Abstract
Chronic fatigue syndrome (CFS) is an idiopathic serious health condition that is accompanied by a serious disablement of affected individuals. Symptoms typical of CFS include post-exertional malaise, cognitive impairment, orthostatic intolerance, pain in muscles and joints, un-refreshing sleep and rest, and complaints of psychological well-being. General medical and neurologic examinations are usually normal. A novel diagnostic algorithm with an increased focus on the central symptoms of the illness has recently been provided to allow identification of patients with CFS in a timely fashion. Despite some curative therapeutic attempts, treatment of CFS is symptom based and aims to improve fatigue and comorbid conditions, sleep disturbances, depression, and pain. Rehabilitation programs comprising cognitive-behavioral therapy, graded exercise, and patients’ education about CFS is considered as the appropriate medical management of these patients. Medical procedures like acupuncture, dry needling, and trigger point injection with a local anesthetic or spray and stretch techniques may reduce symptoms of CFS.
Keywords
Chronic fatigue syndrome, myalgic encephalitis, post-exertional malaise
| Synonyms | |
| |
| ICD-10 Code | |
| R53.82 | Chronic fatigue syndrome |
Definition
Chronic fatigue syndrome (CFS) is a serious, chronic, complex, and multi-system disease that frequently limits the activities and restricts participation of affected patients. The nature and cause of this condition remains unknown, and CFS may be distinguished from myalgic encephalitis (ME). CFS is characterized by severe, disabling, medically unexplained fatigue of more than 6 months and prominently features subjective impairments in concentration, short-term memory, and sleep as well as musculoskeletal pain. Criteria for ME partially overlap with those of CFS but differ by the presence of post-exertional malaise and cognitive impairments, whereas fatigue does not necessarily have to be a leading symptom. Sufferers of ME/CFS complain about significant disability and distress, which may be further exacerbated by a lack of understanding from others, including health professionals. CFS affects both adults and children. Recently, the National Academy of Medicine (NAM) of the United States (formerly the Institute of Medicine) has provided a novel definition of CFS that incorporates criteria consistent with features of CFS and ME. The NAM advocated also changing the name of this illness to “systemic exercise intolerance disease.”
The prevalence of CFS and ME are known to vary considerably, depending on the definition used and the geographic region. A recent systematic review found pooled prevalence rates of 3.28% for self-reporting assessment and 0.76% for clinical assessment, respectively. Women have CFS more commonly, as do minority groups and people with lower educational status and educational attainment.
The causes of CFS remain uncertain. CFS may start either gradually or suddenly. In the latter case, it is often triggered by an influenza-like viral or similar illness. Some progress in the understanding of the disease was made when causes were divided into predisposing, triggering or precipitating, and perpetuating factors. Personality (neuroticism, introversion) and lifestyle factors, inactivity in childhood and inactivity after infectious mononucleosis, and genetic influence are presumed to influence vulnerability to CFS. Certain infectious illnesses (e.g., Epstein-Barr virus infection, Q fever, and Lyme disease), precipitating somatic events (e.g., serious injuries), and psychological distress (e.g., serious life events) may precipitate the disorder. The perceptions, illness attributions, and beliefs of patients may encourage avoidant coping and perpetuate the illness.
Several physiologic abnormalities have repeatedly been observed in CFS/ME patients and recently summarized. At the cell level, mitochondria dysfunction and impaired immune regulations with increased cytokine synthesis, as well as inflammation, immune suppression, and exaggerated production of inducible nitric oxide (NO) synthase by peripheral lymphocytes, were found related with the illness. On a tissue level, some evidence has emerged supporting lower oxygen uptake by muscle cells, increased intramuscular acidosis with maximum voluntary contractions, and a delayed pH recovery as well as subtle hypoactivity in the hypothalamic-pituitary-adrenal axis with lower than normal cortisol response to increased corticotropin levels as physiologic correlates. No convincing evidence exists to support CFS as a continuing viral infection. Increasing evidence suggests that in a large subgroup of CFS patients, central sensitization with widespread hyperalgesia, delayed diffuse noxious inhibitory control, and dysfunction of endogenous inhibition during exercise seems to corroborate several psychological influences on the illness. Functional magnetic resonance imaging studies in patients with CFS revealed findings indicative of increased neuronal resource allocation or dysfunctional motor planning, which seems to be consistent with cognitive impairment in these patients.
Symptoms
Patients with CFS typically present with a variety of symptoms that may widely overlap with symptoms of functional somatic syndromes, including irritable bowel syndrome, fibromyalgia, multiple chemical sensitivity, chronic pelvic pain, temporomandibular joint dysfunction, and Gulf War illness.
Patients experience profound, overwhelming exhaustion, both mentally and physically, which is worsened by exertion and is not completely relieved by rest. Fatigue is highly subjective, multidimensional, and variable in nature, and it does not necessarily need to be the major and most debilitating symptom in this condition. Patients may express their complaints of fatigue in different ways. Patients’ expectations and causal attribution of symptoms to somatic factors, hidden agenda involving insurance issues, and invalidity of benefit claims have been related to an increase in symptoms and may contribute to a diversity of symptoms reported.
In addition to fatigue, patients with CFS usually complain of a wide variety of multisystem symptoms that are nonspecific and variable in both nature and severity over time. These may be just as prominent as fatigue and have been summarized in different categories:
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Post-exertional malaise. Patients report a prolonged exacerbation of baseline symptoms after physical and mental exertion or orthostatic stress. They may describe it as crash, relapse, or collapse and feel physically sick after mild activity and/or mentally tired after slightest efforts. The onset may be delayed relative to the trigger. The more demanding the activity, the more severe and prolonged are the symptoms.
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Complaints of cognitive impairment. CFS patients may experience forgetfulness, absent-mindedness, confusion, difficulties in thinking, disorientation, inability to concentrate and process information, problems with decision making, and “mental fatigue” or “brain fog.” These problems may be exacerbated by exertion, effort, emotional stress, or time pressure.
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Orthostatic intolerance. Patients complain about lightheadedness, dizziness, or spatial disorientation. These symptoms worsen upon assuming and maintaining upright posture and improve by recumbence.
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Complaints of pain. These include headaches of a new type, pattern, or severity; muscle pain; and multi-joint pain. Patients may also report pain in bones, eyes, and testicles; abdominal and chest pain; chills; and painful skin sensitivity.
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Unrefreshing sleep and rest is a hallmark of CFS, and insomnia is also common. Patients report feeling unrefreshed despite sleeping many hours and sleep disturbances like difficulty in falling asleep, more interrupted sleep, and more daytime napping. It is extremely difficult for many patients to maintain a sleep schedule. Patients report that exercise, unlike in healthy persons, worsens the insomnia and unrefreshing sleep symptoms alike.
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History of prior triggering infection—typically a viral-like, respiratory, or gastrointestinal infection—from which the patient never fully recovered. Patients may further report that they are more or less susceptible to infections.
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Psychological complaints of emotional lability, anxiety, depressive mood, irritability, and sometimes a curious emotional “flattening” most likely due to exhaustion may be reported by CFS patients. CFS patients with preexisting psychiatric symptoms may report that these worsen with the onset of CFS. Treatment of psychiatric symptoms alone does not relieve the physical symptoms of CFS, indicating that the disease is not only psychological in nature.
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Other frequently reported complaints refer to general hypersensitivity and poor temperature control; these include low-grade fevers, photophobia, vertigo, nausea, allergies, hot flashes, and rashes.
Physical Examination
The physical examination is directed toward determination of whether symptoms are caused by any other disease or illness. The general medical and neurologic examinations should be normal. There may be low-grade fever with temperatures between 37.5°C and 38.5°C orally, non-exudative pharyngitis, and tender cervical or axillary lymph nodes up to 2 cm in diameter. A mild hypotension, elicited mainly with tilt-table testing and reversed by mineralocorticoids, may be observed. In some patients, orthostatic hypotension with wide swings in blood pressure resulting in syncope as well as intermittent hypertension may be found. Complaints of paresthesias usually prove to be odd on sensory testing, particularly numbness in the bones or muscles or fluctuating patches of numbness or paresthesias on the chest, face, or nose. A few patients report blurred or “close to” double vision. In neither case are there physical findings to corroborate the sensory experiences. Unsteadiness on standing with closed eyes may be found.
A thorough mental status examination is performed to rule out any exclusionary psychiatric disorders. The psychological examination may reveal abnormalities in mood, intellectual function, memory, concentration, and personality. Particular attention should be paid to anxiety, self-destructive thoughts, and observable signs such as psychomotor retardation.
The musculoskeletal examination findings should be normal except for muscle weakness. In CFS patients with arthralgia and myalgia, joint swelling and inflammation and other superimposed pain generators, such as bursitis, tendinitis, and radiculopathy, have to be ruled out. Palpation of muscles may reveal tender muscles, tender points that are not numerous enough to be classified as fibromyalgia, and individual trigger points.
Functional Limitations
The level of functional loss varies widely among patients with CFS. Whereas some are able to lead a relatively normal life, others are totally bed bound and unable to care for themselves. In a rehabilitative assessment, body functions that represent the patient’s core subjective symptoms may reveal the most pronounced impairment; these are energy and drive, pain, sleep, attention, emotions, memory, and exercise tolerance. Both muscle and cardiopulmonary function as demonstrated by laboratory testing may be reduced in these patients. Avoidance behavior as a consequence of patients’ experiencing worsening of symptoms after previously well-tolerated levels of exercise and kinesiophobia—a specific kind of fear-avoidance behavior that is defined as an excessive, irrational, and debilitating fear of physical movement and activity resulting from a feeling of vulnerability to painful injury or re-injury—may increase sedentariness in CFS patients. However, kinesiophobia does not correlate with reduced exercise capacity in bicycle exercise testing.
CFS patients may be able to begin but not to complete mental or physical activities that were previously easily accomplished. Thus, tasks that predominantly challenge cognition such as focusing attention, solving problems, handling stress, making decisions, undertaking multiple tasks, or driving a car, may limit patients in carrying out their daily routine, especially at the workplace. Tasks that require predominantly physical performance, like walking or household tasks, may limit the patient’s activities of daily life. Many patients have to modify or give up physical hobbies and exercise and find themselves unable to work full-time or at all. Categories related to intimate relationships, family relationships, communication, and complex interpersonal relationships may be altered in CFS patients, thereby restricting them from participation in social and work life.
Cognitive avoidance coping as a major illness-perpetuating factor was found negatively related to social functioning, and a strong association seems to exist between kinesiophobia and self-reported activity limitations and participation restrictions in CFS patients. In addition to environmental factors related to the immediate family and friends, health professionals may reinforce patients’ symptom severity and illness behavior and facilitate further impaired functioning in these patients. Personal beliefs, practices, ideologies, spirituality, laws, and societal norms may also facilitate or hinder functioning in CFS patients. A considerable number of patients with CFS in many countries are receiving disability benefits or private insurance or have made claims and been denied.
Diagnostic Studies
There are no accepted diagnostic tests for CFS. Diagnosis of CFS is primarily based on the patient’s symptoms that fit scientific case definitions of CFS, which aim to effectively distinguish CFS from other types of unexplained fatigue. Among numerous scientific case definitions available, the U.S. Centers for Disease Control and Prevention criteria are the most widely supported. This case definition characterizes CFS by a grouping of nonspecific symptoms and a diagnosis of exclusion ( Table 126.1 ). To receive a diagnosis of CFS, fatigue must have persisted or recurred during 6 or more consecutive months. Concomitant symptoms should have persisted or recurred during 6 or more consecutive months of illness and cannot have predated the fatigue. The diagnostic criteria and algorithm ( Fig. 126.1 ) proposed by the NAM should allow a more appropriate identification of patients with CFS/ME in a timely way. These novel criteria put more focus on the central symptoms of the illness, and diagnosis requires that patients have all of the following three symptoms :
| Characterized by persistent or relapsing unexplained chronic fatigue |
| Fatigue lasts for at least 6 months |
| Fatigue is of new or definite onset |
| Fatigue is not the result of an organic disease or of continuing exertion |
| Fatigue is not alleviated by rest |
| Fatigue results in a substantial reduction in previous occupational, educational, social, and personal activities |
| Four or more of the following symptoms, concurrently present for ≥ 6 months: impaired memory or concentration, sore throat, tender cervical or axillary lymph nodes, muscle pain, pain in several joints, new headaches, unrefreshing sleep, or malaise after exertion |
| Exclusion criteria |
| Medical condition explaining fatigue |
| Major depressive disorder (psychotic features) or bipolar disorder |
| Schizophrenia, dementia, or delusional disorder |
| Anorexia nervosa, bulimia nervosa |
| Alcohol or substance abuse |
| Severe obesity |
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