Chapter 35 Chronic fatigue syndrome
OVERVIEW
Chronic fatigue syndrome (CFS) is a complex yet defined spectrum disorder. It is characterised by expert consensus to include persistent disabling fatigue lasting more than 6 months with other symptoms as listed in the box below. This definition is based upon the USA’s Centers for Disease Control’s description of this illness.1 Importantly there are medical conditions by their nature that may mimic CFS and need to be excluded prior to making an accurate diagnosis. These include untreated thyroid disease, sleep disorders such as sleep apnoea, alcohol abuse, major depressive disorders and schizophrenia. The presence of past and treated malignancy or unresolved infectious hepatitis is also considered exclusive of CFS.1–4 However, the persistence of symptoms despite adequate treatment of the above conditions, including thyroid conditions or infections such as Lyme disease, fibromyalgia and anxiety disorders, may possibly co-exist with a diagnosis of CFS.2 CFS presents significant difficulties in diagnosis and assessment, as there is no single laboratory or clinically significant specific diagnostic test. Patients often appear
CDC CRITERIA FOR THE DIAGNOSIS OF CFS1,2,3,4
clinically well, though express profound deterioration of social and occupational functioning and have significant physical and psychological distress.
AETIOLOGY
Infectious agents
Clinically it is well known that many patients commence their illness after what appears to be an infectious episode. Certainly no single agent has been shown consistently to create all CFS cases; however, the CDC state ‘the possibility remains that CFS may have multiple causes leading to a common endpoint, in which case some viruses or other infectious agents might have a contributory role for a subset of CFS cases, and infection with Epstein-Barr virus, Ross River virus and Coxiella burnetti will lead to a postinfective condition that meets the criteria for CFS in approximately 12% of cases’.4
Immunologic abnormalities
CFS quite possibly may be the result of a complex interplay between an infectious insult and/or a disordered immune response in a susceptible individual. This complexity is revealed in research in the area of immunity and CFS; it clearly has not shown any one consistent abnormality (concerning interleukin abnormalities and altered cell-mediated immunity).11–13 Combined with the consistently observed possibility of multiple infectious aetiological agents and the possibility of persistent or relapsing infections, the resulting immunologic disorders such as elevated pro-inflammatory cytokines ‘may explain some of the manifestations such as fatigue and flu-like symptoms and influence NK activity’.14
Neuroendocrine abnormalities
Hypoactivity of the hypothalamic–pituitary–adrenal (HPA) axis combined with hyperactivity of the serotonergic system has been postulated as a cause of CFS.15,16 Other research suggests that up-regulation of hypothalamic serotonergic receptors may be the cause some of the HPA disorders—distinctly different from depression17 and ‘adrenal exhaustion’. With respect to the HPA axis, lowered levels of dehydroepiandrosterone (DHEA, an adrenal steroidal hormone) have been assessed in CFS patients.18 The interplay of dysfunctional immunity, cytokine imbalances leading to subtle neurotransmitter changes is demonstrated in Figure 35.1. Importantly, as mentioned above, depression and its manifestations are distinctly different from CFS both in psychological distress and in physiological dysfunctioning (see Section 4 on the nervous system for treatment details).19
Orthostatic intolerance
Patients with CFS have been shown to have abnormal autonomic responses to prolonged standing or even sitting for long periods.20 This ‘orthostatic intolerance’ manifests as fatigue plus elevated pulse rates, often associated with faintness when the above activities occur. The condition is diagnosable with a severe hypotensive response to ‘tilt table’ testing, where a patient is subjected to a head tilt when lying flat.21
Nutritional causes
As the diagnosis is defined by the absence of other medical conditions, the fatigue that arises from iron deficiency, vitamin B and B12 deficiency is necessarily excluded as a cause. However, lowered levels of essential fatty acids, L-carnitine and magnesium have been assessed in patients with CFS.17 Interestingly, these nutrients give direct support to mitochondrial function—an essential pathway for the production of cellular energy.22 Empiric research has shown that vitamin B12 injections may improve energy and cognitive ability and mood often with normal serum B12 levels.23,24 Serum folic acid levels have been assayed in patients with CFS and 50% of 60 patients have been shown to have lowered levels.25 Oral nicotinamide (NADH) has been shown in a randomised placebo-controlled trial to give benefit to 31% of CFS patients treated.26
RISK FACTORS
No single risk factor has been strongly associated with CFS. With a spectrum disorder with multiple aetiological factors it seems prudent to individually assess the clinical case as it presents. However study has commenced on what makes a person vulnerable to CFS with the general consensus based upon observation that disordered immunity and infectious agents intervene in a susceptible individual. A summary of the recent researched factors is shown in Table 35.1.
| Older age | Female > male (4:1) |
| Low or middle rather than high educational level | The presence of an anxiety disorder |
| Mood disorder (pre-morbid or 2 months postinfection) | Personality trait—emotional instability |
| Musculoskeletal pain | Low fitness 2 months postinfection |
| Lower physical functioning at baseline assessment | The presence of fatigue at time of viral illness |
| Fatigue severity | Other family members with symptoms of CFS |
Very recent research has revealed that childhood trauma—abuse of sexual or emotional type—may predispose an individual to developing CFS in the presence of other initiating factors.28 Neuroendocrine dysfunction, as discussed in Chapter 15 on adrenal exhaustion, explains how the combination of these factors develop as a definite risk for CFS.29
CONVENTIONAL TREATMENT
There remains much contention in some medical services about the existence of CFS, let alone its management. Fatigue is a common presentation to general practice; however, CFS is a unique and separate entity that requires understanding and knowledge of the condition itself and those things that may mimic it. Confusion arises because of the lack of a definitive laboratory test, plus uncertainty about management options available to patients.17 Thus much conventional therapy is directed to symptomatic control of distress in the absence of single or definitive interventions. Key areas of conventional therapy that are summarised in one study30 include:
KEY TREATMENT PROTOCOLS
The primary clinical protocol is to be supportive and patient, and to address the individual needs of the person with CFS. Negotiate a personalised plan recognising the person knows the effect of their illness better than anyone else. The following discussion provides choices that may be individually assessed as appropriate to the person’s needs.
Decrease suffering
Reduce pain and stiffness
Conventional therapies to reduce pain and suffering include regular doses of paracetamol and the use of a nocturnal dose of a tricyclic anti-depressant such as amitryptylline—10–50 mg at night.31,32 Integrative interventions most favoured by people with CFS include massage and chiropractic therapies.33 Recent research suggests that, in the presence of accompanying myofascial pain, manual therapies such as manipulation and myofascial trigger point therapy may have some benefit.34 Nutritional interventions such as magnesium is a nutrient that is an essential cofactor in enzymes of energy metabolism; it acts on muscle tissue as a relaxant (through its calcium channel blocking actions), and also is an essential cofactor in neurotransmitter regulation of pain.35 In CFS it has been used by injection of either magnesium sulfate or oral chelates (such as citrate) at 500 mg two or three times a day to assist pain management.36
Herbal interventions may include combinations of Curcuma longa, Boswellia serrata, Zingiber officinale and Apium graveolens41 with an emphasis on management of pain and stiffness.
Improve sleep
Increase physical conditioning
Graded physical activity
Negotiate a balanced and achievable exercise plan with the patient (after a medical check-up). A graded exercise program supervised by a qualified Health professional e.g. exercise physiologist or equivalent. Two reviews40,
