Subtypes of Chronic Fatigue Syndrome: A Review of Findings

Journal: J of Chronic Fatigue Syndrome, Vol. 8, Numbers 3/4, 2001, pp. 1-21
Authors: Leonard A. Jason, PhD; Renée R. Taylor, PhD; Cara L. Kennedy, BA; Susan Torres Harding, MA; Sharon Song, MA; Danielle Johnson, BA; Radhika Chimata, BA
Affiliation: Department of Psychology, DePaul University
Address correspondence to: Leonard A. Jason, Department of Psychology, DePaul University, 2219 North Kenmore Avenue, Chicago, IL 60614 USA.
Financial support for this study was provided by NIAID grant number AI36295.

SUMMARY. Most studies of Chronic Fatigue Syndrome (CFS) have been based on patients recruited from primary or tertiary care settings. Patients from such settings might not be typical of patients in the general population and may not accurately reflect the heterogeneity among individuals diagnosed with this condition. The current paper reviews four community-based studies that examined subtypes of individuals with CFS. Distinctions between subtype groups based on sociodemographics, illness onset and duration, stressful precipitating events, symptom frequency, and comorbidity characteristics are made with respect to outcome measures of fatigue and symptom severity, functional ability, and psychiatric comorbidity.

KEYWORDS. CFS definition, symptomatology, population studies

INTRODUCTION: Chronic Fatigue Syndrome (CFS) is a highly heterogeneous condition, affecting different people in different ways, and fluctuating in terms of symptoms and severity during illness course (Anderson & Ferrans, 1997). It can affect virtually every major system in the body; neurological, immunological, hormonal, gastrointestinal and musculoskeletal problems have been reported (Friedberg & Jason, 1998). One major challenge facing CFS research is the issue of patient heterogeneity. Across studies, individuals with CFS have been found to differ with respect to characteristics such as gender, ethnicity, and socioeconomic status, mode of illness onset and duration of illness, symptom severity, functional disability, psychiatric comorbidity, and coping styles (Friedberg & Jason, 1998). As a result of this heterogeneity, findings emerging from studies in a number of areas are, at best, discrepant, and at worst, contradictory, and the field has become highly polarized with respect to issues involving etiology, diagnosis, epidemiology, and treatment. Uncontrolled patient heterogeneity in empirical studies is one consequence of ignoring this important issue of sub-classification. When unique patient groups are unwittingly combined, any distinctions pertaining to specific subtypes of CFS become blurred.

For years, investigators have noted many biological abnormalities among patients with CFS, including over-activated immune systems (Landay, Jessop, Lennette, & Levy, 1991), biochemical dysregulation in the 2-5A synthetase/RNase L pathway (Suhadolnik et al., 1997), cardiac dysfunction (Lerner, Lawrie, & Dworkin, 1993), EEG abnormalities (Donati, Fagioli, Komaroff, & Duffy, 1994), abnormalities in cerebral white matter (Natelson, Cohen, Brassloff, & Lee, 1993), decreases in blood flow in certain areas of the brain (Schwartz et al., 1994), and autonomic nervous system dysfunction (Freeman & Komaroff, 1997). However, there has been a lack of consistency in such laboratory findings, which may be a function of combining distinctive groups of patients into a large heterogeneous group rather than analyzing them within subtypes.

Recent studies illustrate that sociodemographic variables can play an important role in highlighting key distinctions between individuals with CFS surrounding illness severity and functional disability. Several studies have highlighted commonalities among individuals with CFS, including greater likelihood of being female, Caucasian, and of higher socioeconomic status (Reyes et al., 1997; Gunn, Connell, & Randall, 1993). However, community-based studies involving representative samples of ethnically and socioeconomically diverse populations indicate that the prevalence of CFS is actually higher for minority groups of Latinos and African-Americans than for Caucasians (Jason, Richman et al., 1999), and higher for individuals of lower socioeconomic status than for those of higher socioeconomic status (Wessely, Chalder, Hirsch, Wallace, & Wright, 1997). CFS continues to be found to be more prevalent among women than men (Jason, Richman et al., 1999), and there is some evidence to indicate that there are gender-related differences in the impact of CFS as well as in prevalence. Among a sample of individuals with CFS, women were found to have a higher frequency of fibromyalgia, tender/enlarged lymph nodes, and lower scores on the physical functioning subscale of the MOS, while men had higher frequency of pharyngeal inflammation and a higher lifetime prevalence of alcoholism (Buchwald, Pearlman, Kith, & Schmaling, 1994). It is important for investigators to more frequently examine sociodemographic subtype differences like these in patients with CFS.

Findings from many empirical investigations of CFS suggest that subtypes of patients can be also distinguished with respect to the mode of illness onset (whether gradual or sudden) (DeLuca, Johnson, Ellis, & Natelson, 1997; Reyes et al., 1999; Komaroff, 1988, 1994; Levine, 1997), the presence of a stressful life event preceding or precipitating onset of CFS (Ray, Jeffries, & Weir; 1995; Salit, 1997; Theorell, Blomkvist, Lindh, & Evengard, 1999), and the duration of the illness. Reyes and associates (1999), examined symptoms experienced at illness onset for individuals with either sudden or gradual onset of CFS. Those with sudden onset reported significantly more symptoms at onset than those with gradual onset, and symptoms were more likely to be of infectious nature, including fever, sore throat, chills, and tender lymph nodes. This is consistent with other research (Komaroff, 1988, 1994) suggesting that sudden onset of CFS may be indicative of viral or other infectious illness. Some evidence indicates that individuals with CFS have experienced a higher frequency of negative life events in the time directly preceding the onset than matched controls ( Salit, 1997; Theorell et al., 1999). With respect to duration of illness, some researchers (Clark et al., 1995; Ray, Jeffries, & Weir, 1997) have determined that persistent illness and poorer outcomes could be predicted by longer duration of CFS symptoms. Wilson and associates (1994), however, did not find duration of illness to be a predictor of outcome, and Hill, Tiersky, Scavalla, and Natelson (1999) found that neither duration of illness nor mode of onset predicted illness outcome. Clearly, more research is needed to examine these important subtypes.

Findings suggest that patients with CFS can also be distinguished in terms of symptom frequency and severity. In a US sample, Manu and associates (1988) found a bimodal distribution of symptoms among 100 chronic fatigue patients, including 21 patients with 10-15 symptoms and 79 patients with 0-9 symptoms. In two follow-up studies of patients with CFS, persistent symptoms and disability at the follow-up were associated with having eight or more medically unexplained symptoms at initial evaluation (Clark et al., 1995; Bombardier & Buchwald, 1995). A comparison group of non-CFS chronic fatigue patients exhibited fewer symptoms and higher functioning (Bombardier & Buchwald, 1995). It seems apparent that patients with a higher number of symptoms are more functionally impaired than those with fewer symptoms.

Many of the symptoms associated with CFS are also characteristic of Fibromyalgia (FM). In the absence of definitive diagnostic markers or laboratory tests to distinguish these conditions, clinical diagnosis is largely based on self-report symptoms and behavioral criteria. Several previous studies have suggested that CFS and FM have many similarities (Buchwald, 1996; Goldenberg, 1988; Goldenberg, Simms, Geiger & Komaroff, 1990), although rates of comorbidity between CFS and FM are highly disparate. Another subtype that would be useful to investigate in future studies involves comparing those patients with only CFS versus those patients with CFS and FM.

In addition to comorbidity of medical illnesses such as FM with CFS, debate exists with respect to the issue of psychiatric comorbidity among individuals with CFS, and the research community is polarized as to the role of psychiatric illness in the etiology, course, and progress of CFS. Some researchers ( Gold et al., 1990; Katon, Buchwald, Simon, Russo, & Mease, 1991; Manu, Lane, and Matthews, 1988; Taerk, Toner, Salit, Garfinkel, & Ozersky, 1987) have found psychiatric illness to play a primary role in development and course of CFS, while others (Hickie, Lloyd, Wakefield, & Parker, 1990; Yeomans & Conway, 1991; Stone et al., 1994) have provided evidence against such findings. Comparing patients with psychiatric comorbidity versus those without psychiatric comorbidity involves another important area of subtyping for CFS research.

Findings from a community-based epidemiologic study of CFS have examined several distinctive subtype groups of individuals with CFS, including subtypes based on sociodemographic variables (Jason et al., 2000a), variables related to illness onset and duration (Jason et al., 2000b), symptom frequency (Jason et al., 2001a), and comorbidity with other illness, including fibromyalgia and psychiatric illness (Jason et al., 2001b). This article reviews and summarizes results of these studies, and highlights the implications of subtype findings for future research.

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