Multiple chemical sensitivity

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Multiple chemical sensitivity
Classification and external resources
MeSH D018777

Multiple chemical sensitivity (MCS) is described as a chronic condition characterized by adverse and variable 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.[1] Dr. Martin Pall, molecular bioscience professor at Washington State University, finds 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.[2]MCS has also been termed toxic injury (TI), chemical sensitivity (CS), chemical injury syndrome (CI),[3] 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,[4] and
  4. not a single case has been scientifically validated.[5]

These claims are challenged, particularly (1) and (2), insofar as both definitions[6] and physiological pathways[7][8] have actually been proposed. The scientific community remains divided, however, with many proponents of the psychosomatic school rejecting physiological explanations outright.

Contents

[edit] Definition

In 1989 and later edited in 1999, six consensus criteria were identified by researchers for the diagnosis and definition of MCS:[6]

  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).[9]

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".[10] Claudia Miller, M.D., University of Texas Health Science Center, 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.[11]

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.[12][13]

Detractors such as Ronald E. Gots, M.D., who is an environmental toxicologist and frequent defense consultant in toxic tort litigation,[14] 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."[15] 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."[16]

[edit] 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.[17][18][16] The AMA has, however, modified its position since the aforecited report of 1992. In a joint statement with the American Lung Association, US EPA and US Consumer Product Safety Commission, the AMA announced that the "current consensus" on MCS is that "complaints should not be dismissed as psychogenic, and a thorough workup is essential."[19]

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.

By one count, 25 U.S. administrative agencies afford varying degrees of support to claims filed under MCS.[20] 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."[21] 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.[22] 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.[23] Furthermore, accommodations sought for MCS are sometimes denied as being unreasonable as a matter of law.[24]

In short, government agencies as well as the scientific community reflect the ongoing controversy over MCS. Given the division of informed opinion, a consensus in recognition must await further developments in research.

[edit] 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.[25][12]

[edit] 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.[26] 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.[26] 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.[26] Scientists are still working to discover the etiology behind MCS.

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.[18]

[edit] Etiology (cause)

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

[edit] Misdiagnosis

Just like most patients who have chest pain are not actually having a heart attack, nearly all patients who have symptoms which could be related to MCS actually have some other disease. More than half of the people who talk to their doctor about MCS have somatoform disorder[27] or panic disorder.[28] 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"[29] or simply a disturbingly acute sense of smell.[30] It is critical that these alternative diagnoses be properly investigated.

[edit] 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.[31]

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.[32] 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".[33] 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.[34]

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.[35]

Science rejects mind-body dualism, so the distinction between physiological and psychological causes is difficult to test.[33]

[edit] 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.[36] Later studies examined the role of the inflammatory process and found that brain inflammation was correlated with symptoms of MCS.[36] 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.[37] 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.[38] 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.[36] 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.[39] 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.[13][40][41][42]

[edit] 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.[38] Data showed that five genetic polymorphisms have a statistically significant role in determining MCS prevalence.[38] 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.[43] A new study by Schnakenberg et al (2006) confirmed the genetic variation previously found by McKeown-Eyssen and Haley.[44] 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."[45] 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.

[edit] 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.[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.

A recent study at Northwestern University shows that people who have stronger emotional states will react more strongly to a smell.[1] 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.[2] This information may explain the cause of MCS and may result in better treatments for MCS patients.

[edit] Diagnosis

People who believe they may have 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.[6] 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.

[edit] Treatment

About one half of the patients who believe they may have MCS in various studies meet the criteria for depressive and anxiety disorders, and these conditions must be treated when present.[46] 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, 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.[47]

Another study showed psychotherapy resulted in significant, long-term improvement in MCS symptoms, although there was no control group to compare results to.[48]

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.[35]

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).[12] 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.[13]

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.[49]

[edit] Possible triggers

Multiple chemicals are reported to trigger MCS symptoms.[13][18] 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 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)

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
  • Solvents and volatile organic compounds (VOC's)

[edit] 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.

[edit] References

  1. ^ Bob Michaels (1998). Frequently Asked Questions about Multiple Chemical Sensitivity. Retrieved on 2008-03-20.
  2. ^ Martin Pall, Explaining 'Unexplained Illnesses': Disease Paradigm for Chronic Fatigue Syndrome, Multiple Chemical Sensitivity, Fibromyalgia, Post-Traumatic Stress Disorder, Gulf War Syndrome and Others, (Binghampton, New York: Harrington Park Press, 2007), see esp. chapter seven, "Multiple Chemical Sensitivity," pp. 111-138; M. Pall, “NMDA Sensitization and Stimulation by Peroxynitrite, Nitric Oxide, and Organic Solvents as the Mechanism of Chemical Sensitivity in Multiple Chemical Sensitivity,” The FASEB Journal 16 (Sept 2002): 1407-1417.
  3. ^ Michaels, supra, states: "Some advocates refer to this disability as Chemical Injury Syndrome (CIS), which they believe more effectively communicates the severity of this disability."
  4. ^ Staudenmayer H, Selner JC. Failure to assess psychopathology in patients presenting with chemical sensitivities. Journal of Occupational Medicine 37:704–709, 1995.
  5. ^ S. Barrett, A close look at "Multiple Chemical Sensitivity", 1998
  6. ^ a b c Joffres MR, Sampalli T, Fox RA. "Physiologic and symptomatic responses to low-level substances in individuals with and without chemical sensitivities: a randomized controlled blinded pilot booth study". Environ Health Perspect 113 (9): 1178-83. PMID 16140624. 
  7. ^ Pall, M (2006). Novel disease paradigm produces explanations for a whole group of illnesses. Washington State University, Department of Biochemistry and Basic Medical Sciences, Retrieved December 3, 2006, from: http://molecular.biosciences.wsu.edu/Faculty/pall/pall_main.htm
  8. ^ Schnackenberg,E. et al (2007).A cross-sectional study of self-reported chemical-related sensitivity is associated with gene variants of drug-metabolizing enzymes. Environmental Health.
  9. ^ "Multiple chemical sensitivity: a 1999 consensus" (1999). Arch. Environ. Health 54 (3): 147-9. PMID 10444033. 
  10. ^ MCSS factsheet — United States National Institute of Environmental Health Sciences
  11. ^ Miller CS. "Toxicant-induced Loss of Tolerance-An Emerging Theory of Disease?". Environ Health Perspect. 105 (2): 445-53. PMID 9167978. 
  12. ^ a b c Gibson, PR, Elms, AN, & Ruding, LA (2003).Perceived treatment efficacy for conventional and alternative therapies reported by persons with multiple chemical sensitivity. Environmental Health Perspectives. 111(12):1498-1504.
  13. ^ a b c d Rea, WJ, Johnson, AR, Ross, GH, Butler, JR, Fenyves, EJ, Griffiths, B,& Laseter, J (2006). Considerations for the Diagnosis of Chemical Sensitivity. Retrieved January 1, 2007 from http://www.aehf.com/articles/A55.htm
  14. ^ An Expert Who Has Been There - Dr. Ronald E. Gots, The Metropolitan Corporate Counsel
  15. ^ Gots RE. Multiple Chemical sensitivities: What is it? North Bethesda, MD: Risk Communication International, Inc., March 31, 1993.
  16. ^ a b Gots RE. Multiple chemical sensitivities--public policy [Editorial]. J Toxicol Clin Toxicol 1995;33:111-3.
  17. ^ American Medical Association Council on Scientific Affairs. Clinical ecology. JAMA 1992;268:3465-7. ("No evidence based on well-controlled clinical trials is available that supports a cause-and-effect relationship between exposure to very low levels of substances and the myriad symptoms reported by clinical ecologists to result from such exposure . . . . Until such accurate, reproducible, and well-controlled studies are available, the American Medical Association Council on Scientific Affairs believes that multiple chemical sensitivity should not be considered a recognized clinical syndrome.")
  18. ^ a b c Michael K. Magill, and Anthony Suruda, Multiple Chemical Sensitivity Syndrome, American Family Physician, September 1, 1998.
  19. ^ "Recognition of MCS as a Legitimate Disease and Disability," MCS Referral & Resources fact sheet "(August 1998).
  20. ^ "Recognition of MCS..., MCSRR, ibid.
  21. ^ Section entitled "Medical Evaluation of Specific Issues: Environmental Illness," SSA Publication 68-0424500, Part 04, Chapter 245, Section 24515.065, Transmittal 12, 1 page excerpt, R-11. On October 31, 1997, Acting SSA Commissioner John Callahan issued a memo to the court officially recognizing MCS "as a medically determinable impairment" on an agency-wide basis. October 31, 1997, R-164, Creamer v. Callahan
  22. ^ ADA Handbook, EEOC-BK-19. U.S. Department of Justice and U.S. Equal Employment Opportunities Commission. 111-121:R-17. 1991.
  23. ^ Frank v. New York, 972 F. Supp. 130 (N.D.N.Y. 1997)
  24. ^ Andrew K. Kelley, "COMMENT: Sensitivity Training: Multiple Chemical Sensitivity and the ADA," 25 B.C. Envtl. Aff. L. Rev. 485; see, for example, Whillock v. Delta Air Lines, 926 F.Supp. 1555 (N.D.Ga. 1995) http://findarticles.com/p/articles/mi_qa3816/is_199801/ai_n8766981/pg_1
  25. ^ Understanding and Accommodating People With MCS, Pamela Reed Gibson, Ph.D.
  26. ^ a b c Miller, Claudia. Toxicant-induced Loss of Tolerance. Addiction 96 (2000), 115–139.
  27. ^ Bailer J, Witthöft M, Paul C, Bayerl C, Rist F (2005). "Evidence for overlap between idiopathic environmental intolerance and somatoform disorders". Psychosom Med 67 (6): 921–9. doi:10.1097/01.psy.0000174170.66109.b7. PMID 16314597. 
  28. ^ Binkley KE, Kutcher S. Panic response to sodium lactate infusion in patients with multiple chemical sensitivity syndrome. J Allergy Clin Immunol 1997;99:570-4.
  29. ^ Idiopathic Environmental Intolerance May Have Psychological Component. Retrieved on 2008-01-13.
  30. ^ stoppingSmell. Retrieved on 2008-01-13.
  31. ^ E. Shorter, Multiple chemical sensitivity: pseudodisease in historical perspective, Scand J Work Environ Health 23 (1997) (suppl 3), pp. 35–42
  32. ^ Saito M, et al. "Symptom profile of multiple chemical sensitivity in actual life.". Psychosomatic Medicine 67 (2 (2005 Mar-Apr)): 318-25. PMID 15784800. 
  33. ^ a b J. Das-Munshi, G. J. Rubin, S. Wessely, Multiple chemical sensitivities: A systematic review of provocation studies, Journal of Allergy and Clinical Immunology, 118, pp.1257-1264 (2006)
  34. ^ H. Staudenmayer, J.C. Selner and M.P. Buhr, Double-blind provocation chamber challenges in 20 patients presenting with "multiple chemical sensitivity.", Regul Toxicol Pharmacol 18 (1993), pp. 44–53.
  35. ^ a b Jewett DL, Fein G, Greenberg MH. A double-blind study of symptom provocation to determine food sensitivity. New England Journal of Medicine 323:429-433, 1990.
  36. ^ a b c Pall, M (2003). Elevated nitric oxide/peroxynitrite theory of multiple chemical sensitivity: central role of N-methyl-D-aspartate receptors in the sensitivity mechanism. Environmental Health Perspectives. 111:12, 1461-1464.
  37. ^ Meggs, WJ (1999). Mechanisms of allergy and chemical sensitivity. Toxicology and Industrial Health. 15:3-4, 331-338.
  38. ^ a b c McKeown-Eyssen G, Baines C, Cole DE, Riley N, Tyndale RF, Marshall L, Jazmaji V. (2004). "Case-control study of genotypes in multiple chemical sensitivity: CYP2D6, NAT1, NAT2, PON1, PON2 and MTHFR." 33 (5): 971–8. PMID 15256524. 
  39. ^ Pall, M (2006). Novel disease paradigm produces explanations for a whole group of illnesses. Washington State University, Department of Biochemistry and Basic Medical Sciences, Retrieved December 3, 2006, from: http://molecular.biosciences.wsu.edu/Faculty/pall/pall_main.htm
  40. ^ Ziem, G (2001). Medical Evaluation and Treatment of Patients with Chemical Injury and Sensitivity. National Institute of Environmental Health Sciences.
  41. ^ Callender, TJ, et al. (1995). Evaluation of chronic neurological sequelae after acute pesticide exposure using SPECT brain scans. Journal Toxicology & Environmental Health. 41:275-284.
  42. ^ Heuser, G, et al. (1994). Neurospect findings in patients exposed to neurotoxic chemicals. Toxicology & Industrial Health. 10:561-571.
  43. ^ Haley, RW, Billecke, S, & La Du, BN (1999). Association of low PON1 type Q (type A) arylesterase activity with neurologic symptom complexes in Gulf War veterans. Toxicology and Applied Pharmacology 157(3):227–33.
  44. ^ Schnackenberg, E. et al (2007). A cross-sectional study of self-reported chemical-related sensitivity is associated with gene variants of drug-metabolizing enzymes. Environmental Health.
  45. ^ "David H. Overstreet & Veljko Djuric, A Genetic Rat Model of Cholinergic Hypersensitivity: Implications for Chemical Intolerance, Chronic Fatigue, and Asthma. Ann. N.Y. Acad. Sci. 933: 92-102 (2001).
  46. ^ Lax MB, Henneberger PK. Patients with multiple chemical sensitivities in an occupational health clinic: presentation and follow-up. Arch Environ Health 1995;50:425-31.
  47. ^ Andine P, Ronnback L, & Jarvholm B. Successful use of a selective serotonin reuptake inhibitor in a patient with multiple chemical sensitivities. Acta Psychiatrica Scandinavica 1997 Jul;96(1):82-3.
  48. ^ Lacour M, Zunder T, Dettenkofer M, Schonbeck S, Ludtke R, & Scheidt C. An interdisciplinary therapeutic approach for dealing with patients attributing chronic fatigue and functional memory disorders to environmental poisoning—a pilot study. Int J Hyg Environ Health. 2002 Feb;204(5-6):339-46.
  49. ^ On Her Last Legs - New York Times. Retrieved on 2008-01-25.

[edit] See also

[edit] External links

[edit] MCS groups

[edit] "Clinical Ecological" perspective

[edit] Scientific analysis