chronic fatigue syndrome vs cancer – American ME and CFS Society

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

Abstract:

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.

Source: Rusin A, Seymour C, Cocchetto A, Mothersill C. Commonalities in the Features of Cancer and Chronic Fatigue Syndrome (CFS): Evidence for Stress-Induced Phenotype Instability? Int J Mol Sci. 2022 Jan 8;23(2):691. doi: 10.3390/ijms23020691. PMID: 35054876. https://pubmed.ncbi.nlm.nih.gov/35054876/

Multidimensional Comparison of Cancer-Related Fatigue and Chronic Fatigue Syndrome: The Role of Psychophysiological Markers

Abstract:

OBJECTIVE: The present study compared cancer-related fatigue (CRF) and chronic fatigue syndrome (CFS) using multidimensional measurements with the aim of better understanding characteristics and exploring markers of two similar fatigue syndromes.

METHODS: Twenty-five patients with CRF and twenty patients with CFS completed questionnaires, including the Fatigue Severity Scale (FSS), Hospital Anxiety Depression Scale (HADS), Perceived Stress Scale (PSS), and Pittsburgh Sleep Quality Index (PSQI). Additionally, levels of high sensitivity C-reactive protein (hs-CRP), heart rate variability (HRV), and electroencephalography (EEG) were obtained. Neurocognitive functioning was also evaluated.

RESULTS: Both groups showed comparable levels of psychological variables, including fatigue. Compared to CFS subjects, CRF patients had significantly higher hs-CRP levels and a reduced HRV-index. The within-group analyses revealed that the FSS score of the CRF group was significantly related to scores on the HADS-anxiety, HADS-depression, and PSQI scales. In the CFS group, FSS scores were significantly associated with scores on the PSS and the absolute delta, theta, and alpha powers in frontal EEG.

CONCLUSION: Findings indicate that different pathophysiological mechanisms underlie CFS and CRF. Inflammatory marker and HRV may be potential biomarkers for distinguishing two fatigue syndromes and frontal EEG parameters may be quantitative biomarkers for CFS.

Source: Park HY, Jeon HJ, Bang YR, Yoon IY. Multidimensional Comparison of Cancer-Related Fatigue and Chronic Fatigue Syndrome: The Role of Psychophysiological Markers. Psychiatry Investig. 2019 Jan 7. doi: 10.30773/pi.2018.10.26. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/30605994

A systematic review of the association between fatigue and genetic polymorphisms

Abstract:

Fatigue is one of the most common and distressing symptoms, leading to markedly decreased quality of life among a large subset of patients with a variety of disorders. Susceptibility to fatigue may be influenced by genetic factors including single nucleotide polymorphisms (SNPs), especially in the regulatory regions, of relevant genes.

To further investigate the association of SNPs with fatigue in various patient populations, a systematic search was conducted on Pubmed, CINAHL, PsycINFO, and Sociological Abstracts Database for fatigue related-terms in combination with polymorphisms or genetic variation-related terms. Fifty papers in total met the inclusion and exclusion criteria for this analysis. These 50 papers were further classified into three subgroups for evaluation: chronic fatigue syndrome (CFS), cancer-related fatigue (CRF) and other disease-related fatigue.

SNPs in regulatory pathways of immune and neurotransmitter systems were found to play important roles in the etiologies of CFS, CRF and other disease-related fatigue. Evidence for associations between elevated fatigue and specific polymorphisms in TNFα, IL1b, IL4 and IL6 genes was revealed for all three subgroups of fatigue.

We also found CFS shared a series of polymorphisms in HLA, IFN-γ, 5-HT and NR3C1 genes with other disease-related fatigue, however these SNPs (excluding IFN-γ) were not found to be adequately investigated in CRF. Gaps in knowledge related to fatigue etiology and recommendations for future research are further discussed.

Source: Wang T, Yin J, Miller AH, Xiao C. A systematic review of the association between fatigue and genetic polymorphisms. Brain Behav Immun. 2017 Jan 12. pii: S0889-1591(17)30007-7. doi: 10.1016/j.bbi.2017.01.007. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/28089639

Differing leukocyte gene expression profiles associated with fatigue in patients with prostate cancer versus chronic fatigue syndrome

Abstract:

BACKGROUND: Androgen deprivation therapy (ADT) often worsens fatigue in patients with prostate cancer, producing symptoms similar to chronic fatigue syndrome (CFS). Comparing expression (mRNA) of many fatigue-related genes in patients with ADT-treated prostate cancer versus with CFS versus healthy controls, and correlating mRNA with fatigue severity may clarify the differing pathways underlying fatigue in these conditions.

METHODS: Quantitative real-time PCR was performed on leukocytes from 30 fatigued, ADT-treated prostate cancer patients (PCF), 39 patients with CFS and 22 controls aged 40-79, together with ratings of fatigue and pain severity. 46 genes from these pathways were included: (1) adrenergic/monoamine/neuropeptides, (2) immune, (3) metabolite-detecting, (4) mitochondrial/energy, (5) transcription factors.

RESULTS: PCF patients showed higher expression than controls or CFS of 2 immune transcription genes (NR3C1 and TLR4), chemokine CXCR4, and mitochondrial gene SOD2. They showed lower expression of 2 vasodilation-related genes (ADRB2 and VIPR2), 2 cytokines (TNF and LTA), and 2 metabolite-detecting receptors (ASIC3 and P2RX7). CFS patients showed higher P2RX7 and lower HSPA2 versus controls and PCF. Correlations with fatigue severity were similar in PCF and CFS for only DBI, the GABA-A receptor modulator (r=-0.50, p<0.005 and r=-0.34, p<0.05). Purinergic P2RY1 was correlated only with PCF fatigue and pain severity (r=+0.43 and +0.59, p=0.025 and p=0.001).

CONCLUSIONS: PCF patients differed from controls and CFS in mean expression of 10 genes from all 5 pathways. Correlations with fatigue severity implicated DBI for both patient groups and P2RY1 for PCF only. These pathways may provide new targets for interventions to reduce fatigue.

Source: Light KC, Agarwal N, Iacob E, White AT, Kinney AY, VanHaitsma TA, Aizad H, Hughen RW, Bateman L, Light AR. Differing leukocyte gene expression profiles associated with fatigue in patients with prostate cancer versus chronic fatigue syndrome. Psychoneuroendocrinology. 2013 Dec;38(12):2983-95. doi: 10.1016/j.psyneuen.2013.08.008. Epub 2013 Sep 6. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3848711/ (Full article)

Chronic Fatigue Syndrome (CFS) and Cancer Related Fatigue (CRF): two “fatigue” syndromes with overlapping symptoms and possibly related aetiologies

Abstract:

In July 2010, at the Muscle Fatigue Meeting, I presented an overview of Chronic Fatigue Syndrome and Cancer Related Fatigue, emphasizing a critical interpretation of the potential association between Chronic Fatigue Syndrome and Cancer Related Fatigue and a newly discovered retrovirus: Xenotropic Murine Related Virus. Since this association was hotly debated at that time, I suggested at the Meeting that it was wrong and most likely due to the identification of the wrong virus culprit.

Today, 20 months after the Meeting, the first part of our prediction has turned out to be correct, as Xenotropic Murine Related Virus was shown to be a laboratory-created artefact. Still, the potential association of fatigue-syndromes with an infection (most likely viral) is sustained by a plethora of evidence and this overview will initially summarize data suggesting prior viral infection(s). The principal hypothesized mechanisms for both peripheral and central Chronic Fatigue Syndrome/Cancer Related Fatigue will be then summarized, also indicating plausible associations and triggering factors.

All evidence accrued so far suggests that further research work should be performed in this interesting area and in order to identify an infectious agent for Chronic Fatigue Syndrome/Cancer Related Fatigue. One candidate RNA virus, Micro-Foci inducing Virus, will be described in this overview.

Source: Rovigatti U. Chronic Fatigue Syndrome (CFS) and Cancer Related Fatigue (CRF): two “fatigue” syndromes with overlapping symptoms and possibly related aetiologies. Neuromuscul Disord. 2012 Dec;22 Suppl 3:S235-41. doi: 10.1016/j.nmd.2012.10.018. https://www.ncbi.nlm.nih.gov/pubmed/23182646

The functional status and well being of people with myalgic encephalomyelitis/chronic fatigue syndrome and their carers

Abstract:

BACKGROUND: Diagnosis of myalgic encephalomyelitis/chronic fatigue syndrome or ME/CFS is largely based on clinical history, and exclusion of identifiable causes of chronic fatigue. Characterization of cases and the impact of interventions have been limited due to clinical heterogeneity and a lack of reliable biomarkers for diagnosis and outcome measures. People with ME/CFS (PWME) often report high levels of disability, which are difficult to measure objectively. The well being of family members and those who care for PWME are also likely to be affected. This study aimed to investigate the functional status and well being of PWME and their lay carers, and to compare them with people with other chronic conditions.

METHODS: We used a cross sectional design to study 170 people aged between 18 and 64 years with well characterized ME/CFS, and 44 carers, using SF-36 v2™. Mean physical and mental domains scores (scales and component summaries) were calculated and compared internally and externally with reference standards for the general population and for population groups with 10 chronic diseases.

: SF-36 scores in PWME were significantly reduced, especially within the physical domain (mean norm-based Physical Component Summary (PCS) score = 26.8), but also within the mental domain (mean norm-based score for Mental Component Summary (MCS) = 34.1). The lowest and highest scale scores were for “Role-Physical” (mean = 25.4) and “Mental Health” (mean = 36.7) respectively. All scores were in general lower than those for the general population and diseased-specific norms for other diseases. Carers of those with ME/CFS tended to have low scores in relation to population norms, particularly within the mental domain (mean = 45.4).

CONCLUSIONS: ME/CFS is disabling and has a greater impact on functional status and well being than other chronic diseases such as cancer. The emotional burden of ME/CFS is felt by lay carers as well as by people with ME/CFS. We suggest the use of generic instruments such as SF-36, in combination of other objective outcome measurements, to describe patients and assess treatments.

Source: Nacul LC, Lacerda EM, Campion P, Pheby D, Drachler Mde L, Leite JC, Poland F, Howe A, Fayyaz S, Molokhia M. The functional status and well being of people with myalgic encephalomyelitis/chronic fatigue syndrome and their carers. BMC Public Health. 2011 May 27;11:402. doi: 10.1186/1471-2458-11-402. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3123211/ (Full article)

Immunological similarities between cancer and chronic fatigue syndrome: the common link to fatigue?

Abstract:

Cancer and chronic fatigue syndrome (CFS) are both characterised by fatigue and severe disability. Besides fatigue, certain aspects of immune dysfunctions appear to be present in both illnesses. In this regard, a literature review of overlapping immune dysfunctions in CFS and cancer is provided.

Special emphasis is given to the relationship between immune dysfunctions and fatigue. Abnormalities in ribonuclease (RNase) L and hyperactivation of nuclear factor kappa beta (NF-kappaB) are present in CFS and in prostate cancer. Malfunctioning of natural killer (NK) cells has long been recognised as an important factor in the development and reoccurrence of cancer, and has been documented repeatedly in CFS patients.

The dysregulation of the RNase L pathway, hyperactive NF-kappaB leading to disturbed apoptotic mechanisms and oxidative stress or excessive nitric oxide, and low NK activity may play a role in the two diseases and in the physiopathology of the common symptom fatigue. However, in cancer the relation between the immune dysfunctions and fatigue has been poorly studied. Immunological abnormalities to such as a dysregulated RNase L pathway, hyperactive NF-kappaB, increased oxidative stress and reduced NK cytotoxicity, among others, are present in both diseases.

These anomalies may be part of the physiopathology of some of the common complaints, such as fatigue. Further studies to confirm the hypotheses given here are warranted.

Source: Meeus M, Mistiaen W, Lambrecht L, Nijs J. Immunological similarities between cancer and chronic fatigue syndrome: the common link to fatigue? Anticancer Res. 2009 Nov;29(11):4717-26. http://ar.iiarjournals.org/content/29/11/4717.long (Full article)

The experience of cancer-related fatigue and chronic fatigue syndrome: a qualitative and comparative study

Abstract:

Cancer-related fatigue (CRF) is a common and disabling symptom complex reported by survivors. This study aimed to better understand the manifestations of CRF in women treated for breast cancer, and to compare them with those of women diagnosed with chronic fatigue syndrome (CFS).

Women with CRF persisting 6 months after treatment for early stage breast cancer, and women with CFS participated in separate, audiotaped focus groups. Transcripts of the sessions were analyzed using the NUD*IST software, and interpreted using grounded theory. Twenty-eight women participated, 16 with CRF and 12 with CFS. Analysis of transcripts from both groups revealed a similar core set of symptoms, featuring fatigue, neurocognitive difficulties, and mood disturbances.

Women with CFS reported additional symptoms including musculoskeletal pain and influenza-like manifestations. Both groups suffered disabling behavioral consequences of the symptom complex. Qualitatively, CRF appears closely related to CFS. These findings raise the emergent hypothesis of a conserved neurobehavioral symptom complex, which results from diverse triggering insults.

Source: Bennett B, Goldstein D, Friedlander M, Hickie I, Lloyd A. The experience of cancer-related fatigue and chronic fatigue syndrome: a qualitative and comparative study. J Pain Symptom Manage. 2007 Aug;34(2):126-35. Epub 2007 Jun 4. https://www.ncbi.nlm.nih.gov/pubmed/17544246