User:Aletheia2020

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I joined MEpedia solely to work on pages related to Multiple Chemical Sensitivity (MCS)—a common comorbid condition with ME

ALETHEIA'S SANDBOX (this is where I work on content)
Multiple chemical sensitivity (MCS), also known as idiopathic environmental intolerances (IEI), is a chronic acquired illness, in which sufferers report a range of symptoms when exposed to certain everyday chemicals.

One 2018 scientific review said the condition was "a complex syndrome that manifests as a result of exposure to a low level of various common contaminants." While another review, from the same year, said it was characterized by "susceptibility to a wide spectrum of environmental compounds, causing symptoms involving various organs and a decrease in quality of life."

Commonly reported triggers for MCS symptoms include products like perfume, fresh paint fumes, tobacco smoke and mold.

Symptoms
The symptoms of MCS have been reported to affect multiple organs and body systems   and to range from mild to disabling. They have also been found to decrease the quality of life of sufferers.

A report from a national government inquiry into MCS found that the following symptoms—in this order—were the most commonly reported in MCS: headache, fatigue, confusion, depression, shortness of breath, arthralgia, myalgia, nausea, dizziness, memory problems, gastrointestinal symptoms, respiratory symptoms. Other commonly reported symptoms of MCS include: cardiac arrhythmia, tachycardia, hypotension, hypertension, nausea, vomiting, skin rashes, visual disturbances, seizures, asthma and anaphylaxis.

A 2018 review of MCS studies said: “MCS is a syndrome that progresses to increasingly serious stages, with the gradual onset of multiple pathlogies."

The following substances have been reported as common triggers for MCS symptoms:
 * synthetic fragrances,
 * tobacco smoke,
 * some pesticides, biocides and fungicides,
 * some laundry detergents and fabric softeners,
 * some petrochemical solvents (fumes from paint and polyurethane),
 * formaldehyde,
 * fumes from some building materials (particleboard and glues),
 * some food additives and colorings (eg. tartrazine),
 * some medications, and
 * some anesthetics.

Diagnosis
A 1999 international consensus on MCS is the most common diagnostic criteria used to diagnose the condition. This consensus was published in The Archives of Environmental Health, as the conclusion of a ten-year study by an international multidisciplinary team of 89 clinicians and researchers, with different points of view about MCS. The team agreed that the clinical characteristics of MCS should be defined as follows: The Quick Environmental Exposure and Sensitivity Inventory (QEESI) is a diagnostic tool that is often used to assess a patient for these criteria.
 * 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.

MCS has also been identified as a common comorbidity of chronic fatigue syndrome (CFS) by several consensus documents:
 * 1) The 2003 Canadian Consensus Criteria for CFS lists "new sensitivities to food, medications and/or chemicals" as a symptom and MCS as a comorbidity;
 * 2) The 2011 International Consensus Criteria lists "sensitivities to food, medications, odors or chemicals" as a symptom and MCS as a comorbidity; and
 * 3) A 2019 publication of the U.S. ME/CFS Clinician Coalition lists "chemical sensitivity" as a symptom of CFS and MCS as a comorbidity.

Treatment
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.

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. Some studies suggest a special focus on correcting any nutritional deficiencies may be beneficial.

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.

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 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 show that in the above countries MCS is not a rare condition.

Causes
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."

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 dilemma.

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 suggestedthat 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 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 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. Psychsomatic, 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 a psychological cause has attracted considerable criticism.

The main arguments used to support the is that MCS has psychological causes have been: 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."
 * 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.

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.

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

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. 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.

Safe (1995)
Safe is a cult film, by writer and director Todd Haynes, known for its depiction of MCS as a profoundly alienating and destabilizing condition.

Safe 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.

Notable studies and publications

 * 1999, Multiple chemical sensitivity: a 1999 consensus - (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)
 * Original title: Consenso Italiano sulla Sensibilita Chimica Multipla (MCS). Documento di consenso e linee guida sulla Sensibilita Chimica Multipla (MCS) del Gruppo di Studio Italiano sulla MCS - (Full text - Italian)

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