triggers – Page 2 – American ME and CFS Society

Patient perceptions of infectious illnesses preceding Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Abstract:

Objectives: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is often reported to be caused by an infectious agent. However, it is unclear whether one infectious agent might be the cause or whether there might be many different infectious agents. The objective of this study was to identify self-reported infectious illnesses associated with the onset of ME/CFS.

Methods: The present study involved data from multiple sites in several countries. 1773 individuals diagnosed with either ME, CFS or ME/CFS provided qualitative data concerning infectious triggers which were coded and classified for analysis.

Results: 60.3% of patients report a variety of infectious illnesses some time before onset of ME/CFS. The most frequently reported infectious illness was Mononucleosis, which occurred in 30% of infections. However, over 100 other infectious illnesses were mentioned.

Discussion: The findings suggest that many infectious agents might be associated with the onset of ME/CFS.

Source: Jason LA, Yoo S, Bhatia S. Patient perceptions of infectious illnesses preceding Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Chronic Illn. 2021 Sep 20:17423953211043106. doi: 10.1177/17423953211043106. Epub ahead of print. PMID: 34541918. https://pubmed.ncbi.nlm.nih.gov/34541918/

Exploring Symptom Fluctuations and Triggers in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Using Novel Patient-Centred N-of-1 Observational Designs: A Protocol for a Feasibility and Acceptability Study

Abstract:

Background: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a chronic condition of unknown aetiology associated with a range of disabling symptoms, including post-exertional malaise, chronic fatigue, musculoskeletal pain, orthostatic intolerance, unrefreshing sleep, and cognitive dysfunction. ME/CFS is a heterogeneous disorder, with significant variation in symptom type and severity between individuals, as well as within individuals over time. The diversity of ME/CFS symptom presentation makes management challenging; treatments supported by data from randomised controlled trials may not work for all individuals due to the variability in experienced symptoms. Studies using quantitative N-of-1 observational designs involve repeated outcome measurements in an individual over time and can generate rigorous individual-specific conclusions about symptom patterns and triggers in individuals with ME/CFS. This study aims to explore the feasibility and acceptability of using novel patient-centred N-of-1 observational designs to explore symptom fluctuations and triggers in ME/CFS at the individual level.

Methods and analysis: Individuals with a medical diagnosis of ME/CFS will be recruited through ME/CFS patient organisations to participate in a series of patient-centred N-of-1 observational studies. Using a wrist-worn electronic diary, participants will complete ecological momentary assessments of fatigue, stress, mood, and cognitive demand, three times per day for a period of 6-12 weeks. Personally relevant symptoms and triggers will also be incorporated into the questionnaire design. Physical activity will be objectively measured via an integrated accelerometer. Feasibility and acceptability outcomes will be assessed including the percentage of diary entries completed, as well as recruitment and retention rate, feasibility of analysing and interpreting the data collected, and participant views about participation elicited via a post-study semi-structured interview.

Discussion: This study will assess the feasibility and acceptability of patient-centred N-of-1 observational studies to assess diseases with complex presentations such as ME/CFS, as well as provide individual-level evidence about fluctuations and triggers of ME/CFS symptoms that may aid self-management.

Trial registration: Australian and New Zealand Clinical Trials Registry: ACTRN12618001898246. Registered on 22 November 2018.

Source: McDonald S, Tan SX, Banu S, van Driel M, McGree JM, Mitchell G, Nikles J. Exploring Symptom Fluctuations and Triggers in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Using Novel Patient-Centred N-of-1 Observational Designs: A Protocol for a Feasibility and Acceptability Study. Patient. 2021 Aug 9. doi: 10.1007/s40271-021-00540-0. Epub ahead of print. PMID: 34368926. https://pubmed.ncbi.nlm.nih.gov/34368926/

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome as a Hyper-Regulated Immune System Driven by an Interplay Between Regulatory T Cells and Chronic Human Herpesvirus Infections

Abstract:

Autoimmunity and chronic viral infections are recurrent clinical observations in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS), a complex disease with an unknown cause. Given these observations, the regulatory CD4+ T cells (Tregs) show promise to be good candidates for the underlying pathology due to their capacity to suppress the immune responses against both self and microbial antigens. Here, we discussed the overlooked role of these cells in the chronicity of Human Herpes Virus 6 (HHV6), Herpes Simplex 1 (HSV1), and Epstein-Barr virus (EBV), as often reported as triggers of ME/CFS.

Using simulations of the cross-regulation model for the dynamics of Tregs, we illustrated that mild infections might lead to a chronically activated immune responses under control of Tregs if the responding clone has a high autoimmune potential. Such infections promote persistent inflammation and possibly fatigue. We then hypothesized that ME/CFS is a condition characterized by a predominance of this type of infections under control of Tregs. In contrast, healthy individuals are hypothesized to trigger immune responses of a virus-specific clone with a low autoimmune potential.

According to this hypothesis, simple model simulations of the CD4+ T-cell repertoire could reproduce the increased density and percentages of Tregs observed in patients suffering from the disease, when compared to healthy controls. A deeper analysis of Tregs in the pathogenesis of ME/CFS will help to assess the validity of this hypothesis.

Source: Sepúlveda N, Carneiro J, Lacerda E, Nacul L. Myalgic Encephalomyelitis/Chronic Fatigue Syndrome as a Hyper-Regulated Immune System Driven by an Interplay Between Regulatory T Cells and Chronic Human Herpesvirus Infections. Front Immunol. 2019 Nov 21;10:2684. doi: 10.3389/fimmu.2019.02684. eCollection 2019. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6883905/ (Full article)

Increased risk of chronic fatigue syndrome following burn injuries

Abstract:

BACKGROUND: The overlapping symptoms and pathophysiological similarities between burn injury and chronic fatigue syndrome (CFS) are noteworthy. Thus, this study explores the possible association between burn injury and the subsequent risk of CFS.

METHOD: We used data from the Taiwan National Health Insurance system to address the research topic. The exposure cohort comprised of 17,204 patients with new diagnoses of burn injury. Each patient was frequency matched according to age, sex, index year, and comorbidities with four participants from the general population who did not have a history of CFS (control cohort). Cox proportional hazards regression analysis was conducted to estimate the relationship between burn injury and the risk of subsequent CFS.

RESULT: The incidence of CFS in the exposure and control cohorts was 1.61 and 0.86 per 1000 person-years, respectively. The exposure cohort had a significantly higher overall risk of subsequent CFS than did the control cohort (adjusted hazard ratio [HR] = 1.48, 95% confidence interval [CI] = 1.41-1.56). The risk of CFS in patients with burn injury in whichever stratification (including sex, age, and comorbidity) was also higher than that of the control cohort.

CONCLUSION: The findings from this population-based retrospective cohort study suggest that thermal injury is associated with an increased risk of subsequent CFS and provided a point of view suggesting burn injuries in sun- exposed areas such as the face and limbs had greater impact on subsequent development of CFS compared with trunk areas. In addition, extensively burned areas and visible scars were predictors of greater physiological and psychosocial that are needed to follow-up in the long run.

Source: Tsai SY, Lin CL, Shih SC, Hsu CW, Leong KH, Kuo CF, Lio CF, Chen YT, Hung YJ, Shi L. Increased risk of chronic fatigue syndrome following burn injuries. J Transl Med. 2018 Dec 5;16(1):342. doi: 10.1186/s12967-018-1713-2. https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-018-1713-2 (Full article)

Peripheral blood gene expression in postinfective fatigue syndrome following from three different triggering infections

Abstract:

BACKGROUND: Several infections trigger postinfective fatigue syndromes, which share key illness characteristics with each other and with chronic fatigue syndrome (CFS). Previous cross-sectional case-control studies of CFS have suggested that unique gene expression signatures are evident in peripheral blood samples.

METHODS: Peripheral blood transcriptomes in samples collected longitudinally, in 18 subjects with a fatigue syndrome lasting ≥ 6 months after acute infection due to Epstein-Barr virus, Ross River virus, or Coxiella burnetii (Q fever), and 18 matched control subjects who had recovered promptly, were studied by microarray (n = 127) and confirmatory quantitative polymerase chain reaction (PCR). Gene expression patterns associated with CFS were sought by univariate statistics and regression modeling.

RESULTS: There were 23 genes with modest differential expression (0.6-2.3-fold change) in within-subject comparisons of early, symptomatic time points with late, recovered time points. There were modest differences found in 63 genes, either in cross-sectional comparison of cases and controls at 6 months after infection onset or in the regression model. There were 223 genes significantly correlated with individual symptom domains. Quantitative PCR confirmed 33 (73%) of 45 genes-none were consistent across cohorts.

CONCLUSIONS: Although the illness characteristics of patients with postinfective fatigue syndromes have more similarities than differences, no reliable peripheral blood gene expression correlate is evident.

Source: Galbraith S, Cameron B, Li H, Lau D, Vollmer-Conna U, Lloyd AR. Peripheral blood gene expression in postinfective fatigue syndrome following from three different triggering infections. J Infect Dis. 2011 Nov 15;204(10):1632-40. doi: 10.1093/infdis/jir612. Epub 2011 Sep 29. http://jid.oxfordjournals.org/content/204/10/1632.long (Full article)

Microbial infections in eight genomic subtypes of chronic fatigue syndrome/myalgic encephalomyelitis

Abstract:

BACKGROUND: The authors have previously reported genomic subtypes of chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) based on expression of 88 human genes.

AIM: To attempt to reproduce these findings, determine the specificity of this signature to CFS/ME, and test for associations between CFS/ME subtype and infection.

METHODS: Expression levels of 88 human genes were determined in blood of 62 new patients with idiopathic CFS/ME (according to Fukuda criteria), six patients with Q-fever-associated CFS/ME from the Birmingham Q-fever outbreak (according to Fukuda criteria), 14 patients with endogenous depression (according to DSM-IV criteria) and 29 normal blood donors.

RESULTS: In patients with CFS/ME, differential expression was confirmed for all 88 genes. Q-CFS/ME had similar patterns of gene expression to idiopathic CFS/ME. Gene expression in patients with endogenous depression was similar to that in the normal controls, except for upregulation of five genes (APP, CREBBP, GNAS, PDCD2 and PDCD6). Clustering of combined gene data in CFS/ME patients for this and the authors’ previous study (117 CFS/ME patients) revealed genomic subtypes with distinct differences in SF36 scores, clinical phenotypes, severity and geographical distribution. Antibody testing for Epstein-Barr virus, enterovirus, Coxiella burnetii and parvovirus B19 revealed evidence of subtype-specific relationships for Epstein-Barr virus and enterovirus, the two most common infectious triggers of CFS/ME.

CONCLUSIONS: This study confirms the involvement of these genes in CFS/ME.

Source: Zhang L, Gough J, Christmas D, Mattey DL, Richards SC, Main J, Enlander D, Honeybourne D, Ayres JG, Nutt DJ, Kerr JR. Microbial infections in eight genomic subtypes of chronic fatigue syndrome/myalgic encephalomyelitis. J Clin Pathol. 2010 Feb;63(2):156-64. doi: 10.1136/jcp.2009.072561. Epub 2009 Dec 2. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2921262/ (Full article)

Precipitating factors for the chronic fatigue syndrome

Abstract:

The etiology of the Chronic Fatigue Syndrome (CFS) is unknown but it is usually considered to be postinfectious or postviral. Many infecting agents have been suspected as causative but none has been proven.

We investigated precipitating factors in 134 CFS patients through the use of a questionnaire, interview, clinical examination and serology for infecting agents; 35 healthy controls completed a similar questionnaire. CFS started with an apparently infectious illness in 96 (72%) but a definite infection was only found in seven of these 96 (7%). Thirty-eight (28%) had no apparent infectious onset: 15/38 (40%) had noninfectious precipitants (trauma, allergy, surgery).

There was no apparent precipitating event in 23/38 (61%). Immunization was not a significant precipitant. Stressful events were very common in the year preceding the onset of CFS (114/134, 85%) but these occurred in only 2/35 (6%) of the controls (p < .0001). The onset of CFS may be associated with preceding stressful events and multiple other precipitants. An infectious illness is not uniformly present at the onset and no single infectious agent has been found; CFS is most likely multifactorial in origin.

Source: Salit IE. Precipitating factors for the chronic fatigue syndrome. J Psychiatr Res. 1997 Jan-Feb;31(1):59-65. http://www.ncbi.nlm.nih.gov/pubmed/9201648

Chronic fatigue and minor psychiatric morbidity after viral meningitis: a controlled study

Abstract:

OBJECTIVE: To test the hypotheses that patients exposed to viral meningitis would be at an increased risk of developing chronic fatigue syndrome and would have an excess of neurological symptoms and physical impairment.

METHODS: Eighty three patients were followed up 6-24 months after viral meningitis and a postal questionnaire was used to compare outcome with 76 controls who had had non-enteroviral, non-CNS viral infections.

RESULTS: For the 159 patients and controls the prevalence of chronic fatigue syndrome was 12.6%, a rate higher than previously reported from primary care attenders, suggesting that moderate to severe viral infections may play a part in the aetiology of some fatigue states. Those with a history of meningitis showed a slight, non-significant increase in prevalence of chronic fatigue syndrome (OR 1.4; 95% CI 0.5-3.6) which disappeared when logistic regression and analysis was used to correct for age, sex, and duration of follow up (OR 1.0; 95% CI 0.3-2.8). Controls showed marginally higher psychiatric morbidity measured on the general health questionnaire-12 (adjusted OR 0.6; 95% CI 0.3-1.3) Both groups had similar rates of neurological symptoms and physical impairment. The best predictor of chronic fatigue was a prolonged duration time of off work after the illness (OR 4.93, 95% CI 1.3-18.8). The best predictor of severe chronic fatigue syndrome diagnosed by Center for Disease Control criteria was past psychiatric illness (OR 7.82, 95% CI 1.8-34.3). Duration of viral illness, as defined by days in hospital, did not predict chronic fatigue syndrome.

CONCLUSIONS: (1) The prevalence of chronic fatigue syndrome is higher than expected for the range of viral illnesses examined; (2) enteroviral infection is unlikely to be a specific risk factor for its development; (3) onset of chronic fatigue syndrome after a viral infection is predicted by psychiatric morbidity and prolonged convalescence, rather than by the severity of the viral illness itself.

Source: Hotopf M, Noah N, Wessely S. Chronic fatigue and minor psychiatric morbidity after viral meningitis: a controlled study. J Neurol Neurosurg Psychiatry. 1996 May;60(5):504-9. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC486361/ (Full article)

A case-control study to assess possible triggers and cofactors in chronic fatigue syndrome

Abstract:

PURPOSE: To assess possible triggers and cofactors for chronic fatigue syndrome (CFS) and to compare levels of selected cytokines between cases and an appropriately matched control group.

PATIENTS AND METHODS: We conducted a case-control study of 47 cases of CFS obtained through a regional CFS research program maintained at a tertiary care medical center. One age-, gender-, and neighborhood-matched control was identified for each case through systematic community telephone sampling. Standardized questionnaires were administered to cases and controls. Sera were assayed for transforming growth factor-beta (TGF-beta), interleukin-1 beta, interleukin-6, tumor necrosis factor-alpha, and antibody to Borrelia burgdorferi and Babesia microti.

RESULTS: Cases were more likely to have exercised regularly before illness onset than controls (67% versus 40%; matched odds ratio (MOR) = 3.4; 95% CI = 1.2 to 11.8; P = 0.02). Female cases were more likely to be nulliparous prior to onset of CFS than controls (51% versus 31%; MOR = 8.0; 95% CI = 1.03 to 170; P = 0.05). History of other major factors, including silicone-gel breast implants (one female case and one female control), pre-morbid history of depression (15% of cases, 11% of controls) and history of allergies (66% of cases, 51% of controls) were similar for cases and controls. However, cases were more likely to have a diagnosis of depression subsequent to their diagnosis of CFS compared to a similar time frame for controls (MOR = undefined; 95% CI lower bound = 2.5; P < 0.001). Positive antibody titers to B burgdorferi (one case and one control) and B microti (zero cases and two controls) were also similar.

CONCLUSIONS: Further investigation into the role of prior routine exercise as a cofactor for CFS is warranted. This study supports the concurrence of CFS and depression, although pre-morbid history of depression was similar for both groups.

Comment in: Etiology of chronic fatigue syndrome. [Am J Med. 1997]

Source: MacDonald KL, Osterholm MT, LeDell KH, White KE, Schenck CH, Chao CC, Persing DH, Johnson RC, Barker JM, Peterson PK. A case-control study to assess possible triggers and cofactors in chronic fatigue syndrome. Am J Med. 1996 May;100(5):548-54. http://www.ncbi.nlm.nih.gov/pubmed/8644768