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 2018 scientific review said MCS was "a complex syndrome that manifests as a result of exposure to a low level of various common contaminants."

While a 2019 consensus paper on MCS defined 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 doses much lower than would cause a reaction in the general population.

Common triggers for MCS symptoms include pesticides, fragranced products, petrochemicals, formaldehyde and mold.

Signs and symptoms

There is a consensus that the symptoms of MCS affect multiple organs and body systems, that symptoms range from mild to severely disabling, and decrease quality of life.

Symptoms of MCS can include headache, migraine, neurocognitive deficits, dizziness, fatigue, cardiac arrhythmia, tachycardia, hypotension, hypertension (high blood pressure), gastrointestinal problems, nausea, vomiting, muscle and joint pain, skin rashes, hives, visual disturbances, seizures, and asthma. And a 2010 review of MCS research said that the following symptoms, in this order, were the most reported in MCS: headache, fatigue, confusion, depression, shortness of breath, arthralgia, myalgia, nausea, dizziness, memory problems, gastrointestinal symptoms, respiratory symptoms.

A 2017 review of MCS studies said: “MCS is a syndrome that progresses to increasingly serious stages, with the gradual onset of multiple pathologies." It can be associated with very high levels of disability.

What triggers multiple chemical sensitivity symptoms? Everyday personal care products, particularly fragranced products, are common triggers and their near-ubiquitous use makes many public spaces inaccessible to people with severe sensitivities. To address this, fragrance-free policies are becoming more common, especially in healthcare settings. The U.S. Centers for Disease Control has been fragrance free since 2009.

Chemicals that trigger symptoms

The following substances are common triggers for adverse symptoms in people with MCS:

• pesticides (insecticides and herbicides), biocides and fungicides
• agricultural chemicals, notably fertilizers
• mold and mycotoxins
• synthetic fragrances and products containing fragrance (e.g. 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 (e.g. tartrazine)
• some medications and anesthetics
• air pollution (e.g. black carbon, nitrogen oxide, ozone)
• natural essential oils.

Diagnosis and diagnostic criteria

Research papers have concluded that knowledge and education about MCS among health professionals is lacking and that this commonly results in delays in the diagnosis and poor management of the condition.

International Consensus Criteria 1999

The 1999 international consensus on MCS is the most commonly used diagnostic criteria for MCS. The consensus is based on the Cullen criteria plus a ten-year study by an international multidisciplinary team of 89 clinicians and researchers with different points of view about MCS. MCS is defined as:

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. with symptoms which occur in multiple organ systems.

Lacour criteria 2005

1. symptom duration of at least 6 months
2. symptoms in response to at least 2 of 11 categories of chemical exposures
3. at least one central nervous system symptom is present (eg fatigue, headaches or neurocognitive deficits, and one symptom from another organ system
4. symptoms causing adjustments of personal lifestyle, or of social or occupational life
5. symptoms occurring when exposed and improving or resolving when exposures are removed
6. symptoms are triggered by exposure levels that do not induce symptoms in other individuals who are exposed to the same levels

Diagnostic tools

The Quick Environmental Exposure and Sensitivity Inventory (QEESI) is a diagnostic tool that is often used to assess a patient for these criteria.

Differential diagnosis

A series of tests are needed to identify other potential causes of the symptoms. Particularly important to rule out are:

• Porphyrias
• Mastocytosis including systematic mastocytosis

Prevalence

Multiple chemical sensitivity is not a rare disease. Some studies show it is increasing in prevalence.

While prevalence rates for MCS vary according to the diagnostic criteria used, the condition is reported across industrialized countries and the data suggests it affects women more than men.

The most extensive epidemiological study into MCS in the U.S. 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.

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

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.

While a 2018 study at the University of Melbourne found that 1 million Australians (6.5% of 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.

Recognition

In 1996, an expert panel at WHO/ICPS (International Classification for Patient Safety) was set up to examine MCS. The panel:

1. "accepted the existence of a disease of unclear pathogenesis",
2. 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 it "could not be explained by a known clinical or psychic disorder,"
3. 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 not included as a separate, discrete disease by the World Health Organization's (WHO) index of diseases (ICD-11). However, existing disease codes in the ICD-10 can be used for MCS, 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 the ICD-10-DM and ICD-10-SGB-V, Germany's adaptions of the ICD-10, multiple chemical sensitivity is recognized as a chemical hypersensitivity or intolerance (Chemical-Sensitivity[MCS]-Syndrom, Multiple-) under the code T78.4; this is also in use in Austria. Japan also recognizes MCS as a separate disease. And in some countries, like Sweden, chemical sensitivities are classified as a form of sensory hyperreactivity (CSS-SHR). In 2012, Denmark introduced code DR688A1 for Symptoms related to chemicals and scents (Symptomer relateret til dufte og kemiske stoffer fra SKS), in the Medically Unexplained Symptoms, under R68.8 Other specified general symptoms and signs.

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.

Treatment

Is there a cure for multiple chemical sensitivity? At this time, there is no clinically proven cure. There is agreement that people with MCS need to avoid triggers to reduce symptoms and the likelihood of the condition worsening over time, which typically happens without avoidance. Medical Oxygen has been shown to reduce the severity of reactions and temporarily improve tolerance in some people.

There is no clinically proven cure for MCS. There is also no scientific consensus on supportive therapies, "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."

A study, which surveyed more than 900 people with MCS about their experiences managing the condition, found that 95% of respondents thought that "creating a chemical-free living space and chemical avoidance" had been the best strategy out of any management or treatment option they had tried.

There is also consensus that a multidisciplinary approach is required for adequately managing the health of someone with MCS.

There is evidence that some patients with MCS might have poor tissue oxygenation when exposed to triggers, perhaps because of oxidative stress or because neural inflammation has reduced blood flow. Breathing medical oxygen following accidental chemical exposures helps some people. 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.

Accessibility needs

People with MCS typically experience significant access barriers to society and accessing services. They are also commonly subject to stigma and lack of understanding, perhaps because the condition is poorly understood. Nevertheless, it is recognised as a disability. For example, "a growing number of people report being affected by sensitivity to chemicals used in the building, maintenance and operation of premises," according to the Australian Human Rights and Equal Opportunity Commission. "This can mean that premises are effectively inaccessible to people with chemical sensitivity.”

Various organisations and workplaces have policies which cite chemical or fragrance sensitivities as a disability access or occupational health and safety issue. The most influential of these may be the indoor air quality policy of the U.S. Centers for Disease Control and Prevention (CDC), which says:

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."

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 have called for fragrance-free policies in hospitals and healthcare settings.

There is anecdotal evidence of people with MCS facing significantly higher levels of disability as a direct result of certain Covid-19 policies. This is said to be "due to greater exposure to disinfectants and fragranced products as well as increased barriers to essential needs such as food and healthcare."

Hospital care

Hospitals with fragrance-free policies are common in Canada and Sweden. Canadian examples include:

• Mount Sinai Hospital has a fragrance-free policy, which says the hospital "is committed to providing a safe and inclusive environment for all and will strive to eliminate the use of products with scents and fragrances to prevent any adverse reactions in patients, staff and other people working and/or visiting the hospital premises."
• Kingston General Hospital is fragrance free "for the safety and comfort of those with allergies and sensitivities," and its web site says "other items that you should not use or bring when you visit the hospital include: perfumes and colognes, scented fabric softeners, stain removers and laundry detergents, scented soaps and deodorant, scented shampoos and hair products, scented body powders and lotions."

As well as fragrance-free policies, to prevent adverse reactions and improve health outcomes in hospital settings, patients with MCS often require adjustments in chemical use, medications and anesthetics.

Some states and regions have specific policies for the hospital care of patients with MCS. For example, in Australia, three states and a territory have detailed hospital policies for patients with MCS. As well, some individual hospitals have their own policies for MCS patients.

Housing

People with MCS commonly encounter difficulties finding housing that is suitable and accessible for their condition; and as a result, homelessness is a systemic problem for those with the condition.

A 2002 housing survey of people with MCS in the United States found that:

• 57% of respondents had experienced homelessness during their illness (compared to 1% of the general population reporting having experienced homeless in their lifetime)
• 25% had lived in a car (nine months average)
• 15% had lived in a tent (eight months average)
• 73% of respondents had lived in a house that made them sick
• 47% said they were spending more than they could afford on accessible housing
• 43% said their current housing was neither accessible nor permanent.

While a 2019 survey in Australia found that 55.2% of respondents with chemical sensitivities reported suffering hardship accessing safe and affordable housing.

A 2016 academic review about the psychosocial impacts of environmental sensitivities found that “as persons acquire sensitivities, it becomes more and more difficult [for them] to find or maintain housing that does not exacerbate the condition." It also said two-thirds of people with environmental sensitivities had reported having had to live in "unusual circumstances" as a result of their condition at some period of their illness.

A 2019 report from Canada about human rights' issues faced by people with environmental illness said: “In focus groups, participants with environmental health disabilities voiced significant concerns about the barriers they experience in finding and maintaining accessible and affordable rental housing". Some of these included:

• mold
• carpet
• fumes from paint
• pesticide residue
• fumes from [nearby] laundry facilities
• fumes from cleaning products in common areas and
• cigarette smoke.

People with MCS suffer as a result of their lack of access to safe housing, according to a 2018 government inquiry from Ontario, Canada. The inquiry concluded that in society at large, there was little recognition of how serious and severe environmental illness could be and that there was "a discouraging shortage of services and supports" for people living with conditions like MCS. It also found that people with environmental illness commonly experienced stigma, including from landlords, who were "often skeptical about the severity and impact of their conditions.”

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. It goes into detail about ways the condition can be better managed in clinical environments, particularly in hospitals. The workgroup published their consensus 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.

Possible causes

MCS patients versus controls: VOCs in breath
Basal exhaled VOCs data for MCS and controls, acquired with the ORT-VOC, are shown in a density plot.
Source: Mazzatenta et al. (2021). Physiological Reports, 9, e15034.

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 (Environmental Sensitivities)/MCS."

The Italian consensus on MCS of 2019 said that the current consensus for the cause of MCS is that it likely has multiple causes: biochemical, neuro-physiological, causes related to the limbic system and perhaps also genetic predisposition.

When speaking at an Australian federal parliamentary inquiry into environmental illness, in 2018, Dr Graeme Edwards, the inquiry's representative of Royal Australasian College of Physicians 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."

These recent statements suggest that earlier depictions of MCS as being either biologically or psychologically caused likely set up a false dichotomy or divide.

In 2021, a small study by Mazzatenta and colleagues found breath analysis of key volatile organic compounds (VOCs) differed between MCS patients and healthy controls, raising the possibility that breath analysis may be able to diagnose MCS in future. Breath analysis can already be used to aid diagnosis for some illnesses.

Toxicological

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

The Toxicant-Induced Loss of Tolerance (TILT) hypothesis proposed by Miller (1996) uses the name TILT for multiple chemical sensitivity, and describes a two-phase process. First, there is either a single major exposure to chemicals or many smaller exposures, which then result in chemical intolerance or sensitization. In the second phase, low or very low levels of exposure to chemicals cause symptoms that did not occur before sensitization. According to the TILT hypothesis, food and medication intolerances frequently occur along with chemical sensitivity. Miller (2021) believes that Mast Cell Activation Syndrome may account for TILT/MCS.

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."

Is multiple chemical sensitivity caused by pesticides? Some MCS researchers think it often is. The most recent consensus paper on MCS (2019) said this hypothesis "had found broad consensus in the scientific community” and was compatible with previous hypotheses.

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, 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 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 a central sensitization syndrome have been 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 Electroencephalography (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 Positron emission tomography (PET) and Single-photon emission computed tomography (SPECT) 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 real 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 multiple chemical sensitivity is a psychological disorder. Psychosomatic, psychiatric and psychological theories of MCS, however, have not been accepted by the most recent medical consensus document on MCS, and the hypothesis that MCS has psychological causes has flaws.

The arguments used to support the hypothesis that MCS has psychological causes 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.

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 (e.g. 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 that it is the cause of the disease. Nocebo responses are found in many biologically caused conditions, including asthma, and they have been shown to be especially pronounced in neurological conditions (including migraine and chronic pain).

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, MTHFR, NAT1, 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.

COVID-19 and Long COVID

There have been anecdotal reports of people with Long COVID, or chronic COVID, developing new allergies, including fragrance and other chemical sensitivities.

ME/CFS and multiple chemical sensitivity

MCS has been called a common comorbidity of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) by several consensus documents:

1. The Canadian Consensus Criteria (2003) for ME/CFS lists "new sensitivities to food, medications and/or chemicals" as a symptom and MCS as a comorbidity;
2. The International Consensus Criteria (2011) for Myalgic Encephalomyelitis lists "sensitivities to food, medications, odors or chemicals" as a symptom and MCS as a comorbidity; and
3. The U.S. ME/CFS Clinician Coalition publication Diagnosing and Treating Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) (2020) lists "chemical sensitivity" as a symptom of ME/CFS, and MCS as a comorbidity.

ME/CFS patients who also have MCS are more likely to face difficulties and complexities associated with accessing healthcare, supportive services and accommodation than those who don't. As well, if they have problems tolerating medications, this could complicate the management of their ME/CFS symptoms

Controversy

MCS sufferers and the physicians treating them have been subject to campaigns aimed at undermining the reality of the illness. This has played out in academia and in the media—and, perhaps with the greatest impact on sufferers, on Wikipedia. These efforts have created a perception that MCS is a controversial or disputed condition, which is not supported by recent academic reviews of MCS research.

Some say chemical industry interest groups have funded these efforts, and indeed some of the most vocal writers with anti-MCS stances have also been industry-paid expert witnesses in legal cases involving alleged chemical injuries.

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, claiming MCS was a "bogus", "fad" or "spurious" diagnosis. Quackwatch's founder, retired psychiatrist Stephen Barrett, has personally written prolifically on the subject of MCS.

Important contexts for these efforts are that: (1) legal actions—including defamation suits in the U.S.—have alleged that Quackwatch and Barrett have been actively and knowingly promoting inaccurate information on a range of medical conditions on Wikipedia (of note, in 2003, a California Appeals Court, for example, found Quackwatch's founder “to be biased and unworthy of credibility”); and (2) in academia, a 2019 consensus on MCS concluded that the studies that hypothesized MCS was a psychogenic disorder had been the object of strong criticism, in part, for "the conflict of interests of the scientists who proposed this thesis."

While those who have argued that MCS isn't real or is psychologically caused have undoubtedly successfully influenced popular perceptions about the condition, their commentaries are at odds with: (1) the current medical consensus about MCS, (2) conclusions of the most recent academic reviews of MCS research in scientific journals, and (3) the recognition of the condition by the WHO/ICPS and by other national and state health agencies, physicians' organizations and hospitals.

In the media

Safe (1995)

Is multiple chemical sensitivity a mental illness? This is a question some critics thought director Todd Haynes was posing in his 1995 film Safe. The film tells the story of Carol, who suddenly develops a mysterious and unexplained environmental illness, and receives little sympathy from her husband and community. But Haynes said that he used MCS as a metaphor for AIDS, and how AIDS sufferers in the 1980s were regarded and treated. In the film he explores stigma, alienation and isolation.

Safe is a cult horror film, by writer and director Todd Haynes, known for its depiction of MCS as a profoundly alienating and destabilizing condition.

It tells the story of Carol White, played by Julianne Moore, a homemaker in Los Angeles, who suddenly develops a range of unexplained symptoms following the renovation of her home.

With severe symptoms, which doctors are unable to treat, and a largely indifferent and unsupportive community, Carol ultimately leaves her home and moves to a desert community for people with environmental illness.

“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.

Early in the Covid-pandemic, Carol's isolation was compared to the psychosocial experience of lockdowns..

Afflicted docuseries (2018)

Netflix's 2018 documentary series Afflicted features several patients with MCS.

After its release, Afflicted was accused of misrepresenting patients with chronic illnesses, with several people who featured in the series suing Neflix for defamation.

An open letter to Netflix, signed by over 40 doctors, medical professionals and patient advocates, accused the media-services provider and production company of presenting flawed medical and scientific information. It also said unethical journalistic methods were used in the making of the series and called for it to be taken off Netflix.

Notable studies and publications

• 1987, Cullen, M.R. The worker with multiple chemical sensitivities: An overview - (Abstract)

• 1999, Multiple chemical sensitivity: a 1999 consensus - (Full text)
• 2005, Multiple Chemical Sensitivity Syndrome (MCS) – suggestions for an extension of the US MCS-case definition - (Abstract)

• 2014, Toxicant-Induced Loss of Tolerance: A Theory to Account for Multiple Chemical Sensitivity (Full text)
• 2016, Association of Odor Thresholds and Responses in Cerebral Blood Flow of the Prefrontal Area during Olfactory Stimulation in Patients with Multiple Chemical Sensitivity - (Full text)
• 2018, Multiple Chemical Sensitivity: Review of the State of the Art in Epidemiology, Diagnosis, and Future Perspectives - (Full text)
• 2018, Perspectives on multisensory perception disruption in idiopathic environmental intolerance: a systematic review - (Abstract)
• 2019, Italian Consensus on Multiple Chemical Sensitivity (MCS) -- Consensus Document and Guidelines on Multiple Chemical Sensitivity (MCS) - (Full text - English)

• 2019, International prevalence of chemical sensitivity, co-prevalences with asthma and autism, and effects from fragranced consumer products - (Full text)
• 2021, Volatile organic compounds (VOCs) in exhaled breath as a marker of hypoxia in multiple chemical sensitivity - (Full text)
• 2021, Mast cell activation may explain many cases of chemical intolerance (Full text)
• 2021, Multiple Chemical Sensitivity (Full text)

News articles and interviews

• 2017, The case against fragrance: The potential harm of our perfumed world - New Zealand Listener

• 2018, MCS--the condtion that affects one million Australia - SBS television, Australia (Video)
• 2019, Fragrance sensitivity: why perfumed products can cause profound health problems - The Guardian

• 2020, Common chemical products making Australians sick, study finds - Melbourne University Press
• 2020, Are scented cleaning products making you sick? - Stuff NZ
• 2021, The unusual headaches that upended this man's life began with a new car - The Washington Post
• 2021, Experts ‘disturbed’ over toxic discovery in popular makeup products - Sydney Morning Herald

See also

• Toxicant-induced loss of tolerance (TILT)
• Mast cell activation syndrome
• Sick building syndrome
• Mold illness
• Gulf War Illness
• New allergies and intolerances
• Psychologization

Learn more

• Multiple Chemical Sensitivity (book chapter) - Malcolm Hooper
• 2010, Allergies and Multiple Chemical Sensitivity in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome - Margaret Williams
• 2019, Italian Consensus on Multiple Chemical Sensitivity (English translation)
• Idiopathic environmental intolerance - MSD Manuals

Centers for Disease Control and Prevention (CDC) - The Centers for Disease Control and Prevention is a U.S. government agency dedicated to epidemiology and public health. It operates under the auspices of the Department of Health and Human Services.

mycotoxin "a poisonous substance produced by a fungus and especially a mold"

adverse reaction Any unintended or unwanted response to a treatment, whether in a clinical trial or licensed treatment. May be minor or serious.

World Health Organization (WHO) - "A specialized agency of the United Nations that is concerned with public health. It was established on 7 April 1948, and is headquartered in Geneva, Switzerland. The WHO is a member of the United Nations Development Group. Its predecessor, the Health Organization, was an agency of the League of Nations." The International Statistical Classification of Diseases and Related Health Problems (ICD) is maintained by WHO.

See World Health Organization.

International Classification of Diseases (ICD) - A system of medical diagnostic codes, created by the World Health Organization (WHO), to classify diseases and other health related conditions for the purpose of international diagnostic consistency. By having common diagnostic codes around the world, health researchers are better able to quantify and track disease burdens. The most current version is called ICD-11. (Learn more: www.who.int)

International Classification of Diseases (ICD) - A system of medical diagnostic codes, created by the World Health Organization (WHO), to classify diseases and other health related conditions for the purpose of international diagnostic consistency. By having common diagnostic codes around the world, health researchers are better able to quantify and track disease burdens. The most current version is called ICD-11. (Learn more: www.who.int)

See myalgic encephalomyelitis.

See chronic fatigue syndrome.

Centers for Disease Control and Prevention (CDC) - The Centers for Disease Control and Prevention is a U.S. government agency dedicated to epidemiology and public health. It operates under the auspices of the Department of Health and Human Services.

See Centers for Disease Control and Prevention.

Concerning living organisms, such as cells or the human body.  Physio logical (as in physio) is not to be confused with psych ological (emotional stress).

physiological Concerning living organisms, such as cells or the human body.  Physio logical (as in physio) is not to be confused with psych ological (emotional stress).

The limbic system is a group of structures between the forebrain and hindbrain mostly linked to emotions, memories and behavior. Includes the amygdala, limbic cortex, hypothalamus, cingulate gyrus, parahippocampal gyrus, hippocampus and hippocampal formation, dentate gyrus, subicular complex and septal area.

limbic system The limbic system is a group of structures between the forebrain and hindbrain mostly linked to emotions, memories and behavior. Includes the amygdala, limbic cortex, hypothalamus, cingulate gyrus, parahippocampal gyrus, hippocampus and hippocampal formation, dentate gyrus, subicular complex and septal area.

antagonist A chemical that reduces or helps block the activity of another chemical in the body. For example, most antihistamines are H1 antagonists because they block the H1 histamine receptor, which helps relieve allergy symptoms. The opposite of an agonist.

"a poisonous substance produced by a fungus and especially a mold"

mycotoxin "a poisonous substance produced by a fungus and especially a mold"

central nervous system (CNS) - One of the two parts of the human nervous system, the other part being the peripheral nervous system. The central nervous system consists of the brain and spinal cord, while the peripheral nervous system consists of nerves that travel from the central nervous system into the various organs and tissues of the body.

1. of or relating to the brain or the intellect 2. of, relating to, affecting, or being the cerebrum.}

cerebral 1. of or relating to the brain or the intellect 2. of, relating to, affecting, or being the cerebrum.

antibodies Antibody/immunoglobulin refers to any of a large number of specific proteins produced by B cells that act against an antigen in an immune response.

antibodies Antibody/immunoglobulin refers to any of a large number of specific proteins produced by B cells that act against an antigen in an immune response.

somatic symptom disorder A psychiatric term to describe an alleged condition whereby a person's thoughts somehow cause physical symptoms. The actual existence of such a condition is highly controversial, due to a lack of scientific evidence. It is related to other psychiatric terms, such as "psychosomatic", "neurasthenia", and "hysteria". Older terms include "somatization", "somatoform disorder", and "conversion disorder". Such terms refer to a scientifically-unsupported theory that claims that a wide range of physical symptoms can be created by the human mind, a theory which has been criticized as "mind over matter" parapsychology, a pseudoscience.

Diagnostic and Statistical Manual of Mental Disorders (DSM) - A psychiatric reference book published by the American Psychiatric Association, often referred to as "the psychiatrist's Bible". Although the most recent version (DSM-5) purports to be the authoritative guide to the diagnosis of mental disorders, the editors of both previous versions of the manual have heavily criticized the current version due to the climate of secrecy that shrouded the development of the latest version. 69% of the people who worked on DSM-5 reported having ties to the pharmaceutical industry. Dr. Allen Frances, who headed the development of the previous version, warned of dangerous unintended consequences such as new false 'epidemics'. The British Psychological Society criticized DSM-5 diagnoses as "clearly based largely on social norms, with 'symptoms' that all rely on subjective judgements" and expressed a major concern that "clients and the general public are negatively affected by the continued and continuous medicalisation of their natural and normal responses to their experiences". A petition signed by over 13,000 mental health professionals stated that the lowered diagnostic thresholds in DSM-5, combined with entirely subjective criteria based on western social norms, would "lead to inappropriate medical treatment of vulnerable populations". The director of the US National Institute of Mental Health, Dr. Thomas R. Insel, pointed out that the diagnoses in DSM-5 had no scientific validity whatsoever. (Learn more: www.scientificamerican.com)

(APA) - The main professional organization of psychiatrists and trainee psychiatrists in the United States, and the largest psychiatric organization in the world. Not to be confused with the American Psychological Association (also APA).

American Psychiatric Association (APA) - The main professional organization of psychiatrists and trainee psychiatrists in the United States, and the largest psychiatric organization in the world. Not to be confused with the American Psychological Association (also APA).

Diagnostic and Statistical Manual of Mental Disorders (DSM) - A psychiatric reference book published by the American Psychiatric Association, often referred to as "the psychiatrist's Bible". Although the most recent version (DSM-5) purports to be the authoritative guide to the diagnosis of mental disorders, the editors of both previous versions of the manual have heavily criticized the current version due to the climate of secrecy that shrouded the development of the latest version. 69% of the people who worked on DSM-5 reported having ties to the pharmaceutical industry. Dr. Allen Frances, who headed the development of the previous version, warned of dangerous unintended consequences such as new false 'epidemics'. The British Psychological Society criticized DSM-5 diagnoses as "clearly based largely on social norms, with 'symptoms' that all rely on subjective judgements" and expressed a major concern that "clients and the general public are negatively affected by the continued and continuous medicalisation of their natural and normal responses to their experiences". A petition signed by over 13,000 mental health professionals stated that the lowered diagnostic thresholds in DSM-5, combined with entirely subjective criteria based on western social norms, would "lead to inappropriate medical treatment of vulnerable populations". The director of the US National Institute of Mental Health, Dr. Thomas R. Insel, pointed out that the diagnoses in DSM-5 had no scientific validity whatsoever. (Learn more: www.scientificamerican.com)

somatic symptom disorder A psychiatric term to describe an alleged condition whereby a person's thoughts somehow cause physical symptoms. The actual existence of such a condition is highly controversial, due to a lack of scientific evidence. It is related to other psychiatric terms, such as "psychosomatic", "neurasthenia", and "hysteria". Older terms include "somatization", "somatoform disorder", and "conversion disorder". Such terms refer to a scientifically-unsupported theory that claims that a wide range of physical symptoms can be created by the human mind, a theory which has been criticized as "mind over matter" parapsychology, a pseudoscience.

myalgic encephalomyelitis (M.E.) - A disease often marked by neurological symptoms, but fatigue is sometimes a symptom as well. Some diagnostic criteria distinguish it from chronic fatigue syndrome, while other diagnostic criteria consider it to be a synonym for chronic fatigue syndrome. A defining characteristic of ME is post-exertional malaise (PEM), or post-exertional neuroimmune exhaustion (PENE), which is a notable exacerbation of symptoms brought on by small exertions. PEM can last for days or weeks. Symptoms can include cognitive impairments, muscle pain (myalgia), trouble remaining upright (orthostatic intolerance), sleep abnormalities, and gastro-intestinal impairments, among others. An estimated 25% of those suffering from ME are housebound or bedbound. The World Health Organization (WHO) classifies ME as a neurological disease.

bias Bias in research is "a systematic deviation of an observation from the true clinical state". (Learn more: me-pedia.org)

chronic illness any long-term illness, regardless of the severity. Chronic illnesses are typically incurable, requiring long-term management.

cerebral 1. of or relating to the brain or the intellect 2. of, relating to, affecting, or being the cerebrum.

limbic cortex Part of the brain (within the cerebral cortex) involved in emotion, memory and behavior. Part of the limbic system.

physiological Concerning living organisms, such as cells or the human body.  Physio logical (as in physio) is not to be confused with psych ological (emotional stress).

metabolite A chemical compound produced by, or involved in, metabolism. The term is often used to refer to the degradation products of drugs in the body.

(DSM) - A psychiatric reference book published by the American Psychiatric Association, often referred to as "the psychiatrist's Bible". Although the most recent version (DSM-5) purports to be the authoritative guide to the diagnosis of mental disorders, the editors of both previous versions of the manual have heavily criticized the current version due to the climate of secrecy that shrouded the development of the latest version. 69% of the people who worked on DSM-5 reported having ties to the pharmaceutical industry. Dr. Allen Frances, who headed the development of the previous version, warned of dangerous unintended consequences such as new false 'epidemics'. The British Psychological Society criticized DSM-5 diagnoses as "clearly based largely on social norms, with 'symptoms' that all rely on subjective judgements" and expressed a major concern that "clients and the general public are negatively affected by the continued and continuous medicalisation of their natural and normal responses to their experiences". A petition signed by over 13,000 mental health professionals stated that the lowered diagnostic thresholds in DSM-5, combined with entirely subjective criteria based on western social norms, would "lead to inappropriate medical treatment of vulnerable populations". The director of the US National Institute of Mental Health, Dr. Thomas R. Insel, pointed out that the diagnoses in DSM-5 had no scientific validity whatsoever. (Learn more: www.scientificamerican.com)

Diagnostic and Statistical Manual of Mental Disorders (DSM) - A psychiatric reference book published by the American Psychiatric Association, often referred to as "the psychiatrist's Bible". Although the most recent version (DSM-5) purports to be the authoritative guide to the diagnosis of mental disorders, the editors of both previous versions of the manual have heavily criticized the current version due to the climate of secrecy that shrouded the development of the latest version. 69% of the people who worked on DSM-5 reported having ties to the pharmaceutical industry. Dr. Allen Frances, who headed the development of the previous version, warned of dangerous unintended consequences such as new false 'epidemics'. The British Psychological Society criticized DSM-5 diagnoses as "clearly based largely on social norms, with 'symptoms' that all rely on subjective judgements" and expressed a major concern that "clients and the general public are negatively affected by the continued and continuous medicalisation of their natural and normal responses to their experiences". A petition signed by over 13,000 mental health professionals stated that the lowered diagnostic thresholds in DSM-5, combined with entirely subjective criteria based on western social norms, would "lead to inappropriate medical treatment of vulnerable populations". The director of the US National Institute of Mental Health, Dr. Thomas R. Insel, pointed out that the diagnoses in DSM-5 had no scientific validity whatsoever. (Learn more: www.scientificamerican.com)

See Diagnostic and Statistical Manual of Mental Disorders.

Diagnostic and Statistical Manual of Mental Disorders (DSM) - A psychiatric reference book published by the American Psychiatric Association, often referred to as "the psychiatrist's Bible". Although the most recent version (DSM-5) purports to be the authoritative guide to the diagnosis of mental disorders, the editors of both previous versions of the manual have heavily criticized the current version due to the climate of secrecy that shrouded the development of the latest version. 69% of the people who worked on DSM-5 reported having ties to the pharmaceutical industry. Dr. Allen Frances, who headed the development of the previous version, warned of dangerous unintended consequences such as new false 'epidemics'. The British Psychological Society criticized DSM-5 diagnoses as "clearly based largely on social norms, with 'symptoms' that all rely on subjective judgements" and expressed a major concern that "clients and the general public are negatively affected by the continued and continuous medicalisation of their natural and normal responses to their experiences". A petition signed by over 13,000 mental health professionals stated that the lowered diagnostic thresholds in DSM-5, combined with entirely subjective criteria based on western social norms, would "lead to inappropriate medical treatment of vulnerable populations". The director of the US National Institute of Mental Health, Dr. Thomas R. Insel, pointed out that the diagnoses in DSM-5 had no scientific validity whatsoever. (Learn more: www.scientificamerican.com)

International Classification of Diseases (ICD) - A system of medical diagnostic codes, created by the World Health Organization (WHO), to classify diseases and other health related conditions for the purpose of international diagnostic consistency. By having common diagnostic codes around the world, health researchers are better able to quantify and track disease burdens. The most current version is called ICD-11. (Learn more: www.who.int)

somatic symptom disorder A psychiatric term to describe an alleged condition whereby a person's thoughts somehow cause physical symptoms. The actual existence of such a condition is highly controversial, due to a lack of scientific evidence. It is related to other psychiatric terms, such as "psychosomatic", "neurasthenia", and "hysteria". Older terms include "somatization", "somatoform disorder", and "conversion disorder". Such terms refer to a scientifically-unsupported theory that claims that a wide range of physical symptoms can be created by the human mind, a theory which has been criticized as "mind over matter" parapsychology, a pseudoscience.

See somatic symptom disorder.