Elsevier

Science of The Total Environment

Volume 408, Issue 24, 15 November 2010, Pages 6047-6061
Science of The Total Environment

Review
Sensitivity-related illness: The escalating pandemic of allergy, food intolerance and chemical sensitivity,☆☆

https://doi.org/10.1016/j.scitotenv.2010.08.047Get rights and content

Abstract

The prevalence of allergic-related diseases, food intolerance, and chemical sensitivities in both the pediatric and adult population has increased dramatically over the last two decades, with escalating rates of associated morbidity. Conditions of acquired allergy, food intolerance and chemical hypersensitivity are frequently the direct sequelae of a toxicant induced loss of tolerance (TILT) in response to a significant initiating toxic exposure. Following the primary toxicant insult, the individuals become sensitive to low levels of diverse and unrelated triggers in their environment such as commonly encountered chemical, inhalant or food antigens. Among sensitized individuals, exposure to assorted inciting stimuli may precipitate diverse clinical and/or immune sequelae as may be evidenced by clinical symptoms as well as varied lymphocyte, antibody, or cytokine responses in some cases. Recently recognized as a mechanism of disease development, TILT and resultant sensitivity-related illness (SRI) may involve various organ systems and evoke wide-ranging physical or neuropsychological manifestations. With escalating rates of toxicant exposure and bioaccumulation in the population-at-large, an increasing proportion of contemporary illness is the direct result of TILT and ensuing SRI. Avoidance of triggers will preclude symptoms, and desensitization immunotherapy or immune suppression may ameliorate symptomatology in some cases. Resolution of SRI generally occurs on a gradual basis following the elimination of bioaccumulated toxicity and avoidance of further initiating adverse environmental exposures. As has usually been the case throughout medical history whenever new evidence regarding disease mechanisms emerges, resistance to the translation of knowledge abounds.

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

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    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.

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