Multiple chemical sensitivity

Multiple chemical sensitivity (MCS) is described as a chronic condition characterized by several adverse and variable affects from exposure to otherwise low levels of substances in modern human environments. It has also been called toxic injury (TI), chemical sensitivity (CS), chemical injury (CI), 20th Century Syndrome, environmental illness (EI), Sick Building Syndrome, idiopathic environmental intolerance (IEI), and Toxicant-induced loss of tolerance (TILT).

The cause and existence of MCS are disputed. In particular, doctors disagree about whether symptoms are physiologically or psychologically generated or both. United States courts and several medical organizations reject MCS as a physiological disease. Critics of clinical ecology, a controversial field of medicine that claims to treat MCS, charge that:

1. MCS has never been clearly defined,
2. no scientifically plausible mechanism has been proposed for it,
3. no diagnostic tests have been substantiated,^[1] and
4. not a single case has been scientifically validated.^[2]

These claims are challenged, particularly (1) and (2), as both definitions^[3] and physiological pathways^[4][5] have been proposed, although these proposals have uniformly been rejected by critics.

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Definition

In 1989 and later edited in 1999, six consensus criteria were identified by researchers for the diagnosis and definition of MCS:^[3]

1. Symptoms are reproducible with repeated (chemical) exposures.
2. The condition has persisted for a significant period of time.
3. Low levels of exposure (lower than previously or commonly tolerated) result in manifestations of the syndrome (i.e. increased sensitivity).
4. The symptoms improve, or resolve completely, when the triggering chemicals are removed.
5. Responses often occur to multiple, chemically unrelated substances.
6. Symptoms involve multiple-organ symptoms (runny nose, itchy eyes, headache, scratchy throat, ear ache, scalp pain, mental confusion or sleepiness, palpitations of the heart, upset stomach, nausea and/or diarrhea, abdominal cramping, aching joints).^[6]

The National Institute of Environmental Health Sciences (a division of the NIH) defines MCS as a "chronic, recurring disease caused by a person's inability to tolerate an environmental chemical or class of foreign chemicals".^[7] Claudia Miller describes MCS as a group of "sensitivities to extraordinarily low levels of environmental chemicals" appearing "to develop de novo in some individuals following acute or chronic exposure to a wide variety of environmental agents including various pesticides, solvents, drugs, and air contaminants" including those found in sick buildings.^[8]

Clinical ecologists claim that MCS causes negative health effects in multiple organ systems, and that respiratory distress, seizures, cognitive dysfunction, heart arrhythmia, nausea, headache, and fatigue can result from exposure to levels of common chemicals that are normally deemed as safe.^[9][10]

Detractors such as Ronald E. Gots, M.D., who is an environmental toxicologist and frequent defense consultant in toxic tort litigation,^[11] describes MCS as "a label given to people who do not feel well for a variety of reasons and who share the common belief that chemical sensitivities are to blame. ... It has no consistent characteristics, no uniform cause, no objective or measurable features. It exists because a patient believes it does and a doctor validates that belief."^[12] An editorial in the Journal of Toxicology - Clinical Toxicology stated that "It may be the only ailment in existence in which the patient defines both the cause and the manifestations of his own condition."^[13]

Recognition

Because of the lack of scientific evidence based on well-controlled clinical trials that supports a cause-and-effect relationship between exposure to very low levels of chemicals and the myriad symptoms reported by clinical ecologists, MCS is not recognized as an established organic disease by the American Academy of Allergy, Asthma, and Immunology, the American Medical Association, the California Medical Association, the American College of Physicians, and the International Society of Regulatory Toxicology and Pharmacology.^[14][15][13]

Many medical doctors who treat MCS are certified by the American Academy of Environmental Medicine, which Theron Randolph founded in 1965 as the Society for Clinical Ecology.

Some U.S. administrative agencies support claims filed under MCS. The Social Security Administration states that "evaluation should be made on an individual case by case basis to determine if the impairment limits substantial gainful activity" in a section entitled "Medical Evaluation of Specific Issues: Environmental Illness."^[16] This decision is consistent with the SSA's mission to provide support for all workers who are in practice totally disabled, no matter the underlying cause.

The Americans with Disabilities (ADA) Handbook defines environmental illness as "sensitivity to environmental elements" and posits that individuals who are severely affected with poor respiratory and neurological function as a result of MCS will satisfy the requirements to be considered disabled.^[17] However, cases filed under the ADA definition have been largely unsuccessful. Some courts have held that MCS "is untested, speculative, and far from generally accepted in the medical or toxicological community," and thus can't be used as the basis for disability claims.^[18] Furthermore, accommodations sought for MCS are sometimes denied as being unreasonable as a matter of law.^[19]

Symptoms

The symptoms are essentially any symptom which the patient finds distressing and chooses to attribute to this cause. A partial list of common symptoms include anaphylactic shock, difficulty breathing, chest pains and asthma, skin irritation, contact dermatitis, and hives or other forms of skin rash, headaches, "brain fog" (short term memory loss, cognitive dysfunction, including attention deficit), neurological symptoms (nerve pain, paralysis, weakness, trembling, restless leg syndrome, etc), tendinitis, seizures, visual disturbances (blurring, halo effect, inability to focus), extreme anxiety, panic and/or anger, suppression of immune system, digestive difficulties, nausea, indigestion/heartburn, vomiting, diarrhea, food intolerances, which may or may not be clinically identifiable (e.g., lactose intolerance, celiac disease): commonly wheat and dairy, joint and muscle pains, extreme fatigue, lethargy and lassitude, vertigo/dizziness, abnormally acute sense of smell, sensitivity to natural plant fragrance, pine turpines, insomnia, dry mouth, dry eyes, and an overactive bladder.^[20][9]

History and epidemiology

Allergist Theron G. Randolph (1906-1995) was the first to describe "the chemical intolerance phenomenon" half a century ago, calling it "unwitting addiction" and comparing it to drug and alcohol addiction, the addiction cycle being transparent to the patient as a masked intolerance.^[21] When Randolph formulated his views, the term allergy was not related to immunology until 1967 when IgE (immunoglobulin) was finally discovered, giving allergists a scientific basis to their practice.^[21] It was then that "these non-immune-mediated hypersensitivities" came to be called "intolerances", or "idiopathic" or "idiosyncratic reactions"; in Europe they became "pseudoallergies" and Randolph's theory was dismissed as the condition is not mediated by IgE.^[21] Scientists are still working to discover the etiology behind MCS.

As Doctors Magill and Seruda report:

Most patients (85 to 90 percent) complaining of MCS syndrome are women. Most present between the ages of 30 and 50 years. Much additional basic descriptive and epidemiologic information is still unknown. The incidence and prevalence are unknown. The question of whether MCS is becoming more or less common is unanswered, as is the question of whether it is preventable. The natural history and biologic outcomes of MCS are unknown, and descriptions of MCS in primary care settings have not been reported. Selected patients from specialty settings comprise reports of the syndrome.^[15]

Etiology (cause)

There is no clear consensus as to what causes the symptoms of MCS. There may be several causes.

Psychological causes

Several mechanisms for psychological etiology have been proposed including theories based on stress, Pavlovian conditioning, or misdiagnoses of an underlying mental illness. Behavior exhibited by MCS sufferers may reflect broader sociological fears about industrial pollution.^[22]

It's difficult to differentiate psychological and physiological etiologies of MCS because substances used to test for sensitivity can often be detected by scent. Odor cues make double blind studies of MCS patients difficult, and scents might provoke a psychosomatic response. Research by Dr Mariko Saito et al from the Department of Psychosomatic Medicine at the University of Tokyo in 2005 found that patients only experienced symptoms when they themselves initiated the challenge tests. When they were given random prompts, there was no difference between MCS patients and controls in terms of physical and psychologic symptoms.^[23] Their conclusion was "MCS patients do not have either somatic or psychologic symptoms under chemical-free conditions, and symptoms may be provoked only when exposed to chemicals," although their results showed that it was not the chemicals themselves that caused the symptoms.

A review of 37 provocation studies concluded that "persons with MCS do react to chemical challenges; however, these responses occur when they can discern differences between active and sham substances, suggesting that the mechanism of action is not specific to the chemical itself and might be related to expectations and prior beliefs".^[24] Critics of such provocation studies assert that they are inconclusive because they often employ masking odors which themselves are alleged to trigger MCS. At least one study attempted to correct for this problem by only using patients who do not respond to the masking odor, and this provocation study similarly showed no correlation between symptoms and chemical exposure.^[25]

Another study found strong evidence of a placebo effect: purported MCS sufferers claimed symptoms in nonblinded tests when fed suspected food extracts, but were unable to produce symptoms consistently when the tests were doubleblinded; similarly, patients responded identically to "treatments" and saline.^[26]

Science rejects mind-body dualism, so the distinction between physiological and psychological causes is difficult to test.^[24]

Physiological causes

One of the first studies on MCS focused on possible long-term potentiation in the hippocampus and neural sensitization as a central mechanism.^[27] Later studies examined the role of the inflammatory process and found that brain inflammation was correlated with symptoms of MCS.^[27] In 1999, Meggs proposed that MCS is caused by low molecular weight chemicals that bind to chemoreceptors on sensory nerve C-fibers leading to the release of inflammatory mediators.^[28] McKeown-Eyssen showed that polymorphisms in the CYP2D6 allele was responsible for variation in toxicant metabolism pathways that may cause differences in susceptibility to MCS. ^[29] Pall identified evidence suggesting elevated nitric oxide and peroxynitrite (NO/ONOO-) as the etiology for MCS and several related conditions including fibromyalgia, post traumatic stress disorder, gulf war syndrome, and chronic fatigue syndrome.^[27] Pall has identified organic solvents and related compounds, organophosphorus/carbamate pesticides, organochlorine (chlordane, lindane) pesticides, and the pyrethroid pesticides as initiating the NO/ONOO- cycle of biochemistry leading to MCS.^[30] Many observable and empirical, scientific facts can help identify MCS including SPECT scans and chemical encephalopathy, vitamin deficiencies, mineral deficiencies, excess amino acid deficiency, and disturbed lipid and carbohydrate metabolism. ^{[10][31][32][33]}

Genetically altered detoxification

McKeown-Eyssen studied 203 MCS sufferers and 162 controls and found that blood tests revealed that genetic differences relating to the body's detoxification processes were present more often in those with MCS than those without.^[29] Data showed that five genetic polymorphisms have a statistically significant role in determining MCS prevalence. ^[29] Each of these genes encode proteins that metabolize chemicals previously implicated in MCS, notably the organophosphorus pesticides (PON1 and PON2 genes) and the organic solvents (CYP2D, NAT1 and NAT2 genes). People with a high expression of two specific genes (CYP2D6 and NAT2) were 18 times more likely to have MCS than those without. It was concluded that "a genetic predisposition for MCS may involve altered biotransformation of environmental chemicals." Haley found similar, confirmatory results with the PON1 gene in studies of the Gulf War syndrome veterans.^[34] A new study by Schnakenberg et al (2006) confirmed the genetic variation previously found by McKeown-Eyssen and Haley.^[35] A total of 521 unrelated individuals participated in the study. Genetic variants of four genes were analyzed: NAT2, GSTM1, GSTT1, and GSTP1. The researchers concluded that individuals who are NAT2 slow acetylators and those with homozygously deleted GSTM1 and GSTT1 genes are significantly more likely to develop chemical sensitivity. According to the study, the glutathione S-transferases act to inactivate chemicals, so people without these GSTM1 and GSTT1 genes are less able to metabolize environmental chemicals because "glutathione S-transferases play an important role in the detoxification of chemicals". The deletion of another gene, the GSTP1 gene, leaves individuals more susceptible to developing these diseases, as lack of these genes means a loss of protection from oxidative stress.

A specific laboratory rat, the Flinders Sensitive Line, has been bred by Dr. Overstreet. It was bred to be sensitive to an organophosphate and displays "Increased sensitivity to cholinergic agents [that] has also been observed in several human populations, including individuals suffering from chemical intolerance."^[36] In particular, Flinders Sensitive rats show increased responses to nicotine, alcohol, and other chemicals known to act on acetylcholine, dopamine, and serotonin receptors. However, these rats have not reacted abnormally to other chemicals thought to trigger MCS, such as perfume, in any known studies. Study of these rats may therefore provide useful clues about the mechanisms involved in some, but not all, forms of chemical intolerance in humans.

Body burden

Many heavy metals and chemicals are known to cause illness when excessive amounts are consumed. Smaller amounts of these substances, at levels which are generally recognized as being safe, generally do not cause health problems because the liver and kidneys remove the toxic substances from the body. Some people theorize that while amounts of individual toxicants that fall within regulatory limits may be safe, the cumulative effect of exposures to multiple toxic substances over a long period of time causes a "body burden", resulting in the symptoms of MCS.^{[citation needed]} While studies have shown that most people have small amounts of many hundreds of toxic chemicals in their body, there is no evidence to show that this correlates to a higher incidence of MCS.^{[citation needed]}

Misdiagnosis

Many patients who present with MCS claims actually have other diseases, especially panic disorder^[37] but also including anxiety disorder, lupus, postural orthostatic tachycardia syndrome or other forms of orthostatic intolerance, hay fever and other allergies, hypercalcemia, hypothyroidism, chronic fatigue syndrome, fibromyalgia or simply a disturbingly acute sense of smell.[1]

Miscellaneous theories

Another hypothesis is that the chemicals triggers a coagulation response and that this is a non-IgE allergy response.^{[citation needed]} In the case of MCS, there appears to be a genetic or acquire coagulation defect^{[citation needed]} resulting in a slow clearing of the coagulation products with the consequence of hypoxia symptoms and is some individuals, poor clearing of toxins from the body.^{[citation needed]} Some individuals with MCS have triggers that might be documented to be coagulation triggers.^{[citation needed]} To date, no studies have been conducted to specifically test MCS patients for coagulation responses.

Diagnosis and treatment

Diagnostic challenges

People diagnosed with MCS suffer widely assorted symptoms from person to person, though symptoms are generally the consistent in each individual based on the exposure. The lack of consistency from individual to individual makes research difficult. Body wash solutions and dryer sheets are widely recognized as triggers of extreme reactions. Researchers use these two products to distinguish between controls and MCS-TILT sufferers based on electrodermal response (which is unconscious) in a controlled environment (a challenge booth)^[3].

Treatment

About one half of the patients with MCS in various studies meet the criteria for co-occurring depressive and anxiety disorders.^[38] Though these psychological conditions have alternative causes, it has been posited that MCS is simply a physical manifestation of a psychological disturbance (a psychosomatic illness) which should be treated with psychotherapy and antidepressants. The use of SSRI antidepressants with a 53-year-old man with multiple chemical sensitivities showed a dramatic improvement, suggests, as with the general population, that a subgroup of MCS patients may have an atypical depression and should be evaluated.^[39] Another study showed psychotherapy resulted in significant, long-term improvement in MCS symptoms, although there was no control group to compare results to.^[40]

Placebo treatment was successful in alleviating symptoms in a variety of MCS sufferers, suggesting the symptoms were entirely psychosomatic.^[26]

A 2003 survey of 917 MCS patients revealed that the top four treatments for MCS, in order of self-perceived efficacy, were a chemical free living space, chemical avoidance, prayer, and meditation.^[9] In comparison, 68.2% of patients self-reported that Zoloft was harmful.^[9] Other treatments with perceived harm included Prozac, Elavil, other antidepressants, Valium, antiseizure medication (except Neurontin), Xanax, Microydrin, Acyclovir, and provocative neutralization.^[9]

Other treatment modalities variably consists of the avoidance of known allergens and irritants, nutritional support to "open up" the body's various detoxification channels designed to purge the body of its toxic load, sauna detoxification, autolymphycyte factor treatment, allergy shots, experimental treatments and several other lifestyle changes.^[10]

Possible triggers

Multiple chemicals are reported to trigger MCS symptoms.^[10][15] In addition to anything which is perfumed or scented, complaints are commonly formed about everyday items:

In the home

• Bleach, fabric softeners, wool-wash, and detergents
• Perfumes, lotion, after-shave lotion, nail polish, or skin care products
• Air-fresheners, deodorizers and scented candles
• Shampoos, hairsprays and hair care products
• Household cleaning chemicals
• Dishwashing liquid and detergent (may cause migraine headaches for those without MCS)
• Marking pens, such as highlighters (significant exposure will cause headaches for anyone)

In food

• Tartrazine (a.k.a Yellow #5 or FD&C E102), and other Azo dyes (True allergy must first be excluded)
• Caffeine (may cause migraine headaches apart from MCS)

Outside the home

• Petrol or gasoline, diesel and exhaust fumes
• Petroleum-based products, including petroleum jelly, tar, asphalt
• Tobacco or any form of smoke
• Pesticides, herbicides, fertilizers, and other agricultural chemicals
• Industrial cleaning chemicals, such as dry cleaning fluid
• Formaldehyde and aldehyde
• Glues (including carpet glue), varnishes, polishes, paints, solvents and paint-thinners
• Volatile organic compound (VOC's)

Any chemicals which off-gas (regardless of odor)^{[citation needed]} and Solvents are reported by patients to trigger symptoms. The associated illness is popularly known as painters' syndrome which affects professional painters.^{[citation needed]} Many countries have banned thinner-based paints and replaced them with water-based paints.^{[citation needed]} Non VOC paints may be obtained. Enclosed, air-conditioned buildings with a recycled air supply such as shopping centers or large office buildings are generally considered bad environments for the chemically-sensitive.[2]. Some find it helpful to avoid certain types of fabrics, hang printed paper outside off gas before reading, purchase only untreated wooden furniture, and eat only organic food.[3] Some avoid contact with the outside world all together in favor of a controlled environment which limits exposure to offending chemicals that otherwise cannot be avoided.^[10]

References

See also

• Clinical ecology
• Gulf War syndrome
• Salicylate Sensitivity

MCS groups

• Chemical Injury Information Network Support, education, and research about multiple chemical Sensitivities for 17 years.
• The Cleaner Indoor Air Campaign Encouraging Businesses, Medical Facilities and Churches to Bring Down the Barriers, by Creating a Less Threatening Environment.
• Planet Thrive a grassroots community for personal wellness with a focus on environmental and other chronic illnesses—with special resources for those with Multiple Chemical Sensitivity (MCS)
• MCS-CanadianSources Support and information for those with MCS, CI, EI and other related illnesses
• Ohio Network for the Chemically Injured Information and tips for those living with MCS
• MCS-International.Org Bringing the hidden dangers of modern synthetic chemicals out into the Light worldwide - while offering a wide range of relevant information and support services to the chemically injured.
• SOS MCS French Association for help people.

"Clinical Ecological" perspective

• Our Toxic Times a monthly magazine by and for those suffering from Multiple Chemical Sensitivities.
• Article from Grist Magazine
• Multiple Chemical Sensitivity - The End of Controversy, Dr Martin L. Pall, theorizing etiology of MCS
• Symptom Profile of Multiple Chemical Sensitivity in Actual Life, Saito M, MD et al. 2005
• Understanding and Accommodating People With MCS, Pamela Reed Gibson, Ph.D., James Madison University]

Skeptical perspective

• Multiple Chemical Sensitivity Syndrome A literature review from the American College of Family Phsyicians
• Multiple Chemical Sensitivity: a spurious diagnosis, Stephen Barrett, MD. — A skeptical article hosted on Quackwatch
• A close look at "Multiple Chemical Sensitivity", Stephen Barrett, MD, 1998
• Comprehensive MCS Bibliography