Chronic Fatigue Immune Dysfunction Syndrome: A Review

Chronic Fatigue Immune Dysfunction Syndrome (CFIDS) is a complex, multi-organ system disease of unknown etiology characterized by functionally debilitating exhaustion and a constellation of associated symptoms. Its diagnosis is complicated; its treatment is largely supportive; and full recovery is rare. As well, lack of medical acknowledgement of CFIDS as a legitimate disease has caused patients to suffer a significant social stigma. However, recent work characterizing improved CFIDS biomarkers coupled with a modified understanding of CFIDS etiology may foreshadow a transformation in the medical approach to this illness. Symptoms and diagnosis of chronic fatigue immune dysfunction syndrome The hallmark symptom of CFIDS is extreme chronic fatigue. In many cases, this follows a period of flu-like illness. However, no physical exam or laboratory finding is diagnostic of the disorder (Prins et al., 2006). Rather, its diagnosis is clinical and relies on the presence of symptomatic criteria outlined in one of several comparable case definitions (for example, the Oxford, London, or Centers for Disease Control [CDC] definitions). Of these, the CDC CFIDS criteria are the most widely employed (Prins et al., 2006). They are: 1) Debilitating, new-onset fatigue present for at least six months which is 2) not alleviated by rest and 3) results in a significant decrease in the ability to function normally in daily life, 4) accompanied by four or more of impaired memory or concentration, sore throat, tender cervical or axillary lymph nodes, muscle or joint pain, new headaches, or post-exertional malaise, also present for six or more months (Fukuda et al., 1994). Despite the availability of diagnostic criteria, a diagnosis of CFIDS is rarely straightforward. First, it is a diagnosis of exclusion. This is an unavoidable consequence of the lack of quantifiable, objective CFIDS biomarkersyet the list of exclusionary criteria is substantial (Afari and Buchwald, 2003). Exclusionary criteria include fatigue caused by a known disease (a list of these would include hypothyroidism, anemia, diabetes, congestive heart failure, chronic obstructive pulmonary disease, kidney failure, adrenal insufficiency, cancer, autoimmune disease, certain medications, and persistent infection), fatigue caused by exertion, several psychiatric disorders including major depressive disorder, bipolar disorder, schizophrenia, dementia, delusional disorder, anorexia or bulimia, substance abuse, and severe obesity (Fukuda et al., 1994; Prins et al., 2006; Gonzales and Nadler, 2009). The time and cost of ruling these out can be quite significant. As well, the CFIDS diagnostic criteria may be incomplete. For example, a significant number of patients report gastrointestinal distress, dizziness, nausea, anorexia, night sweats, muscle fasciculations, sleep disturbances, and orthostatic hypotension in addition to their diagnostically-relevant symptoms. For some, these additional symptoms may be as distressing as those outlined as diagnostic criteriamaking the initial presentation of CFIDS quite heterogeneousyet they are not included in most case definitions (Afari and Buchwald, 2003; Janson et al., 2003; Prins et al., 2006). Finally, CFIDS criteria overlap significantly with those of several other syndromes, including fibromyalgia (unexplained chronic pain and fatigue), irritable bowel syndrome (unexplained gastrointestinal distress accompanied by psychiatric complaints), and others to such a degree that, in many patients, more than one of these diagnoses may adequately explain all symptoms. In fact, some authors suggest these syndromes may actually be varying presentations of the same disease, such that which diagnosis a patient receives is largely dependent on which specialist does the diagnosing (Prins et al., 2006; Wessely et al., 1999). In an attempt to address these concerns, Carruthers et al., (2003) published an expanded clinical case definition that included such symptoms as sleep dysfunction and orthostatic hypotension; nonetheless, there continues to be considerable debate regarding the appropriate case definition of CFIDS (Prins et al., 2006), and as a result, the disorder may be significantly misor under-