Category: Overlapping Illnesses

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Fibromyalgia: Definitions, Similarities, and Differences

Abstract:

This commentary presents a simplified way of making the diagnosis of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) using the 1994 Centers for Disease Control and Prevention case definition. The format used can easily be modified for other case definitions. The commentary then discusses whether ME/CFS is the same or a different illness from fibromyalgia.

Because overlap exists between the 2 syndromes, some investigators have posited that they are variants of the same illness. I have viewed this as an empirically testable hypothesis and have summoned considerable amounts of data that suggest that the 2 illnesses differ. Were differences to exist, that would suggest different pathophysiologic processes for each, leading to different treatments.

Copyright © 2019. Published by Elsevier Inc.

Source: Natelson BH. Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Fibromyalgia: Definitions, Similarities, and Differences. Clin Ther .2019 Feb 19. pii: S0149-2918(19)30003-7. doi: 10.1016/j.clinthera.2018.12.016. [Epub ahead of print]  https://www.ncbi.nlm.nih.gov/pubmed/30795933

Increased risk of chronic fatigue syndrome in patients with inflammatory bowel disease: a population-based retrospective cohort study

Abstract:

BACKGROUND: Similarities in the symptoms of chronic fatigue syndrome (CFS) and inflammatory bowel disease (IBD) have been observed as follows: severe disease activity in IBD correlates with severe fatigue, major psychiatric signs, the common use of medication, and bacterial translocation. One of several hypotheses for explaining the mechanisms underlying CFS suggests a similarity to the impaired intestinal mucosa of IBD. “This study investigated the risk of incident CFS among patients with IBD”.

METHODS: We conducted a population-based retrospective cohort study by using Taiwan’s National Health Insurance Research Database to evaluate the subsequent risk of CFS in patients with IBD, according to demographic characteristics and comorbidities. The exposure cohort comprised 2163 patients with new diagnoses of IBD. Each patient was randomly selected and frequency matching according to gender and age with four participants from the general population who had no history of CFS at the index date (control cohort). Cox proportional hazards regression analysis was conducted to estimate the relationship between IBD and the subsequent risk of CFS.

RESULTS: The exposure cohort had a significantly higher overall risk of subsequent CFS than that of the control group [adjusted hazard ratio (Christophi in Inflamm Bowel Dis 18(12):2342-2356, 2012) = 2.25, 95%, confidence interval (Aaron and Buchwald in Ann Intern Med 134(9 Pt 2):868-881, 2001; Farraye et al. in Am J Gastroenterol 112:241, 2017) 1.70-2.99]. Further analysis indicated a significantly higher risk of CFS in patients who were male (HR = 3.23, 95% CI 2.12-4.91), were older than 35 years, and had IBD but without comorbidity status, e.g. Cancers, diabetes, obesity, depression, anxiety, sleep disorder, renal disease (HR = 2.50, 95% CI 1.63-3.84) after adjustment.

CONCLUSION: The findings from this population-based retrospective cohort study suggest that IBD, especially Crohn’s disease, is associated with an increased risk of subsequent CFS.

Source: Tsai SY, Chen HJ, Lio CF, Kuo CF, Kao AC, Wang WS, Yao WC, Chen C, Yang TY. Increased risk of chronic fatigue syndrome in patients with inflammatory bowel disease: a population-based retrospective cohort study. J Transl Med. 2019 Feb 22;17(1):55. doi: 10.1186/s12967-019-1797-3. https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-019-1797-3 (Full article)

Silicone breast implants and depression, fibromyalgia and chronic fatigue syndrome in a rheumatology clinic population

Abstract:

INTRODUCTION: Silicone breast implants (SBI) may induce systemic autoimmune disease as part of autoimmune syndrome induced by adjuvants (ASIA). This syndrome bears similarities to fibromyalgia and chronic fatigue syndrome (CFS). We sought to determine whether there are any associations between SBI and depression, fibromyalgia and CFS in a rheumatology clinic population.

METHODS: The electronic files of rheumatology clinic patients at the Royal Adelaide Hospital between 2000 and 2017 were searched for patients who had received SBI prior to rheumatological diagnosis. Demographics, diagnosis, implant history and whether the patient had depression, fibromyalgia or CFS were recorded. Controls were rheumatology clinic patients, half of whom had systemic sclerosis (SSc) and the other half had systemic lupus erythematosus (SLE). They were matched to cases 3:1 for age (within 2 years) and gender.

RESULTS: Thirty patients had received SBI (mean age 47.9, 100% female). Twelve had a diagnosis of depression, 6 of fibromyalgia and 3 of CFS. Implant rupture was not associated with any of these (p = 1). There was no difference in the incidence of depression (p = 1), fibromyalgia (p = 0.76) or CFS (p = 0.3) between cases and SLE controls. When compared with SSc controls, there were significantly more patients with fibromyalgia and/or CFS in the case group (20.0% of cases vs 2.2% of SSc controls, p = 0.01) but no difference in depression (p = 0.12).

CONCLUSION: Fibromyalgia and CFS are more common in patients with silicone implants than SSc controls but not SLE controls. Prospective study of development of depression, fibromyalgia and CFS in recipients of SBI is required.

Source: Khoo T, Proudman S, Limaye V. Silicone breast implants and depression, fibromyalgia and chronic fatigue syndrome in a rheumatology clinic population. Clin Rheumatol. 2019 Jan 31. doi: 10.1007/s10067-019-04447-y. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/30706290

Cytokine profiles in patients with Q fever fatigue syndrome

Abstract:

Background: Q fever fatigue syndrome (QFS) is a state of prolonged fatigue following around 20% of acute Q fever cases. It is thought that chronic inflammation plays a role in its aetiology. To test this hypothesis we measured circulating cytokines and the exvivo cytokine production in patients with QFS and compared to various control groups.

Materials/methods: Peripheral blood mononuclear cells (PBMCs), whole blood, and serum were collected from 20 QFS patients, 19 chronic fatigue syndrome (CFS) patients, 19 Q fever seropositive controls, and 25 age- and sex-matched healthy controls. Coxiella-specific ex-vivo production of tumor necrosis factor (TNF)α, interleukin (IL)-1β, IL-6, and interferon (IFN) was measured, together with a total of 92 circulating inflammatory proteins.

Results: PBMCs of QFS patients produced more IL-6 (P = 0.0001), TNFα (P = 0.0002), and IL-1β (P = 0.0005) than the various control groups when stimulated with Coxiella antigen. QFS patients had distinct differences in circulating inflammatory markers compared to the other groups, including higher concentrations of circulating IL-6 and IFNγ.

Conclusion: QFS patients showed signs of chronic inflammation compared to asymptomatic Q fever seropositive controls, CFS patients, and healthy controls, of which the monocyte-derived cytokines TNFα, IL-1β, and especially IL-6, are likely crucial components.

Source: Raijmakers, Ruud P.H. et al. Cytokine profiles in patients with Q fever fatigue syndrome. Journal of Infection , Volume 0 , Issue 0 , DOI: https://doi.org/10.1016/j.jinf.2019.01.006

Hope, disappointment and perseverance: Reflections of people with Myalgic encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and Multiple Sclerosis participating in biomedical research. A qualitative focus group study

Abstract:

BACKGROUND: The Clinical Understanding and Research Excellence in ME/CFS group (CureME) at the London School of Hygiene & Tropical Medicine has supported and undertaken studies in immunology, genetics, virology, clinical medicine, epidemiology and disability. It established the UK ME/CFS Biobank (UKMEB), which stores data and samples from three groups: participants with ME/CFS, Multiple Sclerosis (MS) and healthy controls. Patient and public involvement have played a central role from its inception.

AIM: To explore the views of participants with ME/CFS and MS on CureME research findings, dissemination and future biomedical research priorities.

METHOD: Five ME/CFS and MS focus groups were conducted at two UK sites. Discussions were transcribed and analysed thematically.

RESULTS: A total of 28 UKMEB participants took part: 16 with ME/CFS and 12 with MS. Five themes emerged: (a) Seeking coherence: participants’ reactions to initial research findings; (b) Seeking acceptance: participants explore issues of stigma and validation; (c) Seeking a diagnosis: participants explore issues around diagnosis in their lives; (d) Seeking a better future: participants’ ideas on future research; and (e) Seeking to share understanding: participants’ views on dissemination. Focus groups perceived progress in ME/CFS and MS research in terms of “putting together a jigsaw” of evidence through perseverance and collaboration.

CONCLUSION: This study provides insight into the emotional, social and practical importance of research to people with MS and ME/CFS, suggesting a range of research topics for the future. Findings should inform biomedical research directions in ME/CFS and MS, adding patients’ voices to a call for a more collaborative research culture.

© 2018 The Authors Health Expectations published by John Wiley & Sons Ltd.

Source: Lacerda EM, McDermott C, Kingdon CC, Butterworth J, Cliff JM, Nacul L. Hope, disappointment and perseverance: Reflections of people with Myalgic encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and Multiple Sclerosis participating in biomedical research. A qualitative focus group study. Health Expect. 2019 Jan 10. doi: 10.1111/hex.12857. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/30632248

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

The link between idiopathic intracranial hypertension, fibromyalgia, and chronic fatigue syndrome: exploration of a shared pathophysiology

Abstract:

PURPOSE: Idiopathic intracranial hypertension (IICH) is a condition characterized by raised intracranial pressure (ICP), and its diagnosis is established when the opening pressure measured during a lumbar puncture is elevated >20 cm H2O in nonobese patients or >25 cm H2O in obese patients. Papilledema is caused by forced filling of the optic nerve sheath with cerebrospinal fluid (CSF). Other common but underappreciated symptoms of IICH are neck pain, back pain, and radicular pain in the arms and legs resulting from associated increased spinal pressure and forced filling of the spinal nerves with CSF. Widespread pain and also several other characteristics of IICH share notable similarities with characteristics of fibromyalgia (FM) and chronic fatigue syndrome (CFS), two overlapping chronic pain conditions. The aim of this review was to compare literature data regarding the characteristics of IICH, FM, and CFS and to link the shared data to an apparent underlying physiopathology, that is, increased ICP.

METHODS: Data in the literature regarding these three conditions were compared and linked to the hypothesis of the shared underlying physiopathology of increased cerebrospinal pressure.

RESULTS: The shared characteristics of IICH, FM, and CFS that can be caused by increased ICP include headaches, fatigue, cognitive impairment, loss of gray matter, involvement of cranial nerves, and overload of the lymphatic olfactory pathway. Increased pressure in the spinal canal and in peripheral nerve root sheaths causes widespread pain, weakness in the arms and legs, walking difficulties (ataxia), and bladder, bowel, and sphincter symptoms. Additionally, IICH, FM, and CFS are frequently associated with sympathetic overactivity symptoms and obesity. These conditions share a strong female predominance and are frequently associated with Ehlers-Danlos syndrome.

CONCLUSION: IICH, FM, and CFS share a large variety of symptoms that might all be explained by the same pathophysiology of increased cerebrospinal pressure.

Source: Hulens M, Rasschaert R, Vansant G, Stalmans I, Bruyninckx F, Dankaerts. The link between idiopathic intracranial hypertension, fibromyalgia, and chronic fatigue syndrome: exploration of a shared pathophysiology. J Pain Res. 2018 Dec 10;11:3129-3140. doi: 10.2147/JPR.S186878. eCollection 2018. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6292399/ (Full article)

Stress, inflammation and natural treatments

Abstract:

Stress and inflammation have become the curses of our times and are the main pathogenetic factors in multiple diseases that are often comorbid and include allergies and asthma, eczema and psoriasis, fibromyalgia syndrome, mast cell activation syndrome, irritable bowel syndrome, myalgic encephalomyelitis/chronic fatigue syndrome and autism spectrum disorder (ASD). Unfortunately, there are no effective drugs.

Cross-talk between mast cells and microglia in the hypothalamus and amygdala could explain stress-induced inflammation. We recently showed that the “alarmin” IL-33 could play a major role through its synergistic action with the neuropeptide substance P to stimulate human mast cell secretion of the pro-inflammatory molecules IL-1β, TNF and VEGF. A new formulation using pure luteolin with Ashwagandha has now been developed and could be of significant benefit to patients suffering from these diseases.

Source: Theoharides TC, Kavalioti M. Stress, inflammation and natural treatments. J Biol Regul Homeost Agents. 2018 Nov-Dec;32(6):1345-1347. https://www.ncbi.nlm.nih.gov/pubmed/30574737

Interferon-γ and CXCL10 responses related to complaints in patients with Q fever fatigue syndrome

Abstract:

Approximately 20% of patients with acute Q fever develop Q fever fatigue syndrome (QFS), a debilitating fatigue syndrome. This study further investigates the role of C. burnetii-specific IFNγ, but also IL-2, CXCL9, CXCL10, and CXLC11 production in QFS patients. C. burnetii-specific IFNy, IL-2, CXCL9, CXCL10, and CXCL11 production were tested in ex vivo stimulated whole blood of QFS patients who recovered from their complaints (n = 8), QFS patients with persisting complaints (n = 27), and asymptomatic Q fever seropositive controls (n = 10).

With the exclusion of one outlier, stimulation with C. burnetii revealed significantly higher IFNy and CXCL10 production in QFS patients with persisting complaints (medians 288.0 and 176.0 pg/mL, respectively) than in QFS patients who recovered from their complaints (medians 93.0 and 85.5 pg/mL, respectively) (p = 0.041 and 0.045, respectively). No significant differences between groups were found for C. burnetii-specific IL-2, CXCL9, and CXCL11 production.

These findings point towards a difference in cell-mediated immunity in QFS patients with persisting complaints compared to those who recovered from their complaints. Such a difference may aid to eventually diagnose QFS more objectively and might serve as an indicator of its underlying etiology.

Source: Raijmakers RPH, Jansen AFM, Keijmel SP, Schoffelen T, Scholzen A, van der Meer JWM, Joosten LAB, Netea MG, van Deuren M, Bleeker-Rovers CP. Interferon-γ and CXCL10 responses related to complaints in patients with Q fever fatigue syndrome. Eur J Clin Microbiol Infect Dis. 2018 Jul;37(7):1385-1391. doi: 10.1007/s10096-018-3265-z. Epub 2018 May 26. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6015096/ (Full article)

Recognizing the leaky gut as a trans-diagnostic target for neuro-immune disorders using clinical chemistry and molecular immunology assays

Abstract:

BACKGROUND: Increased intestinal permeability with heightened translocation of Gram-negative bacteria, also known as “leaky gut”, is associated with the pathophysiology of neuroimmune disorders, such as major depressive disorder (MDD), chronic fatigue syndrome (CSF) and (deficit) schizophrenia, as well as with general medical disorders, including irritable bowel syndrome. This review aims to summarize clinical biochemistry and molecular immunology tests that may aid in the recognition of leaky gut in clinical practice.

METHODS: We searched online libraries, including PubMed/MEDLINE, Google Scholar and Scopus, with the key words “diagnosis” or “biomarkers” and “leaky gut”, “bacterial translocation”, and “intestinal permeability” and focused on papers describing tests that may aid in the clinical recognition of leaky gut.

RESULTS: To evaluate tight junction barrier integrity, serum IgG/IgA/IgM responses to occludin and zonulin and IgA responses to actomyosin should be evaluated. The presence of cytotoxic bacterial products in serum can be evaluated using IgA/IgM responses to sonicated samples of common Gram-negative gut commensal bacteria and assays of serum lipopolysaccharides (LPSs) and other bacterial toxins, including cytolethal distenting toxin, subunit B. Major factors associated with increased gut permeability, including gut dysbiosis and yeast overgrowth, use of NSAIDs and alcohol, food hypersensitivities (IgE-mediated), food intolerances (IgG-mediated), small bacterial overgrowth (SIBO), systemic inflammation, psychosocial stressors, some infections (e.g., HIV) and dietary patterns, should be assessed. Stool samples can be used to assay gut dysbiosis, gut inflammation and decreased mucosal defenses using assays of fecal growth of bacteria, yeast and fungi and stool assays of calprotectin, secretory IgA, β-defensin, α-antitrypsin, lysozyme and lactoferrin. Blood and breath tests should be used to exclude common causes of increased gut permeability, namely, food hypersensitivities and intolerances, SIBO, lactose intolerance and fructose malabsorption.

DISCUSSION: Here, we propose strategies to recognize “leaky gut” in a clinical setting using the most adequate clinical chemistry and molecular immunology assays.

Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Source: Simeonova D, Ivanovska M, Murdjeva M, Carvalho AF, Maes M. Recognizing the leaky gut as a trans-diagnostic target for neuro-immune disorders using clinical chemistry and molecular immunology assays. Curr Top Med Chem. 2018 Nov 14. doi: 10.2174/1568026618666181115100610. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/30430944