- Last Updated: 30 November 2015 30 November 2015
Summary of the findings of a number of research efforts to improve the 1988 CDC Definition
What symptoms are the most discriminating in CFS?
In 1996, Komaroff et al. in a paper, "An Examination of the Working Case Definition of Chronic Fatigue Syndrome," published in the American Journal of Medicine (v. 100, Jan. 1996) conducted an exhaustive statistical analysis of the frequency of symptoms in CFS patients compared with the frequency of the same symptoms in samples of healthy control subjects, Multiple Sclerosis(MS) patients, and patients with major depression. The object was to determine which symptoms associated with CFS best discriminated CFS from the healthy controls and the patients in the two disease comparison groups.
Those symptoms which best discriminated CFS would be the basis for an improved case definition.
Of the symptom-criteria in the better 1988 definition "...the discriminating ability was clearest for myalgias, post-exertional malaise, headaches, and a group of infectious-type symptoms (i.e., fever/chills, sore throat, swollen neck glands, swollen arm glands). All these symptoms were found much more frequently...[in the CFS cases than] in either of the two comparison groups (p<0.01)"
However, patients with MS were just as likely to report the symptom of muscle weakness than those patients with CFS. In contrast, patients with major depression were less likely to report muscle weakness than those in the CFS and MS groups.
Interestingly, 84% of the CFS patients experienced sudden onset, while 0% of patients with major depression had a sudden onset.
Komaroff et al. also compared 31 other symptoms characteristic of CFS with their incidence in the control and disease comparison groups. These symptoms were in 5 categories: respiratory, gastrointestinal, neurologic, rheumatological, and miscellaneous.
Four of the 31 symptoms: poor appetite (anorexia), nausea, tingling sensations, and alcohol intolerance were reported significantly less often by patients in the disease comparison groups than by CFS patients.
As already discussed, the 1994 CDC Diagnostic Criteria is deficient in that it reduces, in comparison with the 1988 CDC definition, the number of qualifying physical symptoms—namely it omits fevers or chills, muscle weakness (often indicative of a neurological problem) and sudden onset. By doing so, the characteristic clinical picture of the illness is distorted and undermined.
Based on the Komaroff article, a careful clinician could confirm diagnosis of ME/CFS by the 2003 Canadian Criteria or by using the 1988 CDC definition criteria with the addition of poor appetite, nausea, tingling sensations and alcohol intolerance.
Komaroff et al also proposed eliminating the "Physical Criteria" from the 1988 definition, which require confirmation in the physician's office. As it may be difficult, due to fluctuation of symptoms, to obtain the required temperature during a doctor's visit, the patient can keep a record of his/her own temperature fluctuations. It is probably reasonable to maintain swollen lymph nodes and nonexudative pharyngitis for physician examination.
Are the illnesses described by the 1988 and 1994 CDC definitions the same?
In 1998, at the AACFS Conference, Natelson et al. presented a poster entitled "Do the 1988 and 1994 CFS case definitions identify the same illness?"
The results were as follows: "When subjects who met the 1988 case criteria (n=45) were compared to those who met only the 1994 criteria (n=17), subjects in the 1988 group were found to suffer from a more severe form of the illness. Specifically, subjects in the 1988 group demonstrated more severe symptoms as well as a greater reduction in activity. The latter group also more frequently reported infectious-type symptoms..."
The conclusions were: "The 1988 and 1994 CFS case definition criteria appear to identify distinct patient groups. Given that the subjects of the 1988 group more frequently endorsed infectious symptoms and more frequently reported a sudden flu-like illness onset, an infectious etiology for this group is hypothesized."
Finally, in September of 2001, De Becker, McGregor, and De Meirleir published "A definition-based analysis of symptoms in a large cohort of patients with chronic fatigue syndrome." The article was published in the Journal of Internal Medicine.
The article begins: "The Holmes  and Fukuda  criteria are widely used criteria all over the world...yet a specific European study regarding chronic fatigue syndrome (CFS) symtomatology has not been conducted...This study was performed to answer the need to assess the homogeneity of a large CFS population in relation to the Fukuda and Holmes definition...
"A total of 2073 consecutive patients with major complaints of prolonged fatigue participated in this study...Of the 2073 patients complaining of chronic fatigue (CF), 1578 CFS patients fulfilled the Fukuda criteria (100% of CFS group), and 951 (60.3% of the CFS group) fulfilled the Holmes criteria...The Holmes criteria was more strongly associated than the Fukuda definition with the symptoms that differentiated the CFS patients from the patients that did not comply with the CFS definitions. The inclusion of 10 additional symptoms were found to improve the sensitivity/specificity for the selection of CFS patients.
"Whilst the Fukuda and Holmes definition are very similar, the Fukuda definition is less stringent...and is likely to include a greater and more heterogeneous group of patients with profound fatigue...
"...[This] shows that the patients who were included under the CFS definition using the Fukuda criteria had less severe symptoms and an altered symptom prevalence distribution to those patients classified under the Holmes criteria.
"The different definition groups...were compared using standard discriminant function analysis with the Holmes profile with the addition of attention deficit, paralysis, new sensitivities to food/drugs, difficulties with words, urinary frequency, cold extremities, photophobia, muscle fasiculations, lightheadedness, exertional dyspnea, and gastrointestinal disturbance. The symptoms were chosen as they represented the 10 symptoms with the greatest prevalence differences between the Holmes and Fukuda criteria....
"Thus the addition of 10 extra symptoms to the Holmes criteria results in a small increase in definition sensitivity and a much larger increase in specificity and improves the accuracy of the definitions. [Emphasis added..]
"The study showed that the analysis of individual symptom severity and prevalence revealed that the Holmes criteria patients had increased symptom prevalence and severity of many of the symptoms that determine the difference between CFS patients and CF subjects compared with the Fukuda defined group...Thus, the addition of patients to the CFS definition by the Fukuda criteria has resulted in the selection of less severely affected patients. This has also resulted in the introduction of an increase in patient symptom heterogeneity." [I.e., less of a clearly defined illness entity].