Severe eosinophilic colitis caused by neuropathic agents in a patient with chronic fatigue syndrome and functional abdominal pain: case report and review of the literature

Abstract:

Eosinophilic colitis is a rare clinical condition that belongs to the group of eosinophilic gastrointestinal disorders. Its occurrence can be primary or secondary to infection, medications, or autoimmune/hematological conditions. We present a case of a young female adult with severe chronic fatigue syndrome, widespread chronic pain, including functional abdominal pain, who developed severe eosinophilic colitis following successive treatments with gabapentin and pregabalin. On both occasions, symptoms manifested as abdominal pain, diarrhea, and eosinophilia and improved upon discontinuation of the medications. Magnetic resonance imaging of the small bowel demonstrated an ascending colon colitis, and endoscopic investigations confirmed florid colitis mainly in the ascending colon with biopsies demonstrating a dense eosinophilic infiltrate with micro-abscesses. Serum eosinophil counts correlated well with the timing of the agents’ administration. There was no other organ involvement. Symptoms improved upon discontinuation of the drugs and steroid administration. Eosinophilic colitis is an exceptionally rare entity and its mechanism of action is still unclear. Suspicion of eosinophilic colitis should be raised if a patient presents with abdominal pain, diarrhea, and peripheral eosinophilia following treatment with pregabalin or gabapentin.

Source: Fragkos KC, Barragry J, Fernando CS, Novelli M, Begent J, Zárate-Lopez N.  Severe eosinophilic colitis caused by neuropathic agents in a patient with chronic fatigue syndrome and functional abdominal pain: case report and review of the literature. Z Gastroenterol. 2018 Jun;56(6):573-577. doi: 10.1055/a-0596-7981. Epub 2018 Jun 11. https://www.ncbi.nlm.nih.gov/pubmed/29890559

The High Costs of Low-Grade Inflammation: Persistent Fatigue as a Consequence of Reduced Cellular-Energy Availability and Non-adaptive Energy Expenditure

Abstract:

Chronic or persistent fatigue is a common, debilitating symptom of several diseases. Persistent fatigue has been associated with low-grade inflammation in several models of fatigue, including cancer-related fatigue and chronic fatigue syndrome. However, it is unclear how low-grade inflammation leads to the experience of fatigue. We here propose a model of an imbalance in energy availability and energy expenditure as a consequence of low-grade inflammation.

In this narrative review, we discuss how chronic low-grade inflammation can lead to reduced cellular-energy availability. Low-grade inflammation induces a metabolic switch from energy-efficient oxidative phosphorylation to fast-acting, but less efficient, aerobic glycolytic energy production; increases reactive oxygen species; and reduces insulin sensitivity. These effects result in reduced glucose availability and, thereby, reduced cellular energy.

In addition, emerging evidence suggests that chronic low-grade inflammation is associated with increased willingness to exert effort under specific circumstances. Circadian-rhythm changes and sleep disturbances might mediate the effects of inflammation on cellular-energy availability and non-adaptive energy expenditure.

In the second part of the review, we present evidence for these metabolic pathways in models of persistent fatigue, focusing on chronic fatigue syndrome and cancer-related fatigue. Most evidence for reduced cellular-energy availability in relation to fatigue comes from studies on chronic fatigue syndrome. While the mechanistic evidence from the cancer-related fatigue literature is still limited, the sparse results point to reduced cellular-energy availability as well.

There is also mounting evidence that behavioral-energy expenditure exceeds the reduced cellular-energy availability in patients with persistent fatigue. This suggests that an inability to adjust energy expenditure to available resources might be one mechanism underlying persistent fatigue.

Source: Lacourt TE, Vichaya EG, Chiu GS, Dantzer R, Heijnen CJ. The High Costs of Low-Grade Inflammation: Persistent Fatigue as a Consequence of Reduced Cellular-Energy Availability and Non-adaptive Energy Expenditure. Front Behav Neurosci. 2018 Apr 26;12:78. doi: 10.3389/fnbeh.2018.00078. eCollection 2018.  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5932180/ (Full article)

The putative role of oxidative stress and inflammation in the pathophysiology of sleep dysfunction across neuropsychiatric disorders: Focus on chronic fatigue syndrome, bipolar disorder and multiple sclerosis

Abstract:

Sleep and circadian abnormalities are prevalent and burdensome manifestations of diverse neuro-immune diseases, and may aggravate the course of several neuropsychiatric disorders. The underlying pathophysiology of sleep abnormalities across neuropsychiatric disorders remains unclear, and may involve the inter-play of several clinical variables and mechanistic pathways.

In this review, we propose a heuristic framework in which reciprocal interactions of immune, oxidative and nitrosative stress, and mitochondrial pathways may drive sleep abnormalities across potentially neuroprogressive disorders. Specifically, it is proposed that systemic inflammation may activate microglial cells and astrocytes in brain regions involved in sleep and circadian regulation. Activated glial cells may secrete pro-inflammatory cytokines (for example, interleukin-1 beta and tumour necrosis factor alpha), nitric oxide and gliotransmitters, which may influence the expression of key circadian regulators (e.g., the Circadian Locomotor Output Cycles Kaput (CLOCK) gene). Furthermore, sleep disruption may further aggravate oxidative and nitrosative, peripheral immune activation, and (neuro) inflammation across these disorders in a vicious pathophysiological loop.

This review will focus on chronic fatigue syndrome, bipolar disorder, and multiple sclerosis as exemplars of neuro-immune disorders. We conclude that novel therapeutic targets exploring immune and oxidative & nitrosative pathways (p.e. melatonin and molecular hydrogen) hold promise in alleviating sleep and circadian dysfunction in these disorders.

Source: Morris G, Stubbs B, Köhler CA, Walder K, Slyepchenko A, Berk M, Carvalho AF. The putative role of oxidative stress and inflammation in the pathophysiology of sleep dysfunction across neuropsychiatric disorders: Focus on chronic fatigue syndrome, bipolar disorder and multiple sclerosis. Sleep Med Rev. 2018 Apr 4. pii: S1087-0792(17)30152-1. doi: 10.1016/j.smrv.2018.03.007. [Epub ahead of print]  https://www.ncbi.nlm.nih.gov/pubmed/29759891

Are probiotic treatments useful on fibromyalgia syndrome or chronic fatigue syndrome patients? A systematic review

Abstract:

Evidence suggests that the gut microbiota might play an important role in fibromyalgia syndrome (FMS) and chronic fatigue syndrome (CFS). Our goal is to systematically review the reported effect of probiotic treatments in patients diagnosed with FMS or CFS. A systematic review was carried out using 14 databases (PubMed, Cochrane Library, Scopus, PsycINFO, and others) in February 2016 to search for randomised controlled trials (RCTs) and pilot studies of CFS or FMS patient, published in the last ten years (from 2006 to 2016). The Jadad scale was used to asseverate the quality of the clinical trials considered.

Two studies (n=83) met the inclusion criteria, which were performed in CFS patients and both studies were considered as a ‘High range of quality score’. The administration of Lactobacillus casei strain Shirota in CFS patients, over the course of 8 weeks, reduced anxiety scores. Likewise, this probiotic changed the faecal composition following 8 weeks of treatment. Additionally, the treatment with Bifidobacterium infantis 35624 in CFS patients, during the same period, reduced inflammatory biomarkers.

The evidence about the usefulness of probiotics in CFS and FMS patients remains limited. The studied strains of probiotics have demonstrated a significant effect on modulating the anxiety and inflammatory processes in CFS patients. However, more experimental research, focusing mainly on the symptoms of the pathologies studied, is needed.

Source: Roman P, Carrillo-Trabalón F, Sánchez-Labraca N, Cañadas F, Estévez AF, Cardona D. Are probiotic treatments useful on fibromyalgia syndrome or chronic fatigue syndrome patients? A systematic review.  Benef Microbes. 2018 Apr 26:1-10. doi: 10.3920/BM2017.0125. [Epub ahead of print]  https://www.ncbi.nlm.nih.gov/pubmed/29695180

Metabolic abnormalities in chronic fatigue syndrome/myalgic encephalomyelitis: a mini-review

Abstract:

Chronic fatigue syndrome (CFS), commonly known as myalgic encephalomyelitis (ME), is a debilitating disease of unknown etiology. CFS/ME is a heterogeneous disease associated with a myriad of symptoms but with severe, prolonged fatigue as the core symptom associated with the disease. There are currently no known biomarkers for the disease, largely due to the lack of knowledge surrounding the eitopathogenesis of CFS/ME. Numerous studies have been conducted in an attempt to identify potential biomarkers for the disease.

This mini-review offers a brief summary of current research into the identification of metabolic abnormalities in CFS/ME which may represent potential biomarkers for the disease. The progress of research into key areas including immune dysregulation, mitochondrial dysfunction, 5′-adenosine monophosphate-activated protein kinase activation, skeletal muscle cell acidosis, and metabolomics are presented here. Studies outlined in this mini-review show many potential causes for the pathogenesis of CFS/ME and identify many potential metabolic biomarkers for the disease from the aforementioned research areas.

The future of CFS/ME research should focus on building on the potential biomarkers for the disease using multi-disciplinary techniques at multiple research sites in order to produce robust data sets. Whether the metabolic changes identified in this mini-review occur as a cause or a consequence of the disease must also be established.

Source: Cara Tomas; Julia Newton. Metabolic abnormalities in chronic fatigue syndrome/myalgic encephalomyelitis: a mini-review. Biochemical Society Transactions Apr 17, 2018; DOI: https://doi.org/10.1042/BST20170503. http://www.biochemsoctrans.org/content/early/2018/04/16/BST20170503

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome – Evidence for an autoimmune disease

Abstract:

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a frequent and severe chronic disease drastically impairing life quality. The underlying pathomechanism is incompletely understood yet but there is convincing evidence that in at least a subset of patients ME/CFS has an autoimmune etiology.

In this review, we will discuss current autoimmune aspects for ME/CFS. Immune dysregulation in ME/CFS has been frequently described including changes in cytokine profiles and immunoglobulin levels, T- and B-cell phenotype and a decrease of natural killer cell cytotoxicity. Moreover, autoantibodies against various antigens including neurotransmitter receptors have been recently identified in ME/CFS individuals by several groups. Consistently, clinical trials from Norway have shown that B-cell depletion with rituximab results in clinical benefits in about half of ME/CFS patients.

Furthermore, recent studies have provided evidence for severe metabolic disturbances presumably mediated by serum autoantibodies in ME/CFS. Therefore, further efforts are required to delineate the role of autoantibodies in the onset and pathomechanisms of ME/CFS in order to better understand and properly treat this disease.

Source: Sotzny F, Blanco J, Capelli E, Castro-Marrero J, Steiner S1, Murovska M, Scheibenbogen C; European Network on ME/CFS (EUROMENE). Myalgic Encephalomyelitis/Chronic Fatigue Syndrome – Evidence for an autoimmune disease. Autoimmun Rev. 2018 Apr 7. pii: S1568-9972(18)30088-0. doi: 10.1016/j.autrev.2018.01.009. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/29635081

Pediatric chronic fatigue syndrome: current perspectives

Abstract:

Pediatric chronic fatigue syndrome is an important illness as it is relatively common and also very disabling with a wide range of impacts on the child, the family, and health care systems. It is a complicated illness but the majority of children get better with specialist treatment. This literature review provides an update on the epidemiology of chronic fatigue syndrome/myalgic encephalomyelitis, including factors associated with it, and discusses the current evidence for treatment.

Source: Esther Crawley. Pediatric chronic fatigue syndrome: current perspectives. Dove Press. 29 March 2018 Volume 2018:9 Pages 27—33 https://www.dovepress.com/pediatric-chronic-fatigue-syndrome-current-perspectives-peer-reviewed-article-PHMT (You can download a PDF file of the full article.)

A Systematic Review of Probiotic Interventions for Gastrointestinal Symptoms and Irritable Bowel Syndrome in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME)

Abstract:

Gastrointestinal (GI) symptoms and irritable bowel (IB) symptoms have been associated with chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME). The aim of this study was to conduct a systematic review of these symptoms in CFS/ME, along with any evidence for probiotics as treatment. Pubmed, Scopus, Medline (EBSCOHost) and EMBASE databases were searched to source relevant studies for CFS/ME. The review included any studies examining GI symptoms, irritable bowel syndrome (IBS) and/or probiotic use.

Studies were required to report criteria for CFS/ME and study design, intervention and outcome measures. Quality assessment was also completed to summarise the level of evidence available. A total of 3381 publications were returned using our search terms. Twenty-five studies were included in the review. Randomised control trials were the predominant study type (n = 24). Most of the studies identified examined the effect of probiotic supplementation on the improvement of IB symptoms in IBS patients, or IB symptoms in CFS/ME patients, as well as some other significant secondary outcomes (e.g. quality of life, other gastrointestinal symptoms, psychological symptoms).

The level of evidence identified for the use of probiotics in IBS was excellent in quality; however, the evidence available for the use of probiotic interventions in CFS/ME was poor and limited. There is currently insufficient evidence for the use of probiotics in CFS/ME patients, despite probiotic interventions being useful in IBS. The studies pertaining to probiotic interventions in CFS/ME patients were limited and of poor quality overall. Standardisation of protocols and methodology in these studies is required.

Source: Corbitt M, Campagnolo N, Staines D, Marshall-Gradisnik S. A Systematic Review of Probiotic Interventions for Gastrointestinal Symptoms and Irritable Bowel Syndrome in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME). Probiotics Antimicrob Proteins. 2018 Feb 20. doi: 10.1007/s12602-018-9397-8. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/29464501

Neurologic Abnormalities in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Review

Abstract:

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is an illness characterized by fatigue lasting for at least six months, post-exertional malaise, unrefreshing sleep, cognitive impairment and orthostatic intolerance. ME/CFS has been a controversial illness because it is defined exclusively by subjective complaints. However, recent studies of neuroimaging as well as analysis of blood markers, energy metabolism and mitochondrial function have revealed many objective biological abnormalities. Specifically, it is suspected that the symptoms of ME/CFS may be triggered by immune activation – either inside or outside the brain – through release of inflammatory cytokines. In this review, we summarize potentially important recent findings on ME/CFS, focusing on objective evidence.

Source: Komaroff AL, Takahashi R, Yamamura T, Sawamura M. Neurologic Abnormalities in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Review. Brain Nerve. 2018 Jan;70(1):41-54. doi: 10.11477/mf.1416200948. [Article in Japanese] https://www.ncbi.nlm.nih.gov/pubmed/29348374

An analysis of Dutch hallmark studies confirms the outcome of the PACE trial: cognitive behaviour therapy with a graded activity protocol is not effective for chronic fatigue syndrome and Myalgic Encephalomyelitis

Abstract:

Myalgic Encephalomyelitis (ME) and Chronic Fatigue Syndrome (CFS) are considered to be enigmatic diseases. Several studies propose that the combination of cognitive behaviour therapy with a graded activity protocol (CBT+), justified by a so-called (bio)psychosocial (explanatory) model, is an effective treatment option for CFS (ME).

Objective :A critical review of five Dutch hallmark studies that allegedly support this claim.

Methods: An analysis of the five CBT+ studies with special attention to the patients studied, the criteria (subjective and objective measures and cut-off scores) used to select participants and to define improvement and recovery, the consistency of the definitions of caseness (being diagnosed as a CFS patient at entry) versus the definitions of improvement and recovery after CBT+, and the objective effects.

Results: The studies investigated suffer from various methodological flaws. Apart from these methodological shortcomings, the claim that CBT+ is an effective treatment option for CFS is not substantiated by the data reported. Some studies investigated CFS patients, other studies investigated CF patients, labelled as CFS patients, or combinations of CFS and CF patients. No study investigated the effect of CBT+ in a group of patients meeting the (original) diagnostic criteria for ME. The effects of CBT+ on subjective measures, for example fatigue and disability, if present, are insufficient to achieve normal values. Impressive recovery and improvement rates are based on very loose criteria for subjective measures. Cut-off scores for subjective measures used to define improvement and recovery in studies show overlap with cut-off scores for CFS caseness in one or more of the other studies. More importantly, looking at the objective measures, the proof of clinical improvement after CBT+ is lacking.

Conclusion: Solid evidence of effectiveness of CBT+ for CFS, let alone ME, is lacking in the five hallmark studies. The lack of objective improvement indicates CBT+ is ineffective. This finding confirms the outcome of the large-scale PACE-trial in the UK.

Source: Twisk FNM (2017) An analysis of Dutch hallmark studies confirms the outcome of the PACE trial: cognitive behaviour therapy with a graded activity protocol is not effective for chronic fatigue syndrome and Myalgic Encephalomyelitis. Gen Med Open, 2017 doi: 10.15761/GMO.1000117 (Full article)