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.

Copyright © 2012 Elsevier B.V. All rights reserved.

 

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

 

Altered immune pathway activity under exercise challenge in Gulf War Illness: an exploratory analysis

Abstract:

Though potentially linked to the basic physiology of stress response we still have no clear understanding of Gulf War Illness (GWI), a debilitating illness presenting with a complex constellation of immune, endocrine and neurological symptoms. Here we compared male GWI (n=20) with healthy veterans (n=22) and subjects with chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) (n=7). Blood was drawn during a Graded eXercise Test (GXT) prior to exercise, at peak effort (VO2 max) and 4-h post exercise. Affymetrix HG U133 plus 2.0 microarray gene expression profiling in peripheral blood mononuclear cells (PBMCs) was used to estimate activation of over 500 documented pathways. This was cast against ELISA-based measurement of 16 cytokines in plasma and flow cytometric assessment of lymphocyte populations and cytotoxicity. A 2-way ANOVA corrected for multiple comparisons (q statistic <0.05) indicated significant increases in neuroendocrine-immune signaling and inflammatory activity in GWI, with decreased apoptotic signaling. Conversely, cell cycle progression and immune signaling were broadly subdued in CFS. Partial correlation networks linking pathways with symptom severity via changes in immune cell abundance, function and signaling were constructed.

Central to these were changes in IL-10 and CD2+ cell abundance and their link to two pathway clusters. The first consisted of pathways supporting neuronal development and migration whereas the second was related to androgen-mediated activation of NF-κB. These exploratory results suggest an over-expression of known exercise response mechanisms as well as illness-specific changes that may involve an overlapping stress-potentiated neuro-inflammatory response.

Copyright © 2012 Elsevier Inc. All rights reserved.

 

Source: Broderick G, Ben-Hamo R, Vashishtha S, Efroni S, Nathanson L, Barnes Z, Fletcher MA, Klimas N. Altered immune pathway activity under exercise challenge in Gulf War Illness: an exploratory analysis. Brain Behav Immun. 2013 Feb;28:159-69. doi: 10.1016/j.bbi.2012.11.007. Epub 2012 Nov 29. https://www.ncbi.nlm.nih.gov/pubmed/23201588

 

Improved chronic fatigue symptoms after removal of mercury in patient with increased mercury concentration in hair toxic mineral assay: a case

Abstract:

Clinical manifestations of chronic exposure to organic mercury usually have a gradual onset. As the primary target is the nervous system, chronic mercury exposure can cause symptoms such as fatigue, weakness, headache, and poor recall and concentration. In severe cases chronic exposure leads to intellectual deterioration and neurologic abnormality. Recent outbreaks of bovine spongiform encephalopathy and pathogenic avian influenza have increased fish consumption in Korea. Methyl-mercury, a type of organic mercury, is present in higher than normal ranges in the general Korean population. When we examine a patient with chronic fatigue, we assess his/her methyl-mercury concentrations in the body if environmental exposure such as excessive fish consumption is suspected. In the current case, we learned the patient had consumed many slices of raw tuna and was initially diagnosed with chronic fatigue syndrome. Therefore, we suspected that he was exposured to methyl-mercury and that the mercury concentration in his hair would be below the poisoning level identified by World Health Organization but above the normal range according to hair toxic mineral assay. Our patient’s toxic chronic fatigue symptoms improved after he was given mercury removal therapy, indicating that he was correctly diagnosed with chronic exposure to organic mercury.

 

Source: Shin SR, Han AL. Improved chronic fatigue symptoms after removal of mercury in patient with increased mercury concentration in hair toxic mineral assay: a case. Korean J Fam Med. 2012 Sep;33(5):320-5. doi: 10.4082/kjfm.2012.33.5.320. Epub 2012 Sep 27. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3481032/ (Full article)

 

Is chronic fatigue syndrome the same illness as fibromyalgia: evaluating the ‘single syndrome’ hypothesis

Abstract:

Chronic fatigue syndrome (CFS) and fibromyalgia (FM) are medically unexplained syndromes that can and often do co-occur. For this reason, some have posited that the two are part of the same somatic syndrome–examples of symptom amplification. This hypothesis would suggest that few differences exist between the two syndromes. To evaluate this interpretation, we have searched the literature for articles comparing CFS to FM, reviewing only those articles which report differences between the two. This review presents data showing differences across a number of parameters–implying that the underlying pathophysiology in CFS may differ from that of FM. We hope that our review encourages other groups to look for additional differences between CFS and FM. By continuing to preserve the unique illness definitions of the two syndromes, clinicians will be able to better identify, understand and provide treatment for these individuals.

 

Source: Abbi B, Natelson BH. Is chronic fatigue syndrome the same illness as fibromyalgia: evaluating the ‘single syndrome’ hypothesis. QJM. 2013 Jan;106(1):3-9. doi: 10.1093/qjmed/hcs156. Epub 2012 Aug 26. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3527744/ (Full article)

 

Prognostic factors for recent-onset interstitial cystitis/painful bladder syndrome

Abstract:

Study Type – Prognosis (case series) Level of Evidence 4 What’s known on the subject? and What does the study add? Interstitial cystitis/painful bladder syndrome (IC/PBS) comprises pain perceived to be from the bladder, urinary urgency and frequency, and nocturia. As diagnosed at present, it is primarily identified in adult women. It is a chronic disease yet its natural history has not been well studied. In a prospective study of 304 incident female IC/PBS cases followed for a median of 33 months after onset, women with baseline chronic fatigue syndrome had a worse prognosis for IC/PBS. Mild IC/PBS at baseline was the only variable that was directly associated with a good prognosis.

OBJECTIVE: To identify baseline variables that predict the prognosis of interstitial cystitis/painful bladder syndrome (IC/PBS) in women seeking medical care for recent onset of this syndrome.

SUBJECTS AND METHODS: In a prospective study of women with incident IC/PBS (≤12 months of symptoms), we contacted patients at intervals and asked standardized questions about IC/PBS symptoms in the previous week. Logistic regression analyses assessed baseline variables as predictors of mild vs more severe IC/PBS at the last follow-up.

RESULTS: Median length of follow-up was 33 months after onset of IC/PBS; 304 (97%) patients had at least one follow-up assessment. Mild IC/PBS at baseline was the only variable that was directly associated with a mild IC/PBS endpoint. Conversely, a history of chronic fatigue syndrome (CFS) was inversely associated with a mild endpoint of IC/PBS (i.e. individuals with CFS had a worse prognosis for their IC/PBS symptoms).

CONCLUSIONS: At a median of nearly 3 years after onset, baseline mild IC/PBS was directly associated with a milder disease severity. Baseline co-morbid CFS was associated with more severe disease. Whether CFS was uniquely associated or represented several co-morbid non-bladder syndromes (NBSs) could not be determined.

© 2012 BJU INTERNATIONAL.

Comment in: Re: prognostic factors for recent-onset interstitial cystitis/painful bladder syndrome. [J Urol. 2013]

 

Source: Warren JW, Clauw DJ, Langenberg P. Prognostic factors for recent-onset interstitial cystitis/painful bladder syndrome. BJU Int. 2013 Mar;111(3 Pt B):E92-7. doi: 10.1111/j.1464-410X.2012.11422.x. Epub 2012 Aug 9. http://onlinelibrary.wiley.com/doi/10.1111/j.1464-410X.2012.11422.x/full (Full article)

Attention-deficit hyperactivity disorder in chronic fatigue syndrome patients

Abstract:

Psychopathological disorders are frequent in chronic fatigue syndrome patients. The present study examines the presence of attention-deficit hyperactivity disorder (ADHD) in a sample of adult chronic fatigue syndrome (CFS) patients, and evaluates its clinical consequences in this population. CFS patients were assessed for childhood and adult ADHD by clinical interview and ADHD-specific scales. Psychopathological comorbidities were evaluated by clinical examination and questionnaires.

Forty-seven of 158 CSF patients (29.7%) were diagnosed of childhood ADHD and in 33 (20.9%), the condition persisted into adulthood. CFS patients with adult ADHD had an earlier CSF onset, more severe anxiety and depression symptoms, and a higher risk of suicide than CFS patients without ADHD. Using lineal regression analysis, we found that depressive symptoms and ADHD severity were significant predictors of fatigue intensity. Consequently, ADHD may be common in CFS patients, and is associated with a more severe psychopathologic clinical profile.

Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

 

Source: Sáez-Francàs N, Alegre J, Calvo N, Antonio Ramos-Quiroga J, Ruiz E, Hernández-Vara J, Casas M. Attention-deficit hyperactivity disorder in chronic fatigue syndrome patients. Psychiatry Res. 2012 Dec 30;200(2-3):748-53. doi: 10.1016/j.psychres.2012.04.041. Epub 2012 May 28. https://www.ncbi.nlm.nih.gov/pubmed/22648008

 

Biological underpinnings of the commonalities in depression, somatization, and Chronic Fatigue Syndrome

Abstract:

BACKGROUND: Somatization is a multisomatoform disorder characterized by medically unexplained, functional or psychosomatic symptoms. Similar somatic symptoms are key components of depression and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS).

METHODS: This paper reviews the evidence that such symptoms are organically based. We use the term “physio-somatic” to describe these symptoms.

RESULTS: Inflammation, cell-mediated immune (CMI) activation and alterations in the tryptophan catabolite (TRYCAT) pathway are associated with the physio-somatic symptoms of depression, ME/CFS and/or somatization. Proinflammatory cytokines, decreased tryptophan and aberrations in TRYCATs may cause physio-somatic symptoms, such as fatigue, autonomic symptoms, hyperalgesia and somatic presentations.

CONCLUSIONS: The data suggest co-ordinated and interacting biological pathways driving the occurrence of physio-somatic symptoms across these three disorders, giving a biologically validated “pathway phenotype”. These data have far-reaching implications for DSM-IV diagnostic conceptualizations of somatization (and ME/CFS) suggesting the presence of an emerging organic explanation. Future research should focus on the role of immune regulation, and co-ordination, of neuronal activity and, through larger data sets, ultimately creating new, biologically validated classification rules. These data have implications for the development of novel therapies utilizing these insights, buttressing the role of psychotherapy in psychosomatic presentations.

Copyright © 2012 Elsevier Ltd. All rights reserved.

 

Source: Anderson G, Maes M, Berk M. Biological underpinnings of the commonalities in depression, somatization, and Chronic Fatigue Syndrome. Med Hypotheses. 2012 Jun;78(6):752-6. doi: 10.1016/j.mehy.2012.02.023. Epub 2012 Mar 23. https://www.ncbi.nlm.nih.gov/pubmed/22445460

 

Cervical neuro-muscular syndrome: discovery of a new disease group caused by abnormalities in the cervical muscles

Abstract:

Our previous study of whiplash injury found that abnormalities in the cervical muscles cause autonomic dystonia. Further research has found that abnormalities in the cervical muscles cause headache, chronic fatigue syndrome, vertigo, and dizziness. We named this group of diseases cervical neuro-muscular syndrome. Patients treated within a 2-year period from April 1, 2002 to March 31, 2004 reported good outcomes in 83.8% for headache, 88.4% for vertigo and dizziness, 84.5% for chronic fatigue syndrome, 88.0% for autonomic dystonia, and 83.7% for whiplash-associated disorder. A large number of outpatients present with general malaise, including many general physical complaints without identifiable cause. We propose that treatment of the cervical muscle is effective for general malaise.

 

Source: Matsui T, Ii K, Hojo S, Sano K. Cervical neuro-muscular syndrome: discovery of a new disease group caused by abnormalities in the cervical muscles. Neurol Med Chir (Tokyo). 2012;52(2):75-80. https://www.jstage.jst.go.jp/article/nmc/52/2/52_2_75/_pdf (Full article)

 

Lyme disease in a British referral clinic

Abstract:

BACKGROUND: Concerns about over-diagnosis and inappropriate management of Lyme disease (LD) are well documented in North America and supported by clinical data. There are few parallel data on the situation in the UK.

AIM: To describe the patterns of referral, investigation, diagnosis and treatment of patients with suspected LD referred to an infectious disease unit in Liverpool, UK. Previous management by National Health Service (NHS) and non-NHS practitioners was reviewed.

DESIGN: Descriptive study conducted by retrospective casenotes review.

METHODS: Retrospective case notes review of adults referred with possible LD to an infectious disease unit in Liverpool, UK, over 5 years (2006-2010).

RESULTS: Of 115 patients, 27 (23%) were diagnosed with LD, 38 (33%) with chronic fatigue syndrome (CFS) and 13 (11%) with other medical conditions. No specific diagnosis could be made in 38 (33%). At least 53 unnecessary antibiotic courses had been given by non-NHS practitioners; 21 unnecessary courses had been prescribed by NHS practitioners. Among 38 patients, 17 (45%) with CFS had been misdiagnosed as having LD by non-NHS practitioners.

CONCLUSION: A minority of referred patients had LD, while a third had CFS. LD is over-diagnosed by non-specialists, reflecting the complexities of clinical and/or laboratory diagnosis. Patients with CFS were susceptible to misdiagnosis in non-NHS settings, reinforcing concerns about missed opportunities for appropriate treatment for this group and about the use of inappropriate diagnostic modalities and anti-microbials in non-NHS settings.

Comment in: [Borreliosis]. [Orthopade. 2013]

 

Source: Cottle LE, Mekonnen E, Beadsworth MB, Miller AR, Beeching NJ. Lyme disease in a British referral clinic. QJM. 2012 Jun;105(6):537-43. doi: 10.1093/qjmed/hcs003. Epub 2012 Feb 1. http://qjmed.oxfordjournals.org/content/105/6/537.long (Full article)

 

Adrenal histoplasmosis: a case series and review of the literature

Abstract:

Adrenal histoplasmosis is an uncommon mycotic disease typically caused by Histoplasma capsulatum. The objective was to determine the clinicopathological findings in adrenal histoplasmosis.

Pathological records were searched from the database at the Department of Pathology, Faculty of Medicine Ramathibodi Hospital, Mahidol University from 1993 to 2008 for cases of adrenal histoplasmosis. The keywords were “histoplasmosis” and “adrenal gland”.

Adrenal histoplasmosis was diagnosed by histopathology and Gomori-Grocott methenamine silver staining. Histoplasma capsulatum was confirmed by tissue culture and/or serology. The authors report seven cases of adrenal histoplasmosis in immunocompetent patients. The mean age at diagnosis was 67 years. All patients presented as chronic fatigue syndrome.

The onset of symptoms ranged from one to three months. Addison’s disease was found in adrenal histoplasmosis in one case (14.3%). The computed tomography revealed adrenal nodules measuring 1.2 to 7.8 cm in diameter.

The histopathology showed granulomatous inflammation with caseous necrosis. Culture of adrenal tissue from two patients revealed Histoplasma capsulatum. Serum Histoplasma antibodies were positive in four cases. A cure was accomplished in 6 out of 7 cases (85.7%). The patients were followed up for 2.5 to 16.5 years.

 

Source: Larbcharoensub N, Boonsakan P, Aroonroch R, Rochanawutanon M, Nitiyanant P, Phongkitkarun S, Poonvutikul S, Watcharananan SP, Ngarmukos C. Adrenal histoplasmosis: a case series and review of the literature. Southeast Asian J Trop Med Public Health. 2011 Jul;42(4):920-5. https://www.ncbi.nlm.nih.gov/pubmed/22299474