Multiple chemical sensitivity

Multiple chemical sensitivity (MCS), also known as idiopathic environmental intolerances (IEI), is an acquired, chronic, multi-system illness, in which people experience a range of symptoms in response to exposure to certain everyday chemicals.

A 2017 scientific review described MCS as "a complex syndrome that manifests as a result of exposure to a low level of various common contaminants." A 2019 review described the condition as an "acquired disorder characterized by recurrent symptoms, affecting multiple organs and systems, which arise in response to a demonstrable exposure to chemicals, even at low doses, much lower than those that would cause a reaction in the general population."

Chemicals that are common triggers for MCS symptoms include pesticides, petrochemicals, formaldehyde and fragranced products. Natural irritants like mold and wood-fire smoke are also often triggers.

MCS and ME
MCS has been described as a comorbidity of myalgic encephalomyelitis (ME), also known as myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS): However, MCS has its own specific diagnostic criteria, which do not include medication, food or odor sensitivities.
 * 1) The Canadian Consensus Criteria (2003) for diagnosing ME/CFS lists "new sensitivities to food, medications and/or chemicals" as a symptom and lists MCS as a comorbidity.
 * 2) The International Consensus Criteria (2011) for diagnosing ME lists "sensitivities to food, medications, odors or chemicals" as a symptom and lists MCS as a comorbidity.
 * 3) A 2019 publication of the U.S. ME/CFS Clinician Coalition lists "chemical sensitivity" as a symptom of ME/CFS and lists MCS as a commonly comorbid condition.

Signs and symptoms
In 1999, an international consensus on MCS was published in The Archives of Environmental Health. The consensus was the conclusion of a ten-year study by an international multidisciplinary team of 89 clinicians and researchers, with different points of view about MCS. What they agreed upon was that the clinical characteristics of MCS should be defined as follows: “[1] a chronic condition, [2] with symptoms that recur reproducibly, [3] in response to low levels of exposure, [4] to multiple and unrelated chemicals, and [5] improve or resolve when triggers are removed, [6] MCS involves symptoms in different organs.”

The symptoms of MCS affect multiple organs and body systems, range from mild to disabling  and decrease quality of life.

Common symptoms of MCS include headache, migraine, neurocognitive deficits, dizziness, fatigue, cardiac arrhythmia, tachycardia, hypotension, hypertension, gastrointestinal problems, nausea, vomiting, muscle and joint pain, skin rashes, visual disturbances, seizures, asthma and anaphylaxis.

A 2017 review of MCS studies said: “MCS is a syndrome that progresses to increasingly serious stages, with the gradual onset of multiple pathologies”.

The following substances are common triggers for adverse symptoms people with MCS:
 * pesticides (insecticides and herbicides), biocides and fungicides
 * agricultural chemicals, notably fertilizers
 * mold and mycotoxins
 * synthetic fragrances and products containing fragrance (eg. fragranced deodorant)
 * laundry detergents and fabric softeners
 * cigarette smoke and woodfire smoke
 * petrochemical solvents and plastics
 * formaldehyde
 * some building materials
 * preservatives, food colorings and additives (eg. Tartrazine)
 * some medications and anesthetics
 * air pollution (eg. black carbon, nitrogen oxide, ozone)
 * natural essential oils.

Diagnosis
The 1999 international consensus on MCS is still the primary set of criteria used to assess a patient for MCS. To receive an MCS diagnosis, the patient must satisfy all the following criteria: The patient has (1) a chronic condition (2) with symptoms that recur reproducibly (3) in response to low levels of exposure (4) to multiple and unrelated chemicals, (5) which improve or resolve when triggers are removed and (6) suggest a relation to different organs. The Quick Environmental Exposure and Sensitivity Inventory (QEESI), is a diagnostic tool that is often used to assess a patient for these criteria.

Treatment and management
At this time, there is no clinically proven cure for MCS. There is also no scientific consensus on supportive therapies for MCS, "but the literature agrees on the need for patients with MCS to avoid the specific substances that trigger reactions for them and also on the avoidance of xenobiotics in general, to prevent further sensitization."

There is also consensus that a multidisciplinary approach is required for adequately managing the health of someone with MCS. Some studies suggest a special focus on correcting any nutritional deficiencies may be beneficial.

To avoid their condition being aggravated or worsened while in hospital, patients with MCS require special adjustments around chemical use, medications and anesthetics in hospitals.

There is evidence that some patients with MCS have poor tissue oxygenation when exposed to triggers, likely because of oxidative stress or because neural inflammation has reduced blood flow. Breathing medical oxygen following accidental chemical exposures is a suggested remedy for these patients.

The 2019 consensus and clinical guidelines on MCS said that people with MCS "must be guaranteed, according to their individual needs and level of disability" medical oxygen and the necessary equipment to use it (that is, tubing and a mask from non-triggering materials).

The other aids the 2019 consensus said were necessary for patients with MCS to manage the functional impacts of their condition were: face masks (with HEPA and VOC filters), portable air purifiers for the home and for inside vehicles (made of metal, with HEPA and activated carbon filters) and water purifiers.

These aids may be especially important when sufferers live in areas where they are exposed to agricultural or urban pollution or smoke from forest fires or bushfires.

Epidemiology
Prevalence rates for MCS vary according to the diagnostic criteria used. What is clear is that the condition is reported across industrialized countries and it affects women more than men.

The most extensive epidemiological study into MCS in the United States was in 2005. It found that the national prevalence rate for MCS diagnosed by a doctor was 2.5% and self-reported MCS was 11.2%.

In 2018, the same researchers reported that the prevalence rate of diagnosed MCS had increased by more than 300% and self-reported chemical sensitivity by more than 200% in the previous decade. They found that 12.8% of those surveyed reported medically diagnosed MCS and 25.9% reported having chemical sensitivities.

A 2014 study by the Canadian Ministry of Health estimated, based on its survey, that 0.9% of Canadian males and 3.3% of Canadian females had a diagnosis of MCS by a health professional.

In Denmark, the Ministry of the Environment estimated in 2004 that 10% of the Danish population was sensitive to certain everyday chemicals and that 1% of the population had MCS to a level that was disabling.

While a 2018 study at the University of Melbourne found that 6.5% of Australian adults reported having a medical diagnosis of MCS and that 18.9% reported having adverse reactions to multiple chemicals. The study also found that for 55.4% of those with MCS, the symptoms triggered by chemical exposures could be disabling.

These findings suggest that, in the above countries, MCS is not a rare disease.

Causes
There is a lack of agreement among MCS researchers on the cause or causes of the condition.

In 2017, a Canadian government Task Force on Environmental Health said that there had been very little rigorous peer-reviewed research into MCS and almost a complete lack of funding for such research in North America. "Most recently," it said, "some peer-reviewed clinical research has emerged from centres in Italy, Denmark and Japan suggesting that there are fundamental neurobiologic, metabolic, and genetic susceptibility factors that underlie ES/MCS."

One of the most thorough academic reviews of MCS research to be undertaken was published in Italy in May 2019. It said that the current predominant hypotheses about the causes of MCS were: biochemical, neuro-physiological and related to the limbic system and genetic predisposition.

Some researchers say a consensus that the causes are multifactorial has been reached.

When speaking at an Australian federal parliamentary inquiry into environmental illness, Dr Graeme Edwards, the Royal Australasian College of Physicians' representative, said that there was "relatively good consensus" that causation was multifactorial. "There is no single causative factor," he said. "It is a combination of factors [...] unless you have all the pieces of the puzzle lining up, you actually don't get the disease. And because we are talking about multi-dimensional triggers, any one individual, at any one point in time, may not have exposure to all of those triggers to get a pathological result. And therein lies the complexity."

Toxicological
It has been hypothesized that MCS is caused by exposure to particular chemicals—most commonly certain pesticides.

Professor Martin L. Pall proposed that MCS had a toxicological and biochemical cause, and that "seven individual chemicals or chemical classes—organophosphorus/carbamate, organochloride and pyrethroid pesticides, organic solvents, carbon monoxide, hydrogen sulphide and mercury/mercurial compounds—could initiate MCS through their ability to increase N-methyl-D-aspartate (NMDA) receptor activity."

Pall hypothesized that overactivity of the NMDA receptors, coupled with stress-related increases in nitric oxide and the oxidative product peroxynitrite (known as the NO/ONOO cycle) caused MCS symptoms and worsened the condition. He suggested that hypersensitivity occurred because of limbic kindling, neural sensitization, and/or neurogenic inflammation—processes which could be driven by the NO/ONOO cycle.

A 2019 scientific review said that while further research was required to confirm Pall's theory, that his hypothesis "had found broad consensus in the scientific community” and was compatible with previous hypotheses, including Dr. Iris Bell's theory of neuronal sensitization and William Meggs’ theory of neurogenic inflammation. It also said that Pall's theory may explain the comorbidity of MCS and other pathologies hypothesized to be related to the same mechanism, including Fibromyalgia (FM) and Myalgic Encephalomyelitis / Chronic Fatigue Syndrome (ME/CFS), and that it might be why MCS symptoms tend to lessen after exposure to inhibitors and/or antagonists of NMDA receptors. The review also said that "pesticides, including herbicides, insecticides and agricultural chemicals, are among the substances most commonly implicated in the activation of MCS cases in the United States."

Pall's theory has also been used to explain why Gulf War veterans, particularly those who were exposed to organophosphate pesticides, have been found to be more likely to have MCS than the general population as well as the fact that chemical sensitivities are a known symptom reported in Gulf war syndrome or post-deployment syndrome.

The U.S. Department of Veterans Affairs concluded that "risk factors that may be associated with predisposing, precipitating, and perpetuating chronic multi system illnesses [including MCS] among veterans" included chemical exposure, and notably chemical exposure in the Gulf War, where some military personel were exposed to nerve agents (like sarin and cyclosarine) and toxic smoke.

Mold and mycotoxin exposures have also been hypothesized to trigger the onset of MCS. Exposure to mold has already been associated with initiating inflammation and higher incidences of certain chronic conditions (like asthma), which are common symptoms of MCS.

Neurological
Many common symptoms of MCS are neurological (for example, "dizziness, seizures, head pain, fainting, loss of coordination" ). And neurogenic inflammation and sensitization are widely thought to be mechanisms involved in causing, perpetuating and worsening MCS.

William Meggs said that neurogenic inflammation was a well-defined pathophysiological process, in which chemical irritants triggered nerve fibers to release inflammatory mediators, which led to disease. In a 2017 review, he said that with MCS, an initiating chemical exposure (commonly a respiratory irritant or pesticide) was usually identified in association with the onset of the disease.

Iris Bell researched brain-wave patterns in people with MCS. He showed, in several studies using Electroencephalograms (EEG), that people with MCS often had certain abnormal brain wave patterns. For example, he found that women with MCS were more likely to have greater resting alpha waves than controls, which he said suggested the possibility of central nervous system hypo-activation.

Multiple neuro-imaging studies have shown that people with MCS often have other neurological abnormalities, including abnormal cerebral perfusion patterns, especially in the autonomic nervous system areas. These abnormalities have been documented both in studies using PET (Positron Emission Tomography) and SPECT (Single Photon Emission Computed Tomography) scans.

In addition to people with MCS having documented neurological abnormalities, neuroplasticity is thought by some researchers to be an important mechanism in the disease. In 2018, a representative of the Royal Australasian College of Physicians said: “It could be a multiple chemical sensitivity phenomenon. It could be an irritable bowel phenomenon. It could be fibromyalgia... The common unifying features in all of these conditions is related to what we do know is happening, which is neuroplasticity in the nervous system. We know that, regardless of the initiating trigger—whether it was an overwhelming infection of a mould related organism or some other viral infection—it sets up, within the biological system called the nervous system, neuroplastic changes. They can be, and have been, documented by evidence based research. We can document that there are changes in the nervous system, and that change in the nervous system results in a change in the sensitivity and responsiveness of the human being.”

Immunological
MCS is not an allergy, and subjects with MCS having adverse reactions do not routinely exhibit the immune markers associated with allergies. Nevertheless, certain immune irregularities have been identified in subjects with MCS in a range of studies.

In the 1980s and 1990s, some researchers hypothesized that these immune irregularities suggested that MCS was caused by a chemically induced disturbance of the immune system, which resulted in chronic immune dysfunction. While others concluded that allergic or immunotoxicological reactions could be contributing factors in at least a subset of MCS patients. As more studies were conducted, however, some argued that there was no consistent pattern of immunological reactivity or abnormality in MCS.

More recently, a French study found that subjects with MCS had higher levels of histamine than controls. It also identified damage to the blood-brain barrier in MCS subjects, the production of antibodies against myelin and evidence of inflammatory processes involving the limbic system and thalamus. These findings led the research team to conclude that some level of immune activation was likely occurring in the condition.

There is also evidence that subjects with MCS are more likely than controls to have proper allergies and autoimmune diseases, and the 2019 consensus on MCS notes an association between the condition and Hashimoto's Thyroiditis, Systemic Lupus Erythematosus (SLE), psoriasis and atopic eczema.

Psychological
It has also been hypothesized that MCS is a psychiatric or psychosomatic disorder.

The main arguments used to support these theories have been: (1) there is no certainty about biological causes of MCS, therefore it must be psychological (2) that nocebo responses may operate in MCS and (3) that people with MCS are more likely than controls to have anxiety, depression and the personality trait absorption. These theories have attracted considerable criticism.

The 2019 Italian consensus on MCS concluded that the studies that hypothesize that the condition has a psychological cause "have been the object of strong criticism, both for methodological deficiencies as well as for the conflict of interests of the scientists who propose this thesis." It said there was consensus that MCS reactions could cause psychiatric symptoms through biological processes (eg. neurogenic inflammation) and that symptoms of the condition should not be mistaken for the cause. It also highlighted that "it was researchers at Johns Hopkins University who pointed out that it is ineffective to use personality tests such as MMP2 (i.e. Minnesota Multiphasic Personality Inventory 2) for the study of the pathogenesis of environmental diseases...concluding that the presence of psychological-psychiatric symptoms in patients with MCS was compatible with the objective limitations imposed by the disease, rather than being the cause."

Other researchers have emphasized that the psychosocial impacts of the disease (especially isolation and stigmatization) are likely to have significant impacts on mental health. One study showed that anxiety and depression typically started in people with MCS post onset of the condition.

The presence of nocebo responses in MCS does not indicate the cause of the disease. Nocebo responses are found in many biologically caused conditions, like asthma, and they are known to be especially pronounced in neurological conditions.

It is noteworthy that psychological approaches to care in MCS patients have had “very limited success,” and that neither MCS, MCS/ES nor IEI have been included in any edition of the DSM (American Psychiatric Association Diagnostic and Statistical Manual ) nor have they been listed among somatoform disorders in the International Classification of Diseases.

In Canada, in 2017, following a three-year government inquiry into environmental illness, it was recommended that a public statement be made by the health department dispelling the misperception that MCS/ES is psychological.

Genetic
The 2019 consensus on MCS said that the condition could, at least in part, be caused by genetic alterations affecting detoxification pathways—something which in combination with toxin exposures could make some people more vulnerable to developing MCS than the rest of the population.

Recent Italian studies found that compared to controls, patients with MCS had higher levels of the nitrites and nitrates that are involved in oxidative stress and inflammatory processes, including those that contribute to the oxidative damage of DNA. They also found that the presence of the following genetic polymorphisms were more likely in people with MCS than controls: NOS3, NOS2 and GPX1.

Other genetic markers known to affect detoxification pathways have been identified as being more common in subjects with MCS than controls,    including polymorphisms and differences in expression of the following: CYP2D6, NAT2, GSTM1, and PON1 and PON2.

These findings could support the hypothesis that MCS is caused by a synergy of environmental exposures to toxic substances and the impaired ability to metabolize toxic substances, due to factors related to genetic predisposition.

Recognition
MCS is not included as a separate, discrete disease by the World Health Organization's (WHO) index of diseases (ICD-11). However, existing disease codes can be used to codify the condition, including: "(1) J68.9: unspecified respiratory conditions due to inhalation of fumes, gas, and chemical vapors; and (2) T78.4: unspecified allergies (allergic reaction Nitrous Oxide System (NOS)-hypersensitivity NOS-idiosyncrasy NOS)."

In 1996, an expert panel at WHO/ICPS (International Classification for Patient Safety) was set up to examine MCS. The panel "accepted the existence of a disease of unclear pathogenesis" and proposed that the disease was acquired, that its symptoms were "in close relationship to multiple environmental influences, which are well tolerated by the majority of the population," and that "the condition could not be explained by a known clinical or psychic disorder." The panel also suggested that the broader term "idiopathic environmental intolerances" (IEI) be adopted instead of MCS, to incorporate MCS and several other conditions under a single umbrella term.

MCS is recognized as a discrete pathology, however, on some countries' national indexes of diseases, including in Germany, Austria and Japan. And in some countries, like Sweden, chemical sensitivities are classified as a form of sensory hyperreactivity (CSS-SHR).

And as mentioned above, chemical sensitivities are recognized symptoms of ME/CFS. In 2018 the U.S. Centers for Disease Control and Prevention (CDC) said that ME/CFS patients can have sensitivities to chemicals.

History
In 1956, American allergist Dr. Theron G. Randolph coined the term "environmental illness," to describe symptoms and disorders he observed in some of his patients after they were exposed to various unrelated chemical compounds.

Then in 1987, Dr. Mark R. Cullen, also an American allergist, introduced the term MCS in journals of occupational medicine. He proposed that MCS described: an acquired disorder, characterized by recurrent symptoms, affecting multiple organs and systems, which arose in response to a demonstrable exposure to chemicals, even for low doses, much lower than those causing reactions in the general population.

Two years later, an international multidisciplinary team of 89 clinicians and researchers commenced a study into MCS, which culminated in the first real international consensus on the condition being agreed upon and published in The Archives of Environmental Health in 1999.

In 1996, an expert panel of the World Health Organization/International Classification for Patient Safety (WHO/ICPS) accepted the existence of MCS as a health condition with a cause unknown, and suggested that it be called "idiopathic environmental intolerances"(IEI), a term that incorporates a number of conditions sharing similar symptoms.

In May 2019, the Italian Workgroup on MCS, a group of physicians, research scientists and clinical staff, published a detailed, 30-page consensus paper called the Italian Consensus on MCS. This document may be the most detailed scientific review of research about MCS to date, and it goes into considerable detail about ways the condition can be better managed in clinical environments, particularly in hospitals. The workgroup put their consensus out in Italian and English, asking for input from MDs and other health professionals, biologists and chemists. At the time of writing, the response to the consensus had not been published.

Occupational health and safety
Various organisations and workplaces have policies that include fragrance and/or chemical sensitivities as occupational health and safety (OH&S) issues.

The most significant of these may be the Centers for Disease Control and Prevention (CDC)—the largest health agency in the United States, which in 2009 issued an indoor air quality policy, which says: Common ingredients in synthetic fragrance are recognized as irritants for a range of respiratory conditions. The American Lung Association lists fragrance on their list of "indoor air pollutants" and recommends that healthy workplaces establish fragrance-free policies for employees and visitors." With this in mind, some experts have called for fragrance-free policies in hospitals and healthcare settings, and in some countries (like Sweden and Canada) these already exist.
 * 1) "Scented or fragranced products are prohibited at all times in all interior space owned, rented, or leased by CDC;"
 * 2) "CDC encourages employees to be as fragrance-free as possible when they arrive in the workplace...Employees should avoid using scented detergents and fabric softeners on clothes worn to the office. Many fragrance-free personal care and laundry products are easily available and provide safer alternatives;" and
 * 3) "Fragrance is not appropriate for a professional work environment, and the use of some products with fragrance may be detrimental to the health of workers with chemical sensitivities, allergies, asthma, and chronic headaches/migraines."

Controversy
MCS sufferers and the physicians treating them have been subject to campaigns aimed at undermining the veracity of the condition. This has particularly played out in the media and on Wikipedia.

The blogs Quackwatch and Science-Based Medicine (SBM)—related blogs dominated by the same brand of skepticism —are two groups known to have repeatedly published criticism about MCS's recognition as a medical condition.

The criticisms of Quackwatch/SBM, however, are at odds with: (1) the current medical consensus about MCS,    (2) conclusions of the most recent academic reviews of MCS research, published in respected scientific journals, and (3) the recognition of the condition by the WHO/ICPS, national and state health agencies, hospitals and physicians' organizations.

Some legal actions (including defamation suits in the U.S.) have alleged that Quackwatch and its founder—who has written prolifically about MCS—have been actively and knowingly promoting inaccurate information on a range of medical conditions on Wikipedia. In 2003, a California Appeals Court found Quackwatch's founder “to be biased and unworthy of credibility.”

In popular culture
Safe (1995), a cult film by director Todd Haynes is an iconic depiction of MCS.

Voted best film of the nineties by The Village Voice Film Poll, and described by critics as ”the scariest film of the year”, “a mesmerizing horror movie” and “a work of feminist counter-cinema,” Safe depicts MCS as a destabilizing and alienating condition.

Protagonist Carol White, played by Julianne Moore, is a quiet and subdued housewife, who suddenly develops a range of symptoms following the renovation of her home, in an affluent suburb of polluted Los Angeles. As Carol’s symptoms worsen, the chemicals that are triggering them seem ubiquitous.

Carol's condition isn't given a name in the film, but Haynes has said he is depicting MCS. Doctors are at a loss of how to cure or help Carol. She is initially referred for psychotherapy, but it doesn't improve her symptoms.

Her husband is skeptical; her community, who seem dubious that MCS is real, are indifferent and unsupportive.

So Carol leaves her home, possessions and world behind, and without her husband, moves to an eerie desert community for people with environmental illness. The community is strange, and it's led by a man who seems to blame the residents for the illnesses they developed.

“She is so excruciatingly alone,” Moore said of her character at the end of the film. While Haynes said Carol’s isolation was both the answer and the problem for her.

Twenty years after the film’s release, Haynes said its themes—disease and immunity in a post-industrial landscape and how recovery is a burden often put on victims of illness—were even more relevant than they were when he made the film.

Learn more

 * 2010, Allergies and Multiple Chemical Sensitivity in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome
 * 2016, Multiple Chemical Sensitivity in Fibromyalgia, ME/CFS
 * 2016, Multiple Chemical Sensitivity