Research abstract:
Background: The diagnosis of myalgic encephalomyelitis (ME)/chronic fatigue syndrome (CFS) is based on clinical criteria, yet there has been no consensus regarding which set of criteria best identifies patients with the condition. The Institute of Medicine has recently proposed a new case definition and diagnostic algorithm.
Purpose: To review methods to diagnose ME/CFS in adults and identify research gaps and needs for future research.
Data Sources: MEDLINE, PsycINFO, and Cochrane databases (January 1988 to September 2014); clinical trial registries; and reference lists.
Study Selection: English-language studies describing methods of diagnosis of ME/CFS and their accuracy.
Data Extraction: Data on participants, study design, analysis, follow-up, and results were extracted and confirmed. Study quality was dual-rated by using prespecified criteria, and discrepancies were resolved through consensus.
Data Synthesis: Forty-four studies met inclusion criteria. Eight case definitions have been used to define ME/CFS; a ninth, recently proposed by the Institute of Medicine, includes principal elements of previous definitions. Patients meeting criteria for ME represent a more symptomatic subset of the broader ME/CFS population. Scales rating self-reported symptoms differentiate patients with ME/CFS from healthy controls under study conditions but have not been evaluated in clinically undiagnosed patients to determine validity and generalizability.
Limitations: Studies were heterogeneous and were limited by size, number, applicability, and methodological quality. Most methods were tested in highly selected patient populations.
Conclusion: Nine sets of clinical criteria are available to define ME/CFS, yet none of the current diagnostic methods have been adequately tested to identify patients with ME/CFS when diagnostic uncertainty exists. More definitive studies in broader populations are needed to address these research gaps.
Primary Funding Source: Agency for Healthcare Research and Quality. (PROSPERO: CRD42014009779)
The terms myalgic encephalomyelitis (ME) and chronic fatigue syndrome (CFS) have been used to describe a debilitating multisystemic condition characterized by chronic, disabling fatigue and various other symptoms. The term CFS was introduced in the 1980s after research failed to identify a clear viral association with what was previously labeled chronic Epstein–Barr virus syndrome (1–4).
Other terms, such as postviral fatigue syndrome and chronic fatigue immune dysfunction syndrome, were also used in attempts to associate the syndrome with possible underlying causes (1–2, 5–6). Although the most recent international consensus report advocates moving away from the term CFS in favor of the term ME to better reflect an underlying disease process involving widespread inflammation and neuropathology (7–8), experts do not agree about these mechanisms and the cause of CFS remains unclear.
A recent Institute of Medicine (IOM) report proposes a name, systemic exertion intolerance disease (SEID), that describes the central elements of the disease. The report focuses on the adverse effect that physical, cognitive, or emotional exertion can have on patients with this condition and acknowledges that this is a complex and severe disorder for which specific causes are not yet proven (9).
The diagnosis of ME/CFS is based on clinical criteria that attempt to distinguish it from other conditions that also present with fatigue. Eight published case definitions have been used since the first one established by the Centers for Disease Control and Prevention (CDC) in 1988 (2), and the IOM proposed a ninth in February 2015 (9). All include persistent fatigue not attributable to a known underlying medical condition, as well as additional clinical signs and symptoms that do not all need to be present to establish the diagnosis (10). However, there has been no consensus about which, if any, of these clinical criteria should be considered the reference standard.
The variations in case definitions imply that they may describe different conditions and lead to different diagnoses, complicating ME/CFS research and clinical care. For example, depending on the case definition, prevalence rates of ME/CFS in the United States range from 0.3% to 2.5% (1, 11–12).
This systematic review is part of a larger report to inform a research agenda for the National Institutes of Health (NIH) 2014 Pathways to Prevention Workshop, an evidence-based methodology workshop (13). The purpose of this systematic review was to evaluate and compare studies of methods to diagnose ME/CFS, identify limitations of current studies, and determine needs for future research.
Diagnostic Methods for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Systematic Review for a National Institutes of Health Pathways to Prevention Workshop, by Elizabeth Haney, MD; M.E. Beth Smith, DO; Marian McDonagh, PharmD; Miranda Pappas, MA; Monica Daeges, BA; Ngoc Wasson, MPH; and Heidi D. Nelson, MD, MPH in Ann Intern Med. 2015;162(12):834-840
