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

 

Victimization in chronic fatigue syndrome and fibromyalgia in tertiary care: a controlled study on prevalence and characteristics

Abstract:

The authors studied the prevalence and characteristics of different forms of victimization in 95 patients suffering from chronic fatigue syndrome(CFS) or fibromyalgia (FM) compared with a chronic disease group, including rheumatoid arthritis (RA) and multiple sclerosis (MS) patients, and a matched healthy control group. The authors assessed prevalence rates, nature of victimization (emotional, physical, sexual), life period of occurrence, emotional impact, and relationship with the perpetrator by a self-report questionnaire on burdening experiences.

CFS and FM patients showed significantly higher prevalences of emotional neglect and abuse and of physical abuse, with a considerable subgroup experiencing lifelong victimization. The family of origin and the partner were the most frequent perpetrators. With the exception of sexual abuse, victimization was more severely experienced by the CFS/FM group. No differences were found between healthy control subjects or RA/MS patients, and between CFS and FM patients. These findings support etiological hypotheses suggesting a pivotal role for chronic stress in CFS and FM and may have important therapeutic implications.

 

Source: Van Houdenhove B, Neerinckx E, Lysens R, Vertommen H, Van Houdenhove L, Onghena P, Westhovens R, D’Hooghe MB. Victimization in chronic fatigue syndrome and fibromyalgia in tertiary care: a controlled study on prevalence and characteristics. Psychosomatics. 2001 Jan-Feb;42(1):21-8. http://www.ncbi.nlm.nih.gov/pubmed/11161117

 

The sympathetic nerve–an integrative interface between two supersystems: the brain and the immune system

Abstract:

The brain and the immune system are the two major adaptive systems of the body. During an immune response the brain and the immune system “talk to each other” and this process is essential for maintaining homeostasis. Two major pathway systems are involved in this cross-talk: the hypothalamic-pituitary-adrenal (HPA) axis and the sympathetic nervous system (SNS). This overview focuses on the role of SNS in neuroimmune interactions, an area that has received much less attention than the role of HPA axis.

Evidence accumulated over the last 20 years suggests that norepinephrine (NE) fulfills the criteria for neurotransmitter/neuromodulator in lymphoid organs. Thus, primary and secondary lymphoid organs receive extensive sympathetic/noradrenergic innervation. Under stimulation, NE is released from the sympathetic nerve terminals in these organs, and the target immune cells express adrenoreceptors.

Through stimulation of these receptors, locally released NE, or circulating catecholamines such as epinephrine, affect lymphocyte traffic, circulation, and proliferation, and modulate cytokine production and the functional activity of different lymphoid cells. Although there exists substantial sympathetic innervation in the bone marrow, and particularly in the thymus and mucosal tissues, our knowledge about the effect of the sympathetic neural input on hematopoiesis, thymocyte development, and mucosal immunity is extremely modest.

In addition, recent evidence is discussed that NE and epinephrine, through stimulation of the beta(2)-adrenoreceptor-cAMP-protein kinase A pathway, inhibit the production of type 1/proinflammatory cytokines, such as interleukin (IL-12), tumor necrosis factor-alpha, and interferon-gamma by antigen-presenting cells and T helper (Th) 1 cells, whereas they stimulate the production of type 2/anti-inflammatory cytokines such as IL-10 and transforming growth factor-beta.

Through this mechanism, systemically, endogenous catecholamines may cause a selective suppression of Th1 responses and cellular immunity, and a Th2 shift toward dominance of humoral immunity. On the other hand, in certain local responses, and under certain conditions, catecholamines may actually boost regional immune responses, through induction of IL-1, tumor necrosis factor-alpha, and primarily IL-8 production.

Thus, the activation of SNS during an immune response might be aimed to localize the inflammatory response, through induction of neutrophil accumulation and stimulation of more specific humoral immune responses, although systemically it may suppress Th1 responses, and, thus protect the organism from the detrimental effects of proinflammatory cytokines and other products of activated macrophages.

The above-mentioned immunomodulatory effects of catecholamines and the role of SNS are also discussed in the context of their clinical implication in certain infections, major injury and sepsis, autoimmunity, chronic pain and fatigue syndromes, and tumor growth.

Finally, the pharmacological manipulation of the sympathetic-immune interface is reviewed with focus on new therapeutic strategies using selective alpha(2)- and beta(2)-adrenoreceptor agonists and antagonists and inhibitors of phosphodiesterase type IV in the treatment of experimental models of autoimmune diseases, fibromyalgia, and chronic fatigue syndrome.

 

Source: Elenkov IJ, Wilder RL, Chrousos GP, Vizi ES. The sympathetic nerve–an integrative interface between two supersystems: the brain and the immune system. Pharmacol Rev. 2000 Dec;52(4):595-638. http://pharmrev.aspetjournals.org/content/52/4/595.long (Full article)

 

Specific oxidative alterations in vastus lateralis muscle of patients with the diagnosis of chronic fatigue syndrome

Abstract:

Chronic fatigue syndrome (CFS) is a poorly understood disease characterized by mental and physical fatigue, most often observed in young white females. Muscle pain at rest, exacerbated by exercise, is a common symptom. Although a specific defect in muscle metabolism has not been clearly defined, yet several studies report altered oxidative metabolism.

In this study, we detected oxidative damage to DNA and lipids in muscle specimens of CFS patients as compared to age-matched controls, as well as increased activity of the antioxidant enzymes catalase, glutathione peroxidase, and transferase, and increases in total glutathione plasma levels. From these results we hypothesize that in CFS there is oxidative stress in muscle, which results in an increase in antioxidant defenses.

Furthermore, in muscle membranes, fluidity and fatty acid composition are significantly different in specimens from CFS patients as compared to controls and to patients suffering from fibromyalgia. These data support an organic origin of CFS, in which muscle suffers oxidative damage.

 

Source: Fulle S, Mecocci P, Fanó G, Vecchiet I, Vecchini A, Racciotti D, Cherubini A, Pizzigallo E, Vecchiet L, Senin U, Beal MF. Specific oxidative alterations in vastus lateralis muscle of patients with the diagnosis of chronic fatigue syndrome. Free Radic Biol Med. 2000 Dec 15;29(12):1252-9. http://www.ncbi.nlm.nih.gov/pubmed/11118815

 

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

 

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

 

Fibromyalgia, chronic fatigue syndrome, and myofascial pain syndrome

Abstract:

Fibromyalgia and widespread pain were common in Gulf War veterans with unexplained illness referred to a rheumatology clinic. Increased tenderness was demonstrated in the postmenstrual phase of the cycle compared with the intermenstrual phase in normally cycling women but not in users of oral contraceptives. Patients with fibromyalgia had high levels of symptoms that have been used to define silicone implant-associated syndrome. Tender points were found to be a common transient finding associated with acute infectious mononucleosis, but fibromyalgia was an unusual long-term outcome. The common association of fibromyalgia with other rheumatic and systemic illnesses was further explored. A preliminary study revealed a possible linkage of fibromyalgia to the HLA region. Patients with fibromyalgia were found to have an impaired ability to activate the hypothalamic pituitary portion of the hypothalamic pituitary adrenal axis as well as the sympathoadrenal system, leading to reduced corticotropin and epinephrine response to hypoglycemia. Much interest has been expressed in the literature on the possible role of autonomic dysfunction in the development or exacerbation of fatigue and other symptoms in chronic fatigue syndrome. Mycoplasma genus and mycoplasma fermentans were detected by polymerase chain reaction in patients with chronic fatigue syndrome. It was reported that myofascial temporomandibular disorder does not run in families. No major therapeutic trials in fibromyalgia, chronic fatigue syndrome, or myofascial pain syndrome were reported over the past year. The effectiveness of cognitive behavioral therapy and behavior therapy for chronic pain in adults was emphasized. A favorable outcome of fibromyalgia and chronic fatigue syndrome in children and adolescents was reported.

 

Source: Buskila D. Fibromyalgia, chronic fatigue syndrome, and myofascial pain syndrome. Curr Opin Rheumatol. 2000 Mar;12(2):113-23. http://www.ncbi.nlm.nih.gov/pubmed/10751014

 

Multiple mycoplasmal infections detected in blood of patients with chronic fatigue syndrome and/or fibromyalgia syndrome

Abstract:

The aim of this study was to investigate the presence of different mycoplasmal species in blood samples from patients with chronic fatigue syndrome and/or fibromyalgia syndrome. Previously, more than 60% of patients with chronic fatigue syndrome/fibromyalgia syndrome were found to have mycoplasmal blood infections, such as Mycoplasma fermentans infection.

In this study, patients with chronic fatigue syndrome/fibromyalgia syndrome were examined for multiple mycoplasmal infections in their blood. A total of 91 patients diagnosed with chronic fatigue syndrome/fibromyalgia syndrome and with a positive test for any mycoplasmal infection were investigated for the presence of Mycoplasma fermentans, Mycoplasma pneumoniae, Mycoplasma hominis and Mycoplasma penetrans in blood using forensic polymerase chain reaction.

Among these mycoplasma-positive patients, infections were detected with Mycoplasma pneumoniae (54/91), Mycoplasma fermentans (44/91), Mycoplasma hominis (28/91) and Mycoplasma penetrans (18/91). Multiple mycoplasmal infections were found in 48 of 91 patients, with double infections being detected in 30.8% and triple infections in 22%, but only when one of the species was Mycoplasma pneumoniae or Mycoplasma fermentans. Patients infected with more than one mycoplasmal species generally had a longer history of illness, suggesting that they may have contracted additional mycoplasmal infections with time.

 

Source: Nasralla M, Haier J, Nicolson GL. Multiple mycoplasmal infections detected in blood of patients with chronic fatigue syndrome and/or fibromyalgia syndrome. Eur J Clin Microbiol Infect Dis. 1999 Dec;18(12):859-65. http://www.ncbi.nlm.nih.gov/pubmed/10691196

 

Overlapping conditions among patients with chronic fatigue syndrome, fibromyalgia, and temporomandibular disorder

Abstract:

BACKGROUND: Patients with chronic fatigue syndrome (CFS), fibromyalgia (FM), and temporomandibular disorder (TMD) share many clinical illness features such as myalgia, fatigue, sleep disturbances, and impairment in ability to perform activities of daily living as a consequence of these symptoms. A growing literature suggests that a variety of comorbid illnesses also may commonly coexist in these patients, including irritable bowel syndrome, chronic tension-type headache, and interstitial cystitis.

OBJECTIVE: To describe the frequency of 10 clinical conditions among patients with CFS, FM, and TMD compared with healthy controls with respect to past diagnoses, degree to which they manifested symptoms for each condition as determined by expert-based criteria, and published diagnostic criteria.

METHODS: Patients diagnosed as having CFS, FM, and TMD by their physicians were recruited from hospital-based clinics. Healthy control subjects from a dermatology clinic were enrolled as a comparison group. All subjects completed a 138-item symptom checklist and underwent a brief physical examination performed by the project physicians.

RESULTS: With little exception, patients reported few past diagnoses of the 10 clinical conditions beyond their referring diagnosis of CFS, FM, or TMD. In contrast, patients were more likely than controls to meet lifetime symptom and diagnostic criteria for many of the conditions, including CFS, FM, irritable bowel syndrome, multiple chemical sensitivities, and headache. Lifetime rates of irritable bowel syndrome were particularly striking in the patient groups (CFS, 92%; FM, 77%; TMD, 64%) compared with controls (18%) (P<.001). Individual symptom analysis revealed that patients with CFS, FM, and TMD share common symptoms, including generalized pain sensitivity, sleep and concentration difficulties, bowel complaints, and headache. However, several symptoms also distinguished the patient groups.

CONCLUSIONS: This study provides preliminary evidence that patients with CFS, FM, and TMD share key symptoms. It also is apparent that other localized and systemic conditions may frequently co-occur with CFS, FM, and TMD. Future research that seeks to identify the temporal relationships and other pathophysiologic mechanism(s) linking CFS, FM, and TMD will likely advance our understanding and treatment of these chronic, recurrent conditions.

Comment in: Tobacco use and chronic fatigue syndrome, fibromyalgia, and temporomandibular disorder. [Arch Intern Med. 2000]

 

Source: Aaron LA, Burke MM, Buchwald D. Overlapping conditions among patients with chronic fatigue syndrome, fibromyalgia, and temporomandibular disorder. Arch Intern Med. 2000 Jan 24;160(2):221-7. http://www.ncbi.nlm.nih.gov/pubmed/10647761

 

Chronic Fatigue Syndrome and Primary Fibromyalgia Syndrome as recognized by GPs

Abstract:

BACKGROUND: Prevalence studies on Chronic Fatigue Syndrome (CFS) are rare. Because of the similarity in symptoms, the prevalence of Primary Fibromyalgia Syndrome (PFS) was investigated at the same time.

OBJECTIVES: To determine the prevalence of CFS and PFS as recognized by GPs in The Netherlands and to inform them of the existence of CFS.

METHODS: A postal questionnaire was sent to all GPs.

RESULTS: The questionnaire was returned by 60% of the GPs. Seventy-three per cent reported one or more CFS patients and 83% one or more PFS patients in their practice.

CONCLUSION: The estimated prevalence of CFS as recognized by GPs of 112 (PFS 157) patients per 100,000 is a minimum estimate.

 

Source: Bazelmans E, Vercoulen JH, Swanink CM, Fennis JF, Galama JM, van Weel C, van der Meer JW, Bleijenberg G. Chronic Fatigue Syndrome and Primary Fibromyalgia Syndrome as recognized by GPs. Fam Pract. 1999 Dec;16(6):602-4. http://fampra.oxfordjournals.org/content/16/6/602.long (Full article)