ReviewSensitivity-related illness: The escalating pandemic of allergy, food intolerance and chemical sensitivity☆,☆☆
Introduction
The incidence and prevalence of allergic-related diseases including asthma, (Lau et al., 2002) atopic dermatitis, (Kiyohara et al., 2008) hay fever, (Sih and Mion, 2010) food allergy, (Cochrane et al., 2009) atopic conjunctivitis, (Isolauri et al., 2009) and eosinophilic esophagitis (Nantes Castillejo et al., 2009) has escalated considerably in the last two decades. There has been increasing recognition, however, that not all sensitivities, including many types of food intolerance and chemical hypersensitivity reactions, are related to the classically understood concept of ‘allergic’ phenomenon involving immunoglobulin(Ig)-E antibody-mediated allergic responses (Gelincik et al., 2008, Miller and Ashford, 2000, Sicherer and Sampson, 2010). Food intolerance, for example, can precipitate a variety of outcomes, including headache, that are unrelated to atopic disease (Millichap and Yee, 2003). Despite discussion in the scientific literature of various hypotheses and theories, many consider the source etiology for escalating allergy, intolerance and sensitivities to be an enigma.
In this paper, a brief overview of the public health problem of sensitivities is initially presented to highlight the issue of allergy, food intolerance and environmental sensitivity. This is followed by the specific objective of this work: to present a review of the available research literature examining the etiology and pathogenesis of sensitivities and sensitivity reactions and to then examine interventions that can be used within clinical settings to address sensitivity problems. Finally, four brief case studies illustrating the pathway to sensitivity-related illness and strategies to advance recovery will be discussed.
Section snippets
Methodology
This review was prepared by assessing available medical and scientific literature from MEDLINE/PubMed, as well as by reviewing numerous books, toxicology and allergy journals, conference proceedings, government publications, and environmental health periodicals. References cited in identified publications were also examined for additional relevant writings. Searching techniques included key word searches with terms related to allergy, chemical sensitivity, food intolerance and environmental
Description of terms
With overlap and ambiguity in commonly encountered vernacular, clarification of language is in order. Intolerance is a broad term describing any type of adverse reaction occurring in response to a specific trigger. Allergy commonly refers to conditions or reactions associated with an IgE antibody-mediated immunologic response following antigenic exposure. Antigen or incitant simply refers to material that, when introduced into the human body, is capable of initiating an immune response.
Prevalence of sensitivity-related illness
Sensitivity to various compounds in our environment and our foods has become a ubiquitous phenomenon. The burden of disease related to atopic allergic illness is widespread and rising steadily, particularly in some jurisdictions. Estimates suggest that allergies affect as many as 40 to 50 million American people (University of Maryland Medical Centre, 2010). In Scotland, allergic disorders now affect about one in three of the population at some time in their lives, (Anandan et al., 2009) with
Etiology of chronic illness
In response to a considerable volume of emerging scientific data, the Centers for Disease Control recently concluded that the source of virtually all illness represents the complex interaction of a fixed genome with a modifiable environment (Office of Genomics and Disease Prevention: Centers for Disease Control and Prevention, 2000) (Fig. 1) Rather than primarily genetic in origin, expanding research continues to demonstrate that chronic illness is generally the consequence of various
Origins of sensitivity-related illness
Several determinants and mechanisms have been implicated in the escalating prevalence of SRI. Etiological variables discussed in the literature as contributing to sensitivity states include microbial deprivation as described in the hygiene hypothesis, (Bjorksten, 2009, Kalliomaki and Isolauri, 2002) nutritional transition and other factors resulting in arginine deficiency states, ( Maarsingh et al., 2008, Maarsingh et al., 2009, Meurs et al., 2003) environmental pollution with exposure to
Pathway to development of sensitivity-related illness
The pathway to clinical conditions resulting from allergy and sensitivity appears to involve three successive stages (as displayed in Fig. 2): i) exposure to a primary toxicant; ii) initiation of a state of hypersensitivity (or diminished tolerance resulting from the toxic insult referred to as TILT); and iii) triggering of diverse clinical reactions by exposure to low levels of assorted antigens — this may be referred to as ‘MATES’ (minute assorted triggers evoke symptoms). Accordingly, the
Clinical manifestations of sensitivity-related illness
Manifestations of SRI are diverse and may involve many organ systems (Ashford and Miller, 1998). Although delayed reactions are reported, signs and symptoms usually occur within minutes to an hour following incitant exposure. The reactions range from mild (slight headache, sneezing, minor heartburn) to severe (incapacitating arthritis, panic attacks, migraines, depression, bloody diarrhea, and so on.) (Miller and Ashford, 2000) The severity of morbidity may or may not relate to the intensity of
Proposed pathophysiological mechanism to development of sensitivities
In order to provide a compelling case to explain the unique pathway to SRI — the development of TILT, consequent MATES, and the diverse clinical sequelae — a consistent pathophysiological model must be provided and supported by evidence. Although the exact biochemical and pathophysiologic mechanism for each type of sensitivity response remains an enigma, various general and specific theories have been proposed to explain the sensitivity phenomenon.
Thus far, there has been no specific genetic
Biomarkers for sensitivity-related illness
It would be ideal to have a single characteristic of SRI that could be objectively measured as an indicator of the pathogenic process associated with this condition. The ideal biomarker for SRI would help link specific levels of certain environmental exposures to TILT and subsequent disease outcomes. Such a marker might be an immunological biomarker, indicating impaired tolerance and immune dysregulation. In SRI reactions, there have been various reports of atypical laboratory findings, (Rea,
Clinical approach to sensitivity-related illness
Thus far, most of the management of SRI has focused on symptom control through use of assorted pharmaceutical preparations. For example, those with headaches may be treated with analgesics, those with serious intestinal or airway inflammation may be treated with bronchodilators; and those with joint problems may receive assorted anti-inflammatory therapies. All of these interventions, however, only temporarily conceal symptoms and fail to deal with the etiology of the problem or to achieve
Concluding thoughts
Sensitivity-related illness appears to be a toxigenic condition with three successive components — toxicant exposure, impaired tolerance and hypersensitivity reactions. This mechanism of illness accounts for a considerable proportion of contemporary clinical disease presenting to physicians in various specialty fields. As a result of escalating exposures in the environment commencing in the pre-natal period (Genuis, 2009) and continuing throughout life, increasing numbers of individuals in the
Learning points
- •
Sensitivity-related illness — including allergy, food intolerance and chemical sensitivity — is generally the result of genetic predisposition combining with a toxicant burden resulting from environmental exposure.
- •
A signficant toxic burden on the human body which reaches beyond a threshold level appears to initiate a state of impaired tolerance and hypersensitivity in that individual. This may be referred to as a ‘Toxicant Induced Loss of Tolerance’ or ‘TILT.’
- •
Individual patients with impaired
References (208)
‘Sensitivity syndromes’ related to radiation exposures
Med Hypotheses
(2001)- et al.
An olfactory-limbic model of multiple chemical sensitivity syndrome: possible relationships to kindling and affective spectrum disorders
Biol Psychiatry
(1992) - et al.
Low-dose naltrexone for disease prevention and quality of life
Med Hypotheses
(2009) - et al.
Bovine milk intolerance in celiac disease is related to IgA reactivity to alpha- and beta-caseins
Nutrition
(2009) The vitamin C treatment of allergy and the normally unprimed state of antibodies
Med Hypotheses
(1986)- et al.
Persistent organic pollutants in 9/11 world trade center rescue workers: reduction following detoxification
Chemosphere
(2007) - et al.
Multiple chemical sensitivities: a systematic review of provocation studies
J Allergy Clin Immunol
(2006) - et al.
Treatment of a serious autistic disorder in a child with Naltrexone in an oral suspension form
Encephale
(2009) Differentiation and function of pro-inflammatory Th17 cells
Microbes Infect
(2009)- et al.
Cytokines and other immunological biomarkers in children's environmental health studies
Toxicol Lett
(2007)
Allergy and “toxic mold syndrome”
Ann Allergy Asthma Immunol
Structural brain alterations in schizophrenia following fetal exposure to the inflammatory cytokine interleukin-8
Schizophr Res
Adipose tissue, adipokines, and inflammation
J Allergy Clin Immunol
Chemical sensitivities and the Gulf War: Department of Veterans Affairs Research Center in basic and clinical science studies of environmental hazards
Regul Toxicol Pharmacol
Detection of low-level environmental chemical allergy by a long-term sensitization method
Toxicol Lett
Medical practice and community health care in the 21st century: a time of change
Public Health
Toxic causes of mental illness are overlooked
Neurotoxicology
Nowhere to hide: chemical toxicants and the unborn child
Reprod Toxicol (Elmsford, N.Y.)
Human detoxification of perfluorinated compounds
Public Health
Self-reported chemical sensitivity in Germany: a population-based survey
Int J Hyg Environ Health
The role of stachybotrys in the phenomenon known as sick building syndrome
Adv Appl Microbiol
Effects of solubility of urban air fine and coarse particles on cytotoxic and inflammatory responses in RAW 264.7 macrophage cell line
Toxicol Appl Pharmacol
Epidemiology and disease burden from allergic disease in Scotland: analyses of national databases
J R Soc Med
Anhedonic and anxiogenic effects of cytokine exposure
Milk protein IgG and IgA: the association with milk-induced gastrointestinal symptoms in adults
World J Gastroenterol
Chemical exposures: low levels and high stakes
Multiple chemical sensitivity: a respiratory disorder?
Toxicol Ind Health
Cognitive dysfunction and disability in geriatric veterans with self-reported intolerance to environmental chemicals
J Chron Fatigue Syndr
Patterns of waking EEG spectral power in chemically intolerant individuals during repeated chemical exposures
Int J Neurosci
Prevalence of self-reported symptoms and consequences related to inhalation of airborne chemicals in a Danish general population
Int Arch Occup Environ Health
Time to reconsider the clinical value of immunoglobulin G4 to foods?
Clin Chem Lab Med
The hygiene hypothesis: do we still believe in it?
Nestle Nutr Workshop Ser
Microglia-mediated neurotoxicity: uncovering the molecular mechanisms
Nat Rev Neurosci
Safety of biologics in inflammatory bowel disease
Curr Treat Options Gastroenterol
Anti-TNF antibody therapy in rheumatoid arthritis and the risk of serious infections and malignancies: systematic review and meta-analysis of rare harmful effects in randomized controlled trials
JAMA
Laboratory evaluations in molecular medicine: nutrients, toxicants, and cell regulators
Food allergy among children in the United States
Pediatrics
Silicone breast implants and autoimmunity: causation, association, or myth?
J Biomater Sci
Silica, apoptosis, and autoimmunity
J Immunotoxicol
Comparison of patients with chronic fatigue syndrome, fibromyalgia, and multiple chemical sensitivities
Arch Intern Med
Downregulation of Th17 cells in the small intestine by disruption of gut flora in the absence of retinoic acid
J Immunol
Immunoglobulin production pattern is allergen-specific in polysensitized patients
Int J Immunopathol Pharmacol
Successful oral tolerance induction in severe peanut allergy
Allergy
Factors influencing the incidence and prevalence of food allergy
Allergy
Treatment of chlordecone (Kepone) toxicity with cholestyramine. Results of a controlled clinical trial
N Engl J Med
Physical activity, exercise, and inflammatory markers in older adults: findings from the Health, Aging and Body Composition Study
J Am Geriatr Soc
Acquired intolerance to solvents following pesticide/solvent exposure in a building: a new group of workers at risk for multiple chemical sensitivities?
Toxicol Ind Health
The worker with multiple chemical sensitivities: an overview
Cited by (0)
- ☆
Dr. Stephen J. Genuis is a clinical associate professor and a specialist in the clinical practice of environmental health sciences in the Faculty of Medicine at the University of Alberta.
- ☆☆
There are no conflicting interests. No funding has been provided for any part of this work.