Commonalities in the Features of Cancer and Chronic Fatigue Syndrome (CFS): Evidence for Stress-Induced Phenotype Instability?

Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME) and Cancer-Related Fatigue (CRF) are syndromes with considerable overlap with respect to symptoms. There have been many studies that have compared the two conditions, and some of this research suggests that the etiologies of the conditions are linked in some cases. In this narrative review, CFS/ME and cancer are introduced, along with their known and putative mechanistic connections to multiple stressors including ionizing radiation. Next, we summarize findings from the literature that suggest the involvement of HPA-axis dysfunction, the serotonergic system, cytokines and inflammation, metabolic insufficiency and mitochondrial dysfunction, and genetic changes in CRF and CFS/ME. We further suspect that the manifestation of fatigue in both diseases and its causes could indicate that CRF and CFS/ME lie on a continuum of potential biological effects which occur in response to stress. The response to this stress likely varies depending on predisposing factors such as genetic background. Finally, future research ideas are suggested with a focus on determining if common biomarkers exist in CFS/ME patients and those afflicted with CRF. Both CFS/ME and CRF are relatively heterogenous syndromes, however, it is our hope that this review assists in future research attempting to elucidate the commonalities between CRF and CFS/ME.

Download Full-text

The Experience of Cancer-Related Fatigue and Chronic Fatigue Syndrome: A Qualitative and Comparative Study

Journal of Pain and Symptom Management ◽

10.1016/j.jpainsymman.2006.10.014 ◽

2007 ◽

Vol 34 (2) ◽

pp. 126-135 ◽

Cited By ~ 47

Author(s):

Barbara Bennett ◽

David Goldstein ◽

Michael Friedlander ◽

Ian Hickie ◽

Andrew Lloyd

Keyword(s):

Chronic Fatigue Syndrome ◽

Comparative Study ◽

Chronic Fatigue ◽

Cancer Related Fatigue ◽

Fatigue Syndrome

Download Full-text

Salivary cortisol response to awakening in chronic fatigue syndrome

The British Journal of Psychiatry ◽

10.1192/bjp.184.2.136 ◽

2004 ◽

Vol 184 (2) ◽

pp. 136-141 ◽

Cited By ~ 178

Author(s):

Amanda D. L. Roberts ◽

Simon Wessely ◽

Trudie Chalder ◽

Andrew Papadopoulos ◽

Anthony J. Cleare

Keyword(s):

Chronic Fatigue Syndrome ◽

Hpa Axis ◽

Salivary Cortisol ◽

Area Under The Curve ◽

Chronic Fatigue ◽

Cortisol Response ◽

Non Invasive ◽

Fatigue Syndrome ◽

Invasive Test ◽

Response To Stress

BackgroundThere is accumulating evidence of hypothalamic–pituitary–adrenal (HPA) axis disturbances in chronic fatigue syndrome (CFS). The salivary cortisol response to awakening has been described recently as a non-invasive test of the capacity of the HPA axis to respond to stress. The results of this test correlate closely with those of more invasive dynamic tests reported in the literature; furthermore, it can be undertaken in a naturalistic setting.AimsTo assess the HPA axis using the salivary cortisol response to awakening in CFS.MethodWe measured salivary cortisol upon awakening and 10, 20, 30 and 60 min afterwards in 56 patients with CFS and 35 healthy volunteers.ResultsPatients had a lower cortisol response to awakening, measured by the area under the curve.ConclusionsThis naturalistic test of the HPA axis response to stress showed impaired HPA axis function in CFS.

Download Full-text

Heterogeneity in chronic fatigue syndrome – empirically defined subgroups from the PACE trial

Psychological Medicine ◽

10.1017/s0033291716003615 ◽

2017 ◽

Vol 47 (8) ◽

pp. 1454-1465 ◽

Cited By ~ 16

Author(s):

T. E. Williams ◽

T. Chalder ◽

M. Sharpe ◽

P. D. White

Keyword(s):

Chronic Fatigue Syndrome ◽

Latent Class ◽

Principal Component ◽

Chronic Fatigue ◽

Future Research ◽

Fatigue Syndrome ◽

Biological Variables ◽

Variable Reduction ◽

Combined Features ◽

Irritable Bowel

BackgroundChronic fatigue syndrome is likely to be a heterogeneous condition. Previous studies have empirically defined subgroups using combinations of clinical and biological variables. We aimed to explore the heterogeneity of chronic fatigue syndrome.MethodWe used baseline data from the PACE trial, which included 640 participants with chronic fatigue syndrome. Variable reduction, using a combination of clinical knowledge and principal component analyses, produced a final dataset of 26 variables for 541 patients. Latent class analysis was then used to empirically define subgroups.ResultsThe most statistically significant and clinically recognizable model comprised five subgroups. The largest, ‘core’ subgroup (33% of participants), had relatively low scores across all domains and good self-efficacy. A further three subgroups were defined by: the presence of mood disorders (21%); the presence of features of other functional somatic syndromes (such as fibromyalgia or irritable bowel syndrome) (21%); or by many symptoms – a group which combined features of both of the above (14%). The smallest ‘avoidant–inactive’ subgroup was characterized by physical inactivity, belief that symptoms were entirely physical in nature, and fear that they indicated harm (11%). Differences in the severity of fatigue and disability provided some discriminative validation of the subgroups.ConclusionsIn addition to providing further evidence for the heterogeneity of chronic fatigue syndrome, the subgroups identified may aid future research into the important aetiological factors of specific subtypes of chronic fatigue syndrome and the development of more personalized treatment approaches.

Download Full-text

Genetics and Gene Expression Involving Stress and Distress Pathways in Fibromyalgia with and without Comorbid Chronic Fatigue Syndrome

Pain Research and Treatment ◽

10.1155/2012/427869 ◽

2012 ◽

Vol 2012 ◽

pp. 1-13 ◽

Cited By ~ 6

Author(s):

Kathleen C. Light ◽

Andrea T. White ◽

Scott Tadler ◽

Eli Iacob ◽

Alan R. Light

Keyword(s):

Gene Expression ◽

Chronic Fatigue Syndrome ◽

Expression Profiles ◽

Gene Expression Profiles ◽

Chronic Fatigue ◽

Future Research ◽

Sensory Receptor ◽

Methyl Transferase ◽

Fatigue Syndrome ◽

Inherited Susceptibility

In complex multisymptom disorders like fibromyalgia syndrome (FMS) and chronic fatigue syndrome (CFS) that are defined primarily by subjective symptoms, genetic and gene expression profiles can provide very useful objective information. This paper summarizes research on genes that may be linked to increased susceptibility in developing and maintaining these disorders, and research on resting and stressor-evoked changes in leukocyte gene expression, highlighting physiological pathways linked to stress and distress. These include the adrenergic nervous system, the hypothalamic-pituitary-adrenal axis and serotonergic pathways, and exercise responsive metabolite-detecting ion channels. The findings to date provide some support for both inherited susceptibility and/or physiological dysregulation in all three systems, particularly for catechol-O-methyl transferase (COMT) genes, the glucocorticoid and the related mineralocorticoid receptors (NR3C1, NR3C2), and the purinergic 2X4 (P2X4) ion channel involved as a sensory receptor for muscle pain and fatigue and also in upregulation of spinal microglia in chronic pain models. Methodological concerns for future research, including potential influences of comorbid clinical depression and antidepressants and other medications, on gene expression are also addressed.

Download Full-text

Lessons From Heat Stroke for Understanding Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Frontiers in Neurology ◽

10.3389/fneur.2021.789784 ◽

2021 ◽

Vol 12 ◽

Author(s):

Dominic Stanculescu ◽

Nuno Sepúlveda ◽

Chin Leong Lim ◽

Jonas Bergquist

Keyword(s):

Chronic Fatigue Syndrome ◽

Cell Injury ◽

Heat Stroke ◽

Chronic Fatigue ◽

Myalgic Encephalomyelitis ◽

Future Research ◽

Coagulation Disorder ◽

Gene Expressions ◽

Fatigue Syndrome ◽

Central Nervous System Dysfunction

We here provide an overview of the pathophysiological mechanisms during heat stroke and describe similar mechanisms found in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Both conditions are characterized by disturbed homeostasis in which inflammatory pathways play a central role. Splanchnic vasoconstriction, increased gut permeability, gut-related endotoxemia, systemic inflammatory response, central nervous system dysfunction, blood coagulation disorder, endothelial-cell injury, and mitochondrial dysfunction underlie heat stroke. These mechanisms have also been documented in ME/CFS. Moreover, initial transcriptomic studies suggest that similar gene expressions are altered in both heat stroke and ME/CFS. Finally, some predisposing factors for heat stroke, such as pre-existing inflammation or infection, overlap with those for ME/CFS. Notwithstanding important differences - and despite heat stroke being an acute condition - the overlaps between heat stroke and ME/CFS suggest common pathways in the physiological responses to very different forms of stressors, which are manifested in different clinical outcomes. The human studies and animal models of heat stroke provide an explanation for the self-perpetuation of homeostatic imbalance centered around intestinal wall injury, which could also inform the understanding of ME/CFS. Moreover, the studies of novel therapeutics for heat stroke might provide new avenues for the treatment of ME/CFS. Future research should be conducted to investigate the similarities between heat stroke and ME/CFS to help identify the potential treatments for ME/CFS.

Download Full-text

Long COVID and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)—A Systemic Review and Comparison of Clinical Presentation and Symptomatology

Medicina ◽

10.3390/medicina57050418 ◽

2021 ◽

Vol 57 (5) ◽

pp. 418

Author(s):

Timothy L. Wong ◽

Danielle J. Weitzer

Keyword(s):

Chronic Fatigue Syndrome ◽

Literature Search ◽

Clinical Presentation ◽

Chronic Fatigue ◽

Myalgic Encephalomyelitis ◽

Systemic Review ◽

Future Research ◽

Medical Illness ◽

Case Definitions ◽

Fatigue Syndrome

Background and Objectives: Long COVID defines a series of chronic symptoms that patients may experience after resolution of acute COVID-19. Early reports from studies with patients with long COVID suggests a constellation of symptoms with similarities to another chronic medical illness—myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). A review study comparing and contrasting ME/CFS with reported symptoms of long COVID may yield mutualistic insight into the characterization and management of both conditions. Materials and Methods: A systemic literature search was conducted in MEDLINE and PsycInfo through to 31 January 2021 for studies related to long COVID symptomatology. The literature search was conducted in accordance with PRISMA methodology. Results: Twenty-one studies were included in the qualitative analysis. Long COVID symptoms reported by the included studies were compared to a list of ME/CFS symptoms compiled from multiple case definitions. Twenty-five out of 29 known ME/CFS symptoms were reported by at least one selected long COVID study. Conclusions: Early studies into long COVID symptomatology suggest many overlaps with clinical presentation of ME/CFS. The need for monitoring and treatment for patients post-COVID is evident. Advancements and standardization of long COVID research methodologies would improve the quality of future research, and may allow further investigations into the similarities and differences between long COVID and ME/CFS.

Download Full-text

Chronic fatigue syndrome and fibromyalgia in Canada: prevalence and associations with six health status indicators

Health Promotion and Chronic Disease Prevention in Canada ◽

10.24095/hpcdp.35.1.02 ◽

2015 ◽

Vol 35 (1) ◽

pp. 3-11 ◽

Cited By ~ 23

Author(s):

C Rusu ◽

ME Gee ◽

C Lagacé ◽

M Parlor

Keyword(s):

Health Status ◽

Chronic Fatigue Syndrome ◽

Chronic Fatigue ◽

Canadian Community Health Survey ◽

Health Status Indicators ◽

Population Based ◽

Poor Mental Health ◽

Future Research ◽

Fatigue Syndrome ◽

The Impact

Introduction Few studies have considered the factors independently associated with chronic fatigue syndrome (CFS) and/or fibromyalgia (FM) or considered the impact of these conditions on health status using population-based data. Methods We used data from the nationally representative 2010 Canadian Community Health Survey (n= 59 101) to describe self-reported health professional-diagnosed CFS and/or FM, and their associations with 6 health status indicators. Results In 2010, diagnosed CFS and FM are reported by 1.4% (95% confidence interval [CI]: 1.3%–1.6%) and 1.5% (1.4%–1.7%), respectively, of the Canadian household population aged 12 years and over, with comorbid CFS and FM affecting 0.3% (0.3%–0.4%) of that population. Prevalent CFS and/or FM were more common among women, adults aged 40 years and over, those with lowest income, and those with certain risk factors for chronic disease (i.e. obesity, physical inactivity and smoking). After controlling for differences between the groups, people with CFS and/or FM reported poorer health status than those with neither condition on 5 indicators of health status, but not on the measure of fair/poor mental health. Having both CFS and FM and having multiple comorbid conditions was associated with poorer health status. Conclusion Co-occurrence of CFS and FM and having other chronic conditions were strongly related to poorer health status and accounted for much of the differences in health status. Understanding factors contributing to improved quality of life in people with CFS and/or FM, particularly in those with both conditions and other comorbidities, may be an important area for future research.

Download Full-text

Systematic Review of the Epidemiological Burden of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Across Europe: Current Evidence and EUROMENE Research Recommendations for Epidemiology

Journal of Clinical Medicine ◽

10.3390/jcm9051557 ◽

2020 ◽

Vol 9 (5) ◽

pp. 1557 ◽

Cited By ~ 1

Author(s):

Fernando Estévez-López ◽

Kathleen Mudie ◽

Xia Wang-Steverding ◽

Inger Johanne Bakken ◽

Andrejs Ivanovs ◽

...

Keyword(s):

Chronic Fatigue Syndrome ◽

Grey Literature ◽

Reporting Quality ◽

Chronic Fatigue ◽

Myalgic Encephalomyelitis ◽

Current Evidence ◽

Future Research ◽

Institute Of Medicine ◽

Case Definitions ◽

Fatigue Syndrome

This review aimed at determining the prevalence and incidence of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) in Europe. We conducted a primary search in Scopus, PubMed and Web of Science for publications between 1994 and 15 June 2019 (PROSPERO: CRD42017078688). Additionally, we performed a backward-(reference lists) and forward-(citations) search of the works included in this review. Grey literature was addressed by contacting all members of the European Network on ME/CFS (EUROMENE). Independent reviewers searched, screened and selected studies, extracted data and evaluated the methodological and reporting quality. For prevalence, two studies in adults and one study in adolescents were included. Prevalence ranged from 0.1% to 2.2%. Two studies also included incidence estimates. In conclusion, studies on the prevalence and incidence of ME/CFS in Europe were scarce. Our findings point to the pressing need for well-designed and statistically powered epidemiological studies. To overcome the shortcomings of the current state-of-the-art, EUROMENE recommends that future research is better conducted in the community, reviewing the clinical history of potential cases, obtaining additional objective information (when needed) and using adequate ME/CFS case definitions; namely, the Centers for Disease Control & Prevention−1994, Canadian Consensus Criteria, or Institute of Medicine criteria.

Download Full-text

Chronic fatigue syndrome and an illness-focused approach to care: controversy, morality and paradox

Medical Humanities ◽

10.1136/medhum-2018-011598 ◽

2019 ◽

Vol 45 (2) ◽

pp. 183-187 ◽

Cited By ~ 6

Author(s):

Michael Sharpe ◽

Monica Greco

Keyword(s):

Chronic Fatigue Syndrome ◽

Subjective Experience ◽

Chronic Fatigue ◽

Common Symptom ◽

General Acceptance ◽

Cancer Related Fatigue ◽

Fatigue Syndrome ◽

Established Disease ◽

Contemporary Medicine ◽

Illness And Disease

Contemporary medicine distinguishes between illness and disease. Illness refers to a person’s subjective experience of symptoms; disease refers to objective bodily pathology. For many illnesses, medicine has made great progress in finding and treating associated disease. However, not all illnesses are successfully relieved by treating the disease. In some such cases, the patient’s suffering can only be reduced by treatment that is focused on the illness itself. Chronic disabling fatigue is a common symptom of illness, for which disease-focused treatment is often not effective, but for which illness-focused treatments (psychological or behavioural) often are. In this article, we explore a controversy surrounding illness-focused treatments for fatigue. We do this by contrasting their acceptance by people whose fatigue is associated with a disease (using the example of cancer-related fatigue) with their controversial rejection by some people whose fatigue is not associated with an established disease (chronic fatigue syndrome or CFS, sometimes called ME (myalgic encephalomyelitis)). In order to understand this difference in acceptability we consider the differing moral connotations of illness and disease and then go on to examine the limitations of the concepts of illness and disease themselves. We conclude that a general acceptance of illness-focused treatments by all who might benefit from them will require a major long-term change in thinking about illness, but that improvements to the care of individual patients can be made today.

Download Full-text