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Pricoco R, Meidel P, Hofberger T, Zietemann H, Mueller Y, Wiehler K, Michel K, Paulick J, Leone A, Haegele M, Mayer-Huber S, Gerrer K, Mittelstrass K, Scheibenbogen C, Renz-Polster H, Mihatsch L, Behrends U. One-year follow-up of young people with ME/CFS following infectious mononucleosis by Epstein-Barr virus. Front Pediatr 2024; 11:1266738. [PMID: 38304441 PMCID: PMC10830704 DOI: 10.3389/fped.2023.1266738] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/25/2023] [Accepted: 12/20/2023] [Indexed: 02/03/2024] Open
Abstract
Background Infectious mononucleosis after primary infection with Epstein-Barr virus (EBV-IM) has been linked to the development of myalgic encephalomyelitis/chronic fatigue-syndrome (ME/CFS) in children, adolescents, and young adults. Here, we present clinical phenotypes and follow-up data from a first German cohort of young people with ME/CFS following EBV-IM. Methods 12 adolescents and 13 young adults were diagnosed with IM-triggered ME/CFS at our specialized tertiary outpatient service by clinical criteria requiring post-exertional malaise (PEM) and a history of confirmed EBV primary infection as triggering event. Demographic information, laboratory findings, frequency and severity of symptoms, physical functioning, and health-related quality of life (HRQoL) were assessed and re-evaluated 6 and 12 months later. Results Young adults displayed more severe symptoms as well as worsening of fatigue, physical and mental functioning, and HRQoL throughout the study, compared to adolescents. After one year, 6/12 (54%) adolescents no longer met the diagnostic criteria for ME/CFS while all young adults continued to fulfill the Canadian consensus criteria. Improvement in adolescents was evident in physical functioning, symptom frequency and severity, and HRQoL, while young adults showed little improvement. EBV serology and EBV DNA load did not correlate with distinct clinical features of ME/CFS, and clinical chemistry showed no evidence of inflammation. Remarkably, the median time from symptom onset to ME/CFS diagnosis was 13.8 (IQR: 9.1-34.9) months. Conclusions ME/CFS following EBV-IM is a severely debilitating disease often diagnosed late and with limited responses to conventional medical care, especially in adults. Although adolescents may have a better prognosis, their condition can fluctuate and significantly impact their HRQoL. Our data emphasize that biomarkers and effective therapeutic options are also urgently needed to improve medical care and pave the way to recovery.
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Affiliation(s)
- Rafael Pricoco
- MRI Chronic Fatigue Center for Young People (MCFC), Children’s Hospital, TUM School of Medicine, Technical University of Munich and Munich Municipal Hospital Schwabing, Munich, Germany
| | - Paulina Meidel
- MRI Chronic Fatigue Center for Young People (MCFC), Children’s Hospital, TUM School of Medicine, Technical University of Munich and Munich Municipal Hospital Schwabing, Munich, Germany
| | - Tim Hofberger
- MRI Chronic Fatigue Center for Young People (MCFC), Children’s Hospital, TUM School of Medicine, Technical University of Munich and Munich Municipal Hospital Schwabing, Munich, Germany
| | - Hannah Zietemann
- MRI Chronic Fatigue Center for Young People (MCFC), Children’s Hospital, TUM School of Medicine, Technical University of Munich and Munich Municipal Hospital Schwabing, Munich, Germany
| | - Yvonne Mueller
- MRI Chronic Fatigue Center for Young People (MCFC), Children’s Hospital, TUM School of Medicine, Technical University of Munich and Munich Municipal Hospital Schwabing, Munich, Germany
| | - Katharina Wiehler
- MRI Chronic Fatigue Center for Young People (MCFC), Children’s Hospital, TUM School of Medicine, Technical University of Munich and Munich Municipal Hospital Schwabing, Munich, Germany
| | - Kaja Michel
- MRI Chronic Fatigue Center for Young People (MCFC), Children’s Hospital, TUM School of Medicine, Technical University of Munich and Munich Municipal Hospital Schwabing, Munich, Germany
| | - Johannes Paulick
- MRI Chronic Fatigue Center for Young People (MCFC), Children’s Hospital, TUM School of Medicine, Technical University of Munich and Munich Municipal Hospital Schwabing, Munich, Germany
| | - Ariane Leone
- MRI Chronic Fatigue Center for Young People (MCFC), Children’s Hospital, TUM School of Medicine, Technical University of Munich and Munich Municipal Hospital Schwabing, Munich, Germany
| | - Matthias Haegele
- MRI Chronic Fatigue Center for Young People (MCFC), Children’s Hospital, TUM School of Medicine, Technical University of Munich and Munich Municipal Hospital Schwabing, Munich, Germany
| | - Sandra Mayer-Huber
- MRI Chronic Fatigue Center for Young People (MCFC), Children’s Hospital, TUM School of Medicine, Technical University of Munich and Munich Municipal Hospital Schwabing, Munich, Germany
| | - Katrin Gerrer
- MRI Chronic Fatigue Center for Young People (MCFC), Children’s Hospital, TUM School of Medicine, Technical University of Munich and Munich Municipal Hospital Schwabing, Munich, Germany
| | - Kirstin Mittelstrass
- MRI Chronic Fatigue Center for Young People (MCFC), Children’s Hospital, TUM School of Medicine, Technical University of Munich and Munich Municipal Hospital Schwabing, Munich, Germany
| | - Carmen Scheibenbogen
- Institute of Medical Immunology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt Universität zu Berlin and Berlin Institute of Health (BIH), Berlin, Germany
| | - Herbert Renz-Polster
- Mannheim Institute of Public Health, Social and Preventive Medicine, University Medicine Mannheim, Heidelberg, Germany
| | - Lorenz Mihatsch
- MRI Chronic Fatigue Center for Young People (MCFC), Children’s Hospital, TUM School of Medicine, Technical University of Munich and Munich Municipal Hospital Schwabing, Munich, Germany
| | - Uta Behrends
- MRI Chronic Fatigue Center for Young People (MCFC), Children’s Hospital, TUM School of Medicine, Technical University of Munich and Munich Municipal Hospital Schwabing, Munich, Germany
- German Center for Infection Research (partner site Munich), Munich, Germany
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Krogsgaard LW, Petersen I, Plana-Ripoll O, Bech BH, Lützen TH, Thomsen RW, Rytter D. Infections in temporal proximity to HPV vaccination and adverse effects following vaccination in Denmark: A nationwide register-based cohort study and case-crossover analysis. PLoS Med 2021; 18:e1003768. [PMID: 34495975 PMCID: PMC8457493 DOI: 10.1371/journal.pmed.1003768] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/29/2020] [Revised: 09/22/2021] [Accepted: 08/13/2021] [Indexed: 12/03/2022] Open
Abstract
BACKGROUND Public trust in the human papilloma virus (HPV) vaccination programme has been challenged by reports of potential severe adverse effects. The reported adverse symptoms were heterogeneous and overlapping with those characterised as chronic fatigue syndrome (CFS) and have been described as CFS-like symptoms. Evidence suggests that CFS is often precipitated by an infection. The aim of the study was to examine if an infection in temporal proximity to HPV vaccination is a risk factor for suspected adverse effects following HPV vaccination. METHODS AND FINDINGS The study was a nationwide register-based cohort study and case-crossover analysis. The study population consisted of all HPV vaccinated females living in Denmark, born between 1974 and 2006, and vaccinated between January 1, 2006 and December 31, 2017. The exposure was any infection in the period ± 1 month around time of first HPV vaccination and was defined as (1) hospital-treated infection; (2) redemption of anti-infective medication; or (3) having a rapid streptococcal test done at the general practitioner. The outcome was referral to a specialised hospital setting (5 national HPV centres opened June 1, 2015) due to suspected adverse effects following HPV vaccination. Multivariable logistic regression was used to estimate the association between infection and later HPV centre referral. The participants were 600,400 HPV-vaccinated females aged 11 to 44 years. Of these, 48,361 (9.7%) females had a hospital-treated infection, redeemed anti-infective medication, or had a rapid streptococcal test ± 1 month around time of first HPV vaccination. A total of 1,755 (0.3%) females were referred to an HPV centre. Having a hospital-treated infection in temporal proximity to vaccination was associated with significantly elevated risk of later referral to an HPV centre (odds ratio (OR) 2.75, 95% confidence interval (CI) 1.72 to 4.40; P < 0.001). Increased risk was also observed among females who redeemed anti-infective medication (OR 1.56, 95% CI 1.33 to 1.83; P < 0.001) or had a rapid streptococcal test (OR 1.45, 95% CI 1.10 to 1.93; P = 0.010). Results from a case-crossover analysis, which was performed to adjust for potential unmeasured confounding, supported the findings. A key limitation of the study is that the HPV centres did not open until June 1, 2015, which may have led to an underestimation of the risk of suspected adverse effects, but stratified analyses by year of vaccination yielded similar results. CONCLUSIONS Treated infection in temporal proximity to HPV vaccination is associated with increased risk for later referral with suspected adverse vaccine effects. Thus, the infection could potentially be a trigger of the CFS-like symptoms in a subset of the referred females. To our knowledge, the study is the first to investigate the role of infection in the development of suspected adverse effects after HPV vaccination and replication of these findings are needed in other studies.
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Affiliation(s)
- Lene Wulff Krogsgaard
- Research Unit for Epidemiology, Department of Public Health, Aarhus University, Aarhus C, Denmark
- * E-mail:
| | - Irene Petersen
- Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus N, Denmark
- Department of Primary Care and Population Health, Institute of Epidemiology and Health Care, Faculty of Population Health Sciences, University College London, United Kingdom
| | - Oleguer Plana-Ripoll
- National Centre for Register-based Research, Aarhus University, Aarhus V, Denmark
| | - Bodil Hammer Bech
- Research Unit for Epidemiology, Department of Public Health, Aarhus University, Aarhus C, Denmark
| | - Tina Hovgaard Lützen
- Research Unit for Epidemiology, Department of Public Health, Aarhus University, Aarhus C, Denmark
| | | | - Dorte Rytter
- Research Unit for Epidemiology, Department of Public Health, Aarhus University, Aarhus C, Denmark
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O'Neal AJ, Hanson MR. The Enterovirus Theory of Disease Etiology in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Critical Review. Front Med (Lausanne) 2021; 8:688486. [PMID: 34222292 PMCID: PMC8253308 DOI: 10.3389/fmed.2021.688486] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2021] [Accepted: 05/26/2021] [Indexed: 02/06/2023] Open
Abstract
Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a complex, multi-system disease whose etiological basis has not been established. Enteroviruses (EVs) as a cause of ME/CFS have sometimes been proposed, as they are known agents of acute respiratory and gastrointestinal infections that may persist in secondary infection sites, including the central nervous system, muscle, and heart. To date, the body of research that has investigated enterovirus infections in relation to ME/CFS supports an increased prevalence of chronic or persistent enteroviral infections in ME/CFS patient cohorts than in healthy individuals. Nevertheless, inconsistent results have fueled a decline in related studies over the past two decades. This review covers the aspects of ME/CFS pathophysiology that are consistent with a chronic enterovirus infection and critically reviews methodologies and approaches used in past EV-related ME/CFS studies. We describe the prior sample types that were interrogated, the methods used and the limitations to the approaches that were chosen. We conclude that there is considerable evidence that prior outbreaks of ME/CFS were caused by one or more enterovirus groups. Furthermore, we find that the methods used in prior studies were inadequate to rule out the presence of chronic enteroviral infections in individuals with ME/CFS. Given the possibility that such infections could be contributing to morbidity and preventing recovery, further studies of appropriate biological samples with the latest molecular methods are urgently needed.
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Affiliation(s)
- Adam J O'Neal
- Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY, United States
| | - Maureen R Hanson
- Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY, United States
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Stanculescu D, Larsson L, Bergquist J. Hypothesis: Mechanisms That Prevent Recovery in Prolonged ICU Patients Also Underlie Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). Front Med (Lausanne) 2021; 8:628029. [PMID: 33585528 PMCID: PMC7876311 DOI: 10.3389/fmed.2021.628029] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2020] [Accepted: 01/08/2021] [Indexed: 12/13/2022] Open
Abstract
Here the hypothesis is advanced that maladaptive mechanisms that prevent recovery in some intensive care unit (ICU) patients may also underlie Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Specifically, these mechanisms are: (a) suppression of the pituitary gland's pulsatile secretion of tropic hormones, and (b) a "vicious circle" between inflammation, oxidative and nitrosative stress (O&NS), and low thyroid hormone function. This hypothesis should be investigated through collaborative research projects.
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Affiliation(s)
| | - Lars Larsson
- Basic and Clinical Muscle Biology, Department of Physiology and Pharmacology, Karolinska Institute, Solna, Sweden
| | - Jonas Bergquist
- Analytical Chemistry and Neurochemistry, Department of Chemistry – Biomedical Center, Uppsala University, Uppsala, Sweden
- The Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) Collaborative Research Centre at Uppsala University, Uppsala, Sweden
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Gotaas ME, Stiles TC, Bjørngaard JH, Borchgrevink PC, Fors EA. Cognitive Behavioral Therapy Improves Physical Function and Fatigue in Mild and Moderate Chronic Fatigue Syndrome: A Consecutive Randomized Controlled Trial of Standard and Short Interventions. Front Psychiatry 2021; 12:580924. [PMID: 33912079 PMCID: PMC8071989 DOI: 10.3389/fpsyt.2021.580924] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/19/2020] [Accepted: 03/17/2021] [Indexed: 01/29/2023] Open
Abstract
Objective: To study whether standard cognitive behavioral therapy (CBT) and a shorter, interpersonal oriented cognitive behavioral therapy (I-CBT) can improve physical function and fatigue in patients diagnosed with mild to moderate chronic fatigue syndrome (CFS) in a multidisciplinary fatigue clinic. Design: Consecutively 236 participants 18-62 years old meeting the Centre of Decease Control, CDC 1994 criteria, with a subsample also fulfilling the Canadian criteria for CFS, were randomly allocated to one of three groups. Two intervention groups received either 16 weeks of standard CBT or 8 weeks of I-CBT vs. a waiting-list control group (WLC). Primary outcome was the subscale Physical Function (PF) from SF-36 (0-100). Secondary outcome was amongst others fatigue measured by Chalder Fatigue Questionnaire (CFQ) (0-33). Outcomes were repeatedly measured up to 52 weeks from baseline. Results: The additional effect relative to baseline at post-intervention for SF-36 physical function was 14.2 (95% CI 7.9-20.4 p < 0.001) points higher for standard CBT and 6.8 (0.5-13.2 p = 0.036) points higher for I-CBT compared with the control group. The additional effect relative to baseline at post-intervention for fatigue was 5.9 (95% CI 0.5-10.5 p = 0.03) points lower for standard CBT compared with the control group but did not differ substantially for I-CBT 4.8 (95% CI -0.4 to 9.9 p = 0.07). The positive change in physical function persisted at 1-year follow-up for both treatment groups, and for standard CBT also in fatigue. The two intervention groups did not differ significantly in self-reported physical function and fatigue at the 1-year follow-up. No serious adverse reactions were recorded in any of the groups during the trial period. Interpretation: A 16-week standard, individual CBT intervention improves physical function and fatigue in CFS outpatients with mild to moderate disease. A shorter 8-week I-CBT program improves physical function. Both treatments are safe, and the effect persist 1 year after baseline. Clinical Trial registration: ClinicalTrials.gov, Identifier: NCT00920777, registered June 15, 2009. REK-project number: 4.2008.2586, registered April 2, 2008. Funding: The Liaison Committee for Education, Research and Innovation in Central Norway.
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Affiliation(s)
- Merethe Eide Gotaas
- Department of Circulation and Medical Imaging, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway.,National Competence Centre for Complex Symptom Disorders, St. Olav's University Hospital, Trondheim, Norway
| | - Tore C Stiles
- Department of Psychology, Norwegian University of Science and Technology (NTNU), Trondheim, Norway
| | - Johan Håkon Bjørngaard
- Department of Public Health and Nursing, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway.,Faculty of Nursing and Health Sciences, Nord University, Levanger, Norway
| | - Petter C Borchgrevink
- Department of Circulation and Medical Imaging, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway.,National Competence Centre for Complex Symptom Disorders, St. Olav's University Hospital, Trondheim, Norway
| | - Egil A Fors
- Department of Public Health and Nursing, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway
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Hviid A, Thorsen NM, Valentiner-Branth P, Frisch M, Mølbak K. Association between quadrivalent human papillomavirus vaccination and selected syndromes with autonomic dysfunction in Danish females: population based, self-controlled, case series analysis. BMJ 2020; 370:m2930. [PMID: 32878745 PMCID: PMC7463169 DOI: 10.1136/bmj.m2930] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/14/2023]
Abstract
OBJECTIVE To evaluate the association between quadrivalent human papillomavirus vaccination and syndromes with autonomic dysfunction, such as chronic fatigue syndrome, complex regional pain syndrome, and postural orthostatic tachycardia syndrome. DESIGN Population-based self-controlled case series. SETTING Information on human papillomavirus vaccinations and selected syndromes with autonomic dysfunction (chronic fatigue syndrome, complex regional pain syndrome, and postural orthostatic tachycardia syndrome) identified using ICD-10 (international classification of diseases, revision 10) diagnostic codes from Danish nationwide registers. PARTICIPANTS 869 patients with autonomic dysfunction syndromes from a cohort of 1 375 737 Danish born female participants aged 10 to 44 years during 2007-16. MAIN OUTCOME MEASURES Self-controlled case series rate ratios (95% confidence intervals) of the composite outcome of chronic fatigue syndrome, complex regional pain syndrome, and postural orthostatic tachycardia syndrome, adjusted for age and season, comparing female participants vaccinated and unvaccinated with the quadrivalent human papillomavirus vaccine. Chronic fatigue syndrome, complex regional pain syndrome, and postural orthostatic tachycardia syndrome were also considered separately in secondary analyses. RESULTS During 10 581 902 person years of follow-up, 869 female participants with syndromes of autonomic dysfunction (136 with chronic fatigue syndrome, 535 with complex regional pain syndrome, and 198 with postural orthostatic tachycardia syndrome) were identified. Quadrivalent human papillomavirus vaccination did not statistically significantly increase the rate of a composite outcome of all syndromes with autonomic dysfunction in a 365 day risk period following vaccination (rate ratio 0.99, 95% confidence interval 0.74 to 1.32) or the rate of any individual syndrome in the risk period (chronic fatigue syndrome (0.38, 0.13 to 1.09), complex regional pain syndrome (1.31, 0.91 to 1.90), or postural orthostatic tachycardia syndrome (0.86, 0.48 to 1.54)). CONCLUSIONS When vaccination is introduced, adverse events could occur in close temporal relation to the vaccine purely by chance. These results do not support a causal association between quadrivalent human papillomavirus vaccination and chronic fatigue syndrome, complex regional pain syndrome, or postural orthostatic tachycardia syndrome, either individually or as a composite outcome. An increased risk of up to 32% cannot be formally excluded, but the statistical power of the study suggests that a larger increase in the rate of any syndrome associated with vaccination is unlikely.
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Affiliation(s)
- Anders Hviid
- Department of Epidemiology Research, Statens Serum Institut, Artillerivej 5, 2300 Copenhagen S, Denmark
- Department of Drug Design and Pharmacology, University of Copenhagen, Denmark
| | - Nicklas M Thorsen
- Department of Epidemiology Research, Statens Serum Institut, Artillerivej 5, 2300 Copenhagen S, Denmark
| | | | - Morten Frisch
- Department of Epidemiology Research, Statens Serum Institut, Artillerivej 5, 2300 Copenhagen S, Denmark
- Department of Clinical Medicine, Centre for Sexology Research, Aalborg University, Aalborg, Denmark
| | - Kåre Mølbak
- Division of Infectious Diseases Preparedness, Statens Serum Institut, Copenhagen, Denmark
- Department of Veterinary and Animal Sciences, University of Copenhagen, Denmark
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Islam MF, Cotler J, Jason LA. Post-viral fatigue and COVID-19: lessons from past epidemics. FATIGUE-BIOMEDICINE HEALTH AND BEHAVIOR 2020. [DOI: 10.1080/21641846.2020.1778227] [Citation(s) in RCA: 25] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Affiliation(s)
| | - Joseph Cotler
- Center for Community Research, DePaul University, Chicago, IL, USA
| | - Leonard A. Jason
- Center for Community Research, DePaul University, Chicago, IL, USA
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8
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Blomberg J, Rizwan M, Böhlin-Wiener A, Elfaitouri A, Julin P, Zachrisson O, Rosén A, Gottfries CG. Antibodies to Human Herpesviruses in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Patients. Front Immunol 2019; 10:1946. [PMID: 31475007 PMCID: PMC6702656 DOI: 10.3389/fimmu.2019.01946] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2019] [Accepted: 08/01/2019] [Indexed: 11/13/2022] Open
Abstract
Myalgic encephalomyelitis, also referred to as chronic fatigue syndrome (ME/CFS) is a debilitating disease characterized by myalgia and a sometimes severe limitation of physical activity and cognition. It is exacerbated by physical and mental activity. Its cause is unknown, but frequently starts with an infection. The eliciting infection (commonly infectious mononucleosis or an upper respiratory infection) can be more or less well diagnosed. Among the human herpesviruses (HHV-1-8), HHV-4 (Epstein-Barr virus; EBV), HHV-6 (including HHV-6A and HHV-6B), and HHV-7, have been implicated in the pathogenesis of ME/CFS. It was therefore logical to search for serological evidence of past herpesvirus infection/reactivation in several cohorts of ME/CFS patients (all diagnosed using the Canada criteria). Control samples were from Swedish blood donors. We used whole purified virus, recombinant proteins, and synthetic peptides as antigens in a suspension multiplex immunoassay (SMIA) for immunoglobulin G (IgG). The study on herpesviral peptides based on antigenicity with human sera yielded novel epitope information. Overall, IgG anti-herpes-viral reactivities of ME/CFS patients and controls did not show significant differences. However, the high precision and internally controlled format allowed us to observe minor relative differences between antibody reactivities of some herpesviral antigens in ME/CFS versus controls. ME/CFS samples reacted somewhat differently from controls with whole virus HHV-1 antigens and recombinant EBV EBNA6 and EA antigens. We conclude that ME/CFS samples had similar levels of IgG reactivity as blood donor samples with HHV-1-7 antigens. The subtle serological differences should not be over-interpreted, but they may indicate that the immune system of some ME/CFS patients interact with the ubiquitous herpesviruses in a way different from that of healthy controls.
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Affiliation(s)
- Jonas Blomberg
- Section of Clinical Microbiology, Department of Medical Sciences, Uppsala University, Uppsala, Sweden
| | - Muhammad Rizwan
- Section of Clinical Microbiology, Department of Medical Sciences, Uppsala University, Uppsala, Sweden
| | - Agnes Böhlin-Wiener
- Section of Clinical Microbiology, Department of Medical Sciences, Uppsala University, Uppsala, Sweden
| | - Amal Elfaitouri
- Department of Infectious Disease and Tropical Medicine, Faculty of Public Health, Benghazi University, Benghazi, Libya
| | - Per Julin
- Neurological Rehabilitation Clinic, Stora Sköndal, Sköndal, Sweden.,Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden
| | | | - Anders Rosén
- Division of Cell Biology, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden
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Schultz KR, Katz BZ, Bockian NR, Jason LA. Associations Between Autonomic and Orthostatic Self-report and Physician Ratings of Orthostatic Intolerance in Youth. Clin Ther 2019; 41:633-640. [PMID: 30876666 DOI: 10.1016/j.clinthera.2019.02.010] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2018] [Revised: 02/06/2019] [Accepted: 02/11/2019] [Indexed: 10/27/2022]
Abstract
PURPOSE There is no known biological marker or physical assessment to diagnose chronic fatigue syndrome (CFS), leaving physicians to heavily rely on self-report measures regarding the symptoms associated with CFS. Common symptoms of CFS include difficulty sleeping, joint pain, headaches, sore throat, cognitive dysfunction, physical exhaustion, dizziness, and nausea. Because of the overlap among CFS symptoms and autonomic functioning, we examined the association between 2 self-report measures of orthostatic and autonomic symptoms and a physician's report of autonomic functioning (measures of changes in blood pressure and pulse) to further understand the association among autonomic functioning within individuals with symptoms of CFS. METHODS With data from an ongoing study, we used independent t tests and Pearson correlation tests to assess the association among the orthostatic domain from the DePaul Symptom Questionnaire, Autonomic Symptom Checklist composite scores, and the physician's assessment of orthostatic intolerance obtained from a sample of 191 participants, 42 who were healthy controls. FINDINGS No significant demographic differences were found between the CFS-like group and the healthy controls. Results indicate a significant correlation between orthostatic and autonomic functioning (r = 0.58) and a correlation with a low effect size among autonomic functioning and physician measures of orthostatic functioning (r = -0.01 to 0.29). However, fewer correlations were found between self-reported symptoms of orthostatic functioning and the physician's measures of orthostatic functioning. IMPLICATIONS These results suggest that although orthostatic dysfunction is reported in children and adolescents with CFS-like symptoms, the physical measures of autonomic functioning in this study were unable to detect these symptoms.
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Affiliation(s)
| | - Ben Z Katz
- Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago, IL, USA
| | | | - Leonard A Jason
- Center for Community Research, DePaul University, Chicago, IL, USA.
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10
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Chudleigh C, Savage B, Cruz C, Lim M, McClure G, Palmer DM, Spooner CJ, Kozlowska K. Use of respiratory rates and heart rate variability in the assessment and treatment of children and adolescents with functional somatic symptoms. Clin Child Psychol Psychiatry 2019; 24:29-39. [PMID: 30354283 DOI: 10.1177/1359104518807742] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
Functional somatic symptoms (FSS) emerge when the stress system is activated in response to physical or emotional stress that is either chronic or especially intense. In such cases, the heightened state of physiological arousal and motor activation can be measured through biological markers. Our team have integrated the use of biological markers of body state - respiratory rate, heart rate (HR) and heart rate variability (HRV) measurements - as a way of helping families to understand how physical symptoms can signal activation of the body's stress systems. This study measured respiratory rates, HR and HRV in children and adolescents with FSS (and healthy controls) during baseline assessment to determine whether these biological markers were effective at differentiating patients with FSS. The study also implemented a biofeedback intervention during the assessment to determine whether patients with FSS were able to slow their respiratory rates and increase HRV. Patients with FSS had faster respiratory rates, faster HR, and lower HRV, suggesting activation of the autonomic nervous system coupled with activation of the respiratory motor system. Like controls, patients were able to slow their respiratory rates, but in contrast to controls, they were unable to increase their HRV. Our findings suggest that patients with FSS present in a state of physiological activation and struggle to regulate their body state. Patients with FSS are likely to need ongoing training and practice to regulate body state coupled with interventions that target regulatory capacity across multiple systems.
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Affiliation(s)
- Catherine Chudleigh
- 1 Department of Psychological Medicine, The Children's Hospital at Westmead, NSW, Australia
| | - Blanche Savage
- 1 Department of Psychological Medicine, The Children's Hospital at Westmead, NSW, Australia
| | - Catherine Cruz
- 1 Department of Psychological Medicine, The Children's Hospital at Westmead, NSW, Australia
| | - Melissa Lim
- 1 Department of Psychological Medicine, The Children's Hospital at Westmead, NSW, Australia
| | - Georgia McClure
- 1 Department of Psychological Medicine, The Children's Hospital at Westmead, NSW, Australia
| | - Donna M Palmer
- 2 Brain Dynamics Centre, The Westmead Institute for Medical Research, NSW, Australia.,3 The University of Sydney, NSW, Australia
| | | | - Kasia Kozlowska
- 1 Department of Psychological Medicine, The Children's Hospital at Westmead, NSW, Australia.,2 Brain Dynamics Centre, The Westmead Institute for Medical Research, NSW, Australia.,3 The University of Sydney, NSW, Australia
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Blomberg J, Gottfries CG, Elfaitouri A, Rizwan M, Rosén A. Infection Elicited Autoimmunity and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: An Explanatory Model. Front Immunol 2018; 9:229. [PMID: 29497420 PMCID: PMC5818468 DOI: 10.3389/fimmu.2018.00229] [Citation(s) in RCA: 79] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2017] [Accepted: 01/26/2018] [Indexed: 12/13/2022] Open
Abstract
Myalgic encephalomyelitis (ME) often also called chronic fatigue syndrome (ME/CFS) is a common, debilitating, disease of unknown origin. Although a subject of controversy and a considerable scientific literature, we think that a solid understanding of ME/CFS pathogenesis is emerging. In this study, we compiled recent findings and placed them in the context of the clinical picture and natural history of the disease. A pattern emerged, giving rise to an explanatory model. ME/CFS often starts after or during an infection. A logical explanation is that the infection initiates an autoreactive process, which affects several functions, including brain and energy metabolism. According to our model for ME/CFS pathogenesis, patients with a genetic predisposition and dysbiosis experience a gradual development of B cell clones prone to autoreactivity. Under normal circumstances these B cell offsprings would have led to tolerance. Subsequent exogenous microbial exposition (triggering) can lead to comorbidities such as fibromyalgia, thyroid disorder, and orthostatic hypotension. A decisive infectious trigger may then lead to immunization against autoantigens involved in aerobic energy production and/or hormone receptors and ion channel proteins, producing postexertional malaise and ME/CFS, affecting both muscle and brain. In principle, cloning and sequencing of immunoglobulin variable domains could reveal the evolution of pathogenic clones. Although evidence consistent with the model accumulated in recent years, there are several missing links in it. Hopefully, the hypothesis generates testable propositions that can augment the understanding of the pathogenesis of ME/CFS.
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Affiliation(s)
- Jonas Blomberg
- Department of Medical Sciences, Uppsala University, Clinical Microbiology, Academic Hospital, Uppsala, Sweden
| | | | - Amal Elfaitouri
- Department of Infectious Disease and Tropical Medicine, Faculty of Public Health, Benghazi University, Benghazi, Libya
| | - Muhammad Rizwan
- Department of Medical Sciences, Uppsala University, Clinical Microbiology, Academic Hospital, Uppsala, Sweden
| | - Anders Rosén
- Department of Clinical and Experimental Medicine, Division of Cell Biology, Linköping University, Linköping, Sweden
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Cutler SJ, Rudenko N, Golovchenko M, Cramaro WJ, Kirpach J, Savic S, Christova I, Amaro A. Diagnosing Borreliosis. Vector Borne Zoonotic Dis 2017; 17:2-11. [PMID: 28055580 DOI: 10.1089/vbz.2016.1962] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Borrelia species fall into two groups, the Borrelia burgdorferi sensu lato (Bbsl) complex, the cause of Lyme borreliosis (also known as Lyme disease), and the relapsing fever group. Both groups exhibit inter- and intraspecies diversity and thus have variations in both clinical presentation and diagnostic approaches. A further layer of complexity is derived from the fact that ticks may carry multiple infectious agents and are able to transmit them to the host during blood feeding, with potential overlapping clinical manifestations. Besides this, pathogens like Borrelia have developed strategies to evade the host immune system, which allows them to persist within the host, including humans. Diagnostics can be applied at different times during the clinical course and utilize sample types, each with their own advantages and limitations. These differing methods should always be considered in conjunction with potential exposure and compatible clinical features. Throughout this review, we aim to explore different approaches providing the reader with an overview of methods appropriate for various situations. This review will cover human pathogenic members of Bbsl and relapsing fever borreliae, including newly recognized Borrelia miyamotoi spirochetes.
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Affiliation(s)
- Sally J Cutler
- 1 School of Health, Sport & Bioscience, University of East London , London, United Kingdom
| | - Nataliia Rudenko
- 2 Biology Centre CAS, Institute of Parasitology , Ceske Budejovice, Czech Republic
| | - Maryna Golovchenko
- 2 Biology Centre CAS, Institute of Parasitology , Ceske Budejovice, Czech Republic
| | - Wibke J Cramaro
- 3 Department of Infection and Immunity, Luxembourg Institute of Health , Esch-sur-Alzette, Luxembourg
| | - Josiane Kirpach
- 3 Department of Infection and Immunity, Luxembourg Institute of Health , Esch-sur-Alzette, Luxembourg
| | - Sara Savic
- 4 Scientific Veterinary Institute "Novi Sad ," Rumenacki put 20, Novi Sad, Serbia
| | - Iva Christova
- 5 Department of Microbiology, National Center of Infectious and Parasitic Diseases , Sofia, Bulgaria
| | - Ana Amaro
- 6 National Institute for Agrarian and Veterinarian Research (INIAV) , Lisboa, Portugal
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Abstract
OBJECTIVE To determine appropriate management of the active individual with infectious mononucleosis (IM), including issues of diagnosis, the determination of splenomegaly, and other measures of disease status, the relationship of the disease to chronic fatigue syndrome (CFS), and the risks of exercise at various points in the disease process. DATA SOURCES An Ovid/MEDLINE search (January 1996-June 2015) was widely supplemented by "similar articles" found in Ovid/MEDLINE and PubMed, reference lists, and personal files. MAIN RESULTS Clinical diagnoses of IM are unreliable. Traditional laboratory indicators (lymphocytosis, abnormal lymphocytes, and a heterophile-positive slide test) can be supplemented by more sensitive and more specific but also more costly Epstein-Barr antigen determinations. Clinical estimates of splenomegaly are fallible. Laboratory determinations, commonly by 2D ultrasonography, must take account of methodology, the formulae used in calculations and the individual's body size. The SD of normal values matches the typical increase of size in IM, but repeat measurements can help to monitor regression of the disease. The main risks to the athlete are spontaneous splenic rupture (seen in 0.1%-0.5% of patients and signaled by acute abdominal pain) and progression to chronic fatigue, best avoided by 3 to 4 weeks of restricted activity followed by graded reconditioning. A full recovery of athletic performance is usual with 2 to 3 months of conservative management. CONCLUSIONS Infectious mononucleosis is a common issue for young athletes. But given accurate diagnosis and the avoidance of splenic rupture and progression to CFS through a few weeks of restricted activity, long-term risks to the health of athletes are few.
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Ajdacic-Gross V, Aleksandrowicz A, Rodgers S, Mutsch M, Tesic A, Müller M, Kawohl W, Rössler W, Seifritz E, Castelao E, Strippoli MPF, Vandeleur C, von Känel R, Paolicelli R, Landolt MA, Witthauer C, Lieb R, Preisig M. Infectious, atopic and inflammatory diseases, childhood adversities and familial aggregation are independently associated with the risk for mental disorders: Results from a large Swiss epidemiological study. World J Psychiatry 2016; 6:419-430. [PMID: 28078206 PMCID: PMC5183994 DOI: 10.5498/wjp.v6.i4.419] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/28/2016] [Revised: 09/08/2016] [Accepted: 10/09/2016] [Indexed: 02/05/2023] Open
Abstract
AIM To examine the associations between mental disorders and infectious, atopic, inflammatory diseases while adjusting for other risk factors.
METHODS We used data from PsyCoLaus, a large Swiss Population Cohort Study (n = 3720; age range 35-66). Lifetime diagnoses of mental disorders were grouped into the following categories: Neurodevelopmental, anxiety (early and late onset), mood and substance disorders. They were regressed on infectious, atopic and other inflammatory diseases adjusting for sex, educational level, familial aggregation, childhood adversities and traumatic experiences in childhood. A multivariate logistic regression was applied to each group of disorders. In a complementary analysis interactions with sex were introduced via nested effects.
RESULTS Associations with infectious, atopic and other chronic inflammatory diseases were observable together with consistent effects of childhood adversities and familial aggregation, and less consistent effects of trauma in each group of mental disorders. Streptococcal infections were associated with neurodevelopmental disorders (men), and measles/mumps/rubella-infections with early and late anxiety disorders (women). Gastric inflammatory diseases took effect in mood disorders (both sexes) and in early disorders (men). Similarly, irritable bowel syndrome was prominent in a sex-specific way in mood disorders in women, and, moreover, was associated with early and late anxiety disorders. Atopic diseases were associated with late anxiety disorders. Acne (associations with mood disorders in men) and psoriasis (associations with early anxiety disorders in men and mood disorders in women) contributed sex-specific results. Urinary tract infections were associated with mood disorders and, in addition, in a sex-specific way with late anxiety disorders (men), and neurodevelopmental and early anxiety disorders (women).
CONCLUSION Infectious, atopic and inflammatory diseases are important risk factors for all groups of mental disorders. The sexual dimorphism of the associations is pronounced.
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Le syndrome de fatigue chronique : une nouvelle maladie ? Rev Med Interne 2016; 37:811-819. [DOI: 10.1016/j.revmed.2016.05.003] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2016] [Accepted: 05/02/2016] [Indexed: 01/26/2023]
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Zouikr I, Bartholomeusz MD, Hodgson DM. Early life programming of pain: focus on neuroimmune to endocrine communication. J Transl Med 2016; 14:123. [PMID: 27154463 PMCID: PMC4859995 DOI: 10.1186/s12967-016-0879-8] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2016] [Accepted: 04/27/2016] [Indexed: 01/21/2023] Open
Abstract
Chronic pain constitutes a challenge for the scientific community and a significant economic and social cost for modern societies. Given the failure of current drugs to effectively treat chronic pain, which are based on suppressing aberrant neuronal excitability, we propose in this review an integrated approach that views pain not solely originating from neuronal activation but also the result of a complex interaction between the nervous, immune, and endocrine systems. Pain assessment must also extend beyond measures of behavioural responses to noxious stimuli to a more developmentally informed assessment given the significant plasticity of the nociceptive system during the neonatal period. Finally integrating the concept of perinatal programming into the pain management field is a necessary step to develop and target interventions to reduce the suffering associated with chronic pain. We present clinical and animal findings from our laboratory (and others) demonstrating the importance of the microbial and relational environment in programming pain responsiveness later in life via action on hypothalamo-pituitary adrenal (HPA) axis activity, peripheral and central immune system, spinal and supraspinal mechanisms, and the autonomic nervous system.
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Affiliation(s)
- I Zouikr
- Laboratory of Neuroimmunology, School of Psychology, The University of Newcastle, Newcastle, NSW, Australia. .,Laboratory for Molecular Mechanisms of Thalamus Development, RIKEN BSI East Building 4F 409, 2-1 Hirosawa, Wako, Saitama, 351-0198, Japan.
| | - M D Bartholomeusz
- Laboratory of Neuroimmunology, School of Psychology, The University of Newcastle, Newcastle, NSW, Australia
| | - D M Hodgson
- Laboratory of Neuroimmunology, School of Psychology, The University of Newcastle, Newcastle, NSW, Australia
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Ajdacic-Gross V, Aleksandrowicz A, Rodgers S, Müller M, Kawohl W, Rössler W, Castelao E, Vandeleur C, von Känel R, Mutsch M, Lieb R, Preisig M. Social Phobia Is Associated with Delayed Onset of Chickenpox, Measles, and Mumps Infections. Front Psychiatry 2016; 7:203. [PMID: 28082921 PMCID: PMC5186793 DOI: 10.3389/fpsyt.2016.00203] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/12/2016] [Accepted: 12/08/2016] [Indexed: 01/03/2023] Open
Abstract
OBJECTIVE Evidence showing that infectious diseases in childhood play an important role in the etiopathogenesis of neurodevelopmental and other mental disorders is growing. The aim of this study was to explore the timing of common childhood diseases in early-onset anxiety disorders. MATERIALS AND METHODS We analyzed data from PsyCoLaus, a large Swiss Population Cohort Study (N = 3720). In this study, we regressed overanxious disorder, separation anxiety disorder, social phobia, and specific phobias on the age of onset of several childhood diseases, always adjusting for the other anxiety disorders listed above and for sex. RESULTS The timing of viral childhood diseases (chickenpox, measles, and mumps) was consistently delayed in social phobia, notably both in men and women. We found no evidence for a reversed sequence of onset of phobia symptoms before that of the infections included. CONCLUSION Social phobia was the only early anxiety disorder to show an association with a delayed onset of common viral childhood diseases.
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Affiliation(s)
- Vladeta Ajdacic-Gross
- Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric Hospital, University of Zürich, Zürich, Switzerland; Epidemiology, Biostatistics and Prevention Institute, University of Zürich, Zürich, Switzerland
| | - Aleksandra Aleksandrowicz
- Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric Hospital, University of Zürich , Zürich , Switzerland
| | - Stephanie Rodgers
- Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric Hospital, University of Zürich , Zürich , Switzerland
| | - Mario Müller
- Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric Hospital, University of Zürich , Zürich , Switzerland
| | - Wolfram Kawohl
- Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric Hospital, University of Zürich , Zürich , Switzerland
| | - Wulf Rössler
- Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric Hospital, University of Zürich, Zürich, Switzerland; Collegium Helveticum, Swiss Federal Institute of Technology, University of Zürich, Zürich, Switzerland; Institute of Psychiatry, Laboratory of Neuroscience (LIM27), University of Sao Paulo, Sao Paulo, Brazil
| | - Enrique Castelao
- Department of Psychiatry, University Hospital of Lausanne , Lausanne , Switzerland
| | - Caroline Vandeleur
- Department of Psychiatry, University Hospital of Lausanne , Lausanne , Switzerland
| | - Roland von Känel
- Department of Neurology, Bern University Hospital, Clinic Barmelweid , Barmelweid , Switzerland
| | - Margot Mutsch
- Epidemiology, Biostatistics and Prevention Institute, University of Zürich , Zürich , Switzerland
| | - Roselind Lieb
- Department of Psychology, Division of Clinical Psychology and Epidemiology, University of Basel , Basel , Switzerland
| | - Martin Preisig
- Department of Psychiatry, University Hospital of Lausanne , Lausanne , Switzerland
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Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is associated with pandemic influenza infection, but not with an adjuvanted pandemic influenza vaccine. Vaccine 2015; 33:6173-7. [PMID: 26475444 DOI: 10.1016/j.vaccine.2015.10.018] [Citation(s) in RCA: 52] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2015] [Revised: 09/22/2015] [Accepted: 10/06/2015] [Indexed: 01/02/2023]
Abstract
BACKGROUND Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is associated to infections and it has been suggested that vaccination can trigger the disease. However, little is known about the specific association between clinically manifest influenza/influenza vaccine and CFS/ME. As part of a registry surveillance of adverse effects after mass vaccination in Norway during the 2009 influenza A (H1N1) pandemic, we had the opportunity to estimate and contrast the risk of CFS/ME after infection and vaccination. METHODS Using the unique personal identification number assigned to everybody who is registered as resident in Norway, we followed the complete Norwegian population as of October 1, 2009, through national registries of vaccination, communicable diseases, primary health, and specialist health care until December 31, 2012. Hazard ratios (HRs) of CFS/ME, as diagnosed in the specialist health care services (diagnostic code G93.3 in the International Classification of Diseases, Version 10), after influenza infection and/or vaccination were estimated using Cox proportional-hazards regression. RESULTS The incidence rate of CFS/ME was 2.08 per 100,000 person-months at risk. The adjusted HR of CFS/ME after pandemic vaccination was 0.97 (95% confidence interval [CI]: 0.91-1.04), while it was 2.04 (95% CI: 1.78-2.33) after being diagnosed with influenza infection during the peak pandemic period. CONCLUSIONS Pandemic influenza A (H1N1) infection was associated with a more than two-fold increased risk of CFS/ME. We found no indication of increased risk of CFS/ME after vaccination. Our findings are consistent with a model whereby symptomatic infection, rather than antigenic stimulation may trigger CFS/ME.
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Abstract
Lyme disease, caused by the Borrelia burgdorferi bacterium, is the most common vector-borne disease in the northern hemisphere. The clinical presentation varies with disease stage, and neurological manifestations (often referred to as Lyme neuroborreliosis) are reported in up to 12% of patients with Lyme disease. Most aspects of the epidemiology, clinical manifestation and treatment of Lyme neuroborreliosis are well known and accepted; only the management of so-called chronic Lyme disease is surrounded by considerable controversy. This term is used for disparate patient groups, including those who have untreated late-stage infection (for example, late neuroborreliosis), those with subjective symptoms that persist after treatment (termed 'post-treatment Lyme disease syndrome' [PTLDS]), and those with unexplained subjective complaints that may or may not be accompanied by positive test results for B. burgdorferi infection in serum (here called 'chronic Lyme disease'). The incidence of PTLDS is still a matter of debate, and its pathogenesis is unclear, but there is evidence that these patients do not have ongoing B. burgdorferi infection and, thus, do not benefit from additional antibiotic therapy. Chronic Lyme disease lacks an accepted clinical definition, and most patients who receive this diagnosis have other illnesses. Thus, a careful diagnostic work-up is needed to ensure proper treatment.
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Affiliation(s)
- Uwe Koedel
- Clinic Grosshadern of the Ludwig-Maximilians University of Munich, Department of Neurology, Marchioninistrasse 15, D-81377 Munich, Germany
| | - Volker Fingerle
- Bavarian Health and Food Safety Authority &German National Reference Centre for Borrelia, Veterinärstrasse 2, 85764 Oberschleissheim, Germany
| | - Hans-Walter Pfister
- Clinic Grosshadern of the Ludwig-Maximilians University of Munich, Department of Neurology, Marchioninistrasse 15, D-81377 Munich, Germany
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Twisk FNM. Accurate diagnosis of myalgic encephalomyelitis and chronic fatigue syndrome based upon objective test methods for characteristic symptoms. World J Methodol 2015; 5:68-87. [PMID: 26140274 PMCID: PMC4482824 DOI: 10.5662/wjm.v5.i2.68] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/05/2014] [Revised: 02/10/2015] [Accepted: 05/27/2015] [Indexed: 02/06/2023] Open
Abstract
Although myalgic encephalomyelitis (ME) and chronic fatigue syndrome (CFS) are considered to be synonymous, the definitional criteria for ME and CFS define two distinct, partially overlapping, clinical entities. ME, whether defined by the original criteria or by the recently proposed criteria, is not equivalent to CFS, let alone a severe variant of incapacitating chronic fatigue. Distinctive features of ME are: muscle weakness and easy muscle fatigability, cognitive impairment, circulatory deficits, a marked variability of the symptoms in presence and severity, but above all, post-exertional “malaise”: a (delayed) prolonged aggravation of symptoms after a minor exertion. In contrast, CFS is primarily defined by (unexplained) chronic fatigue, which should be accompanied by four out of a list of 8 symptoms, e.g., headaches. Due to the subjective nature of several symptoms of ME and CFS, researchers and clinicians have questioned the physiological origin of these symptoms and qualified ME and CFS as functional somatic syndromes. However, various characteristic symptoms, e.g., post-exertional “malaise” and muscle weakness, can be assessed objectively using well-accepted methods, e.g., cardiopulmonary exercise tests and cognitive tests. The objective measures acquired by these methods should be used to accurately diagnose patients, to evaluate the severity and impact of the illness objectively and to assess the positive and negative effects of proposed therapies impartially.
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Chijiwa T, Oka T, Lkhagvasuren B, Yoshihara K, Sudo N. Prior chronic stress induces persistent polyI:C-induced allodynia and depressive-like behavior in rats: Possible involvement of glucocorticoids and microglia. Physiol Behav 2015; 147:264-73. [PMID: 25936823 DOI: 10.1016/j.physbeh.2015.04.050] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/26/2014] [Revised: 04/03/2015] [Accepted: 04/29/2015] [Indexed: 10/23/2022]
Abstract
When animals suffer from viral infections, they develop a set of symptoms known as the "sickness response." Recent studies suggest that psychological stress can modulate the sickness response. However, it remains uncertain whether acute and chronic psychosocial stresses have the same effect on viral infection-induced sickness responses. To address this question, we compared changes in polyI:C-induced sickness responses, such as fever, change of body weight and food intake, mechanical allodynia, and depressive-like behavior, in rats that had been pre-exposed to single and repeated social defeat stresses. Intraperitoneal injection of polyI:C induced a maximal fever of 38.0°C 3h after injection. Rats exposed to prior social defeat stress exhibited blunted febrile responses, which were more pronounced in the repeated stress group. Furthermore, only the repeated stress group showed late-onset and prolonged mechanical allodynia lasting until 8days after injection in the von Frey test and prolonged immobility time in the forced swim test 9days post-injection. To assess the role of glucocorticoids and microglia in the delayed and persistent development of these sickness responses in rats exposed to repeated stress, we investigated the effect of pretreatment with RU486, a glucocorticoid receptor antagonist, and minocycline, an inhibitor of microglial activation, on polyI:C-induced allodynia and depressive-like behavior. Pretreatment with either drug inhibited both the delayed allodynia and depressive-like behavior. The present study demonstrates that repeated, but not single, social defeat stress followed by systemic polyI:C administration induced prolonged allodynia and depressive-like behavior in rats. Our results show that even though a single-event psychosocial stress does not have any effect by itself, animals may develop persistent allodynia and depressive-like behavior when they suffer from an infectious disease if they are pre-exposed to repeated or chronic psychosocial stress. Furthermore, this study suggests that stress-induced corticosterone and microglial activation play a pivotal role in this phenomenon.
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Affiliation(s)
- Takeharu Chijiwa
- Department of Psychosomatic Medicine, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan
| | - Takakazu Oka
- Department of Psychosomatic Medicine, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
| | - Battuvshin Lkhagvasuren
- Department of Psychosomatic Medicine, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan
| | - Kazufumi Yoshihara
- Department of Psychosomatic Medicine, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan
| | - Nobuyuki Sudo
- Department of Psychosomatic Medicine, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan
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Twisk FNM. A critical analysis of the proposal of the Institute of Medicine to replace myalgic encephalomyelitis and chronic fatigue syndrome by a new diagnostic entity called systemic exertion intolerance disease. Curr Med Res Opin 2015; 31:1333-47. [PMID: 25912615 DOI: 10.1185/03007995.2015.1045472] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
Abstract
The Institute of Medicine (IOM) recently published their report in response to an assignment "to define diagnostic criteria for Myalgic Encephalomyelitis (ME)/chronic fatigue syndrome (CFS), to propose a process for reevaluation of these criteria in the future, and to consider whether a new name for this disease is warranted". The basic pre-assumption of the IOM committee for the development of evidence-based diagnostic criteria for ME/CFS was that ME and CFS denote conditions with similar symptoms, hence ME/CFS. The IOM committee recommends: (1) that ME/CFS will be renamed 'systemic exertion intolerance disease' (SEID); and that a new code should be assigned to SEID in the International Classification of Diseases (ICD), replacing the existing codes for ME (a neurological disease: G93.3) and CFS ('signs, symptoms, and abnormal clinical and laboratory findings, not elsewhere classified': R53.82); (2) that a diagnosis of SEID should be made if the new diagnostic criteria are met; (3) that the Department of Health and Human Services develops a toolkit appropriate for screening and diagnosing patients; and (4) that a multidisciplinary group re-examines the new diagnostic criteria when necessary. This editorial reviews the working procedure of the IOM and two of the outcomes: the recommendation to introduce a new clinical entity (SEID) and new diagnostic criteria. Based upon the contents of the report, and the arguments of the IOM, a search of PubMed and the archive of the Journal of Chronic Fatigue Syndrome using the search terms ME (and old synonyms) and CFS, and a search of PubMed related to the five core symptoms of SEID was conducted. Reviewing the working method and the recommendations, it is concluded that the new diagnostic criteria for SEID are based upon important methodological shortcomings and that the introduction of SEID to replace both ME and CFS has several profound negative consequences outweighing the advantages.
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Klineberg E, Rushworth A, Bibby H, Bennett D, Steinbeck K, Towns S. Adolescent chronic fatigue syndrome and somatoform disorders: a prospective clinical study. J Paediatr Child Health 2014; 50:775-81. [PMID: 24944088 DOI: 10.1111/jpc.12653] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 03/23/2014] [Indexed: 11/27/2022]
Abstract
AIM To examine and compare the presenting characteristics and the change in the physical and psychosocial functioning of adolescents with chronic fatigue syndrome (CFS) or somatoform disorders who have received an adaptable multidisciplinary intervention over a 12-month period. METHODS Fifty adolescents presenting to the Complex Adolescent Clinic at The Children's Hospital at Westmead, Sydney, Australia were assessed. Their physical and psychosocial functioning was rated by the adolescents and their parents using the Child Health Questionnaire. Participants were assessed at baseline, 4 months and 12 months after initiating treatment. Analyses examined whether diagnosis and/or illness precipitants were related to treatment outcome. RESULTS Adolescents with both CFS and somatoform disorders demonstrated improvement in physical and psychosocial functioning over the first 4 months of treatment, sustained at 12-month follow-up. A diagnosis of CFS was associated with poorer physical functioning over time and a trend towards a longer illness time course compared with somatoform disorder. Adjustment for a physical precipitant reduced the association between diagnosis and physical functioning. Those who had a physical precipitant to their illness had significantly poorer physical functioning over time than those who did not, regardless of diagnostic category. Diagnosis and physical precipitant were not associated with psychosocial functioning. CONCLUSIONS Improvement in adolescent physical and psychosocial functioning over time suggests that a multidisciplinary treatment model may be effective for varied complex medico-psychosocial presentations, irrespective of diagnosis and illness precipitant. Illness precipitant may have a greater influence on treatment outcome than diagnostic category.
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Affiliation(s)
- Emily Klineberg
- Academic Department of Adolescent Medicine, The Children's Hospital at Westmead, Sydney, New South Wales, Australia; Sydney Medical School, The University of Sydney, Sydney, New South Wales, Australia
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Normal Salivary Cortisol and NK Cell Function in Adolescents With Chronic Fatigue Syndrome Following Infectious Mononucleosis. ARCHIVES OF PEDIATRIC INFECTIOUS DISEASES 2013. [DOI: 10.5812/pedinfect.13107] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
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Abstract
PURPOSE OF REVIEW Functional somatic symptoms (FSS) are common in children and adolescents, but explanatory models that synthesize research findings are lacking. This article reviews the studies published from January 2012 to March 2013 that investigate the neurophysiological mechanisms that may underlie FSS. RECENT FINDINGS Studies from diverse medical disciplines suggest that FSS are associated with functional differences in hypothalamic-pituitary-adrenal function, imbalances in vagal-sympathetic tone, upregulation of immune-inflammatory function, and primed cognitive-emotional responses that serve to amplify reactivity to threatening stimuli, thereby contributing to the subjective experience of somatic symptoms. SUMMARY FSS appear to reflect dysregulations of the stress system. When seemingly disparate research findings are interpreted together within an overarching 'stress-system' framework, a coherent explanatory model begins to emerge.
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