Chronic fatigue syndrome 5 years after giardiasis: differential diagnoses, characteristics and natural course

Abstract:

BACKGROUND: A high prevalence of chronic fatigue has previously been reported following giardiasis after a large waterborne outbreak in Bergen, Norway in 2004. The aim of this study was to describe and evaluate differential diagnoses and natural course of fatigue five years after giardiasis among patients who reported chronic fatigue three years after the infection.

METHODS: Patients who three years after Giardia infection met Chalder’s criteria for chronic fatigue (n=347) in a questionnaire study among all patients who had laboratory confirmed giardiasis during the Bergen outbreak (n=1252) were invited to participate in this study five years after the infection (n=253). Structured interviews and clinical examination were performed by specialists in psychiatry, neurology and internal medicine/infectious diseases. Fukuda et al’s 1994 criteria were used to diagnose chronic fatigue syndrome (CFS) and idiopathic chronic fatigue (ICF). Self-reported fatigue recorded with Chalder Fatigue Questionnaire three and five years after infection were compared.

RESULTS: 53 patients were included. CFS was diagnosed in 41.5% (22/53) and ICF in 13.2% (7/53). Chronic fatigue caused by other aetiology was diagnosed in 24.5% (13/53); five of these patients had sleep apnoea/hypopnoea syndrome, six had depression and five anxiety disorder, and among these two had more than one diagnosis. Fatigue had resolved in 20.8% (11/53). Self-reported fatigue score in the cohort was significantly reduced at five years compared to three years (p<0.001).

CONCLUSION: The study shows that Giardia duodenalis may induce CFS persisting as long as five years after the infection. Obstructive sleep apnoea/hypopnoea syndrome, depression and anxiety were important differential diagnoses, or possibly comorbidities, to post-infectious fatigue in this study. Improvement of chronic fatigue in the period from three to five years after giardiasis was found.

 

Source: Mørch K, Hanevik K, Rivenes AC, Bødtker JE, Næss H, Stubhaug B, Wensaas KA, Rortveit G, Eide GE, Hausken T, Langeland N. Chronic fatigue syndrome 5 years after giardiasis: differential diagnoses, characteristics and natural course. BMC Gastroenterol. 2013 Feb 12;13:28. doi: 10.1186/1471-230X-13-28. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3598369/ (Full article)

 

Is chronic fatigue syndrome in older patients a different disease? — a clinical cohort study

Abstract:

BACKGROUND: Chronic fatigue syndrome (CFS) is a disabling disorder characterised by persistent fatigue with a typical age of diagnosis of 35-50 years. CFS does present in those aged over 50 but whether this is a different disease in older age groups has not been considered. Therefore, we performed a clinical cohort study to examine and differentiate the clinical and autonomic features in CFS patients aged over 50.

DESIGN: A total of 179 Fukuda diagnosed CFS patients were recruited, and 25 older CFS patients (50 + years) were matched case by case for gender and length of history to 25 younger CFS patients (16-29 years). A range of symptomatic-based questionnaires were used in addition to heart rate variability and baroreceptor sensitivity to assess autonomic function.

RESULTS: Chronic fatigue syndrome can present for the first time in an older population. Older CFS patients demonstrate increased fatigue (Fatigue impact scale; 85 ± 33 vs. 107 ± 27, P = 0·02) (Chalder fatigue scale; 9 ± 3 vs. 11 ± 1, P = 0·002) and caseness for depression (Hospital Anxiety and Depression scale; 7 ± 3 vs. 10 ± 4; P = 0·005). There is a greater autonomic dysfunction in older CFS patients, with reduced parasympathetic function (HFnu; 49·1 ± 18 vs. 36·2 ± 18, P = 0·01, RR30 : 15; ± , P = 0·02) and increased sympathetic function (LFnu; 51·5 ± 17 vs. 63·8 ± 18, P = 0·01). Baroreflex sensitivity was substantially reduced (BRS; 19·7 ± 12 vs. 9·9 ± 5, P = 0·0004), and left ventricular ejection time prolonged (LVET; 274·6 ± 16 vs. 285·8 ± 9, P = 0·004).

CONCLUSIONS: Older CFS patients demonstrate a disease phenotype very different from younger patients. The combination of differing underlying pathogenic mechanisms and the physiological aspects of ageing result in a greater disease impact in older CFS patients.

© 2013 The Authors. European Journal of Clinical Investigation

© 2013 Stichting European Society for Clinical Investigation Journal Foundation.

 

Source: Lewis I, Pairman J, Spickett G, Newton JL. Is chronic fatigue syndrome in older patients a different disease? — a clinical cohort study. Eur J Clin Invest. 2013 Mar;43(3):302-8. doi: 10.1111/eci.12046. Epub 2013 Feb 9. https://www.ncbi.nlm.nih.gov/pubmed/23397955

 

Chronic fatigue syndrome: 3 cases and a discussion of the natural history of attention-deficit/hyperactivity disorder

Abstract:

Fatigue is commonly reported in the primary care setting; however, its cause is often unclear. This article presents 3 cases involving patients with chronic fatigue syndrome who responded poorly to treatment. After clinical evaluation, all patients were found to meet criteria for attention-deficit/hyperactivity disorder (ADHD) and underwent a standard regimen of a psychostimulant medication.

After treatment with psychostimulants, the 3 patients reported improved symptoms of fatigue and pain, and cognitive and core ADHD symptoms. These cases suggest that ADHD and chronic fatigue syndrome (and possibly fibromyalgia) share a common underlying mechanism. This article presents a model suggesting that over time, ADHD (predominantly inattentive type) develops into a syndrome of chronic fatigue and pain. These cases indicate that fatigue may be an important presenting symptom of adult ADHD. These cases also suggest the need for additional research to determine the prevalence of ADHD in patients who present with fatigue, and, in those meeting criteria for ADHD, the responsiveness of fatigue to psychostimulant treatment.

 

Source: Young JL. Chronic fatigue syndrome: 3 cases and a discussion of the natural history of attention-deficit/hyperactivity disorder. Postgrad Med. 2013 Jan;125(1):162-8. doi: 10.3810/pgm.2013.01.2631. https://www.ncbi.nlm.nih.gov/pubmed/23391682

 

A Chronic Fatigue Syndrome (CFS) severity score based on case designation criteria

Abstract:

BACKGROUND: Chronic Fatigue Syndrome case designation criteria are scored as physicians’ subjective, nominal interpretations of patient fatigue, pain (headaches, myalgia, arthralgia, sore throat and lymph nodes), cognitive dysfunction, sleep and exertional exhaustion.

METHODS: Subjects self-reported symptoms using an anchored ordinal scale of 0 (no symptom), 1 (trivial complaints), 2 (mild), 3 (moderate), and 4 (severe). Fatigue of 3 or 4 distinguished “Fatigued” from “Not Fatigued” subjects. The sum of the 8(Sum8) ancillary criteria was tested as a proxy for fatigue. All subjects had history and physical examinations to exclude medical fatigue, and ensure categorization as healthy or CFS subjects.

RESULTS: Fatigued subjects were divided into CFS with ≥4 symptoms or Chronic Idiopathic Fatigue (CIF) with ≤3 symptoms. ROC of Sum8 for CFS and Not Fatigued subjects generated a threshold of 14 (specificity=0.934; sensitivity=0.928). CFS (n=256) and CIF (n=55) criteria were refined to include Sum8≥14 and ≤13, respectively. Not Fatigued subjects had highly skewed Sum8 responses. Healthy Controls (HC; n=269) were defined by fatigue≤2 and Sum8≤13. Those with Sum8≥14 were defined as CFS-Like With Insufficient Fatigue Syndrome (CFSLWIFS; n=20). Sum8 and Fatigue were highly correlated (R(2)=0.977; Cronbach’s alpha=0.924) indicating an intimate relationship between symptom constructs. Cluster analysis suggested 4 clades each in CFS and HC. Translational utility was inferred from the clustering of proteomics from cerebrospinal fluid.

CONCLUSIONS: Plotting Fatigue severity versus Sum8 produced an internally consistent classifying system. This is a necessary step for translating symptom profiles into fatigue phenotypes and their pathophysiological mechanisms.

 

Source: Baraniuk JN, Adewuyi O, Merck SJ, Ali M, Ravindran MK, Timbol CR, Rayhan R, Zheng Y, Le U, Esteitie R, Petrie KN. A Chronic Fatigue Syndrome (CFS) severity score based on case designation criteria. Am J Transl Res. 2013;5(1):53-68. Epub 2013 Jan 21. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3560481/ (Full article)

 

Relationship between autonomic cardiovascular control, case definition, clinical symptoms, and functional disability in adolescent chronic fatigue syndrome: an exploratory study

Abstract:

Chronic Fatigue Syndrome (CFS) is characterized by severe impairment and multiple symptoms. Autonomic dysregulation has been demonstrated in several studies. We aimed at exploring the relationship between indices of autonomic cardiovascular control, the case definition from Centers for Disease Control and Prevention (CDC criteria), important clinical symptoms, and disability in adolescent chronic fatigue syndrome.

38 CFS patients aged 12-18 years were recruited according to a wide case definition (ie. not requiring accompanying symptoms) and subjected to head-up tilt test (HUT) and a questionnaire. The relationships between variables were explored with multiple linear regression analyses. In the final models, disability was positively associated with symptoms of cognitive impairments (p<0.001), hypersensitivity (p<0.001), fatigue (p=0.003) and age (p=0.007).

Symptoms of cognitive impairments were associated with age (p=0.002), heart rate (HR) at baseline (p=0.01), and HR response during HUT (p=0.02). Hypersensitivity was associated with HR response during HUT (p=0.001), high-frequency variability of heart rate (HF-RRI) at baseline (p=0.05), and adherence to the CDC criteria (p=0.005). Fatigue was associated with gender (p=0.007) and adherence to the CDC criteria (p=0.04).

In conclusion, a) The disability of CFS patients is not only related to fatigue but to other symptoms as well; b) Altered cardiovascular autonomic control is associated with certain symptoms; c) The CDC criteria are poorly associated with disability, symptoms, and indices of altered autonomic nervous activity.

 

Source: Wyller VB, Helland IB. Relationship between autonomic cardiovascular control, case definition, clinical symptoms, and functional disability in adolescent chronic fatigue syndrome: an exploratory study. Biopsychosoc Med. 2013 Feb 7;7(1):5. doi: 10.1186/1751-0759-7-5. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3570350/ (Full article)

 

Recovery from chronic fatigue syndrome after treatments given in the PACE trial

Abstract:

BACKGROUND: A multi-centre, four-arm trial (the PACE trial) found that rehabilitative cognitive behaviour therapy (CBT) and graded exercise therapy (GET) were more effective treatments for chronic fatigue syndrome (CFS) than specialist medical care (SMC) alone, when each was added to SMC, and more effective than adaptive pacing therapy (APT) when added to SMC. In this study we compared how many participants recovered after each treatment.

METHOD: We defined recovery operationally using multiple criteria, and compared the proportions of participants meeting each individual criterion along with two composite criteria, defined as (a) recovery in the context of the trial and (b) clinical recovery from the current episode of the illness, however defined, 52 weeks after randomization. We used logistic regression modelling to compare treatments.

RESULTS: The percentages (number/total) meeting trial criteria for recovery were 22% (32/143) after CBT, 22% (32/143) after GET, 8% (12/149) after APT and 7% (11/150) after SMC. Similar proportions met criteria for clinical recovery. The odds ratio (OR) for trial recovery after CBT was 3.36 [95% confidence interval (CI) 1.64–6.88] and for GET 3.38 (95% CI 1.65–6.93), when compared to APT, and after CBT 3.69 (95% CI 1.77–7.69) and GET 3.71 (95% CI 1.78–7.74), when compared to SMC (p values < or =0.001 for all comparisons). There was no significant difference between APT and SMC. Similar proportions recovered in trial subgroups meeting different definitions of the illness.

CONCLUSIONS: This study confirms that recovery from CFS is possible, and that CBT and GET are the therapies most likely to lead to recovery.

Comment in: Reports of recovery in chronic fatigue syndrome may present less than meets the eye. [Evid Based Ment Health. 2014]

 

Source: White PD, Goldsmith K, Johnson AL, Chalder T, Sharpe M. Recovery from chronic fatigue syndrome after treatments given in the PACE trial. Psychol Med. 2013 Oct;43(10):2227-35. doi: 10.1017/S0033291713000020. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3776285/ (Full study)

 

Postural orthostatic tachycardia syndrome as a clinically important subgroup of chronic fatigue syndrome: further evidence for central nervous system dysfunctioning

In this issue of the Journal of Internal Medicine, Lewis and colleagues [1] provide compelling data for a novel subgroup within the chronic fatigue syndrome (CFS) population. They show that approximately 13% (24/179) of CFS patients have postural orthostatic tachycardia syndrome (POTS), a form of dysautonomia implying that when patients change their body position from supine to upright, their heart rate will increase abnormally (tachycardia). POTS is associated with several symptoms often seen in CFS patients: fatigue, lightheadedness, dizziness, neurocognitive deficits and exercise intolerance. Importantly, this was a confirmatory study of a previously published pilot study that found a prevalence rate for POTS of 29% in a smaller sample (n = 63) of CFS patients [2]. Another significant finding is the differences in fatigue severity, depressive thoughts and daytime hypersomnolence between CFS patients with and without POTS, providing evidence for the clinical importance of POTS in CFS.

You can read the full comment here: http://onlinelibrary.wiley.com/doi/10.1111/joim.12034/full

Comment on: Clinical characteristics of a novel subgroup of chronic fatigue syndrome patients with postural orthostatic tachycardia syndrome. [J Intern Med. 2013]

 

Source: Nijs J, Ickmans K. Postural orthostatic tachycardia syndrome as a clinically important subgroup of chronic fatigue syndrome: further evidence for central nervous system dysfunctioning. J Intern Med. 2013 May;273(5):498-500. doi: 10.1111/joim.12034. Epub 2013 Feb 8. http://onlinelibrary.wiley.com/doi/10.1111/joim.12034/full (Full article)

 

Cost-effectiveness of supported self-management for CFS/ME patients in primary care

Abstract:

BACKGROUND: Nurse led self-help treatments for people with chronic fatigue syndrome/myalgic encephalitis (CFS/ME) have been shown to be effective in reducing fatigue but their cost-effectiveness is unknown.

METHODS: Cost-effectiveness analysis conducted alongside a single blind randomised controlled trial comparing pragmatic rehabilitation (PR) and supportive listening (SL) delivered by primary care nurses, and treatment as usual (TAU) delivered by the general practitioner (GP) in North West England. A within trial analysis was conducted comparing the costs and quality adjusted life years (QALYs) measured within the time frame of the trial. 296 patients aged 18 and over with CFS/ME diagnosed using the Oxford criteria were included in the cost-effectiveness analysis.

RESULTS: Treatment as usual is less expensive and leads to better patient outcomes compared with Supportive Listening. Treatment as usual is also less expensive than Pragmatic Rehabilitation. PR was effective at reducing fatigue in the short term, but the impact of the intervention on QALYs was uncertain. However, based on the results of this trial, PR is unlikely to be cost-effective in this patient population.

CONCLUSIONS: This analysis does not support the introduction of SL. Any benefits generated by PR are unlikely to be of sufficient magnitude to warrant recommending PR for this patient group on cost-effectiveness grounds alone. However, dissatisfaction with current treatment options means simply continuing with ‘treatment as usual’ in primary care is unlikely to be acceptable to patients and practitioners.

TRIAL REGISTRATION: The trial registration number is IRCTN74156610.

 

Source: Richardson G, Epstein D, Chew-Graham C, Dowrick C, Bentall RP, Morriss RK, Peters S, Riste L, Lovell K, Dunn G, Wearden AJ; FINE Trial Writing group on behalf of the FINE Trial group. Collaborators (23). Cost-effectiveness of supported self-management for CFS/ME patients in primary care. BMC Fam Pract. 2013 Jan 18;14:12. doi: 10.1186/1471-2296-14-12. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3556109/ (Full article)

 

Acute psychosocial stress-mediated changes in the expression and methylation of perforin in chronic fatigue syndrome

Abstract:

Perforin (PRF1) is essential for immune surveillance and studies report decreased perforin in chronic fatigue syndrome (CFS), an illness potentially associated with stress and/or infection. We hypothesize that stress can influence regulation of PRF1 expression, and that this regulation will differ between CFS and non-fatigued (NF) controls.

We used the Trier Social Stress Test (TSST) as a standardized acute psychosocial stress, and evaluated its effect on PRF1 expression and methylation in CFS (n = 34) compared with NF (n = 47) participants. During the TSST, natural killer (NK) cells increased significantly in both CFS (P = <0.0001) and NF subjects (P = <0.0001). Unlike previous reports, there was no significant difference in PRF1 expression at baseline or during TSST between CFS and NF. However, whole blood PRF1 expression increased 1.6 fold during the TSST in both CFS (P = 0.0003) and NF (P = <0.0001). Further, the peak response immediately following the TSST was lower in CFS compared with NF (P = 0.04).

In addition, at 1.5 hours post TSST, PRF1 expression was elevated in CFS compared with NF (whole blood, P = 0.06; PBMC, P = 0.02). Methylation of seven CpG sites in the methylation sensitive region of the PRF1 promoter ranged from 38%-79% with no significant differences between CFS and NF. Although, the average baseline methylation of all seven CpG sites did not differ between CFS and NF groups, it showed a significant negative correlation with PRF1 expression at all TSST time points in both CFS (r = -0.56, P = <0.0001) and NF (r = -0.38, P = <0.0001). Among participants with high average methylation (≥65%), PRF1 expression was significantly lower in CFS than NF subjects immediately following TSST.

These findings suggest methylation could be an important epigenetic determinant of inter-individual differences in PRF1 expression and that the differences in PRF1 expression and methylation between CFS and NF in the acute stress response require further investigation.

 

Source: Falkenberg VR, Whistler T, Murray JR, Unger ER, Rajeevan MS. Acute psychosocial stress-mediated changes in the expression and methylation of perforin in chronic fatigue syndrome. Genet Epigenet. 2013 Jan 28;5:1-9. doi: 10.4137/GEG.S10944. ECollection 2013. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4222335/ (Full article)

 

Inflammatory and oxidative and nitrosative stress cascades as new drug targets in myalgic encephalomyelitis and chronic fatigue syndrome

Abstract:

Myalgic encephalomyelitis (ME), chronic fatigue syndrome (CFS) and chronic fatigue (CF) are distinct diagnostic categories with regard to clinical symptoms, severity of illness and biomarkers. Patients with ME and CFS show higher scores on fatigue, neurocognitive disorders, hyperalgesia, autonomic symptoms, postexertional malaise and a subjective feeling of infection than patients with CF. ME is characterized by increased postexertional malaise, a subjective feeling of infection and neurocognitive disorders and is a more severe variant than CFS.

Fukuda’s 1994 CDC criteria are adequate to make a distinction between patients with ME/CFS and CF, while ME/CFS patients should be subdivided into those with and without postexertional malaise into ME and CFS, respectively. Different interrelated pathophysiological mechanisms play a role in ME/CFS, i.e. (1) inflammation and immune activation, (2) oxidative and nitrosative stress and lowered antioxidant defenses, (3) activation of cell signaling networks, e.g. nuclear factor ĸβ, the 2 9 ,5 9 -oligoadenylate/RNase-L and/or protein kinase R pathway, (4) a transition towards autoimmune reactions, and (5) bacterial translocation.

The inflammatory biomarkers are higher in ME/CFS than in CF and higher in ME than in CFS. The above-mentioned pathways may explain the onset of characteristic ME/CFS symptoms, such as fatigue, malaise, autonomic symptoms, hyperalgesia, and neurocognitive symptoms. Different etiological factors may trigger ME/CFS/CF, e.g. viral and bacterial infections, and (auto)immune and inflammatory disorders, while psychosocial and physical stressors act as modulating factors. New pathophysiologically driven drug candidates for ME and CFS are discussed which target the pathways that play a role in ME/CFS.

Copyright © 2013 S. Karger AG, Basel.

 

Source: Maes M. Inflammatory and oxidative and nitrosative stress cascades as new drug targets in myalgic encephalomyelitis and chronic fatigue syndrome. Mod Trends Pharmacopsychiatri. 2013;28:162-74. doi: 10.1159/000343982. Epub 2013 Feb 27. https://www.ncbi.nlm.nih.gov/pubmed/25224898