Peter H. Schur Elena M. Massarotti. Editors. Lupus Erythematosus. Clinical Evaluation and Treatment
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2 Lupus Erythematosus
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4 Peter H. Schur Elena M. Massarotti Editors Lupus Erythematosus Clinical Evaluation and Treatment
5 Editors Peter H. Schur Division of Rheumatology, Immunology, Allergy Brigham and Women s Hospital Boston, MA, USA Elena M. Massarotti Division of Rheumatology, Immunology, Allergy Center for Clinical Therapeutics Brigham and Women s Hospital Boston, MA, USA ISBN ISBN (ebook) DOI / Springer New York Heidelberg Dordrecht London Library of Congress Control Number: Springer Science+Business Media New York 2012 This work is subject to copyright. All rights are reserved by the Publisher, whether the whole or part of the material is concerned, speci fi cally the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on micro fi lms or in any other physical way, and transmission or information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed. Exempted from this legal reservation are brief excerpts in connection with reviews or scholarly analysis or material supplied speci fi cally for the purpose of being entered and executed on a computer system, for exclusive use by the purchaser of the work. Duplication of this publication or parts thereof is permitted only under the provisions of the Copyright Law of the Publisher s location, in its current version, and permission for use must always be obtained from Springer. Permissions for use may be obtained through RightsLink at the Copyright Clearance Center. Violations are liable to prosecution under the respective Copyright Law. The use of general descriptive names, registered names, trademarks, service marks, etc. in this publication does not imply, even in the absence of a speci fi c statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use. While the advice and information in this book are believed to be true and accurate at the date of publication, neither the authors nor the editors nor the publisher can accept any legal responsibility for any errors or omissions that may be made. The publisher makes no warranty, express or implied, with respect to the material contained herein. Printed on acid-free paper Springer is part of Springer Science+Business Media (
6 Preface Most physicians, regardless of their area of expertise, will encounter a patient with lupus during the course of their careers, or must consider the diagnosis when evaluating a patient with a particular complaint. Often considered the prototypic autoimmune disease, it is characterized by protean manifestations and affects a wide range of organ systems. Despite the widespread availability of antinuclear antibody testing and other technological diagnostic advances, the diagnosis of lupus can be elusive, dif fi cult, and inexact. Treatment of the disease can also be challenging, and focused upon the immune system and the speci fi c organ system affected. Advances in immunology and biotechnology have led to a burgeoning world of new therapies in development that offer patients the real possibility of new therapies, and physicians and scientists insights into the pathogenesis of this complicated immunological disease. This textbook summarizes the clinical aspects of lupus facing the general clinician in the twenty- fi rst century. The reader will fi nd introductory chapters regarding general diagnostic and treatment principles, followed by chapters addressing the lupus-speci fi c organ manifestations. Special topics regarding pregnancy and comorbidities are also presented. All these chapters were written by highly experienced physicians with special expertise in lupus. We hope you will fi nd this text to be a valuable, single source, go-to reference for the common and not so common problems affecting patients with lupus that you may confront in your practices. Boston, MA, USA Peter H. Schur, M.D., F.A.C.P. Elena M. Massarotti, M.D. v
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8 Contents 1 SLE Epidemiology: Epidemiologic Subtypes and Risk Factors for Development... 1 Julia F. Simard and Karen H. Costenbader 2 The Immunopathogenesis and Immunopathology of Systemic Lupus Erythematosus David S. Pisetsky 3 Diagnosing and Monitoring Lupus Elena M. Massarotti and Peter H. Schur 4 Recommendations on How to Monitor the Patient with Systemic Lupus Erythematosus in the Clinic or at the Bedside Vivian P. Bykerk 5 The Treatment of Lupus: General Principles Elena M. Massarotti and Peter H. Schur 6 Cutaneous Manifestations of Lupus Erythematosus Henry Townsend and Ruth Ann Vleugels 7 Musculoskeletal Manifestations of SLE Simon M. Helfgott 8 Cardiac and Vascular Disease in SLE Robert A. Sands 9 Pulmonary Manifestations of Systemic Lupus Erythematosus Hilary J. Goldberg and Paul F. Dellaripa 10 Hematologic Manifestations of SLE Ami S. Bhatt and Nancy Berliner vii
9 viii Contents 11 Lupus Nephritis Mary Anne Dooley 12 Gastrointestinal Manifestations of Systemic Lupus Erythematosus R.S. Kalman and J.L. Wolf 13 Neuropsychiatric Aspects of Lupus S. Khoshbin 14 Systemic Lupus Erythematosus and Pregnancy Bonnie L. Bermas 15 Antiphospholipid Syndrome Bonnie L. Bermas 16 Lupus-Like Syndromes Related to Drugs Joseph F. Merola 17 New and Emerging Therapies Elena M. Massarotti 18 Co-morbidities in Systemic Lupus Erythematosus Mary Gayed, Chee-Seng Yee, Sasha Bernatsky, and Caroline Gordon Index
10 Contributors Nancy Berliner, M.D. Division of Hematology, Brigham and Women s Hospital, Boston, MA, USA Bonnie L. Bermas, M.D. Division of Rheumatology, Director, Lupus Center, Brigham and Women s Hospital, Boston, MA, USA Sasha Bernatsky, Ph.D. Royal Victoria Hospital, Montreal, QC, Canada Ami S. Bhatt Harvard Medical School, Boston, MA, USA Clinical Fellow in Hematology and Oncology, Brigham and Women s Hospital and Dana Farber Cancer Institute, Boston, MA, USA Vivian P. Bykerk, M.D. Hospital for Special Surgery, New York, NY, USA Karen H. Costenbader, M.D., M.P.H. Lupus Center, Brigham and Women s Hospital, Boston, MA, USA Paul F. Dellaripa, M.D. Division of Rheumatology, Brigham and Women s Hospital, Boston, MA, USA Interstitial Lung Disease (ILD) Clinic, Brigham and Women s Hospital, Boston, MA, USA Mary Anne Dooley, M.D., M.P.H. Division of Rheumatology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA Mary Gayed, M.B.Ch.B. Rheumatology Department, City Hospital, Sandwell and West Birmingham Hospitals, NHS Trust, Birmingham, UK Hilary J. Goldberg, M.D., M.P.H. Division of Pulmonary and Critical Care Medicine, Brigham and Women s Hospital, Boston, MA, USA ix
11 x Contributors Caroline Gordon, M.D. Rheumatology Department, City Hospital, Sandwell and West Birmingham Hospitals, NHS Trust, Birmingham, UK Rheumatology Research Group, School of Immunity and Infection, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK Simon Helfgott, M.D. Division of Rheumatology, Brigham and Women s Hospital, Boston, MA, USA R.S. Kalman, M.D. Beth Israel Deaconess Medical Center, Boston, MA, USA S. Khoshbin, M.D. Division of Neurology, Brigham and Women s Hospital, Boston, MA, USA Elena M. Massarotti, M.D. Division of Rheumatology, Center for Clinical Therapeutics, Brigham and Women s Hospital, Boston, MA, USA Joseph F. Merola, M.D. Department of Medicine, Division of Rheumatology and Department of Dermatology, Brigham and Women s Hospital, Boston, MA, USA Department of Medicine, David Pisetsky, M.D., Ph.D. Department of Medicine and Immunology, Duke University Medical Center, Durham, NC, USA Medical Research Service, Durham VA Hospital, Durham, NC, USA Robert A. Sands, M.D. Division of Rheumatology, Brigham and Women s Hospital, Boston, MA, USA Peter H. Schur, M.D., F.A.C.P. Division of Rheumatology, Brigham and Women s Hospital, Boston, MA, USA Julia F. Simard, Sc.D. Clinical Epidemiology Unit, Karolinska University Hospital, Stockholm, Sweden Henry Townsend, M.D. Division of Clinical Immunology and Rheumatology, Department of Medicine, The University of Alabama at Birmingham, Birmingham, AL, USA Ruth Ann Vleugels, M.D., M.P.H. Connective Tissue Disease Clinic, Brigham and Women s Dermatology, Boston, MA, USA
12 Contributors xi J.L. Wolf, M.D. Beth Israel Deaconess Medical Center, Boston, MA, USA Chee-Seng Yee, Ph.D. Rheumatology Department, City Hospital, Sandwell and West Birmingham Hospitals, NHS Trust, Birmingham, UK Rheumatology Research Group, School of Immunity and Infection, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK
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14 Chapter 1 SLE Epidemiology: Epidemiologic Subtypes and Risk Factors for Development Julia F. Simard and Karen H. Costenbader Epidemiology While the etiology of systemic lupus erythematosus (SLE) is still enigmatic, epidemiologic research is continuously informing our understanding, with new insights into environmental risk factors and gene environment interactions that play a role in disease susceptibility. SLE is a heterogeneous multisystem autoimmune disorder characterized by organ system manifestations which vary over time and autoantibodies that target mainly intracellular constituents. Antinuclear antibodies (ANA) are observed in over 95% of patients, while other characteristic autoantibodies [anti-double-stranded DNA (anti-dsdna), anti-smith (anti-sm), anti-ro, and anti-la antibodies] are less common. These autoantibodies have been detected years prior to fi rst symptoms of SLE and are responsible for certain disease manifestations such as photosensitive rashes, cytopenias, thromboses, and glomerulonephritis. SLE Classification Clinical presentation and laboratory testing are used together in making a diagnosis. The current criteria for disease classi fi cation were developed by the American College of Rheumatology (ACR) in 1982 and revised in 1997, with the addition of antiphospholipid antibody testing (Table 1.1 ). These criteria aim to J.F. Simard, Sc.D. (*) Clinical Epidemiology Unit, T2, Karolinska University Hospital, Stockholm, Sweden julia.simard@ki.se K.H. Costenbader, M.D., M.P.H. Lupus Center, Brigham and Women s Hospital, Boston, MA, USA P.H. Schur and E.M. Massarotti (eds.), Lupus Erythematosus: Clinical Evaluation and Treatment, DOI / _1, Springer Science+Business Media New York
15 2 J.F. Simard and K.H. Costenbader Table 1.1 The evolution of the American College of Rheumatology classi fi cation criteria for SLE Criterion 1971a 1982 b c 1997 Malar rash Malar rash Malar rash Malar rash Discoid rash Discoid rash Discoid rash Discoid rash Raynaud s Raynaud s phenomenon phenomenon Alopecia Alopecia Photosensitivity Photosensitivity Photosensitivity Photosensitivity Oral or nasopharyngeal ulcers Arthritis Oral or nasopharyngeal ulcers Arthritis without deformity Oral or nasopharyngeal ulcers Nonerosive arthritis in at least two peripheral joints Oral or nasopharyngeal ulcers Nonerosive arthritis in at least two peripheral joints Serositis Pleurisy Pleurisy Pleurisy Pericarditis Pericarditis Pericarditis Renal disorder Profuse proteinuria Profuse proteinuria Profuse proteinuria Cellular casts Cellular casts Cellular casts Neurologic disorder Hematologic disorder Immunologic disorder Psychosis Psychosis Psychosis Convulsions Seizures Seizures Hemolytic anemia Leukopenia Thrombocytopenia LE cells False-positive serologic test for syphilis (STS) Hemolytic anemia Leukopenia Thrombocytopenia Lymphopenia LE cells False-positive STS Anti-DNA Anti-Sm Hemolytic anemia Leukopenia Thrombocytopenia Lymphopenia False-positive STS Anti-DNA Anti-Sm Antiphospholipid antibodies Lupus anticoagulant Antinuclear Positive ANA Positive ANA Positive ANA antibody a Cohen AS, Reynolds WE, Franklin EC, et al. Preliminary criteria for the classi fi cation of systemic lupus erythematosus. Bull Rheum Dis 1971; 21: b Tan EM, Cohen AS, Fries JF, et al. The 1982 revised criteria for the classi fi cation of systemic lupus erythematosus (SLE). Arthritis Rheum 192; 25: c Hochberg MC. Updating the American College of Rheumatology revised criteria for the classi fi cation of systemic lupus erythematosus (letter). Arthritis Rheum 1997; 40: 1725 be comprehensive, requiring at least 4 of 11 criteria, but are far from exhaustive given the many clinical manifestations of SLE that are not included. These classi fi cation criteria were developed to allow de fi nition of disease populations for research purposes not clinical diagnosis. The shortcomings of the current system have been outlined and modi fi ed criteria, including weighting of the different manifestations (more weight for severe organ involvement and less weight for more subjective signs and symptoms such as photosensitivity and oral ulcers)
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