Psychological stress contributed to the development of low-grade fever in a patient with chronic fatigue syndrome: a case report

Abstract:

BACKGROUND: Low-grade fever is a common symptom in patients with chronic fatigue syndrome (CFS), but the mechanisms responsible for its development are poorly understood. We submit this case report that suggests that psychological stress contributes to low-grade fever in CFS.

CASE PRESENTATION: A 26-year-old female nurse with CFS was admitted to our hospital. She had been recording her axillary temperature regularly and found that it was especially high when she felt stress at work. To assess how psychological stress affects temperature and to investigate the possible mechanisms for this hyperthermia, we conducted a 60-minute stress interview and observed the changes in the following parameters: axillary temperature, fingertip temperature, systolic blood pressure, diastolic blood pressure, heart rate, plasma catecholamine levels, and serum levels of interleukin (IL)-1β and IL-6 (pyretic cytokines), tumor necrosis factor-α and IL-10 (antipyretic cytokines). The stress interview consisted of recalling and talking about stressful events. Her axillary temperature at baseline was 37.2°C, increasing to 38.2°C by the end of the interview. In contrast, her fingertip temperature decreased during the interview. Her heart rate, systolic and diastolic blood pressures, and plasma levels of noradrenaline and adrenaline increased during the interview; there were no significant changes in either pyretic or antipyretic cytokines during or after the interview.

CONCLUSIONS: A stress interview induced a 1.0°C increase in axillary temperature in a CFS patient. Negative emotion-associated sympathetic activation, rather than pyretic cytokine production, contributed to the increase in temperature induced by the stress interview. This suggests that psychological stress may contribute to the development or the exacerbation of low-grade fever in some CFS patients.

 

Source: Oka T, Kanemitsu Y, Sudo N, Hayashi H, Oka K. Psychological stress contributed to the development of low-grade fever in a patient with chronic fatigue syndrome: a case report. Biopsychosoc Med. 2013 Mar 8;7(1):7. doi: 10.1186/1751-0759-7-7. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3599992/ (Full article)

 

A narrative review on the similarities and dissimilarities between myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and sickness behavior

Abstract:

It is of importance whether myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a variant of sickness behavior. The latter is induced by acute infections/injury being principally mediated through proinflammatory cytokines. Sickness is a beneficial behavioral response that serves to enhance recovery, conserves energy and plays a role in the resolution of inflammation.

There are behavioral/symptomatic similarities (for example, fatigue, malaise, hyperalgesia) and dissimilarities (gastrointestinal symptoms, anorexia and weight loss) between sickness and ME/CFS. While sickness is an adaptive response induced by proinflammatory cytokines, ME/CFS is a chronic, disabling disorder, where the pathophysiology is related to activation of immunoinflammatory and oxidative pathways and autoimmune responses.

While sickness behavior is a state of energy conservation, which plays a role in combating pathogens, ME/CFS is a chronic disease underpinned by a state of energy depletion. While sickness is an acute response to infection/injury, the trigger factors in ME/CFS are less well defined and encompass acute and chronic infections, as well as inflammatory or autoimmune diseases. It is concluded that sickness behavior and ME/CFS are two different conditions.

 

Source: Morris G, Anderson G, Galecki P, Berk M, Maes M. A narrative review on the similarities and dissimilarities between myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and sickness behavior. BMC Med. 2013 Mar 8;11:64. doi: 10.1186/1741-7015-11-64. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3751187/ (Full article)

 

A case of lyme disease requiring over 1 year to diagnose at an infectious-disease clinic

Abstract:

A 42-year-old woman presenting with years of fever and vague symptoms could not be satisfactorily diagnosed in physical examination or conventional workups. She was presumptively diagnosed with chronic fatigue syndrome and treated symptomatically. Fourteen months after the initial visit, she developed left facial palsy. Lyme disease serology was positive. Four weeks of oral amoxicillin ameliorated symptoms. Only 5 to 15 cases of Lyme disease are reported annually in Japan, mostly from the northeastern-most island of Hokkaido. It may occur anywhere in Japan, however; probably is underdiagnosed. Lyme disease may cause fevers of unknown origin. Astute clinical suspicion and appropriate workups are thus needed to diagnose this infection.

 

Source: Iwata K, Shimada T, Kawabata H. A case of lyme disease requiring over 1 year to diagnose at an infectious-disease clinic. Kansenshogaku Zasshi. 2013 Jan;87(1):44-8. [Article in Japanese] https://www.ncbi.nlm.nih.gov/pubmed/23484378

 

Diagnosis of myalgic encephalomyelitis: where are we now?

Abstract:

INTRODUCTION: The World Health Organization has classified myalgic encephalomyelitis (ME) as a neurological disease since 1969 considering chronic fatigue syndrome (CFS) as a synonym used interchangeably for ME since 1969. ME and CFS are considered to be neuro-immune disorders, characterized by specific symptom profiles and a neuro-immune pathophysiology. However, there is controversy as to which criteria should be used to classify patients with “chronic fatigue syndrome.”

AREAS COVERED: The Centers for Disease Control and Prevention (CDC) criteria consider chronic fatigue (CF) to be distinctive for CFS, whereas the International Consensus Criteria (ICC) stresses the presence of post-exertion malaise (PEM) as the hallmark feature of ME. These case definitions have not been subjected to rigorous external validation methods, for example, pattern recognition analyses, instead being based on clinical insights and consensus.

EXPERT OPINION: Pattern recognition methods showed the existence of three qualitatively different categories: (a) CF, where CF evident, but not satisfying full CDC syndrome criteria. (b) CFS, satisfying CDC criteria but without PEM. (c) ME, where PEM is evident in CFS. Future research on this “chronic fatigue spectrum” should, therefore, use the above-mentioned validated categories and novel tailored algorithms to classify patients into ME, CFS, or CF.

Comment in: Comment and reply on: ME is a distinct diagnostic entity, not part of a chronic fatigue spectrum. [Expert Opin Med Diagn. 2013]

 

Source: Maes M, Anderson G, Morris G, Berk M. Diagnosis of myalgic encephalomyelitis: where are we now? Expert Opin Med Diagn. 2013 May;7(3):221-5. doi: 10.1517/17530059.2013.776039. Epub 2013 Feb 27. https://www.ncbi.nlm.nih.gov/pubmed/23480562

 

Altered functional B cell subset populations in patients with chronic fatigue syndrome compared to healthy controls

Abstract:

Chronic fatigue syndrome (CFS) is a heterogeneous disorder of unknown aetiology characterized by disabling fatigue, headaches, sleep disturbance and several other symptoms. The onset of CFS may follow a viral infection or period of stress. Patients with CFS do not have hypogammaglobulinaemia, predisposition to recurrent bacterial infections or symptoms of autoimmunity.

To date, defects in B cell numbers or function have not been shown in the literature. However, treatment with anti-B cell therapy using Rituximab has recently shown benefit to CFS patients. We therefore postulated that patients with CFS had a subtle humoral immune dysfunction, and performed extended B cell immunophenotyping.

We undertook a detailed characterization of the proportions of the different B cell subsets in 33 patients with CFS fulfilling the Canadian and Fukada criteria for CFS and compared these with 24 age- and gender-matched healthy controls (HC). CFS patients had greater numbers of naive B cells as a percentage of lymphocytes: 6·3 versus 3·9% in HC (P = 0·034), greater numbers of naive B cells as a percentage of B cells: 65 versus 47% in controls (P = 0·003), greater numbers of transitional B cells: 1·8 versus 0·8% in controls (P = 0·025) and reduced numbers of plasmablasts: 0·5 versus 0·9% in controls (P = 0·013). While the cause of these changes is unclear, we speculate whether they may suggest a subtle tendency to autoimmunity.

© 2012 British Society for Immunology.

 

Source: Bradley AS, Ford B, Bansal AS. Altered functional B cell subset populations in patients with chronic fatigue syndrome compared to healthy controls. Clin Exp Immunol. 2013 Apr;172(1):73-80. doi: 10.1111/cei.12043. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3719933/ (Full article)

 

Dyspnea in Chronic Fatigue Syndrome (CFS): comparison of two prospective cross-sectional studies

Abstract:

Chronic Fatigue Syndrome (CFS) subjects have many systemic complaints including shortness of breath. Dyspnea was compared in two CFS and control cohorts to characterize pathophysiology. Cohort 1 of 257 CFS and 456 control subjects were compared using the Medical Research Council chronic Dyspnea Scale (MRC Score; range 0-5). Cohort 2 of 106 CFS and 90 controls answered a Dyspnea Severity Score (range 0-20) adapted from the MRC Score. Subsets of both cohorts completed CFS Severity Scores, fatigue, and other questionnaires. A subset had pulmonary function and total lung capacity measurements.

Results show MRC Scores were equivalent between sexes in Cohort 1 CFS (1.92 [1.72-2.16]; mean [95% C.I.]) and controls (0.31 [0.23-0.39]; p<0.0001). Receiver-operator curves identified 2 as the threshold for positive MRC Scores in Cohort 1. This indicated 54% of CFS, but only 3% of controls, had significant dyspnea.

In Cohort 2, Dyspnea Score threshold of 4 indicated shortness of breath in 67% of CFS and 23% of controls. Cohort 2 Dyspnea Scores were higher for CFS (7.80 [6.60-9.00]) than controls (2.40 [1.60-3.20]; p<0.0001). CFS had significantly worse fatigue and other complaints compared to controls. Pulmonary function was normal in CFS, but Borg scores and sensations of chest pain and dizziness were significantly greater during testing than controls. General linear model of Cohort 2 CFS responses linked Dyspnea with rapid heart rate, chest pain and dizziness.

In conclusion, sensory hypersensitivity without airflow limitation contributed to dyspnea in CFS. Correlates of dyspnea in controls were distinct from CFS suggesting different mechanisms.

 

Source: Ravindran M, Adewuyi O, Zheng Y, Rayhan RU, Le U, Timbol C, Merck S, Esteitie R, Read C, Cooney M, Baraniuk J. Dyspnea in Chronic Fatigue Syndrome (CFS): comparison of two prospective cross-sectional studies. Glob J Health Sci. 2012 Dec 12;5(2):94-110. doi: 10.5539/gjhs.v5n2p94. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4209305/ (Full article)

 

A qualitative natural history study of ME/CFS in the community

Abstract:

In previous qualitative research on Myalgic Encephalomyelitis/chronic fatigue syndrome (ME/CFS), researchers have focused on the experiences of patients with ME/CFS in tertiary care samples. This qualitative study examined the natural history of people with ME/CFS (n = 19) from a community-based sample. Findings highlighted multilayered themes involving the illness experience and the physical construction of ME/CFS.

In addition, this study further illuminated unique subthemes regarding community response and treatment, which have implications for understanding the progression of ME/CFS as well as experiences of those within patient networks. There is a need for more longitudinal qualitative research on epidemiological samples of patients with ME/CFS.

 

Source: Anderson VR, Jason LA, Hlavaty LE. A qualitative natural history study of ME/CFS in the community. Health Care Women Int. 2014 Jan;35(1):3-26. doi: 10.1080/07399332.2012.684816. Epub 2013 Feb 27. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4852694/ (Full article)

 

The neuropsychiatric and neuropsychological features of chronic fatigue syndrome: revisiting the enigma

Abstract:

The aim of this article is to provide a comprehensive and updated review of the key neuropsychiatric and neuropsychological complaints associated with chronic fatigue syndrome (CFS). Neuropsychiatric and neuropsychological difficulties are common in CFS and are linked primarily to disorders of mood, affect and behaviour.

The neuropsychiatric complaint most frequently encountered amongst CFS patients is depression and in particular major depressive disorder (MDD). Despite decades of research, the precise aetiological relationship between CFS and MDD remains poorly understood. This has resulted in the development of a number of interesting and polarised hypotheses regarding the aetiological nature of CFS. Recent scientific advances have however begun to unravel a number of interesting inflammatory and immunological explanations that suggest CFS and MDD are distinct yet interrelated conditions.

The possibility that the overlap between CFS and MDD might be explained in terms of shared oxidative and nitrosative (IO&NS) pathways is an area of intense research interest and is reviewed in detail in this article. The overlap between CFS and MDD is further differentiated by variations in HPA axis activity between the two disorders. Important immunological differences between MDD and CFS are also reviewed with particular emphasis on antiviral RNase L pathways in CFS.

In addition to the presence of neuropsychiatric complaints, CFS is also associated with neuropsychological symptoms such as impaired attention, memory and reaction time. The key neuropsychological problems reported by CFS patients are also included in the review in an effort to understand the significance of cognitive impairment in CFS.

 

Source: Christley Y, Duffy T, Everall IP, Martin CR. The neuropsychiatric and neuropsychological features of chronic fatigue syndrome: revisiting the enigma. Curr Psychiatry Rep. 2013 Apr;15(4):353. doi: 10.1007/s11920-013-0353-8. https://www.ncbi.nlm.nih.gov/pubmed/23440559

 

Fatigue heralding multiple sclerosis

Abstract:

BACKGROUND: Fatigue is a common symptom in multiple sclerosis (MS) and is an important determinant of overall well-being and disability.

OBJECTIVE: To assess the frequency with which fatigue precedes the diagnosis of MS using a retrospective database analysis.

METHODS: Between January 1, 2003 and September 30, 2008, patients diagnosed with fatigue with and without fatigue-related medications within a 3-year period prior to newly diagnosed MS were identified from the MarketScan Databases. All statistical analysis was performed using SAS.

RESULTS: Of the 16,976 patients with MS in the overall population, 5305 (31.3%) were newly diagnosed with MS and had three years of continuous healthcare coverage prior to MS diagnosis. Of these patients, 1534 (28.9%) were labeled with chronic fatigue syndrome (ICD9-780.71) or malaise or fatigue (ICD9-780.79) prior to the diagnosis of MS. One-third of these patients were labeled with fatigue one to two years before the diagnosis; 30.8% were diagnosed only with fatigue and had no other MS symptoms prior to their MS diagnosis. Among the patients diagnosed with fatigue, 10.4% were also prescribed medication for fatigue.

CONCLUSION: This study demonstrates that fatigue may herald MS, often by years. A careful history for transient neurological symptoms and a physical examination is warranted in any patient presenting with fatigue.

 

Source: Berger JR, Pocoski J, Preblick R, Boklage S. Fatigue heralding multiple sclerosis. Mult Scler. 2013 Oct;19(11):1526-32. doi: 10.1177/1352458513477924. Epub 2013 Feb 25. https://www.ncbi.nlm.nih.gov/pubmed/23439577

 

Plasmacytoid dendritic cells in the duodenum of individuals diagnosed with myalgic encephalomyelitis are uniquely immunoreactive to antibodies to human endogenous retroviral proteins

Abstract:

Myalgic encephalomyelitis (ME) is a debilitating illness of unknown etiology characterized by neurocognitive dysfunction, inflammation, immune abnormalities and gastrointestinal distress. An increasing body of evidence suggests that disruptions in the gut may contribute to the induction of neuroinflammation. Therefore, reports of human endogenous retroviral (HERV) expression in association with neuroinflammatory diseases prompted us to investigate the gut of individuals with ME for the presence of HERV proteins.

In eight out of 12 individuals with ME, immunoreactivity to HERV proteins was observed in duodenal biopsies. In contrast, no immunoreactivity was detected in any of the eight controls. Immunoreactivity to HERV Gag and Env proteins was uniquely co-localized in hematopoietic cells expressing the C-type lectin receptor CLEC4C (CD303/BDCA2), the co-stimulatory marker CD86 and the class II major histocompatibility complex HLA-DR, consistent with plasmacytoid dendritic cells (pDCs). Although the significance of HERVs present in the pDCs of individuals with ME has yet to be determined, these data raise the possibility of an involvment of pDCs and HERVs in ME pathology. To our knowledge, this report describes the first direct association between pDCs and HERVs in human disease.

 

Source: De Meirleir KL, Khaiboullina SF, Frémont M, Hulstaert J, Rizvanov AA, Palotás A, Lombardi VC. Plasmacytoid dendritic cells in the duodenum of individuals diagnosed with myalgic encephalomyelitis are uniquely immunoreactive to antibodies to human endogenous retroviral proteins. In Vivo. 2013 Mar-Apr;27(2):177-87. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3776582/ (Full article)