What is "fatigue"?

To differentiate the various causes of mental and physical fatigue, the doctor should focus on the description of the complaint (Box 2.1). Fatigue in people with CFS is typically exacerbated by physical tasks previously achieved with ease, and recovery from periods of worsened fatigue can take hours or even days. Pathological fatigue can be differentiated from somnolence as it is not relieved by sleep, and from neuromuscular weakness as people with CFS can generate muscle strength and endurance when circumstances demand a response (Lloyd et al. 1988b, 1991). Fatigue should be differentiated from a lack of motivation and loss of pleasure from usual daily activities, which suggest a depressive illness.  

How should a doctor evaluate fatigue?

CFS is distinguished from similar fatigue-related illnesses not only by carefully characterising the fatigue, but also by evaluating other symptoms and signs. People with CFS also report:

• unrefreshing sleep
• myalgia
• arthralgia
• concentration loss
• memory impairment
• irritable mood

-- all of which may be exacerbated by minor physical activity.

Although these symptoms are common in people with CFS, they are not specific. They may also occur in a range of other medical and neuropsychiatric disorders (e.g., sleep apnoea, hypothyroidism, major depression, somatoform disorders -- Katon and Russo 1992; Hickie et al. 1995b; Komaroff et al. 1996b).

Perspectives "CFS is a sufficient indignity by itself; do not compound it. It takes considerable time and infinite patience to take an accurate history from a frail patient with impaired memory and concentration, especially if that history is long and complex. Resist the temptation of a hurried, superficial evaluation." -- Thomas English, MD, JAMA 1991; 8: 265 "My cognitive difficulties were frightening and confusing. I often feared I was going crazy. I was ordinarily an intelligent man and avid learner, but suddenly my thinking was clouded and confused. I forgot things extremely easily. I mixed up words and I couldn't think of phrases I wanted to use. My concentration span was extremely short and my mathematical ability almost disappeared." -- a person with CFS

When taking a medical history, the questions should focus on key symptoms that might suggest alternative explanations for the fatigue state (see Boxes 2.1 and 2.3). Fatigue accompanied by fever, malaise, and weight loss suggests an inflammatory or infective process, and fatigue accompanied by weight gain and cold intolerance may indicate hypothyroidism. Fatigue commonly accompanies many other medical conditions, particularly those directly involving the central nervous system and affecting information processing, the sleep-wake cycle, or arousal mechanisms (e.g., multiple sclerosis). Many commonly prescribed medications (e.g., antihistamines, sedatives), and other substances (e.g., alcohol, marijuana, amphetamines) cause fatigue directly, or indirectly via a disturbance of the sleep-wake cycle.

Similarly, the physical examination should be directed towards elucidating alternative diagnoses. The physical examination of people with CFS is normal (Fukuda et al. 1994), so evidence of objective muscle weakness, neurological signs, evidence of cardiorespiratory disease or fever all indicate diagnoses other than CFS (see Box 2.3). Although people with CFS often complain of tender cervical lymph nodes, demonstrable lymphadenopathy is rarely present (Fukuda et al. 1994).

When adults present for medical assessment with fatigue states the most common alternative diagnosis to consider is major depression (Taerk et al. 1987; Manu et al. 1988a; Kruesi et al. 1989; Wessely and Powell 1989; Gold et al. 1990; Hickie et al. 1990; Katon et al. 1991; Wood et al. 1991; Buchwald et al. 1995, 1997; Wessely et al. 1995b; Lawrie et al. 1997). Other commonly detected disorders (Box 2.3) are sleep apnoea, hypothyroidism, anaemia, chronic hepatitis, panic disorder, generalised anxiety, and somatoform disorders (Lane et al. 1991; Buchwald et al. 1995; Hickie et al. 1995a; Fischler et al. 1997; Lawrie et al. 1997).

When patients are being treated for an alternative medical disorder (e.g., hypothyroidism and receiving thyroxine replacement) or a psychiatric condition (e.g., manic-depressive illness and receiving lithium carbonate), a separate diagnosis of CFS is not justified.  

What psychological evaluation is required?

Brief standardised approaches to psychological evaluation in primary care are available and have been shown to be effective (Ellen et al. 1997). These include self-report questionnaires such as the GHQ-30 (Goldberg and Williams 1988) and SPHERE (Hickie et al. 1996a), or structured interview schedules such as PRIME-MD (Spitzer et al. 1994).  

History

• prior episodes of anxiety or depression
• a past history of multiple, unexplained physical symptoms
• prior alcohol or other substance abuse.

Most people with depressive disorders present to primary care complaining of fatigue or pain rather than overt psychological symptoms such as tearfulness or sadness. The family history should be reviewed for depressive disorder, self-destructive behaviour or substance abuse. The relationship between the onset of the fatigue state and relevant psychosocial stressors should be noted. Whenever possible an independent, corroborating history should be sought from a spouse, partner or other family member.

The characteristic mood state of people with CFS is irritation, frustration and transient depression, rather than persistent and profound sadness. This is unlike people with typical depression, who report severe anorexia, weight loss, self-reproach and guilt, suicidal plans, persistent loss of motivation or a pervasive loss of pleasure (DSM-IV; ICD-10; Hickie et al. 1990; Johnson et al. 1996).

A careful review of the history of ill-health before the onset of CFS is the key to resolving the differential diagnosis of somatoform and somatisation disorders. A long-standing history of frequent medical investigation and treatment for unexplained physical symptoms, persistent fear of medical ill-health despite adequate assessment, preoccupation with unusual physical explanations of illness, and persistent rejection of the potential relevance of psychosocial factors may suggest the diagnosis (DSM-IV; ICD-10).

Perspectives "We have had members of our support group who have been diagnosed with CFS, but who in fact did not have CFS but another disease. One woman endured five years of suffering until the correct diagnosis of systemic lupus erythematosus was made. She experienced substantial relief from drugs given to treat her lupus." -- a patient support group "Health professionals find it easier to label patients with depression, rather than recognise and acknowledge the natural grief reaction to the profound losses which occur with CFS -- loss of health, disrupted family life, interrupted education and career, low self-esteem, etcetera. You can't dispense antigrief pills." -- a person with CFS

 

Mental state

Evaluating a person's risk of suicide is an important task. The major psychological risk factor for suicide is untreated depression. Most people who attempt suicide first present to a health care agency, although they typically complain of non-specific symptoms such as poor sleep, poor appetite and tiredness rather than depressed mood (Power et al. 1997; Appleby et al. 1996; Rutz et al. 1989). Other risk factors for suicide include being male, social isolation, concurrent drug and alcohol use and access to lethal means (Moscicki 1997; Maris 1997).

Perspectives "CFS is one of the loneliest illnesses in the world, because we don't have anything to show for it." -- a person with CFS

 

How should the context of the illness be assessed?

• the consequences of the illness for the person's ability to participate in work or school
• the effects of the illness on key relationships with spouse, partner, or parents
• and the financial impact of the illness on the person with CFS and family.

The functional impairment of people with CFS has been shown to be similar to, or greater than, that of people with other chronic disabling medical conditions (e.g., rheumatoid arthritis) and psychological conditions (e.g., major depression) (Vercoulen et al. 1996a; Buchwald et al. 1996b; Komaroff et al. 1996a). Accordingly, the current level of disability should be carefully assessed, with a review of the duration and intensity of physical activity that can be undertaken without precipitating prolonged fatigue. For example, it may be evident that an adolescent's 45-minute walk to school produces fatigue and other symptoms that last all day. At the severe end of the spectrum of CFS, people may be housebound and experience profound fatigue simply from the necessities of self-care such as showering or dressing.

The diagnosis of CFS is made after six months or more of disabling symptoms. By this time, people with CFS are commonly in crisis with their school or workplace as a result of the accumulated time lost due to the illness. Similarly, by the time of diagnosis, parents, friends and partners of people with CFS are often questioning the nature of the unexplained illness. The doctor should specifically evaluate the effect of the illness upon the patient's key interpersonal relationships. This is preliminary to education and advocacy on behalf of the patient with these individuals and institutions.  

What laboratory tests are appropriate?

The only laboratory tests recommended for the standard evaluation of people with fatigue states (Box 2.4) are intended for the detection of alternative medical conditions.

The diagnostic yield of investigations beyond this restricted list is very low (Valdini et al. 1989; Lane et al. 1990; Buchwald and Komaroff 1991). If specific alternative diagnoses are suggested by the clinical history or examination (e.g., sleep apnoea or multiple sclerosis), further investigations may be warranted.

Many other laboratory procedures have been proposed as "diagnostic tests" by non-medical or alternative practitioners, but have not been subjected to scientific standards of evaluation. Consequently, these "tests" (e.g., dark field blood testing for red cell morphology or "candida" identification; environmental sensitivity testing) are not recommended.  

Does chronic fatigue overlap with other illnesses?

Fibromyalgia, in particular, is a closely related syndrome, differing mainly in its relative emphasis on musculoskeletal pain rather than fatigue (Goldenberg 1996; Wolfe et al. 1990). However, treatment approaches may vary (see Part 4).

The number of non-specific medical symptoms reported by a person with CFS is strongly correlated with the presence of psychological symptoms (Katon and Russo 1992; Hickie et al. 1995a). Up to two-thirds of adults with CFS have either a prior, or concurrent, diagnosis of major depression (Katon and Walker 1993; Taerk et al. 1987; Manu et al. 1988a; Kruesi et al. 1989; Wessely and Powell 1989; Gold et al. 1990; Hickie et al. 1990; Katon et al. 1991; Wood et al. 1991; Buchwald et al. 1995; Wessely et al. 1995b; Lawrie et al. 1997), as do people with fibromyalgia (Hudson and Pope 1996) and irritable bowel syndrome (Langeluddecke 1985; Walker et al. 1995). By comparison, the lifetime rate of comparable depressive disorders in the general community is 15%-25% (Reiger et al. 1988; Wells 1989; Kessler et al. 1994; Blazer et al. 1994; Mason and Wilkinson 1996).

The high rate of comorbidity is not surprising as diagnostic criteria for both CFS and major depression (DSM-IV; ICD-10) include fatigue, sleep disturbance, cognitive impairment and mood alteration.

Perhaps the most difficult diagnostic uncertainty between CFS and psychological illness is in relation to somatoform disorders. In these disorders, people present with medically inexplicable physical symptoms that are assumed to be due to underlying psychological processes. As the causes of CFS are "unexplained", there is obvious overlap between the diagnostic criteria for the somatoform disorders and CFS (Lane et al. 1991; Katon and Russo 1992; Abbey 1993; Hickie et al. 1995b; Johnson et al. 1996; Fischler et al. 1997). Patients with the most severe somatoform disorders typically have a lifelong pattern of presentation to medical practice with unexplained symptoms and chronic disability, and a pattern of excessive and poorly justified laboratory investigation and invasive medical treatments (DSM-IV; ICD-10).  

When should a doctor seek another opinion?

For example, a history of snoring and daytime somnolence is an appropriate indication for assessment by a sleep physician, which may be followed by overnight sleep study. People with severe or prolonged depression, severe anxiety symptoms, or those assessed as being at risk of self-harm may require psychiatric evaluation. Adolescents who are absent from school or occupational training for prolonged periods may benefit from assessment by a paediatrician. People who are persistently housebound with severe disability arising from CFS may require the assessment and advice of a team including specialists in rehabilitation medicine, pain management, physiotherapy, occupational therapy, and social work.

Perspectives "My GP has the greatest role in helping me manage my illness on a day-to-day basis, although he refers me to a specialist when he thinks we could use help with a particular problem. For instance, when it was getting too hard for me even to manage my kitchen, he found an occupational therapist to help me redesign my domestic arrangements." -- a person with CFS

 

What are the expectations in medicolegal assessments of people with CFS?

Expert witnesses are frequently asked to comment on the likelihood that CFS arose as a consequence of a risk factor in the occupational setting (e.g., infection, chemical exposure, or the emotional demands of the workplace). Given that the pathophysiological basis of CFS is unknown (see Part 5), definitive statements about occupational risk factors are unwise. The legal system also frequently requests an assessment of the current level of disability. As CFS is a subjective illness, the evaluation of disability includes two components: first, a systematic review of the patient's report of his/her functional capacity (with corroborating reports of the spouse, partner or parent), and, second, an assessment of whether the patient is an accurate and reliable historian.

Another key expectation of the medicolegal evaluation is the prognosis for recovery. Statements about prognosis should be expressed in terms of probabilities, based on the existing data regarding natural history (see Part 3). These judgements are best made after adequate symptomatic and behavioural treatment (see Part 4). The likelihood of spontaneous resolution of CFS of short duration (i.e., 6-12 months) is about 50% over the following year, but when the illness has been present for several years the remission rate is lower (Box 3.2).

The notion of "permanent" disability is problematic, as the great majority of people with CFS improve gradually or eventually recover. However, a reasonable approach is to suggest that, when the likelihood of substantial improvement is less than 10%-20% over the following decade (as is the case in people with more than five years of disability) and the person is incapable of gainful employment, this should be regarded as "permanent disability" for medicolegal purposes.

Perspectives "People with CFS seeking financial support from superannuation funds often experience drawn out applications, ill informed and hostile review panels, further medical tests, lack of consultation with the treating doctor and the need to resort to legal action in an effort to obtain some financial support. This puts people with CFS under significant stress and may impede recovery." -- a patient support group

 

What are the benefits of a diagnosis of CFS?

A formal diagnosis is essential for the transfer of information between those involved directly or indirectly in patient care. Once patients have engaged with their doctors in this process, a series of personal, social and legal obligations result (Mechanic 1986, 1993). All persons, including relevant third parties, are then expected to behave in ways that provide support during the illness and facilitate recovery (Mechanic 1986).

Making the diagnosis should mark the end of investigations to exclude alternative diagnoses.  

What drawbacks can occur as a consequence of a diagnosis of CFS?

Implications of diagnosis Making a diagnosis of CFS encourages appropriate treatment planning (Level IV) A diagnosis of CFS does not establish a specific aetiology (Level I)