Idiopathic environmental intolerance is characterized by recurrent, nonspecific symptoms attributed to low-level exposure to chemically unrelated substances commonly occurring in the environment or sometimes to hypersensitivity to electromagnetic fields. Symptoms are numerous, often involving multiple organ systems, but physical findings are unremarkable. Diagnosis is by exclusion. Treatment is psychological support and avoidance of perceived triggers, although triggers rarely can be defined.
Idiopathic environmental intolerance is generally defined as a subjective illness caused by the development of multiple symptoms attributed to exposure to any number of identifiable or unidentifiable chemical, biologic, or physical substances (inhaled, touched, or ingested) in the absence of clinically detectable organ dysfunction or related physical signs; however, this is not a universally accepted definition (1). Idiopathic environmental intolerance was formerly called multiple chemical sensitivity (MCS).
In one nationally representative, cross-sectional study of 1137 adults in the United States, 12.8% reported a medical diagnosis of multiple chemical sensitivities; 25.9% reported chemical sensitivity (2).
Idiopathic environmental intolerance is more prevalent in women (3). It is variably associated with socioeconomic status; however, many patients with the condition have been reported to be out of work (2, 4).
General references
1. Idiopathic environmental intolerances. American Academy of Allergy, Asthma and Immunology (AAAAI) Board of Directors. J Allergy Clin Immunol. 1999;103(1 Pt 1):36-40.
2. Steinemann A. National Prevalence and Effects of Multiple Chemical Sensitivities. J Occup Environ Med. 2018;60(3):e152-e156.doi:10.1097/JOM.0000000000001272
3. Kreutzer R, Neutra RR, Lashuay N. Prevalence of people reporting sensitivities to chemicals in a population-based survey. Am J Epidemiol. 1999;150(1):1-12. doi:10.1093/oxfordjournals.aje.a009908
4. Simon GE, Daniell W, Stockbridge H, et al. Immunologic, psychological, and neuropsychological factors in multiple chemical sensitivity. A controlled study. Ann Intern Med. 1993;119(2):97-103. doi:10.7326/0003-4819-119-2-199307150-00001
Etiology of Idiopathic Environmental Intolerance
Triggers
Reported triggers for idiopathic environmental intolerance include:
Alcohol and medications
Caffeine and food additives
Carpet and furniture odors
Fuel odors and engine exhaust
Painting materials
Perfume and other scented products
Pesticides and herbicides
Mobile telecommunication devices
Electromagnetic fields
Mechanism
Immunologic and nonimmunologic theories have been proposed. They are hampered by lack of a consistent dose response to proposed causative substances; ie, symptoms may not be replicated after exposure to high levels of a substance that previously, at much lower levels, seemed to provoke a reaction. Many physicians consider the etiology to be psychological, probably a form of somatic symptom disorder. Others suggest that the syndrome is a type of panic attack or agoraphobia.
Idiopathic environmental intolerance occurs in 40% of people with chronic fatigue syndrome (also called myalgic encephalomyelitis/chronic fatigue syndrome [ME/CFS]) and in 16% of people with fibromyalgia (1).
Some proposed mechanisms include sensitization of transient receptor potential (TRP) receptors (TRPV1, TRPA1) and N-methyl-D-aspartate (NMDA) receptors, elevated pro-inflammatory cytokines such as interleukins (eg, IL-1 beta, IL-2, IL-4, IL-6), and altered limbic system processing of sensory stimuli; however, the pathophysiology has not been determined (2, 3, 4). Although measurable biologic abnormalities (eg, decreased levels of B cells, elevated levels of IgE) are rare, some patients have such abnormalities. However, these abnormalities appear without a consistent pattern, their significance is uncertain, and testing for these abnormalities to establish an immunologic basis for the disorder should be discouraged.
Etiology references
1. 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;62(5):655-663. doi:10.1097/00006842-200009000-00009
2. Dantoft TM, Elberling J, Brix S, et al. An elevated pro-inflammatory cytokine profile in multiple chemical sensitivity. Psychoneuroendocrinology. 2014;40:140-150. doi:10.1016/j.psyneuen.2013.11.012
3. Molot J, Sears M, Anisman H. Multiple chemical sensitivity: It's time to catch up to the science. Neurosci Biobehav Rev. 2023;151:105227. doi:10.1016/j.neubiorev.2023.105227
4. Viziano A, Micarelli A, Pasquantonio G, et al. Perspectives on multisensory perception disruption in idiopathic environmental intolerance: a systematic review. Int Arch Occup Environ Health. 2018;91(8):923-935. doi:10.1007/s00420-018-1346-z
Symptoms and Signs of Idiopathic Environmental Intolerance
Many patients may report symptoms several years before an official diagnosis is made. Symptoms of idiopathic environmental intolerance (eg, palpitations, chest pain, sweating, shortness of breath, fatigue, flushing, dizziness, nausea, choking, trembling, numbness, coughing, hoarseness, difficulty concentrating) are numerous and usually involve more than one organ system.
Most patients present with a long list of suspected agents, self-identified or identified by a physician during previous testing. Such patients often go to great lengths to avoid these agents by changing residence and employment, avoiding foods containing “chemicals,” sometimes wearing masks in public, or avoiding public settings altogether. Physical examination is typically characteristically unremarkable.
Diagnosis of Idiopathic Environmental Intolerance
Exclusion of other causes
The diagnosis of idiopathic environmental intolerance initially involves the exclusion of known organic disorders with similar manifestations:
Allergies (eg, allergic rhinitis, food allergies)
Atopic disorders (eg, asthma, angioedema)
Endocrine disorders (eg, carcinoid syndrome, pheochromocytoma, mastocytosis)
Cardiac disorders (eg, arrhythmias)
Pulmonary disorders (eg, COPD, interstitial lung disease, occupational lung disease)
Atopic disorders are excluded based on a typical clinical history, skin-prick testing, serum assays of specific IgE, or all 3. Consultation with an allergy specialist may be helpful. Building-related illnesses, in which many people who spend time in the same building develop symptoms, should be considered.
If symptoms and signs are not strongly suggestive of a systemic rheumatic disease (eg, objective joint, skin, and/or mucous membrane manifestations), testing for autoantibodies (eg, antinuclear antibodies [ANA], rheumatoid factor, extractable nuclear antigens [ENA]) should be avoided. In such cases, pretest probability is low and false-positive results are far more likely than true-positive results (1).
Diagnosis reference
1. Yeo AL, Le S, Ong J, et al. Utility of repeated antinuclear antibody tests: a retrospective database study. Lancet Rheumatol. 2020;2(7):e412-e417. doi:10.1016/S2665-9913(20)30084-9
Treatment of Idiopathic Environmental Intolerance
Sometimes avoiding suspected triggers
Psychological treatments (eg, cognitive behavioral therapy)
The treatment of idiopathic environmental intolerance is sometimes aimed at avoiding the suspected precipitating agents, which may be difficult because many are ubiquitous. However, evidence to support such avoidance is limited. Social isolation and costly and highly disruptive avoidance behaviors should be discouraged. A supportive relationship with a primary care physician who offers reassurance and protects patients from unnecessary tests and procedures is helpful.
Psychological evaluation and intervention may help patients overcome some avoidant behaviors (1), but characteristically many patients resist this approach. The point of this approach is not to convince patients that the cause is psychological but rather to help them cope with their symptoms and improve quality of life (2). Useful techniques include psychological desensitization (often as part of cognitive behavioral therapy) (2) and graded exposure therapy (see Specific Phobic Disorders, Treatment). Pharmacotherapy can be beneficial if targeted toward coexisting psychiatric disorders (eg, major depression, panic disorder).
Treatment references
1. Binkley KE. Multiple Chemical Sensitivity/Idiopathic Environmental Intolerance: A Practical Approach to Diagnosis and Management. J Allergy Clin Immunol Pract. 2023;11(12):3645-3649. doi:10.1016/j.jaip.2023.08.039
2. Hauge CR, Rasmussen A, Piet J, et al. Mindfulness-based cognitive therapy (MBCT) for multiple chemical sensitivity (MCS): Results from a randomized controlled trial with 1 year follow-up. J Psychosom Res. 2015;79(6):628-634. doi: 10.1016/jpsychores.2015.06.010
Key Points
Idiopathic environmental intolerance cannot at present be fully explained by non-psychological factors.
For diagnosis, exclude organic medical disorders that can have similar intermittent manifestations (eg, allergic disorders) and consider building-related illnesses.
Test for immunologic abnormalities only if indicated by objective clinical or laboratory findings.
Encourage psychological therapies (eg, cognitive behavioral therapy, desensitization, graded exposure) and coping skills; pharmacological and behavioral treatment of coexisting psychiatric disorders may also be beneficial.
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