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

 

Cytokines and chronic fatigue syndrome

Abstract:

Chronic fatigue syndrome (CFS) patients show evidence of immune activation, as demonstrated by increased numbers of activated T lymphocytes, including cytotoxic T cells, as well as elevated levels of circulating cytokines. Nevertheless, immune cell function of CFS patients is poor, with low natural killer cell cytotoxicity (NKCC), poor lymphocyte response to mitogens in culture, and frequent immunoglobulin deficiencies, most often IgG1 and IgG3.

Immune dysfunction in CFS, with predominance of so-called T-helper type 2 and proinflammatory cytokines, can be episodic and associated with either cause or effect of the physiological and psychological function derangement and/or activation of latent viruses or other pathogens. The interplay of these factors can account for the perpetuation of disease with remission/exacerbation cycles. A T-helper type 2 predominance has been seen among Gulf War syndrome patients and this feature may also be present in other related disorders, such as multiple chemical sensitivity. Therapeutic intervention aimed at induction of a more favorable cytokine expression pattern and immune status appears promising.

 

Source: Patarca R. Cytokines and chronic fatigue syndrome.  Ann N Y Acad Sci. 2001 Mar;933:185-200. http://www.ncbi.nlm.nih.gov/pubmed/12000020

 

An interdisciplinary therapeutic approach for dealing with patients attributing chronic fatigue and functional memory disorders to environmental poisoning–a pilot study

Abstract:

Nonspecific symptoms and a general feeling of ill health that is difficult to objectify are the commonest health problems with which patients present to an Environmental Medicine Outpatient Department (OPD). Of this group, a great proportion meets the classification criteria for Chronic Fatigue Syndrome (CFS) or Functional Memory Disorders in association with Idiopathic Chronic Fatigue (FMD-ICF).

This is a longitudinal study of the OPD of Environmental Medicine, Freiburg University Hospital, Germany, to determine the feasibility and impact of an interdisciplinary therapeutic approach (self-help program, acupuncture, psychosomatic support by group interventions) in 8 patients with CFS, FMD-ICF, or CFS in association with self-reported Multiple Chemical Sensitivities (sr-MCS). The intervention took into consideration the patients’ need for treatment of physical aspects of their disease. This is an important step to motivate patients into required psychosomatic support.

Although none of the patients was willing to accept psychosomatic support or psychotherapy at study outset, acceptance of psychosomatic group interventions was high during the study course. Additionally five patients started with personal counseling at the Psychosomatic Clinic, and, without feeling stigmatized, 4 patients started with specific psychotherapy.

The patients’ quality of life showed no increase after four months, but, as shown by the Sum-Score of SF-36, it had improved significantly at the end of the study, which covered eight months’ treatment (p = 0.015). Two follow-up investigations showed that this improvement probably persisted in part (mainly in the dimensions mental health, social function, physical role function, and vitality).

In conclusion our interdisciplinary therapeutic approach indicates successful treatment of patients attributing CFS, CFS/sr-MCS, and FMD-ICF to environmental poisoning. We now plan to conduct a randomized controlled trial in the future.

 

Source: Lacour M, Zunder T, Dettenkofer M, Schönbeck S, Lüdtke R, Scheidt C. An interdisciplinary therapeutic approach for dealing with patients attributing chronic fatigue and functional memory disorders to environmental poisoning–a pilot study. Int J Hyg Environ Health. 2002 Feb;204(5-6):339-46. http://www.ncbi.nlm.nih.gov/pubmed/11885358

 

Common etiology of posttraumatic stress disorder, fibromyalgia, chronic fatigue syndrome and multiple chemical sensitivity via elevated nitric oxide/peroxynitrite

Abstract:

Three types of overlap occur among the disease states chronic fatigue syndrome (CFS), fibromyalgia (FM), multiple chemical sensitivity (MCS) and posttraumatic stress disorder (PTSD). They share common symptoms. Many patients meet the criteria for diagnosis for two or more of these disorders and each disorder appears to be often induced by a relatively short-term stress which is followed by a chronic pathology, suggesting that the stress may act by inducing a self-perpetuating vicious cycle. Such a vicious cycle mechanism has been proposed to explain the etiology of CFS and MCS, based on elevated levels of nitric oxide and its potent oxidant product, peroxynitrite.

Six positive feedback loops were proposed to act such that when peroxynitrite levels are elevated, they may remain elevated. The biochemistry involved is not highly tissue-specific, so that variation in symptoms may be explained by a variation in nitric oxide/peroxynitrite tissue distribution. The evidence for the same biochemical mechanism in the etiology of PTSD and FM is discussed here, and while less extensive than in the case of CFS and MCS, it is nevertheless suggestive. Evidence supporting the role of elevated nitric oxide/peroxynitrite in these four disease states is summarized, including induction of nitric oxide by common apparent inducers of these disease states, markers of elevated nitric oxide/peroxynitrite in patients and evidence for an inductive role of elevated nitric oxide in animal models.

This theory appears to be the first to provide a mechanistic explanation for the multiple overlaps of these disease states and it also explains the origin of many of their common symptoms and similarity to both Gulf War syndrome and chronic sequelae of carbon monoxide toxicity. This theory suggests multiple studies that should be performed to further test this proposed mechanism. If this mechanism proves central to the etiology of these four conditions, it may also be involved in other conditions of currently obscure etiology and criteria are suggested for identifying such conditions.

Copyright 2001 Harcourt Publishers Ltd.

Comment in: Nitric oxide and the etiology of chronic fatigue syndrome: giving credit where credit is due. [Med Hypotheses. 2005]

 

Source: Pall ML. Common etiology of posttraumatic stress disorder, fibromyalgia, chronic fatigue syndrome and multiple chemical sensitivity via elevated nitric oxide/peroxynitrite. Med Hypotheses. 2001 Aug;57(2):139-45. http://www.ncbi.nlm.nih.gov/pubmed/11461161

 

Chemical sensitivity and chronic fatigue in Gulf War veterans: a brief report

Abstract:

The foci of this brief report are to (1) describe the prevalence of chemical sensitivity (CS) and chronic fatigue (CF) symptomatology and of presumptive multiple CS and CF syndrome diagnoses, and (2) explore the potential overlap between one purported case definition (i.e., chronic multi-symptom illness) and these unexplained symptom syndromes in a well-characterized group of Gulf War veterans. The number of subjects with CS and CF symptomatology and presumptive multiple CS and CF syndrome diagnoses was higher in the Gulf War-deployed group compared with a group deployed to Germany during the Gulf War. However, the percent differences were not significant when comparing the presumptive diagnoses of multiple CS and CF syndrome. The characteristic differences between the groups and the overlap with chronic multi-symptom illness are also discussed.

 

Source: Proctor SP, Heaton KJ, White RF, Wolfe J. Chemical sensitivity and chronic fatigue in Gulf War veterans: a brief report. J Occup Environ Med. 2001 Mar;43(3):259-64. http://www.ncbi.nlm.nih.gov/pubmed/11285874

 

Multiple chemical sensitivity and chronic fatigue syndrome in British Gulf War veterans

Abstract:

The objective of this study was to measure the prevalence of multiple chemical sensitivity (MCS) and chronic fatigue syndrome (CFS) in British Gulf War veterans and to investigate their association with reported exposures and psychologic morbidity. In 1997–1998, the authors undertook a cross-sectional survey of three cohorts of British military personnel comprising Gulf veterans (n = 3,531), those who had served in Bosnia (n = 2,050), and those serving during the Gulf War but not deployed there (Era cohort, n = 2,614). MCS and CFS were defined according to operational criteria.

The prevalence of MCS in the Gulf, Bosnia, and Era cohorts was 1.3%, 0.3%, and 0.2%, respectively. For CFS, the prevalence was 2.1% (Gulf cohort), 0.7% (Bosnia cohort), and 1.8% (Era cohort). In Gulf veterans, MCS was strongly associated with exposure to pesticides (adjusted odds ratio = 12.3, 95% confidence interval: 5.1, 30.0). Both syndromes were associated with high levels of psychologic morbidity.

These findings suggest that CFS and MCS account for some of the medically unexplained illnesses reported by veterans after deployment to the Gulf. MCS was particularly associated with Gulf deployment and self-reported exposure to pesticides, findings that merit further exploration given the controversial status of this diagnosis and the potential for recall bias in a questionnaire survey.

 

Source: Reid S, Hotopf M, Hull L, Ismail K, Unwin C, Wessely S. Multiple chemical sensitivity and chronic fatigue syndrome in British Gulf War veterans. Am J Epidemiol. 2001 Mar 15;153(6):604-9. http://aje.oxfordjournals.org/content/153/6/604.long (Full article)

 

Comorbid clinical conditions in chronic fatigue: a co-twin control study

Abstract:

OBJECTIVES: Chronically fatiguing illness, defined as fatigue for at least 6 months, has been associated with various physical health conditions. Our objective was to determine whether there is a significant relationship between chronically fatiguing illness and 10 clinical conditions that frequently appear to be associated with fatigue, adjusting for the potentially confounding effects of psychiatric illness.

DESIGN: A co-twin control study controlling for genetic and many environmental factors by comparing chronically fatigued twins with their nonfatigued co-twins.

SETTING: A nationally distributed volunteer twin registry.

PARTICIPANTS: The study included 127 twin pairs in which one member of the pair experienced fatigue of at least 6 months’ duration and the co-twin was healthy and denied chronic fatigue. Fatigued twins were classified into 3 levels using increasingly stringent diagnostic criteria.

MEASUREMENTS AND MAIN RESULTS: Twins reported on a history of fibromyalgia, irritable bowel syndrome, multiple chemical sensitivities, temporomandibular disorder, interstitial cystitis, postconcussion syndrome, tension headache, chronic low back pain, chronic pelvic pain (women), and chronic nonbacterial prostatitis (men). The prevalence of these comorbid clinical conditions was significantly higher in the fatigued twins compared to their nonfatigued co-twins. Most notably, compared to their nonfatigued co-twins, the chronically fatigued twins had higher rates of fibromyalgia (> 70% vs < 10%) and irritable bowel syndrome (> 50% vs < 5%). The strongest associations were observed between chronic fatigue and fibromyalgia (odds ratios > 20), irritable bowel syndrome, chronic pelvic pain, multiple chemical sensitivities, and temporomandibular disorder (all with odds ratios > or = 4). Regression analysis suggested that the number of comorbid clinical conditions associated with chronic fatigue could not be attributed solely to psychiatric illness.

CONCLUSIONS: Chronically fatiguing illnesses were associated with high rates of many other clinical conditions. Thus, patients with chronic fatigue may present a complex clinical picture that poses diagnostic and management challenges. Nonetheless, clinicians should assess such patients for the presence of comorbid clinical conditions. Future research should provide a better understanding of the temporal relationship of the onset of fatigue and these conditions, and develop strategies for early intervention.

 

Source: Aaron LA, Herrell R, Ashton S, Belcourt M, Schmaling K, Goldberg J, Buchwald D. Comorbid clinical conditions in chronic fatigue: a co-twin control study. J Gen Intern Med. 2001 Jan;16(1):24-31. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1495162/ (Full article)

 

Toxicant-induced loss of tolerance

Abstract:

Drug addiction and multiple chemical intolerance (abdiction) appear to be polar opposites–the former characterized by craving and dependency, the latter by aversion. However, when the two are viewed in juxtaposition similarities emerge, revealing a common underlying dynamic, one which appears to be a new paradigm of disease. TILT, or toxicant-induced loss of tolerance, bridges the gap between addiction and abduction and has the potential to explain a variety of illnesses, including certain cases of asthma, migraine headaches and depression, as well as chronic fatigue syndrome, fibromyalgia and “Gulf War syndrome”.

This paper argues that both addiction and chemical intolerance involve a fundamental breakdown in innate tolerance, resulting in an amplification of various biological effects, particularly withdrawal symptoms. While addicts seek further exposures so as to avoid unpleasant withdrawal symptoms, chemically intolerant individuals shun their problem exposures, but for the same reason–to avoid unpleasant withdrawal symptoms.

These observations raise critical questions: do addictive drugs and environmental pollutants initiate an identical disease process? Once this process begins, can both addictants and pollutants trigger symptoms and cravings? TILT opens a new window between the fields of addiction and environmental medicine, one that has the potential to transform neighboring realms of medicine, psychology, psychiatry and toxicology.

 

Source: Miller CS. Toxicant-induced loss of tolerance. Addiction. 2001 Jan;96(1):115-37. http://www.ncbi.nlm.nih.gov/pubmed/11177524

 

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

 

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