Prevalence, incidence, and classification of chronic fatigue syndrome in Olmsted County, Minnesota, as estimated using the Rochester Epidemiology Project

Abstract:

OBJECTIVE: To estimate the prevalence and incidence of chronic fatigue syndrome in Olmsted County, Minnesota, using the 1994 case definition and describe exclusionary and comorbid conditions observed in patients who presented for evaluation of long-standing fatigue.

PATIENTS AND METHODS: We conducted a retrospective medical record review of potential cases of chronic fatigue syndrome identified from January 1, 1998, through December 31, 2002, using the Rochester Epidemiology Project, a population-based database. Patients were classified as having chronic fatigue syndrome if the medical record review documented fatigue of 6 months’ duration, at least 4 of 8 chronic fatigue syndrome-defining symptoms, and symptoms that interfered with daily work or activities. Patients not meeting all of the criteria were classified as having insufficient/idiopathic fatigue.

RESULTS: We identified 686 potential patients with chronic fatigue, 2 of whom declined consent for medical record review. Of the remaining 684 patients, 151 (22%) met criteria for chronic fatigue syndrome or insufficient/idiopathic fatigue. The overall prevalence and incidence of chronic fatigue syndrome and insufficient/idiopathic fatigue were 71.34 per 100,000 persons and 13.16 per 100,000 person-years vs 73.70 per 100,000 persons and 13.58 per 100,000 person-years, respectively. The potential cases included 482 patients (70%) who had an exclusionary condition, and almost half the patients who met either criterion had at least one nonexclusionary comorbid condition.

CONCLUSION: The incidence and prevalence of chronic fatigue syndrome and insufficient/idiopathic fatigue are relatively low in Olmsted County. Careful clinical evaluation to identify whether fatigue could be attributed to exclusionary or comorbid conditions rather than chronic fatigue syndrome itself will ensure appropriate assessment for patients without chronic fatigue syndrome.

Copyright © 2012 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.

 

Source: Vincent A, Brimmer DJ, Whipple MO, Jones JF, Boneva R, Lahr BD, Maloney E, St Sauver JL, Reeves WC. Prevalence, incidence, and classification of chronic fatigue syndrome in Olmsted County, Minnesota, as estimated using the Rochester Epidemiology Project. Mayo Clin Proc. 2012 Dec;87(12):1145-52. doi: 10.1016/j.mayocp.2012.08.015. Epub 2012 Nov 8. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3518652/ (Full article)

 

Modulation of the axon-reflex response to local heat by reactive oxygen species in subjects with chronic fatigue syndrome

Abstract:

Local cutaneous heating causes vasodilation as an initial first peak, a nadir, and increase to plateau. Reactive oxygen species (ROS) modulate the heat plateau in healthy controls. The initial peak, due to C-fiber nociceptor-mediated axon reflexes, is blunted with local anesthetics and may serve as a surrogate for the cutaneous response to peripheral heat. Chronic fatigue syndrome (CFS) subjects report increased perception of pain. To determine the role of ROS in this neurally mediated response, we evaluated changes in cutaneous blood flow from local heat in nine CFS subjects (16-22 yr) compared with eight healthy controls (18-26 yr).

We heated skin to 42°C and measured local blood flow as a percentage of maximum cutaneous vascular conductance (%CVC(max)). Although CFS subjects had significantly lower baseline flow [8.75 ± 0.56 vs. 12.27 ± 1.07 (%CVC(max), CFS vs. control)], there were no differences between groups to local heat. We then remeasured this with apocynin to inhibit NADPH oxidase, allopurinol to inhibit xanthine oxidase, tempol to inhibit superoxide, and ebselen to reduce H(2)O(2). Apocynin significantly increased baseline blood flow (before heat, 14.91 ± 2.21 vs. 8.75 ± 1.66) and the first heat peak (69.33 ± 3.36 vs. 59.75 ± 2.75). Allopurinol and ebselen only enhanced the first heat peaks (71.55 ± 2.48 vs. 61.72 ± 2.01 and 76.55 ± 5.21 vs. 58.56 ± 3.66, respectively). Tempol had no effect on local heating. None of these agents changed the response to local heat in control subjects. Thus the response to heat may be altered by local levels of ROS, particularly H(2)O(2) in CFS subjects, and may be related to their hyperesthesia/hyperalgesia.

 

Source: Medow MS, Aggarwal A, Baugham I, Messer Z, Stewart JM. Modulation of the axon-reflex response to local heat by reactive oxygen species in subjects with chronic fatigue syndrome. J Appl Physiol (1985). 2013 Jan 1;114(1):45-51. doi: 10.1152/japplphysiol.00821.2012. Epub 2012 Nov 8. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3544512/ (Full article)

 

Improved chronic fatigue symptoms after removal of mercury in patient with increased mercury concentration in hair toxic mineral assay: a case

Abstract:

Clinical manifestations of chronic exposure to organic mercury usually have a gradual onset. As the primary target is the nervous system, chronic mercury exposure can cause symptoms such as fatigue, weakness, headache, and poor recall and concentration. In severe cases chronic exposure leads to intellectual deterioration and neurologic abnormality. Recent outbreaks of bovine spongiform encephalopathy and pathogenic avian influenza have increased fish consumption in Korea. Methyl-mercury, a type of organic mercury, is present in higher than normal ranges in the general Korean population. When we examine a patient with chronic fatigue, we assess his/her methyl-mercury concentrations in the body if environmental exposure such as excessive fish consumption is suspected. In the current case, we learned the patient had consumed many slices of raw tuna and was initially diagnosed with chronic fatigue syndrome. Therefore, we suspected that he was exposured to methyl-mercury and that the mercury concentration in his hair would be below the poisoning level identified by World Health Organization but above the normal range according to hair toxic mineral assay. Our patient’s toxic chronic fatigue symptoms improved after he was given mercury removal therapy, indicating that he was correctly diagnosed with chronic exposure to organic mercury.

 

Source: Shin SR, Han AL. Improved chronic fatigue symptoms after removal of mercury in patient with increased mercury concentration in hair toxic mineral assay: a case. Korean J Fam Med. 2012 Sep;33(5):320-5. doi: 10.4082/kjfm.2012.33.5.320. Epub 2012 Sep 27. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3481032/ (Full article)

 

Why do young people with CFS/ME feel anxious? A qualitative study

Abstract:

Young people with chronic fatigue syndrome or myalagic encephalopathy (CFS/ME) (CFS/ME) experience higher levels of psychological distress than healthy controls and young people with other chronic illnesses, and it was recently demonstrated that 38% of this population scored above the clinical cut-off on the Spence Child Anxiety Scale. Subscales of social and separation anxiety were consistently high across gender and age groups.

In this study, we used qualitative methods to help us understand more about these two types of anxiety in young people with CFS/ME. Eleven young people (age 12-18) were interviewed. Interviews were self-directed by the participants and were wide ranging. The transcripts were analysed using interpretative phenomenological analysis. Five superordinate themes were identified: social loss and adjustment; introduction of uncertainty and unpredictability; the vulnerable self; individual differences; and contributions towards recovery.

Many themes were identical to those described in young people coping with other chronic illnesses in adolescence. In addition, young people with CFS/ME describe experiences associated with the perceived illegitimacy of this condition, namely: feeling unable to explain their illness; bullying from peers; disbelief; and distrust from adults around them. This becomes an additional challenge for these young people. Clinicians need to be aware of these problems, and offer appropriate support.

 

Source: Fisher H, Crawley E. Why do young people with CFS/ME feel anxious? A qualitative study. Clin Child Psychol Psychiatry. 2013 Oct;18(4):556-73. doi: 10.1177/1359104512460862. Epub 2012 Oct 23. https://www.ncbi.nlm.nih.gov/pubmed/23093520

 

Response to valganciclovir in chronic fatigue syndrome patients with human herpesvirus 6 and Epstein-Barr virus IgG antibody titers

Abstract:

Valganciclovir has been reported to improve physical and cognitive symptoms in patients with chronic fatigue syndrome (CFS) with elevated human herpesvirus 6 (HHV-6) and Epstein-Barr virus (EBV) IgG antibody titers. This study investigated whether antibody titers against HHV-6 and EBV were associated with clinical response to valganciclovir in a subset of CFS patients.

An uncontrolled, unblinded retrospective chart review was performed on 61 CFS patients treated with 900 mg valganciclovir daily (55 of whom took an induction dose of 1,800 mg daily for the first 3 weeks). Antibody titers were considered high if HHV-6 IgG ≥ 1:320, EBV viral capsid antigen (VCA) IgG ≥ 1:640, and EBV early antigen (EA) IgG ≥ 1:160. Patients self-rated physical and cognitive functioning as a percentage of their functioning prior to illness. Patients were categorized as responders if they experienced at least 30% improvement in physical and/or cognitive functioning. Thirty-two patients (52%) were categorized as responders. Among these, 19 patients (59%) responded physically and 26 patients (81%) responded cognitively. Baseline antibody titers showed no significant association with response.

After treatment, the average change in physical and cognitive functioning levels for all patients was +19% and +23%, respectively (P < 0.0001). Longer treatment was associated with improved response (P = 0.0002). No significant difference was found between responders and non-responders among other variables analyzed. Valganciclovir treatment, independent of the baseline antibody titers, was associated with self-rated improvement in physical and cognitive functioning for CFS patients who had positive HHV-6 and/or EBV serologies. Longer valganciclovir treatment correlated with an improved response.

Copyright © 2012 Wiley Periodicals, Inc.

 

Source: Watt T, Oberfoell S, Balise R, Lunn MR, Kar AK, Merrihew L, Bhangoo MS, Montoya JG. Response to valganciclovir in chronic fatigue syndrome patients with human herpesvirus 6 and Epstein-Barr virus IgG antibody titers. J Med Virol. 2012 Dec;84(12):1967-74. doi: 10.1002/jmv.23411. https://www.ncbi.nlm.nih.gov/pubmed/23080504

 

Functional somatic syndromes: sensitivities and specificities of self-reports of physician diagnosis

Abstract:

OBJECTIVE: Functional somatic syndromes have no laboratory or pathologic abnormalities and so are diagnosed by symptom-based case definitions. However, many studies, including recent ones, have used self-reports of physician diagnosis rather than the case definitions. Our objective was to determine the sensitivities and specificities of self-report of physician diagnosis for chronic fatigue syndrome (CFS), fibromyalgia (FM), irritable bowel syndrome (IBS), panic disorder, and migraine.

METHODS: Each of 312 female patients with incident interstitial cystitis/bladder pain syndrome and matched population-based controls were queried on self-report of physician diagnosis and separately on established case definitions for each of these syndromes.

RESULTS: Using the symptom-based case definitions as standards, we found that self-report of physician diagnosis did not identify 90% of the controls who had CFS, 77% who had FM, 69% who had IBS, 43% who had panic disorder, and 23% who had migraine. In addition, it missed most individuals with multiple syndromes. Findings in one cohort (controls) were confirmed in another (patients with interstitial cystitis/bladder pain syndrome).

CONCLUSIONS: Self-report of physician diagnosis did not identify most of the three most venerable functional somatic syndromes, IBS, FM, and, especially, CFS; nor did it identify substantial minorities of individuals with panic disorder and migraine. Self-report of physician diagnosis was particularly poor in recognizing persons with multiple syndromes. The insensitivity of this diagnostic test has effects on not only prevalence and incidence estimates but also correlates, comorbidities, and case recruitment. To reveal individuals with these syndromes, singly or together, queries of symptoms, not diagnoses, are necessary.

Comment in: Recalling, reporting, and thinking about diagnoses. [Psychosom Med. 2012]

 

Source: Warren JW, Clauw DJ. Functional somatic syndromes: sensitivities and specificities of self-reports of physician diagnosis. Psychosom Med. 2012 Nov-Dec;74(9):891-5. doi: 10.1097/PSY.0b013e31827264aa. Epub 2012 Oct 15. https://www.ncbi.nlm.nih.gov/pubmed/23071343

 

Use of lisdexamfetamine dimesylate in treatment of executive functioning deficits and chronic fatigue syndrome: a double blind, placebo-controlled study

Abstract:

The purpose of this study was to assess the efficacy of lisdexamfetamine dimesylate (LDX) for the treatment of executive functioning deficits in adults (ages 18-60) with chronic fatigue syndrome (CFS). The study’s primary outcome measure was the Behavior Rating Inventory of Executive Function-Adult (BRIEF-A). Secondary outcome measures were standardized assessments of fatigue, pain and global functioning.

Twenty-six adults who met criteria for CFS and had clinically significant executive functioning deficits were randomly assigned to a flexible morning dose (30, 50, 70 mg/day) of either placebo or LDX for a 6-week trial. The data were analyzed with standard analysis of variance (ANOVA) procedures. Participants in the LDX group showed significantly more positive change in BRIEF-A scores (Mchange=21.38, SD=15.85) than those in the placebo group (Mchange=3.36, SD=7.26).

Participants in the active group also reported significantly less fatigue and generalized pain relative to the placebo group. Although future studies with LDX should examine whether these benefits generalize to larger, more diverse samples of patients, these results suggest that LDX could be a safe and efficacious treatment for the executive functioning deficits often associated with CFS. The possibility that dopaminergic medications could play an important role addressing the symptoms of CFS is also discussed.

Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

 

Source: Young JL. Use of lisdexamfetamine dimesylate in treatment of executive functioning deficits and chronic fatigue syndrome: a double blind, placebo-controlled study. Psychiatry Res. 2013 May 15;207(1-2):127-33. doi: 10.1016/j.psychres.2012.09.007. Epub 2012 Oct 9. https://www.ncbi.nlm.nih.gov/pubmed/23062791

 

Chronic fatigue syndrome: diagnosis and treatment

Abstract:

Chronic fatigue syndrome is characterized by debilitating fatigue that is not relieved with rest and is associated with physical symptoms. The Centers for Disease Control and Prevention criteria for chronic fatigue syndrome include severe fatigue lasting longer than six months, as well as presence of at least four of the following physical symptoms: postexertional malaise; unrefreshing sleep; impaired memory or concentration; muscle pain; polyarthralgia; sore throat; tender lymph nodes; or new headaches. It is a clinical diagnosis that can be made only when other disease processes are excluded. The etiology of chronic fatigue syndrome is unclear, is likely complex, and may involve dysfunction of the immune or adrenal systems, an association with certain genetic markers, or a history of childhood trauma. Persons with chronic fatigue syndrome should be evaluated for concurrent depression, pain, and sleep disturbances. Treatment options include cognitive behavior therapy and graded exercise therapy, both of which have been shown to moderately improve fatigue levels, work and social adjustment, anxiety, and postexertional malaise. No pharmacologic or alternative medicine therapies have been proven effective.

Comment in: Article on CFS does not reflect current best treatment practices. [Am Fam Physician. 2013]

 

Source: Yancey JR, Thomas SM. Chronic fatigue syndrome: diagnosis and treatment. Am Fam Physician. 2012 Oct 15;86(8):741-6. http://www.aafp.org/afp/2012/1015/p741.html (Full article)

 

Immunophenotyping in post-giardiasis functional gastrointestinal disease and chronic fatigue syndrome

Abstract:

BACKGROUND: A Giardia outbreak was associated with development of post-infectious functional gastrointestinal disorders (PI-FGID) and chronic fatigue syndrome (PI-CFS). Markers of immune dysfunction have given conflicting results in CFS and FGID patient populations. The aim of this study was to evaluate a wide selection of markers of immune dysfunction in these two co-occurring post-infectious syndromes.

METHODS: 48 patients, reporting chronic fatigue in a questionnaire study, were clinically evaluated five years after the outbreak and grouped according to Fukuda criteria for CFS (n=19) and idiopathic chronic fatigue (n=5) and Rome II criteria for FGIDs (n=54). 22 Giardia exposed non-fatigued individuals and 10 healthy unexposed individuals were recruited as controls. Peripheral blood lymphocyte subsets were analyzed by flow cytometry.

RESULTS: In peripheral blood we found significantly higher CD8 T-cell levels in PI-FGID, and significantly lower NK-cell levels in PI-CFS patients. Severity of abdominal and fatigue symptoms correlated negatively with NK-cell levels. A tendency towards lower T-cell CD26 expression in FGID was seen.

CONCLUSION: Patients with PI-CFS and/or PI-FGID 5 years after Giardia lamblia infection showed alterations in NK-cell and CD8-cell populations suggesting a possible immunological abnormality in these conditions. We found no significant changes in other markers examined in this well-defined group of PI-CFS and PI-FGID elicited by a gastrointestinal infection. Controlling for co-morbid conditions is important in evaluation of CFS-biomarkers.

 

Source: Hanevik K, Kristoffersen EK, Sørnes S, Mørch K, Næss H, Rivenes AC, Bødtker JE, Hausken T, Langeland N. Immunophenotyping in post-giardiasis functional gastrointestinal disease and chronic fatigue syndrome. BMC Infect Dis. 2012 Oct 14;12:258. doi: 10.1186/1471-2334-12-258. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3553045/ (Full article)

 

Sleep in the chronic fatigue syndrome

Abstract:

Chronic fatigue syndrome (CFS) is a disabling condition characterized by severe fatigue lasting for more than six months and the presence of at least four out of eight minor criteria. Sleep disturbance presenting as unrefreshing or nonrestorative sleep is one of these criteria and is very common in CFS patients. Biologically disturbed sleep is a known cause of fatigue and could play a role in the pathogenesis of CFS. However, the nature of presumed sleep impairment in CFS remains unclear. Whilst complaints of NRS persist over time, there is no demonstrable neurophysiological correlate to substantiate a basic deficit in sleep function in CFS. Polysomnographic findings have not shown to be significantly different between subjects with CFS and normal controls. Discrepancies between subjectively poor and objectively normal sleep suggest a role for psychosocial factors negatively affecting perception of sleep quality. Primary sleep disorders are often detected in patients who otherwise qualify for a CFS diagnosis. These disorders could contribute to the presence of daytime dysfunctioning. There is currently insufficient evidence to indicate that treatment of primary sleep disorders sufficiently improves the fatigue associated with CFS. Therefore, primary sleep disorders may be a comorbid rather than an exclusionary condition with respect to CFS.

Copyright © 2012 Elsevier Ltd. All rights reserved.

 

Source: Mariman AN, Vogelaers DP, Tobback E, Delesie LM, Hanoulle IP, Pevernagie DA. Sleep in the chronic fatigue syndrome. Sleep Med Rev. 2013 Jun;17(3):193-9. doi: 10.1016/j.smrv.2012.06.003. Epub 2012 Oct 6. https://www.ncbi.nlm.nih.gov/pubmed/23046847