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Firestein & Kelley's Textbook of Rheumatology, 2-Volume Set. Edition No. 11

  • Book

  • July 2020
  • Elsevier Health Science
  • ID: 5008029
Through 10 outstanding editions, Kelley & Firestein's Textbook of Rheumatology has provided authoritative, in-depth guidance in rheumatology with an ideal balance of basic science and clinical application. The 11th Edition of this classic text continues this tradition of excellence, while keeping you abreast of recent advances in genetics and the microbiome, new therapies such as biologics and biosimilars, and other rapid changes in the field. It provides comprehensive, global coverage of all aspects of diagnosis, screening, and treatment in both adults and children, in a user-friendly, full color reference.

- Covers everything from basic science, immunology, anatomy, and physiology to diagnostic tests, procedures, and specific disease processes-including key data on therapeutic outcomes to better inform clinical decision making.

- Includes new chapters on Innate Lymphoid Cells and Natural Killer Cells, Pathogenesis of Inflammasome Mediated Diseases, Bisphosphonates, Ultrasound Evaluation of the Musculoskeletal System, and Evaluation of Monoarticular and Polyarticular Arthritis.

- Features 1,200 high-quality illustrations, including superb line art, quick-reference tables, and full-color clinical photographs.

- Shares the knowledge and expertise of internationally renowned scientists and clinicians, including new editor Dr. Gary Koretzky, specialist in immunology and rheumatology.

- Demonstrates the complete musculoskeletal exam in online videos, including abnormal findings and the arthroscopic presentation of diseased joints. - Enhanced eBook version included with purchase. Your enhanced eBook allows you to access all of the text, figures, and references from the book on a variety of devices.

Table of Contents


Part 1: Structure and Function of Bone, Joints, and Connective Tissue

1. Biology of the Normal Joint, 1 Carla R. Scanzello and Steven R. Goldring

2. Synovium, 20 Douglas J. Veale and Gary S. Firestein

3. Cartilage and Chondrocytes, 34 Ali Mobasheri, Mary B. Goldring, and Richard F. Loeser

4. Biology, Physiology, and Morphology of Bone, 60 Aline Bozec, Anika Gr�neboom, and Georg Schett

5. Muscle: Anatomy, Physiology, and Biochemistry, 67 Mark S. Miller, Edward P. Debold, and Michael J. Toth

6. Biomechanics, 80 Kenton R. Kaufman and KaiNan An

7. Regenerative Medicine and Tissue Engineering, 92 Frank P. Luyten, Cosimo De Bari, and Francesco Dell'Accio

8. Proteinases and Matrix Degradation, 109 Yoshifumi Itoh

Part 2: Cells Involved in Autoimmune Diseases and Inflammation

9. Dendritic Cells, 132 Mansi Saxena, Nicolas Vabret, Luciana Ribeiro Muniz, and Nina Bhardwaj

10. Mononuclear Phagocytes, 149 Deborah R. Winter, Anna Montgomery, and Harris Perlman

11. Neutrophils, 161 Binita Shah, Nathalie Burg, and Michael H. Pillinger

12. T Lymphocytes, 182 Ralph C. Budd

13. B Cells, 199 Yong-Rui Zou, Christine Grimaldi, and Betty Diamond

14. Fibroblasts and Fibroblast-like Synoviocytes, 222 Christopher D. Buckley and Andrew Filer

15. Mast Cells, 241 Peter A. Nigrovic

16. Innate Lymphoid Cells and Natural Killer Cells, 254 Michael A. Paley and Wayne M. Yokoyama

17. Platelets and Megakaryocytes, 262 Eric Boilard and Peter A. Nigrovic

Part 3: Effector Mechanisms in Autoimmunity and Inflammation

18. Principles of Signaling, 273 Abel Suarez-Fueyo, Vaishali R. Moulton, and George C. Tsokos

19. The Immunologic Repercussions of Cell Death, 286 Helen M. Beere and Douglas R. Green

20. Innate Immunity, 306 Gregoire Lauvau and Steven A. Porcelli

21. Adaptive Immunity, 320 Martha S. Jordan and Gary A. Koretzky

22. Autoimmunity and Tolerance, 337 Dwight H. Kono and Argyrios N. Theofilopoulos

23. The Microbiome in Health and Disease, 355 Rob Knight

24. Metabolic Regulation of Immunity, 368 Ruoning Wang, Tingting Wang, and Stephen Tait

25. Genetics of Rheumatic Diseases, 378 Stephen Eyre and Anne Barton

26. Epigenetics of Rheumatic Diseases, 393 Amr H. Sawalha and Matlock A. Jeffries

27. Complement System, 409 V. Michael Holers and Leendert A. Trouw

28. Prostaglandins, Leukotrienes, and Related Compounds, 420 Robert B. Zurier

29. Chemokines and Cellular Recruitment, 437 Gerard Graham

30. Angiogenesis, 445 Ursula Fearon, Zolt�n Szekanecz, and Douglas J. Veale

31. Cytokines, 455 Iain B. McInnes

32. Experimental Models for Rheumatoid Arthritis, 467 Rikard Holmdahl

33. Neuronal Regulation of Pain and Inflammation, 480 Camilla I. Svensson and Linda S. Sorkin

Part 4: Broad Issues in the Approach to Rheumatic Disease

34. Clinical Research Methods in Rheumatic Disease, 495 Jeffrey R. Curtis, Yvonne M. Golightly, and Kenneth G. Saag

35. Economic Impact of Arthritis and Rheumatic Conditions, 510 Louise B. Murphy

36. Assessment of Health Outcomes, 522 Dorcas E. Beaton, Maarten Boers, Peter Tugwell, and Lara Maxwell

37. Biomarkers in Rheumatology, 536 Michael J. Townsend, Saloumeh K. Fischer, and Andrew C. Chan

38. Occupational and Recreational Musculoskeletal Disorders, 551 Richard S. Panush

39. Cardiovascular Risk in Inflammatory Rheumatic Disease, 563 Cynthia S. Crowson, Sherine E. Gabriel, and Anne Grete Semb

40. Cancer Risk in Rheumatic Diseases, 579 Eric L. Matteson

41. Introduction to Physical Medicine and Rehabilitation, 592 Sara J. Cuccurullo, Jaclyn Joki, and Ofure Luke

42. Pregnancy and Rheumatic Diseases, 604 Lisa R. Sammaritano and Bonnie L. Bermas

Part 5: Evaluation of Generalized and Localized Symptoms

43. History and Physical Examination of the Musculoskeletal System, 621 John M. Davis III, Kevin G. Moder, and Gene G. Hunder

44. Ultrasound in Rheumatology, 638 Eugene Y. Kissin, Paul J. DeMarco, and Amy C. Cannella

45. Evaluation of Monoarticular and Polyarticular Arthritis, 663 Ronald F. van Vollenhoven

46. Skin and Rheumatic Diseases, 678 David F. Fiorentino and Victoria P. Werth

47. The Eye and Rheumatic Diseases, 702 James T. Rosenbaum

Part 6: Differential Diagnosis of Regional and Diffuse Musculoskeletal� Pain

48. Neck Pain, 711 Jennifer Kosty, Rani Nasser, Raul A. Vasquez, Cyrus C. Wong, and Joseph S. Cheng

49. Shoulder Pain, 727 Scott David Martin and Thomas S. Thornhill

50. Low Back Pain, 753 Rajiv Dixit

51. Hip and Knee Pain, 776 James I. Huddleston, III, and Stuart Goodman

52. Foot and Ankle Pain, 792 Christopher P. Chiodo, Mark D. Price, and Adam P. Sangeorzan

53. Hand and Wrist Pain, 800 Kenneth W. Donohue, Felicity G. Fishman, and Carrie R. Swigart

54. Temporomandibular Joint Pain, 813 Daniel M. Laskin

55. Fibromyalgia, 825 Leslie J. Crofford

Part 7: Diagnostic Tests and Procedures in Rheumatic Diseases

56. Synovial Fluid Analyses, Synovial Biopsy, and Synovial Pathology, 841 Hani S. El-Gabalawy and Stacy Tanner

57. Arthrocentesis and Injection of Joints and Soft Tissues, 859 Ahmed S. Zayat, Andrea di Matteo, and Richard J. Wakefield

58. Anti-nuclear Antibodies, 875 Stanford L. Peng and Joseph E. Craft

59. Autoantibodies in Rheumatoid Arthritis, 890 Erika Darrah, Antony Rosen, and Felipe Andrade

60. Acute Phase Reactants, 907 Rebecca Haberman, Cesar E. Fors Nieves, Bruce N. Cronstein, and Amit Saxena

61.Imaging�in�Rheumatic� Diseases,� 920 Mikkel �stergaard, Ho Jen, Jacob L. Jaremko, and Robert G.W. Lambert

Part 8:� Pharmacology of Anti-rheumatic Drugs

62. Therapeutic Targeting of Prostanoids, 965 Leslie J. Crofford

63. Glucocorticoid Therapy, 985 Marlies C. van der Goes and Johannes W.G. Jacobs

64. Traditional DMARDs: Methotrexate, Lefl, Sulfasalazine, Hydroxychloroquine, and Combination Therapies, 1007 Amy C. Cannella and James R. O'Dell

65. Immunosuppressive Drugs, 1031 Jacob M. van Laar

66. Anti-cytokine�Therapies,�� 1046 Katharine McCarthy, Arthur Kavanaugh, and Christopher T. Ritchlin

67. Cell-Targeted Biologics and Emerging Targets: Rituximab, Abatacept, and Other Biologics, 1068 Peter C. Taylor

68. Intra-cellular Targeting Agents in Rheumatic Disease, 1091 Virginia Reddy and Stanley Cohen

69. Urate-Lowering Therapy, 1111 Ted R. Mikuls

70. Bisphosphonates, 1125 Arthur C. Santora II and Kenneth G. Saag

71. Analgesic Agents in Rheumatic Disease, 1135 Gregory R. Polston and Mark S. Wallace

72. Nutrition and Rheumatic Diseases, 1156 Lisa K. Stamp and Leslie G. Cleland

73. Evaluation and Management of Early Undifferentiated Arthritis, 1173 Karim Raza


Part 9:� Rheumatoid Arthritis

74. Etiology of Rheumatoid Arthritis, 1181 Gary S. Firestein

75. Pathogenesis of Rheumatoid Arthritis, 1200 Gary S. Firestein

76. Clinical Features of Rheumatoid Arthritis, 1236 Bryant R. England and Ted R. Mikuls

77. Treatment of Rheumatoid Arthritis, 1258 James R. O'Dell

78. Sj�gren's Syndrome, 1284 E. William St. Clair and David L. Leverenz

Part 10: Spondyloarthritis

79. Etiology and Pathogenesis of Spondyloarthritis, 1307 Keith A. Sikora and Robert A. Colbert

80. Ankylosing Spondylitis and Other Forms of Axial Spondyloarthritis,� 1319 Sjef van der Linden, Matthew Brown, Lianne S. Gensler, Tony Kenna, Walter P. Maksymowych, and William J. Taylor

81. Reactive Arthritis, 1344 John D. Carter and Alan P. Hudson

82. Psoriatic Arthritis, 1359 Oliver FitzGerald and Conor Magee

83. Inflammatory Bowel Disease-Associated Arthritis and Other Enteropathic Arthropathies, 1381 Richard Zamore, Meenakshi Bewtra, and Alexis Ogdie

Part 11: Systemic Lupus Erythematosus and Related Syndromes

84. Etiology and Pathogenesis of Systemic Lupus Erythematosus, 1396 Mary K. Crow

85. Clinical Features of Systemic Lupus Erythematosus, 1413 Maria Dall'Era and David Wofsy

86. Treatment of Systemic Lupus Erythematosus, 1437 Antonis Fanouriakis, George Bertsias, and Dimitrios T. Boumpas

87. Antiphospholipid Syndrome, 1460 Medha Barbhaiya, Jane E. Salmon, and Doruk Erkan

Part 12: Systemic Sclerosis, Inflammatory Myopathies, and Overlap Syndromes

88. Etiology and Pathogenesis of Systemic Sclerosis, 1473 John Varga

89. Clinical Features and Treatment of Scleroderma, 1499 Fredrick M. Wigley and Francesco Boin

90. Inflammatory Diseases of Muscle and Other Myopathies, 1539 Kanneboyina Nagaraju, Rohit Aggarwal, and Ingrid E. Lundberg

91. Overlap Syndromes, 1569 Jonathan Graf

Part 13:� Vasculitis

92. Classification and Epidemiology of Systemic Vasculitis, 1584 Rennie L. Rhee and Peter A. Merkel

93. Giant Cell Arteritis, Polymyalgia Rheumatica, and Takayasu's Arteritis, 1595 David B. Hellmann

94. Anti-neutrophil Cytoplasmic Antibody- Associated Vasculitis, 1617 Sharon A. Chung and Paul A. Monach

95. Polyarteritis Nodosa and Related Disorders, 1634 Raashid Luqmani and Abid Awisat

96. Immune Complex-Mediated Small Vessel Vasculitis, 1649 John H. Stone

97. Primary Angiitis of the Central Nervous System, 1659 Rula A. Hajj-Ali and Carol A. Langford

98. Beh�et's Disease, 1666 Christine S. Ahn, Lindsay C. Strowd, and Joseph L. Jorizzo

Part 14: Crystal-Induced and Inflammasome- Mediated Inflammation

99. Pathogenesis of Inflammasome-Mediated Diseases, 1676 Hal M. Hoffman and Lori Broderick

100. Etiology and Pathogenesis of Hyperuricemia and Gout, 1687 Robert T. Keenan, Michael Toprover, and Michael H. Pillinger

101. Clinical Features and Treatment of Gout, 1710 Nicola Dalbeth

102. Calcium Crystal Disease: Calcium Pyrophosphate Dihydrate and Basic Calcium Phosphate, 1732 Robert Terkeltaub

103. Familial Autoinflammatory Syndromes, 1752 Catharina M. Mulders-Manders, Anna Simon, and Jos W.M. van der Meer

Part 15: Cartilage, Bone, and Heritable Connective Tissue Disorders

104. Pathogenesis of Osteoarthritis, 1770 Paul E. Di Cesare, Dominik R. Haudenschild, Steven B. Abramson, and Jonathan Samuels

105. Clinical Features of Osteoarthritis, 1789 Amanda E. Nelson

106. Treatment of Osteoarthritis, 1803 Devyani Misra, Deepak Kumar, and Tuhina Neogi

107. Metabolic Bone Disease, 1819 Nancy E. Lane

108. Proliferative Bone Diseases, 1839 Reuven Mader

109. Osteonecrosis, 1852 Christopher Chang, Adam Greenspan, and M. Eric Gershwin

110. Relapsing Polychondritis, 1876 Gaye Cunnane

111. Heritable Diseases of Connective Tissue, 1886 Deborah Krakow

Part 16: Rheumatic Diseases of Childhood

112. Etiology and Pathogenesis of Juvenile Idiopathic Arthritis, 1905 Edward M. Behrens

113. Clinical Features and Treatment of Juvenile Idiopathic Arthritis, 1911 Joyce J. Hsu, Tzielan C. Lee, and Christy I. Sandborg

114. Childhood-Onset Systemic Lupus Erythematosus, Drug-Induced Lupus in Children, and Neonatal Lupus, 1931 Stacy P. Ardoin and Fatima Barbar-Smiley

115.Juvenile Dermatomyositis, Scleroderma, Vasculitis, and Autoimmune Brain Disease,� 1942 Angela B. Robinson, Jeffrey Dvergsten, Kathryn S. Torok, Heather Van Mater, William Gallentine, and Ann M. Reed

Part 17: Infection and Arthritis

116. Bacterial Arthritis, 1979 Paul P. Cook and Dawd S. Siraj

117. Lyme Disease, 1994 Linda K. Bockenstedt

118. Mycobacterial Infections of Bones and Joints, 2009 Eric M. Ruderman and John P. Flaherty

119. Fungal Infections of Bones and Joints, 2022 Eric M. Ruderman and John P. Flaherty

120. Rheumatic Manifestations of HIV Infection, 2033 Jonathan Dau and John D. Reveille

121. Viral Arthritis, 2048 Philippe Gasque and Xavier Guillot

122. Rheumatic Fever and Post-streptococcal Arthritis, 2061 Luiza Guilherme, Pedro Ming Azevedo, and Jorge Kalil

Part 18: Arthritis Accompanying Systemic Disease

123. Amyloidosis, 2077 Helen J. Lachmann and Faye A. Sharpley

124. Sarcoidosis, 2088 Peter Korsten, Nadera J. Sweiss, and Robert P. Baughman

125. Hemochromatosis, 2105 Gaye Cunnane

126. Hemophilic Arthropathy, 2115 Astrid E. Pulles, Lize F. D. van Vulpen, and Floris P.J.G. Lafeber

127. Rheumatic Manifestations of Hemoglobinopathies,� 2127 Carlos J. Lozada and Elaine C. Tozman

128. IgG4-Related Disease, 2135 John H. Stone and Shiv Pillai

129. Arthritis Accompanying Endocrine and Metabolic Disorders, 2149 Sebastian E. Sattui and Joseph A. Markenson

130. Rheumatic� Paraneoplastic� Syndromes-Links Between Malignancy and Autoimmunity, 2161 Bernhard Manger and Georg Schett

131. Tumors and Tumor-like Lesions of Joints and Related Structures, 2167 Darcy A. Kerr and Andrew E. Rosenberg

132. Autoimmune Complications of Immune Checkpoint Inhibitors for Cancer, 2189 Laura C. Cappelli, Clifton O. Bingham III, and Ami A. Shah

Index, I-1


Gary S. Firestein Distinguished Professor of Medicine, Senior Associate Vice Chancellor for Health Sciences, Director, Altman Clinical & Translational Research Institute. Gary Firestein, MD, is a board-certified rheumatologist who diagnoses and treats patients with autoimmune conditions as well as diseases of the joints, muscles and bones. A professor at UC San Diego School of Medicine, Dr. Firestein is distinguished for his research and serves as director of the Altman Clinical and Translational Research Institute and the senior associate vice chancellor for health sciences. Dr. Firestein's research interest focuses on the pathogenesis and treatment of rheumatoid arthritis.
Dr. Firestein is the recipient of many awards and honors, including the Arthritis Foundation's Jane Wyman Humanitarian Award in 2010 for his contributions to rheumatology; the Arthritis Foundation Lee C. Howley Sr. Prize for Arthritis Research; and the American College of Rheumatology Distinguished Investigator Award. He has been elected to the American Society for Clinical Investigation and the Association of American Physicians. He has served as an editor for the Textbook of Rheumatology for since the 7th edition (2004). Ralph C. Budd Professor of Medicine and Microbiology and Molecular Genetics, Director, Vermont Center for Immunology and Infectious Diseases, University of Vermont College of Medicine Distinguished University Professor, The University of Vermont College of Medicine, Burlington, Vermont. Sherine E Gabriel Professor and Dean, Rutgers Robert Wood Johnson Medical School, CEO, Robert Wood Johnson Medical Group, Emeritus Professor, Mayo Clinic, New Brunswick, New Jersey. Iain B McInnes Muirhead Professor of Medicine, Arthritis Research UK Professor of Rheumatology, Director of Institute of Infection,Immunity, and Inflammation, College of Medical, Veterinary, and Life Sciences, University of Glasgow, Glasgow, Scotland, United Kingdom. Iain McInnes is Director of the Institute of Infection, Immunity and Inflammation at the University of Glasgow, UK. He has extensive experience in leading multicenter programs nationally and internationally. He is Director of the Scottish MRC Clinical Pharmacology and Pathology Clinical PhD Training Program, Chief Investigator for the Scottish Early RA Cohort (SERA) and the related SMS-IC biomarker discovery program (PROMISERA), and chief investigator of numerous global phase II and III clinical trials of novel immune therapies. He has served as member or chair of numerous national grant-funding panels and as chair of several European League Against Rheumatism (EULAR) scientific committees - he is now Treasurer and President Elect of EULAR serving on its Steering Committee. He is formerly Chairman of the Foundation for European Rheumatology Research (Foreum) Scientific Committee and leads the EULAR-supported European Roadmap Program that is defining the research agenda for rheumatology for the next decade. James R. O'Dell Bruce Professor and Vice Chairman of Internal Medicine, University of Nebraska Medical Center, Chief of Rheumatology, Department of Medicine, Omaha Veterans Affairs, Omaha, Nebraska. James R. O'Dell, MD is the Stokes Shackleford Professor of Internal Medicine, Vice-Chairman of Internal Medicine and Chief of the Division of Rheumatology at the University of Nebraska Medical Center (UNMC) in Omaha. Dr. O'Dell founded and has directed the Rheumatoid Arthritis Investigational Network (RAIN) for the last 25 years. Dr. O'Dell is the PI of the large multinational RA research study based at the VA through their cooperative studies program. Dr. O'Dell has published extensively, mostly in the area of rheumatoid arthritis. He has presented frequently at national and international meetings and has more than 100 published articles in top-level rheumatology journals. He has served on numerous American College of Rheumatology (ACR) committees over the last 20 years, including time on both the ACR and REF BOD, as well as a two-year term as President of the Research and Education Foundation of the ACR and was President of the College (2011-2012). Additionally, he is Editor-in-Chief of Up To Date for Rheumatology.