Increased Risk of Chronic Fatigue Syndrome Following Atopy: A Population-Based Study

Abstract:

Several hypotheses have been proposed to explain the etiopathogenesis of chronic fatigue syndrome (CFS), including immune dysregulation. However, few population-based prospective cohort studies have been conducted on CFS and atopy.

We investigated the relationship between atopy and CFS by using a population-based cohort study. In this prospective, population-based cohort study of the National Health Insurance Research Database, we identified 42,558 patients with atopy and 170,232 patients without atopy from 2005 to 2007 with follow-up to 2011. The incidence rates and risks for CFS were estimated using Cox proportion hazards regression.

The overall incidence rate of CFS was higher in the atopy cohort compared with the nonatopy cohort (1.37 versus 0.87 per 1000 person-year), with an adjusted hazard ratio of 1.48 (95% confidence interval 1.30-1.69). The risk of CFS in the atopy cohort increased 1.47- to 1.50-fold for each nonexisting comorbidity. Patients with numerous atopic symptoms exhibited a biological gradient of increasing risk for CFS, and the risk changed significantly after adjustment for age, sex, and comorbidities, increasing from 1.46- to 2.59-fold.

We revealed that atopy is associated with CFS, particularly in patients with numerous atopic syndromes. The actual mechanism for CFS development in patients with atopy remains unclear and requires further investigation. We recommend researching the subsequent fatigue symptom in patients with atopy, particularly those with multiple atopic syndromes.

 

Source: Yang TY, Kuo HT, Chen HJ, Chen CS, Lin WM, Tsai SY, Kuo CN, Kao CH. Increased Risk of Chronic Fatigue Syndrome Following Atopy: A Population-Based Study. Medicine (Baltimore). 2015 Jul;94(29):e1211. doi: 10.1097/MD.0000000000001211. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4603016/ (Full article)

 

Role of polymorphisms of inducible nitric oxide synthase and endothelial nitric oxide synthase in idiopathic environmental intolerances

Abstract:

Oxidative stress and inflammation play a pathogenetic role in idiopathic environmental intolerances (IEI), namely, multiple chemical sensitivity (MCS), fibromyalgia (FM), and chronic fatigue syndrome (CFS). Given the reported association of nitric oxide synthase (NOS) gene polymorphisms with inflammatory disorders, we aimed to investigate the distribution of NOS2A -2.5 kb (CCTTT) n as well as Ser608Leu and NOS3 -786T>C variants and their correlation with nitrite/nitrate levels, in a study cohort including 170 MCS, 108 suspected MCS (SMCS), 89 FM/CFS, and 196 healthy subjects.

Patients and controls had similar distributions of NOS2A Ser608Leu and NOS3 -786T>C polymorphisms. Interestingly, the NOS3 -786TT genotype was associated with increased nitrite/nitrate levels only in IEI patients. We also found that the NOS2A -2.5 kb (CCTTT)11 allele represents a genetic determinant for FM/CFS, and the (CCTTT)16 allele discriminates MCS from SMCS patients. Instead, the (CCTTT)8 allele reduces by three-, six-, and tenfold, respectively, the risk for MCS, SMCS, and FM/CFS. Moreover, a short number of (CCTTT) repeats is associated with higher concentrations of nitrites/nitrates. Here, we first demonstrate that NOS3 -786T>C variant affects nitrite/nitrate levels in IEI patients and that screening for NOS2A -2.5 kb (CCTTT) n polymorphism may be useful for differential diagnosis of various IEI.

 

Source: De Luca C, Gugliandolo A, Calabrò C, Currò M, Ientile R, Raskovic D, Korkina L, Caccamo D. Role of polymorphisms of inducible nitric oxide synthase and endothelial nitric oxide synthase in idiopathic environmental intolerances. Mediators Inflamm. 2015;2015:245308. doi: 10.1155/2015/245308. Epub 2015 Mar 24. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4387900/ (Full article)

 

An investigation of symptoms predating CFS onset

Abstract:

The Fukuda et al. (1994) criteria for chronic fatigue syndrome (CFS) specifies that a symptom can only be included within a diagnosis if it is experienced concurrently or following the onset of fatigue. In order to investigate this issue, participants provided information on persisting symptoms (lasting greater than six months) and whether those symptoms occurred prior to, concurrently, or following the onset of their fatigue.

More symptoms were experienced after the fatigue onset than prior to the fatigue onset; however, a considerable number of participants reported experiencing persisting symptoms prior to the onset of CFS. Particularly, rates of hay fever and asthma were higher prior to the illness. Investigating symptoms prior to the onset of the illness might provide investigators with ways to better understand the etiology of this illness.

 

Source: Evans M, Barry M, Im Y, Brown A, Jason LA. An investigation of symptoms predating CFS onset. J Prev Interv Community. 2015;43(1):54-61. doi: 10.1080/10852352.2014.973240. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4830334/ (Full article)

 

Longitudinal follow-up of employment status in patients with chronic fatigue syndrome after mononucleosis

Abstract:

OBJECTIVE: To examine the effect of early clinical and demographic factors on occupational outcome, return to work or awarded permanent disability pension in young patients with chronic fatigue syndrome (CFS).

DESIGN: Longitudinal cohort study.

INTERVENTION: A written self-management programme including a description of active coping strategies for daily life was provided.

SETTING, PARTICIPANTS: Patients with CFS after mononucleosis were evaluated at Department of Neurology, Haukeland University Hospital during 1996-2006 (contact 1). In 2009 self-report questionnaires were sent to all patients (contact 2).

PRIMARY AND SECONDARY OUTCOME MEASURES: Primary measure was employment status at contact 2. Secondary measures included clinical symptoms, and Fatigue Severity Scale (FSS) scores on both contacts, and Work and Social Adjustment Scale (WSAS) at contact 2.

RESULTS: Of 111 patients at contact 1, 92 (83%) patients returned the questionnaire at contact 2. Mean disease duration at contact 1 was 4.7 years and at contact 2 11.4 years. At contact 1, 9 (10%) were part-time or full-time employed. At contact 2, 49 (55%) were part-time or full-time employed. Logical regression analysis showed that FSS≥5 at contact 2 was associated with depression, arthralgia and long disease duration (all at contact 1).

CONCLUSIONS: About half of younger patients with CFS with long-term incapacity for work experienced marked improvement including full-time or part-time employment showing better outcomes than expected. Risk factors for transition to permanent disability were depression, arthralgia and disease duration.

Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

 

Source: Nyland M, Naess H, Birkeland JS, Nyland H. Longitudinal follow-up of employment status in patients with chronic fatigue syndrome after mononucleosis. BMJ Open. 2014 Nov 26;4(11):e005798. doi: 10.1136/bmjopen-2014-005798. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4248085/ (Full article)

 

Chronic fatigue syndrome and fibromyalgia following immunization with the hepatitis B vaccine: another angle of the ‘autoimmune (auto-inflammatory) syndrome induced by adjuvants’ (ASIA)

Abstract:

The objectives of this study were to gather information regarding demographic and clinical characteristics of patients diagnosed with either fibromyalgia (FM) or chronic fatigue (CFS) following hepatitis B vaccination (HBVv) and furthermore to apply the recently suggested criteria of autoimmune (auto-inflammatory) syndromes induced by adjuvants (ASIA), in the aim of identifying common characteristics that may suggest an association between fibromyalgia, chronic fatigue and HBV vaccination.

Medical records of 19 patients with CFS and/or fibromyalgia following HBVv immunization were analyzed. All of which were immunized during 1990-2008 in different centers in the USA. All medical records were evaluated for demographics, medical history, the number of vaccine doses, as well as immediate and long term post-immunization adverse events and clinical manifestations. In addition, available blood tests, imaging results, treatments and outcomes were analyzed. ASIA criteria were applied to all patients.

The mean age of patients was 28.6 ± 11 years, of which 68.4 % were females. 21.05 % had either personal or familial background of autoimmune disease. The mean latency period from the last dose of HBVv to onset of symptoms was 38.6 ± 79.4 days, ranging from days to a year. Eight (42.1 %) patients continued with the immunization program despite experiencing adverse events. Manifestations that were commonly reported included neurological manifestations (84.2 %), musculoskeletal (78.9 %), psychiatric (63.1 %), fatigue (63.1 %), gastrointestinal complains (58 %) and mucocutaneous manifestations (36.8 %). Autoantibodies were detected in 71 % of patients tested. All patients fulfilled the ASIA criteria.

This study suggests that in some cases CFS and FM can be temporally related to immunization, as part of ASIA syndrome. The appearance of adverse event during immunization, the presence of autoimmune susceptibility and higher titers of autoantibodies all can be suggested as risk factors. ASIA criteria were fulfilled in all patients eluding the plausible link between ASIA and CFS/FM.

 

Source: Agmon-Levin N, Zafrir Y, Kivity S, Balofsky A, Amital H, Shoenfeld Y. Chronic fatigue syndrome and fibromyalgia following immunization with the hepatitis B vaccine: another angle of the ‘autoimmune (auto-inflammatory) syndrome induced by adjuvants’ (ASIA). Immunol Res. 2014 Dec;60(2-3):376-83. doi: 10.1007/s12026-014-8604-2. https://www.ncbi.nlm.nih.gov/pubmed/25427994

 

Chronic fatigue syndrome is associated with the risk of fracture: a nationwide cohort study

Abstract:

PURPOSE: Chronic fatigue syndrome (CFS) is a complex disorder that is associated with unreasonable persistent fatigue. CFS has also been reported to be a possible risk factor for osteopathy. We propose that CFS might be associated with an increased risk of fracture.

METHODS: We used the National Health Insurance Research Database to conduct a prospective cohort study, identifying 3744 patients with a CFS diagnosis (International Classification of Diseases, Ninth Revision, Clinical Modification code 780.71) and 14 976 patients without CFS until 2006, with follow-up observed until the end of 2010.

RESULTS: The incidence rate of fracture was higher in the CFS cohort than in the non-CFS cohort (17.44 vs. 14.53 per 1000 person-year, respectively), with an adjusted hazard ratio of 1.14 (95% confidence interval = 1.00-1.30). The risks of fracture between CFS and non-CFS were shown without comorbidity for each would be elevated than with other comorbidities, particularly in osteoporosis. The patients without osteoporosis in the CFS cohort exhibited a 1.16-fold higher risk of fracture than did those in the non-CFS cohort.

CONCLUSIONS: We propose that CFS-related fracture might not be associated with osteoporosis. The mechanism for developing CFS-related fracture remains unclear; however, we recommend noticing the prevention of fracture for CFS patients before clarifying the aetiology of CFS-related fracture.

© The Author 2014. Published by Oxford University Press on behalf of the Association of Physicians. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

 

Source: Chen CS, Lin WM, Yang TY, Chen HJ, Kuo CN, Kao CH. Chronic fatigue syndrome is associated with the risk of fracture: a nationwide cohort study. QJM. 2014 Aug;107(8):635-41. doi: 10.1093/qjmed/hcu037. Epub 2014 Mar 11. https://www.ncbi.nlm.nih.gov/pubmed/24619129

 

Chronic fatigue syndrome and subsequent risk of cancer among elderly US adults

Abstract:

BACKGROUND: The cause of chronic fatigue syndrome (CFS) is unknown but is thought to be associated with immune abnormalities or infection. Because cancer can arise from similar conditions, associations between CFS and cancer were examined in a population-based case-control study among the US elderly.

METHODS: Using linked Surveillance, Epidemiology, and End Results (SEER)-Medicare registry data, approximately 1.2 million cancer cases and 100,000 controls (age range, 66-99 years; 1992-2005) were evaluated. CFS was identified in the period more than 1 year prior to selection, using linked Medicare claims. Unconditional logistic regression was used to estimate the odds ratios (ORs) comparing the CFS prevalence in cases and controls, adjusting for age, sex, and selection year. All statistical tests were 2-sided.

RESULTS: CFS was present in 0.5% of cancer cases overall and 0.5% of controls. CFS was associated with an increased risk of non-Hodgkin lymphoma (NHL) (OR = 1.29, 95% confidence interval [CI] = 1.16-1.43, P = 1.7 × 10(-6) ). Among NHL subtypes, CFS was associated with diffuse large B cell lymphoma (OR = 1.34, 95% CI = 1.12-1.61), marginal zone lymphoma (OR = 1.88, 95% CI = 1.38-2.57), and B cell NHL not otherwise specified (OR = 1.51, 95% CI = 1.03-2.23). CFS associations with NHL overall and NHL subtypes remained elevated after excluding patients with medical conditions related to CFS or NHL, such as autoimmune conditions. CFS was also associated, although not after multiple comparison adjustment, with cancers of the pancreas (OR = 1.25, 95% CI = 1.07-1.47), kidney (OR = 1.27, 95% CI = 1.07-1.49), breast (OR = 0.85, 95% CI = 0.74-0.98), and oral cavity and pharynx (OR = 0.70, 95% CI = 0.49-1.00).

CONCLUSIONS: Chronic immune activation or an infection associated with CFS may play a role in explaining the increased risk of NHL.

Copyright © 2012 American Cancer Society.

 

Source: Chang CM, Warren JL, Engels EA. Chronic fatigue syndrome and subsequent risk of cancer among elderly US adults. Cancer. 2012 Dec 1;118(23):5929-36. doi: 10.1002/cncr.27612. Epub 2012 May 30. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3434293/ (Full article)

 

Attention-deficit hyperactivity disorder in chronic fatigue syndrome patients

Abstract:

Psychopathological disorders are frequent in chronic fatigue syndrome patients. The present study examines the presence of attention-deficit hyperactivity disorder (ADHD) in a sample of adult chronic fatigue syndrome (CFS) patients, and evaluates its clinical consequences in this population. CFS patients were assessed for childhood and adult ADHD by clinical interview and ADHD-specific scales. Psychopathological comorbidities were evaluated by clinical examination and questionnaires.

Forty-seven of 158 CSF patients (29.7%) were diagnosed of childhood ADHD and in 33 (20.9%), the condition persisted into adulthood. CFS patients with adult ADHD had an earlier CSF onset, more severe anxiety and depression symptoms, and a higher risk of suicide than CFS patients without ADHD. Using lineal regression analysis, we found that depressive symptoms and ADHD severity were significant predictors of fatigue intensity. Consequently, ADHD may be common in CFS patients, and is associated with a more severe psychopathologic clinical profile.

Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

 

Source: Sáez-Francàs N, Alegre J, Calvo N, Antonio Ramos-Quiroga J, Ruiz E, Hernández-Vara J, Casas M. Attention-deficit hyperactivity disorder in chronic fatigue syndrome patients. Psychiatry Res. 2012 Dec 30;200(2-3):748-53. doi: 10.1016/j.psychres.2012.04.041. Epub 2012 May 28. https://www.ncbi.nlm.nih.gov/pubmed/22648008

 

Chronic fatigue syndrome: acute infection and history of physical activity affect resting levels and response to exercise of plasma oxidant/antioxidant status and heat shock proteins

Abstract:

OBJECTIVES: A history of high-level physical activity and/or acute infection might constitute stress factors affecting the plasma oxidant-antioxidant status and levels of heat shock proteins (HSPs) in patients with chronic fatigue syndrome (CFS).

DESIGN: This case-control study compared data from 43 CFS patients to results from a matched control group of 23 healthy sedentary subjects.

SETTING AND SUBJECTS: Five patients had no relevant previous history (group I). Eighteen had practised high-level sport (group II), and severe acute infection had been diagnosed in nine patients (group III). A combination of sport practice and infection was noted in 11 patients (group IV).

INTERVENTIONS: After examination at rest, all subjects performed a maximal cycling exercise test. Plasma levels of two markers of oxidative stress [thiobarbituric acid reactive substances (TBARS) and reduced ascorbic acid (RAA)] and both HSP27 and HSP70 were measured.

RESULTS: At rest, compared with the control group, the TBARS level was higher in groups II, III and IV patients, and the RAA level was lower in groups III and IV. In addition, HSP70 levels were significantly lower in all CFS groups, compared with controls, but negative correlations were found between resting HSP27 and HSP70 levels and the history of physical activity. After exercise, the peak level of TBARS significantly increased in groups II, III and IV, and the variations in HSP27 and HSP70 were attenuated or suppressed, with the greatest effects in groups III and IV.

CONCLUSION: The presence of stress factors in the history of CFS patients is associated with severe oxidative stress and the suppression of protective HSP27 and HSP70 responses to exercise.

© 2011 The Association for the Publication of the Journal of Internal Medicine.

 

Source: Jammes Y, Steinberg JG, Delliaux S. Chronic fatigue syndrome: acute infection and history of physical activity affect resting levels and response to exercise of plasma oxidant/antioxidant status and heat shock proteins. J Intern Med. 2012 Jul;272(1):74-84. doi: 10.1111/j.1365-2796.2011.02488.x. Epub 2012 Jan 4. http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2796.2011.02488.x/full

 

Premorbid risk markers for chronic fatigue syndrome in the 1958 British birth cohort

Abstract:

BACKGROUND: Little is known about the aetiology of chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME); prospective studies suggest a role for premorbid mood disorder.

AIMS: To examine childhood and early adult adversity, ill health and physical activity as premorbid risk markers for CFS/ME by 42 years, taking psychopathology into account.

METHOD: Data were from the 1958 British birth cohort, a prospective study from birth to 42 years (n = 11 419). The outcomes were self-reported CFS/ME (n = 127) and operationally defined CFS-like illness (n = 241) at 42 years.

RESULTS: Adjusting for psychopathology, parental physical abuse (odds ratio (OR) = 2.10, 95% CI 1.16-3.81), childhood gastrointestinal symptoms (OR = 1.58, 95% CI 1.00-2.50) and parental reports of many colds (OR = 1.65, 95% CI 1.09-2.50) were independently associated with self-reported CFS/ME. Female gender and premorbid psychopathology were the only risk markers for CFS-like illness, independent of comorbid psychopathology.

CONCLUSIONS: This confirms the importance of premorbid psychopathology in the aetiological pathways of CFS/ME, and replicates retrospective findings that childhood adversity may play a role in a minority.

Comment in: Childhood sexual abuse and chronic fatigue syndrome. [Br J Psychiatry. 2012]

 

Source: Clark C, Goodwin L, Stansfeld SA, Hotopf M, White PD. Premorbid risk markers for chronic fatigue syndrome in the 1958 British birth cohort. Br J Psychiatry. 2011 Oct;199(4):323-9. doi: 10.1192/bjp.bp.110.083956. Epub 2011 Aug 18. http://bjp.rcpsych.org/content/199/4/323.long (Full article)