A review of the evidence for overlap among unexplained clinical conditions

Abstract:

PURPOSE: Unexplained clinical conditions share features, including symptoms (fatigue, pain), disability out of proportion to physical examination findings, inconsistent demonstration of laboratory abnormalities, and an association with “stress” and psychosocial factors. This literature review examines the nature and extent of the overlap among these unexplained clinical conditions and the limitations of previous research.

DATA SOURCES: English-language articles were identified by a search of the MEDLINE database from 1966 to January 2001 by using individual syndromes and their hallmark symptoms as search terms.

STUDY SELECTION: Studies that assessed patients with at least one unexplained clinical condition and that included information on symptoms, overlap with other unexplained clinical conditions, or physiologic markers. Conditions examined were the chronic fatigue syndrome, fibromyalgia, the irritable bowel syndrome, multiple chemical sensitivity, temporomandibular disorder, tension headache, interstitial cystitis, and the postconcussion syndrome.

DATA EXTRACTION: Information on authorship, patient and control groups, eligibility criteria, case definitions, study methods, and major findings.

DATA SYNTHESIS: Many similarities were apparent in case definition and symptoms, and the proportion of patients with one unexplained clinical condition meeting criteria for a second unexplained condition was striking. Tender points on physical examination and decreased pain threshold and tolerance were the most frequent and consistent objective findings. A major shortcoming of all proposed explanatory models is their inability to account for the occurrence of unexplained clinical conditions in many affected patients.

CONCLUSIONS: Overlap between unexplained clinical conditions is substantial. Most studies are limited by methodologic problems, such as case definition and the selection and recruitment of case-patients and controls.

 

Source: Aaron LA, Buchwald D. A review of the evidence for overlap among unexplained clinical conditions. Ann Intern Med. 2001 May 1;134(9 Pt 2):868-81. http://www.ncbi.nlm.nih.gov/pubmed/11346323

 

Sleep and circadian rhythm disorders in fibromyalgia

Abstract:

Fibromyalgia (FM) is a syndrome of generalized muscle pain that is also associated with equally distressing symptoms of sleep disturbance and fatigue. FM shows clinical overlap with other stress-associated disorders, including chronic fatigue syndrome (CFS) and depression. All of these conditions have the features of disrupted sleep patterns and dysregulated biologic circadian rhythms, such as stress hormone secretion. This review focuses on the role of sleep and circadian rhythm disorders in FM and, in the absence of any specific treatment for FM, presents a pragmatic therapeutic approach aimed at identifying and treating comorbid sleep and depressive disorders, optimizing sleep habits, and judicious use of pharmacologic agents.

 

Source: Korszun A. Sleep and circadian rhythm disorders in fibromyalgia. Curr Rheumatol Rep. 2000 Apr;2(2):124-30. http://www.ncbi.nlm.nih.gov/pubmed/11123049

 

Chronic fatigue syndrome, fibromyalgia, and multiple chemical sensitivities in a community-based sample of persons with chronic fatigue syndrome-like symptoms

Abstract:

OBJECTIVE: The aim of this study was to determine illness comorbidity rates for individuals with chronic fatigue syndrome (CFS), fibromyalgia (FM), and multiple chemical sensitivities (MCS). An additional objective was to identify characteristics related to the severity of fatigue, disability, and psychiatric comorbidity in each of these illness groups.

METHODS: A random sample of 18,675 residents in Chicago, Illinois, was first interviewed by telephone. A control group and a group of individuals with chronic fatigue accompanied by at least four minor symptoms associated with CFS received medical and psychiatric examinations.

RESULTS: Of the 32 individuals with CFS, 40.6% met criteria for MCS and 15.6% met criteria for FM. Individuals with MCS or more than one diagnosis reported more physical fatigue than those with no diagnosis. Individuals with more than one diagnosis also reported greater mental fatigue and were less likely to be working than those with no diagnosis. Individuals with CFS, MCS, FM, or more than one diagnosis reported greater disability than those with no diagnosis.

CONCLUSIONS: Rates of coexisting disorders were lower than those reported in prior studies. Discrepancies may be in part attributable to differences in sampling procedures. People with CFS, MCS, or FM endure significant disability in terms of physical, occupational, and social functioning, and those with more than one of these diagnoses also report greater severity of physical and mental fatigue. The findings illustrate differences among the illness groups in the range of functional impairment experienced.

 

Source: Jason LA, Taylor RR, Kennedy CL. Chronic fatigue syndrome, fibromyalgia, and multiple chemical sensitivities in a community-based sample of persons with chronic fatigue syndrome-like symptoms. Psychosom Med. 2000 Sep-Oct;62(5):655-63. http://www.ncbi.nlm.nih.gov/pubmed/11020095

 

Longitudinal analysis of symptoms reported by patients with chronic fatigue syndrome

Abstract:

PURPOSE: To determine the effect of chronic fatigue syndrome (CFS) illness duration and onset type on the likelihood of reporting a symptom during successive follow-up periods.

METHODS: In 1997, a two-phase RDD survey in Wichita, Kansas, was conducted to estimate the prevalence of CFS. Phase I identified 56,154 respondents 18-69 years of age and screened for severe fatigue, extreme tiredness or exhaustion lasting for 1 month or longer. In phase II an equal number of fatigued (n = 7,176) and randomly selected non-fatigued subjects were asked about 8 CFS and 13 non-CFS symptoms, as well as the presence of specific medical and psychiatric conditions. Eligible respondents were clinically evaluated to establish CFS diagnosis. Phase II respondents were re-contacted at 12- (n = 4,331) and 24-months (n = 4,266) for additional follow-up and diagnosis. In this study we considered symptoms reported as being present most of the time during each successive observation period. Generalized estimating equations were used to model symptoms over time and to address study questions. Such a model accounts for correlations among repeated symptoms for each subject. We used an auto-regressive structure for the correlation matrix, assuming the correlations between each pair of repeated symptoms should decrease as the time between symptoms increased.

RESULTS: There were 74 CFS patients who had been ill for 1 to 20 years (median = 6.3 years). Among these, 46 reported gradual and 28 reported sudden onset. Symptoms fluctuated over the course of illness. However, only stomach pain (non-CFS symptom) was more likely to be reported as duration of illness increased (p < 0.05). There was no association between onset type and the likelihood of reporting a symptom during an interview, except that chills and severe headaches were more likely to be reported by sudden cases.

CONCLUSIONS: The likelihood of expressing CFS and non-CFS symptom “most of the time” is the same across years of illness. More analyses are warranted to consider expression of symptoms for >/=6 months and severe symptoms.

 

Source: Nisenbaum R, Jones A, Jones J, Reeves W. Longitudinal analysis of symptoms reported by patients with chronic fatigue syndrome. Ann Epidemiol. 2000 Oct 1;10(7):458. http://www.ncbi.nlm.nih.gov/pubmed/11018368

 

Pain complaints in patients with fibromyalgia versus chronic fatigue syndrome

Abstract:

Individuals with fibromyalgia (FM) and/or chronic fatigue syndrome (CFS) report arthralgias and myalgias. However, only persons with FM alone exhibit abnormal pain responses to mild levels of stimulation, or allodynia. We identify the abnormalities in the neuroendocrine axes that are common to FM and CFS as well as the abnormalities in central neuropeptide levels and functional brain activity that differentiate these disorders. These two sets of factors, respectively, may account for the similarities and differences in the pain experiences of persons with FM and CFS.

 

Source: Bradley LA, McKendree-Smith NL, Alarcón GS. Pain complaints in patients with fibromyalgia versus chronic fatigue syndrome. Curr Rev Pain. 2000;4(2):148-57. http://www.ncbi.nlm.nih.gov/pubmed/10998728

 

Blood parameters indicative of oxidative stress are associated with symptom expression in chronic fatigue syndrome

Abstract:

Full blood counts, ESR, CRP, haematinics and markers for oxidative stress were measured for 33 patients diagnosed with chronic fatigue syndrome (CFS) and 27 age and sex matched controls. All participants also completed symptom questionnaires. CFS patients had increases in malondialdehyde (P <0.006), methaemoglobin (P <0.02), mean erythrocyte volume (P <0.02) and 2,3-diphosphoglycerate (P <0.04) compared with controls.

Multiple regression analysis found methaemoglobin to be the principal component that differentiated between CFS patients and control subjects. Methaemoglobin was found to be the major component associated with variation in symptom expression in CFS patients (R(2) = 0.99, P <0.00001), which included fatigue, musculoskeletal symptoms, pain and sleep disturbance. Variation in levels of malondialdehyde and 2,3-diphosphoglycerate were associated with variations in cognitive symptoms and sleep disturbance (R(2) = 0.99, P <0.00001).

These data suggest that oxidative stress due to excess free radical formation is a contributor to the pathology of CFS and was associated with symptom presentation.

 

Source: Richards RS, Roberts TK, McGregor NR, Dunstan RH, Butt HL. Blood parameters indicative of oxidative stress are associated with symptom expression in chronic fatigue syndrome. Redox Rep. 2000;5(1):35-41. http://www.ncbi.nlm.nih.gov/pubmed/10905542

 

Self-reported sensitivity to chemical exposures in five clinical populations and healthy controls

Abstract:

Two hundred and twenty-five subjects, including normal volunteers and patients with previously documented seasonal affective disorder (SAD),chronic fatigue syndrome (CFS), Cushing’s syndrome, Addison’s disease and obsessive-compulsive disorder (OCD), completed a self-rated inventory of reported sensitivity to various chemical exposures.

Patients with CFS, Addison’s disease and SAD self-reported more sensitivity to chemical exposures than normal controls. In addition, women reported more sensitivity than men.

This report suggests that chemical sensitivity may be a relevant area to explore in certain medical and psychiatric populations. A possible relationship between reported chemical sensitivity and hypothalamic-pituitary-adrenal (HPA)-axis functioning is discussed.

 

Source: Nawab SS, Miller CS, Dale JK, Greenberg BD, Friedman TC, Chrousos GP, Straus SE, Rosenthal NE. Self-reported sensitivity to chemical exposures in five clinical populations and healthy controls. Psychiatry Res. 2000 Jul 24;95(1):67-74. http://www.ncbi.nlm.nih.gov/pubmed/10904124

 

Chronic fatigue syndrome: a form of Addison’s disease

Dear Sir, Evengård et al.’s article [1] on chronic fatigue syndrome (CFS) is disappointing, because in their review, despite its 15 pages and 165 references, there is not a single word about the staggering similarity between CFS and Addison’s disease. As someone whose CFS symptoms resolved dramatically with an old remedy for Addison’s disease [2], I understandably found that review even more disappointing.

To compensate for Evengård et al.’s failure to mention both the impressive overlap of CFS with Addison’s disease and its clinical implications, I summarize here these issues.

CFS and Addison’s disease share 36 features [3–6]. Three others, however, are to be added. In fact, reduction in adrenal gland size [7], antibodies against the adrenal gland [8] and respiratory muscle dysfunction [9], besides being present in CFS [7–9], have also been found in Addison’s disease [10–12]. In view of the 39 features that CFS shares with Addison’s disease [3–12] (see Table 1), which constitute a similarity between two distinctly named diseases that is probably unequalled in the medical literature, it seems arguable that CFS should practically be viewed as a form of Addison’s disease [13]. One could object that CFS patients, unlike Addisonian subjects, do not display hyperpigmentation or basal hypocortisolaemia. Neither abnormality, however, is a constant presenting feature of Addison’s disease [14].

You can read the rest of this comment here: http://onlinelibrary.wiley.com/doi/10.1046/j.1365-2796.2000.00695.x/full

 

Source: Baschetti R. Chronic fatigue syndrome: a form of Addison’s disease. J Intern Med. 2000 Jun;247(6):737-9. http://onlinelibrary.wiley.com/doi/10.1046/j.1365-2796.2000.00695.x/full (Full article)

 

Nighttime sleep and daytime functioning (sleepiness and fatigue) in less well-defined chronic rheumatic diseases with particular reference to the ‘alpha-delta NREM sleep anomaly’

Abstract:

For the past 25 years, the ‘alpha-delta NREM sleep abnormality’ has been used by some as a defining or legitimizing marker for poorly defined rheumatic diseases such as fibromyalgia and chronic fatigue syndrome. Comprehensive review of the literature reveals no support for such a conclusion. Most studies involve small numbers of patients. The lack of control subjects, non-standardized recording techniques, and confusion between tonic and phasic alpha frequency activity patterns make comparison difficult.

There is much evidence that this sleep EEG pattern is not only non-specific, but may actually reflect a sleep maintaining process. The ‘sleep fragmentation’ theory of the complaint of non-restorative sleep in this patient population is invalidated by the fact that conditions characterized by severe sleep fragmentation, such as obstructive sleep apnea, are not associated with musculoskeletal symtoms. It is difficult to attribute musculoskeletal symptoms to disorders of sleep in view of the fact that the only organ of the body known to benefit from sleep, or to be adversely affected by lack of sleep, is the brain. It is concluded that fibromyalgia and chronic fatigue syndrome are associated with subjective sleep complaints, but do not represent sleep disorders.

 

Source: Mahowald ML, Mahowald MW. Nighttime sleep and daytime functioning (sleepiness and fatigue) in less well-defined chronic rheumatic diseases with particular reference to the ‘alpha-delta NREM sleep anomaly’. Sleep Med. 2000 Jul 1;1(3):195-207. http://www.ncbi.nlm.nih.gov/pubmed/10828430

 

Symptom patterns in long-duration chronic fatigue syndrome

Abstract:

OBJECTIVE: Our objective was to evaluate symptom patterns in patients with chronic fatigue syndrome (CFS) who were ill for 10 or more years.

METHODS: This cross-sectional self-report study compared patient groups with long-duration (median = 18 years; n = 258) and short-duration (median = 3 years; n = 28) CFS to a group of healthy significant others (n = 79) on symptomatic, neurocognitive, and psychological variables. Data were gathered from a 574-item postal questionnaire.

RESULTS: A principal-components analysis of CFS symptom data yielded a three-factor solution: cognitive problems; flu-like symptoms; and neurologic symptoms. Compared with the short-duration CFS group, the long-duration group had significantly higher CFS symptom severity scores (p < 0.04), largely attributable to increased cognitive difficulties. A subgroup comparison of subjects ill for < 3 years versus those ill 4-7 years suggested that denial coping strategies were more likely in those participants with the shorter illness duration. Significant differences between both CFS groups and healthy controls were found in a number of comorbid disorders. Participants with CFS most often endorsed immune/viral abnormalities and persistent stress as important perceived causes of their illness.

CONCLUSION: Participants with long-duration CFS reported a large number of specific cognitive difficulties that were greater in severity than those reported by participants with short-duration CFS. The pattern of comorbid disorders in the CFS groups was consistent with hypersensitivity and viral reactivation hypotheses.

 

Source: Friedberg F, Dechene L, McKenzie MJ 2nd, Fontanetta R. Symptom patterns in long-duration chronic fatigue syndrome. J Psychosom Res. 2000 Jan;48(1):59-68. http://www.ncbi.nlm.nih.gov/pubmed/10750631