Clinical typology of chronic fatigue syndrome: classificatory hypothesis

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Primary (or pure) chronic fatigue syndrome (pCFS) is a complex and severe chronic and disabling disease of unknown causes, excluding secondary chronic fatigue syndrome (sCFS) related to some other medical condition. It is characterized by intense fatigue in addition to cognitive, autonomic, neuroendocrine, immunoallergic and musculoskeletal symptoms, which are of recent appearance and that cannot be explained by other clinical reasons, lasting for at least 6 months, is non-remitting significantly with rest and which worsens with physical or mental activity, with very slow recovery and a reduction of >50% of activities of daily living previously performed by the patient.1–4 It is diagnosed according to the 1994 Fukuda criteria,1 the Canadian consensus document published in 20032 or, more recently, the international consensus criteria of 2011; with the name of myalgic encephalomyelitis that offers a review on its physiopathology, symptoms and treatment.3 Prevalence is estimated to be between 0.5% and 2.5% of the general population.1–3,5 In spite of it being recognized as a disease by the WHO since 1989, and classified with the code G93.3 in the ICD-10,5,6 and that evidence accumulated from different fields during the past 2 decades, it is possible that pCFS is still largely unknown by most health professionals.

You can read the rest of this article here: http://www.reumatologiaclinica.org/en/clinical-typology-chronic-fatigue-syndrome/articulo/S2173574313001329/ 

Comment in

 

Source: Qanneta R, Fontova R, Poveda MJ, Castro S. Clinical typology of chronic fatigue syndrome: classificatory hypothesis. Reumatol Clin. 2014 Mar-Apr;10(2):132-3. doi: 10.1016/j.reuma.2013.04.004. Epub 2013 Jul 9.[Article in English, Spanish] http://www.reumatologiaclinica.org/es/linkresolver/tipologia-clinica-del-sindrome-fatiga/S1699258X13000971/ (Full article)

 

CFS in Children and Adolescent: Ten Years of Retrospective Clinical Evaluation

Abstract:

Aim. To estimate number of children being diagnosed with chronic fatigue syndrome (CFS). Methods. For a period of 10 years (2002-2011) data from children being referred for fatigue symptoms were collected retrospectively.

Results. Thirty-seven children were referred. Four were excluded due to incorrect coding. Six (18%) patients received other diagnoses at the end of evaluation time. Of the 27 who received the diagnosis G93.3, four had a previous chronic illness, while 23 patients were previously healthy. All patients reported onset of fatigue symptom in relation to an infection, and all tested positive for IgG to either Epstein-Barr virus, cytomegalovirus or borrelia, indicating previous infection. There were 16 (59%) boys among the 27 patients. The mean age at the debut of fatigue symptoms was 141 months (SD 30) for boys and 136 months (SD 31) for girls, respectively. Being underweight, defined as BMI < 17.5, was found in 12 (44%) patients.

Conclusion. An increasing number of children and adolescents are evaluated for CFS. The clinical assessment of children and adolescents with possible CFS need systematically evaluation. Nutritional status, possible eating disorder, and psychosocial issues need to be addressed and evaluated carefully. A multidisciplinary approach is essential when assessing CFS in children and adolescents. There is a need for European guidelines.

 

Source: Elgen I, Hikmat O, Aspevik TN, Hagen EM. CFS in Children and Adolescent: Ten Years of Retrospective Clinical Evaluation. Int J Pediatr. 2013;2013:270373. doi: 10.1155/2013/270373. Epub 2013 Jun 16. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3697308/ (Full article)

 

Bifidobacterium infantis 35624 modulates host inflammatory processes beyond the gut

Abstract:

Certain therapeutic microbes, including Bifidobacteria infantis (B. infantis) 35624 exert beneficial immunoregulatory effects by mimicking commensal-immune interactions; however, the value of these effects in patients with non-gastrointestinal inflammatory conditions remains unclear.

In this study, we assessed the impact of oral administration of B. infantis 35624, for 6‒8 weeks on inflammatory biomarker and plasma cytokine levels in patients with ulcerative colitis (UC) (n = 22), chronic fatigue syndrome (CFS) (n = 48) and psoriasis (n = 26) in three separate randomized, double-blind, placebo-controlled interventions. Additionally, the effect of B. infantis 35624 on immunological biomarkers in healthy subjects (n = 22) was assessed.

At baseline, both gastrointestinal (UC) and non-gastrointestinal (CFS and psoriasis) patients had significantly increased plasma levels of C-reactive protein (CRP) and the pro-inflammatory cytokines tumor necrosis factor α (TNF-α) and interleukin-6 (IL-6) compared with healthy volunteers. B. infantis 35624 feeding resulted in reduced plasma CRP levels in all three inflammatory disorders compared with placebo.

Interestingly, plasma TNF-α was reduced in CFS and psoriasis while IL-6 was reduced in UC and CFS. Furthermore, in healthy subjects, LPS-stimulated TNF-α and IL-6 secretion by peripheral blood mononuclear cells (PBMCs) was significantly reduced in the B. infantis 35624-treated groups compared with placebo following eight weeks of feeding.

These results demonstrate the ability of this microbe to reduce systemic pro-inflammatory biomarkers in both gastrointestinal and non-gastrointestinal conditions. In conclusion, these data show that the immunomodulatory effects of the microbiota in humans are not limited to the mucosal immune system but extend to the systemic immune system.

 

Source: Groeger D, O’Mahony L, Murphy EF, Bourke JF, Dinan TG, Kiely B, Shanahan F, Quigley EM. Bifidobacterium infantis 35624 modulates host inflammatory processes beyond the gut. Gut Microbes. 2013 Jul-Aug;4(4):325-39. doi: 10.4161/gmic.25487. Epub 2013 Jun 21. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3744517/ (Full article)

 

Heart rate variability in patients with fibromyalgia and patients with chronic fatigue syndrome: a systematic review

Abstract:

OBJECTIVE: The goal of this systematic literature review is to determine whether there are differences and similarities in heart rate variability (HRV) between adult patients with fibromyalgia

(FM), chronic fatigue syndrome (CFS), and healthy pain-free control subjects.

METHODS: To obtain relevant articles, PubMed and Web of Knowledge were searched for case-control studies. Selection of the literature was based on selection criteria ascertaining studies with adult human patient groups comparing HRV. Risk of bias and levels of evidence were determined.

RESULTS: Sixteen case-control studies were included, 10 comparing FM patients to controls and 6 comparing CFS patients to controls. Methodological quality was moderate to good. Both time domain and frequency domain measurements were used. The majority of the researchers observed lower HRV in FM patients compared to healthy control persons, as well as increased sympathetic activity and a blunted autonomic response to stressors. Resistance training improved HRV in FM patients. In CFS patients HRV was only reduced during sleep.

CONCLUSION: FM patients show more HRV aberrances and indices of increased sympathetic activity. Increased sympathetic activity is only present in CFS patients at night. Since direct comparisons are lacking and some confounders have to be taken into account, further research is warranted. The role of pain and causality can be subject of further research, as well as therapy studies directed to reduced HRV.

© 2013 Elsevier Inc. All rights reserved.

Comment in

Source: Meeus M, Goubert D, De Backer F, Struyf F, Hermans L, Coppieters I, De Wandele I, Da Silva H, Calders P. Heart rate variability in patients with fibromyalgia and patients with chronic fatigue syndrome: a systematic review. Semin Arthritis Rheum. 2013 Oct;43(2):279-87. doi: 10.1016/j.semarthrit.2013.03.004. Epub 2013 Jul 6. https://www.ncbi.nlm.nih.gov/pubmed/23838093

 

The role of mitochondrial dysfunctions due to oxidative and nitrosative stress in the chronic pain or chronic fatigue syndromes and fibromyalgia patients: peripheral and central mechanisms as therapeutic targets?

Abstract:

INTRODUCTION: Chronic fatigue syndrome (CFS) and fibromyalgia (FM) are characterized by persistent pain and fatigue. It is hypothesized that reactive oxygen species (ROS), caused by oxidative and nitrosative stress, by inhibiting mitochondrial function can be involved in muscle pain and central sensitization as typically seen in these patients.

AREAS COVERED: The current evidence regarding oxidative and nitrosative stress and mitochondrial dysfunction in CFS and FM is presented in relation to chronic widespread pain. Mitochondrial dysfunction has been shown in leukocytes of CFS patients and in muscle cells of FM patients, which could explain the muscle pain. Additionally, if mitochondrial dysfunction is also present in central neural cells, this could result in lowered ATP pools in neural cells, leading to generalized hypersensitivity and chronic widespread pain.

EXPERT OPINION: Increased ROS in CFS and FM, resulting in impaired mitochondrial function and reduced ATP in muscle and neural cells, might lead to chronic widespread pain in these patients. Therefore, targeting increased ROS by antioxidants and targeting the mitochondrial biogenesis could offer a solution for the chronic pain in these patients. The role of exercise therapy in restoring mitochondrial dysfunction remains to be explored, and provides important avenues for future research in this area.

 

Source: Meeus M, Nijs J, Hermans L, Goubert D, Calders P. The role of mitochondrial dysfunctions due to oxidative and nitrosative stress in the chronic pain or chronic fatigue syndromes and fibromyalgia patients: peripheral and central mechanisms as therapeutic targets? Expert Opin Ther Targets. 2013 Sep;17(9):1081-9. doi: 10.1517/14728222.2013.818657. Epub 2013 Jul 9. https://www.ncbi.nlm.nih.gov/pubmed/23834645

 

Discriminative validity of metabolic and workload measurements for identifying people with chronic fatigue syndrome

Abstract:

BACKGROUND: Reduced functional capacity and postexertion fatigue after physical activity are hallmark symptoms of chronic fatigue syndrome (CFS) and may even qualify for biomarker status. That these symptoms are often delayed may explain the equivocal results for clinical cardiopulmonary exercise testing in people with CFS. Test reproducibility in people who are healthy is well documented. Test reproducibility may not be achievable in people with CFS because of delayed symptoms.

OBJECTIVE: The objective of this study was to determine the discriminative validity of objective measurements obtained during cardiopulmonary exercise testing to distinguish participants with CFS from participants who did not have a disability but were sedentary.

DESIGN: A prospective cohort study was conducted.

METHODS: Gas exchange data, workloads, and related physiological parameters were compared in 51 participants with CFS and 10 control participants, all women, for 2 maximal exercise tests separated by 24 hours.

RESULTS: Multivariate analysis showed no significant differences between control participants and participants with CFS for test 1. However, for test 2, participants with CFS achieved significantly lower values for oxygen consumption and workload at peak exercise and at the ventilatory or anaerobic threshold. Follow-up classification analysis differentiated between groups with an overall accuracy of 95.1%.

LIMITATIONS: Only individuals with CFS who were able to undergo exercise testing were included in this study. Individuals who were unable to meet the criteria for maximal effort during both tests, were unable to complete the 2-day protocol, or displayed overt cardiovascular abnormalities were excluded from the analysis.

CONCLUSIONS: The lack of any significant differences between groups for the first exercise test would appear to support a deconditioning hypothesis for CFS symptoms. However, the results from the second test indicated the presence of CFS-related postexertion fatigue. It might be concluded that a single exercise test is insufficient to reliably demonstrate functional impairment in people with CFS. A second test might be necessary to document the atypical recovery response and protracted fatigue possibly unique to CFS, which can severely limit productivity in the home and workplace.

 

Source: Snell CR, Stevens SR, Davenport TE, Van Ness JM.Discriminative validity of metabolic and workload measurements for identifying people with chronic fatigue syndrome. Phys Ther. 2013 Nov;93(11):1484-92. doi: 10.2522/ptj.20110368. Epub 2013 Jun 27. https://academic.oup.com/ptj/article/93/11/1484/2735315/Discriminative-Validity-of-Metabolic-and-Workload?searchresult=1 (Full article)

 

Functional improvement is accompanied by reduced pain in adolescent chronic fatigue syndrome

Dear Editor:

Chronic fatigue syndrome (CFS) in adolescents is a complex, disabling condition characterized by severe and unexplained fatigue lasting more than 6 months, and often accompanied by pain symptoms. CFS in adolescents has substantial long-term consequences for educational and social development ⇓.

Chronic pain symptoms in CFS are disabling and affect physical and social functioning ⇓. Adult patients with CFS show lower pain thresholds than healthy subjects ⇓.

In a recently published review about pain in patients with CFS, Nijs et al. stated that pain appears to be one out of many symptoms related to central sensitization in adult CFS ⇓. They concluded that pain-catastrophizing thoughts and depression partly account for these pain symptoms. They suggested that it is important to understand the symptoms of pain in CFS better in order to assess whether it requires a specific treatment approach other than the main treatment focused on fatigue ⇓. Previous research has suggested to view the pathophysiological state of pain in CFS as an increase in the excitability and synaptic efficacy of neurons in central nociceptive pathways ⇓. We present original data on pain symptoms in adolescent CFS and their relation to treatment focused on fatigue.

We hypothesized that adolescent CFS patients have a lowered pain threshold at the time of diagnosis and that both pain experience and pain threshold improve when CFS is successfully treated.

You can read the rest of this article here: http://painmedicine.oxfordjournals.org/content/14/9/1435.long

 

Source: Nijhof SL, Priesterbach LP, Bleijenberg G, Engelbert RH, van de Putte EM. Functional improvement is accompanied by reduced pain in adolescent chronic fatigue syndrome. Pain Med. 2013 Sep;14(9):1435-8. doi: 10.1111/pme.12181. Epub 2013 Jun 26. http://painmedicine.oxfordjournals.org/content/14/9/1435.long (Full article)

 

A comparison of sex-specific immune signatures in Gulf War illness and chronic fatigue syndrome

Abstract:

BACKGROUND: Though potentially linked to the basic physiology of stress response we still have no clear understanding of Gulf War Illness (GWI), a debilitating condition presenting complex immune, endocrine and neurological symptoms. Here we compared male (n = 20) and female (n = 10) veterans with GWI separately against their healthy counterparts (n = 21 male, n = 9 female) as well as subjects with chronic fatigue syndrome/ myalgic encephalomyelitis (CFS/ME) (n = 12 male, n = 10 female).

METHODS: Subjects were assessed using a Graded eXercise Test (GXT) with blood drawn prior to exercise, at peak effort (VO2 max) and 4-hours post exercise. Using chemiluminescent imaging we measured the concentrations of IL-1a, 1b, 2, 4, 5, 6, 8, 10, 12 (p70), 13, 15, 17 and 23, IFNγ, TNFα and TNFβ in plasma samples from each phase of exercise. Linear classification models were constructed using stepwise variable selection to identify cytokine co-expression patterns characteristic of each subject group.

RESULTS: Classification accuracies in excess of 80% were obtained using between 2 and 5 cytokine markers. Common to both GWI and CFS, IL-10 and IL-23 expression contributed in an illness and time-dependent manner, accompanied in male subjects by NK and Th1 markers IL-12, IL-15, IL-2 and IFNγ. In female GWI and CFS subjects IL-10 was again identified as a delineator but this time in the context of IL-17 and Th2 markers IL-4 and IL-5. Exercise response also differed between sexes: male GWI subjects presented characteristic cytokine signatures at rest but not at peak effort whereas the opposite was true for female subjects.

CONCLUSIONS: Though individual markers varied, results collectively supported involvement of the IL-23/Th17/IL-17 axis in the delineation of GWI and CFS in a sex-specific way.

 

Source: Smylie AL, Broderick G, Fernandes H, Razdan S, Barnes Z, Collado F, Sol C, Fletcher MA, Klimas N. A comparison of sex-specific immune signatures in Gulf War illness and chronic fatigue syndrome. BMC Immunol. 2013 Jun 25;14:29. doi: 10.1186/1471-2172-14-29. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3698072/ (Full article)

 

Examining the impact of obesity on individuals with chronic fatigue syndrome

Abstract:

Chronic fatigue syndrome (CFS) is a complex disorder affecting multiple body systems. The most commonly used definition of CFS is 6 or more months of fatigue and the presence of at least four of eight minor symptoms. In addition, many health and psychological conditions, including severe obesity-body mass index (BMI) of 40 kg/m(2) or greater-exclude individuals from a diagnosis of CFS. Obesity has been correlated with fatigue, sleep problems, and less satisfaction with general health, functioning, and vitality.

The current study investigated weight trends over time in a community-based sample of individuals with CFS and healthy controls. The study further investigated the impact of comorbid weight issues on several health and disability outcomes in a subset of overweight individuals.

Overweight and obese individuals with CFS demonstrated poorer functioning than controls who were similarly weighted. One participant was excluded because she had gained weight at a monitoring visit and her BMI was greater than 40 kg/m(2). The implications of these findings for health care workers are discussed.

Copyright 2013, SLACK Incorporated.

 

Source: Flores S, Brown A, Adeoye S, Jason LA, Evans M. Examining the impact of obesity on individuals with chronic fatigue syndrome.Workplace Health Saf. 2013 Jul;61(7):299-307. doi: 10.3928/21650799-20130617-12. Epub 2013 Jun 24. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3899694/ (Full article)

 

Mediators of the effects on fatigue of pragmatic rehabilitation for chronic fatigue syndrome

Abstract:

OBJECTIVE: To examine potential mediators of the effect of pragmatic rehabilitation on improvements in fatigue following a randomized controlled trial for patients with chronic fatigue syndrome (CFS/ME) in primary care (IRCTN 74156610).

METHOD: Patients fulfilled the Oxford criteria for CFS. Ninety-five patients were randomized to pragmatic rehabilitation and 100 to general practitioner (GP) treatment as usual. The outcome was the Chalder fatigue scale score (0123 scoring) at end of treatment (20 weeks) and 1-year follow up (70 weeks). First, the effect of treatment on potential mediators was assessed. Then fatigue was regressed on significant mediators, treatment allocation, and baseline measures of fatigue and significant mediators.

RESULTS: Reduction in limiting activities at 20 weeks mediated the positive effect of pragmatic rehabilitation on fatigue at 70 weeks (mediated effect size = -2.64, SE = 0.81, p = .001, proportion of effect mediated = 82.0%). Reduction in catastrophizing at 20 weeks mediated the positive effect of pragmatic rehabilitation on fatigue at 70 weeks (mediated effect size = -1.39, SE = 0.61, p = .023, proportion of effect mediated = 43.2%). Reductions in 70-week measures of fear avoidance, embarrassment avoidance, limiting activities, and all-or-nothing behavior all mediated improvement in fatigue at 70 weeks, although the causal direction of these cross-sectional effects cannot be determined. There were no between-group differences on measures of exercise capacity (a timed step test).

CONCLUSIONS: Improvements in fatigue following pragmatic rehabilitation are related to changes in behavioral responses to and beliefs about fatigue.

 

Source: Wearden AJ, Emsley R. Mediators of the effects on fatigue of pragmatic rehabilitation for chronic fatigue syndrome. J Consult Clin Psychol. 2013 Oct;81(5):831-8. doi: 10.1037/a0033561. Epub 2013 Jun 24. https://www.ncbi.nlm.nih.gov/pubmed/23796316