A natural history study of chronic fatigue syndrome.

There is a clear need to better understand the course of CFS over time. White (2007) summarized findings from five cohort studies involving postinfectious illness. These studies indicate that a postinfectious fatigue syndrome does exist, and that it is not a mood disorder. It appears that there are two postinfectious fatigue syndromes, one characterized by excessive sleep and the other by insomnia associated with muscle and joint pain. However, many of the natural history studies that are available have either not included a physician examination and psychiatric interview (Harvey, Wadsworth, Wessely, & Hotopf, 2008), were not based on a representative sample (Friedberg, Dechene, McKenzie, & Fontanetta, 2000), or were based on relatively short follow-up periods (Hickie et al., 2006). As an example, Ciccone, Chandler, and Natelson (2010) employed a two and half year follow up with participants seen at a tertiary clinic, and they found that those with CFS and co-occurring Fibromyalgia were 3.2 times more likely to be non-improvers than those with CFS alone. There is a clear need for research on the course of CFS in ethnically and socioeconomically diverse community populations. Epidemiologic work on CFS began with attempts to determine the prevalence of CFS. While initial studies were limited to treatment-based samples along with their methodological biases (Richman, Flaherty & Rospenda, 1994), subsequent studies addressed the prevalence of CFS in community-based samples (Jason, Richman et al. 1999; Njoku, Jason, & Torres-Harding, 2007; Reeves et al., 2007; Reyes et al. 2003). While we now have varying estimates of the prevalence of CFS, and controversies about case definitions used in such studies (Jason, Najar, Porter, & Reh, 2008), an important next epidemiologic step involves the clear need for longitudinal cohort studies with representative samples that identify risk factors for both recovery/improvement and relapse. Below we review some of the more prominent risk factors that have been associated with either CFS onset or maintenance over time. There is a steady increase of fatigue from middle to old age (Hammond, 1964). In an influential review article, Joyce, Hotopf, and Wessely (1997) concluded that older age was a risk factor for poor prognosis among individuals with CFS. For example, Clark and associates (1995) found that being over 38 years old predicted persistent illness in participants with chronic fatigue. Tiersky et al. (2001) also found the prognosis for CFS to be poor, with age being a significant predictor of outcome. Furthermore, Schmaling, Fiedelak, Katon, Bader, and Buchwald (2003) found that older age predicted a decline in physical functioning among individuals with unexplained chronic fatigue. Finally, in the Chicago community-based sample, Jason, Taylor, Kennedy, Jordan et al. (2000) found that those participants with CFS who were older had higher frequencies of symptoms and were more severely disabled. Conceivably, those who are older are less physically fit and/or have had more time to experience other physical illnesses or stressors that can cause fatigue. CFS is more prevalent among women than men (Jason, Richman et al., 1999; Reyes et al., 2003). In the Chicago community-based sample, gender predicted fatigue severity, with women exhibiting higher fatigue scores than men (Torres-Harding, Jason, & Taylor, 2002). Also, within this sample, women had significantly poorer physical functioning, more bodily pain, poorer emotional role functioning, significantly more severe muscle pain, and significantly greater impairment in work activities (Jason, Taylor, Kennedy, Jordan et al., 2000). Greater numbers of minorities than expected have been found in community-based studies (Dinos et al., 2009). In a Chicago community-based study, the prevalence of CFS was higher for Latinos and African-Americans than for Caucasians (Jason, Richman et al., 1999). Symptom severity outcome measures revealed that when compared to Caucasians, minorities had more severe sore throat pain, fatigue following exercise, headaches, unrefreshing sleep, and poorer general health (Jason, Taylor, Kennedy, Jordan, et al., 2000). In addition, Latinas who were older reported the highest relative severity of fatigue (Song, Jason, & Taylor, 1999). While CFS has frequently been referred to as the “Yuppie Disease” because it was thought to primarily affect middle to upper class women, it should be noted that these findings were obtained from tertiary care clinics (Friedberg & Jason, 1998). Bierl et al. (2004) reported on a national US study that involved 2,728 households and found that lower income and education were associated with higher levels of chronic fatigue. Moreover, Jason, Jordan et al. (1999) found that individuals in a Chicago community-based sample with lower educational and occupational status reported higher levels of fatigue than those with higher educational and occupational status. Those from the lowest SES group had significantly higher disability ratings than those from the highest SES group. Fatigue severity is strongly implicated in a poor prognosis for CFS. This is understandable given that fatigue severity is associated with more severe Fukuda et al. (1994) somatic symptoms and functional limitations (Taylor, Jason, & Torres, 2000). In Joyce et al.'s (1997) review article of prognostic studies, fatigue severity was one of the most consistent and important predictors of a more severe illness and poorer outcome. In the Chicago community-based study, Taylor, Jason, and Curie (2002) discovered that higher baseline fatigue scores predicted higher fatigue severity at a follow-up assessment. Those who are more fatigued experience a greater number of somatic symptoms and an increase in functional limitations. These factors might likely make it more difficult to recover from CFS. Psychological distress has been found to play a significant role in relation to the onset and/or course of many health conditions. Prospective studies have examined the relationship between chronic fatigue and psychological distress (Joyce et al., 1997). In one study, predictors of post-infectious fatigue six months following infectious illness included fatigue before infection and psychological distress before and at the time of infection (Wessely, Chalder, Hirsch, Wallace, & Wright, 1997). Bombardier and Buchwald (1995) also found the coexistence of dysthymia predicted poorer outcomes. In contrast, Hickie et al. (2006) followed up with people who had cases of mononucleosis (glandular fever), Q fever, and Ross River virus, who later met the criteria for CFS, and they found CFS was predicted largely by the severity of the acute illness rather than by psychological or demographic factors. Stressful life events have also been implicated as a risk factor for CFS. Buchwald, Rea, Katon, Russo, and Ashley (2000) found that a greater number of stressful life events predicted a worse functional and fatigue symptom profile at six months. Lim et al. (2003) found those who recovered from CFS over one year reported lower levels of life stress than those who did not recover. Jason, Taylor, Kennedy, Song, et al. (2000) indicated that half of the individuals with CFS in their community based sample were able to identify a stressful event occurring at the time of onset. Jason, Porter, Hunnell, Rademaker, and Richman (in press) recently examined a group of individuals in a community-based sample with risk factor data collected from 1995-1997 (Wave 1) to their diagnostic status (CFS, Idiopathic chronic fatigue (ICF) which indicates the person has 6 months of fatigue but insufficient symptoms to meet the case definition of CFS, Medical reasons for the chronic fatigue, or controls) approximately 10 years (Wave 2). The CFS group at Wave 2 had significantly more impairment than the Controls only for Wave 1 Physical Composite Score, fatigue, and several somatic symptoms but not for any of the other measures of stress, support or coping. These findings suggest that physical measures of disability and fatigue, along with measures of specific somatic symptoms, better differentiate individuals who are later diagnosed with CFS than more psychosocial measures such as stress and coping. In addition, they found those in the group whose CFS had remitted over time were significantly younger than the group that developed CFS. There is a dearth of studies that have followed representative samples of participants with CFS over time. Jason et al. (in press) examined risk factors gathered 10 years earlier and used this information to predict differences in diagnostic outcomes (CFS, ICF, Exclusionary, controls) a decade later. In contrast, the present study examined individuals who had been diagnosed with CFS, ICF, Exclusionary, or controls between 1995 to 1997 and followed them up over the next decade. In other words, the present study examined the course of CFS and other chronic fatiguing conditions over approximately a ten year period of time, with a random, community-based, multi-ethnic population. We examined a number of factors including life stressors, female gender, older age, minority status, lower SES, and higher fatigue severity and other types of symptomatology. We therefore assessed whether these socio-environmental and the course of illness symptomatology factors might be associated with CFS status over a ten year period of time.