Multiple chemical sensitivity, Central sensitization, Environmental medicine, Peroxynitrite, NMDA receptor (N-methyl-D-aspartate)

Multiple Chemical Sensitivity: The Paradigm Breaker for Doctors

Don Want

Multiple chemical sensitivity (MCS), or toxicant induced loss of tolerance, was first recognised in 1954 by Dr Theron Randolph. The sufferer experiences sensitised reactions to various manufactured chemicals.¹

The resulting symptoms of MCS vary from one individual to another, although they are usually consistent/repeatable in each individual in response to the same triggers. The symptoms overlap with those of closely related health conditions such as chronic fatigue, fibromyalgia, and Gulf War syndrome. There can be from one to multiple organs/body systems affected. An unfortunate feature of this condition is that the sensitisation and reactions can progressively get worse with repeated exposures. The symptoms can conversely abate if exposures to such incitants are avoided.

MCS sufferers react to very low concentration levels of the inciting chemicals, such as experiencing headaches and fatigue symptoms due to deodoriser or perfume presence at levels not able to be smelt. Depending upon how sensitive the individual is, triggering concentrations may be orders of magnitude lower than normally accepted exposure levels derived from classical toxicology approaches. It is this aspect that creates general disbelief about the existence of this condition. The multiple symptoms also result in disbelief by conventional medical profession practitioners: their training frequently leads them to regard individuals complaining of multiple organ problems and accompanying neurological symptoms as having a psychological problem. No characteristically unique signs, laboratory test abnormalities, tissue pathology, or course of illness have been clearly established for diagnosis purposes. Thus, the general trend by the conventional medical system is to give the sufferers a diagnosis of somatoform disorder or other psychological diagnoses. The mainstream medical system operates without recognition of the central sensitivity condition. As there is no training in environmental factors initiating health conditions, most doctors do not recognise their significance.

The incidence of people with chemical sensitivities in the population is significant, with figures ranging between 2% and 22% of the population.^2-14

Central Sensitisation

Central sensitivity (CS) refers to a heightened sensitivity condition through the central nervous system. This frequently precipitates chronic pain. It has an initial wind-up period in respect to pain intensity over time. Peripheral, repeated nociceptive input establishes improved neuronal pathways for such pain transmission producing functional changes in the brain.^15-17 Even after the initial source of pain may have healed, the same pain pathways may remain active with pain still being felt by the sufferer.¹⁸ A source of chronic inflammation, e.g., arthritis, can act as a source of nociception. Neuroendocrine-immune pathology can also develop CS.¹⁹

Many doctors fail to recognise a CS condition in patients: it needs a different approach than would otherwise be taken from a non-detailed diagnosis approach.²⁰ It is a challenging idea that localised pain is not necessarily an indicator of a local physiological problem

As explained later for MCS, N-methyl-D-aspartate (NMDA) receptors seem to play an essential role in human chronic pain and are vital for nervous system functioning: they are widely present in both the peripheral and the central nervous system tissues. NMDA agonists are involved in CS and MCS.

So, there is an increasingly recognised CS condition which loosely fits sensitisation phenomena typical of MCS. Recognition of MCS and overlapping conditions as being a CS is gradually occurring.²⁰

The Growing Awareness of Environmental Effects on Health

The incidence of many diseases has significantly increased over the past five decades: autism, Alzheimer’s, chronic obstructive pulmonary disease, diabetes, sleep apnea, celiac disease, ADHD, asthma, depression, bipolar disease in youth, osteoarthritis, lupus, inflammatory bowel disease, chronic fatigue syndrome, fibromyalgia, multiple sclerosis, and hypothyroidism. The cause of, or a pathogen for, each of these diseases has not been established. As the general human genome has not significantly altered in this time, it has been suggested that environmental exposures are highly suspect.^21-23

Centuries ago, Hippocrates stated that one’s diet, lifestyle and environment have profound consequences for health and wellbeing.²⁴ In 2011, it was estimated by the World Health Organisation that 4.9 million deaths and 86 million Disability Adjusted Life Years could be attributed to environmental chemicals.^23,25 Furthermore, approximately one-quarter of the global disease burden and more than one-third of the burden among children under the age of five were due to modifiable environmental factors.^23,26

Recent studies on epigenetics and new terms such as “exposome” (total exposures over a lifetime) are increasingly being associated with chronic disease.^27,28 These represent a paradigm shift for chronic diseases aetiology as it is gradually recognised that infectious diseases are primarily only encountered in developing countries.²⁹

As will be seen below, peroxynitrite (ONOO-) is postulated by Martin Pall to be a key player in the MCS exposure mechanism. In 2007, prominent scientists from the US National Institute of Health identified this chemical as a key factor in more than 60 chronic diseases through its chemical disruption, cytotoxic effects, and tissue damage.³⁰ These diseases include neurodegenerative disorders, heart disease, vascular disease, accelerated aging, hypertension, inflammatory disease, cancer, stroke, arthritis, IBS, kidney disease, liver disease, Alzheimer’s, multiple sclerosis, and diabetes.

The MCS condition is commonly initiated by an environmental exposure, and the subsequent sensitivities result in reactions from most chemical exposures. So, is this condition highlighting environmental effects on human health? Shouldn’t there then be more interest in the MCS condition because it signals heightened sensitivity? If MCS sufferers are on the leading edge of a trend curve for the general population, it is an important and immediate problem which needs addressing.³¹

Possible Mechanisms For MCS

To propose biological mechanisms to explain MCS is, in itself, a display of ‘normalisation’ in a medical system with a ‘positivist’ view. To some experienced doctors, it is apparent that susceptible individuals are suffering neurotoxic injuries, so to focus on underlying hypersensitivity mechanisms is missing the point in addressing the real problem.³¹ There are clearly people affected, so let’s take care of them rather than ignore or dismiss them due to no established mechanism being found. Nevertheless, it can be worthwhile to examine a popular hypothesised mechanism in light of recent studies.

A quite plausible MCS mechanism has been put together over the last 15 years. This started with genetically modified mice with enhanced NMDA receptors being used in Alzheimer’s disease research.³² NMDA is a receptor for glutamate which is a primary excitatory neurotransmitter. As NMDA is known to be a key factor in the formation of memory, hence intelligence, the mice were unusually smart. But what the researchers also noticed was that the mice felt pain more acutely than normal. The researchers went on to determine whether this was because the mice remembered the pain, but concluded that they were sensitised to pain.

It is believed by many psychologists that the most basic form of learning is in experiencing pain. Increasing sensitivity with each exposure is normal in such learning processes.³² This is reinforced with neurons in the spinal cord becoming hypersensitive to sustained pain signals,³³ thus lowering the pain threshold. Furthermore, as long-term memory is established by the brain creating permanent new branches and connections between neurons, the same can happen with pain-sensing neurons after severe or prolonged pain. So enhanced pain neural pathways can also be created as typical of the central sensitivity condition. The memory-pain duality and the enhanced neural connections have been suggested as a model for MCS.^34,35 It was also found, separately, that NMDA receptor antagonists, such as dextromethorphan and ketamine, administered shortly after exposure can block an MCS reaction,³⁶ adding additional support for such a model.

Dr. Martin Pall, in 2000,³⁷ argued that an initial chemical exposure (citing 7 chemical groups in particular) creates hypersensitivity in brain neurons³⁸ which then react by increasing inflammatory cytokines, in turn increasing the levels of nitric oxide (NO), which then reacts with superoxide to form peroxynitrite, which in turn increases the cytokines, etc. The NO stimulates the release of glutamate and aspartate, stimulating NMDA receptors, which then further elevate NO levels causing a dramatic sensitisation of neural pathways. The increased peroxinitrite can also damage cell mitochondria (initiating inflammations³⁹) and damage DNA leading to downstream genotoxic effects cultivating an ideal biological environment for disease.²¹ Peroxynitrite can also break down the blood brain barrier allowing greater chemical access to the brain. NO and peroxynitrite can interact with the regulatory system governing synthesis of porphyrin biosynthetic enzymes: reduced enzymes can then lead to disruption of porphyrin metabolism (accounting for many of the simultaneous MCS symptoms).⁴⁰ NO also inhibits cytochrome P450 activity (a detoxification pathway).⁴⁰ A complex mechanism results for the MCS condition due to the clear possibility of synergism between these reactions.

A more recent study on suppressed redox defences incorporating the above discussed substances,⁴¹ and another documenting polymorphism of CCK-B in MCS patients,⁴² further develop the proposed MCS mechanism. Other studies reinforce that many neurological conditions, such as depression, are related to NMDA receptors and NO.^43,44 Recently research has emerged relating elevated nitrosine, a peroxynitrate marker, as a possible indicator for MCS.⁴⁵

Over the same period, studies have identified six genes whose products have roles in the metabolism of organic solvents and related compounds, and in some cases the metabolism of pesticides, and that influence susceptibility.^46-49 Four of these genes particularly help determine susceptibility.⁵⁰ Pall asserted that there is only one way that all these genes could be involved, namely where a chemical from an exposure would act as a toxicant. Enzymes that influence the metabolism of such toxicants then determine how sensitive the individual is in their chemical sensitivity. For example, one of these enzymes, also a gene, MTHFR, has long been recognised as important for clearing environmental chemicals via the methylation process. Testing for MTHFR deficiency has been used for testing the risk in reacting to adjuvant chemicals in vaccines^51-53 although the simple test is rarely used by doctors prior to vaccine injections.

Implications for Conventional Medical Practitioners

In general, MCS has been dismissed by conventional doctors as a psychological problem.^2,5,37,54 If MCS were accepted as having a physiological basis, this would constitute a radical change in direction for the conventional medical system. At the most basic level, a physiological mechanism recognises the modern environment as causing health problems, whereas in the past medical authorities have actively criticised any practitioner considering such a mechanism. Environmental causation of MCS challenges the one-size-fits-all mentality of a medical system, influenced by the pharmaceutical industry, according to which diagnosis, drug administration, and vaccination are done on the basis that everyone is similar. Drug research and treatment of patients are based on an ‘average’ human, never making any allowance for a sensitive subset of the population.

Rather than doctors establishing a diagnosis based on a short list of symptoms in a brief visit, environmental causation of MCS suggests they should carefully listen to the patient’s history and observations on cause and effect. The outcome would be far different than a typical visit ending in the doctor handing out a prescription for drugs based on symptoms.

In endeavouring to address an MCS potential condition in patients, the condition recognised as ‘adaptation’ needs to be adequately dealt with. Adaptation, or acclimatisation, has been recognised in workers who become accustomed to exposures in their workplace.⁵⁵ Such workers can undergo withdrawal symptoms over the weekend and perhaps start peaking in symptom intensity on the Monday morning, which gradually disappears as exposures begin again. Workers in the dynamite industry of the past, for example, would adapt to nitro-glycerine exposure and have to place some under their hatbands to avoid withdrawal, or breathe in their clothes over the weekend. The adaption phenomenon appears to be the body’s first response to chemical exposures until it seems to reach a limit, varying in individuals, from which it can no longer tolerate the exposures and descends into an MCS condition. To determine whether a patient is exhibiting a degree of adaptation, minor symptoms such as irritability, moodiness, drowsiness, fatigue, migraines, runny nose, etc would need to be noted as to whether they relate to an underlying condition. The doctor who makes a quick diagnosis from such symptoms, such as cold/flu, would be missing something more systemic and serious.

The best way to unmask adaptation is through the use of an Environmental Isolation Unit.⁵⁶ The unit protects the patient from all environmental exposures, including most foods, for about five days. Then different food groups and exposures are measurably re-introduced. Since all adaptations are unmasked, such a unit can define a patient’s sensitivities. Health authorities effectively closed down most such units 20 to 30 years ago after making the situation intolerable for the doctors (mostly clinical ecologists) to keep operating such clinics.^56,57

The approaches used by clinical ecologists are quite foreign to conventional doctors’. It is generally known that many doctors will not even diagnose conditions for which they do not have any training or background, and sometimes simply because they cannot bring themselves to recognise a condition questioned by health departments or in media reports. Many chronic fatigue syndrome (CFS), fibromyalgia syndrome (FMS) and Lyme disease sufferers can recount situations going from one doctor to another until they find one who actually will recognise and diagnose their condition. This is even more so for MCS.^58,59

Industry has long been opposed to the recognition of MCS. ^5,60 A recognition of this illness on a pathological basis would acknowledge that many industrial products can affect human health in low doses. Industry-backed studies and scientists dismissing the growing mountain of research on MCS would be expected to be welcomed and even supported by many conventional practitioners so that they do not have to change their beliefs or practices.

Recognising the Kuhnian Crisis

Kuhn put forward that a paradigm crisis can occur when many observations/occurrences conflict with the current paradigm. In some cases, a ‘scientific revolution’ can gradually lead to the end of the current paradigm.

To most doctors there is no Kuhnian crisis in relation to MCS and related conditions. There is no need to question their training or knowledge. MCS can be attributed to odour aversion or other subjective psychiatric conditions.

The extent to which a doctor may apply a conventional line of reasoning to an emergent condition will determine whether they become a skeptic or a sympathiser.

The skeptic’s positivist requirements will demand clear pathology for mainstream conformance as well as their own standard of proof. As in all scientific controversies, it is common for experts to claim their approach is more scientific: more logical, more objective and closer to pure fact. This “affords an impregnable position from which to snipe at the enemy.”⁶¹ These doctors will not focus on their profession’s lack of knowledge on low-level chemical exposures but rather focus on clear-cut areas of advancement, e.g., neural imaging advancements, successful drugs, etc.

The skeptical doctors also reference ‘weight of evidence’ and ‘scientific consensus’ to circularly reinforce their paradigm. So, an emergent health condition is pushed aside until this scientific precipice is considered to be reached. As already commented, there are many acknowledged health conditions, documented for decades in medical journals, which do not have clear pathology. Added to this, the pharmaceutical and chemical industries actively try to confuse the science on MCS recognition, just as the tobacco industry attempted to confound recognition of the health effects from smoking.

Many studies on doctor and patient communication have been performed⁶² and prominent in these are the importance of listening to the needs and preferences of the patient and avoiding unjustified psychological explanation. However, with the absence of training for doctors in the effects of low-level chemical exposures, and the MCS condition not yet fully recognised, the affected patients commonly experience dissatisfaction interfacing with doctors.^58,63 In all too many cases, a parent has seen cause and effect situations with common everyday chemical exposure, eg, with deodorisers, pesticide use, etc, and the doctor seemingly dismisses the importance of such reports. Some doctors may even accuse the parents of making fictitious claims (Munchausen Syndrome by Proxy).^64,65 The use of convenient psychological diagnoses such as this appears to have been used in an apparent retaliatory approach by some doctors when mothers of young patients have questioned diagnoses or made a complaint.⁶⁵ Of course there are many variations and degrees of such behaviour by skeptical doctors that tend to be more vocal/questioning. Nowhere in the Hippocratic oath is the requirement that service and respect must be only to those with structured pathology.

The sympathetic doctor is more ready to rely on experiential knowledge. This may come from their experience with a number of patients through observation, consistencies and logical reasoning: fundamental scientific approaches. The patient’s story and experience with their health condition is respected. The doctor doesn’t try to fit a subjective psychosomatic condition to the patient, instead remaining open to different possible understandings of the problem. If they are questioned about the MCS mechanism they are likely to reply along the lines of “medicine doesn’t know” illustrating their own acceptance of questioning of the current paradigm. In respect to doubts on the MCS condition, it would be one of doubting the medical system’s understanding of health effects from low level exposures and the level of proof required for an emerging condition rather than one of doubting the patient.⁵⁴

Both sides think the other is not being scientific or logical. Scientific reasoning by both sides comes to different conclusions. The skeptics remain undeterred. The sympathisers become disillusioned with their profession’s attitudes and lack of understanding.

Closing Remarks

The sceptical response to MCS is typical of how many emergent conditions are treated by the medical system. Even the central concepts of individual sensitisation and the environmental triggering are not in the vocabulary of most doctors. If a portion of the population reacts to environmental triggers, thereby highlighting environmental effects on health, why isn’t this attracting significant interest from the medical system which has no explanation for the cause and rise of so many illnesses and diseases?

Accepting the environmental triggering of health effects from manufactured products would create many problems for industry. In these days of synthetic consumer products, from paints to deodorants, recognition would be commercially disastrous. Furthermore, if this condition can highlight environmental causation of health effects then a Pandora’s box may be opened on the many other unexplained health problems suspected of having similar links. There is, perhaps, more money to be made in simply treating the symptoms than recognising the causes. Hence, it is politically advantageous for the medical profession to debunk this condition, creating the impression of MCS being a ‘contentious’ issue in medical science.

References

1. Randolph T. Allergic Type Reactions to Industrial Solvents and Liquid Fuels, Allergic Type Reactions to Mosquito Abatement Fogs and Mists, Allergic Type Reactions to Motor Exhaust, Allergic Type Reactions to Indoor Utility Gas and Oil Fumes, Allergic Type Reactions to Chemical Additives of Foods and Drugs Journal of Laboratory and Clinical Medicine, 1954; 44(6):910-914.

2. Ashford NA, Miller CS. Chemical Exposures: Low Levels High Stakes. New York: Van Nostrand Reinhold; 1991:26

3. Katerndahl DA, et al. Chemical Intolerance in primary care settings: prevalence, comorbidity and outcomes. The Annals of Family Medicine. 2012; 10: 4:357.

4. Kreutzer R, et al. Prevalence of people reporting sensitivities to chemicals in a population-based survey. Am J Epidemiol. 1999; 150(1):1-12.

5. McCampbell A. Multiple chemical sensitivity under siege. Townsend Letter for Doctors and Patients. Jan 2001

6. Caress M, Steinemann A. A Review of a Two-Phase Population Study of Multiple Chemical Sensitivities. Environ Health Persp. Sep 2003;11:12

7. Bell IR, et al. Self reported illness from chemical odors in young adults without clinical syndromes or occupational exposures. Arch Environ Health. 1993;48:6-13.

8. Azuma K, et al. Prevalence and Characteristics of Chemical Intolerance: A Japanese Population-Based Study. Arch Environ & Occ Health: 2015; 70/6:341-353

Bell IR, et al. Increased limbic system symptomatology and sensitizability of young adults with chemical and noise sensitivities. Environ Res. 1995;70:84-97.

Bell IR, et al. Medical histories and psychological profiles of middle-aged women with and without self-reported illness from environmental chemicals. J Clin Psychiatry. 1995;56:151–60.

Caress SM, Steinemann AC. A national population study of the prevalence of multiple chemical sensitivity. Arch Intern Med. 2004;59:300-5.

Katerndahl DA, et al. Chemical intolerance in primary care settings: prevalence, comorbidity, and outcomes. Ann Fam Med. 2012;10:357-65.

Donnay A. On the Recognition of Multiple Chemical Sensitivity in Medical Literature and Government Policy. Int’l J Toxicology. 1999;18:383

Park J, Knudson S. Statistics Canada, Health Division, How Healthy are Canadians?. Health Reports. Feb 2006;supra note 9, at 44

Yunus MB. Fibromyalgia and overlapping disorders: the unifying concept of central sensitivity syndromes. Semin Arthritis Rheum. 2007;36:339–356

Wallace DJ, Clauw DJ, editors. Fibromyalgia and other central pain syndromes. Lippincott Williams & Wilkins; 2005.

Seifert F, Maihöfner C. Functional and structural imaging of pain-induced neuroplasticity. Curr Opin Anaesthesiol. 2011;24:515–523

Institute for Chronic Pain. Central Sensitisation. Available at: http://www.instituteforchronicpain.org/understanding-chronic-pain/what-is-chronic-pain/central-sensitization. Accessed 4 Sep 2016

Desmeules J, et al. Neurophysiologic evidence for a central sensitization in patients with fibromyalgia. Arthritis Rheum. 2003;48: 1420-9.

Yunus M. Central Sensitivity Syndromes: A New Paradigm and Group Nosology for Fibromyalgia and Overlapping Conditions, and the Related Issue of Disease versus Illness. Semin Arthritis Rheum. 2008;37:339-352

Rappaport S, Smith M, Epidemiology. Environment and disease risks. Science. 2010;330(6003):460-1

Reichard A, et al. Diagnosis isn’t enough: Understanding the connections between high health care utilization, chronic conditions and disabilities among U.S. working age adults. Disabil. Health J. 2015;8;535–546.

Bijlsma N, Cohen M. Environmental Chemical Assessment in Clinical Practice: Unveiling the Elephant in the Room. Int J Env Res & Pub Hth. 2 Feb 2016;13;181

Kleisiaris C, et al. Health care practices in ancient Greece: The Hippocratic ideal. J. Med. Ethics Hist. Med. 2014;7;6.

9. United Nations Environment Programme. Global Chemicals Outlook. Towards Sound Management of Chemicals. Geneva, Switzerland; 2012.

10. WHO. Preventing Disease through Healthy Environments. Towards an Estimate of the Environmental Burden of Disease. Geneva, Switzerland; 2006

11. Paoloni-Giacobino A. Post genomic decade – The epigenome and exposome challenges. Swiss Med. Wkly. 2011;141:w13321.

12. Lopez A, et al. Remembering the forgotten non-communicable diseases. BMC Med. 2014.

13. Laborde A, et al. Children’s Health in Latin America: The Influence of Environmental Exposures. Environ. Health Perspect. 2015;123:201-209.

14. Pacher P, et al. Nitric oxide and peroxynitrite in health and disease. Physiol Rev. 2007 Jan; 87(1):315-424.

15. Donohoe M, Killing Us Softly. Internet Creative Commons release 2008: 59

Crumpler D. Prostituting Science: The Psychologisation of MCS, CFS and EHS for political gain. Maryborough, VIC; Inkling Australia; 2014:10:93

16. Woolf C. Evidence for a central component of post-injury pain hypersensitivity. Nature. 1983; 306:686-688

17. Ji R, et al. Central sensitisation and LTP: do pain and memory share similar mechanisms? Trends in Neuroscience. 2003;28:12:696-705

18. Crumpler D. MCS and the molecules of memory: a point to ponder. Sensitivity Matters. 2002;34:17-22

Donohoe, op.cit. note 31:101

19. Pall M. Elevated sustained peroxinitrite levels as the cause of chronic fatigue syndrome. Medical Hypotheses. 2000;54:115-125; Pall M. Elevated peroxynitrite as the cause of chronic fatigue syndrome. Other inducers and mechanisms of symptom generation. Journal of Chronic Fatigue Syndrome. 2000;7:4:139-145

Pall M. Explaining “Unexplained Illness”: Disease Paradigm for Chronic Fatigue Syndrome,Multiple Chemical Sensitivity, Fibromyalgia; Post-Traumatic Stress Disorder, Gulf War Syndrome and Others. New York, NY: Harrington Park Press; 2007;Ch 5

20. Meggs W. Neurogenic inflammation and sensitivity to environmental chemicals. Environmental Health Perspectives. 1993;101:3:234-238; Meggs W. Neurogenic switching: a hypothesis for a mechanism for shifting the site of inflammation in allergy and chemical sensitivity. Environmental Health Perspectives. 1995;103:1:54-56

Donohoe, op. cit. note 31:107

21. De Luca C, et al. Biological definition of multiple chemical sensitivity from redox state and cytokline profiling and not from polymorphisms of xenobiotic-metabolising enzymes. Toxicology and Applied Pharmacology. 2010;238:285-292

22. Joffres M, et al. Physiologic and symptomatic responses to low-level substances in individuals with and without chemical sensitivities: a randomised controlled blinded pilot booth study. Environmental Health Perspectives. 2005;113:1178-1183

23. Zomkowski A, et al. Involvement of NMDA receptors and l-arginine-nitric oxide-cyclic guanosine monophosphate pathway in the antidepressant-like effects of escitalopram in the forced swimming test. European Neuropsychopharmacology. 2010;20;11:793–801

24. Dhir A, Kulkarni S. Nitric oxide and major depression. Nitric Oxide. 2011;24;125–131

Belpomme D, et al. Reliable disease biomarkers characterizing and identifying electrohypersensitivity and multiple chemical sensitivity as two etiopathogenic aspects of a unique pathological disorder. Rev Environ Health. 2015;30(4):251-71.

25. Haley R, et al. Association of low PON1 type Q (type A) arylesterase activity with neurologic symptom complexes in Gulf War veterans. Toxicol Appl Pharmacol. 1999;157:227-233.

26. McKeown-Eyssen G, et al. Case-control study of genotypes in multiple chemical sensitivity: CYP2D6, NAT1, NAT2, PON1, PON2 and MTHFR. Int J Epidemiol. 2004;33,971-978.

27. Schnakenberg E, et al. A cross-sectional study of self-reported chemical-related sensitivity is associated with gene variants of drug-metabolizing enzymes. Environ Health. 2007;6,6-16.

28. Müller K, Schnakenberg E. Die Bedeutung der Glukuronidierung bei umweltmedizinischen Erkrankungen am Beispiel der UDP-Glukuronosyltransferase 1A1. Umwelt Medizin Gesellschaft 2008;21(4):295-300

29. Pall M. Multiple Chemical Sensitivity: Toxicological and Sensitivity Mechanisms. 2012: Available: http://bobnorson.com/pubs/Pall_english.pdf. Accessed: 5 Nov 2015

30. Lynch B. MTHFR and Vaccines/Immunizations – Contraindicated? Available: MTHFR.net, http://mthfr.net/forums/topic/mthfr-and-vaccinesimmunizations-contraindicated/. Accessed 7 Mar 2012

31. Reif D, et al. Genetic basis for adverse events after smallpox vaccination. J Infect Dis 2008;198:16–22

32. Homeopathy for Women. MTHFR. Available: http://www.homeopathyforwomen.org/MTHFR.htm. Accessed 21 Aug 2016

33. Phillips T. Law, Environmental Illness and Medical Uncertainty. Abingdon. Routledge; 2015

Ashford, op. cit., note 2:34-54

Donohoe, op. cit., note 31:71-73

Donohoe, op. cit., note 31:29

Personal Testimonies

Donohoe, op. cit., note 31:50

Chemical Manufacturers Association. Environmental illness briefing paper. The Reactor. 1990;4:1-13

Barnes B. Scientific Knowledge and Sociological Theory. Abingdon. Routledge; 2009

Deledda G, et al. How patients want their doctor to communicate. A literature review on primary care patients’ perspective. Patient Ed Tr. 2013;90:297-306

Crumpler, op. cit., note 35:Chap 6

Onconurse. Solving Problems With Your Doctor: Factsheet. Available: http://www.oreilly.com/onconurse/factsheets/solving_doctor.pdf. Accessed 21 Aug 2016

Hayward-Brown H. False and Highly Questionable Allegations of Munchausen Syndrome by Proxy. 7th Australasian Child Abuse and Neglect Conference, Perth, Australia. Oct 1999.

Acknowledgements: For useful discussion and feedback on drafts, I thank Brian Martin and Andrew Whelan. This research is supported by an Australian Government Research Training Program (RTP) Scholarship.

BIO

Don Want is doing a PhD in the School of Humanities and Social Inquiry at the University of Wollongong, Australia. While his professional background is as a specialist engineer, he has been in supportive roles for people with MCS for the last 35 years.