Category: Overlapping Illnesses

A pilot registry of unexplained fatiguing illnesses and chronic fatigue syndrome

Abstract:

BACKGROUND: Chronic fatigue syndrome (CFS) has no diagnostic clinical signs or biomarkers, so diagnosis requires ruling out conditions with similar signs and symptoms. We conducted a pilot registry of unexplained fatiguing illnesses and CFS to determine the feasibility of establishing and operating a registry and implementing an education outreach initiative. The pilot registry was conducted in Bibb County, Georgia. Patient referrals were obtained from healthcare providers who were identified by using various education outreach initiatives. These referrals were later supplemented with self-referrals by members of a local CFS support group. All patients meeting referral criteria were invited to participate in a screening interview to determine eligibility. If patients met registry criteria, they were invited to a one-day clinic for physical and laboratory evaluations. We classified patients based on the 1994 case definition.

RESULTS: We registered 827 healthcare providers. Forty-two providers referred 88 patients, and 58 patients (66%) completed clinical evaluation. Of the 188 CFS support group members, 53 were self-referred and 46 (87%) completed the clinical evaluation. Of the 104 participants completing evaluation, 36% (n = 37) met the criteria for CFS, 17% (n = 18) had insufficient fatigue or symptoms (ISF), and 47% (n = 49) were found to have exclusionary medical or psychiatric illnesses. Classification varied significantly by type of referral but not by previous history of CFS diagnosis. Healthcare providers referred more patients who were classified as CFS as compared to support group referrals in which more exclusionary conditions were identified. Family practice and internal medicine specialties made the most referrals and had the highest number of CFS cases. We conducted three CME events, held three “Meet and Greet” sessions, visited four large clinical health practices and health departments, mailed five registry newsletters, and conducted in-person office visits as part of education outreach, which contributed to patient referrals.

CONCLUSIONS: Referrals from healthcare providers and self-referrals from the patient support group were important to registry enrollment. The number of potentially treatable conditions that were identified highlights the need for continued medical management in this population, as well as the limitations of registries formed without clinical examination. Education initiatives were successful in part because of partnerships with local organizations.

 

Source: Brimmer DJ, Maloney E, Devlin R, Jones JF, Boneva R, Nagler C, LeRoy L, Royal S, Tian H, Lin JM, Kasten J, Unger ER. A pilot registry of unexplained fatiguing illnesses and chronic fatigue syndrome. BMC Res Notes. 2013 Aug 2;6:309. doi: 10.1186/1756-0500-6-309. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3750716/ (Full article)

 

Migraine in gulf war illness and chronic fatigue syndrome: prevalence, potential mechanisms, and evaluation

Abstract:

OBJECTIVE: To assess the prevalence of headache subtypes in Gulf War Illness (GWI) and Chronic Fatigue Syndrome (CFS) compared to controls.

BACKGROUND: Approximately, 25% of the military personnel who served in the 1990-1991 Persian Gulf War have developed GWI. Symptoms of GWI and CFS have considerable overlap, including headache complaints. Migraines are reported in CFS. The type and prevalence of headaches in GWI have not been adequately assessed.

METHODS: 50 GWI, 39 CFS and 45 controls had structured headache evaluations based on the 2004 International Headache Society criteria. All subjects had history and physical examinations, fatigue and symptom related questionnaires, measurements of systemic hyperalgesia (dolorimetry), and assessments for exclusionary conditions.

RESULTS: Migraines were detected in 64% of GWI (odds ratio = 11.6 [4.1-32.5]) (mean [±95% CI]) and 82% of CFS subjects (odds ratio = 22.5 [7.8-64.8]) compared to only 13% of controls. There was a predominance of females in the CFS compared to GWI and controls. However, migraine status was independent of gender in GWI and CFS groups (x (2) = 2.7; P = 0.101). Measures of fatigue, pain, and other ancillary criteria were comparable between GWI and CFS subjects with and without headache.

CONCLUSION: The high prevalence of migraine in CFS was confirmed and extended to GWI subjects. GWI and CFS may share dysfunctional central pathophysiological pathways that contribute to migraine and subjective symptoms. The high migraine prevalence warrants the inclusion of a structured headache evaluation in GWI and CFS subjects, and treatment when present.

 

Source: Rayhan RU, Ravindran MK, Baraniuk JN. Migraine in gulf war illness and chronic fatigue syndrome: prevalence, potential mechanisms, and evaluation. Front Physiol. 2013 Jul 24;4:181. doi: 10.3389/fphys.2013.00181. ECollection 2013. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3721020/ (Full article)

 

A comparison of sex-specific immune signatures in Gulf War illness and chronic fatigue syndrome

Abstract:

BACKGROUND: Though potentially linked to the basic physiology of stress response we still have no clear understanding of Gulf War Illness (GWI), a debilitating condition presenting complex immune, endocrine and neurological symptoms. Here we compared male (n = 20) and female (n = 10) veterans with GWI separately against their healthy counterparts (n = 21 male, n = 9 female) as well as subjects with chronic fatigue syndrome/ myalgic encephalomyelitis (CFS/ME) (n = 12 male, n = 10 female).

METHODS: Subjects were assessed using a Graded eXercise Test (GXT) with blood drawn prior to exercise, at peak effort (VO2 max) and 4-hours post exercise. Using chemiluminescent imaging we measured the concentrations of IL-1a, 1b, 2, 4, 5, 6, 8, 10, 12 (p70), 13, 15, 17 and 23, IFNγ, TNFα and TNFβ in plasma samples from each phase of exercise. Linear classification models were constructed using stepwise variable selection to identify cytokine co-expression patterns characteristic of each subject group.

RESULTS: Classification accuracies in excess of 80% were obtained using between 2 and 5 cytokine markers. Common to both GWI and CFS, IL-10 and IL-23 expression contributed in an illness and time-dependent manner, accompanied in male subjects by NK and Th1 markers IL-12, IL-15, IL-2 and IFNγ. In female GWI and CFS subjects IL-10 was again identified as a delineator but this time in the context of IL-17 and Th2 markers IL-4 and IL-5. Exercise response also differed between sexes: male GWI subjects presented characteristic cytokine signatures at rest but not at peak effort whereas the opposite was true for female subjects.

CONCLUSIONS: Though individual markers varied, results collectively supported involvement of the IL-23/Th17/IL-17 axis in the delineation of GWI and CFS in a sex-specific way.

 

Source: Smylie AL, Broderick G, Fernandes H, Razdan S, Barnes Z, Collado F, Sol C, Fletcher MA, Klimas N. A comparison of sex-specific immune signatures in Gulf War illness and chronic fatigue syndrome. BMC Immunol. 2013 Jun 25;14:29. doi: 10.1186/1471-2172-14-29. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3698072/ (Full article)

 

Examining the impact of obesity on individuals with chronic fatigue syndrome

Abstract:

Chronic fatigue syndrome (CFS) is a complex disorder affecting multiple body systems. The most commonly used definition of CFS is 6 or more months of fatigue and the presence of at least four of eight minor symptoms. In addition, many health and psychological conditions, including severe obesity-body mass index (BMI) of 40 kg/m(2) or greater-exclude individuals from a diagnosis of CFS. Obesity has been correlated with fatigue, sleep problems, and less satisfaction with general health, functioning, and vitality.

The current study investigated weight trends over time in a community-based sample of individuals with CFS and healthy controls. The study further investigated the impact of comorbid weight issues on several health and disability outcomes in a subset of overweight individuals.

Overweight and obese individuals with CFS demonstrated poorer functioning than controls who were similarly weighted. One participant was excluded because she had gained weight at a monitoring visit and her BMI was greater than 40 kg/m(2). The implications of these findings for health care workers are discussed.

Copyright 2013, SLACK Incorporated.

 

Source: Flores S, Brown A, Adeoye S, Jason LA, Evans M. Examining the impact of obesity on individuals with chronic fatigue syndrome.Workplace Health Saf. 2013 Jul;61(7):299-307. doi: 10.3928/21650799-20130617-12. Epub 2013 Jun 24. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3899694/ (Full article)

 

Cognitive impairments associated with CFS and POTS

Abstract:

Chronic fatigue syndrome (CFS) is characterized by fatigue, sleep dysfunction, and cognitive deficits (Fukuda et al., 1994). Research surrounding cognitive functioning among patients with CFS has found difficulty with memory, attention, and information processing. A similar disorder, postural tachycardia syndrome (POTS), is characterized by increased heart rate, fatigue, and mental cloudiness (Raj et al., 2009). Potential implications of cognitive deficits for patients with CFS and/or POTS are discussed, including difficulties with school and/or employment.

A few biological theories (i.e., kindling, impairments in the central nervous system, and difficulty with blood flow) have emerged as potential explanations for the cognitive deficits reported in both CFS and POTS Future research should continue to examine possible explanations for cognitive impairments in CFS and POTS, and ultimately use this information to try and reduce cognitive impairments for these patients.

 

Source: Shanks L, Jason LA, Evans M, Brown A. Cognitive impairments associated with CFS and POTS. Front Physiol. 2013 May 16;4:113. doi: 10.3389/fphys.2013.00113. ECollection 2013. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3655280/ (Full article)

 

Could mitochondrial dysfunction be a differentiating marker between chronic fatigue syndrome and fibromyalgia?

Abstract:

Chronic fatigue syndrome (CFS) and fibromyalgia (FM) are complex and serious illnesses that affect approximately 2.5% and 5% of the general population worldwide, respectively. The etiology is unknown; however, recent studies suggest that mitochondrial dysfunction has been involved in the pathophysiology of both conditions. We have investigated the possible association between mitochondrial biogenesis and oxidative stress in patients with CFS and FM.

We studied 23 CFS patients, 20 FM patients, and 15 healthy controls. Peripheral blood mononuclear cell showed decreased levels of Coenzyme Q10 from CFS patients (p<0.001 compared with controls) and from FM subjects (p<0.001 compared with controls) and ATP levels for CFS patients (p<0.001 compared with controls) and for FM subjects (p<0.001 compared with controls).

On the contrary, CFS/FM patients had significantly increased levels of lipid peroxidation, respectively (p<0.001 for both CFS and FM patients with regard to controls) that were indicative of oxidative stress-induced damage. Mitochondrial citrate synthase activity was significantly lower in FM patients (p<0.001) and, however, in CFS, it resulted in similar levels than controls. Mitochondrial DNA content (mtDNA/gDNA ratio) was normal in CFS and reduced in FM patients versus healthy controls, respectively (p<0.001). Expression levels of peroxisome proliferator-activated receptor gamma-coactivator 1-alpha and transcription factor A, mitochondrial by immunoblotting were significantly lower in FM patients (p<0.001) and were normal in CFS subjects compared with healthy controls.

These data lead to the hypothesis that mitochondrial dysfunction-dependent events could be a marker of differentiation between CFS and FM, indicating the mitochondria as a new potential therapeutic target for these conditions.

 

Source: Castro-Marrero J, Cordero MD, Sáez-Francas N, Jimenez-Gutierrez C, Aguilar-Montilla FJ, Aliste L, Alegre-Martin J. Could mitochondrial dysfunction be a differentiating marker between chronic fatigue syndrome and fibromyalgia? Antioxid Redox Signal. 2013 Nov 20;19(15):1855-60. doi: 10.1089/ars.2013.5346. Epub 2013 May 29. https://www.ncbi.nlm.nih.gov/pubmed/23600892

 

A case of lyme disease requiring over 1 year to diagnose at an infectious-disease clinic

Abstract:

A 42-year-old woman presenting with years of fever and vague symptoms could not be satisfactorily diagnosed in physical examination or conventional workups. She was presumptively diagnosed with chronic fatigue syndrome and treated symptomatically. Fourteen months after the initial visit, she developed left facial palsy. Lyme disease serology was positive. Four weeks of oral amoxicillin ameliorated symptoms. Only 5 to 15 cases of Lyme disease are reported annually in Japan, mostly from the northeastern-most island of Hokkaido. It may occur anywhere in Japan, however; probably is underdiagnosed. Lyme disease may cause fevers of unknown origin. Astute clinical suspicion and appropriate workups are thus needed to diagnose this infection.

 

Source: Iwata K, Shimada T, Kawabata H. A case of lyme disease requiring over 1 year to diagnose at an infectious-disease clinic. Kansenshogaku Zasshi. 2013 Jan;87(1):44-8. [Article in Japanese] https://www.ncbi.nlm.nih.gov/pubmed/23484378

 

Fatigue heralding multiple sclerosis

Abstract:

BACKGROUND: Fatigue is a common symptom in multiple sclerosis (MS) and is an important determinant of overall well-being and disability.

OBJECTIVE: To assess the frequency with which fatigue precedes the diagnosis of MS using a retrospective database analysis.

METHODS: Between January 1, 2003 and September 30, 2008, patients diagnosed with fatigue with and without fatigue-related medications within a 3-year period prior to newly diagnosed MS were identified from the MarketScan Databases. All statistical analysis was performed using SAS.

RESULTS: Of the 16,976 patients with MS in the overall population, 5305 (31.3%) were newly diagnosed with MS and had three years of continuous healthcare coverage prior to MS diagnosis. Of these patients, 1534 (28.9%) were labeled with chronic fatigue syndrome (ICD9-780.71) or malaise or fatigue (ICD9-780.79) prior to the diagnosis of MS. One-third of these patients were labeled with fatigue one to two years before the diagnosis; 30.8% were diagnosed only with fatigue and had no other MS symptoms prior to their MS diagnosis. Among the patients diagnosed with fatigue, 10.4% were also prescribed medication for fatigue.

CONCLUSION: This study demonstrates that fatigue may herald MS, often by years. A careful history for transient neurological symptoms and a physical examination is warranted in any patient presenting with fatigue.

 

Source: Berger JR, Pocoski J, Preblick R, Boklage S. Fatigue heralding multiple sclerosis. Mult Scler. 2013 Oct;19(11):1526-32. doi: 10.1177/1352458513477924. Epub 2013 Feb 25. https://www.ncbi.nlm.nih.gov/pubmed/23439577

 

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

 

Clinical characteristics of a novel subgroup of chronic fatigue syndrome patients with postural orthostatic tachycardia syndrome

Abstract:

OBJECTIVES: A significant proportion of patients with chronic fatigue syndrome (CFS) also have postural orthostatic tachycardia syndrome (POTS). We aimed to characterize these patients and differentiate them from CFS patients without POTS in terms of clinical and autonomic features.

METHODS: A total of 179 patients with CFS (1994 Centers for Disease Control and Prevention criteria) attending one of the largest Department of Health-funded CFS clinical services were included in this study. Outcome measures were as follows: (i) symptom assessment tools including the fatigue impact scale, Chalder fatigue scale, Epworth sleepiness scale (ESS), orthostatic grading scale (OGS) and hospital anxiety and depression scale (HADS-A and -D, respectively), (ii) autonomic function analysis including heart rate variability and (iii) haemodynamic responses including left ventricular ejection time and systolic blood pressure drop upon standing.

RESULTS: CFS patients with POTS (13%, n = 24) were younger (29 ± 12 vs. 42 ± 13 years, P < 0.0001), less fatigued (Chalder fatigue scale, 8 ± 4 vs. 10 ± 2, P = 0.002), less depressed (HADS-D, 6 ± 4 vs. 9 ± 4, P = 0.01) and had reduced daytime hypersomnolence (ESS, 7 ± 6 vs. 10 ± 5, P = 0.02), compared with patients without POTS. In addition, they exhibited greater orthostatic intolerance (OGS, 11 ± 5; P < 0.0001) and autonomic dysfunction. A combined clinical assessment tool of ESS ≤9 and OGS ≥9 identifies accurately CFS patients with POTS with 100% positive and negative predictive values.

CONCLUSIONS: The presence of POTS marks a distinct clinical group of CFS patents, with phenotypic features differentiating them from those without POTS. A combination of validated clinical assessment tools can determine which CFS patients have POTS with a high degree of accuracy, and thus potentially identify those who require further investigation and consideration for therapy to control heart rate.

© 2013 The Association for the Publication of the Journal of Internal Medicine.

Comment in: Postural orthostatic tachycardia syndrome as a clinically important subgroup of chronic fatigue syndrome: further evidence for central nervous system dysfunctioning. [J Intern Med. 2013]

 

Source: Lewis I, Pairman J, Spickett G, Newton JL. Clinical characteristics of a novel subgroup of chronic fatigue syndrome patients with postural orthostatic tachycardia syndrome. J Intern Med. 2013 May;273(5):501-10. doi: 10.1111/joim.12022. Epub 2013 Jan 7. http://onlinelibrary.wiley.com/doi/10.1111/joim.12022/full (Full article)