Category: Diagnosis

An evaluation of exclusionary medical/psychiatric conditions in the definition of chronic fatigue syndrome

Abstract:

BACKGROUND: The diagnosis of chronic fatigue syndrome (CFS) in research studies requires the exclusion of subjects with medical and psychiatric conditions that could confound the analysis and interpretation of results. This study compares illness parameters between individuals with CFS who have and those who do not have exclusionary conditions.

METHODS: We used a population-based telephone survey of randomly selected individuals, followed by a clinical evaluation in the study metropolitan, urban, and rural counties of Georgia, USA. The medical and psychiatric histories of the subjects were examined and they underwent physical and psychiatric examinations and laboratory screening. We also employed the multidimensional fatigue inventory (MFI), the medical outcomes survey short form-36 (SF-36) and the US Centres for Disease Control and Prevention symptom inventory (SI).

RESULTS: Twenty-nine percent (1,609) of the 5623 subjects who completed the detailed telephone interview reported exclusionary diagnoses and we diagnosed an exclusionary condition in 36% of 781 clinically evaluated subjects. Both medical and psychiatric exclusionary conditions were more common in women, blacks and participants from rural areas. Subjects with and without exclusions had similar levels of fatigue and impairment as measured by the MFI and SF-36; those with CFS-like illness (not meeting the formal CFS definition) were more likely to have an exclusionary diagnosis. After adjusting for demographics, body mass index, fatigue subscales, SF-36 subscales and CFS symptoms, CFS-like illness did not remain significantly associated with having an exclusionary diagnosis.

CONCLUSION: Medical and psychiatric illnesses associated with fatigue are common among the unwell. Those who fulfill CFS-like criteria need to be evaluated for potentially treatable conditions. Those with exclusionary conditions are equally impaired as those without exclusions.

Comment in: Chronic fatigue syndrome: identifying zebras amongst the horses. [BMC Med. 2009]

 

Source: Jones JF, Lin JM, Maloney EM, Boneva RS, Nater UM, Unger ER, Reeves WC. An evaluation of exclusionary medical/psychiatric conditions in the definition of chronic fatigue syndrome. BMC Med. 2009 Oct 12;7:57. doi: 10.1186/1741-7015-7-57. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2768736/ (Full article)

 

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)

 

Autoantibodies to lens epithelium-derived growth factor/transcription co-activator P75 (LEDGF/P75) in children with chronic nonspecific complaints and with positive antinuclear antibodies

Abstract:

Autoimmune fatigue syndrome (AIFS) is characterized by chronic nonspecific complaints, consistently positive antinuclear antibodies (ANA), and lack of alternate medical explanations. A newly recognized antibody, named anti-Sa, was detected in approximately 40% of the patients by Western blot (WB) using HeLa extract.

Some patients with AIFS later develop chronic fatigue syndrome (CFS), and most of them are positive for anti-Sa. On the other hand, Muro et al. reported anti-DFS70 in patients with CFS. Anti-Sa and anti-DFS70 were turned out to be same specificities by exchanging studies of blind sera. The target antigen of anti-DFS70 was identified as lens epithelium derived growth factor/transcription co-activator p75 (LEDGF/p75).

The objectives of this study are to confirm whether the target antigen of anti-Sa is also LEDGF/p75, and to develop ELISA system by using recombinant protein. Recombinant protein of LEDGF/p75 was purchased from Protein One (Bethesda, MD, USA). We developed an ELISA system to detect anti-LEDGF/p75 by coating this recombinant protein. 226 sera of AIFS patients (including 36 CFS patients) were applied to this ELISA assay and Western immunoblot, and it was revealed that anti-Sa-positive sera defined by WB and sera positive for anti-LEDGF/p75 on ELISA were identical.

Moreover, reactivities of anti-Sa on WB were inhibited by pre-incubating with recombinant LEDGF/p75, and eluted antibodies from the nitrocellulose membrane could react on the ELISA. These results confirm that the Sa antigen is LEDGF/p75. The ELISA assay using recombinant LEDGF/p75 could be a promising tool for measuring anti-Sa and consequently for diagnosing CFS.

 

Source: Kuwabara N, Itoh Y, Igarshi T, Fukunaga Y. Autoantibodies to lens epithelium-derived growth factor/transcription co-activator P75 (LEDGF/P75) in children with chronic nonspecific complaints and with positive antinuclear antibodies. Autoimmunity. 2009 Sep;42(6):492-6. Doi: 10.1080/08916930902736663. https://www.ncbi.nlm.nih.gov/pubmed/19657776

 

Are chronic fatigue and chronic fatigue syndrome valid clinical entities across countries and health-care settings?

Abstract:

OBJECTIVE: The validity of the diagnosis of chronic fatigue syndrome and related chronic fatigue states remains controversial, particularly in psychiatry. This project utilized international epidemiological and clinical research data to test construct validity across diagnostic categories, health-care settings and countries. Relevant demographic, symptom and diagnostic data were obtained from 33 studies in 21 countries. The subjects had fatigue lasting 1-6 months (prolonged fatigue), or >6 months (chronic fatigue), or met diagnostic criteria for chronic fatigue syndrome.

METHOD: Common symptom domains were derived by factor analytic techniques. Mean scores on each symptom factor were compared across diagnostic categories, health-care settings and countries.

RESULTS: Data were obtained on 37,724 subjects (n = 20,845 female, 57%), including from population-based studies (n = 15,749, 42%), studies in primary care (n = 19 472, 52%), and secondary or specialist tertiary referral clinics (n = 2503, 7%). The sample included 2013 subjects with chronic fatigue, and 1958 with chronic fatigue syndrome. A five-factor model of the key symptom domains was preferred (‘musculoskeletal pain/fatigue’, ‘neurocognitive difficulties’, ‘inflammation’, ‘sleep disturbance/fatigue’ and ‘mood disturbance’) and was comparable across subject groups and settings. Although the core symptom profiles were similar, some differences in symptoms were observed across diagnostic categories, health-care settings and between countries.

CONCLUSIONS: The construct validity of chronic fatigue and chronic fatigue syndrome is supported by an empirically derived factor structure from existing international datasets.

 

 

Source: Hickie I, Davenport T, Vernon SD, Nisenbaum R, Reeves WC, Hadzi-Pavlovic D, Lloyd A; International Chronic Fatigue Syndrome Study Group. Collaborators (28) Are chronic fatigue and chronic fatigue syndrome valid clinical entities across countries and health-care settings? Aust N Z J Psychiatry. 2009 Jan;43(1):25-35. Doi: 10.1080/00048670802534432. https://www.ncbi.nlm.nih.gov/pubmed/19085525

 

Spectroscopic diagnosis of chronic fatigue syndrome by multivariate analysis of visible and near-infrared spectra

Abstract:

We have recently evaluated the possibility of visible and near-infrared (Vis-NIR) spectroscopy for diagnosis of chronic fatigue syndrome(CFS). Vis-NIR spectra in the 600-1,100 nm region for sera from CFS patients and healthy donors were subjected to principal component analysis (PCA) and soft independent modeling of class analogy (SIMCA) to develop multivariate models to discriminate between CFS patients and healthy donors. The PCA and SIMCA model predicted successful prediction of the masked samples. Furthermore, taking advantage of Vis-NIR spectroscopy to enable noninvasive analysis, our preliminary results have shown that SIMCA model from Vis-NIR spectra of thumb has achieved 70-80% correct determinations. In this review, we will introduce the potential of the Vis-NIR spectroscopy for CFS diagnosis.

 

Source: Sakudo A, Kuratsune H, Hakariya Y, Kobayashi T, Ikuta K. Spectroscopic diagnosis of chronic fatigue syndrome by multivariate analysis of visible and near-infrared spectra. Nihon Rinsho. 2007 Jun;65(6):1051-6. [Article in Japanese] https://www.ncbi.nlm.nih.gov/pubmed/17561696

 

Overview of chronic fatigue syndrome focusing on prevalence and diagnostic criteria

Abstract:

Chronic fatigue syndrome (CFS) is an operational concept proposed by Centers for Disease Control and Prevention to clarify the unknown etiology of the syndrome characterized by the sensation of abnormally prolonged fatigue. Lots of investigators reported various abnormalities such as virus infection, immune abnormalities, HPA axis abnormalities, metabolic abnormalities, etc., but there are a few abnormalities common to vast majority cases of CFS. Therefore, lots of people as well as medical doctors are still skeptical about the presence of CFS.

However, recent studies reveal that CFS can be understood to be a special condition based on the abnormality of neuroendocrine-immunologic system caused by the psycho-social stress and some genetic components. Under these conditions, a reactivation of various kinds of herpes virus infections and/or chronic infections might occur as a result of immune dysfunction, causing the abnormal production of several cytokines. A distinctive feature of CFS is thought to be the secondary brain dysfunction caused by the abnormal production of several cytokines. In this paper, I show the overview of CFS focusing around prevalence, economic impact and diagnostic criteria in Japan.

 

Source: Kuratsune H. Overview of chronic fatigue syndrome focusing on prevalence and diagnostic criteria. Nihon Rinsho. 2007 Jun;65(6):983-90. [Article in Japanese] https://www.ncbi.nlm.nih.gov/pubmed/17561686

 

Differential diagnosis of chronic fatigue syndrome and major depressive disorder

Abstract:

The goal of this study was to identify variables that successfully differentiated patients with chronic fatigue syndrome, major depressive disorder, and controls. Fifteen participants were recruited for each of these three groups, and discriminant function analyses were conducted.

Using symptom occurrence and severity data from the Fukuda et al. (1994) definitional criteria, the best predictors were postexertional malaise, unrefreshing sleep, and impaired memory-concentration. Symptom occurrence variables only correctly classified 84.4% of cases, whereas 91.1% were correctly classified when using symptom severity ratings. Finally, when using percentage of time fatigue reported, postexertional malaise severity, unrefreshing sleep severity, confusion-disorientation severity, shortness of breath severity, and self-reproach to predict group membership, 100% were classified correctly.

 

Source: Hawk C, Jason LA, Torres-Harding S. Differential diagnosis of chronic fatigue syndrome and major depressive disorder. Int J Behav Med. 2006;13(3):244-51. https://www.ncbi.nlm.nih.gov/pubmed/17078775

 

Spectroscopic diagnosis of chronic fatigue syndrome by visible and near-infrared spectroscopy in serum samples

Abstract:

To investigate visible and near-infrared (Vis-NIR) spectroscopy enabling chronic fatigue syndrome (CFS) diagnosis, we subjected sera from CFS patients as well as healthy donors to Vis-NIR spectroscopy. Vis-NIR spectra in the 600-1100 nm region for sera from 77 CFS patients and 71 healthy donors were subjected to principal component analysis (PCA) and soft independent modeling of class analogy (SIMCA) to develop multivariate models to discriminate between CFS patients and healthy donors. The model was further assessed by the prediction of 99 masked other determinations (54 in the healthy group and 45 in the CFS patient group).

The PCA model predicted successful discrimination of the masked samples. The SIMCA model predicted 54 of 54 (100%) healthy donors and 42 of 45 (93.3%) CFS patients of Vis-NIR spectra from masked serum samples correctly. These results suggest that Vis-NIR spectroscopy for sera combined with chemometrics analysis could provide a promising tool to objectively diagnose CFS.

 

Source: Sakudo A, Kuratsune H, Kobayashi T, Tajima S, Watanabe Y, Ikuta K. Spectroscopic diagnosis of chronic fatigue syndrome by visible and near-infrared spectroscopy in serum samples. Biochem Biophys Res Commun. 2006 Jul 14;345(4):1513-6. Epub 2006 May 22. https://www.ncbi.nlm.nih.gov/pubmed/16730652

 

An empirical delineation of the heterogeneity of chronic unexplained fatigue in women

Abstract:

OBJECTIVES: To test the hypothesis that medically unexplained chronic fatigue and chronic fatigue syndrome (CFS) are heterogeneous conditions, and to define the different conditions using both symptom and laboratory data.

METHODS: We studied 159 women from KS, USA. A total of 51 of these suffered from fatigue consistent with established criteria for CFS, 55 had chronic fatigue of insufficient symptoms/severity for a CFS diagnosis and 53 were healthy controls matched by age and body mass index (BMI) against those with CFS. We used principal components analyses to define factors that best described the variable space and to reduce the number of variables. The 38 most explanatory variables were then used in latent class analyses to define discrete subject groups.

RESULTS: Principal components analyses defined six discrete factors that explained 40% of the variance. Latent class analyses provided several interpretable solutions with four, five and six classes. The four-class solution was statistically most convincing, but the six-class solution was more interpretable. Class 1 defined 41 (26%) subjects with obesity and relative sleep hypnoea. Class 2 were 38 (24%) healthy subjects. Class 3 captured 24 (15%) obese relatively hypnoeic subjects, but with low heart rate variability and cortisol. Class 4 were 23 (14%) sleep-disturbed and myalgic subjects without obesity or significant depression. The two remaining classes with 22 (14%) and 11 (7%) subjects consisted of the most symptomatic and depressed, but without obesity or hypnoea. Class 5 had normal sleep indices. Class 6 was characterized by disturbed sleep, with low sleep heart rate variability, cortisol, and sex hormones.

CONCLUSION: Chronic medically unexplained fatigue is heterogeneous. The putative syndromes were differentiated by obesity, sleep hypnoea, depression, physiological stress response, sleep disturbance, interoception and menopausal status. If these syndromes are externally validated and replicated, they may prove useful in determining the causes, pathophysiology and treatments of CFS.

 

Source: Vollmer-Conna U, Aslakson E, White PD. An empirical delineation of the heterogeneity of chronic unexplained fatigue in women. Pharmacogenomics. 2006 Apr;7(3):355-64. https://www.ncbi.nlm.nih.gov/pubmed/16610946

 

Challenges for molecular profiling of chronic fatigue syndrome

Abstract:

Chronic fatigue syndrome (CFS) is prevalent, disabling and costly. Despite extensive literature describing the epidemiology and clinical aspects of CFS, it has been recalcitrant to diagnostic biomarker discovery and therapeutic intervention. This is due to the fact that CFS is a complex illness defined by self-reported symptoms and diagnosed by the exclusion of medical and psychiatric diseases that may explain the symptoms.

Studies attempting to dissect the pathophysiology are challenging to design as CFS affects multiple body systems, making the choice of which system to study dependent on an investigators area of expertise. However, the peripheral blood appears to be facilitating the molecular profiling of several diseases, such as CFS, that involve bodywide perturbations that are mediated by the CNS. Successful molecular profiling of CFS will require the integration of genetic, genomic and proteomic data with environmental and behavioral data to define the heterogeneity in order to optimize intervention.

 

Source: Vernon SD, Whistler T, Aslakson E, Rajeevan M, Reeves WC. Challenges for molecular profiling of chronic fatigue syndrome. Pharmacogenomics. 2006 Mar;7(2):211-8. https://www.ncbi.nlm.nih.gov/pubmed/16515400