Pain in patients with chronic fatigue syndrome: time for specific pain treatment?

Abstract:

BACKGROUND: Besides chronic fatigue, patients with chronic fatigue syndrome (CFS) have debilitating widespread pain. Yet pain from CFS is often ignored by clinicians and researchers.

OBJECTIVES: To examine whether pain is a unique feature of CFS, or does it share the same underlying mechanisms as other CFS symptoms? Second, it is examined whether effective treatments for pain from CFS are currently available.

STUDY DESIGN: Narrative review covering the scientific literature up through December 2011.

SETTING: Several universities.

RESULTS: From the available literature, it is concluded that musculoskeletal factors are unlikely to account for pain from CFS. Pain seems to be one out of many symptoms related to central sensitization from CFS. This idea is supported by the findings of generalized hyperalgesia (including widespread increased responsiveness to painful stimuli) and dysfunctional endogenous analgesia in response to noxious thermal stimuli. Pain catastrophizing and depression partly account for pain from CFS. Pain increases during exercise is probably due to the lack of endogenous analgesia and activation of several genes in response to exercise in CFS. There is currently no evidence in support for the efficacy of complementary medicine in the treatment of pain from CFS. Intensive education about the biology of pain from CFS (within the framework of central sensitization) has positive short-term effects for patients with CFS, and fatigue-targeting cognitive behavioral therapy appears to be effective for pain from CFS as well.

LIMITATIONS: The role of the deficient hypothalamus-pituitary-adrenal axis in relation to pain from CFS, as well as the interactions with immune (dys)functioning require further study.

CONCLUSION: Recent research has increased our understanding of pain from CFS, including its treatment. It is advocated to optimize current CFS treatment protocols by targeting the underlying mechanism for those patients having severe pain.

 

Source: Nijs J, Crombez G, Meeus M, Knoop H, Damme SV, Cauwenbergh V, Bleijenberg G. Pain in patients with chronic fatigue syndrome: time for specific pain treatment? Pain Physician. 2012 Sep-Oct;15(5):E677-86. http://www.painphysicianjournal.com/linkout?issn=1533-3159&vol=15&page=E677 (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)

 

Biomarkers for chronic fatigue

Abstract:

Fatigue that persists for 6 months or more is termed chronic fatigue. Chronic fatigue (CF) in combination with a minimum of 4 of 8 symptoms and the absence of diseases that could explain these symptoms, constitute the case definition for chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME).

Inflammation, immune system activation, autonomic dysfunction, impaired functioning in the hypothalamic-pituitary-adrenal axis, and neuroendocrine dysregulation have all been suggested as root causes of fatigue. The identification of objective markers consistently associated with CFS/ME is an important goal in relation to diagnosis and treatment, as the current case definitions are based entirely on physical signs and symptoms.

This review is focused on the recent literature related to biomarkers for fatigue associated with CFS/ME and, for comparison, those associated with other diseases. These markers are distributed across several of the body’s core regulatory systems. A complex construct of symptoms emerges from alterations and/or dysfunctions in the nervous, endocrine and immune systems. We propose that new insight will depend on our ability to develop and deploy an integrative profiling of CFS/ME pathogenesis at the molecular level. Until such a molecular signature is obtained efforts to develop effective treatments will continue to be severely limited.

Copyright © 2012 Elsevier Inc. All rights reserved.

 

Source: Klimas NG, Broderick G, Fletcher MA. Biomarkers for chronic fatigue. Brain Behav Immun. 2012 Nov;26(8):1202-10. doi: 10.1016/j.bbi.2012.06.006. Epub 2012 Jun 23. https://www.ncbi.nlm.nih.gov/pubmed/22732129

 

How to exercise people with chronic fatigue syndrome: evidence-based practice guidelines

Abstract:

BACKGROUND: Despite the large number of studies emphasizing the effectiveness of graded exercise therapy (GET) and cognitive behavioural therapy (CBT) for people with chronic fatigue syndrome (CFS), clinicians are left wondering how exactly to apply exercise therapy to their patients with CFS. The aim of this literature review is to identify the appropriate exercise modalities (i.e. exercise duration, mode, number of treatment sessions, session length, duration of treatment, exercise intensity and whether or not to apply home exercise program) for people with CFS.

MATERIALS AND METHODS: All studies that were identified through electronic databases (PubMed and PEDro) were assessed for methodological quality by using selection criteria (Delphi score).

RESULTS: In this literature review, 12 studies fulfilled all study requirements. One study had a low methodological quality. The parameters used in the GET and CBT interventions were divided into subgroups: (i) time or symptom contingent, (ii) exercise frequency and (iii) exercise modality.

CONCLUSION: The lack of uniformity in outcome measures and CFS diagnostic criteria make it difficult to compare the findings across studies. Based on the available evidence, exercise therapy for people with CFS should be aerobic and must comprise of 10-11 sessions spread over a period of 4-5 months. A time-contingent approach is preferred over a symptom-contingent way of exercising. In addition, people with CFS can perform home exercises five times a week with an initial duration of 5-15 min per exercise session. The exercise duration can be gradually increased up to 30 min.

© 2012 The Authors. European Journal of Clinical Investigation

© 2012 Stichting European Society for Clinical Investigation Journal Foundation.

Comment in:

Graded exercise therapy (GET)/cognitive behavioural therapy (CBT) is often counterproductive in myalgic encephalomyelitis (ME) and chronic fatigue syndrome (CFS). [Eur J Clin Invest. 2012]

Exercise and chronic fatigue syndrome: maximize function, minimize post-exertional malaise. [Eur J Clin Invest. 2012]

Objective compliance and outcome measures should be used in trials of exercise interventions for Chronic Fatigue Syndrome. [Eur J Clin Invest. 2012]

 

Source: Van Cauwenbergh D De Kooning M, Ickmans K, Nijs J. How to exercise people with chronic fatigue syndrome: evidence-based practice guidelines. Eur J Clin Invest. 2012 Oct;42(10):1136-44. doi: 10.1111/j.1365-2362.2012.02701.x. Epub 2012 Jun 23. https://www.ncbi.nlm.nih.gov/pubmed/22725992

 

A neuro-immune model of Myalgic Encephalomyelitis/Chronic fatigue syndrome

Abstract:

This paper proposes a neuro-immune model for Myalgic Encephalomyelitis/Chronic fatigue syndrome (ME/CFS). A wide range of immunological and neurological abnormalities have been reported in people suffering from ME/CFS. They include abnormalities in proinflammatory cytokines, raised production of nuclear factor-κB, mitochondrial dysfunctions, autoimmune responses, autonomic disturbances and brain pathology. Raised levels of oxidative and nitrosative stress (O&NS), together with reduced levels of antioxidants are indicative of an immuno-inflammatory pathology. A number of different pathogens have been reported either as triggering or maintaining factors.

Our model proposes that initial infection and immune activation caused by a number of possible pathogens leads to a state of chronic peripheral immune activation driven by activated O&NS pathways that lead to progressive damage of self epitopes even when the initial infection has been cleared. Subsequent activation of autoreactive T cells conspiring with O&NS pathways cause further damage and provoke chronic activation of immuno-inflammatory pathways. The subsequent upregulation of proinflammatory compounds may activate microglia via the vagus nerve.

Elevated proinflammatory cytokines together with raised O&NS conspire to produce mitochondrial damage. The subsequent ATP deficit together with inflammation and O&NS are responsible for the landmark symptoms of ME/CFS, including post-exertional malaise. Raised levels of O&NS subsequently cause progressive elevation of autoimmune activity facilitated by molecular mimicry, bystander activation or epitope spreading. These processes provoke central nervous system (CNS) activation in an attempt to restore immune homeostatsis.

This model proposes that the antagonistic activities of the CNS response to peripheral inflammation, O&NS and chronic immune activation are responsible for the remitting-relapsing nature of ME/CFS. Leads for future research are suggested based on this neuro-immune model.

 

Source: Morris G, Maes M. A neuro-immune model of Myalgic Encephalomyelitis/Chronic fatigue syndrome. Metab Brain Dis. 2013 Dec;28(4):523-40. doi: 10.1007/s11011-012-9324-8. Epub 2012 Jun 21. https://www.ncbi.nlm.nih.gov/pubmed/22718491

 

Inflammatory fatigue and sickness behaviour – lessons for the diagnosis and management of chronic fatigue syndrome

Abstract:

Persistent and severe fatigue is a common part of the presentation of a diverse range of disease processes. There is a growing body of evidence indicating a common inflammatory pathophysiology underlying many conditions where fatigue is a primary patient concern, including chronic fatigue syndrome. This review explores current models of how inflammatory mediators act on the central nervous system to produce fatigue and sickness behaviour, and the commonality of these processes in conditions as diverse as surgical trauma, infection, various cancers, inflammatory bowel disease, connective tissue diseases and autoimmune diseases. We also discuss evidence indicating chronic fatigue syndrome may have important pathophysiological similarities with cytokine mediated sickness behaviour, and what lessons can be applied from sickness behaviour to chronic fatigue syndrome with regards to the diagnosis and management.

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

 

Source: Arnett SV, Clark IA. Inflammatory fatigue and sickness behaviour – lessons for the diagnosis and management of chronic fatigue syndrome. J Affect Disord. 2012 Dec 10;141(2-3):130-42. doi: 10.1016/j.jad.2012.04.004. Epub 2012 May 11. https://www.ncbi.nlm.nih.gov/pubmed/22578888

 

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

 

Pediatric Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Abstract:

Research on pediatric Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is reviewed in this article. Many recent articles in this area highlight the existence of key differences between the adult and pediatric forms of the illness. This review article provides an overview of pediatric ME/CFS, including epidemiology, diagnostic criteria, treatment, and prognosis. Challenges to the field are identified with the hope that in the future pediatric cases of ME/CFS can be more accurately diagnosed and successfully managed.

 

Source: Jason LA, Barker K, Brown A. Pediatric Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Rev Health Care. 2012 Jan 1;3(4):257-270. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3856907/ (Full article)

 

Treating chronic fatigue syndrome – a study into the scientific evidence for pharmacological treatments

Abstract:

BACKGROUND: Chronic fatigue syndrome, or myalgic encephalomyelitis (CFS), is a severe disabling condition. Patients with CFS usually trial many different medicines, both conventional and complementary. An overview of the pharmacological treatments used by CFS patients and the available evidence underpinning the use of these treatments would be of great value to both patients and their healthcare providers.

METHODS: Ninety-four CFS patients recruited into an Australian study investigating immunological biomarkers filled out a questionnaire assessing the medicines they were taking. Evidence from randomised clinical trials was sought in biomedical databases.

RESULTS: The 94 CFS patients used 474 different medicines and supplements. The most commonly used medicines were antidepressants, analgesics, sedatives, and B vitamins. We identified 20 randomised controlled trials studying these medicines in CFS patients.

DISCUSSION: While conventional and complementary medicines are widely used by CFS patients, the evidence for effectiveness in CFS is very limited.

 

Source: Kreijkamp-Kaspers S, Brenu EW, Marshall S, Staines D, Van Driel ML. Treating chronic fatigue syndrome – a study into the scientific evidence for pharmacological treatments. Aust Fam Physician. 2011 Nov;40(11):907-12. http://www.racgp.org.au/download/documents/AFP/2011/November/201111kkaspers.pdf (Full article)

 

The common immunogenic etiology of chronic fatigue syndrome: from infections to vaccines via adjuvants to the ASIA syndrome

Abstract:

Chronic fatigue syndrome (CFS) is characterized by unexplained fatigue that lasts for at least 6 months with a constellation of other symptoms. Most cases start suddenly, and are usually accompanied by a flu-like illness. It is a symptom-based diagnosis of exclusion, the pathogenesis of which is unknown. Studies have examined and hypothesized about the possible biomedical and epidemiologic characteristics of the disease, including genetic predisposition, infections, endocrine abnormalities, and immune dysfunction and psychological and psychosocial factors. Recently, the AISA (autoimmune/inflammatory syndrome induced by adjuvants) syndrome was recognized, indicating the possible contribution of adjuvants and vaccines to the development of autoimmunity.

Copyright © 2011 Elsevier Inc. All rights reserved.

 

Source: Rosenblum H, Shoenfeld Y, Amital H. The common immunogenic etiology of chronic fatigue syndrome: from infections to vaccines via adjuvants to the ASIA syndrome. Infect Dis Clin North Am. 2011 Dec;25(4):851-63. doi: 10.1016/j.idc.2011.07.012. Epub 2011 Sep 9. https://www.ncbi.nlm.nih.gov/pubmed/22054760