Tag: chronic fatigue syndrome vs fibromyalgia

The effect of comorbid medical diagnoses on disturbed sleep in chronic fatigue syndrome

Abstract:

Background: Chronic fatigue syndrome [CFS] may occur alone or with fibromyalgia. This has led some to believe the two occur along a common illness spectrum. Evaluating whether this is the case is important as differences in burden or severity of CFS with fibromyalgia (FM) would suggest different underlying pathophysiological processes.

Objective: To determine if Insomnia Severity Index [ISI] scores differ between patients with CFS and those with CFS plus FM. In addition, we aim to determine if insomnia severity is impacted by other comorbid medically unexplained diagnoses.

Methods: 247 patients with CFS completed the ISI and the Centers for Epidemiological Study – Depression. Patient groups were stratified on CFS severity and the presence of FM. A secondary analysis was conducted to evaluate insomnia severity related to the number of comorbid medically unexplained diagnoses including, FM, multiple chemical sensitivity and/or irritable bowel syndrome.

Results: When controlling for depressed mood, ISI did not differ significantly across patient groups defined by CFS severity and FM status. However, independent of mood, ISI was sensitive to multiple diagnoses showing a significant increasing trend from CFS alone to CFS plus one, two or three comorbid diagnoses.

Conclusion: Although CFS severity and FM status do not impact insomnia severity, increased illness burden as manifested by multiple medically unexplained diagnoses does appear to influence insomnia. In contrast to our earlier studies, this study did not find that a comorbid diagnosis of FM in patients with CFS is related to a worse outcome in the variable of interest.

Source: Aaron J. Stegner, Michelle Blate & Benjamin H. Natelson (2024) The effect of comorbid medical diagnoses on disturbed sleep in chronic fatigue syndrome, Fatigue: Biomedicine, Health & Behavior, DOI: 10.1080/21641846.2024.2322915 https://www.tandfonline.com/doi/full/10.1080/21641846.2024.2322915

Nutrition and Chronobiology as Key Components of Multidisciplinary Therapeutic Interventions for Fibromyalgia and Associated Chronic Fatigue Syndrome: A Narrative and Critical Review

Abstract:

Fibromyalgia (FM) is often accompanied by chronic fatigue syndrome (CFS). It is a poorly understood disorder that mainly affects women and leads to chronic pain, fatigue, and insomnia, among other symptoms, which decrease quality of life. Due to the inefficiency of current pharmacological treatments, increasing interest is being directed towards non-pharmacological multicomponent therapies. However, nutrition and chronobiology are often overlooked when developing multicomponent therapies.

This narrative and critical review explore the relevance of nutritional and chronobiological strategies in the therapeutic management of FM and the often-associated CFS. Reviewed literature offers scientific evidence for the association of dietary habits, nutrient levels, body composition, gut microbiota imbalance, chronobiological alterations, and their interrelation with the development and severity of symptoms. This review highlights the key role of nutrition and chronobiology as relevant and indispensable components in a multidisciplinary approach to FM and CFS.

Source: Carrasco-Querol N, Cabricano-Canga L, Bueno Hernández N, Gonçalves AQ, Caballol Angelats R, Pozo Ariza M, Martín-Borràs C, Montesó-Curto P, Castro Blanco E, Dalmau Llorca MR, et al. Nutrition and Chronobiology as Key Components of Multidisciplinary Therapeutic Interventions for Fibromyalgia and Associated Chronic Fatigue Syndrome: A Narrative and Critical Review. Nutrients. 2024; 16(2):182. https://doi.org/10.3390/nu16020182 https://www.mdpi.com/2072-6643/16/2/182 (Full text)

DNA Methylation Changes in Blood Cells of Fibromyalgia and Chronic Fatigue Syndrome Patients

Abstract:

Purpose: Fibromyalgia (FM) and Chronic Fatigue Syndrome (CFS) affect 0.4% and 1% of society, respectively, and the prevalence of these pain syndromes is increasing. To date, no strong association between these syndromes and the genetic background of affected individuals has been shown. Therefore, it is plausible that epigenetic changes might play a role in the development of these syndromes.

Patients and Methods: Three previous studies have attempted to elaborate the involvement of genome-wide methylation changes in blood cells in the development of fibromyalgia and chronic fatigue syndrome. These studies included 22 patients with fibromyalgia and 127 patients with CFS, and the results of the studies were largely discrepant. Contradicting results of those studies may be attributed to differences in the omics data analysis approaches used in each study. We reanalyzed the data collected in these studies using an updated and coherent data-analysis framework.

Results: Overall, the methylation changes that we observed overlapped with previous results only to some extent. However, the gene set enrichment analyses based on genes annotated to methylation changes identified in each of the analyzed datasets were surprisingly coherent and uniformly associated with the physiological processes that, when affected, may result in symptoms characteristic of fibromyalgia and chronic fatigue syndrome

Conclusion: Methylomes of the blood cells of patients with FM and CFS in three independent studies have shown methylation changes that appear to be implicated in the pathogenesis of these syndromes.

Source: Przybylowicz PK, Sokolowska KE, Rola H, Wojdacz TK. DNA Methylation Changes in Blood Cells of Fibromyalgia and Chronic Fatigue Syndrome Patients. J Pain Res. 2023;16:4025-4036 https://doi.org/10.2147/JPR.S439412 https://www.dovepress.com/dna-methylation-changes-in-blood-cells-of-fibromyalgia-and-chronic-fat-peer-reviewed-fulltext-article-JPR (Full text)

A systematic review of quantitative EEG findings in Long COVID, Fibromyalgia and Chronic Fatigue Syndrome

Abstract:

Long COVID (LC) is a multisymptom clinical syndrome with similarities to Fibromyalgia Syndrome (FMS) and Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME). All these conditions are believed to be associated with centrally driven mechanisms such as central sensitisation.

There is a lack of consensus on quantitative EEG (qEEG) changes observed in these conditions. This review aims to synthesise and appraise the literature on resting-state qEEG in LC, FMS and CFS/ME, to help uncover possible mechanisms of central sensitisation in these similar clinical syndromes.

A systematic search of MEDLINE, Embase, CINHAL, PsycINFO and Web of Science databases for articles published between December 1994 and September 2023 was performed. Following screening for predetermined selection criteria and out of the initial 2510 studies identified, 17 articles were retrieved that met all the inclusion criteria, particularly of assessing qEEG changes in one of the three conditions compared to healthy controls. All studies scored moderate to high quality on the Newcastle-Ottawa scale.

There was a general trend for decreased low frequency EEG band activity (delta, theta, and alpha) and increased high-frequency EEG beta activity in FMS, whereas an opposite trend was found in CFS/ME. The limited LC studies included in this review focused mainly on cognitive impairments and showed mixed findings not consistent with patterns seen in FMS and CFS/ME.

Further research is required to explore whether there are phenotypes within LC that have EEG signatures similar to FMS or CFS/ME. This could inform identification of reliable diagnostic markers and possible targets for neuromodulation therapies.

Source: Bárbara Silva-Passadouro, Arnas Tamasauskas, Omar Khoja, Alexander J. Casson, Ioannis Delis, Christopher Brown, Manoj Sivan. A systematic review of quantitative EEG findings in Long COVID, Fibromyalgia and Chronic Fatigue Syndrome. medRxiv [Preprint] https://www.medrxiv.org/content/10.1101/2023.11.06.23298171v1.full-text (Full text)

HERV activation segregates ME/CFS from fibromyalgia and defines a novel nosological entity for patients fulfilling both clinical criteria

Abstract:

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and fibromyalgia (FM) are chronic diseases with poorly understood pathophysiology and diagnosis based on clinical assessment of unspecific symptoms. The recent post-COVID-19 condition, which shares similarities with ME/CFS and FM, has raised concerns about viral-induced transcriptome changes in post-viral syndromes. Viral infections, and other types of stress, are known to unleash human endogenous retroviruses (HERV) repression that if maintained could lead to symptom chronicity. This study evaluated this possibility for ME/CFS and FM on a selected cohort of female patients complying with diagnosis criteria for ME/CFS, FM, or both, and matched healthy controls (n=43).

The results show specific HERV fingerprints for each disease, confirming biological differences between ME/CFS and FM. Unexpectedly, HERV profiles segregated patients that met both ME/CFS and FM clinical criteria from patients complying only with ME or FM criteria, while clearly differentiating patients from healthy subjects, supporting that the highly prevalent comorbidity condition must constitute a different nosological entity.

Moreover, HERV profiles exposed significant quantitative differences within the ME/CFS group that correlated with differences in immune gene expression and patient symptomatology, supporting ME/CFS patient subtyping and confirming immunological disturbances in this disease. Pending issues include validation of HERV profiles as disease biomarkers of post-viral syndromes and understanding the role of HERV during infection and beyond.

Source: Karen Gimenez-Orenga, Eva Martin-Martinez, Lubov Nathanson, Elisa Oltra. HERV activation segregates ME/CFS from fibromyalgia and defines a novel nosological entity for patients fulfilling both clinical criteria. bioRxiv 2023.10.05.561025; doi: https://doi.org/10.1101/2023.10.05.561025 https://www.biorxiv.org/content/10.1101/2023.10.05.561025v1 (Full text available as PDF file)

 

Prevalence of Fibromyalgia and Chronic Fatigue Syndrome among Individuals with Irritable Bowel Syndrome: An Analysis of United States National Inpatient Sample Database

Abstract:

Background and Aim: Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder associated with other somatic disorders. We studied the prevalence and predictors of fibromyalgia and chronic fatigue syndrome (CFS) in IBS patients.
Methods: We used the National Inpatient Sample and included hospitalization of individuals with IBS, using ICD-10 codes, from 2016–2019. The prevalence and predictors of fibromyalgia and CFS in IBS patients were studied. Univariate and multivariate patient- and hospital-level regression models were used to calculate the adjusted odds of fibromyalgia and CFS in the IBS patient population.
Results: Of 1,256,325 patients with an ICD-10 code of IBS included in the study, 10.73% (134,890) also had ICD-10 codes for fibromyalgia and 0.42% (5220) for CFS. The prevalence of fibromyalgia and CFS was significantly higher in IBS patients (adjusted odds ratio (AOR) 5.33, 95% confidence interval (CI) 5.24–5.41, p < 0.001, and AOR 5.40, 95% CI 5.04–5.78, p < 0.001, respectively) compared to the general adult population without IBS. IBS-diarrhea, IBS-constipation, and IBS-mixed types were independently associated with increased odds of fibromyalgia and CFS. Increasing age (AOR 1.02, 95% CI 1.01–1.04, p 0.003; AOR 1.02, 95% CI 1.01–1.03, p 0.001), female gender (AOR 11.2, 95% CI 11.1–11.4, p < 0.001; AOR 1.86, 95% CI 1.78–1.93, p < 0.001) and white race (AOR 2.04, 95% CI 1.95–2.12, p < 0.001; AOR 1.69, 95% CI 1.34–2.13, p < 0.001) were independent predictors of increased odds of fibromyalgia and CFS, respectively.
Conclusions: It appears that IBS is associated with an increased prevalence of somatic disorders such as fibromyalgia and CFS.
Source: Tarar ZI, Farooq U, Nawaz A, Gandhi M, Ghouri YA, Bhatt A, Cash BD. Prevalence of Fibromyalgia and Chronic Fatigue Syndrome among Individuals with Irritable Bowel Syndrome: An Analysis of United States National Inpatient Sample Database. Biomedicines. 2023; 11(10):2594. https://doi.org/10.3390/biomedicines11102594 https://www.mdpi.com/2227-9059/11/10/2594 (Full text)

Myalgic encephalomyelitis/chronic fatigue syndrome and fibromyalgia are indistinguishable by their cerebrospinal fluid proteomes

Abstract:

Background: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and fibromyalgia have overlapping neurologic symptoms particularly disabling fatigue. This has given rise to the question whether they are distinct central nervous system (CNS) entities or is one an extension of the other.

Material and methods: To investigate this, we used unbiased quantitative mass spectrometry-based proteomics to examine the most proximal fluid to the brain, cerebrospinal fluid (CSF). This was to ascertain if the proteome profile of one was the same or different from the other. We examined two separate groups of ME/CFS, one with (n = 15) and one without (n = 15) fibromyalgia.

Results: We quantified a total of 2083 proteins using immunoaffinity depletion, tandem mass tag isobaric labelling and offline two-dimensional liquid chromatography coupled to tandem mass spectrometry, including 1789 that were quantified in all the CSF samples. ANOVA analysis did not yield any proteins with an adjusted p value <.05.

Conclusion: This supports the notion that ME/CFS and fibromyalgia as currently defined are not distinct entities.

Key message: ME/CFS and fibromyalgia as currently defined are not distinct entities. Unbiased quantitative mass spectrometry-based proteomics can be used to discover cerebrospinal fluid proteins that are biomarkers for a condition such as we are studying.

Source: Schutzer SE, Liu T, Tsai CF, Petyuk VA, Schepmoes AA, Wang YT, Weitz KK, Bergquist J, Smith RD, Natelson BH. Myalgic encephalomyelitis/chronic fatigue syndrome and fibromyalgia are indistinguishable by their cerebrospinal fluid proteomes. Ann Med. 2023 Dec;55(1):2208372. doi: 10.1080/07853890.2023.2208372. Epub 2023 Sep 18. PMID: 37722890. https://www.tandfonline.com/doi/full/10.1080/07853890.2023.2208372 (Full text)

Increased gut permeability and bacterial translocation are associated with fibromyalgia and myalgic encephalomyelitis/chronic fatigue syndrome: implications for disease-related biomarker discovery

Abstract:

Background: There is growing evidence of the significance of gastrointestinal complaints in the impairment of the intestinal mucosal barrier function and inflammation in fibromyalgia and myalgic encephalomyelitis/chronic fatigue syndrome. However, data on intestinal permeability and gut barrier dysfunction in FM and ME/CFS are still limited with conflicting results. This study aimed to assess circulating biomarkers potentially related to intestinal barrier dysfunction and bacterial translocation and their association with self-reported symptoms in these conditions.

Methods: A pilot multicentre, cross-sectional cohort study with consecutive enrolment of 22 patients with FM, 30 with ME/CFS, and 26 matched healthy controls. Plasma levels of anti-beta-lactoglobulin antibodies (IgG anti-beta-LGB), zonulin-1 (ZO-1), LPS, sCD14, and IL-1β) were assayed using ELISA. Demographic and clinical characteristics of the participants were recorded using validated self-reported outcome measures. The diagnostic accuracy of each biomarker was assessed using the ROC curve analysis.

Results: FM patients had significantly higher levels of anti-β-LGB, ZO-1, LPS, and sCD14 than healthy controls (all P < 0.0001). In ME/CFS patients, levels of anti-β-LGB, ZO-1, LPS, and sCD14 were significantly higher than controls, but lower than in FM (all P < 0.01), while there was no significant difference in IL-1β level. In the FM and ME/CFS cohorts, both anti-β-LGB and ZO-1 correlated significantly with LPS and sCD14 (P < 0.001 for both). In the FM group, both anti-beta-LGB and ZO-1 were correlated significantly with physical and mental health components on the SF-36 scale (P < 0.05); whereas IL-1beta negatively correlated with the COMPASS-31 score (P < 0.05). In the ME/CFS cohort, ZO-1 was positively correlated with the COMPASS-31 score (P < 0.05). The ROC curve analysis indicated a strong ability of anti-β-LGB, ZO-1, LPS, and sCD14 to predictively distinguish between FM and ME/CFS from healthy controls (P < 0.0001).

Conclusions: Biomarkers of intestinal barrier function and inflammation were associated with autonomic dysfunction assessed by COMPASS-31 scores in FM and ME/CFS respectively. Anti-β-LGB antibodies, ZO-1, LPS, and sCD14 may be putative predictors of intestinal barrier dysfunction in these cohorts. Further studies are needed to assess whether these findings are causal and can therefore be applied in clinical practice.

Source: Franz Martin, Manuel Blanco Suárez2 Paola Zambrano, Óscar Cáceres Calle, Miriam Almirall, Jose Alegre-Martín, Beatriz Lobo, Ana María Gonzalez-Castro, Javier Santos, Joan Carles Domingo, Joanna Jurek, Jesús Castro-Marrero. Increased gut permeability and bacterial translocation are associated with fibromyalgia and myalgic encephalomyelitis/chronic fatigue syndrome: implications for disease-related biomarker discovery. Front. Immunol., Sec. Mucosal Immunity, Volume 14 – 2023 | doi: 10.3389/fimmu.2023.1253121 https://www.frontiersin.org/articles/10.3389/fimmu.2023.1253121/abstract

DNA methylation signatures of functional somatic syndromes: Systematic review

Abstract:

Objective: Functional somatic syndromes (FSS) are highly prevalent across all levels of healthcare. The fact that they are characterised by medically unexplained symptoms, such as fatigue and pain, raises the important question of their underlying pathophysiology. Psychosocial stress represents a significant factor in the development of FSS and can induce long-term modifications at the epigenetic level. The aim of this review was to systematically review, for the first time, whether individuals with FSS are characterised by specific alterations in DNA methylation.

Methods: MEDLINE and PsycINFO were searched from the first available date until September 2022. The inclusion criteria were: 1) adults fulfilling research diagnostic criteria for chronic fatigue syndrome, fibromyalgia syndrome, and/or irritable bowel syndrome, 2) healthy control group, and 3) candidate-gene or genome-wide study of DNA methylation.

Results: Sixteen studies (N = 957) were included. In candidate-gene studies, specific sites within NR3C1 were identified, which were hypomethylated in individuals with chronic fatigue syndrome compared to healthy controls. In genome-wide studies in chronic fatigue syndrome, a hypomethylated site located to LY86 and hypermethylated sites within HLA-DQB1 were found. In genome-wide studies in fibromyalgia syndrome, differential methylation in sites related to HDAC4 , TMEM44 , KCNQ1 , SLC17A9 , PRKG1 , ALPK3 , TFAP2A , and LY6G5C was found.

Conclusions: Individuals with chronic fatigue syndrome and fibromyalgia syndrome appear to be characterised by altered DNA methylation of genes regulating cellular signalling and immune functioning. In chronic fatigue syndrome, there is preliminary evidence for these to be implicated in key pathophysiological alterations, such as hypocortisolism and low-grade inflammation, and to contribute to the debilitating symptoms these individuals experience.

Preregistration PROSPERO identifier: CRD42022364720.

Source: Fischer S, Kleinstäuber M, Fiori LM, Turecki G, Wagner J, von Känel R. DNA methylation signatures of functional somatic syndromes: Systematic review. Psychosom Med. 2023 Aug 21. doi: 10.1097/PSY.0000000000001237. Epub ahead of print. PMID: 37531610. https://pubmed.ncbi.nlm.nih.gov/37531610/

A Thesis on Immune Differences in Chronic Fatigue Syndrome, Fibromyalgia and Healthy Controls

Abstract:

Background: Chronic Fatigue Syndrome (CFS) and Fibromyalgia (FM) are debilitating disorders that significantly affect the daily lives of those suffering from them, as well as their loved ones. Both conditions have overlapping clinical features that resemble inflammatory disorders, and overlapping symptoms, such as depression, suggest central nervous system (CNS) involvement. The role of the immune system’s soluble messengers in the pathogenesis of CFS and FM has been under investigation, but so far the results are inconclusive. In addition, there is growing evidence that the kynurenine pathway is involved in the pathology of diseases related to the CNS, yet the role of each metabolite is not clear. The relationship between kynurenine metabolism and CFS and FM has not been extensively explored. Few studies have simultaneously examined the immunological status in both CFS and FM, making this thesis the first to comprehensively evaluate the potential distinct immunological differences between the two disorders.

Objective: The objective of this study was to compare the CFS and FM with healthy controls, regarding the levels of several soluble blood markers related to the immune system. The markers chosen were:

  • The inflammatory marker high-sensitive CRP (hsCRP)
  • The following cytokines and chemokines: Interferon (IFN)-γ, Interleukin (IL)-1β, IL1ra, IL-4, IL-6, IL-8, IL-10, IL-17, Interferon gamma-induced protein (IP)-10, Monocyte Chemoattractant Protein (MCP)-1, Transforming Growth Factor (TGF)-β1, TGF-β2, TGF-β3 and Tumour Necrosis Factor (TNF)-α
  • The metabolites and their ratios of the kynurenine pathway: Tryptophan (Try), kynurenine (Kyn), kynurenic acid (KA), 3-hydroxykykynurenine (HK), anthranilic acid (AA), xanthurenic acid (XA), 3-hydroxyanthranilic acid (HAA), quinolinic acid (QA) and picolinic acid (Pic).

Method: The population consisted of three groups: CFS patients (n = 49), FM patients (n = 58), and healthy controls (n = 54). All participants were females aged 18–60. Patients were recruited from a specialised university hospital clinic and controls were recruited by advertisement among the staff and students at the hospital and university.

Plasma levels of hsCRP were analysed at the hospital. The cytokines and chemokines IFN-γ, IL-1β, IL-1ra, xii IL-4, IL-6, IL-8, IL-10, IL-17, IP-10, MCP-1, TGF-β1, TGF-β2, TGF-β3, and TNF-α were analysed by multiplex. Kynurenine metabolites were analysed by LC-MS/MS.

Linear regression models of log-transformed data for hsCRP and the kynurenine metabolites were conducted for comparison of the three groups CFS, FM and controls. The Kruskal-Wallis test was used to analyse differences of cytokines between the three groups. Main findings were controlled for age, body mass index (BMI), and symptoms of anxiety and depression.

Results: hsCRP levels were significantly higher for both the CFS and FM groups compared to healthy controls when adjusting for age and BMI (p = .006). There was no difference between the two patient groups. Level of hsCRP was affected by BMI (p < .001) but not age.

MCP-1 was significantly increased in both patient groups compared to healthy controls (p < .001). IL-1β, Il-4, IL-6, TNF-α, TGF-β1, TGF-β2, TGF-β3 (all p < .001), IL-10 (p = .003) and IL17 (p = .002) all were significantly lower in the patient groups compared to healthy controls. IFN-γ was significantly lower in the FM group (p < .001). For IL-8, IP-10 and IL1ra there were no significant difference.

QA differed between CFS and FM patients (p = .036) and was related to higher levels of BMI (p = .002). The KA/QA ratio was lower for CFS patients compared to healthy controls (p = .016). The KA/HK ratio was lower for FM patients compared to healthy controls, and this lower ratio was associated with increased symptoms of pain (p = .002). The kynurenine aminotransferase II (KAT II) enzymatic activity given by XA/HK was lower for FM patients compared to healthy controls (p = .013). In addition, BMI was negatively associated with enhanced KAT II enzymatic activity (p = .039).

Symptoms of anxiety and depression were not associated with any of the immune markers studied.

Conclusion: In our material hsCRP and MCP-1 are increased in patients both with CFS and with FM, while several other cytokines are either similar or significantly lower in patients than controls. Our study also indicates associations between kynurenine metabolism and CFS and FM. Kynurenine also is associated with single symptoms such as fatigue and pain. Forthcoming studies indicating interactions and causative effects, or restoration of the inflammatory status, may place cytokines and kynurenine metabolites as a target for treatment as well as prevention of these conditions in the future.

Source: Groven, Nina. A Thesis on Immune Differences in Chronic Fatigue Syndrome, Fibromyalgia and Healthy Controls. PhD Thesis [Norwegian University of Science and Technology] https://ntnuopen.ntnu.no/ntnu-xmlui/handle/11250/3072207 (Full text available as PDF file)