chronic fatigue – Page 4 – American ME and CFS Society

Myalgic Encephalomyelitis, Chronic Fatigue Syndrome, and Chronic Fatigue: Three Distinct Entities Requiring Complete Different Approaches

Abstract:

PURPOSE OF REVIEW: A recent review implicates that myalgic encephalomyelitis (ME), chronic fatigue syndrome (CFS), and chronic fatigue are part of the “fatigue spectrum” and recommends “longitudinal studies integrating biopsychosocial approaches to inform early management and targeted rehabilitation strategies.”

RECENT FINDINGS: ME is a neuromuscular disease distinguished by muscle fatigability (prolonged muscle weakness after minor exertion) and specific signs of neurological dysfunction. ME is not equivalent to CFS, as proposed by the authors. CFS is defined as unexplained chronic fatigue accompanied by at least four out of a list of eight specific symptoms. CFS is a distinct clinical entity and not merely a severe variant of CF, as suggested. Proof that CF, CFS, and ME are part of a “fatigue continuum” and that CF can convert to CFS at a later stage is lacking. Biopsychosocial approaches for early management and rehabilitation of CF, as promoted by the authors, are at odds with the current understandings of ME, CFS, and CF. The (bio)psychosocial explanatory models for ME and CFS have proven to be invalid, and the associated interventions, cognitive behavioral therapy and graded exercise therapy, have shown to be ineffective and even potentially harmful. ME, CFS, and CF are three very distinct clinical entities. Interventions justified by (bio)psychosocial models appear to be unsuccessful and potentially noxious. To develop effective treatments, it is crucial to make a clear distinction between ME, CFS, and CF and to leave the (bio)psychosocial explanations and therapies behind us.

Source: Twisk FNM. Myalgic Encephalomyelitis, Chronic Fatigue Syndrome, and Chronic Fatigue: Three Distinct Entities Requiring Complete Different Approaches. Curr Rheumatol Rep. 2019 May 9;21(6):27. doi: 10.1007/s11926-019-0823-z. https://www.ncbi.nlm.nih.gov/pubmed/31073713

Fatigue in Epstein-Barr virus infected adolescents and healthy controls: A prospective multifactorial association study

Abstract:

OBJECTIVE: Acute Epstein-Barr virus (EBV) infection is a known trigger of both acute and chronic fatigue. The aim of this study was to investigate associations to fatigue in adolescents with EBV infection during the initial stage and six months after, as well as in healthy controls.

METHODS: 200 adolescents (12-20 years old) with EBV infection were assessed as soon as possible after the onset of symptoms (EBVbaseline) and six months later (EBVsix months, 5 drop-outs). Also, 70 healthy controls (HC) were included. Associations between current fatigue and 148 different variables (including symptoms, functional abilities and biomarkers) were investigated separately for EBVbaseline, EBVsix months and HC using linear regression modelling.

RESULTS: Fatigue was associated with symptoms of sleeping difficulties, negative emotions, and quality of life under all circumstances. Fatigue was independently associated with markers of immune response at EBVsix months and in HC, not at EBVbaseline. An association between fatigue and markers of autonomic cardiovascular control was only present at EBVsix months. Cognitive functioning shifted from a positive association to fatigue at EBVbaseline to a negative trend at EBVsix months. Markers of infection were not associated with fatigue at EBVbaseline, EBVsix months nor in HC.

CONCLUSION: Irrespective of the cause, fatigue is important for quality of life and is highly associated with negative emotions. Markers of infection and immune response had respectively none and barely any association to fatigue. Autonomic alterations and cognitive dysfunction were exclusively associated with fatigue long after infection, corroborating findings from studies of the Chronic Fatigue Syndrome.

Source: Pedersen M, Asprusten TT, Godang K, Leegaard TM, Osnes LT, Skovlund E, Tjade T, Øie MG, Wyller VBB. Fatigue in Epstein-Barr virus infected adolescents and healthy controls: A prospective multifactorial association study. J Psychosom Res. 2019 Apr 10. pii: S0022-3999(18)30946-2. doi: 10.1016/j.jpsychores.2019.04.008. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/31003854

Persistent fatigue induced by interferon-alpha: a novel, inflammation-based, proxy model of chronic fatigue syndrome

Abstract:

The role of immune or infective triggers in the pathogenesis of Chronic Fatigue Syndrome (CFS) is not yet fully understood. Barriers to obtaining immune measures at baseline (i.e., before the trigger) in CFS and post-infective fatigue model cohorts have prevented the study of pre-existing immune dysfunction and subsequent immune changes in response to the trigger. This study presents interferon-alpha (IFN-α)-induced persistent fatigue as a model of CFS. IFN-α, which is used in the treatment of chronic Hepatitis C Virus (HCV) infection, induces a persistent fatigue in some individuals, which does not abate post-treatment, that is, once there is no longer immune activation. This model allows for the assessment of patients before and during exposure to the immune trigger, and afterwards when the original trigger is no longer present.

Fifty-five patients undergoing IFN-α treatment for chronic HCV were assessed at baseline, during the 6-12 months of IFN-α treatment, and at six-months post-treatment. Measures of fatigue, cytokines and kynurenine pathway metabolites were obtained. Fifty-four CFS patients and 57 healthy volunteers completed the same measures at a one-off assessment, which were compared with post-treatment follow-up measures from the HCV patients. Eighteen patients undergoing IFN-α treatment (33%) were subsequently defined as having ‘persistent fatigue’ (the proposed model for CFS), if their levels of fatigue were higher six-months post-treatment than at baseline; the other 67% were considered ‘resolved fatigue’.

Patients who went on to develop persistent fatigue experienced a greater increase in fatigue symptoms over the first four weeks of IFN-α, compared with patients who did not (Δ Treatment Week (TW)-0 vs. TW4; PF: 7.1 ± 1.5 vs. RF: 4.0 ± 0.8, p = 0.046). Moreover, there was a trend towards increased baseline interleukin (IL)-6, and significantly higher baseline IL-10 levels, as well as higher levels of these cytokines in response to IFN-α treatment, alongside concurrent increases in fatigue. Levels increased to more than double those of the other patients by Treatment Week (TW)4 (p = 0.011 for IL-6 and p = 0.001 for IL-10).

There was no evidence of an association between persistent fatigue and peripheral inflammation six-months post-treatment, nor did we observe peripheral inflammation in the CFS cohort. While there were changes in kynurenine metabolites in response to IFN-α, there was no association with persistent fatigue. CFS patients had lower levels of the ratio of kynurenine to tryptophan and 3-hydroxykynurenine than controls. Future studies are needed to elucidate the mechanisms behind the initial exaggerated response of the immune system in those who go on to experience persistent fatigue even if the immune trigger is no longer present, and the change from acute to chronic fatigue in the absence of continued peripheral immune activation.

Source: Russell A, Hepgul N, Nikkheslat N, Borsini A, Zajkowska Z, Moll N, Forton D, Agarwal K, Chalder T, Mondelli V, Hotopf M, Cleare A, Murphy, G, Foster G, Wong T, Schütze GA, Schwarz MJ, Harrison N, Zunszain PA, Pariante CM. Persistent fatigue induced by interferon-alpha: a novel, inflammation-based, proxy model of chronic fatigue syndrome. Psychoneuroendocrinology. 2018 Dec 14. pii: S0306-4530(18)30196-3. doi: 10.1016/j.psyneuen.2018.11.032. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/30567628

Chronic Fatigue Syndrome: From Chronic Fatigue to More Specific Syndromes

Abstract:

In the last decade, a group of chronic disorders associated with fatigue (CDAF) emerged as the leading cause of chronic fatigue, chronic pain, and functional impairment, all of which have been often labeled in clinical practice as chronic fatigue syndrome (CFS) or fibromyalgia. While these chronic disorders arise from various pathophysiologic mechanisms, a shared autoimmune or immune-mediated etiology could shift the focus from symptomatic treatment of fatigue and pain to targeted immunomodulatory and biological therapy.

A clinical paradigm shift is necessary to reevaluate CFS and fibromyalgia diagnoses and its relationship to the CDAF entities, which would ultimately lead to a change in diagnostic and therapeutic algorithm for patients with chronic fatigue and chronic pain. Rather than uniformly apply the diagnoses of CFS or fibromyalgia to any patient presenting with unexplained chronic fatigue or chronic pain, it may be more beneficial and therapeutically effective to stratify these patients into more specific diagnoses in the CDAF group.

Source: Blitshteyn S, Chopra P. Chronic Fatigue Syndrome: From Chronic Fatigue to More Specific Syndromes. Eur Neurol. 2018 Oct 4;80(1-2):73-77. doi: 10.1159/000493531. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/30286454

Rheumatism and chronic fatigue, the two facets of post-chikungunya disease: the TELECHIK cohort study on Reunion island

Abstract:

Prolonged fatigue is increasingly reported among chikungunya virus (CHIKV)-infected populations. We investigated the relationships between CHIKV exposure, long-lasting rheumatic musculoskeletal pain (LRMSP) and chronic fatigue. 1094 participants (512 CHIKV seropositive and 582 seronegative) of the TELECHIK population-based cohort were analysed considering the duration of the manifestations throughout an average 2-year follow-up.

Weighted prevalence rates and prevalence ratios for LRMSP, idiopathic chronic fatigue (ICF), and chronic fatigue syndrome (CFS)-like illness, both latter syndromes adapted from Centers for Disease Control (CDC)-1994/Fukuda criteria, were compared. Population attributable fractions (PAF) were estimated to assess the contribution of CHIKV infection to each of the three phenotypes.

Among 362 adult subjects who had reported either rheumatic pain or fatigue at the onset of the infection, weighted prevalence rates of LRMSP, ICF and CFS-like illness were respectively of 32.9%, 38.7% and 23.9%, and of 8.7%, 8.5% and 7.4% among initially asymptomatic peers (P < 0.01, respectively). Each of the three outcomes was highly attributable to chikungunya (PAF of 43.2%, 36.2% and 41.0%, respectively).

In the sub-cohort of CHIKV-infected subjects, LRMSP, ICF and CFS-like illness, which overlapped in 70%, accounted for 53% of the chronic manifestations. In addition to rheumatic disease, chronic fatigue could be considered in caring for patients with chronic chikungunya disease.

Source: Duvignaud A, Fianu A, Bertolotti A, Jaubert J, Michault A, Poubeau P, Fred A, Méchain M, Gaüzère BA, Favier F, Malvy D, Gérardin P. Rheumatism and chronic fatigue, the two facets of post-chikungunya disease: the TELECHIK cohort study on Reunion island. Epidemiol Infect. 2018 Feb 28:1-9. doi: 10.1017/S0950268818000031. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/29486812

High flow variant postural orthostatic tachycardia syndrome amplifies the cardiac output response to exercise in adolescents

Abstract:

Postural orthostatic tachycardia syndrome (POTS) is characterized by chronic fatigue and dizziness and affected individuals by definition have orthostatic intolerance and tachycardia. There is considerable overlap of symptoms in patients with POTS and chronic fatigue syndrome (CFS), prompting speculation that POTS is akin to a deconditioned state.

We previously showed that adolescents with postural orthostatic tachycardia syndrome (POTS) have excessive heart rate (HR) during, and slower HR recovery after, exercise – hallmarks of deconditioning. We also noted exaggerated cardiac output during exercise which led us to hypothesize that tachycardia could be a manifestation of a high output state rather than a consequence of deconditioning.

We audited records of adolescents presenting with long-standing history of any mix of fatigue, dizziness, nausea, who underwent both head-up tilt table test and maximal exercise testing with measurement of cardiac output at rest plus 2-3 levels of exercise, and determined the cardiac output () versus oxygen uptake () relationship. Subjects with chronic fatigue were diagnosed with POTS if their HR rose ≥40 beat·min(-1) with head-up tilt.

Among 107 POTS patients the distribution of slopes for the , relationship was skewed toward higher slopes but showed two peaks with a split at ~7.0 L·min(-1) per L·min(-1), designated as normal (5.08 ± 1.17, N = 66) and hyperkinetic (8.99 ± 1.31, N = 41) subgroups. In contrast, cardiac output rose appropriately with in 141 patients with chronic fatigue but without POTS, exhibiting a normal distribution and an average slope of 6.10 ± 2.09 L·min(-1) per L·min(-1). Mean arterial blood pressure and pulse pressure from rest to exercise rose similarly in both groups.

We conclude that 40% of POTS adolescents demonstrate a hyperkinetic circulation during exercise. We attribute this to failure of normal regional vasoconstriction during exercise, such that patients must increase flow through an inappropriately vasodilated systemic circulation to maintain perfusion pressure.

Source: Pianosi PT, Goodloe AH, Soma D, Parker KO, Brands CK, Fischer PR. High flow variant postural orthostatic tachycardia syndrome amplifies the cardiac output response to exercise in adolescents. Physiol Rep. 2014 Aug 28;2(8). pii: e12122. doi: 10.14814/phy2.12122. Print 2014 Aug 1. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4246579/ (Full article)

Cost-effectiveness of counselling, graded-exercise and usual care for chronic fatigue: evidence from a randomised trial in primary care

Abstract:

BACKGROUND: Fatigue is common and has been shown to result in high economic costs to society. The aim of this study is to compare the cost-effectiveness of two active therapies, graded-exercise (GET) and counselling (COUN) with usual care plus a self-help booklet (BUC) for people presenting with chronic fatigue.

METHODS: A randomised controlled trial was conducted with participants consulting for fatigue of over three months’ duration recruited from 31 general practices in South East England and allocated to one of three arms. Outcomes and use of services were assessed at 6-month follow-up. The main outcome measure used in the economic evaluation was clinically significant improvements in fatigue, measured using the Chalder fatigue scale. Cost-effectiveness was assessed using the net-benefit approach and cost-effectiveness acceptability curves.

RESULTS: Full economic and outcome data at six months were available for 163 participants; GET = 51, COUN = 58 and BUC = 54. Those receiving the active therapies (GET and COUN) had more contacts with care professionals and therefore higher costs, these differences being statistically significant. COUN was more expensive and less effective than the other two therapies. The incremental cost-effectiveness ratio of GET compared to BUC was equal to £987 per unit of clinically significant improvement. However, there was much uncertainty around this result.

CONCLUSION: This study does not provide a clear recommendation about which therapeutic option to adopt, based on efficiency, for patients with chronic fatigue. It suggests that COUN is not cost-effective, but it is unclear whether GET represents value for money compared to BUC.

Clinical Trial Registration number at ISRCTN register: 72136156.

Source: Sabes-Figuera R, McCrone P, Hurley M, King M, Donaldson AN, Ridsdale L. Cost-effectiveness of counselling, graded-exercise and usual care for chronic fatigue: evidence from a randomised trial in primary care. BMC Health Serv Res. 2012 Aug 20;12:264. doi: 10.1186/1472-6963-12-264. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3480915/ (Full article)

What is fatigue? Pathological and nonpathological fatigue

Abstract:

Aid in understanding issues surrounding the construct validity of fatigue including the distinction between pathological versus nonpathological fatigue. Fatigue is a universal symptom reported by individuals in the general population as well as by those suffering from different medical and psychological illnesses, including cancer, multiple sclerosis, chronic fatigue syndrome, depression, and anxiety. Chronic fatigue is a significant problem in many primary care settings, and the debilitating and prolonged nature of fatigue can pose significant economic consequences for society. Researchers have struggled to better assess and understand the etiology and classification of fatigue within different illness groups.

Source: Jason LA, Evans M, Brown M, Porter N. What is fatigue? Pathological and nonpathological fatigue. PM R. 2010 May;2(5):327-31. doi: 10.1016/j.pmrj.2010.03.028. https://www.ncbi.nlm.nih.gov/pubmed/20656613

Fatigue and chronic fatigue syndrome-like complaints in the general population

Abstract:

BACKGROUND: Most knowledge on chronic fatigue (CF) and chronic fatigue syndrome (CFS) is based on clinical studies, not representative of the general population. This study aimed to assess the prevalence of fatigue in an adult general population and to identify associations with lifestyle factors.

METHODS: Total 22,500 residents of Nijmegen were selected at random and interviewed by questionnaire. Data on 9062 respondents (43% response) were analysed, taken into account age, gender and concomitant disease. Subjects were classified into four groups: not fatigued (NF, reference group), short-term fatigue (SF, <6 months), chronic fatigue (CF, >or=6 months) and CFS-like fatigue (in accordance with the Center for Disease Control criteria for CFS, without clinical confirmation).

RESULTS: Our study population showed the following breakdown: NF 64.4% (95% CI 63.6-65.6%), SF 4.9% (95% CI 4.5-5.4%), CF 30.5% (95% CI 29.5-31.4%) and CFS-like fatigue 1.0% (95% CI 0.8-1.2%). Compared with the NF group, more of the CFS respondents were female [odds ratio (OR) = 1.9], obese (OR = 4.1), using analgesics (OR = 7.8), had a low alcohol intake (OR = 0.4), were eating less healthy food (OR = 0.5) and were physically less active (OR = 0.1). These associations largely applied to the SF and CF group. The fatigue could have been due to a concomitant disease in 34 and 55.5% of the SF and CF cases, respectively.

CONCLUSION: The prevalence of CF in the general population appears to be much higher than previously indicated. Even with strict criteria for CFS, it is estimated that approximately 1% of the adult population experiences this condition. Interestingly, a large part of this group remains unrecognized by the general practitioner. A striking similarity in lifestyle pattern between SF, CF and CFS calls for further research.

Source: van’t Leven M, Zielhuis GA, van der Meer JW, Verbeek AL, Bleijenberg G. Fatigue and chronic fatigue syndrome-like complaints in the general population. Eur J Public Health. 2010 Jun;20(3):251-7. doi: 10.1093/eurpub/ckp113. Epub 2009 Aug 18. http://eurpub.oxfordjournals.org/content/20/3/251.long (Full article)

The relationship between chronic fatigue and somatization syndrome: a general population survey

Abstract:

OBJECTIVE: The objective of this study was to assess the prevalence of chronic fatigue (CF) and its association with somatization syndrome [Somatization Syndrome Index (SSI) 4/6: >/=4 somatoform symptoms in men, 6 in women] in the general population.

METHODS: A representative sample of the German population (N=2412) completed a fatigue questionnaire and a screening instrument for current somatoform symptoms (Screening for Somatoform Symptoms 7).

RESULTS: The prevalence rate of CF was 6.1% (n=147). Females were affected significantly more often as compared with males (7% vs. 5.1%). The mean number of somatoform symptoms was higher in CF cases than in control subjects without CF (11 vs. 2; P<.001). Seventy-two percent of the subjects with CF fulfilled the SSI4/6 criterion for somatization syndrome. Quality of life (EUROHIS-QOL and 8-item Short-Form Health Survey) and well-being (5-item WHO Well-Being Index) were markedly decreased in CF and SSI4/6. The results of regression analyses suggest that fatigue and somatization severity had a similar impact on quality of life.

CONCLUSIONS: The results suggest that CF is relevant in the general population. Its substantial overlap with somatization syndrome supports the hypothesis that the two syndromes are only partially different manifestations of the same underlying processes.

Source: Martin A, Chalder T, Rief W, Braehler E. The relationship between chronic fatigue and somatization syndrome: a general population survey. J Psychosom Res. 2007 Aug;63(2):147-56. https://www.ncbi.nlm.nih.gov/pubmed/17662751