Case Studies in Immunology: Autoimmune Hemolytic Anemia: A Clinical Companion 9781136982491, 0815341458, 9780815341451, 0203853393, 1136982493

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Autoimmune Hemolytic Anemia

• Harvard Medical School

This edition published in the Taylor & Francis e-Library, 2009. To purchase your own copy of this or any of Taylor & Francis or Routledge’s collection of thousands of eBooks please go to www.eBookstore.tandf.co.uk. Vice President: Denise Schanck Senior Editor: Janet Foltin Text Editor: Eleanor Lawrence Assistant Editor: Sigrid Masson Editorial Assistant: Katherine Ghezzi Senior Production Editor: Simon Hill Copyeditor: Bruce Goatly Indexer: Merrall-Ross International Ltd. Illustration: Blink Studio Layout: Georgina Lucas © 2008 by Garland Science, Taylor & Francis Group, LLC This book contains information obtained from authentic and highly regarded sources. Reprinted material is quoted with permission, and sources are indicated. Every attempt has been made to source the figures accurately. Reasonable efforts have been made to publish reliable data and information, but the author and publisher cannot assume responsibility for the validity of all materials or for the consequences of their use. All rights reserved. No part of this book covered by the copyright herein may be reproduced or used in any format in any form or by any means—graphic, electronic, or mechanical, including photocopying, recording, taping, or information storage and retrieval systems—without permission of the publisher. 10-digit ISBN 0-8153-4145-8 (paperback) 13-digit ISBN 978-0-8153-4145-1 (paperback)

Library of Congress Cataloging-in-Publication Data Geha, Raif S. Case studies in immunology : a clinical companion / Raif Geha, Fred Rosen. -- 5th ed. p. ; cm. Rosen's name appears first on the earlier edition. Includes index. ISBN 978-0-8153-4145-1 1. Clinical immunology--Case studies. I. Rosen, Fred S. II. Title. [DNLM: 1. Immune System Diseases--Case Reports. 2. Allergy and Immunology-Case Reports. 3. Immunity--genetics--Case Reports. WD 300 G311c 2007] RC582.R67 2007 616.07'9--dc22 2007002977

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Preface

The science of immunology started as a case study. On May 15, 1796 Edward Jenner inoculated a neighbor’s son, James Phipps, with vaccinia (cowpox) virus. Six weeks later, on July 1, 1796, Jenner challenged the boy with live smallpox and found that he was protected against this infection. During its 208 year history the basic science of immunology has been closely related to clinical observations and has shed light on the pathogenesis of disease. The study of immunology provides a rare opportunity in medicine to relate the findings of basic scientific investigations to clinical problems. The case histories in this book are chosen for two purposes: to illustrate in a clinical context essential points about the mechanisms of immunity; and to describe and explain some of the immunological problems often seen in the clinic. For this fifth edition, we have added five completely new cases that illustrate both recently discovered genetic immunodeficiencies and some more familiar and common diseases with interesting immunology. We have revised other cases to add newly acquired information about these diseases. Fundamental mechanisms of immunity are illustrated by cases of genetic defects in the immune system, immune complex diseases, immune mediated hypersensitivity reactions and autoimmune and alloimmune diseases. These cases describe real events from case histories, largely but not solely drawn from the records of the Boston Children’s Hospital and the Brigham and Women’s Hospital. Names, places, and time have been altered to obscure the identity of the patients described; all other details are faithfully reproduced. The cases are intended to help medical students and pre-medical students to learn and understand the importance of basic immunological mechanisms, and particularly to serve as a review aid; but we hope and believe they will be useful and interesting to any student of immunology. Each case is presented in the same format. The case history is preceded by basic scientific facts that are needed to understand the case history. The case history is followed by a brief summary of the disease under study. Finally there are several questions and discussion points that highlight the lessons learned from the case. These are not intended to be a quiz but rather to shed further light on the details of the case. The Garland Science website (www.garlandscience.com) now provides instructors who adopt Case Studies with a link to Garland Science Classwire, where the textbook art can be found in a downloadable, web-ready format, as well as in PowerPoint-ready format. We are grateful to Dr. Peter Densen of the University of Iowa for C8 deficiency case material, Dr. Sanjiv Chopra of Harvard Medical School for the case on mixed essential cryoglobulinemia and Dr. Peter Schur of the Brigham and Women’s Hospital for the rheumatoid arthritis case. We also thank Dr. Jane Newburger of the Boston Children’s Hospital for the case on rheumatic fever and Dr. Eric Rosenberg of the Massachusetts General Hospital for the AIDS case. We are also greatly indebted to our colleagues Drs. David Dawson, Susan Berman, Lawrence Shulman and David Hafler of the Brigham and Women’s Hospital, to Dr. Razzaque Ahmed of the Harvard School of Dental Medicine, to Drs. Ernesto Gonzalez and Scott Snapper of the Massachusetts General Hospital and to Drs. Peter Newburger and Jamie Ferrara of the Departments of Pediatrics of the University of Massachusetts and the University of Michigan and Dr. Robertson Parkman of the Los Angeles Children’s Hospital as well as Henri de la Salle of the Centre régional de Transfusion sanguine in Strasbourg and Professor Michael

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Levin of St. Mary’s Hospital, London for supplying case materials. Our colleagues in the Immunology Division of the Children’s Hospital have provided invaluable service by extracting summaries of long and complicated case histories; we are particularly indebted to Drs. Lynda Schneider, Leonard Bacharier, Francisco Antonio Bonilla, Hans Oettgen, Jonathan Spergel, Rima Rachid, Scott Turvey, Jordan Orange, Eamanuela Castigli, Andrew McGinnitie, Marybeth Son, Melissa Hazen, Douglas McDonald and John Lee, and to Lilit Garibyan, third year medical student at Harvard Medical School, in constructing several case histories. In the course of developing these cases, we have been indebted for expert and pedagogic advice to Fred Alt, Mark Anderson, John Atkinson, Hugh Auchincloss, Stephen Baird, Zuhair K. Ballas, Leslie Berg, Corrado Betterle, Kurt Bloch, Jean-Laurent Casanova, John J. Cohen, Michael I. Colston, Anthony DeFranco, Peter Densen, Ten Feizi, Alain Fischer, Christopher Goodnow, Edward Kaplan, George Miller, Luigi Notarangelo, Peter Parham, Jaakko Perheentupa, Jennifer Puck, Westley Reeves, Patrick Revy, Peter Schur, Anthony Segal, Lisa Steiner, Stuart Tangye, Cox Terhorst, Emil Unanue, André Veillette, Jan Vilcek, Mark Walport, Fenella Woznarowska, and John Zabriskie. Eleanor Lawrence has spent many hours honing the prose as well as the content of the cases and we are grateful to her for this. We would also like to acknowledge the Garland Science team for their work on the fifth edition.

A note to the reader The cases presented in this book have been ordered so that the main topics addressed in each case follow as far as possible the order in which these topics are presented in the seventh edition of Janeway’s Immunobiology by Kenneth Murphy, Paul Travers, and Mark Walport. However, inevitably many of the early cases raise important issues that are not addressed until the later chapters of Immunobiology. To indicate which sections of Immunobiology contain material relevant to each case, we have listed on the first page of each case the topics covered in it. The color code follows the code used for the five main sections of Immunobiology: yellow for the introductory chapter and innate immunity, blue for the section on recognition of antigen, red for the development of lymphocytes, green for the adaptive immune response, purple for the response to infection and clinical topics, and orange for methods.

Dedication This fifth edition is dedicated to Fred Rosen (1935-2005). Fred dedicated his career of more than 50 years to the investigation and care of patients with primary immunodeficiency disease. Above all, he loved to teach and he did so superbly, aided by an encyclopedic knowledge of immunology, an incisive intelligence, an incredible memory, and charisma combined with an aura of authority. Fred had an enormous influence on many generations of both basic and clinical immunologists. This book is his brainchild and his contribution to it will be sorely missed.

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CONTENTS

Case 1 Case 2 Case 3 Case 4 Case 5 Case 6 Case 7 Case 8 Case 9 Case 10 Case 11 Case 12 Case 13 Case 14 Case 15 Case 16 Case 17 Case 18 Case 19 Case 20

Congenital Asplenia Chronic Granulomatous Disease Leukocyte Adhesion Deficiency Hereditary Angioneurotic Edema Factor I Deficiency Deficiency of the C8 Complement Component Hereditary Periodic Fever Syndromes Interleukin 1 Receptor-associated Kinase 4 Deficiency X-linked Hypohydrotic Ectodermal Dysplasia and Immunodeficiency X-linked Agammaglobulinemia X-linked Hyper IgM Syndrome Activation-induced Cytidine Deaminase (AID) Deficiency Common Variable Immunodeficiency X-linked Severe Combined Immunodeficiency Adenosine Deaminase Deficiency Omenn Syndrome MHC Class I Deficiency MHC Class II Deficiency Multiple Myeloma T-Cell Lymphoma

Case 21 Case 22 Case 23 Case 24 Case 25

Interferon-g Receptor Deficiency Wiskott-Aldrich Syndrome X-linked Lymphoproliferative Syndrome Autoimmune Lymphoproliferative Syndrome (ALPS) Immune Dysregulation, Polyendocrinopathy, Enteropathy X-linked Disease Toxic Shock Syndrome Acute Infectious Mononucleosis Mixed Essential Cryoglobulinemia Rheumatic Fever Lepromatous Leprosy Acquired Immune Deficiency Syndrome (AIDS)

Case 26 Case 27 Case 28 Case 29 Case 30 Case 31

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Case 32 Case 33 Case 34 Case 35 Case 36 Case 37 Case 38 Case 39 Case 40 Case 41 Case 42 Case 43 Case 44 Case 45 Case 46 Case 47

Acute Systemic Anaphylaxis Allergic Asthma Atopic Dermatitis Drug-Induced Serum Sickness Celiac Disease Contact Sensitivity to Poison Ivy Autoimmune Polyendocrinopathy-Candidiasis-Ectodermal Dystrophy Autoimmune Hemolytic Anemia Myasthenia Gravis Pemphigus Vulgaris Rheumatoid Arthritis Systemic Lupus Erythematosus Multiple Sclerosis Hemolytic Disease of the Newborn A Kidney Graft for Complications of Autoimmune Insulin-Dependent Diabetes Mellitus Graft-Versus-Host Disease

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Autoimmune Hemolytic Anemia

Autoimmune disease triggered by infection. There are various ways in which an infection could induce autoimmunity: disruption of a tissue barrier might expose a normally sequestered autoantigen; the infecting microorganism might act as an adjuvant; microbial antigen might bind to self proteins and act as haptens; and the microorganism might share cross-reactive antigens with the host (molecular mimicry). The major histocompatibility antigens carried by an individual may also confer susceptibility to, or protection against, certain autoimmune diseases that can be incited by infection (Fig. 39.1).

Topics bearing on this case: Coombs test Humoral autoimmunity Mechanisms for breaking tolerance

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Autoimmune Hemolytic Anemia

Fig. 39.1 Association of infection with autoimmune diseases. Several autoimmune diseases occur after specific infections and are presumably triggered by the infection. The case of post-streptococcal disease is best known. Most of these post-infection autoimmune diseases also show susceptibility linked to the MHC.

Associations of infection with immune-mediated tissue damage Infection

HLA association

Consequence

Group A Streptococcus

?

Rheumatic fever (carditis, polyarthritis)

Chlamydia trachomatis

HLA-B27

Reiter's syndrome (arthritis)

Shigella flexneri, Salmonella typhimurium, Salmonella enteritidis, Yersinia enterocolitica, Campylobacter jejuni

HLA-B27

Reactive arthritis

HLA-DR2, -DR4

Chronic arthritis in Lyme disease

Borrelia burgdorferi

There are only a few conditions in which the infection has been identified as the direct cause of the autoimmune disease. We have seen how some infections with Streptococcus pyogenes may lead to rheumatic fever (see Case 29). Some strains of S. pyogenes lead to a type III autoimmune disease (caused by immune-complex formation; see also Case 43) of the renal glomeruli called post-streptococcal acute glomerulonephritis. These streptococcal strains are said to be nephritogenic (causing nephritis). About 3–4% of children infected with a nephritogenic strain of streptococcus will develop acute glomerulonephritis within a week or two of the onset of the streptococcal infection. What predisposes this subset of children to develop the complication is unknown. A direct association of infection with autoimmune disease also occurs in patients with pneumonia caused by Mycoplasma pneumoniae, the case we shall discuss here. About 30% of patients with this infection develop a transient increase in serum antibody to a red blood cell antigen, and a small proportion of these patients develop hemolytic anemia, a type II autoimmune disease (see Fig. 40.1). In this case, the decrease in the number of red blood cells (anemia) results from their immunological destruction (hemolysis) as a result of the binding of an IgM autoantibody to a carbohydrate antigen on the red cell surface. When the infection subsides, either spontaneously or after treatment, the autoimmune disorder disappears. The IgM autoantibody agglutinates red blood cells at temperatures below 37°C. Thus the antibodies are called cold hemagglutinins or cold agglutinins, and the hemolytic disorder is known as cold agglutinin disease. Low titers of cold agglutinins (detectable at up to 1 in 30 dilution of serum) occur in healthy people. In about one-third of patients with mycoplasma infection there is a transient increase in the titer, but without symptoms; the rise usually goes unnoticed unless the patient happens to have a blood test, when clumping of the erythrocytes will be apparent. The autoantibodies in the transient cold agglutinin syndrome resemble those in the chronic autoimmune disorder known as chronic cold agglutinin disease, which is of unknown etiology. This runs a protracted course in which the autoantibodies are characteristically oligoclonal, and lymphoproliferative disorders commonly develop. Thus chronic cold agglutinin disease behaves as a variant of an IgM gammopathy called Waldenström’s macroglobulinemia. A gammopathy is an abnormal monoclonal or oligoclonal spike in the immunoglobulin electrophoretic pattern; see also Case 19.

Autoimmune Hemolytic Anemia

The case of Gwendolen Fairfax: the sudden onset of fever, cough, and anemia.

Gwendolen Fairfax was a healthy, unmarried 34-year-old who worked as a manager in a bank. She had never had any illness other than minor colds and the usual childhood infections. After developing a feverish cough her symptoms got progressively worse over the next few days and she decided to seek the advice of her physician, Dr Wilde. Dr Wilde noted that Gwendolen was extremely pale; this was particularly noticeable in the palms of her hands, which were completely white. (Look at your palms; they have a healthy reddish pink color, unless your hemoglobin level is