Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Redefining an Illness

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Committee on the Diagnostic Criteria for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome; Board on the Health of Select Populations; Institute of Medicine

ISBN 978-0-309-31689-7

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Beyond Myalgic Encephalomyelitis/
Chronic Fatigue Syndrome
Redeﬁning an Illness

Committee on the Diagnostic Criteria for
Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Board on the Health of Select Populations

PREPUBLICATION COPY—Uncorrected Proofs

THE NATIONAL ACADEMIES PRESS 500 Fifth Street, NW Washington, DC 20001

NOTICE: The project that is the subject of this report was approved by the Governing Board of the National Research Council, whose members are drawn from the councils of the National Academy of Sciences, the National Academy of Engineering, and the Institute of Medicine. The members of the committee responsible for the report were chosen for their special competences and with regard for appropriate balance.

This study was supported by Contract No. HHSN263201200074I between the National Academy of Sciences and the National Institutes of Health. Any opinions, ﬁndings, conclusions, or recommendations expressed in this publication are those of the author(s) and do not necessarily reﬂect the views of the organizations or agencies that provided support for the project.

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Cover design by LeAnn Locher, LeAnn Locher & Associates. Suggested citation: IOM (Institute of Medicine). 2015. Beyond myalgic encepha-

lomyelitis/chronic fatigue syndrome: Redeﬁning an illness. Washington, DC: The

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COMMITTEE ON THE DIAGNOSTIC CRITERIA FOR MYALGIC
ENCEPHALOMYELITIS/CHRONIC FATIGUE SYNDROME

ELLEN WRIGHT CLAYTON (Chair), Center for Biomedical Ethics and

Society, Vanderbilt University Medical Center, Nashville, TN

MARGARITA ALEGRÍA, Harvard Medical School, Boston, MA

LUCINDA BATEMAN, Fatigue Consultation Clinic, Salt Lake City, UT

LILY CHU, International Association for Chronic Fatigue Syndrome/

Myalgic Encephalomyelitis, Chicago, IL; Stanford University ME/CFS Initiative, Stanford, CA
CHARLES S. CLEELAND, University of Texas MD Anderson Cancer
Center, Houston

RONALD DAVIS, Stanford University School of Medicine, Stanford, CA

BETTY DIAMOND, The Feinstein Institute for Medical Research,
Manhasset, NY

THEODORE GANIATS, University of Miami, Miami, FL BETSY KELLER, Ithaca College, Ithaca, NY

NANCY KLIMAS, Nova Southeastern University, Miami, FL A. MARTIN LERNER, Oakland University, William Beaumont School of
Medicine, Rochester, MI

CYNTHIA MULROW, University of Texas Health Science Center, San

Antonio
BENJAMIN NATELSON, Mount Sinai Beth Israel, New York, NY PETER ROWE, Johns Hopkins University, Baltimore, MD

MICHAEL SHELANSKI, Columbia University, New York, NY

Consultants

RONA BRIERE, Briere Associates Inc., Felton, PA

RENÉ GONIN, Westat, Inc., Rockville, MD

TROY PETENBRINK, Caduceus Marketing, Washington, DC

IOM Staff

CARMEN C. MUNDACA-SHAH, Study Director

KATE MECK, Associate Program Ofﬁcer (until September 2014)

JONATHAN SCHMELZER, Research Associate (from September 2014) ADRIANA MOYA, Senior Program Assistant (until May 2014) SULVIA DOJA, Senior Program Assistant (from May 2014) DORIS ROMERO, Financial Associate

FREDERICK ERDTMANN, Director, Board on the Health of Select
Populations

v

Reviewers

his report has been reviewed in draft form by individuals chosen for their diverse perspectives and technical expertise, in accordance with

T

procedures approved by the National Research Council’s Report
Review Committee. The purpose of this independent review is to provide candid and critical comments that will assist the institution in making its published report as sound as possible and to ensure that the report meets institutional standards for objectivity, evidence, and responsiveness to the study charge. The review comments and draft manuscript remain conﬁdential to protect the integrity of the deliberative process. We wish to thank the following individuals for their review of this report:

Italo Biaggioni, Vanderbilt University Susan Cockshell, University of Adelaide Stephen Gluckman, University of Pennsylvania Maureen R. Hanson, Cornell University

Ben Katz, Ann and Robert H. Lurie Children’s Hospital of Chicago

Charles Lapp, Hunter-Hopkins Center, P.A.

Michael L. LeFevre, University of Missouri School of Medicine Susan Levine, Medical Ofﬁce of Susan M. Levine Jose Montoya, Stanford University Medical Center

Daniel Peterson, Sierra Internal Medicine Michael I. Posner, University of Oregon Katherine Rowe, Royal Children’s Hospital Christopher Snell, University of the Paciﬁc

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REVIEWERS

Rudd Vermeulen, CFS/ME Medical Centre Yasuyoshi Watanabe, RIKEN Center for Life Science Technologies

Although the reviewers listed above provided many constructive comments and suggestions, they were not asked to endorse the report’s conclusions or recommendations, nor did they see the ﬁnal draft of the report before its release. The review of this report was overseen by David

Challoner, University of Florida, and Georges Benjamin, American Public

Health Association. Appointed by the Institute of Medicine, they were responsible for making certain that an independent examination of this report was carried out in accordance with institutional procedures and that all review comments were carefully considered. Responsibility for the ﬁnal content of this report rests entirely with the authoring committee and the institution.

Contents

PREFACE

xv

xvii
1
ACRONYMS AND ABBREVIATIONS SUMMARY

1

INTRODUCTION

15

Charge to the Committee, 16 Context for This Study, 17 The Committee’s Approach, 19 Overview of the Report, 24 References, 25

23
BACKGROUND

History of ME/CFS, 27 Terminology, 29 Burden of ME/CFS, 31 References, 33

27 37
CURRENT CASE DEFINITIONS AND DIAGNOSTIC CRITERIA, TERMINOLOGY, AND SYMPTOM CONSTRUCTS AND CLUSTERS

Case Deﬁnitions and Diagnostic Criteria, 38 Terminology, 57

ix

x

CONTENTS

Symptom Constructs and Clusters, 60 References, 66

4

REVIEW OF THE EVIDENCE ON MAJOR ME/CFS

SYMPTOMS AND MANIFESTATIONS

Limitations of the Research Base, 71 Fatigue and Its Impact on Function, 73 Post-Exertional Malaise (PEM), 78 Sleep-Related Symptoms, 86

71

Neurocognitive Manifestations, 96 Orthostatic Intolerance and Autonomic Dysfunction, 107 References, 119

56
REVIEW OF THE EVIDENCE ON OTHER ME/CFS SYMPTOMS AND MANIFESTATIONS

Pain, 141 Immune Impairment, 147 Neuroendocrine Manifestations, 152 Infection, 157

141 181

References, 162

PEDIATRIC ME/CFS

Post-Exertional Malaise (PEM), 184 Orthostatic Intolerance and Autonomic Dysfunction, 185 Neurocognitive Manifestations, 189 Sleep-Related Symptoms, 190 Infection, 191 Immune Impairment, 193 Neuroendocrine Manifestations, 195 Other Symptoms, 198 Symptom Constructs, 199 Summary, 200 References, 201

7

RECOMMENDATIONS

209

Making the Diagnosis, 213 Disseminating the Diagnostic Criteria, 225 Updating the Diagnostic Criteria, 226 Naming the Disorder, 227 Closing Thoughts, 228 References, 228

CONTENTS

xi

8

DISSEMINATION STRATEGY

Objective, 231

231

Context, 231 Strategic Choices, 235 Dissemination Activities, 239 Evaluation, 246 References, 246

APPENDIXES ABCD

PUBLIC SESSION AGENDAS GRADE GRID TEMPLATE DISABILITY IN ME/CFS QUESTIONNAIRES AND TOOLS THAT MAY BE USEFUL FOR ASSESSING ME/CFS SYMPTOMS BIOGRAPHICAL SKETCHES OF COMMITTEE MEMBERS, CONSULTANTS, AND STAFF
249 253 257

269

E

273

Boxes, Figures, and Tables

BOXES

S-1 Proposed Diagnostic Criteria for ME/CFS, 6 1-1 Institute of Medicine Study on Diagnostic Criteria for ME/CFS:
Statement of Task, 18

3-1 ME/CFS Research Subgroups, 57 3-2 Suggestions for a New Name Received from Members of the Public, 58

4-1 Sleep-Related Symptoms in Case Deﬁnitions and Diagnostic
Criteria for ME/CFS, 88
4-2 Prolonged Orthostatic Testing, 112 4-3 Common Orthostatic Intolerance Syndromes, 114

7-1 Proposed Diagnostic Criteria for ME/CFS, 210

FIGURES

S-1 Diagnostic algorithm for ME/CFS, 7 1-1 Initial results (as of January 2014) of the committee’s broad literature search, 21

xiii

xiv

BOXES, FIGURES, AND TABLES

4-1 Percentage of ME/CFS patients and healthy controls reporting PEM symptoms of at least moderate severity that occurred at least half of the time during the past 6 months, 81
4-2 Percentage of ME/CFS patients and healthy controls reporting sleeprelated symptoms of at least moderate severity that occurred at least half of the time during the past 6 months, 87
4-3 Percentage of ME/CFS patients and healthy controls reporting neurocognitive manifestations of at least moderate severity that occurred at least half of the time during the past 6 months, 98

5-1 Percentage of ME/CFS patients and healthy controls reporting pain symptoms of at least moderate severity that occurred at least half of the time for the past 6 months, 143
5-2 Percentage of ME/CFS patients and healthy controls reporting immune-related symptoms of at least moderate severity that occurred at least half of the time for the past 6 months, 148
5-3 Percentage of ME/CFS patients and healthy controls reporting neuroendocrine manifestations of at least moderate severity that occurred at least half of the time for the past 6 months, 153

7-1 Diagnostic algorithm for ME/CFS, 212

TABLES

1-1 Targeted Search Results: Adults, 23 1-2 Targeted Search Results: Pediatrics, 23

3-1 Elements of Selected Case Deﬁnitions and Diagnostic Criteria for
ME/CFS, 40

4-1 Mean VT Score on the MOS SF-36 for ME/CFS Versus Other
Fatigue Conditions, 76

7-1 Operationalizing the Proposed Criteria for Diagnosis of ME/CFS for
Major Symptoms of the Illness, 214
7-2 Assessing Other Symptoms/Manifestations of ME/CFS That May
Support Diagnosis, 220

Preface

his study was sponsored by the U.S. Department of Health and Human Services Ofﬁce on Women’s Health, National Institutes of

T

Health, Centers for Disease Control and Prevention (CDC), Food and Drug Administration, Agency for Healthcare Research and Quality, and the Social Security Administration, and conducted by a committee convened by the Institute of Medicine (IOM). The committee was asked to define diagnostic criteria for myalgic encephalomyelitis/chronic fatigue syndrome, to propose a process for reevaluation of these criteria in the future, and to consider whether a new name for this disease is warranted. The committee carefully reviewed the peer-reviewed literature on the multifaceted manifestations of this disease, and taking into account the clearly expressed views of hundreds of patients and their advocates, developed evidence-informed diagnostic criteria for this complex, multisystem, frequently undiagnosed, and often life-altering condition. The committee was able to redefine the diagnostic criteria for this disease so that they are easy to understand and apply and capture the essence of the disease’s unique symptomatology. The committee recommends an evidence-based, disinterested procedure by which these criteria can be refined in the future on the basis of new research.
Listening to the comments and testimony provided for this study, as well as examining advocacy websites and the Voice of the Patient report, the committee determined that the name “chronic fatigue syndrome” has done a disservice to many patients and that the name “myalgic encephalomyelitis” does not accurately describe the major features of the disease. In their place, the committee proposes “systemic exertion intolerance disease” as a name that better captures the full scope of this disorder.

xv

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PREFACE

The committee owes a debt of gratitude to all of those who volunteered their time and shared their expertise by presenting at its public meetings, including Dr. Sara Eggers, Dr. Leonard A. Jason, Dr. Akifumi Kishi, Dr. Gudrun Lange, Dr. Nancy Lee, Dr. Susan Maier, and Dr. Elizabeth Unger. The committee also thanks all the patient advocates who spoke during its public sessions, including Lori Chapo-Kroger, Carol Head, Gabby Klein, Joseph Landson, Pat LaRosa, Denise Lopez-Majano, Robert Miller, Charmian Proskauer, Jennie Spotila, and Annette Whittemore. Collectively, the wide variety of viewpoints expressed by these speakers provided valuable insight into the complexity of the disease and helped the committee develop its approach to and thought process regarding its statement of task.
The committee wishes to express its sincere appreciation to National
Academies research staff Daniel Bearss and Rebecca Morgan for their support with the comprehensive literature review conducted for this study. The evidence reviewed was enriched by research materials shared by agencies and organizations such as the CDC Multi-Site Clinical Study of CFS, Chronic Fatigue Initiative, Massachusetts CFIDS/ME & FM Association, PANDORA Org, Phoenix Rising, Solve ME/CFS Initiative, and by researchers and advocates, including Dr. Byron Hyde, Dr. Leonard Jason, Dr. Lisa Petrison, Dr. Suzanne Vernon, Mary Dimmock, Denise Lopez-Majano, Courtney Miller, and Jennie Spotila. The committee is extremely grateful for these contributions.
The committee also is grateful to the study consultants: Rona Briere for copyediting the report; René Gonin for his support in interpreting the methodology of relevant literature; LeAnn Locher for designing the cover of the report; and Troy Petenbrink, who provided his expertise in health communications to help the committee develop a dissemination plan for the recommendations in this report.
The committee could not have done its work without the extraordinary efforts of the staff of the IOM, including Carmen Mundaca-Shah, study director; Kate Meck, associate program ofﬁcer; Jonathan Schmelzer, research associate; and Adriana Moya and Sulvia Doja, senior program assistants. Their work was invaluable.
Finally, the committee would like to offer its profound thanks to the many patients and advocates who offered their knowledge, experiences, and feedback to inform its work throughout the study process. The success of this project is directly related to the support and assistance received from those passionate about this topic. The committee’s goal in addressing this task was to ensure that these patients receive the diagnoses and treatment they require and deserve. It is to them and to their return to health that this work is dedicated.