Multiple chemical sensitivity

​Multiple Chemical Sensitivity (MCS) also known as Multiple Chemical Sensitivity Syndrome or Idiopathic Environmental Intolerance, is a term used to describe a debilitating condition presenting as a complex array of symptoms linked to low level exposure to chemicals ¹. Several theories have been advanced to explain the cause of multiple chemical sensitivity, including allergy, toxic effects and neurobiologic sensitization. There is insufficient scientific evidence to confirm a relationship between any of these possible causes and symptoms. Patients with multiple chemical sensitivity have high rates of depression, anxiety and somatoform disorders, but it is unclear if a causal relationship or merely an association exists between multiple chemical sensitivity and psychiatric problems ¹. Physicians should compassionately evaluate and care for patients who have this distressing condition, while avoiding the use of unproven, expensive or potentially harmful tests and treatments. The first goal of management is to establish an effective physician-patient relationship. The patient’s efforts to return to work and to a normal social life should be encouraged and supported.

Multiple chemical sensitivity has been described under various names since the 1940s ². Multiple chemical sensitivity syndrome is characterized by the patient’s belief that his or her symptoms are caused by very low-level exposure to environmental chemicals ¹. The term “chemical” is used to refer broadly to many natural and man-made chemical agents, some of which have several chemical constituents. Health care professionals who focus on multiple chemical sensitivity often refer to themselves as practicing “clinical ecology.” Multiple chemical sensitivity syndrome has led to great controversy among clinicians, researchers, patients, lawyers, legislators and regulatory agencies. The absence of scientific agreement on multiple chemical sensitivity has contributed to the development of emotionally charged, extreme and entrenched positions. Gots summarized the controversy as follows ²:

• “[multiple chemical sensitivity] has been rejected as an established organic disease by the American Academy of Allergy and Immunology, the American Medical Association, the California Medical Association, the American College of Physicians, and the International Society of Regulatory Toxicology and Pharmacology. It may be the only ailment in existence in which the patient defines both the cause and the manifestations of his own condition. Despite this, it has achieved credibility in workmen’s [sic] compensation claims, tort liability, and regulatory actions.”

Position statements from a variety of medical and governmental organizations on multiple chemical sensitivity and clinical ecology are shown in Table 1 ³. No consensus has been reached as to whether multiple chemical sensitivity is a new illness or has a biologic basis, what causes it or how it should be treated. As scientists await answers to these questions, clinicians must care responsibly and compassionately for patients experiencing this syndrome ⁴.

Several definitions have been proposed for multiple chemical sensitivity ⁵. Cullen’s ⁶ definition is widely used. It includes four elements:

1. Multiple Chemical Sensitivity Syndrome is acquired after a documentable environmental exposure that may have caused objective evidence of health effects;
2. Multiple Chemical Sensitivity Syndrome symptoms are referable to multiple organ systems and vary predictably in response to environmental stimuli;
3. Multiple Chemical Sensitivity Syndrome symptoms occur in relation to measurable levels of chemicals, but the levels are below those known to harm health; and
4. No objective evidence of organ damage can be found.

Cullen’s definition has the practical advantage of describing a syndrome without specifying individual symptoms or mechanisms of disease. Other definitions have been proposed that describe specific symptoms or postulate disease mechanisms ⁵. These definitions are reflected in the other names that have been used for multiple chemical sensitivity and overlapping conditions, such as environmental illness, chemical AIDS, 20th century disease, total allergy syndrome, sick building syndrome, chemophobia, immune dysregulation and others.

The term “multiple chemical sensitivity” refers to the clinical syndrome without implying a mechanism of disease, in recognition of the lack of reliable scientific evidence to clarify such a mechanism. Indeed, the syndrome of multiple chemical sensitivity is likely heterogeneous, with multiple etiologic contributors in individual patients or different patterns of illness in response to a single mechanism of disease, or both ⁷. Multiple chemical sensitivity may represent a new, yet-to-be determined mechanism of disease ⁷. If so, it would have in common with previous “new” mechanisms of disease, such as infection and malignancy, an apparent chaos of symptoms that begin to make sense only after elucidation of the common underlying pathology.

Table 1. Statements from medical and governmental organizations about Multiple Chemical Sensitivity Syndrome and Clinical Ecology

American Medical Association, 1992: “No evidence based on well-controlled clinical trials is available that supports a cause-and-effect relationship between exposure to very low levels of substances and the myriad symptoms reported by clinical ecologists to result from such exposure . . . . Until such accurate, reproducible, and well-controlled studies are available, the American Medical Association Council on Scientific Affairs believes that multiple chemical sensitivity should not be considered a recognized clinical syndrome” 8.

American College of Physicians, 1989: “Review of the clinical ecology literature provides inadequate support for the beliefs and practices of clinical ecology. The existence of an environmental illness as presented in clinical ecology theory must be questioned because of the lack of a clinical definition. Diagnoses and treatments involve procedures of no proven efficacy” 9.

American College of Occupational and Environmental Medicine, 1993: “The science is indeterminate about MCS as a specific entity and the cause and effect relationships have not been clearly established” 3.

American Academy of Allergy and Immunology, 1986: “An objective evaluation of the diagnostic and therapeutic principles used to support the concept of clinical ecology indicates that it is an unproven and experimental methodology” 10.

American Lung Association, Environmental Protection Agency, Consumer Product Safety Commission and American Medical Association, 1994: “The diagnostic label of multiple chemical sensitivity (MCS)—also referred to as ‘chemical hypersensitivity’ or ‘environmental illness’—is being applied increasingly, although definition of the phenomenon is elusive and its pathogenesis as a distinct entity is not confirmed” 11.

Environmental Protection Agency, 1996: “There is at present no medical consensus concerning the definition or nature of this disorder” 12.

Most patients (85 to 90 percent) complaining of multiple chemical sensitivity syndrome are women. Most present between the ages of 30 and 50 years. Much additional basic descriptive and epidemiologic information is still unknown. The incidence and prevalence are unknown. The question of whether multiple chemical sensitivity is becoming more or less common is unanswered, as is the question of whether it is preventable. The natural history and biologic outcomes of multiple chemical sensitivity are unknown, and descriptions of multiple chemical sensitivity in primary care settings have not been reported. Selected patients from specialty settings comprise reports of Multiple Chemical Sensitivity syndrome ¹³.

Chemical sensitivity causes

Theories of the cause of multiple chemical sensitivity can be grouped into four broad categories: physical, stress, misdiagnosis and illness belief ¹⁴.

The symptoms of multiple chemical sensitivity are reportedly triggered by exposure to very low levels of perceived triggers, i.e. background levels of exposure, which do not cause concern for the vast majority of the population.

It is not known what causes the condition and how it develops. Despite extensive research over the past 50 years, there is little understanding of the causes and pathophysiological mechanisms of multiple chemical sensitivity. Several toxicological mechanisms have been proposed, but the scientific evidence is lacking.

Physical

Three basic physical mechanisms have been proposed to explain multiple chemical sensitivity: allergy, direct toxic effects and neurobiologic sensitization.

• Allergy. Followers of the clinical ecology movement believe chemical exposure causes the development of allergy to low levels of many chemicals, not just the initiating one. Supporters point to a spectrum of immune system tests that have been found to be abnormal in patients with multiple chemical sensitivity syndrome. However, there are many problems with these tests, such as wide natural variation in the test results, few reference standards to determine what statistically “normal” is and lack of reproducibility. Finally, careful studies comparing patients with multiple chemical sensitivity and control patients have found no differences on immunologic testing ¹⁵. Thus, it is not possible to rely on immunologic testing to demonstrate the etiology of multiple chemical sensitivity.

• Toxicologic Effects. Others propose a toxicologic effect of low-dose exposure—in effect, poisoning. However, objective evidence for such an effect is lacking ¹⁶. Patients with multiple chemical sensitivity experience symptoms at levels of chemical exposure far lower than those considered toxic.

• Neurobiologic Sensitization. The third proposed physical mechanism is that affected persons develop increasing neurologic sensitivity to the adverse effects of chemicals ¹⁷. Animal models for such neurologic changes include limbic kindling and time-dependent neurologic sensitization. In these models, animals repeatedly exposed to seizure-inducing chemicals or electrical stimulation have been found to develop lower thresholds for seizure induction than the thresholds observed before exposure. With other stimuli, animals have been found to have an amplification of the response to the stimulus over time ¹⁸. However, these events have been documented only with pharmacologic doses and only in animals, not in humans and not at the low doses purported to cause multiple chemical sensitivity.

Stress

About one half of the patients with multiple chemical sensitivity in various studies meet the criteria for depressive and anxiety disorders ¹⁹. Many patients meet the diagnostic criteria for somatoform disorders. There are marked similarities between multiple chemical sensitivity and post-traumatic stress disorder ¹⁵. Therefore, generalized “stress” or anxiety and depression have been suggested as precipitants of multiple chemical sensitivity, but studies suggesting causality, rather than merely an association between multiple chemical sensitivity and psychiatric problems, are fraught with methodologic problems ²⁰.

Clearly, patients with multiple chemical sensitivity have a higher prevalence of psychiatric conditions such as somatization, depression and anxiety. It is not clear whether psychiatric conditions cause multiple chemical sensitivity, are caused by it or are simply associated with multiple chemical sensitivity. It is possible, for example, that both multiple chemical sensitivity and psychiatric illness are results of a common underlying neurobiologic mechanism.

Misdiagnosis

Some believe that multiple chemical sensitivity is not a syndrome separate from the psychiatric disorders but just a variant presentation of them.

Illness Belief

Whatever its physiologic, toxic or psychiatric origins are, multiple chemical sensitivity has become the focus for great efforts to support a particular set of beliefs about its mechanism and manifestations. Multiple chemical sensitivity is discussed in an array of patient support groups and clinics, by clinicians, hotlines and lawyers, in journals and other media, and on World Wide Web sites. It has become the subject of disability laws and settlements.

Multiple chemical sensitivity differential diagnosis

The differential diagnosis for multiple chemical sensitivity includes various psychiatric and somatic illnesses. Psychiatric illnesses that may coexist with multiple chemical sensitivity, present as multiple chemical sensitivity or mimic multiple chemical sensitivity include somatoform disorders, panic and other anxiety disorders, depression and personality disorders. Malingering and factitious illness may also be considered. However, stable multiple chemical sensitivity might be a relatively unusual presentation for malingering, and factitious illness usually has associated objective findings, which are absent in multiple chemical sensitivity.

It has been suggested that Gulf War syndrome may be a variant of multiple chemical sensitivity. However, the etiology of Gulf War syndrome and the potential relationship between it and multiple chemical sensitivity are unclear. Symptoms of multiple chemical sensitivity may also overlap with chronic fatigue syndrome, but the diagnostic criteria for chronic fatigue syndrome differ from those for multiple chemical sensitivity. A major distinction is that the patient with multiple chemical sensitivity has a history of chemical exposure before the onset of symptoms.

Somatic illnesses that can mimic multiple chemical sensitivity include those with vague or subtle presentations, such as hypercalcemia, hypothyroidism, systemic lupus erythematosus and fibromyalgia.

Chemical sensitivity symptoms

Patients with multiple chemical sensitivity syndrome can have severe symptoms that interfere with daily life and work. They often report that they had no symptoms before a single large exposure, which is then followed by exacerbation of symptoms in response to previously tolerated low-level exposures. Virtually any symptom has been attributed to the syndrome, but the symptoms generally occur in one of three categories: central nervous system symptoms, respiratory and mucosal irritation, or gastrointestinal problems.

Common symptoms include fatigue, difficulty concentrating, depressed mood, memory loss, weakness, dizziness, headaches, heat intolerance and arthralgias ²¹. The typical patient with multiple chemical sensitivity presents with a firmly stated belief that the symptoms result from chemical exposure. Symptoms are precipitated by a wide array of common environmental agents, as listed below ²¹. Patients exposed to pesticides have been reported to have more severe symptoms than those exposed to chemicals during a building remodeling ²².

Patients often significantly alter their behavior in an attempt to avoid presumed precipitants of symptoms. They may have withdrawn from activities, friends and family in an attempt to eliminate chemical exposures. In one study of 35 patients with occupationally related multiple chemical sensitivity evaluated in an occupational medicine clinic, 97 percent of the patients had stopped activities outside the home, 91 percent had limited their travel, 89 percent had limited their contact with friends and 77 percent had left a job ²¹. Many changed home routines: 97 percent had stopped using cleaning compounds, 69 percent removed home furnishings and 63 percent limited their contact with family members. In their personal care, 94 percent stopped using fragrances, 91 percent changed their diet and 86 percent changed the type of clothing they wore.

Individuals with multiple chemical sensitivity (Idiopathic Environmental Intolerance) identify a wide and diverse range of chemical, biological and physical factors as symptom triggers, including:

• Aerosol air freshener
• Aerosol deodorant
• After-shave lotion
• Asphalt pavement
• Carpet/carpet glues
• Carpet cleaning products
• Cleaning products
• Cigar smoke
• Cigarette Smoke
• Colognes, perfumes
• Deodorant and anti-perspirant that are perfumed
• Diesel exhaust
• Diesel fuel
• Dry-cleaning fluid
• Floor cleaner Varnish, shellac, lacquer
• Furniture polish
• Garage fumes
• Gasoline exhaust
• Hair spray
• Insect repellant
• Insecticide spray
• Laundry detergent
• Marking pens
• Nail polish and Nail polish remover
• Oil-based paint
• Paint thinner
• Perfumes and body sprays
• Perfumed shampoo and other hair products
• Pesticides and herbicides
• Public restroom deodorizers
• Shampoo
• Tar fumes from roof or road
• Tile cleaners
• Wood smoke
• Varnish, shellac, lacquer

Does trigger avoidance help?

Trigger avoidance is a common approach to the management of multiple chemical sensitivity or idiopathic environmental intolerance symptoms because many individuals with multiple chemical sensitivity or idiopathic environmental intolerance report feeling better when they intentionally avoid the factors they report as triggers for their symptoms.

However, there is no conclusive scientific evidence that perceived trigger avoidance is effective in treating the condition. Several controlled exposure studies showed that individuals reporting multiple chemical sensitivity or idiopathic environmental intolerance tend to develop symptoms only when they are aware of being exposed to a trigger. More research is needed in this area.

It is prudent at all times to strive to maintain a healthy environment in the home and at work.

Better air quality, particularly good building ventilation, helps to maintain good health and benefits people with many medical conditions, including those who report multiple chemical sensitivity or idiopathic environmental intolerance.

It is also wise to minimize the use of household chemicals, such as pesticides, disinfectants, solvents and others. Use them only when needed, and always follow the label instructions.

At work and in public settings it is important to appreciate that for some individuals, exposure to certain chemical or physical agents may result in considerable distress. Workplaces and public settings should, therefore, endeavor to take reasonable steps to accommodate the needs of people reporting multiple chemical sensitivity or idiopathic environmental intolerance whenever possible.

Multiple chemical sensitivity diagnosis

There are no universally accepted diagnostic criteria for multiple chemical sensitivity or idiopathic environmental intolerance. There are no laboratory tests and no clinical guideline documents. multiple chemical sensitivity is not recognized as a medical condition in the United States and most countries.

A careful initial history, physical examination and basic laboratory investigation at the outset of providing medical care to a patient with multiple chemical sensitivity syndrome will substantially improve the physician-patient relationship and the quality of care. These patients are truly suffering as a result of their symptoms and deserve compassionate evaluation and management from a clinician who is sympathetic to their plight, but who also will protect them from unwarranted, dangerous, expensive or unproven evaluation and management.

The physician should empathetically confirm that he or she recognizes the intensity and reality of the symptoms while being clear about the degree to which a biologic relationship to chemical exposures can or cannot be confirmed. Not all data necessarily need to be obtained at the first visit, but this visit should initiate a shared plan for a systematic and thorough initial evaluation of the patient’s problems ²³.

The initial history should include a thorough review of each of the many symptoms that may be present. Information should be obtained about the initial and subsequent exposures thought to exacerbate symptoms. This information should include specific chemicals or other agents to which the patient was exposed, the mechanism and duration of exposure, protective measures, symptoms, other workers exposed and their symptoms, and nonoccupational exposures. A psychiatric history should be a standard part of the evaluation. Records of previous medical evaluations and treatment should be obtained and reviewed before embarking on an extensive subsequent evaluation.

The physical examination should focus particularly on organ systems with referable symptoms. Laboratory testing should be limited to standard basic testing as indicated to evaluate specific historical items and abnormal physical findings.

Multiple chemical sensitivity testing

Laboratory evaluation by “challenge testing” refers to having the patient inhale low concentrations of the offending chemical(s). Unfortunately, truly “blind” challenges may often not be possible because of the smell of the agent(s) ²⁴. It is difficult to separate reactions to the smell of the chemicals from physiologic effects. The biologic basis of reactions in patients with multiple chemical sensitivity appears similar to those occurring in panic disorder ²⁵. Although many patients report cognitive impairment between exposures, this effect is not reproducible on neuropsychologic testing ²⁶.

Tests that are not recommended for routine evaluation of multiple chemical sensitivity include environmental challenge testing, quantitative encephalography, brain electrical activity mapping, neuropsychologic testing, brainstem evoked potentials, positron emission tomography, immunologic testing and determination of blood levels of trace volatile organic compounds or pesticides ²³.

Multiple chemical sensitivity treatment

There are no clear evidence-based treatment options for multiple chemical sensitivity or idiopathic environmental intolerance. Individuals with multiple chemical sensitivity or idiopathic environmental intolerance should consider education, support and acknowledgement as the most beneficial interventions.

A huge array of treatment strategies for multiple chemical sensitivity have been proposed, including antifungal therapies, diets rotated to avoid the offending agents and the “radical separatist avoidance approach,” which is an attempt to avoid all exposures to man-made chemicals ⁴. However, randomized controlled trials of the treatment of multiple chemical sensitivity are lacking. Therefore, the clinician should be cautious in supporting any untested management plan. Other effective treatments reported in the literature include psychotherapy and cognitive behavioral therapy.

Some groups promote a wide range of interventions, ranging from intravenous injections of vitamins and nutritional supplements to ‘detoxification therapies’ such as sauna, colonic irrigation and others. The efficacy of these interventions in the treatment of multiple chemical sensitivity  or idiopathic environmental intolerance has not been tested systematically and they are not supported by medical practitioners.

The principle goals of treatment are summarized below. The first goal of management is to establish an effective physician-patient relationship ²⁷. This is possible if the physician is respectful of the patient, compassionate about the symptoms and genuinely interested in helping to evaluate and manage the patient’s problems. The overall goal of treatment is to maximize rehabilitation and to control, not cure, the patient’s symptoms.

Standard treatment should be provided for identified psychiatric and physical disorders. Treatment of psychiatric and non–multiple chemical sensitivity somatic disorders does not imply that multiple chemical sensitivity is either “all in the patient’s head” or entirely explained by concomitant somatic illness. Rather, treatment of these problems can reduce the patient’s total burden of suffering and may improve his or her ability to cope with the multiple chemical sensitivity symptoms and to achieve maximal function.

The patient should be encouraged to work and to socialize despite the symptoms. The major disability from multiple chemical sensitivity is often the isolation and withdrawal experienced as the patient seeks to avoid chemical exposures. Yet there is no evidence that such avoidance is effective or that continued exposure leads to any adverse biologic effects. Therefore, the physician should not encourage the patient to avoid low-dose exposure to a variety of chemicals. Indeed, according to Sparks and associates ²³, “[a] recommendation for long-term avoidance of chemical exposures is contraindicated. It is also impossible to accomplish.”

The patient should be encouraged to increase activity gradually, while keeping anxiety or other symptoms at tolerable levels. This can be accomplished by following a systematic plan of behavioral treatment, desensitizing the patient to the distress experienced in symptom-producing situations. Relaxation or breath-control exercises may be helpful, as well as teaching the patient that autonomic symptoms of arousal, such as palpitations and tremor, are not dangerous and that activity can persist despite their occurrence ²⁸.

Principles of management of multiple chemical sensitivity syndrome

• Above all, establish a respectful and empathetic physician-patient relationship principle goals:
  • Maximize rehabilitation
  • Control (not cure) symptoms
  • Treat concomitant psychiatric and somatic illness
• Encourage the following:
  • Activity as tolerated
  • Desensitization to symptom-producing situations
  • Relaxation exercises
  • Understanding that autonomic symptoms are not dangerous
• Avoid the following:
  • Unproven therapies such as antifungal medication (for “chronic candidiasis”)
  • Rotating diets
  • Extreme avoidance of chemicals
  • Isolation, social withdrawal
• If consultation is desired, contact an occupational and environmental health physician or the Association of Occupational and Environmental Clinics (http://www.aoec.org/).

References

1. Multiple Chemical Sensitivity Syndrome. Am Fam Physician. 1998 Sep 1;58(3):721-728. https://www.aafp.org/afp/1998/0901/p721.html
2. Gots RE. Multiple chemical sensitivities—public policy [Editorial]. J Toxicol Clin Toxicol. 1995;33:111–3.
3. American College of Occupational and Environmental Medicine. Position statement. Multiple chemical sensitivities, environmental tobacco smoke, and indoor air quality.
4. Rest KM. Advancing the understanding of multiple chemical sensitivity (MCS): overview and recommendations from an AOEC workshop. Toxicol Ind Health. 1992;8(4):1–13.
5. Miller CS. White paper. Chemical sensitivity: history and phenomenology. Toxicol Ind Health. 1994;10(4-5):253–76.
6. Cullen MR. The worker with multiple chemical sensitivities: an overview. Occup Med. 1987;2:655–61.
7. Miller CS. Chemical sensitivity: symptom, syndrome or mechanism for disease? Toxicology. 1996;111:69–86.
8. American Medical Association Council on Scientific Affairs. Clinical ecology. JAMA. 1992;268:3465–7.
9. American College of Physicians. Clinical ecology. Ann Intern Med. 1989;111:168–78.
10. Executive Committee of the American Academy of Allergy and Immunology. Clinical ecology. J Allergy Clin Immunol. 1986;78:269–71
11. Environmental Protection Agency, American Lung Association, Consumer Product Safety Commission, American Medical Association. Indoor air pollution: an introduction for health professionals. U.S. Government Printing Office Publication no. 1994-523-217/81322;
12. Environmental Protection Agency. Hazardous air pollutant list. Federal Register 1996;61(118):30816-23.
13. Neutra RR. Some preliminary thoughts on the potential contribution of epidemiology to the question of multiple chemical sensitivity. Public Health Rev. 1994;22:271–8.
14. Sparks PJ, Daniell W, Black DW, Kipen HM, Altman LC, Simon GE, et al. Multiple chemical sensitivity syndrome: a clinical perspective. I. Case definition, theories of pathogenesis, and research needs. J Occup Med. 1994;36:718–30 Published erratum in J Occup Med 1994;36:1334
15. Simon GE, Daniell W, Stockbridge H, Claypoole K, Rosenstock L. Immunologic, psychological, and neuropsychological factors in multiple chemical sensitivity. A controlled study. Ann Intern Med. 1993;119:97–103.
16. Wolf C. Multiple chemical sensitivities. Is there a scientific basis? Int Arch Occup Environ Health. 1994;66:213–6.
17. Friedman MJ. Neurobiological sensitization models of post-traumatic stress disorder: their possible relevance to multiple chemical sensitivity syndrome. Toxicol Ind Health. 1994;10(4–5):449–62.
18. Bell IR, Miller CS, Schwartz GE, Peterson JM, Amend D. Neuropsychiatric and somatic characteristics of young adults with and without self-reported chemical odor intolerance and chemical sensitivity. Arch Environ Health. 1996;51:9–21.
19. Simon GE. Psychiatric symptoms in multiple chemical sensitivity. Toxicol Ind Health. 1994;10(4-5):487–96.
20. Davidoff AL, Fogarty L. Psychogenic origins of multiple chemical sensitivities syndrome: a critical review of the research literature. Arch Environ Health. 1994;49:316–25.
21. Lax MB, Henneberger PK. Patients with multiple chemical sensitivities in an occupational health clinic: presentation and follow-up. Arch Environ Health. 1995;50:425–31.
22. Miller CS, Mitzel HC. Chemical sensitivity attributed to pesticide exposure versus remodeling. Arch Environ Health. 1995;50:119–29.
23. Sparks PJ, Daniell W, Black DW, Kipen HM, Altman LC, Simon GE, et al. Multiple chemical sensitivity syndrome: a clinical perspective. II. Evaluation, diagnostic testing, treatment, and social considerations. J Occup Med. 1994;36:731–7.
24. Staudenmayer H. Multiple chemical sensitivities or idiopathic environmental intolerances: psychophysiologic foundation of knowledge for a psychogenic explanation [Editorial]. J Allergy Clin Immunol. 1997;99:434–7.
25. Binkley KE, Kutcher S. Panic response to sodium lactate infusion in patients with multiple chemical sensitivity syndrome. J Allergy Clin Immunol. 1997;99:570–4.
26. Fiedler N, Kipen HM, DeLuca J, Kelly-McNeil K, Natelson B. A controlled comparison of multiple chemical sensitivities and chronic fatigue syndrome. Psychosom Med. 1996;58:38–49.
27. Simon GE. Psychiatric treatments in multiple chemical sensitivity. Toxicol Ind Health. 1992;8(4):67–72.
28. Guglielmi RS, Cox DJ, Spyker DA. Behavioral treatment of phobic avoidance in multiple chemical sensitivity. J Behav Ther Exp Psychiatry. 1994;25:197–209.