Infection, vaccination, and autoantibodies in chronic fatigue syndrome, cause or coincidence?

Abstract:

Chronic fatigue syndrome (CFS) is a heterogeneous syndrome of unknown etiology and physiopathology. CFS patients complain about disabling fatigue, depression, difficulty with memory, and concomitant skeletal and muscular pain. Interestingly enough, there is certain overlap between CFS symptoms, autoimmune rheumatic disease, and infectious diseases.

Certain neuroendocrine-immune abnormalities have also been described, and autoantibodies commonly described in some autoimmune diseases have been found in CFS patients as well. An increasing number of autoantibodies, mainly directed against other nuclear cell components, have been illustrated. Likewise, an association between some infectious agents, antibody production, and later CFS onset has been reported. Similarly, vaccination is depicted as playing an important role in CFS onset.

Recently, a case report pointed toward a causal association between silicone breast linkage, hepatitis B virus vaccination, and CFS onset in a previous healthy woman. Such findings suggest that there is a likely deregulation of the immune system influenced by specific agents (infections, vaccination, and products, such as silicone).

Evidence suggests that CFS is a complex disease in which several risk factors might interact to cause its full expression. Thus, although different alterations have been found in CFS patients, undoubtedly the main feature is central nervous system involvement with immunological alterations. Therefore, a new term neuro-psycho-immunology must be quoted. New studies based on this concept are needed in order to investigate syndromes, such as CFS, in which immunological alterations are thought to be associated with concomitant psychological and health disturbances.

 

Source: Ortega-Hernandez OD, Shoenfeld Y. Infection, vaccination, and autoantibodies in chronic fatigue syndrome, cause or coincidence? Ann N Y Acad Sci. 2009 Sep;1173:600-9. doi: 10.1111/j.1749-6632.2009.04799.x. https://www.ncbi.nlm.nih.gov/pubmed/19758205

 

Chronic fatigue syndrome: a psychoneuroimmunological perspective

Abstract:

This article casts light on the contribution that psychoneuroimmunology can make in the search for the cause of chronic fatigue syndrome (cfs). Several studies suggest that psychosocial and physical stress may play an important predisposing, precipitating and perpetuating role in cfs. Moving on from these studies we now discuss recent research into the stress-related pathophysiological mechanisms of the illness. Although there is evidence for a hypofunctional stress response, a hyperactive immune response and disturbances in the interaction between both, the findings are not consistent. Longitudinal studies are needed to unravel the pathophysiology of cfs still further. In such studies the concept of ‘sickness response’ and ‘sickness behaviour’ may perform an important heuristic function.

 

Source: van Houdenhove B, Heijnen CJ. Chronic fatigue syndrome: a psychoneuroimmunological perspective. Tijdschr Psychiatr. 2009;51(8):603-10. [Article in Dutch] http://www.tijdschriftvoorpsychiatrie.nl/en/issues/413/articles/2821 (Full article)

 

Pharmacological treatment of chronic fatigue syndrome: focusing on the role of antidepressants

Abstract:

Chronic fatigue syndrome (CFS) is characterized by chronic, medically unexplained fatigue associated with effort- and stress-intolerance, widespread pain, and impairment in sleep and concentration. Although this constellation of symptoms is highly prevalent in clinical practice, the pathophysiological mechanisms underlying CFS are poorly understood. Current evidence indicates similarities in symptomatology, and possibly etiology and pathogenesis, between CFS and depression. Additionally, there is significant overlap between CFS and the syndrome of fibromyalgia for which antidepressants have shown consistent efficacy.

Data regarding antidepressant treatment of CFS is less copious and less uniformly positive, such that antidepressant use in CFS remains controversial. The current review aims to summarize available data related to antidepressants and other psychotropic agents in CFS to provide a platform for clinicians to make decisions in their treatment of this challenging syndrome.

We identified relevant studies through a PubMed literature search with a combination of the following search terms: ‘fatigue,’ ‘depression,’ ‘antidepressant,’ ‘etiology’ (e.g., ‘neurobiology,’ ‘neurotransmitter,’ ‘genetic’), ‘diagnosis,’ and ‘treatment’ (e.g., ‘antidepressant’ plus the specific name). In addition, studies were also identified via the reference sections of retrieved articles. The authors thoroughly reviewed major findings from the scanned literatures and eventually synthesized them, providing summary, interpretation, and future directions.

 

Source: Pae CU, Marks DM, Patkar AA, Masand PS, Luyten P, Serretti A. Pharmacological treatment of chronic fatigue syndrome: focusing on the role of antidepressants. Expert Opin Pharmacother. 2009 Jul;10(10):1561-70. Doi: 10.1517/14656560902988510. https://www.ncbi.nlm.nih.gov/pubmed/19514866

 

A systematic review of chronic fatigue, its syndromes and ethnicity: prevalence, severity, co-morbidity and coping

Abstract:

BACKGROUND: Chronic Fatigue Syndrome (CFS) is characterized by unexplained fatigue that lasts for at least 6 months alongside a constellation of other symptoms. CFS was historically thought to be most common among White women of higher socio-economic status. However, some recent studies in the USA suggest that the prevalence is actually higher in some minority ethnic groups. If there are convincing differences in prevalence and risk factors across all or some ethnic groups, investigating the causes of these can help unravel the pathophysiology of CFS.

METHODS: A systematic review was conducted to explore the relationship between fatigue, chronic fatigue (CF–fatigue lasting for 6 months), CFS and ethnicity. Studies were population-based and health service-based. Meta-analysis was also conducted to examine the population prevalence of CF and CFS across ethnic groups.

RESULTS: Meta-analysis showed that compared with the White American majority, African Americans and Native Americans have a higher risk of CFS [Odds Ratio (OR) 2.95, 95% confidence interval (CI): 0.69-10.4; OR = 11.5, CI: 1.1-56.4, respectively] and CF (OR = 1.56, CI: 1.03-2.24; OR = 3.28, CI: 1.63-5.88, respectively). Minority ethnic groups with CF and CFS experience more severe symptoms and may be more likely to use religion, denial and behavioural disengagement to cope with their condition compared with the White majority.

CONCLUSIONS: Although available studies and data are limited, it does appear that some ethnic minority groups are more likely to suffer from CF and CFS compared with White people. Ethnic minority status alone is insufficient to explain ethnic variation of prevalence. Psychosocial risk factors found in high-risk groups and ethnicity warrant further investigation to improve our understanding of aetiology and the management of this complex condition.

 

Source: Dinos S, Khoshaba B, Ashby D, White PD, Nazroo J, Wessely S, Bhui KS. A systematic review of chronic fatigue, its syndromes and ethnicity: prevalence, severity, co-morbidity and coping. Int J Epidemiol. 2009 Dec;38(6):1554-70. doi: 10.1093/ije/dyp147. Epub 2009 Apr 6. http://ije.oxfordjournals.org/content/38/6/1554.long (Full article)

 

Inflammatory and oxidative and nitrosative stress pathways underpinning chronic fatigue, somatization and psychosomatic symptoms

Abstract:

PURPOSE OF REVIEW: The aim of this paper is to review recent findings on inflammatory and oxidative and nitrosative stress (IO&NS) pathways in chronic fatigue and somatization disorder.

RECENT FINDINGS: Activation of IO&NS pathways is the key phenomenon underpinning chronic fatigue syndrome (CFS): intracellular inflammation, with an increased production of nuclear factor kappa beta (NFkappabeta), cyclo-oxygenase-2 (COX-2) and inducible NO synthase (iNOS); and damage caused by O&NS to membrane fatty acids and functional proteins. These IO&NS pathways are induced by a number of trigger factors, for example psychological stress, strenuous exercise, viral infections and an increased translocation of LPS from gram-bacteria (leaky gut). The ‘psychosomatic’ symptoms experienced by CFS patients are caused by intracellular inflammation (aches and pain, muscular tension, fatigue, irritability, sadness, and the subjective feeling of infection); damage caused by O&NS (aches and pain, muscular tension and fatigue); and gut-derived inflammation (complaints of irritable bowel). Inflammatory pathways (monocytic activation) are also detected in somatizing disorder.

SUMMARY: ‘Functional’ symptoms, as occurring in CFS and somatization, have a genuine organic cause, that is activation of peripheral and central IO&NS pathways and gut-derived inflammation. The development of new drugs, aimed at treating those disorders, should target these IO&NS pathways.

 

Source: Maes M. Inflammatory and oxidative and nitrosative stress pathways underpinning chronic fatigue, somatization and psychosomatic symptoms. Curr Opin Psychiatry. 2009 Jan;22(1):75-83. https://www.ncbi.nlm.nih.gov/pubmed/19127706

 

CFS: A Review of Epidemiology and Natural History Studies

Abstract:

Almost all studies with samples of patients who have chronic fatigue syndrome (CFS) have relied on referrals from physicians or health facilities. Under-served minorities, who not only tend to manifest higher levels of chronic illness, but are also less likely to seek and receive adequate medical care, have not been represented in these studies (1). This may have contributed to an under-estimation of CFS among minority groups (2). Few studies have derived their samples from socioeconomically and ethnically diverse community-based populations. A technical report issued by the Agency for Healthcare Research and Quality (3) concluded that estimating rates of recovery/improvement or relapse from CFS are not possible because there are so few natural history studies and those that are available have involved selected referral populations.

This paper provides a review of epidemiologic studies of CFS followed by a discussion of diagnostic issues and risk factors for the illness. Findings from Jason et al.’s (4) epidemiologic study in a multi-ethnic, economically diverse urban area are highlighted as this research group is now examining the natural course of CFS over the past 10 years with this community-based sample. The current study will add to current epidemiologic and risk factors research by assessing the course, progression, and risk factors of CFS among a demographically diverse sample of participants who are unbiased by illness, help-seeking behaviors, or differential access to the health care system.

 

Source: Jason LA, Porter N, Brown M, Anderson V, Brown A, Hunnell J, Lerch A. CFS: A Review of Epidemiology and Natural History Studies. Bull IACFS ME. 2009;17(3):88-106. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3021257/ (Full article)

 

Chronic fatigue syndrome and the central nervous system

Abstract:

An increasing amount of neuroimaging evidence supports the hypothesis that chronic fatigue syndrome patients have structural or functional abnormalities within the brain. Moreover, some neurotrophic factors, neurotransmitters and cytokines have also been evaluated in order to elucidate the mechanism of abnormal neuropsychic findings in chronic fatigue syndrome. In this review, we suggest that the focal point of chronic fatigue syndrome research should be transferred to the central nervous system.

 

Source: Chen R, Liang FX, Moriya J, Yamakawa J, Sumino H, Kanda T, Takahashi T. Chronic fatigue syndrome and the central nervous system. J Int Med Res. 2008 Sep-Oct;36(5):867-74. https://www.ncbi.nlm.nih.gov/pubmed/18831878

 

Immunological aspects of chronic fatigue syndrome

Abstract:

Chronic fatigue syndrome (CFS) is a specific clinical condition that characterises unexplained disabling fatigue and a combination of non-specific accompanying symptoms for at least 6 months, in the absence of a medical diagnosis that would otherwise explain the clinical presentation. Other common symptoms include headaches, myalgia, arthralgia, and post-exertional malaise; cognitive difficulties, with impaired memory and concentration; unrefreshing sleep; and mood changes.

Similar disorders have been described for at least two centuries and have been differently named neurasthenia, post-viral fatigue, myalgic encephalomyelitis and chronic mononucleosis. Recent longitudinal studies suggest that some people affected by chronic fatigue syndrome improve with time but that most remain functionally impaired for several years. The estimated worldwide prevalence of CFS is 0.4-1% and it affects over 800,000 people in the United States and approximately 240,000 patients in the UK.

No physical examination signs are specific to CFS and no diagnostic tests identify this syndrome. The pathophysiological mechanism of CFS is unclear. The main hypotheses include altered central nervous system functioning resulting from an abnormal immune response against a common antigen; a neuroendocrine disturbance; cognitive impairment caused by response to infection or other stimuli in sentient people. The current concept is that CFS pathogenesis is a multifactorial condition.

Various studies have sought evidence for a disturbance in immunity in people with CFS. An alteration in cytokine profile, a decreased function of natural killer (NK) cells, a presence of autoantibodies and a reduced responses of T cells to mitogens and other specific antigens have been reported. The observed high level of pro-inflammatory cytokines may explain some of the manifestations such as fatigue and flu-like symptoms and influence NK activity. Abnormal activation of the T lymphocyte subsets and a decrease in antibody-dependent cell-mediated cytotoxicity have been described. An increased number of CD8+ cytotoxic T lymphocytes and CD38 and HLA-DR activation markers have been reported, and a decrease in CD11b expression associated with an increased expression of CD28+ T subsets has been observed. This review discusses the immunological aspects of CFS and offers an immunological hypothesis for the disease processes.

 

Source: Lorusso L, Mikhaylova SV, Capelli E, Ferrari D, Ngonga GK, Ricevuti G. Immunological aspects of chronic fatigue syndrome. Autoimmun Rev. 2009 Feb;8(4):287-91. doi: 10.1016/j.autrev.2008.08.003. Epub 2008 Sep 16. https://www.ncbi.nlm.nih.gov/pubmed/18801465

 

Cognitive behaviour therapy for chronic fatigue syndrome in adults

Abstract:

BACKGROUND: Chronic fatigue syndrome (CFS) is a common, debilitating and serious health problem. Cognitive behaviour therapy (CBT) may help to alleviate the symptoms of CFS.

OBJECTIVES: To examine the effectiveness and acceptability of CBT for CFS, alone and in combination with other interventions, compared with usual care and other interventions.

SEARCH STRATEGY: CCDANCTR-Studies and CCDANCTR-References were searched on 28/3/2008. We conducted supplementary searches of other bibliographic databases. We searched reference lists of retrieved articles and contacted trial authors and experts in the field for information on ongoing/completed trials.

SELECTION CRITERIA: Randomised controlled trials involving adults with a primary diagnosis of CFS, assigned to a CBT condition compared with usual care or another intervention, alone or in combination.

DATA COLLECTION AND ANALYSIS: Data on patients, interventions and outcomes were extracted by two review authors independently, and risk of bias was assessed for each study. The primary outcome was reduction in fatigue severity, based on a continuous measure of symptom reduction, using the standardised mean difference (SMD), or a dichotomous measure of clinical response, using odds ratios (OR), with 95% confidence intervals (CI).

MAIN RESULTS: Fifteen studies (1043 CFS participants) were included in the review. When comparing CBT with usual care (six studies, 373 participants), the difference in fatigue mean scores at post-treatment was highly significant in favour of CBT (SMD -0.39, 95% CI -0.60 to -0.19), with 40% of CBT participants (four studies, 371 participants) showing clinical response in contrast with 26% in usual care (OR 0.47, 95% CI 0.29 to 0.76). Findings at follow-up were inconsistent. For CBT versus other psychological therapies, comprising relaxation, counselling and education/support (four studies, 313 participants), the difference in fatigue mean scores at post-treatment favoured CBT (SMD -0.43, 95% CI -0.65 to -0.20). Findings at follow-up were heterogeneous and inconsistent. Only two studies compared CBT against other interventions and one study compared CBT in combination with other interventions against usual care.

AUTHORS’ CONCLUSIONS: CBT is effective in reducing the symptoms of fatigue at post-treatment compared with usual care, and may be more effective in reducing fatigue symptoms compared with other psychological therapies. The evidence base at follow-up is limited to a small group of studies with inconsistent findings. There is a lack of evidence on the comparative effectiveness of CBT alone or in combination with other treatments, and further studies are required to inform the development of effective treatment programmes for people with CFS.

Comment inReview: CBT reduces fatigue in adults with chronic fatigue syndrome but effects at follow-up unclear. [Evid Based Ment Health. 2009]

Update of:  Cognitive behaviour therapy for adults with chronic fatigue syndrome. [Cochrane Database Syst Rev. 2000]

 

Source: Price JR, Mitchell E, Tidy E, Hunot V. Cognitive behaviour therapy for chronic fatigue syndrome in adults. Cochrane Database Syst Rev. 2008 Jul 16;(3):CD001027. doi: 10.1002/14651858.CD001027.pub2.https://www.ncbi.nlm.nih.gov/pubmed/18646067

 

Chronic fatigue syndrome: implications for women and their health care providers during the childbearing years

Abstract:

Chronic fatigue syndrome is a complex debilitating medical disorder that affects approximately 4 million persons in the United States, predominantly women. There has been little scientific exploration about the experience of pregnancy, childbirth, and the postpartum period for women with this disorder. A review of the literature and current research findings addressing the epidemiology, diagnosis, symptoms, and treatment of chronic fatigue syndrome are presented, as well as the currently available data regarding the experience of women with chronic fatigue syndrome anticipating or experiencing pregnancy and the postpartum period. Expert opinion is presented along with current evidence to provide guidelines for the care of women with chronic fatigue syndrome during pregnancy, labor and birth, lactation, and the postpartum period.

 

Source: Allen PR. Chronic fatigue syndrome: implications for women and their health care providers during the childbearing years. J Midwifery Womens Health. 2008 Jul-Aug;53(4):289-301; quiz 399. doi: 10.1016/j.jmwh.2007.12.001. https://www.ncbi.nlm.nih.gov/pubmed/18586181