Despite significant research into chronic fatigue syndrome (CFS), the disorder remains poorly understood. Accordingly, this author takes a look at the current research focus and shares practical diagnostic insights to help clinicians recognize the signs and symptoms of CFS.

The Centers For Disease Control and Prevention (CDC) estimates that chronic fatigue syndrome (CFS) has an economic burden of $9.1 billion per year in the United States due to lost productivity. This figure is comparable to losses from digestive, immune and nervous system diseases.¹ People with CFS often function at substantially lower levels of activity in comparison to their capacities prior to the onset of the syndrome.

A debilitating and complex syndrome involving multiple body systems, CFS is characterized by profound fatigue that is not improved by bed rest. The syndrome may be exacerbated by physical or mental activity. Other diverse symptoms associated with CFS include: cognitive deficits, impaired sleep, myalgia, arthralgia, headache, sore throat, gastrointestinal symptoms and tender lymph nodes.
The range of symptoms for CFS suggests there may be subtle perturbations in multiple physiological pathways triggered by diverse causes such as: infection, stress, brain structure abnormalities, hormone levels, proinflammatory cytokines and others.

Although there has been considerable research of these issues, no definitive marker for CFS has been identified to date. Researchers have yet to identify a specific cause for CFS nor is there any specific diagnostic testing or treatment for the syndrome.

Understanding The Current Research Focus For CFS
It is possible that multiple subcategories of conditions are subsumed under the rubric of CFS.² There is growing evidence of familial aggregation in a number of comorbid illnesses such as fibromyalgia and irritable bowel syndrome.^3-5 Other studies distinguish between the cognitive differences apparent in CFS and those common in depressed patients.^6-8 The combination of evidence from these studies provides support for the validity of CFS despite the absence of established biological markers.

A scientific workshop, “Neuroimmune Mechanisms and Chronic Fatigue Syndrome: Will Understanding Central Mechanisms Enhance the Search for the Causes, Consequences and Treatment of CFS?,” was recently convened at the National Institutes of Health (NIH). The workshop’s purpose was to develop the proper research questions that would help identify a unified approach to explaining how these diverse symptoms involve all systems of the body.⁹

Based on the recommendations presented, the NIH issued a request for applications to clarify how the brain fits into the schema for understanding CFS as the mediator of the various body systems involved.¹⁰

These NIH studies, some genetic in nature, may help confirm integrative systems hypotheses and lead to the establishment of biological markers and treatments.¹⁰

The CDC has completed a series of biometric analyses of a carefully defined population of patients with CFS. These molecular epidemiology program findings are consistent with integrative systems hypotheses. Further studies of this population may lead to development of markers and treatments as well as new hypotheses to be examined. Other groups have also proposed strategies based on reproducible genetic alterations in CFS patients that may lead to better diagnosis and treatment for CFS.^11,12

The scientific process is a long and arduous one. The continued absence of a solid explanation for the causes, consequences and treatment of CFS remains a burden that practitioners must bear alongside the patients.

Who Does CFS Affect The Most?
The epidemiological evidence of CFS is limited and requires further study. Approximately one percent of the U.S. population is affected with the syndrome while it appears that Caucasian women suffer with CFS more frequently than men or women from other ethnic or racial groups.

However, epidemiologic studies point to gaps in a clear understanding of the syndrome’s distribution. There is also a substantial pediatric population with this condition.

It is important to note that 80 percent of the people reporting a history of CFS in epidemiological studies of the general population have not been diagnosed or treated.¹³

What You Should Consider In The Diagnostic Workup
We know the challenges of CFS. As previously noted, the condition has no known cause and diagnostic criteria are continually being refined. The only treatments one can recommend, based on controlled clinical trials, are cognitive behavioral therapy and graded exercise. Therefore, it becomes imperative to tailor treatment recommendations and management to the individual patient and his or her milieu.¹⁴

The cluster of symptoms we know as CFS has been described over the years under many names with varying definitions and suspected causes.

However, there are two major elements necessary to consider the diagnosis of CFS.

First, your patient’s fatigue must be unexplained and unlike fatigue that typically accompanies his or her physical or mental exertion. The patient’s fatigue must not be a result of another medical condition or treatment. Rest or sleep will not alleviate this fatigue. This fatigue typically results in a substantial decrease in your patient’s established levels of occupational, educational, social or personal activities.

Secondly, your patient’s fatigue may be accompanied by four or more of the following symptoms. The symptoms should not have predated the fatigue and must have persisted or recurred during six or more consecutive months of the illness. These symptoms include:
• self-reported impairment in memory or concentration that significantly impacts functioning;
• tender cervical or axillary lymph nodes;
• muscle or joint pain without redness or swelling;
• headaches of a new type or severity; and/or
• non-revitalizing sleep and malaise following physical activity and lasting more than 24 hours.

Also bear in mind with your differential diagnosis that symptoms of CFS can overlap with those of other difficult to diagnose conditions such as sleep apnea, hormonal abnormalities and neurological conditions such as multiple sclerosis and certain psychiatric disorders.¹⁵

Patient history also plays a key role when you have a high index of suspicion for CFS. After ascertaining the nature of the primary complaint, clinicians should determine if there are any past or present medical conditions that may explain the fatigue and whether any medication, substance use or abuse could be an underlying factor. Get a good picture of the patient’s social, psychological and environmental status, both past and present, in order to rule out any potential clues in those areas.

Proceed to consider appropriate laboratory tests. This will assist you in ruling out comorbid conditions that may be underlying causes.

Other Considerations In Managing Patients With CFS
The established rapport and information you gather through the initial assessment will allow you to tailor the subsequent treatment regimen. They also provide for effective coping and management tools that help educate your patient on his or her condition, and/or assist in facilitating an appropriate referral to a cardiologist, psychiatrist, physical therapist or other specialist. In the event you find it necessary to turn to other specialists to assist in the diagnosis, be sure you engage your patient in the purpose of the referral and assure him or her that you are not being dismissive in order to alleviate any unnecessary emotional impact.

The diagnosis of CFS remains one of exclusion and involves an ongoing process of monitoring symptoms and ruling out other conditions. It can be costly, time consuming and frustrating for both you and your patient.

An Overview Of Potential Diagnostic Signs For CFS

It is important to keep the negative emotional consequences of so many unknowns in mind as you conduct your assessment of any particular patient. Overlooking such consequences could impact whether your patient is willing to participate in the complex process and affect your patient’s compliance to treatment.^16-17

Accordingly, one should pay a great deal of attention to the patient’s own perceptions of his or her condition and its impact on his or her quality of life during the assessment process.

In Conclusion
Patients with CFS should always be aware that you respect their perceptions and explanations for their symptoms. When a clinician diagnoses CFS, let the patient know that while the disorder can have a debilitating and sometimes lengthy duration, one can successfully manage the condition with help. Engage the patient in a partnership to help ensure he or she follows through with the treatment recommendations and regimen.

Always reinforce that the patient is in charge of enacting these recommendations and should let you know whether there is any need for alteration.

In terms of treatment options for the individual patient with CFS, consider the potential benefit of the following options:
• a personalized, graded exercise program to avoid deconditioning;
• appropriate medications to facilitate symptom relief;
• referring the patient for cognitive behavioral therapy if necessary to facilitate effective self management; and/or
• appropriate referral to specialists in these areas.¹⁸

I also encourage you to visit the NIH Web site http://orwh.od.nih.gov/cfs/
aboutcfs.html, where you may access information about all aspects of CFS. A preset literature review tool enables you to see descriptions of ongoing and past NIH supported research of the type and to the degree you wish. You may also download publications and other documents of interest.

In addition, the CDC has recently published a CFS tool kit (www.cdc.gov/cfs) for health care professionals. The kit contains an excellent brochure on the recognition and management of CFS that one can use as a guide.¹⁹