Definitions

chemical-sensitivity

Multiple chemical sensitivity

Multiple chemical sensitivity (MCS) is described as a chronic condition characterized by adverse effects from exposure to low levels of chemicals or other substances in modern human environments. Suspected substances include smoke, pesticides, plastics, synthetic fabrics, scented products, petroleum products, and paints.

Biochemist Martin L. Pall says that MCS sufferers “report being exquisitely sensitive to a wide range of organic chemicals,” and from 100 to 1000 times more sensitive to hydrophobic organic solvents than normal people.

MCS has also been termed toxic injury (TI), chemical sensitivity (CS), chemical injury syndrome (CI), 20th Century Syndrome, environmental illness (EI), sick building syndrome, idiopathic environmental intolerance (IEI), and toxicant-induced loss of tolerance (TILT).

Definition

Six consensus criteria were identified by researchers for the diagnosis and definition of MCS in 1989 (later edited in 1999) :

  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).

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". MCS has also been described 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.

Environmental Medicine Specialists 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.

Ronald E. Gots, M.D., an environmental toxicologist and frequent defense consultant in toxic tort litigation, 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. 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."

Lack of widespread 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 (AMA), the California Medical Association, the American College of Physicians, and the International Society of Regulatory Toxicology and Pharmacology. In 1994, the AMA, American Lung Association, US EPA and US Consumer Product Safety Commission published a booklet on indoor air pollution that discusses MCS among other issues. Although sometimes misrepresented as evidence that these entities no longer oppose MCS as a specific disease, the booklet describes MCS as unproven and indicates that other misdiagnosed or undiagnosed diseases cause the symptoms that the patient incorrectly attributes to MCS.

By one count, 25 U.S. administrative agencies afford varying degrees of support to claims filed under MCS. The Social Security Administration states, for example, that "evaluation should be made on an individual case by case basis to determine if the impairment limits substantial gainful activity. 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 says 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. However, lawsuits filed under the ADA's 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. Furthermore, accommodations sought for MCS are sometimes denied as being unreasonable as a matter of law.

Clinical trials

When MCS sufferers have been tested in double-blinded placebo controlled trials, exposure to chemicals has not reproducibly elicited symptoms. In a 1993 study of MCS sufferers, test subjects could not discriminate between their chemical triggers and clean air when an olfactory masker was introduced that eliminated the ability to discriminate on the basis of odor . In a more recent study (2008), a variety of responses including the subjective perception of being exposed to solvents, increases in blood pressure or heart rate, rash, hypoxia, or increased symptom severity were measured following the double-blinded exposure to several solvents. MCS suffers showed no differences in these parameters whether exposed to clean air or solvents . This evidence refutes the hypothesis that MCS is directly related to the effects of chemical exposures. Since MCS sufferers seem to only have symptoms when they perceive exposure to chemicals, it has been proposed that the syndrome is a result of odor hypersensitivity in which individuals have an exaggerated response to scents.

Symptoms

Symptoms of MCS may be mild to disabling. The symptoms are essentially any symptom which the patient finds distressing and attributes 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, 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, natural pine turpines, insomnia, dry mouth, dry eyes, and an overactive bladder.

Causes

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

Misdiagnosis

More than half of 54 people from one study about MCS instead had somatoform disorder or panic disorder. Other possible explanations include anxiety disorder, lupus, postural orthostatic tachycardia syndrome or other forms of orthostatic intolerance, hay fever and other allergies, hypercalcemia, hypothyroidism, chronic fatigue syndrome, or fibromyalgia. Sufferers may also have a tendency to "catastrophically misinterpret benign physical symptoms" or simply a disturbingly acute sense of smell. It is critical that these alternative diagnoses be properly investigated.

Psychological

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.

The distinction between physiological and psychological causes is often difficult to test and it is particularly challenging for 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. 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". 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.

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.

An alternative psychological cause has been suggested by a recent case-control study in which MCS was an associated with a personality trait called absorption in which individuals are predisposed to becoming deeply immersed in sensory experiences leading to self-altered states of consciousness. When 54 MCS sufferers were compared to 44 subjects with a somatoform disorder and 54 normal individuals, only those with MCS was related to increased absorption scores leading the authors to suggest that absorption contributes to MCS by making individuals more susceptible harboring beliefs in MCS and that these beliefs are reinforced by conditioning

Physiological

One of the first studies on MCS focused on possible long-term potentiation in the hippocampus and neural sensitization as a central mechanism. Later studies examined the role of the inflammatory process and found that brain inflammation was correlated with symptoms of MCS. 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. 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. 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. 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. 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.

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. Data showed that five genetic polymorphisms have a statistically significant role in determining MCS prevalence. 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. A new study by Schnakenberg et al (2006) confirmed the genetic variation previously found by McKeown-Eyssen and Haley. 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. 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.

Chemical triggers

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

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)

Environmental

  • 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, varnishes, polishes, paints, solvents, paint-thinners, and volatile organic compounds (VOC's)
  • Bleach, fabric softeners, wool-wash, and laundry 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 dishwasher detergent (may cause migraine headaches for those without MCS)
  • Marking pens, such as highlighters (significant exposure will cause headaches for anyone)

Miscellaneous theories

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. 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.

Emotional Stresses A recent study at Northwestern University shows that people who have stronger emotional states will react more strongly to a smell. They found that the brain's emotional regions did not better discriminate among the different odors. That discrepancy between brain regions is where anxiety disorders may come in. If someone's olfactory region does not distinguish a dangerous odor signal from a similar one, the brain's emotional fight-or-flight region can overreact.

Pyschological Illness 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, and
  4. not a single case has been scientifically validated.

These claims are challenged, particularly (1) and (2), insofar as both definitions and physiological pathways have actually been proposed. The scientific community remains divided, however, with many proponents of the psychosomatic school rejecting physiological explanations outright.Ronald E. Gots, M.D., an environmental toxicologist and frequent defense consultant in toxic tort litigation, 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. 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."

Diagnosis

People who have developed symptoms of MCS have attributed a wide assortment of symptoms to chemical exposure, though symptoms are generally consistent for each individual. The first step in diagnosing a potential MCS sufferer is to identify and treat all other conditions which are present and which often explain the reported symptoms. For example, true allergy, thyroid disorders, orthostatic syndromes, anxiety, and depression need to be carefully evaluated and, if present, properly treated.

The "gold standard" procedure for identifying a person who has MCS is to test his or her response to the random introduction of chemicals that the patient has self-identified as relevant, such as scented soaps or dryer sheets. This may be done in a carefully designed challenge booth to eliminate the possibility of contaminants in the room. Chemicals and controls, sometimes called prompts, are introduced in a random method, usually scent-masked. The test subject does not know when a prompt is being given. Objective and subjective responses are measured. Objective measures often include the galvanic skin response. The galvanic skin response, which is also called electrodermal response, is a reflex that indicates psychological arousal, such as fear, anxiety, or anger. Subjective responses include patient self-reports. A diagnosis of MCS can only be justified when the subject cannot consciously distinguish between chemicals and controls, and when responses are consistently present with exposure to chemicals and consistently absent when prompted by a control.

Treatment

In various studies about one half of the patients who present with symptoms of MCS meet the criteria for depressive and anxiety disorders, and these conditions must be treated when present. The use of SSRI antidepressants with a 53-year-old man with multiple chemical sensitivities showed a dramatic improvement, which suggests, as with the general population, that a subgroup of MCS patients may have an atypical depression and should be evaluated for this condition.

Another study showed psychotherapy resulted in significant, long-term improvement in MCS symptoms, although there was no control group to compare results to.

Saline injections were as successful in alleviating symptoms of food sensitivities as intradermal injection of antigens, suggesting that improvements of food symptoms seen with antigen injection treatment was psychosomatic.

While patients typically resist the potentially stigmatizing diagnosis of an anxiety disorder, many MCS sufferers benefit strongly from lifestyle changes. A 2003 survey of 917 MCS patients revealed that the two most-effective treatments for MCS, in order of self-perceived harm/benefit ratio, were a chemical-free living space and chemical avoidance. Next came prayer and meditation, (which presumably did no harm). By comparison, two-thirds of patients who had tried Zoloft thought it was harmful. Other treatments with perceived harm included other pharmaceutical drugs, provocative neutralization, hydrogen peroxide, Metagenics' UltraClear medical food, and Microhydrin antioxidants. Overall, one or more antidepressants and anxiolytics were rated harmful by about half of survey respondents who had tried them, and as either harmless or helpful by the remaining respondents.

Other treatment modalities variably consists of the avoidance of known irritants, nutritional support to purge the body of its toxic load, sauna detoxification and autolymphycyte factor treatment.

Because many people eliminate whole categories of food in an effort to reduce symptoms, a complete review of the patient's diet may be needed to avoid nutritional deficiencies.

Epidemiology

Allergist Theron G. Randolph (1906-1995) was the first to describe "the chemical intolerance phenomenon" in the mid-20th century, calling it "unwitting addiction" and comparing it to drug and alcohol addiction, with the addiction cycle being transparent to the patient as a masked intolerance. When Randolph formulated his views, the term allergy was not connected with immunology, as it has been since the late 1960s. It was then that non-immune-mediated hypersensitivities came to be called "intolerances", "idiopathic" or "idiosyncratic reactions" or "pseudoallergies". Randolph's theory was dismissed from the realm of allergology as the condition is not mediated by the humoral immune system.

As 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.

Cultural references

  • (1991) In the TV series Northern Exposure, the character Mike Monroe is portrayed as suffering from MCS.
  • (1995) Safe is a film about a woman who develops MCS.

References

See also

External links

MCS groups

"Clinical Ecological" perspective

Scientific analysis

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