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
INSTITUTE OF MEDICINE
OF THE NATIONAL ACADEMIES
THE NATIONAL ACADEMIES PRESS
Washington, D.C.
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.
International Standard Book Number-13: 978-0-309-31689-7
International Standard Book Number-10: 0-309-31689-8
Library of Congress Control Number: 2015934699
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Copyright 2015 by the National Academy of Sciences. All rights reserved.
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Cover design by LeAnn Locher, LeAnn Locher & Associates.
Suggested citation: IOM (Institute of Medicine). 2015. Beyond myalgic encephalomyelitis/chronic fatigue syndrome: Redefining an illness. Washington, DC: The National Academies Press.
“Knowing is not enough; we must apply.
Willing is not enough; we must do.”
—Goethe
INSTITUTE OF MEDICINE
OF THE NATIONAL ACADEMIES
Advising the Nation. Improving Health.
THE NATIONAL ACADEMIES
Advisers to the Nation on Science, Engineering, and Medicine
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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 W. DAVIS, Stanford University School of Medicine, Stanford, CA
BETTY DIAMOND, The Feinstein Institute for Medical Research, Manhasset, NY
THEODORE G. GANIATS, University of 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 H. 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
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Reviewers
This report has been reviewed in draft form by individuals chosen for their diverse perspectives and technical expertise, in accordance with 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
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.
Symptom Constructs and Clusters
4 REVIEW OF THE EVIDENCE ON MAJOR ME/CFS SYMPTOMS AND MANIFESTATIONS
Limitations of the Research Base
Fatigue and Its Impact on Function
Orthostatic Intolerance and Autonomic Dysfunction
5 REVIEW OF THE EVIDENCE ON OTHER ME/CFS SYMPTOMS AND MANIFESTATIONS
Orthostatic Intolerance and Autonomic Dysfunction
Disseminating the Diagnostic Criteria
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Boxes, Figures, and Tables
BOXES
S-1 Proposed Diagnostic Criteria for ME/CFS
1-1 Institute of Medicine Study on Diagnostic Criteria for ME/CFS: Statement of Task
3-2 Suggestions for a New Name Received from Members of the Public
4-1 Sleep-Related Symptoms in Case Definitions and Diagnostic Criteria for ME/CFS
4-2 Prolonged Orthostatic Testing
4-3 Common Orthostatic Intolerance Syndromes
7-1 Proposed Diagnostic Criteria for ME/CFS
C-1 Social Security Administration Evaluation of Disability
FIGURES
S-1 Diagnostic algorithm for ME/CFS
1-1 Initial results (as of January 2014) of the committee’s broad literature search
7-1 Diagnostic algorithm for ME/CFS
TABLES
1-1 Targeted Search Results: Adults
1-2 Targeted Search Results: Pediatrics
3-1 Elements of Selected Case Definitions and Diagnostic Criteria for ME/CFS
4-1 Mean VT Score on the MOS SF-36 for ME/CFS Versus Other Fatigue Conditions
7-1 Operationalizing the Proposed Criteria for Diagnosis of ME/CFS for Major Symptoms of the Illness
7-2 Assessing Other Symptoms/Manifestations of ME/CFS That May Support Diagnosis
This study was sponsored by the U.S. Department of Health and Human Services Office on Women’s Health, the National Institutes of Health, the Centers for Disease Control and Prevention (CDC), the Food and Drug Administration, the 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.
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 Center 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.
Ellen Wright Clayton, Chair
Committee on the Diagnostic Criteria for
Myalgic Encephalomyelitis/Chronic Fatigue Syndrome
5-HT |
5 hydroxytryptamine |
5-HTT |
serotonin transporter |
17-OHP |
17-hydroxyprogesterone |
A4 |
androstenedione |
AAMC |
Association of American Medical Colleges |
ACR |
American College of Rheumatology |
ACTH |
adrenocorticotropin hormone |
ADH |
antidiuretic hormone |
AHRQ |
Agency for Healthcare Research and Quality |
AIDS |
acquired immune deficiency syndrome |
ANA |
antinuclear antibody |
ANT |
Attention Network Test |
ASP |
Autonomic Symptom Profile |
AVP |
arginine vasopressin |
B. |
Borrelia |
BMI |
body mass index |
BPI |
Brief Pain Inventory |
bpm |
beats per minute |
CANTAB |
Cambridge Neuropsychological Test Automated Battery |
CART |
classification and regression tree |
CBT |
cognitive-behavioral therapy |
CCC |
Canadian Consensus Criteria |
CDC |
Centers for Disease Control and Prevention |
CFIDS |
chronic fatigue and immune dysfunction syndrome |
CFS |
chronic fatigue syndrome |
CFSAC |
Chronic Fatigue Syndrome Advisory Committee |
CHF |
congestive heart failure |
CHQ |
Child Health Questionnaire |
CMV |
cytomegalovirus |
COMPASS |
Composite Autonomic Symptom Score |
CPAP |
continuous positive airway pressure |
CPET |
cardiopulmonary exercise test |
CRH |
corticotropin-releasing hormone |
CVDB |
Chronic Viral Diseases Branch |
DHEA |
dehydroepiandrosterone |
DPHQ |
DePaul Pediatric Health Questionnaire |
dsDNA |
double-stranded deoxyribonucleic acid |
DSM |
Diagnostic and Statistical Manual of Mental Disorders |
EBV |
Epstein-Barr virus |
EDS |
Ehlers-Danlos syndrome |
EEG |
electroencephalogram |
ELISA |
enzyme-linked immunosorbent assay |
FDA |
Food and Drug Administration |
FDI |
Functional Disability Inventory |
FIQ |
Fibromyalgia Impact Questionnaire |
FIQR |
Revised Fibromyalgia Impact Questionnaire |
FM |
fibromyalgia |
fMRI |
functional magnetic resonance imaging |
FMS |
fibromyalgia syndrome |
GAO |
Government Accountability Office1 |
HC |
healthy control |
HD |
hemodialysis |
HepC |
chronic hepatitis C |
HHS |
Department of Health and Human Services |
HHV |
human herpes virus |
HIV |
human immunodeficiency virus |
HPA |
hypothalamic-pituitary-adrenal (axis) |
HRQOL |
health-related quality of life |
_____________
1 Known as General Accounting Office until 2004.
HTLV |
human T-cell lymphotropic virus |
IACFS/ME |
International Association for Chronic Fatigue Syndrome/Myalgic Encephalomyelitis |
IADL |
instrumental activity of daily living |
IBS |
irritable bowel syndrome |
ICD-10 |
International Classification of Diseases (Tenth Revision) |
IDEA |
Individuals with Disabilities Education Act |
IFA |
immunofluorescence assay |
IGF-1 |
insulin-like growth factor 1 |
IGFBP-1 |
insulin-like growth factor-binding protein 1 |
IgG |
immunoglobulin G |
IgM |
immunoglobulin M |
IL |
interleukin |
IOM |
Institute of Medicine |
IVIG |
intravenous immunoglobulin |
JAK-STAT |
Janus kinase/signal transducer and activator of transcription |
LBNP |
lower-body negative pressure |
LDST |
low-dose synacthen test |
MCS |
multiple chemical sensitivity |
MD |
major depression |
MDI |
medically determinable impairment |
ME |
myalgic encephalomyelitis |
ME-ICC |
International Consensus Criteria for ME |
MOS |
Medical Outcomes Study |
MPS |
myofascial pain syndrome |
MRI |
magnetic resonance imaging |
MRS |
magnetic resonance spectroscopy |
MS |
multiple sclerosis |
MSD |
musculoskeletal disease |
MSIDS |
multi-systemic infectious disease syndrome |
MSLT |
multiple sleep latency test |
NICE |
British National Institute for Health and Clinical Excellence |
NIH |
National Institutes of Health |
NK |
natural killer |
NKCS |
nature killer cells syndrome |
NMH |
neurally mediated hypotension |
NREM |
non-rapid eye movement |
NYHA |
New York Heart Association Functional Classification |
ODP |
Office of Disease Prevention |
OFFER |
Organization for Fatigue & Fibromyalgia Education & Research |
OGS |
Orthostatic Grading Scale |
OH |
orthostatic hypotension |
OHQ |
Orthostatic Hypotension Questionnaire |
ORWH |
Office of Research on Women’s Health |
OWH |
Office on Women’s Health |
P2P |
Pathways to Prevention |
PANDORA |
Patient Alliance for Neuro-endocrine-immune Disorders Organization for Research and Advocacy |
PASAT |
Paced Auditory Serial Addition Test |
PBL |
peripheral blood lymphocyte |
PBMC |
peripheral blood mononuclear cell |
PCOCA |
Patient-Centered Outreach and Communication Activity |
PCP |
primary care provider |
PCR |
polymerase chain reaction |
Peds QL |
Pediatrics Quality of Life Inventory |
PEM |
post-exertional malaise |
PENE |
post-exertional neuroimmune exhaustion |
PET |
positron emission tomography |
POTS |
postural orthostatic tachycardia syndrome |
PPS |
post-polio syndrome |
PROMIS |
Patient-Reported Outcomes Measurement Information System |
PSG |
polysomnography |
PSQI |
Pittsburgh Sleep Quality Index |
PTSD |
posttraumatic stress disorder |
QOL |
quality of life |
QUADAS |
Quality Assessment of Diagnostic Accuracy Studies (tool) |
RA |
rheumatoid arthritis |
REM |
rapid eye movement |
RNA |
ribonucleic acid |
RP |
role-physical |
SAHS |
sleep apnea/hypopnea syndrome |
SDB |
sleep disordered breathing |
SEID |
systemic exertion intolerance disease |
SF-36 |
Short Form 36-Item Questionnaire |
SI |
Symptom Inventory |
SIP-ab |
Sickness Impact Profile-alertness behavior |
SSA |
Social Security Administration |
SSc |
scleroderma/systemic sclerosis |
SWS |
slow wave sleep |
TMJ |
temporomandibular joint syndrome |
TNF |
tumor necrosis factor |
TPRI |
total peripheral resistance index |
TSH |
thyroid-stimulating hormone |
VAS |
visual analog scale |
VCA |
viral capsid antigen |
VT |
vitality (subscale of the MOS SF-36) |
WMS-R |
Wechsler Memory Scale-Revised |
WSAS |
Work and Social Adjustment Scale |