Exploratory study into the relationship between the symptoms of chronic fatigue syndrome (CFS)/myalgic encephalomyelitis (ME) and fibromyalgia (FM) using a quasiexperimental design

Abstract:

Objective: To explore the relationship between symptoms of chronic fatigue syndrome (CFS)/myalgic encephalomyelitis (ME) and fibromyalgia (FM). The hypothesis predicated that there would be no significant differences between the group’s symptom experience.

Design: A quasiexperimental design. Structural equation modelling (SEM) and invariance testing.

Participants: Males (M) and females (F) >16 with a confirmed diagnosis of CFS/ME or FM by a general practitioner or specialist. CFS/ME (n=101, F: n=86, M: n=15, mean (M) age M=45.5 years). FM (n=107, F: n=95, M: n=12, M=47.2 years).

Outcome measures: Diagnostic criteria: the American Centers for Disease Control and Prevention (CDC) for CFS/ME and the American College of Rheumatology (ACR) criteria for FM. Additional symptom questionnaires measuring: pain, sleep quality, fatigue, quality of life, anxiety and depression, locus of control and self-esteem.

Results: Invariance was confirmed with the exception of the American CDC Symptom Inventory, Fibromyalgia Impact Questionnaire and Hospital Anxiety and Depression Scale (p<0.05) based on five questions. Consequently, it was erroneous to conclude differences. Therefore, the Syndrome Model was created. SEM could not have tested the ACR previously, as it comprised a single data point. Thus, it was combined with these three questionnaires, increasing the data points, to create this new measurable model. Results confirmed no significant differences between groups (p=0.07 (p<0.05)).

Conclusion: Participants responded in a similar manner to the questionnaire, confirming the same symptom experience. It is important to consider this in context with differing criteria and management guidelines, as this may influence diagnosis and the trajectory of patient’s management. With the biomedical cause currently unclear, it is the symptom experience and the impact on quality of life that is important. These findings are meaningful for patients, clinicians and policy development and support the requirement for future research.

Source: Mckay PG, Walker H, Martin CR, Fleming M. Exploratory study into the relationship between the symptoms of chronic fatigue syndrome (CFS)/myalgic encephalomyelitis (ME) and fibromyalgia (FM) using a quasiexperimental design. BMJ Open. 2021 Feb 1;11(2):e041947. doi: 10.1136/bmjopen-2020-041947. PMID: 33526500. https://bmjopen.bmj.com/content/11/2/e041947.long (Full text)

Treatment Avenues in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Split-gender Pharmacogenomic Study of Gene-expression Modules

Abstract:

PURPOSE: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating multisymptom illness impacting up to 1 million people in the United States. As the pathogenesis and etiology of this complex condition are unclear, prospective treatments are limited. Identifying US Food and Drug Administration-approved drugs that may be repositioned as treatments for ME/CFS may offer a rapid and cost-effective solution.

METHODS: Here we used gene-expression data from 33 patients with Fukuda-defined ME/CFS (23 females, 10 males) and 21 healthy demographically comparable controls (15 females, 6 males) to identify differential expression of predefined gene-module sets based on nonparametric statistics. Differentially expressed gene modules were then annotated via over-representation analysis using the Consensus Pathway database. Differentially expressed modules were then regressed onto measures of fatigue and cross-referenced with drug atlas and pharmacogenomics databases to identify putative treatment agents.

FINDINGS: The top 1% of modules identified in males indicated small effect sizes in modules associated with immune regulation and mitochondrial dysfunction. In females, modules identified included those related to immune factors and cardiac/blood factors, returning effect sizes ranging from very small to intermediate (0.147 < Cohen δ < 0.532). Regression analysis indicated that B-cell receptors, T-cell receptors, tumor necrosis factor α, transforming growth factor β, and metabolic and cardiac modules were strongly correlated with multiple composite measures of fatigue. Cross-referencing identified genes with pharmacogenomics data indicated immunosuppressants as potential treatments of ME/CFS symptoms.

IMPLICATIONS: The findings from our analysis suggest that ME/CFS symptoms are perpetuated by immune dysregulation that may be approached via immune modulation-based treatment strategies. (Clin Ther. 2019;41:XXX-XXX) © 2019 Elsevier Inc.

Copyright © 2019. Published by Elsevier Inc.

Source: Jeffrey MG, Nathanson L, Aenlle K, Barnes ZM, Baig M, Broderick G, Klimas NG, Fletcher MA, Craddock TJA. Treatment Avenues in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Split-gender Pharmacogenomic Study of Gene-expression Modules. Clin Ther. 2019 Mar 6. pii: S0149-2918(19)30047-5. doi: 10.1016/j.clinthera.2019.01.011. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/30851951

Examining case definition criteria for chronic fatigue syndrome and myalgic encephalomyelitis

Abstract:

BACKGROUND: Considerable controversy has transpired regarding the core features of myalgic encephalomyelitis (ME) and chronic fatigue syndrome (CFS). Current case definitions differ in the number and types of symptoms required. This ambiguity impedes the search for biological markers and effective treatments.

PURPOSE: This study sought to empirically operationalize symptom criteria and identify which symptoms best characterize the illness.

METHODS: Patients (n=236) and controls (n=86) completed the DePaul Symptom Questionnaire, rating the frequency and severity of 54 symptoms. Responses were compared to determine the threshold of frequency/severity ratings that best distinguished patients from controls. A Classification and Regression Tree (CART) algorithm was used to identify the combination of symptoms that most accurately classified patients and controls.

RESULTS: A third of controls met the symptom criteria of a common CFS case definition when just symptom presence was required; however, when frequency/severity requirements were raised, only 5% met criteria. Employing these higher frequency/severity requirements, the CART algorithm identified three symptoms that accurately classified 95.4% of participants as patient or control: fatigue/extreme tiredness, inability to focus on multiple things simultaneously, and experiencing a dead/heavy feeling after starting to exercise.

CONCLUSIONS: Minimum frequency/severity thresholds should be specified in symptom criteria to reduce the likelihood of misclassification. Future research should continue to seek empirical support of the core symptoms of ME and CFS to further progress the search for biological markers and treatments.

 

Source: Jason LA, Sunnquist M, Brown A, Evans M, Vernon SD, Furst J, Simonis V. Examining case definition criteria for chronic fatigue syndrome and myalgic encephalomyelitis. Fatigue. 2014 Jan 1;2(1):40-56. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3912876/ (Full article)

 

Symptom occurrence in persons with chronic fatigue syndrome

Abstract:

This investigation compared differences in the occurrence of symptoms in participants with CFS, melancholic depression, and no fatigue (controls). The following Fukuda et al. [Ann. Intern. Med. 121 (1994) 953] criteria symptoms differentiated the CFS group from controls, but did not differentiate the melancholic depression group from controls: headaches, lymph node pain, sore throat, joint pain, and muscle pain. In addition, participants with CFS uniquely differed from controls in the occurrence of muscle weakness at multiple sites as well as in the occurrence of various cardiopulmonary, neurological, and other symptoms not currently included in the current case definition. Implications of these findings are discussed.

 

Source: Jason LA, Torres-Harding SR, Carrico AW, Taylor RR. Symptom occurrence in persons with chronic fatigue syndrome. Biol Psychol. 2002 Feb;59(1):15-27. http://www.ncbi.nlm.nih.gov/pubmed/11790441

 

Co-existence of chronic fatigue syndrome with fibromyalgia syndrome in the general population. A controlled study

Abstract:

OBJECTIVE: To determine the proportion of adults with fibromyalgia syndrome (FMS) in the general population who also meet the 1988 Centre for Disease Control (CDC) criteria for chronic fatigue syndrome (CFS).

METHODS: Seventy-four FMS cases were compared with 32 non-FMS controls with widespread pain and 23 with localized pain, all recruited in a general population survey.

RESULTS: Among females, 58.0% of fibromyalgia cases met the full criteria for CFS, compared to 26.1% and 12.5% of controls with widespread and localized pain, respectively (p=0.0006). Male percentages were 80.0, 22.2, and zero, respectively (p=0.003). Compared to those with FMS alone, those meeting the case definitions for both FMS and CFS reported a worse course, worse overall health, more dissatisfaction with health, more non-CFS symptoms, and greater disease impact. The number of total symptoms and non-CFS symptoms were the best predictors of co-morbid CFS.

CONCLUSIONS: There is significant clinical overlap between CFS and FMS.

 

Source: White KP, Speechley M, Harth M, Ostbye T. Co-existence of chronic fatigue syndrome with fibromyalgia syndrome in the general population. A controlled study. Scand J Rheumatol. 2000;29(1):44-51. http://www.ncbi.nlm.nih.gov/pubmed/10722257

 

Monitoring and assessing symptoms of chronic fatigue syndrome: use of time series regression

Abstract:

Chronic Fatigue Syndrome’s principal symptoms are severe and include prolonged fatigue and a number of other minor symptoms. Behavioral data collection methods were used in a case study to show some of the benefits that can be derived from monitoring symptoms hourly and daily. Using time series regression, several statistically significant correlates of fatigue were found both within days and between days. Perceived energy, physical exertion, and mental exertion were significantly related to fatigue in both analyses. Collection of such data may help resolve a number of theoretical and methodological problems in research on the Chronic Fatigue Syndrome.

 

Source: Jason LA, Tryon WW, Taylor RR, King C, Frankenberry EL, Jordan KM. Monitoring and assessing symptoms of chronic fatigue syndrome: use of time series regression. Psychol Rep. 1999 Aug;85(1):121-30. http://www.ncbi.nlm.nih.gov/pubmed/10575979

 

Correlates of somatic causal attributions in primary care patients with fatigue

Abstract:

Researchers in the field of chronic fatigue in tertiary care found that patients’ somatic (e.g. viral) explanations for their condition may lead to chronicity of symptoms. We studied the influence of a somatic attributional bias on outcome and reported symptoms in primary care patients with fatigue.

We compared fatigue scores on a specific scale, and number of presented symptoms, in two groups of primary care patients with ‘functional’ fatigue: 75 with a high score on the somatic subscale of the Fatigue Attribution Scale (S-FAS), and 95 with a low score on the S-FAS. At the index visit, patients with low and high scores on the S-FAS were not different for age, sex, fatigue scores, and levels of depressive symptoms.

Patients with high scores on the S-FAS presented significantly more somatic and psychological symptoms-a total of 36 symptoms for 24 patients (25.3%) in the low-score group, and a total of 52 symptoms for 31 patients (41.3%) in the high-score group.

Forty-two days later, at the follow-up visit, the fatigue scores were similar in both groups. In primary care patients with fatigue not due to somatic illness or major depression, the tendency to attribute fatigue to somatic causes is not associated with a worse outcome, but with a higher number of reported symptoms.

 

Source: Cathébras P, Jacquin L, le Gal M, Fayol C, Bouchou K, Rousset H. Correlates of somatic causal attributions in primary care patients with fatigue. Psychother Psychosom. 1995;63(3-4):174-80. http://www.ncbi.nlm.nih.gov/pubmed/7624463

 

Chronic fatigue syndrome–symptoms, signs, laboratory tests, and prognosis

Abstract:

Chronic fatigue syndrome (CFS) is an undefined clinical problem and is perceived as a complex of multiple symptomatology with an unexplained persistent fatigue. Major symptoms include fatigue lasting for more than 6 months, low-grade fever, moderate lymphadenopathy, muscle and joint pain, and various psychological presentations. Since no specific laboratory tests are available, clinical diagnosis demands that known causes of chronic fatigue should be excluded. The pathogenesis is at present unknown, but it is suspected that CFS is a physical and psychological condition associated with some unrecognized infectious agent. Further study is needed to clarify the precise pathophysiology of this newly recognized entity.

 

Source: Kanayama Y. Chronic fatigue syndrome–symptoms, signs, laboratory tests, and prognosis. Nihon Rinsho. 1992 Nov;50(11):2586-90. [Article in Japanese] http://www.ncbi.nlm.nih.gov/pubmed/1287234

 

Myth of the chronic fatigue syndrome

THE CHRONIC FATIGUE SYNDROME is a symptom complex characterized by fatigue, myalgias, arthralgias, neurologic symptoms-headaches, paresthesias, dizziness-lymph node swelling or tenderness, cognitive dysfunction, sleep disorders, and depression. The symptoms are similar to those seen in inflammatory illnesses and can be induced by the systemic administration of interferon beta. Severe fatigue is a perplexing and constant complaint in many patients with multiple sclerosis. This indicates that the perception of energy level has a sensitive physiologic basis that is dependent on the homeostasis of other body systems.

The chronic fatigue syndrome has gained popularity among the lay public and has stimulated considerable scientific debate about its existence. Many investigators and practitioners have attributed the disorder to chronic depression. Difficulty arises from the diverse symptoms associated with fatigue states; fatigue is a prominent feature of many systemic, neurologic, and psychiatric disorders. Also, fatigue is a subjective complaint without a quantifiable measure. This interweaving of many symptoms and diagnoses with disabling fatigue makes it difficult to compare patient groups. Terms applied to disorders that probably represent chronic fatigue syndrome are chronic infectious mononucleosis, myalgic encephalomyelitis, idiopathic chronic fatigue and myalgia syndrome, epidemic neuromyasthenia, postviral fatigue syndrome, and fibrositis-fibromyalgia.

You can read the rest of this article here: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1002920/pdf/westjmed00095-0070a.pdf

 

Source: Murray RS. Myth of the chronic fatigue syndrome. West J Med. 1991 Jul;155(1):68. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1002920/