Category: Overlapping Illnesses

The role of environmental factors in medically unexplained symptoms and related syndromes: conference summary and recommendations

Abstract:

This monograph of peer-reviewed articles is based on presentations at the conference “Environmental Factors in Medically Unexplained Physical Symptoms and Related Syndromes” held 10-12 January 2001 in Piscataway, New Jersey, USA. The purpose of the conference was to determine research priorities for elucidating the role of environmental factors in medically unexplained symptoms and symptom syndromes. These include conditions such as chronic fatigue syndrome, multiple chemical sensitivities, sick building syndrome, Gulf War illness, and the like. Approximately 1 1/2 days were devoted to plenary talks and 1 day was devoted to break-out sessions to discuss epidemiologic, psychosocial, and experimental research. Recommendations were made for a series of epidemiologic, psychosocial, and experimental research approaches, with acknowledgment that nosology issues are clearly fundamental to advancing understanding of these conditions.

 

Source: Kipen HM, Fiedler N. The role of environmental factors in medically unexplained symptoms and related syndromes: conference summary and recommendations. Environ Health Perspect. 2002 Aug;110 Suppl 4:591-5. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1241210/ (Full article)

 

A computational analysis of Canale-Smith syndrome: chronic lymphadenopathy simulating malignant lymphoma

Abstract:

OBJECTIVE: The objective of this study was to simulate changes in the human T cell system representing Canale-Smith syndrome using a dynamic computer model of T cell development and comparing with available human data.

STUDY DESIGN: Physiological stepwise maturation and function of T lymphocytes in the computer model is altered by introducing functional disturbances following lymphotropic virus infection. In the present model, acute and chronic persistent infection with the human herpesvirus-6 (HHV-6) was simulated, and ensuing changes in T cell populations were compared with those measured in human patients.

RESULTS: Using our computer model we previously found that simulated acute HHV-6 infection produced T cell computer data, which resembled an infectious mononucleosis-like disease in patients. Simulated chronic persistent infection, instead, resulted in variable cell changes comparing well to patients with chronic fatigue syndrome. In one setting, however, persistent immature lymphocytosis was observed similar to what initial has been described in this journal as Canale-Smith syndrome.

CONCLUSION: Using a computer model developed by us we were able to produce simulations that resemble the immune system features of Canale-Smith syndrome. Further understanding of these simulation results may possibly guide future investigations into this disorder.

 

Source: Krueger GR, Brandt ME, Wang G, Berthold F, Buja LM. A computational analysis of Canale-Smith syndrome: chronic lymphadenopathy simulating malignant lymphoma. Anticancer Res. 2002 Jul-Aug;22(4):2365-71. http://www.ncbi.nlm.nih.gov/pubmed/12174928

 

Long-term follow-up of patients from the 1989 Q fever outbreak: no evidence of excess cardiac disease in those with fatigue

Abstract:

BACKGROUND: In 1989, an outbreak of Q fever (C. burnetii infection) with 147 confirmed cases occurred in Solihull, West Midlands. Three patients developed cardiomyopathy in the subsequent 10 years. The cohort has been followed up with respect to the development of fatigue and, in this instance, cardiac effects after the original infection.

AIM: To determine whether persisting fatigue after Q fever represented sub-clinical cardiomyopathy.

DESIGN: Prospective follow-up study.

METHODS: All traceable subjects from the original outbreak, and community age-, sex- and smoking-matched controls, were studied. Questionnaires for idiopathic fatigue, 12-lead ECG, echocardiography, spirometry and shuttle walk distance were undertaken, and a subset with CDC-defined chronic fatigue syndrome had gated cardiac scans.

RESULTS: Of the original cohort, 19 had died, three had emigrated and 10 were untraceable. Of the remaining 115, 108 responded to a mailed questionnaire and 87 were investigated further, of whom 85 provided complete data. Two developed aortic valve vegetations, one of whom died. Chronic fatigue syndrome was found in 20% of cases and 5.3% of controls (including those with co-morbidities), falling to 8.2% and 0 when excluding those with co-morbidities. There were no significant differences in ECG and echocardiographic investigations or shuttle-walk distance between those with fatigue and those without. Six of the seven patients with CFS had gated cardiac scans: all were within normal limits.

CONCLUSIONS: These findings do not support the existence of a sub-clinical cardiomyopathy in the patients in this cohort who suffer from fatigue after acute Q fever, although endocarditis can occur after acute infection.

Comment in: Q fever: still a mysterious disease. [QJM. 2002]

 

Source: Ayres JG, Wildman M, Groves J, Ment J, Smith EG, Beattie JM. Long-term follow-up of patients from the 1989 Q fever outbreak: no evidence of excess cardiac disease in those with fatigue. QJM. 2002 Aug;95(8):539-46. http://qjmed.oxfordjournals.org/content/95/8/539.long (Full article)

 

Chronic fatigue following infection by Coxiella burnetii (Q fever): ten-year follow-up of the 1989 UK outbreak cohort

Abstract:

BACKGROUND: Some patients exposed to Q fever (Coxiella burnetii infection) may develop chronic fatigue.

AIM: To determine whether subjects involved in the West Midlands Q fever outbreak of 1989 had increased fatigue, compared to non-exposed controls, 10 years after exposure.

DESIGN: Matched cohort study comparing cases to age-, sex- and smoking-history-matched controls not exposed to Q fever.

METHODS: A postal questionnaire was sent to subjects at home, followed by further assessment in hospital, including a physical examination and blood tests.

RESULTS: Of 108 Q-exposed subjects, 70 (64.8%) had fatigue, 37 idiopathic chronic fatigue (ICF) (34.3%), vs. 29/80 (36.3%) and 12 (15.0%), respectively, in controls. In 77 matched pairs, fatigue was commoner in Q-exposed subjects than in controls: 50 (64.9%) vs. 27 (35.1%), p<0.0001. ICF was found in 25 (32.5%) of Q-exposed patients and 11(14.3%) of controls (p=0.01). There were 36 (46.8%) GHQ cases in Q-exposed subjects, vs. 18 (23.4%) controls (p=0.004). A matched analysis of those more intensively studied showed fatigue in 48 (66.7%) Q-exposed patients and 25 (34.7%) controls, (p<0.0001), ICF in 25 (34.7%) Q-exposed and 10 (13.9%) controls (p=0.004), and chronic fatigue syndrome (CFS) in 14 (19.4%) Q-exposed patients and three (4.2%) controls (p=0.003). Thirty-four (47.2%) Q-exposed patients were GHQ cases compared to 17 (23.6%) controls (p=0.004).

DISCUSSION: Subjects who were exposed to Coxiella in 1989 had more fatigue than did controls, and some fulfilled the criteria for CFS. Whether this is due to ongoing antigen persistence or to the psychological effects of prolonged medical follow-up is uncertain.

Comment in: Q fever: still a mysterious disease. [QJM. 2002]

 

Source: Wildman MJ, Smith EG, Groves J, Beattie JM, Caul EO, Ayres JG. Chronic fatigue following infection by Coxiella burnetii (Q fever): ten-year follow-up of the 1989 UK outbreak cohort. QJM. 2002 Aug;95(8):527-38. http://qjmed.oxfordjournals.org/content/95/8/527.long (Full article)

 

Elevated nitric oxide/peroxynitrite mechanism for the common etiology of multiple chemical sensitivity,chronic fatigue syndrome, and posttraumatic stress disorder

Abstract:

Various types of evidence implicate nitric oxide and an oxidant, possibly peroxynitrite, in MCS and chemical intolerance (CI). The positive feedback loops proposed earlier for CFS may explain the chronic nature of MCS (CI) as well as several of its other reported properties. These observations raise the possibility that this proposed elevated nitric oxide/peroxynitrite mechanism may be the mechanism of a new disease paradigm, answering the question raised by Miller earlier: “Are we on the threshold of a new theory of disease?”

 

Source: Pall ML, Satterlee JD. Elevated nitric oxide/peroxynitrite mechanism for the common etiology of multiple chemical sensitivity,chronic fatigue syndrome, and posttraumatic stress disorder.  Ann N Y Acad Sci. 2001 Mar;933:323-9. http://www.ncbi.nlm.nih.gov/pubmed/12000033

 

Controlled exposures to volatile organic compounds in sensitive groups

Abstract:

Sensitivities to chemicals are characterized by symptoms in multiple organ systems in response to low-level chemical exposures. This paper reviews studies of controlled exposures to odorants and to mixtures of volatile organic compounds. Sensitive subgroups include subjects who met Cullen’s 1987 criteria for multiple chemical sensitivity (MCS), Gulf War veterans with chronic fatigue syndrome and chemical sensitivity (CFS/CS), and subjects with specific self-reported sensitivities to methyl terbutyl ether (MTBE) in gasoline (MTBE-sensitive). All studies include comparison of age- and sex-matched healthy controls.

Studies of olfaction did not support unusual sensitivity, defined as lower odor thresholds, among MCS subjects; however, a dose-response pattern of symptoms was observed in response to suprathreshold concentrations of phenyl ethyl alcohol. In blinded, controlled exposures to clean air, gasoline, gasoline/11% MTBE, and gasoline/15% MTBE, a threshold effect was observed with MTBE-sensitive subjects reporting significantly increased symptoms to gasoline/15% MTBE exposure. Autonomic arousal (heart and respiration rate; end-tidal CO2) in response to odor of chemical mixtures may mediate symptoms for subjects with generalized chemical sensitivities, but not for those whose sensitivities are confined to specific chemicals.

For example, Gulf War veterans with CFS/CS experienced reduced end-tidal CO2 when exposed to diesel fumes, while exposure to MTBE did not produce any psychophysiologic changes in MTBE-sensitive subjects. Controlled olfactory and exposure studies reveal that significant responses can be observed in chemically sensitive subjects even when de-adaptation has not occurred. However, these studies suggest that symptoms are not necessarily accompanied by changes in physiologic arousal. Subject characteristics play a critical role in outcomes.

 

Source: Fiedler N, Kipen HM. Controlled exposures to volatile organic compounds in sensitive groups. Ann N Y Acad Sci. 2001 Mar;933:24-37. http://www.ncbi.nlm.nih.gov/pubmed/12000025

 

Potential mechanisms in chemical intolerance and related conditions

Abstract:

The symptom of chemical intolerance may occur in isolation, but often occurs in conjunction with other chronic symptoms such as pain, fatigue, memory disturbances, etc. This frequent clustering of symptoms in individuals has led to the definition of several chronic multisymptom syndromes, such as multiple chemical sensitivity, fibromyalgia, chronic fatigue syndrome, and Gulf War illnesses. The aggregate research into these syndromes has suggested some unifying mechanisms that contribute to symptomatology. Multiple lines of evidence suggest that there is aberrant function of numerous efferent neural pathways, such as the autonomic nervous system and hypothalamic-pituitary axes, in subsets of individuals with these conditions.

There is perhaps the greatest evidence for abnormal sensory processing in these syndromes, with a low “unpleasantness threshold” for multiple types of sensory stimuli. Psychological and behavioral factors are known to play a significant role in initiating or perpetuating symptoms in some persons with these illnesses. In the field of pain research, the interrelationship between physiologic and psychologic factors in symptom expression has been well studied. Using both established and novel methodologies, studies have suggested that psychologic factors such as hypervigilance and expectancy are playing a relatively minor role in most individuals with fibromyalgia and that clear evidence exists of physiologic amplification of sensory stimuli.

These studies need to be extended to more sensory tasks and to larger numbers of subjects with related conditions. It is of note, though, that existing data on this spectrum of illnesses would suggest that there may be greater psychologic contributions to symptomatology if an illness is defined in part by behavior (e.g., avoidance of chemical exposures) rather than on the basis of symptoms alone.

 

Source: Clauw DJ. Potential mechanisms in chemical intolerance and related conditions.  Ann N Y Acad Sci. 2001 Mar;933:235-53. http://www.ncbi.nlm.nih.gov/pubmed/12000024

 

Generation of classification criteria for chronic fatigue syndrome using an artificial neural network and traditional criteria set

Abstract:

OBJECTIVE: The definition of chronic fatigue syndrome (CFS) is still disputed and no validated classification criteria have been published. Artificial neural networks (ANN) are computer-based models that can help to evaluate complex correlations. We examined the utility of ANN and other conventional methods in generating classification criteria for CFS compared to other diseases with prominent fatigue, systemic lupus erythematosus (SLE) and fibromyalgia syndrome (FMA).

PATIENTS AND METHODS: Ninety-nine case patients with CFS, 41 patients with SLE and 58 with FMA were recruited from a generalist outpatient population. Clinical symptoms were documented with help of a predefined questionnaire. The patients were randomly divided into two groups. One group (n = 158) served to derive classification criteria sets by two-fold cross-validation, using a) unweighted application of criteria, b) regression coefficients, c) regression tree analysis, and d) artificial neural networks in parallel. These criteria were validated with the second group (n = 40).

RESULTS: Classification criteria developed by ANN were found to have a sensitivity of 95% and a specificity of 85%. ANN achieved a higher accuracy than any of the other methods.

CONCLUSION: We present validated criteria for the classification of CFS versus SLE and FMA, comparing different classification approaches. The most accurate criteria were derived with the help of ANN. We therefore recommend the use of ANN for the classification of syndromes with complex interrelated symptoms like CFS.

 

Sour ce: Linder R, Dinser R, Wagner M, Krueger GR, Hoffmann A. Generation of classification criteria for chronic fatigue syndrome using an artificial neural network and traditional criteria set. In Vivo. 2002 Jan-Feb;16(1):37-43. http://www.ncbi.nlm.nih.gov/pubmed/11980359

 

Dry eyes and mouth syndrome–a subgroup of patients presenting with sicca symptoms

Abstract:

OBJECTIVE: To evaluate the characteristics of patients presenting with symptoms suggestive of Sjögren’s syndrome (SS) but failing to satisfy diagnostic criteria.

METHODS: Clinical, serological and histological data were collected on 34 patients presenting with dry eyes and/or mouth who did not satisfy the Vitali criteria for the diagnosis of SS. They were compared with 136 patients with primary SS, 38 patients with secondary SS, and 13 patients without SS. Questionnaires on symptoms from each group were compared with 43 healthy controls.

RESULTS: The 34 patients who did not satisfy the diagnostic criteria for SS or any other connective tissue disease were designated dry eyes and mouth syndrome (DEMS). Their demography including age was similar to that of a primary SS group and there was no more atrophy seen on their biopsies compared with SS and non-SS controls. They scored highly on visual analogue scales of symptoms but had few objective signs. All were negative for anti-Ro and anti-La although the prevalence of antinuclear antibodies (19%) was increased compared with a normal population. There was no excess of SS-associated tissue types.

CONCLUSION: There was no evidence that age, salivary gland atrophy or subclinical SS accounted for the symptoms in DEMS. Most of the patients fitted into a spectrum of disease which tended more towards fibromyalgia and/or chronic fatigue syndrome.

Comment in: Dry eyes and mouth syndrome or sicca, asthenia and polyalgia syndrome? [Rheumatology (Oxford). 2003]

 

Source: Price EJ, Venables PJ. Dry eyes and mouth syndrome–a subgroup of patients presenting with sicca symptoms. Rheumatology (Oxford). 2002 Apr;41(4):416-22. http://rheumatology.oxfordjournals.org/content/41/4/416.long (Full article)

 

 

 

Brainstem conundrum: the Chiari I malformation

Abstract:

PURPOSE: To describe the Chairi I Malformation in relation to the anatomy of the brain and spinal cord, the common manifestations of the condition, diagnostic considerations, and management for the primary care provider.

DATA SOURCES: Extensive review of the world-wide scientific literature on the condition, supplemented with actual case studies.

CONCLUSIONS: The adult Chairi I Malformation is an insidious congenital brainstem anomaly that consists of caudal displacement of the cerebellar tonsils, brainstem and fourth ventricle into the upper cervical space, resulting in overcrowding of the posterior fossa.

IMPLICATIONS FOR PRACTICE: Due to the vague, and often ambiguous presenting symptoms of Chiari I Malformation, many patients are misdiagnosed with conditions such as multiple sclerosis, fibromyalgia, chronic fatigue syndrome, or psychiatric disorders. Patients frequently experience symptoms months to years prior to accurate diagnosis and often incur irreversible neurologic deficits.

 

Source: Mueller D. Brainstem conundrum: the Chiari I malformation. J Am Acad Nurse Pract. 2001 Apr;13(4):154-9. http://www.ncbi.nlm.nih.gov/pubmed/11930527