Chronic Fatigue Syndrome

Dr. Nicholas Kaloudis

Chronic fatigue syndrome (CFS) is a disorder characterized by a state of chronic fatigue that persists for more than 6 months, has no clear cause, and is accompanied by cognitive difficulties. More recently, the US Institute of Medicine (IOM) proposed that the condition be renamed “systemic exertion intolerance disease” (SEID) to better reflect the condition’s hallmark defining symptom, “postexertional malaise”.

The cause of CFS is unknown, but the disorder is probably an infectious disease with immunologic manifestations. Many viruses have been studied as potential causal agents, including: EBV, HHV-6, coxsackievirus B, spumaviruses, and even human T-cell leukemia virus strains; however, no definitive causal relation has been determined.

Because no direct tests aid in the diagnosis of CFS, the diagnosis is one of exclusion but that meets certain clinical criteria, which are further supported by certain nonspecific tests. The diagnosis of CFS also rests on historical criteria (ie, otherwise unexplained fatigue for more than 6 months accompanied by cognitive dysfunction). The absence of cognitive dysfunction should exclude CFS as a potential diagnosis.

According to the Centers for Disease Control and Prevention (CDC),  in order to receive a diagnosis of CFS, a patient must (1) have severe chronic fatigue of at least 6 months’ duration, with other known medical conditions excluded by clinical diagnosis, and (2) concurrently have four or more of the following symptoms:

• Substantial impairment in short-term memory or concentration
• Sore throat
• Tender lymph nodes
• Muscle pain
• Multijoint pain without swelling or redness
• Headaches of a new type, pattern or severity
• Unrefreshing sleep
• Postexertional malaise lasting more than 24 hours

The symptoms must have persisted or recurred during 6 or more consecutive months of illness and must not have predated the fatigue.

The CDC case definition also states that any unexplained abnormality detected on examination or other testing that strongly suggests an exclusionary condition must be resolved before further classification is attempted. Conditions that do not exclude CFS include the following:

• Any condition defined primarily by symptoms that cannot be confirmed by diagnostic laboratory tests, including fibromyalgia, anxiety disorders, somatoform disorders, nonpsychotic or melancholic depression, neurasthenia, and multiple chemical sensitivity disorder
• Any condition under specific treatment sufficient to alleviate all symptoms related to that condition and for which the adequacy of treatment has been documented, including hypothyroidism for which the adequacy of replacement hormone has been verified by normal thyroid-stimulating hormone levels, or asthma in which the adequacy of treatment has been determined by pulmonary function and other testing
• Any condition, such as Lyme disease or syphilis, that was treated with definitive therapy before development of chronic symptoms
• Any isolated and unexplained physical examination finding, or laboratory or imaging test abnormality that is insufficient to strongly suggest the existence of an exclusionary condition, including an elevated antinuclear antibody titer that is inadequate, without additional laboratory or clinical evidence, to strongly support a diagnosis of a discrete connective tissue disorder

As suggested by the term chronic, the clinical course of CFS is punctuated by remissions and relapses, often triggered by intercurrent infection, stress, exercise, or lack of sleep.

Laboratory tests have 2 functions in chronic fatigue syndrome (CFS). First, they may be used to assess the possibility that another condition is causing the fatigue; second, they may be used to help diagnose CFS. CFS laboratory abnormalities are not specific, but, taken together, they can make up a pattern consistent with CFS in patients who have a cognitive dysfunction in whom other diseases have been excluded as a cause for their fatigue.

The Centers for Disease Control and Prevention (CDC) has recommended a “basic battery” that includes the following:

• Complete blood count (CBC)
• Liver function tests
• Thyroid function tests
• Erythrocyte sedimentation rate (ESR)
• Serum electrolyte level measurement

Some clinicians also include antinuclear antibody and morning cortisol measurements. Adrenal function tests are useful for the purposes of exclusion.

The most consistent laboratory abnormality in patients with CFS is an extremely low ESR, typically in the range of 0-3 mm/h. A normal ESR or one that is in the upper reference range suggests another diagnosis.

Most patients with CFS usually have 2 or 3 of the following nonspecific abnormalities:

• Elevated immunoglobulin M (IgM)/immunoglobulin G (IgG) coxsackievirus B titer
• Elevated IgM/IgG human herpesvirus 6 (HHV-6) titer
• Elevated IgM/IgG C pneumoniae titer
• Decrease in natural killer (NK) cells (either percentage or activity)

Because most cases of chronic fatigue syndrome (CFS) may be due to a viral infection, no uniformly effective therapy exists for CFS. Trials of antiviral agents have been ineffective in relieving the symptoms of chronic fatigue syndrome (CFS). Various medications have been shown to be ineffective, including steroids, liver extract, chelating agents, intravenous (IV) vitamins, vitamin B-12, and IV or oral vitamin or mineral supplements. Antidepressants have no major role to play in the treatment of CFS. Otherwise, treatment is largely supportive and responsive to symptoms.