the Board of Directors of the United Scleroderma Foundation and the Medical Advisory Board of the Sjogren's Syndrome Foundation. He has been Chief of Rheumatology at the City of Hope and Cedars-Sinai Medical Center, and chairman of the Research and Education Foundation of the American College of Rheumatology. Dr. Hahn received her MD from the Johns Hopkins University School of Medicine, where she later trained in Rheumatology. She trained in internal medicine at Washington University in St. Louis. Dr. Hahn heads research groups that do basic studies in the immune abnormalities that cause systemic lupus erythematosus (SLE) and is developing interventions that help restore the immune response to normal. She also heads a group that studies clinical problems in patients with SLE, including accelerated atherosclerosis and potential new therapies (clinical trials). In addition, Dr. Hahn provides clinical consultations for patients with rheumatic diseases, particularly SLE. She also teaches Rheumatology and heads the administration of the Division of Rheumatology, which has 25 full-time faculty, 8 fellows and several undergraduate students, medical students, PhD students, postdoctoral trainees, and an administrative staff.

Preface, vii

List of Contributors, viii

SECTION 1 What Is Lupus?

1 History of Lupus, 1

2 Definition and Classification of Lupus and Lupus-Related

Disorders, 15

3 The Epidemiology of Lupus, 23

SECTION 2 Pathogenesis

4 Overview of Lupus Pathogenesis, 44

5 Genetics of Human SLE, 54

6 Epigenetics of Lupus, 69

7 The Environment and the Host, 86

8 The Innate Immune System in SLE, 93

9 B Cells and Generation of Antibodies, 101

10 T Cells, 116

11 Adaptive and Innate Immunoregulatory Cells, 125

12 Cytokines in Lupus, 137

13 Immunometabolism, 153

14 Animal Models in Lupus, 164

SECTION 3 Mechanisms of Tissue Injury

15 Abnormalities in Immune Complex Clearance and

Apoptotic Cell Clearance, 216

16 The Role of Complement in SLE, 224

17 Apoptosis and Inflammatory Forms of Cell Death, 237

18 Tissue Damage in Lupus: Free Radicals and Fibrosis, 248

19 Pathogenesis of Fibrosis-The Lung as a Model, 261

20 Pathogenesis of Lupus Nephritis, 269

21 Pathogenesis of Accelerated Atherosclerosis and

Vascular Injury in Systemic Lupus Erythematosus, 294

22 Pathogenesis of Cutaneous Lupus, 305

23 Pathogenesis of Neuropsychiatric Lupus, 317

24 Pathogenesis of Antiphospholipid Antibody

Syndrome, 324

25 Pathogenesis of Sjögren's, 338

SECTION 4 Autoantibodies

26 Structure and Derivation of Autoantibodies, 340

27 Antinuclear Antibodies, Antibodies to DNA, Histones, and Nucleosomes, 355

28 Antibodies Against ENA (Sm, RNP, SSA, SSB), 366

29 Antibodies Against C1q, 372

30 Antilipoprotein and Antiendothelial Cell

Antibodies, 375

31 Drug-Induced Lupus Erythematosus, 377

SECTION 5 Clinical Aspects of Lupus

Erythematosus

32 Overview and Clinical Presentation, 389

33 Skin Disease in Cutaneous Lupus Erythematosus, 395

34 The Musculoskeletal System and Bone

Metabolism, 407

35 Lupus and the Cardiopulmonary System, 418

36 Lupus and the Nervous System: Clinical Aspects, Psychopathology, and Imaging, 434

37 Gastrointestinal and Hepatic Systems, 457

38 Hematologic and Lymphoid Abnormalities in SLE, 473

39 Neonatal Lupus: Pathogenesis and Clinical

Approaches, 486

40 Pregnancy and Autoimmune Disease, Reproductive and

Hormonal Issues, 499

41 Systemic Lupus Erythematosus in Childhood and

Adolescence, 520

42 Clinical Aspects of Antiphospholipid Syndrome, 532

43 Lupus and Infections, 543

44 Ocular, Aural, and Oral Manifestations of Lupus, 556

45 Clinical Aspects of Sjögren's, 566

SECTION 6 Assessment of Lupus

46 Clinical Application of Serologic Tests, Serum Protein

Abnormalities, and Other Clinical Laboratory Tests in

Systemic Lupus Erythematosus, 579

47 Differential Diagnosis and Disease Associations, 598

48 Incomplete Lupus, Undifferentiated Connective Tissue

Disease, and Mixed Connective Tissue Disease, 606

49 Clinical Markers, Metrics, Indices, and Clinical

Trials, 614

50 Lupus Biomarkers, 631

SECTION 7 Management of Lupus

51 Principles of Therapy, Local Measures, and NSAIDs, 640

52 Antimalarial Medications, 650

53 Systemic Glucocorticoid Therapy for SLE, 661

54 Immunosuppressive Drug Therapy, 673

55 Complementary and Alternative Medications, Specialized and Niche Therapies, 689

56 Adjunctive Treatments and Preventive Measures, 702

57 Targeted Therapies in SLE, 710

58 Management of Cutaneous Lupus Erythematosus, 719

59 Epidemiology and Management of Lupus Nephritis, 727

60 Management of Sjögren's, 745

SECTION 8 Outcomes

61 Socioeconomic and Disability Aspects, 759

62 Prognosis and Mortality of SLE, 770

Index, 782