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

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

Chronic Fatigue Syndrome: From Chronic Fatigue to More Specific Syndromes

Abstract:

In the last decade, a group of chronic disorders associated with fatigue (CDAF) emerged as the leading cause of chronic fatigue, chronic pain, and functional impairment, all of which have been often labeled in clinical practice as chronic fatigue syndrome (CFS) or fibromyalgia. While these chronic disorders arise from various pathophysiologic mechanisms, a shared autoimmune or immune-mediated etiology could shift the focus from symptomatic treatment of fatigue and pain to targeted immunomodulatory and biological therapy.

A clinical paradigm shift is necessary to reevaluate CFS and fibromyalgia diagnoses and its relationship to the CDAF entities, which would ultimately lead to a change in diagnostic and therapeutic algorithm for patients with chronic fatigue and chronic pain. Rather than uniformly apply the diagnoses of CFS or fibromyalgia to any patient presenting with unexplained chronic fatigue or chronic pain, it may be more beneficial and therapeutically effective to stratify these patients into more specific diagnoses in the CDAF group.

Source: Blitshteyn S, Chopra P. Chronic Fatigue Syndrome: From Chronic Fatigue to More Specific Syndromes. Eur Neurol. 2018 Oct 4;80(1-2):73-77. doi: 10.1159/000493531. [Epub ahead of print]  https://www.ncbi.nlm.nih.gov/pubmed/30286454

Unraveling the Molecular Determinants of Manual Therapy: An Approach to Integrative Therapeutics for the Treatment of Fibromyalgia and Chronic Fatigue Syndrome/Myalgic Encephalomyelitis

Abstract:

Application of protocols without parameter standardization and appropriate controls has led manual therapy (MT) and other physiotherapy-based approaches to controversial outcomes. Thus, there is an urgency to carefully define standard protocols that elevate physiotherapy treatments to rigorous scientific demands. One way in which this can be achieved is by studying gene expression and physiological changes that associate to particular, parameter-controlled, treatments in animal models, and translating this knowledge to properly designed, objective, quantitatively-monitored clinical trials (CTs).

Here, we propose a molecular physiotherapy approach (MPTA) requiring multidisciplinary teams, to uncover the scientific reasons behind the numerous reports that historically attribute health benefits to MT-treatments. The review focuses on the identification of MT-induced physiological and molecular responses that could be used for the treatment of fibromyalgia (FM) and chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME).

The systemic effects associated to mechanical-load responses are considered of particular relevance, as they suggest that defined, low-pain anatomic areas can be selected for MT treatment and yet yield overall benefits, an aspect that might result in it being essential to treat FM. Additionally, MT can provide muscle conditioning to sedentary patients without demanding strenuous physical effort, which is particularly detrimental for CFS/ME patients, placing MT as a real option for integrative medicine programs to improve FM and CFS/ME.

Source: Espejo JA, García-Escudero M, Oltra E. Unraveling the Molecular Determinants of Manual Therapy: An Approach to Integrative Therapeutics for the Treatment of Fibromyalgia and Chronic Fatigue Syndrome/Myalgic Encephalomyelitis. Int J Mol Sci. 2018 Sep 9;19(9). pii: E2673. doi: 10.3390/ijms19092673. http://www.mdpi.com/1422-0067/19/9/2673 (Full article)

Recent insights into 3 underrecognized conditions

The Ontario Ministry of Health and Long-Term Care recently released the interim report of a task force charged with providing recommendations on 3 symptom-based conditions that have both shared and distinctive features (Box 1): myalgic encephalomyelitis–chronic fatigue syndrome (ME-CFS), fibromyalgia (FM), and environmental sensitivities–multiple chemical sensitivity (ES-MCS).

You can read the report HERE.

Poor self-reported sleep quality and health-related quality of life in patients with chronic fatigue syndrome/myalgic encephalomyelitis

Abstract:

Non-restorative sleep is a hallmark symptom of chronic fatigue syndrome/myalgic encephalomyelitis. However, little is known about self-reported sleep disturbances in these subjects. This study aimed to assess the self-reported sleep quality and its impact on quality of life in a Spanish community-based chronic fatigue syndrome/myalgic encephalomyelitis cohort.

A prospective cross-sectional cohort study was conducted in 1,455 Spanish chronic fatigue syndrome/myalgic encephalomyelitis patients. Sleep quality, fatigue, pain, functional capacity impairment, psychopathological status, anxiety/depression and health-related quality of life were assessed using validated subjective measures. The frequencies of muscular, cognitive, neurological, autonomic and immunological symptom clusters were above 80%.

High scores were recorded for pain, fatigue, psychopathological status, anxiety/depression, and low scores for functional capacity and quality of life, all of which correlated significantly (all p < 0.01) with quality of sleep as measured by the Pittsburgh Sleep Quality Index. Multivariate regression analysis showed that after adjusting for age and gender, the pain intensity (odds ratio, 1.11; p <0.05), psychopathological status (odds ratio, 1.85; p < 0.001), fibromyalgia (odds ratio, 1.39; p < 0.05), severe autonomic dysfunction (odds ratio, 1.72; p < 0.05), poor functional capacity (odds ratio, 0.98; p < 0.05) and quality of life (odds ratio, 0.96; both p < 0.001) were significantly associated with poor sleep quality.

These findings suggest that this large chronic fatigue syndrome/myalgic encephalomyelitis sample presents poor sleep quality, as assessed by the Pittsburgh Sleep Quality Index, and that this poor sleep quality is associated with many aspects of quality of life.

Source: Castro-Marrero J, Zaragozá MC, González-Garcia S, Aliste L, Sáez-Francàs N, Romero O, Ferré A, Fernández de Sevilla T, Alegre J.  Poor self-reported sleep quality and health-related quality of life in patients with chronic fatigue syndrome/myalgic encephalomyelitis. J Sleep Res. 2018 May 16:e12703. doi: 10.1111/jsr.12703. [Epub ahead of print]  https://www.ncbi.nlm.nih.gov/pubmed/29770505

Balance deficits in Chronic Fatigue Syndrome with and without fibromyalgia

Abstract:

OBJECTIVE: Chronic Fatigue Syndrome (CFS) is a disorder of unknown etiology associated with debilitating fatigue. One symptom commonly reported is disequilibrium. The goal of this study was to determine if CFS patients demonstrated verified balance deficits and if this was effected by comorbid fibromyalgia (FM).

METHODS: Twenty-seven patients with CFS (12 with comorbid FM) and 22 age and gender matched controls performed posturography.

RESULTS: Balance scores were significantly correlated with physical functional status in the CFS group (R2 = 0.43, P < 0.001), which was not found for mental functional status (R2 = 0.06, P > 0.5). CFS patients (regardless of FM) had significantly higher anxiety subscale of the vertigo symptom scale scores. CFS patients, regardless of FM status, demonstrated significantly lower overall composite balance scores (Controls – 78.8±1.5; CFS – 69.0±1.4, P < 0.005) even when controlling for anxiety and also had worse preference scores, indicating they relied on visual information preferentially even when visual information was incorrect. Interestingly, the CFS+FM group, not CFS only, demonstrated significantly worse vestibular scores (Controls – 70.2±2.4; CFS only – 67.9±3.8; CFS with FM – 55.4±4.6, P = 0.013).

INTERPRETATION: The major findings are that poor balance may be associated with poorer self-reported physical health. In addition, CFS patients seemed to rely preferentially on visual inputs, regardless of whether it was correct. The finding that vestibular function may be impaired in patients with CFS+FM but not in those with CFS alone suggests that the pathophysiology of CFS+FM may differ as has been suggested by some.

Source: Serrador JM, Quigley K, Zhao C, Findley T, Natelson BH. Balance deficits in Chronic Fatigue Syndrome with and without fibromyalgia. NeuroRehabilitation. 2018;42(2):235-246. doi: 10.3233/NRE-172245.

Influence of morphine and naloxone on pain modulation in Rheumatoid Arthritis, Chronic Fatigue Syndrome/Fibromyalgia and controls: a double blind randomized placebo-controlled cross-over study

Abstract:

BACKGROUND: Impaired pain inhibitory and enhanced pain facilitatory mechanisms are repeatedly reported in patients with central sensitization pain. However, the exact effects of frequently prescribed opioids on central pain modulation are still unknown.

METHODS: A randomized, double-blind, placebo-controlled cross-over trial was carried out. Ten CFS/FM patients, 11 RA patients and 20 controls were randomly allocated to the experimental (10 mg morphine or 0.2 mg/ml Naloxone) and placebo (2 ml Aqua) group. Pressure Pain Thresholds (PPTs) and temporal summation at the Trapezius and Quadriceps were assessed by algometry. Conditioned Pain Modulation (CPM) efficacy and Deep Tissue Pain pressure were assessed by adding ischemic occlusion at the opposite upper arm.

RESULTS: Deep Tissue Pain pressure was lower and temporal summation higher in CFS/FM (p=0.002 respectively p=0.010) and RA patients (p=0.011 respectively p=0.047) compared to controls at baseline. Morphine had only a positive effect on PPTs in both patient groups (p time =0.034). Accordingly, PPTs increased after placebo, and no effects on the other pain parameters were objectified. There were no significant effects of naloxone nor nocebo on PPT, Deep Tissue Pain, temporal summation or CPM in the control group.

CONCLUSIONS: This study revealed anti-hyperalgesia effects of morphine in CFS/FM and RA patients. Nevertheless, these effects were comparable to placebo. Besides, neither morphine nor naloxone influenced Deep Tissue Pain, temporal summation or CPM. Therefore, these results suggest that the opioid system is not dominant in (enhanced) bottom-up sensitization (temporal summation) or (impaired) endogenous pain inhibition (CPM) in patients with CFS/FM or RA.

This article is protected by copyright. All rights reserved.

Source: Hermans L, Nijs J, Calders P, De Clerck L, Moorkens G, Hans G, Grosemans S, Roman De Mettelinge T, Tuynman J, Meeus M. Influence of morphine and naloxone on pain modulation in Rheumatoid Arthritis, Chronic Fatigue Syndrome/Fibromyalgia and controls: a double blind randomized placebo-controlled cross-over study. Pain Pract. 2017 Jul 19. doi: 10.1111/papr.12613. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/28722815

A diagnostic biomarker profile for fibromyalgia syndrome based on an NMR metabolomics study of selected patients and controls

Abstract:

BACKGROUND: Fibromyalgia syndrome (FMS) is a chronic pain syndrome. A plausible pathogenesis of the disease is uncertain and the pursuit of measurable biomarkers for objective identification of affected individuals is a continuing endeavour in FMS research. Our objective was to perform an explorative metabolomics study (1) to elucidate the global urinary metabolite profile of patients suffering from FMS, and (2) to explore the potential of this metabolite information to augment existing medical practice in diagnosing the disease.

METHODS: We selected patients with a medical history of persistent FMS (n = 18), who described their recent state of the disease through the Fibromyalgia Impact Questionnaire (FIQR) and an in-house clinical questionnaire (IHCQ). Three control groups were used: first-generation family members of the patients (n = 11), age-related individuals without any indications of FMS or related conditions (n = 10), and healthy young (18-22 years) individuals (n = 20). All subjects were female and the biofluid under investigation was urine. Correlation analysis of the FIQR showed the FMS patients represented a well-defined disease group for this metabolomics study. Spectral analyses of urine were conducted using a 500 MHz 1H nuclear magnetic resonance (NMR) spectrometer; data processing and analyses were performed using Matlab, R, SPSS and SAS software.

RESULTS AND DISCUSSION: Unsupervised and supervised multivariate analyses distinguished all three control groups and the FMS patients, and significant increases in metabolites related to the gut microbiome (hippuric, succinic and lactic acids) were observed. We have developed an algorithm for the diagnosis of FMS consisting of three metabolites – succinic acid, taurine and creatine – that have a good level of diagnostic accuracy (Receiver Operating Characteristic (ROC) analysis – area under the curve 90%) and on the pain and fatigue symptoms for the selected FMS patient group.

CONCLUSION: Our data and comparative analyses indicated an altered metabolic profile of patients with FMS, analytically detectable within their urine. Validation studies may substantiate urinary metabolites to supplement information from medical assessment, tender-point measurements and FIQR questionnaires for an improved objective diagnosis of FMS.

Source: Malatji BG, Meyer H, Mason S, Engelke UFH, Wevers RA, van Reenen M, Reinecke CJ. A diagnostic biomarker profile for fibromyalgia syndrome based on an NMR metabolomics study of selected patients and controls. BMC Neurol. 2017 May 11;17(1):88. doi: 10.1186/s12883-017-0863-9. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5426044/ (Full article)

Post-Exertional Malaise in Patients with ME and CFS with Comorbid Fibromyalgia

Abstract:

BACKGROUND: Myalgic encephalomyelitis (ME) and chronic fatigue syndrome (CFS) share some similar symptoms with fibromyalgia (FM). Prior research has found increased illness severity when patients have FM that is comorbid with ME and CFS. For example, post-exertional malaise (PEM) has been shown to be more severe in those with comorbid FM. However, PEM can be separated into two factors, Muscle and General PEM. It is unknown if the more severe PEM findings in comorbid FM are due to the Muscle or General PEM factor.

PURPOSE:The purpose of this study was to determine if the PEM differences seen between patients with and without comorbid FM exist for the Muscle or General PEM factors.

METHOD: An international convenience sample was collected via an online questionnaire. The questionnaire assessed the frequency and severity of several PEM-related symptoms. Additionally, participants provided information regarding the course and characteristics of their illness.

RESULTS: Participants that indicated a comorbid diagnosis of FM displayed significantly more frequent and severe PEM symptoms in the Muscle and General PEM factors. The FM group also indicated significantly worse physical functioning compared to the group without comorbid FM.

DISCUSSION: The secondary diagnosis of FM in addition to ME and CFS appears to amplify the PEM symptomatology and worsen patients' physical functioning. The findings of this study have notable implications on the inclusion of patients with comorbid FM in ME and CFS research studies.

Source: McManimen SL, Jason LA. Post-Exertional Malaise in Patients with ME and CFS with Comorbid Fibromyalgia. SRL Neurol Neurosurg. 2017;3(1):22-27. Epub 2017 Mar 10. https://www.ncbi.nlm.nih.gov/pubmed/28603794