chronic fatigue syndrome vs chronic fatigue – American ME and CFS Society

Diagnosis of myalgic encephalomyelitis: where are we now?

Abstract:

INTRODUCTION: The World Health Organization has classified myalgic encephalomyelitis (ME) as a neurological disease since 1969 considering chronic fatigue syndrome (CFS) as a synonym used interchangeably for ME since 1969. ME and CFS are considered to be neuro-immune disorders, characterized by specific symptom profiles and a neuro-immune pathophysiology. However, there is controversy as to which criteria should be used to classify patients with “chronic fatigue syndrome.”

AREAS COVERED: The Centers for Disease Control and Prevention (CDC) criteria consider chronic fatigue (CF) to be distinctive for CFS, whereas the International Consensus Criteria (ICC) stresses the presence of post-exertion malaise (PEM) as the hallmark feature of ME. These case definitions have not been subjected to rigorous external validation methods, for example, pattern recognition analyses, instead being based on clinical insights and consensus.

EXPERT OPINION: Pattern recognition methods showed the existence of three qualitatively different categories: (a) CF, where CF evident, but not satisfying full CDC syndrome criteria. (b) CFS, satisfying CDC criteria but without PEM. (c) ME, where PEM is evident in CFS. Future research on this “chronic fatigue spectrum” should, therefore, use the above-mentioned validated categories and novel tailored algorithms to classify patients into ME, CFS, or CF.

Comment in: Comment and reply on: ME is a distinct diagnostic entity, not part of a chronic fatigue spectrum. [Expert Opin Med Diagn. 2013]

Source: Maes M, Anderson G, Morris G, Berk M. Diagnosis of myalgic encephalomyelitis: where are we now? Expert Opin Med Diagn. 2013 May;7(3):221-5. doi: 10.1517/17530059.2013.776039. Epub 2013 Feb 27. https://www.ncbi.nlm.nih.gov/pubmed/23480562

Myalgic Encephalomyelitis (ME), Chronic Fatigue Syndrome (CFS), and Chronic Fatigue (CF) are distinguished accurately: results of supervised learning techniques applied on clinical and inflammatory data

Abstract:

There is much debate on the diagnostic classification of Myalgic Encephalomyelitis (ME), Chronic Fatigue Syndrome (CFS) and chronic fatigue (CF). Post-exertional malaise (PEM) is stressed as a key feature. This study examines whether CF and CFS, with and without PEM, are distinct diagnostic categories.

Fukuda’s criteria were used to diagnose 144 patients with chronic fatigue and identify patients with CFS and CF, i.e. those not fulfilling the Fukuda’s criteria. PEM was rated by means of a scale with defined scale steps between 0 and 6. CFS patients were divided into those with PEM lasting more than 24h (labeled: ME) and without PEM (labeled: CFS). The 12-item Fibromyalgia and Chronic Fatigue Syndrome (FF) Rating Scale was used to measure severity of illness. Plasma interleukin-1 (IL-1), tumor necrosis factor (TNF)α, and lysozyme, and serum neopterin were employed as external validating criteria.

Using fatigue, a subjective feeling of infection and PEM we found that ME, CFS, and CF were distinct categories. Patients with ME had significantly higher scores on concentration difficulties and a subjective experience of infection, and higher levels of IL-1, TNFα, and neopterin than patients with CFS. These biomarkers were significantly higher in ME and CFS than in CF patients. PEM loaded highly on the first two factors subtracted from the data set, i.e. “malaise-sickness” and “malaise-hyperalgesia”. Fukuda’s criteria are adequate to make a distinction between ME/CFS and CF, but ME/CFS patients should be subdivided into ME (with PEM) and CFS (without PEM).

Source: Maes M, Twisk FN, Johnson C. Myalgic Encephalomyelitis (ME), Chronic Fatigue Syndrome (CFS), and Chronic Fatigue (CF) are distinguished accurately: results of supervised learning techniques applied on clinical and inflammatory data. Psychiatry Res. 2012 Dec 30;200(2-3):754-60. doi: 10.1016/j.psychres.2012.03.031. Epub 2012 Apr 21. https://www.ncbi.nlm.nih.gov/pubmed/22521895

The effect of counselling, graded exercise and usual care for people with chronic fatigue in primary care: a randomized trial

Abstract:

BACKGROUND: To evaluate the effectiveness of graded exercise therapy (GET), counselling (COUNS) and usual care plus a cognitive behaviour therapy (CBT) booklet (BUC) for people presenting with chronic fatigue in primary care.

METHOD: A randomized controlled trial in general practice. The main outcome measure was the change in the Chalder fatigue score between baseline and 6 months. Secondary outcomes included a measure of global outcome, including anxiety and depression, functional impairment and satisfaction.

RESULTS: The reduction in mean Chalder fatigue score at 6 months was 8.1 [95% confidence interval (CI) 6.6-10.4] for BUC, 10.1 (95% CI 7.5-12.6) for GET and 8.6 (95% CI 6.5-10.8) for COUNS. There were no significant differences in change scores between the three groups at the 6- or 12-month assessment. Dissatisfaction with care was high. In relation to the BUC group, the odds of dissatisfaction at the 12-month assessment were less for the GET [odds ratio (OR) 0.11, 95% CI 0.02-0.54, p=0.01] and COUNS groups (OR 0.13, 95% CI 0.03-0.53, p=0.004).

CONCLUSIONS: Our evidence suggests that fatigue presented to general practitioners (GPs) tends to remit over 6 months to a greater extent than found previously. Compared to BUC, those treated with graded exercise or counselling therapies were not significantly better with respect to the primary fatigue outcome, although they were less dissatisfied at 1 year. This evidence is generalizable nationally and internationally. We suggest that GPs ask patients to return at 6 months if their fatigue does not remit, when therapy options can be discussed further.

Source: Ridsdale L, Hurley M, King M, McCrone P, Donaldson N. The effect of counselling, graded exercise and usual care for people with chronic fatigue in primary care: a randomized trial. Psychol Med. 2012 Oct;42(10):2217-24. doi: 10.1017/S0033291712000256. Epub 2012 Feb 28. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3435871/ (Free article)

Adolescent chronic fatigue syndrome: prevalence, incidence, and morbidity

Abstract:

OBJECTIVE: To determine nationwide general practitioner (GP)-diagnosed prevalence and pediatrician-diagnosed incidence rates of adolescent chronic fatigue syndrome (CFS), and to assess CFS morbidity.

DESIGN AND SETTING: We collected data from a cross-sectional national sample among GPs and prospective registration of new patients with CFS in all pediatric hospital departments in the Netherlands.

PATIENTS AND METHODS: Study participants were adolescents aged 10 to 18 years. A representative sample of GPs completed questionnaires on the prevalence of CFS in their adolescent patients. Pediatric hospital departments prospectively reported new cases of CFS in adolescent patients. For every new reported case, a questionnaire was sent to the reporting pediatrician and the reported patient to assess CFS morbidity. Prevalence was estimated through the data from GP questionnaires and incidence was estimated on the basis of cases newly reported by pediatricians from January to December 2008.

RESULTS: Prevalence was calculated as 111 per 100 000 adolescents and incidence as 12 per 100 000 adolescents per year. Of newly reported patients with CFS, 91% scored at or above cutoff points for severe fatigue and 93% at or above the cutoff points for physical impairment. Forty-five percent of patients with CFS reported >50% school absence during the previous 6 months.

CONCLUSIONS: Clinically diagnosed incidence and prevalence rates show that adolescent CFS is uncommon compared with chronic fatigue. The primary adverse impact of CFS is extreme disability associated with considerable school absence.

Source: Nijhof SL, Maijer K, Bleijenberg G, Uiterwaal CS, Kimpen JL, van de Putte EM. Adolescent chronic fatigue syndrome: prevalence, incidence, and morbidity. Pediatrics. 2011 May;127(5):e1169-75. doi: 10.1542/peds.2010-1147. Epub 2011 Apr 18. https://www.ncbi.nlm.nih.gov/pubmed/21502228

Twin analyses of fatigue

Abstract:

Prolonged fatigue equal to or greater than 1 month duration and chronic fatigue equal to or greater than 6 months duration are both commonly seen in clinical practice, yet little is known about the etiology or epidemiology of either symptom. Chronic fatigue syndrome (CFS), while rarer, presents similar challenges in determining cause and epidemiology. Twin studies can be useful in elucidating genetic and environmental influences on fatigue and CFS. The goal of this article was to use biometrical structural equation twin modeling to examine genetic and environmental influences on fatigue, and to investigate whether these influences varied by gender. A total of 1042 monozygotic (MZ) twin pairs and 828 dizygotic (DZ) twin pairs who had completed the University of Washington Twin Registry survey were assessed for three fatigue-related variables: prolonged fatigue, chronic fatigue, and CFS. Structural equation twin modeling was used to determine the relative contributions of additive genetic effects, shared environmental effects, and individual-specific environmental effects to the 3 fatigue conditions. In women, tetrachoric correlations were similar for MZ and DZ pairs for prolonged and chronic fatigue, but not for CFS. In men, however, the correlations for prolonged and chronic fatigue were higher in MZ pairs than in DZ pairs. About half the variance for both prolonged and chronic fatigue in males was due to genetic effects, and half due to individual-specific environmental effects. For females, most variance was due to individual environmental effects.

Source: Schur E, Afari N, Goldberg J, Buchwald D, Sullivan PF. Twin analyses of fatigue. Twin Res Hum Genet. 2007 Oct;10(5):729-33. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2953372/ (Full article)

Longitudinal analysis of pro- and anti-inflammatory cytokine production in severely fatigued adolescents

Abstract:

In the adolescent population, fatigue is associated with somatic complaints, unrefreshing sleep, cognitive disturbances and symptoms of depression and anxiety. This pattern of symptoms resembles the one described in chronic fatigue syndrome (CFS). Since immunological alterations have been reported in CFS patients, we wondered whether also severely fatigued girls from a healthy population would show comparable alterations in psychological and immunological parameters. We tested this hypothesis in a longitudinal design, allowing a reliable assessment of the participants’ characteristic immune status. Groups of severely fatigued (N=67) and non-fatigued (N=61) participants were selected. Severely fatigued girls reported more depressive symptoms, anxiety, reduced sleep quality, and somatic and CFS-related symptoms than non-fatigued participants across three measurements during one year (T1: spring, T2: autumn, T3: spring). In contrast, no group differences in mitogen-induced cytokine production or T-cell proliferation in vitro or in leukocyte subset counts were observed. Although absolute cytokine production and cell counts were affected by seasonal variation, the within-subject values, relatively to the rest of the participants, were fairly stable. Data from a small group of CFS patients (N=11) showed similarities in self-reported complaints between CFS patients and fatigued participants. Interestingly, CFS patients showed a distinct immune profile when compared to the severely fatigued or non-fatigued participants, i.e. increased levels of anti-inflammatory cytokines (IL-10, decreased IFN-gamma/IL-10 ratio) and reduced levels of pro-inflammatory cytokines (IL-6, TNF-alpha) over all three time points analyzed. These results show that, although overlap in symptomatology between the general population and patients with CFS was observed, only CFS patients show a skewing of the cytokine balance towards an anti-inflammatory profile.

Source: ter Wolbeek M, van Doornen LJ, Kavelaars A, van de Putte EM, Schedlowski M, Heijnen CJ. Longitudinal analysis of pro- and anti-inflammatory cytokine production in severely fatigued adolescents.Brain Behav Immun. 2007 Nov;21(8):1063-74. Epub 2007 Jun 1. https://www.ncbi.nlm.nih.gov/pubmed/17544255