Chronic fatigue syndrome: identifying zebras amongst the horses

Abstract:

There are currently no investigative tools or physical signs that can confirm or refute the presence of chronic fatigue syndrome(CFS). As a result, clinicians must decide how long to keep looking for alternative explanations for fatigue before settling on a diagnosis of CFS. Too little investigation risks serious or easily treatable causes of fatigue being overlooked, whilst too many increases the risk of iatrogenic harm and reduces the opportunity for early focused treatment.

A paper by Jones et al published this month in BMC Medicine may help clinicians in deciding how to undertake such investigations. Their results suggest that if clinicians look for common psychiatric and medical conditions in those complaining of prolonged fatigue, the rate of detection will be higher than previously estimated. The most common co-morbid condition identified was depression, suggesting a simple mental state examination remains the most productive single investigation in any new person presenting with unexplained fatigue. Currently, most diagnostic criteria advice CFS should not be diagnosed when an active medical or psychiatric condition which may explain the fatigue is identified.

We discuss a number of recent prospective studies that have provided valuable insights into the aetiology of chronic fatigue and describe a model for understanding chronic fatigue which may be equally relevant regardless of whether or not an apparent medical cause for fatigue can be identified. See the associated research paper by Jones et al: http://www.biomedcentral.com/1741-7015/7/57.

Comment on: An evaluation of exclusionary medical/psychiatric conditions in the definition of chronic fatigue syndrome. [BMC Med. 2009]

 

Source: Harvey SB, Wessely S. Chronic fatigue syndrome: identifying zebras amongst the horses. BMC Med. 2009 Oct 12;7:58. doi: 10.1186/1741-7015-7-58. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2766380/ (Full article)

 

Does hypocortisolism predict a poor response to cognitive behavioural therapy in chronic fatigue syndrome?

Abstract:

BACKGROUND: There is evidence that patients with chronic fatigue syndrome (CFS) have mild hypocortisolism. The clinical significance of this is unclear. We aimed to determine whether hypocortisolism exerted any effect on the response of CFS to cognitive behavioural therapy (CBT).

METHOD: We measured 24-h urinary free cortisol (UFC) in 84 patients with Centers for Disease Control and Prevention (CDC)-defined CFS (of whom 64 were free from psychotropic medication) who then received CBT in a specialist, tertiary out-patient clinic as part of their usual clinical care. We also measured salivary cortisol output from 0800 to 2000 h in a subsample of 56 psychotropic medication-free patients.

RESULTS: Overall, 39% of patients responded to CBT after 6 months of treatment. Lower 24-h UFC output was associated with a poorer response to CBT but only in psychotropic medication-free patients. A flattened diurnal profile of salivary cortisol was also associated with a poor response to CBT.

CONCLUSIONS: Low cortisol is of clinical relevance in CFS, as it is associated with a poorer response to CBT. Hypocortisolism could be one of several maintaining factors that interact in the persistence of CFS.

 

Source: Roberts AD, Charler ML, Papadopoulos A, Wessely S, Chalder T, Cleare AJ. Does hypocortisolism predict a poor response to cognitive behavioural therapy in chronic fatigue syndrome? Psychol Med. 2010 Mar;40(3):515-22. doi: 10.1017/S0033291709990390. Epub 2009 Jul 17. https://www.ncbi.nlm.nih.gov/pubmed/19607750

 

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)

 

Comparative epidemiology of chronic fatigue syndrome in Brazilian and British primary care: prevalence and recognition

Abstract:

BACKGROUND: Although fatigue is a ubiquitous symptom across countries, clinical descriptions of chronic fatigue syndrome have arisen from a limited number of high-income countries. This might reflect differences in true prevalence or clinical recognition influenced by sociocultural factors.

AIMS: To compare the prevalence, physician recognition and diagnosis of chronic fatigue syndrome in London and São Paulo.

METHOD: Primary care patients in London (n=2459) and São Paulo (n=3914) were surveyed for the prevalence of chronic fatigue syndrome. Medical records were reviewed for the physician recognition and diagnosis.

RESULTS: The prevalence of chronic fatigue syndrome according to Centers for Disease Control 1994 criteria was comparable in Britain and Brazil: 2.1% v. 1.6% (P=0.20). Medical records review identified 11 diagnosed cases of chronic fatigue syndrome in Britain, but none in Brazil (P<0.001).

CONCLUSIONS: The primary care prevalence of chronic fatigue syndrome was similar in two culturally and economically distinct nations. However, doctors are unlikely to recognise and label chronic fatigue syndrome as a discrete disorder in Brazil. The recognition of this illness rather than the illness itself may be culturally induced.

Comment in: Diagnosing chronic fatigue syndrome. [Br J Psychiatry. 2009]

 

Source: Cho HJ, Menezes PR, Hotopf M, Bhugra D, Wessely S. Comparative epidemiology of chronic fatigue syndrome in Brazilian and British primary care: prevalence and recognition. Br J Psychiatry. 2009 Feb;194(2):117-22. doi: 10.1192/bjp.bp.108.051813. http://bjp.rcpsych.org/content/194/2/117.long (Full article)

 

Salivary cortisol output before and after cognitive behavioural therapy for chronic fatigue syndrome

Abstract:

BACKGROUND: There is evidence that patients with chronic fatigue syndrome (CFS) have mild hypocortisolism. One theory about the aetiology of this hypocortisolism is that it occurs late in the course of CFS via factors such as inactivity, sleep disturbance, chronic stress and deconditioning. We aimed to determine whether therapy aimed at reversing these factors–cognitive behavioural therapy for CFS–could increase cortisol output in CFS.

METHODS: We measured diurnal salivary cortisol output between 0800 and 2000 h before and after 15 sessions (or 6 months) of CBT in 41 patients with CDC-defined CFS attending a specialist, tertiary outpatient clinic.

RESULTS: There was a significant clinical response to CBT, and a significant rise in salivary cortisol output after CBT.

LIMITATIONS: We were unable to control for the passage of time using a non-treated CFS group.

CONCLUSIONS: Hypocortisolism in CFS is potentially reversible by CBT. Given previous suggestions that lowered cortisol may be a maintaining factor in CFS, CBT offers a potential way to address this.

 

Source: Roberts AD, Papadopoulos AS, Wessely S, Chalder T, Cleare AJ. Salivary cortisol output before and after cognitive behavioural therapy for chronic fatigue syndrome. J Affect Disord. 2009 May;115(1-2):280-6. doi: 10.1016/j.jad.2008.09.013. Epub 2008 Oct 19. https://www.ncbi.nlm.nih.gov/pubmed/18937978

 

‘Physical or psychological?’- a comparative study of causal attribution for chronic fatigue in Brazilian and British primary care patients

Abstract:

OBJECTIVE: Causal attribution influences symptom experience, help-seeking behaviour and prognosis in chronic fatigue syndrome. We compared causal attribution of patients with unexplained chronic fatigue (UCF) in Brazil and Britain.

METHOD: Primary care attenders in São Paulo (n = 3914) and London (n = 2459) were screened for the presence of UCF. Those with UCF (São Paulo n = 452; London n = 178) were assessed for causal attribution (physical vs. psychosocial), perceived chronicity (i.e. reported duration of fatigue) and disability.

RESULTS: British UCF patients were more likely to attribute their fatigue to physical causes (adjusted odds ratio 1.70, P = 0.037) and perceived their fatigue to be more chronic (adjusted beta 0.15, P = 0.002). There was no significant difference in current disability (adjusted beta -0.01, P = 0.81).

CONCLUSION: Despite similar disability levels, UCF patients in different cultural settings presented different attributions and perceptions about their illness. Sociocultural factors may have an important role in shaping illness attribution and perception around chronic fatigue.

 

Source: Cho HJ, Bhugra D, Wessely S. ‘Physical or psychological?’- a comparative study of causal attribution for chronic fatigue in Brazilian and British primary care patients. Acta Psychiatr Scand. 2008 Jul;118(1):34-41. doi: 10.1111/j.1600-0447.2008.01200.x. Epub 2008 May 22. https://www.ncbi.nlm.nih.gov/pubmed/18498433

 

Etiology of chronic fatigue syndrome: testing popular hypotheses using a national birth cohort study

Abstract:

OBJECTIVE: To review the etiology of chronic fatigue syndrome (CFS) and test hypotheses relating to immune system dysfunction, physical deconditioning, exercise avoidance, and childhood illness experiences, using a large prospective birth cohort.

METHODS: A total of 4779 participants from the Medical Research Council’s National Survey of Health and Development were prospectively followed for the first 53 years of their life with >20 separate data collections. Information was collected on childhood and parental health, atopic illness, levels of physical activity, fatigue, and participant’s weight and height at multiple time points. CFS was identified through self-report during a semistructured interview at age 53 years with additional case notes review.

RESULTS: Of 2983 participants assessed at age 53 years, 34 (1.1%, 95% Confidence Interval 0.8-1.5) reported a diagnosis of CFS. Those who reported CFS were no more likely to have suffered from childhood illness or atopy. Increased levels of exercise throughout childhood and early adult life and a lower body mass index were associated with an increased risk of later CFS. Participants who later reported CFS continued to exercise more frequently even after they began to experience early symptoms of fatigue.

CONCLUSIONS: Individuals who exercise frequently are more likely to report a diagnosis of CFS in later life. This may be due to the direct effects of this behavior or associated personality factors. Continuing to be active despite increasing fatigue may be a crucial step in the development of CFS.

 

Source: Harvey SB, Wadsworth M, Wessely S, Hotopf M. Etiology of chronic fatigue syndrome: testing popular hypotheses using a national birth cohort study. Psychosom Med. 2008 May;70(4):488-95. doi: 10.1097/PSY.0b013e31816a8dbc. Epub 2008 Mar 31. https://www.ncbi.nlm.nih.gov/pubmed/18378866

 

The awareness of chronic fatigue syndrome: a comparative study in Brazil and the United Kingdom

Abstract:

OBJECTIVE: While in many Western affluent countries there is widespread awareness of chronic fatigue syndrome (CFS), also known as myalgic encephalomyelitis (ME), little is known about the awareness of CFS/ME in low- and middle-income countries. We compared the awareness of CFS in Brazil and the United Kingdom.

METHODS: Recognition and knowledge of CFS were assessed among 120 Brazilian specialist doctors in two major university hospitals using a typical case vignette of CFS. We also surveyed 3914 and 2435 consecutive attenders in Brazilian and British primary care clinics, respectively, concerning their awareness of CFS.

RESULTS: When given a typical case vignette of CFS, only 30.8% [95% confidence interval (CI), 22.7-39.9%] of Brazilian specialist doctors mentioned chronic fatigue or CFS as a possible diagnosis, a proportion substantially lower than that observed in Western affluent countries. Similarly, only 16.2% (95% CI, 15.1-17.4%) of Brazilian primary care attenders were aware of CFS, in contrast to 55.1% (95% CI, 53.1-57.1%) of their British counterparts (P<.001). This difference remained highly significant after controlling for patients’ sociodemographic and socioeconomic characteristics (P<.001).

CONCLUSIONS: The awareness of CFS was substantially lower in Brazil than the United Kingdom. The observed difference may influence patients’ help-seeking behavior and both doctors’ and patients’ beliefs and attitudes in relation to fatigue-related syndromes. Attempts to promote the awareness of CFS should be considered in Brazil, but careful plans are required to ensure the delivery of sound evidence-based information.

 

Source: Cho HJ, Menezes PR, Bhugra D, Wessely S. The awareness of chronic fatigue syndrome: a comparative study in Brazil and the United Kingdom. J Psychosom Res. 2008 Apr;64(4):351-5. doi: 10.1016/j.jpsychores.2007.12.006. https://www.ncbi.nlm.nih.gov/pubmed/18374733

 

Chronic fatigue syndrome

Abstract:

INTRODUCTION: Chronic fatigue syndrome (CFS) affects between 0.006% and 3% of the population depending on the criteria of definition used, with women being at higher risk than men.

METHODS AND OUTCOMES: We conducted a systematic review and aimed to answer the following clinical question: What are the effects of treatments for chronic fatigue syndrome? We searched: Medline, Embase, The Cochrane Library, and other important databases up to September 2007 (BMJ Clinical evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).

RESULTS: We found 45 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.

CONCLUSIONS: In this systematic review we present information relating to the effectiveness and safety of the following interventions: antidepressants, cognitive behavioural therapy (CBT), corticosteroids, dietary supplements, evening primrose oil, galantamine, graded exercise therapy, homeopathy, immunotherapy, intramuscular magnesium, oral nicotinamide adenine dinucleotide, and prolonged rest.

 

Source: Reid SF, Chalder T, Cleare A, Hotopf M, Wessely S. Chronic fatigue syndrome. BMJ Clin Evid. 2008 Aug 28;2008. pii: 1101. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2907931/ (Full article)

 

The relationship between prior psychiatric disorder and chronic fatigue: evidence from a national birth cohort study

Abstract:

BACKGROUND: Increased rates of psychiatric disorder have previously been reported in those diagnosed with chronic fatigue syndrome (CFS) or myalgic encephalomyelitis (ME), although the direction of causation in this relationship has not been established. We aimed to test the hypothesis that individuals with self-reported CFS/ME have increased levels of psychiatric disorder prior to the onset of their fatigue symptoms.

METHOD: A total of 5,362 participants were prospectively followed with various measures of personality, psychiatric disorder and fatigue levels collected over the first 43 years of their life. CFS/ME was identified through self-report during a semi-structured interview at age 53 years.

RESULTS: Thirty-four (1.1%) of the 3,035 subjects assessed at age 53 years reported a diagnosis of CFS/ME. CFS/ME was more common among females, but there was no association between CFS/ME and either social class, social mobility or educational level. Those with psychiatric illness between the ages of 15 and 36 years were more likely to report CFS/ME later in life with an odds ratio (OR, adjusted for sex) of 2.65 [95% confidence interval (CI) 1.26-5.57, p=0.01]. Increased levels of psychiatric illness, in particular depression and anxiety, were present prior to the occurrence of fatigue symptoms. There was a dose-response relationship between the severity of psychiatric symptoms and the likelihood of later CFS/ME. Personality factors were not associated with a self-reported diagnosis of CFS/ME.

CONCLUSIONS: This temporal, dose-response relationship suggests that psychiatric disorders, or shared risk factors for psychiatric disorders, are likely to have an aetiological role in some cases of CFS/ME.

 

Source: Harvey SB, Wadsworth M, Wessely S, Hotopf M. The relationship between prior psychiatric disorder and chronic fatigue: evidence from a national birth cohort study. Psychol Med. 2008 Jul;38(7):933-40. Epub 2007 Nov 2. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3196526/ (Full article)