Chronic Fatigue Syndrome: Case Definitions and Diagnostic Assessment

Abstract

Chronic fatigue syndrome (CFS) is a chronic, debilitating illness that has posed considerable challenges for both patients and health care providers. Individuals with CFS often deal with considerable stigma and difficulties accessing appropriate care. Many medical professionals are increasingly recognizing the devastating nature of this illness, but at this time, few health care workers are knowledgeable and experienced enough to provide adequate patient care. There is a need for further efforts to educate health care workers on CFS diagnostic, assessment, and treatment issues. The present article reviews controversies regarding CFS case definitions, diagnostic criteria, the name of the illness, and epidemiological and treatment studies. We conclude that an imprecise case definition underlies many of the problems with diagnostic and treatment issues..

Chronic fatigue syndrome (CFS) affects more than one million people in the United States (Jason, King, Richman, Taylor, & Song, 1999), yet it has posed considerable challenges for the research and health care communities. This illness has symptoms that are as debilitating as Type II diabetes mellitus, congestive heart failure, Multiple sclerosis, and end-stage renal disease (Anderson & Ferrans, 1997; Buchwald, Pearlman, Umali, Schmaling, & Katon, 1996). Individuals with CFS often feel incapacitated by the illness, and experience multiple symptoms including post-exertional malaise, unrefreshing sleep, and memory and concentration problems (Fukuda et al., 1994). In addition, people with CFS often have difficulties accessing appropriate health care for their illness. Although the mainstream medical community is beginning to recognize the seriousness of the illness, there still remain a limited number of physicians and health care workers who are experienced enough in this area to provide adequate care. We begin this review of a CFS case definition and diagnostic issues with a brief history of CFS.

History

Patients with what might have been CFS were described at least 150 years ago, and some had the condition known as neurasthenia. By World War I this diagnosis had almost entirely disappeared due to increased medical skepticism regarding neurasthenia and the view that neurasthenia was a psychiatric rather than neurological disorder. There were a number of outbreaks of CFS-like illnesses as early as the 1930s (Friedberg & Jason, 1998). In the mid-1980s, there were several prominent outbreaks in the United States that received national media attention. Over the past 30 years, patients have described the illness as serious and physically disabling, whereas many within the medical profession have been more skeptical of the legitimacy of this diagnosis.

Name Controversy

Before the Centers for Disease Control and Prevention gave this illness the name CFS in 1988 (see below), it had been known as myalgic encephalomyelitis. The name CFS has been controversial, as it is both misleading and contributes to the stigma associated with this illness. For example, when undergraduate and medical students were asked to provide their attributions about a patient with CFS-like symptoms, those who were told that the case study was for a patient with the diagnosis “myalgic encephalopathy” were more likely to attribute a biomedical cause to the illness than did those who were told that the patient had a diagnosis of “chronic fatigue syndrome” (Jason, Eisele, & Taylor, 2001).

Many patient activists feel that because (a) the symptom of fatigue can be found in a wide array of diseases, such as depression, cancer, multiple sclerosis, and rheumatoid arthritis, and (b) fatigue is experienced by healthy people, having this term so prominent in the illness’ name contributes to the disrespect and stigma they feel. Therefore, many patient groups throughout the world prefer the term myalgic encephalomyelitis.

Case Definitions

The term CFS was first developed by the CDC following reports of a patient cluster in Incline Village, Nevada (Holmes et al., 1988). The original case definition by Holmes et al. (1988) described CFS as “the new onset of persistent or relapsing, debilitating fatigue…severe enough to reduce or impair average daily activity below 50% of the patient’s premorbid activity level for a period of at least six months (p. 388).” Furthermore, a person had to exhibit eight or more symptoms (e.g., sore throat, painful lymph nodes, muscle weakness). There was general dissatisfaction with the original case definition due, in part, to the realization that an illness with so many unexplained somatic symptoms could inadvertently identify those who in reality have either somatization or affective disorders (Friedberg & Jason, 1998).

In 1994 a new CFS definition was published, which is now used internationally. According to Fukuda et al. (1994), a case of CFS must have persistent or relapsing chronic fatigue and the concurrent occurrence of four or more symptoms (memory or concentration problems, sore throat, tender lymph nodes, muscle pain, joint paint, headaches, unrefreshing sleep, and post-exertional malaise). Although these diagnostic criteria now required four rather than eight symptoms, many criticized these criteria for not requiring core symptoms of the illness, such as post-exertional malaise.

In 2003, a group of international clinicians and researchers (Carruthers et al., 2003) established the Clinical Canadian Criteria for Myalgic Encephalomyelitis (ME/CFS), also referred to as the Canadian ME/CFS consensus criteria. These criteria required the cardinal symptoms of the illness such as memory and concentration problems, and post-exertional malaise, which were not a requirement of the Fukuda et al. (1994) CFS definition. The Canadian ME/CFS case definition required seven symptoms. Later in 2011, another consensus based case definition proposed was called Myalgic Encephalomyelitis: International Consensus Criteria (ME-ICC; Carruthers et al., 2011), which increased the number of required symptoms to eight.

The Canadian ME/CFS consensus criteria and the later ME-ICC criteria are both consensus-based rather than empirical. Because these case definitions require more core symptoms, they tend to identify a smaller number of patients, and these patients often have more severe symptoms and increased physical functioning impairment (Jason, Brown, Evans, Sunnquist, & Newton, 2013). In addition, case definitions that require a larger number of core symptoms may also contribute to higher rates of psychiatric comorbidity (Brown, Jason, Evans, & Flores, 2013; Katon, & Russo, 1992), as was evident with the Holmes et al. (1988) criteria. A recent systematic review (Brurberg, Fønhus, Larun, Flottorp, & Malterud, 2014) identified 20 case definitions, with the Fukuda et al. (1994) criteria being the most frequently applied. There is inconsistency in the validation of any of the case definitions, and no studies have rigorously assessed their reliability or practicality.

Diagnostic Challenges

There are a number of factors that make it challenging for physicians to diagnose CFS, such as an absence of similar biomarkers (i.e., blood test or other lab tests) for all patients. The considerable variability in patient cohorts due to reliability problems in how cases are defined exacerbates the difficulty in identifying possible biomarkers. In addition, fatigue is a common symptom across many illnesses, including psychiatric disorders such as major depressive disorder. The symptoms of CFS vary from person to person and can fluctuate in their severity and frequency, requiring health care workers to first rule out other possible causes before making a diagnosis of CFS. For example, Friedberg, Dechene, McKenzie, and Fontanetta (2000) illustrated the potential for CFS to be misdiagnosed when using the Fukuda et al. (1994) criteria alone. This study by Friedberg et al. (2000) assessed CFS symptomatology in a sample comprised of 179 healthy adults who did not have CFS. From this sample, 15% of the healthy adults met the Fukuda et al. (1994) criteria for CFS.

When diagnostic criteria vary and markers are unclear or unknown, then CFS case assessments and diagnostics rely heavily upon information obtained through clinical interviews (Fukuda et al., 1994), and unreliability is increases. In addition, without clear diagnostic assessment criteria, problems emerge for the legitimacy of this illness. Consequently, efforts are currently ongoing by scientists, government officials, and patient groups to develop a better consensus regarding which case definition to use for clinical care and research.

Epidemiology

Early prevalence estimates by the CDC suggested CFS to be a rare disorder (2–7.3 individuals per 100,000 cases). However, later findings derived from a community-based epidemiological study estimated the prevalence rate for CFS to be at 420 per 100,000 (Jason et al., 1999). This later prevalence statistic would suggest that about a million individuals in the United States have this chronic health condition. Furthermore, Jason et al. found a higher risk of CFS among women, Latinos, middle- aged individuals, and persons of middle-to lower socioeconomic status, thereby contradicting the assumption that CFS primarily affected upper-class white women, the so- called “yuppie flu” myth.

Clearly, epidemiological statistics may vary considerably due to unresolved diagnostic issues and disagreement surrounding the CFS case definition. Using a case definition that lacks specificity increases the chance for people with other diseases to be incorrectly diagnosed with CFS. For example, in a community-based prevalence study in Georgia, Reeves et al. (2005) attempted to operationalize the CFS Fukuda et al. (1994) case definition. The results from that study indicated that 2.54% of, or over four million, Americans had CFS. Conversely, when Jason Najar, Porter, and Reh (2009) applied this case definition to patients with major depressive disorder, 38% were misclassified as having CFS. Therefore, it is critical to develop case definitions that better identify patients who have the illness (sensitivity) and exclude those who do not (specificity).

Assessment Instruments

The Diagnostic Interview Schedule

The Diagnostic Interview Schedule (DIS) is a structured psychiatric instrument that was designed to be used in community surveys (Robins & Reiger, 1991). However, it was not designed to be used with medically ill populations. For example, when using the DIS, if several physicians diagnosed a patient as having a medical disorder, but only one attributed the symptom to a psychiatric disorder, the item would be scored as counting toward a psychiatric disorder. Unfortunately, because some physicians still do not accept CFS as a legitimate medical disorder, it is possible that some patients would have at least one physician who diagnosed their medical complaint as being psychiatric, subsequently increasing the likelihood that people with CFS would receive a psychiatric disorder diagnosis instead.

Structured Clinical Interview for the DSM-IV (SCID)

The Structured Clinical Interview for the DSM-IV (SCID) utilizes unstructured open-ended questions to gain a rich and detailed understanding of the patient’s issues. Taylor and Jason (1998) conducted a study where both the DIS and the SCID were administered to a CFS sample. Their findings revealed that 50% of those with CFS received a current Axis I psychiatric diagnosis when using the DIS, while only 22% received a current diagnosis using the SCID. The SCID is the more appropriate instrument to use in the diagnosis of psychiatric conditions among patients with CFS (Taylor & Jason, 1998).

Symptom Questionnaires

In order to reduce reliability issues, there is a need not only to develop consensus for a better case definition but also for clinicians and researchers to use similar assessment instruments as they collect self-report and other more biological data. One such self-report instrument that is being increasingly used is the DePaul Symptom Questionnaire (DSQ; Jason, Evans, Brown, & Porter, 2010), a self-report measure of symptomatology, demographics, and medical, occupational, and social history. In one part of the DSQ, patients are asked to rate the frequency and severity of 54 symptoms on a 5-point Likert scale. Symptom frequency is rated as 0 = none of the time, 1 = a little of the time, 2 = about half the time, 3 = most of the time, and 4 = all of the time. Likewise, severity is rated as 0 = symptom not present, 1 = mild, 2 = moderate, 3 = severe, and 4 = very severe. The DSQ has evidenced good test-retest reliability among both patient and control groups (Jason, So, Sunnquist, Brown, & Evans, 2014). A factor analysis by Brown and Jason (2014) revealed a three-factor solution, with the factors evidencing good internal consistency. The DSQ is available at REDCap’s shared library: https://redcap.is.depaul.edu/surveys/?s=tRxytSPVVw

Assessing fatigue

The National Institutes of Health Activity Record (ACTRE; Gerber & Furst, 1992) is a self-report assessment that allows individuals to rate feelings of fatigue and pain as they relate to activities—including the type, level, and meaningfulness of the activities—every 30 minutes. The ACTRE is a functional tool for clinicians because it allows patients to document their daily activity levels, thereby allowing clinicians to gain better insight into a patient’s daily activities and resting periods. Jason and Brown (2013) found three different trajectories when using the ACTRE in a sample of 90 patients. One group evidenced high fatigue intensity and low fatigue variability, with fatigue intensity staying the same over time. A second group had moderate fatigue intensity and high fatigue variability, with fatigue intensity decreasing over time. A third group had moderate fatigue intensity and high fatigue variability, with fatigue intensity increasing over time. These three clusters differed on measures of actigraphy (i.e., movement), pain, and immune functioning. This study suggested that activity logs can provide investigators and clinicians with valuable sources of data for understanding patterns of behavior and activity among patients with CFS.

Quality of Life

CFS can have a devastating impact on an individual’s quality of life (Jason, Fennel, & Taylor, 2003). Although some patients are able to maintain a full-time job, many cannot. As work and life plans are drastically curtailed due to this illness, economic problems are often encountered. In addition, many people with CFS find it difficult to have co-workers, medical personnel, and family and friends understand the seriousness of the illness, thus contributing to patient alienation. In addition to the difficulties of maintaining employment, those with this illness might have difficulties with housing and obtaining adequate medical care. When symptoms’ medical underpinnings are complex and difficult to understand, health care workers may inappropriately give a diagnosis to patients who in reality have an affective disorder. Furthermore, physicians who treat patients with CFS might be subjected to criticism from their medical colleagues for taking on such time-involving complex cases, which might generate less income for a medical practice than patients with easier to treat illnesses.

Treatments

Curative treatments are not available for CFS, and patients often explore an assortment of traditional and nontraditional treatment methods. Although studies have indicated that non pharmacologic interventions, such as cognitive behavior therapy (CBT) and graded exercise therapy (GET), can produce improvements in health-related quality of life for those with cancer and other diseases, the use of CBT and GET for CFS has produced more mixed and controversial outcomes. Price, Mitchell, Tidy, and Hunot (2008) reviewed 15 studies of CBT with a total of 1,043 CFS participants. At treatment’s end, 40% of people in the CBT group showed clinical improvement in contrast to only 26% in usual care, but these changes were not maintained at a 1- to 7- month follow-up when including patients who had dropped out. In addition, some have argued that activity-based interventions, such as GET, may be inappropriate for those with CFS, as patients typically experience post-exertional malaise (PEM), with exercise exacerbating these symptoms. Results from surveys of patients suggest high levels of dissatisfaction with CBT and GET.

Most patients prefer illness management techniques such as pacing (i.e., a set of techniques to reduce overexertion), which have been developed to reduce symptom exacerbation as a result of overexertion. One variation of this is called the Envelope Theory, which encourages patients to estimate their amount of daily perceived available energy on a scale from 0 to 100 and to exert no more energy than they perceive they have available to them. According to this theory, patients can remain within their “energy envelope” and prioritize their day’s activities based on their self-estimated available energy. Jason, Benton, Torres-Harding, and Muldowney (2009) found that patients who operated within their energy envelop after participating in nonpharmacologic interventions experienced lower fatigue than those who did not.

Some patients with CFS have reported using other types of complementary and alternative medicine, such as acupuncture, in relieving pain and producing relaxation. Some individuals with CFS have modified their diets due to allergies or food sensitivity to certain foods such as dairy products or wheat. Unfortunately, few studies have evaluated the effectiveness of these alternative treatments (Porter, Jason, Boultron, Bothne, & Coleman, 2010).

Conclusion

The lack of a reliable case definition underlies many issues in our understanding of the epidemiology and pathophysiology of this illness, which contributes to ambiguities among scientists, and ultimately impacts patients. These types of factors contribute to the diminished quality of life for individuals with this illness. Improving the current case definition and including the various stakeholders, such as scientists, clinicians, patients, policymakers, and community psychologists in the process could be extremely beneficial to the CFS community. Developing a more reliable and valid case definition has the potential to identify more homogenous patient samples that could consequently aid in the pursuit of biomarkers for CFS and ultimately better treatments for patients (Nacul et al., 2011). Health care researchers can contribute by helping identify critical domains and symptoms that are part of this illness, as well as by using consistent methods and assessment instrument to capture those specific symptoms. Practicing psychologists can be alert to these issues, and by doing so can form more empathetic relationships and better serve as advocates for their patients.

Biographies

Yolonda J. Williams received her PhD in community psychology from National Louis University in 2012. She is currently a Project Director at DePaul University for the Center for Community Research where she oversees a longitudinal NIH-funded prospective health study to examine the biological and psychological factors that would cause college students to develop chronic fatigue syndrome after the onset of infectious mononucleosis.

Rachel L. Jantke is a Project Director at DePaul University’s Center for Community Research, where she oversees a large-scale NIH-funded epidemiological study to examine the prevalence of pediatric chronic fatigue syndrome. Concurrently, Rachel is finishing her dissertation and is near completion of a community psychology doctoral program at National Louis University in Chicago, IL.

Leonard A. Jason received his PhD in clinical psychology from the University of Rochester in 1975. He is currently a Professor of Psychology at DePaul University and the Director of the Center for Community Research. He served as the Chairperson of the Research Subcommittee of the U.S. Chronic Fatigue Syndrome Advisory Committee, which makes recommendations to the Secretary of Health and Human Services.