Examine individual changes

'@@ -1,63 +1,35 @@ {{alternative medicine sidebar|diagnoses}} -'''Multiple chemical sensitivity''' ('''MCS'''), also known as '''idiopathic environmental intolerances''' ('''IEI'''), is a chronic acquired illness, in which sufferers report a range of symptoms when exposed to certain everyday chemicals. +'''Multiple chemical sensitivity''' ('''MCS'''), also known as '''idiopathic environmental intolerances''' ('''IEI'''), is an unrecognized and controversial diagnosis characterized by chronic [[symptoms]] attributed to exposure to low levels of commonly used chemicals.<ref name="Genuis2013">{{cite journal|last1=Genuis|first1=SJ|date=May 2013|title=Chemical sensitivity: pathophysiology or pathopsychology?|journal=Clinical Therapeutics|volume=35|issue=5|pages=572–7|doi=10.1016/j.clinthera.2013.04.003|pmid=23642291}}</ref><ref>{{cite journal|doi = 10.1615/CritRevNeurobiol.v13.i3.30|pmid = 10803638|title = Multiple Chemical Sensitivity: Potential Role for Neural Sensitization|journal = Critical Reviews in Neurobiology|volume = 13|issue = 3|pages = 283–316|year = 1999|last1 = Sorg|first1 = Barbara A.}}</ref> Symptoms are typically [[vagueness|vague]] and [[non-specific symptoms|non-specific]]. They may include [[fatigue (medical)|fatigue]], [[headache]]s, [[nausea]], and [[dizziness]]. -A 2018 scientific review said MCS was "a complex syndrome that manifests as a result of exposure to a low level of various common contaminants."<ref name="Rossi2018">{{cite journal | vauthors = Rossi S, Pitidis A | title = Multiple Chemical Sensitivity: Review of the State of the Art in Epidemiology, Diagnosis, and Future Perspectives | journal = Journal of Occupational and Environmental Medicine | volume = 60 | issue = 2 | pages = 138–146 | date = February 2018 | pmid = 29111991 | pmc = 5794238 | doi = 10.1097/JOM.0000000000001215 | author-link = }}</ref> Another review, also from 2018, said it was characterized by "susceptibility to a wide spectrum of environmental compounds, causing symptoms involving various organs and a decrease in quality of life."<ref name="pmid30088144" /> +Although these symptoms can be debilitating, MCS is not recognized as an organic, chemical-caused illness by the [[World Health Organization]], [[American Medical Association]], nor any of several other professional medical organizations.<ref name="Sears" /><ref name="Gots">{{cite journal|author=Gots RE|year=1995|title=Multiple chemical sensitivities--public policy|journal=J. Toxicol. Clin. Toxicol.|volume=33|issue=2|pages=111–3|doi=10.3109/15563659509000459|pmid=7897748|quote=The phenomenon of multiple chemical sensitivities is a peculiar manifestation of our technophobic and chemophobic society. It has been rejected as an established organic disease by the American Academy of Allergy and Immunology, the American Medical Association, the California Medical Association, the American College of Physicians, and the International Society of Regulatory Toxicology and Pharmacology. It may be the only ailment in existence in which the patient defines both the cause and the manifestations of his own condition.}}</ref>{{Primary source inline|date=June 2020|reason=1995 Gots source also too old}} [[Blinding (medicine)|Blinded]] clinical trials show that people with MCS react as often and as strongly to [[placebo]]s as they do to chemical stimuli; the existence and severity of symptoms is seemingly related to perception that a chemical stimulus is present.<ref name="Das-Munshi 2006">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)</ref><ref name="Bornschein">{{cite journal |vauthors=Bornschein S, Hausteiner C, Römmelt H, Nowak D, Förstl H, Zilker T |title=Double-blind placebo-controlled provocation study in patients with subjective Multiple Chemical Sensitivity (MCS) and matched control subjects |journal=Clin Toxicol |volume=46 |issue=5 |pages=443–9 |year=2008 |pmid=18568800 |doi=10.1080/15563650701742438|s2cid=205901786 |url=http://mediatum.ub.tum.de/doc/694041/document.pdf }}</ref>{{Primary source inline|date=June 2020|reason=Bornschein is primary source}} -Commonly reported triggers for MCS symptoms include products like perfume, fresh paint fumes, tobacco smoke and mold.<ref name="Valderrama2015" /><ref name=":50">{{cite journal | vauthors = Pigatto PD, Guzzi G | title = Prevalence and risk factors for multiple chemical sensitivity in Australia | journal = Preventive Medicine Reports | volume = 14 | pages = 100856 | date = June 2019 | pmid = 31193443 | pmc = 6527960 | doi = 10.1016/j.pmedr.2019.100856 }}</ref> +Commonly attributed substances include scented products (e.g. perfumes), [[pesticide]]s, plastics, synthetic fabrics, smoke, [[petroleum]] products, and paint fumes.<ref name="Genuis2013"/> -The cause of the condition is unknown.<ref name=":1" /> +== Symptoms == +Symptoms are typically [[Vagueness|vague]] and [[Non-specific symptoms|non-specific]], such as [[Fatigue (medical)|fatigue]] or [[Headache|headaches]].<ref name=":6" /> These symptoms, although they can be disabling, are called non-specific because they are not associated with any single specific medical condition. -== Symptoms == A 2010 review of MCS literature said that the following symptoms, in this order, were the most reported in the condition: headache, fatigue, confusion, depression, shortness of breath, arthralgia, myalgia, nausea, dizziness, memory problems, gastrointestinal symptoms, respiratory symptoms.<ref name=":6" /> + +Symptoms mainly arise from the [[autonomic nervous system]] (such as [[nausea]] or [[dizziness]]) or have psychiatric or psychological aspects (such as difficulty concentrating).<ref name=":12">{{Cite journal |last=Katoh |first=Takahiko |date=2018 |title=Multiple Chemical Sensitivity (MCS): History, Epidemiology and Mechanism |journal=Nihon Eiseigaku Zasshi |trans-journal=Japanese Journal of Hygiene |language=ja|volume=73|issue=1|pages=1–8|doi=10.1265/jjh.73.1|issn=1882-6482|pmid=29386440|doi-access=free}}</ref> == Possible causes == +There is a general agreement among most MCS researchers that the cause is not specifically related to sensitivity to chemicals, but this does not preclude the possibility that symptoms are caused by other known or unknown factors. Various health care professionals and government agencies are working on giving those who report the symptoms proper care while searching for a cause.<ref name=":7">Task Force on Environmental Health (2017). ''[http://www.health.gov.on.ca/en/common/ministry/publications/reports/environmental_health_2017/task_force_on_environmental_health_report.pdf Time for leadership: recognizing and improving care for those with ME/CFS, FM and ES/MCS]''. Phase 1 report. Toronto, Ontario: Ministry of Health and Long-Term Care; 2017.</ref> + In 2017, a Canadian government Task Force on Environmental Health said that there had been very little rigorous peer-reviewed research into MCS and almost a complete lack of funding for such research in North America.<ref name=":8">Task Force on Environmental Health (2017). ''[http://www.health.gov.on.ca/en/common/ministry/publications/reports/environmental_health_2017/task_force_on_environmental_health_report.pdf Time for leadership: recognizing and improving care for those with ME/CFS, FM and ES/MCS]''. Phase 1 report. Toronto, Ontario: Ministry of Health and Long-Term Care; 2017. p. 53.</ref> "Most recently," it said, "some peer-reviewed clinical research has emerged from centres in Italy, Denmark and Japan suggesting that there are fundamental neurobiologic, metabolic, and genetic susceptibility factors that underlie ES/MCS."<ref name=":8" /> -The US [[Occupational Safety and Health Administration]] (OSHA) said, [as of June 2021], “Chemical sensitivity is generally accepted as a reaction to chemicals but debate continues as to whether MCS is classifiable as an illness...Proposed theories to explain the cause of MCS include allergy, dysfunction of the immune system, neurobiological sensitization, and various psychological theories. There is insufficient scientific evidence to confirm a relationship between any of these possible causes and symptoms.”<ref>{{cite web|title=Safety and Health Topics &#124; Multiple Chemical Sensitivities|url=https://www.osha.gov/multiple-chemical-sensitivities|access-date=2021-06-15|publisher=Osha.gov}}</ref> - -=== Risk factors === -Contact with a wide range of environmental exposure factors increases the incidence of chronic inflammatory diseases such as MCS. In addition to pollution and mold pollution, electromagnetic fields are increasingly coming into play due to the expansion of mobile communications.<ref name="Hill_2010" />{{rp|3}} - -Some areas in everyday life pose a particular health risk:<ref name="Hill_2010" />{{rp|3/4}} - -* chemically unbound [[plasticizers]] (mainly [[Phthalate|phthalates]]) in food packaging, toys for children or medical utensils such as infusion sets or catheters. As plasticizers in packaging films, phthalates are easily stored in foods with a high fat content. -* Fumigation of freight containers during overseas transports with pesticides / [[halogenated hydrocarbons]] such as [[dibromoethane]] or [[dichloroethane]] -* Use of [[Insecticide|insecticides]] / [[pyrethroids]] in the private sector but also in aircraft cabins or train wagons -* Easy access to toxic pesticides, disinfectants and biocides in cleaning products in supermarkets and drugstores -* Contamination of food with up to 16 different pesticides in order to comply with the limit values. However, these limits are often exceeded. -* synthetic fragrances in soaps, detergents, dishwashing detergents and cleaning agents -* Computer and electronic devices with [[flame retardants]] such as [[diphenyl ether]], [[tetrabromobisphenol A]] or [[Trialkyl phosphate|trialkylphosphates]], which outgas during operation -* Outgassing flame retardants, insecticides and fungicides as well as plasticizers and plastic monomers in floor coverings, furniture and textiles. Phthalates, for example, are chemically unbound and therefore constantly release gas in small quantities and, like PCBs or [[dioxins]], can accumulate or deposit on wall surfaces. With rising temperatures (e.g. heating in winter) they evaporate again and lead to short-term high exposure. -* increasing proportion of [[flavor]] substances, [[emulsifiers]], [[colorants]], synthetic [[sweeteners]] and sugar in industrial foods -* Expansion of waste incineration plants as well as incineration of hazardous waste in waste-to-energy plants, which ideally still just comply with the limit values. Small amounts of chlorinated dioxins and [[Biphenylene|biphenylenes]] are allowed to be released into the environment, but extrapolated over a year, accumulations in the gram range are possible. In humans, the substances are stored in adipose tissue, the accumulation is favored by the chemical stability and they also have a long half-life. -* Production and use of persistent organic pollutants and [[Hazardous substance|CMR-substances]] -* [[Wood preservatives]] ([[Lindane]]) in the living room - -There are a large number of studies on the MCS prevalence in collectives who became ill after increased exposure to harmful substances. The percentage of people with subsequent chemical intolerances or MCS in these groups was between 25% and 60%.<ref>Overview in: Ashford and Miller 1998, Maschewsky 1996</ref> - -MCS is more common in people with additional chronic conditions. Vulnerability of those affected is suspected here: - -* [[Bronchial asthma| Asthma]] and hyperreactive bronchial system -* allergic disposition -* other intolerances (food, medication) -* post-traumatic stress disorder -* psychosocial stress -* anxious disposition or anxiety disorders -* female gender - -The MCS risk is disproportionately increased if several of the risk factors are present (e.g. exposure to solvents, allergic disposition and stress).<ref name="E">E. Schwarz, A. Bauer, U. Martens: "Allergies, stress and pollutants as risk factors for chemical intolerance and" Multiple Chemical Sensitivity "(MCS)." In: "Allergo Journal." (2006); 15, pp. 139–140.</ref> Income, social status or ethnic affiliation, on the other hand, do not influence the frequency of MCS.<ref>Buchwald and Garrity 1994, Kreutzer et al. 1999.</ref> +The US [[Occupational Safety and Health Administration]] (OSHA) says that MCS is highly controversial and that there is insufficient scientific evidence to explain the relationship between any of the suggested causes of MCS – it lists "allergy, dysfunction of the immune system, neurobiological sensitization, and various psychological theories" as the suggested causes – and its symptoms.<ref>{{cite web|title=Safety and Health Topics &#124; Multiple Chemical Sensitivities|url=http://www.osha.gov/SLTC/multiplechemicalsensitivities/index.html|access-date=2014-06-08|publisher=Osha.gov}}</ref> ===Immunological=== MCS was originally promoted as a type of allergy, and later as a type of non-allergic immunological disorder. However, these ideas have largely been rejected. Unlike people with allergic disorders, [[autoimmune disease]]s, or [[Immunodeficiencies|immunodeficiences]], people with MCS have no objective immunological abnormalities.<ref name=":0" /> The absence of immunological abnormalities in people with MCS (such as different [[white blood cell]] counts or the presence of abnormal [[Autoantibody|autoantibodies]]) indicates that the problem lies elsewhere.<ref name=":0" /> -People who are experiencing symptoms of MCS do not routinely exhibit the immune markers associated with allergies.<ref name="Australia2010-allergy">{{Cite web|title=A Scientific Review of Multiple Chemical Sensitivity: Identifying Key Research Needs.''|date=2010|publisher=National Industrial Chemicals Notification and Assessment Scheme, Australian Government|location=Canberra, Australia|pages=21–22|url=http://test.nicnas.gov.au/Media/Latest_News/MCS.asp|url-status=dead|quote=A classical allergic reaction involves a specific cell or antibody-mediated response that alerts the body to the allergen and results in changes to some immunological parameters (such as increased serum IgE, IgG, complement levels or lymphocyte counts) that can be measured biochemically. Early immunological testing of MCS patients did not find levels of immunoglobulins, complement, B-cell, T-cell or T-cell subsets in MCS subjects outside normal limits that would indicate either allergic sensitisation or aberrant immune reactivities (Terr, 1986). Subsequent studies have reported out of range values in individual MCS patients for immunoglobulins, complement components, peripheral blood lymphocyte subsets, activated T cells or abnormal serum antibodies to tissue antigens and chemical-protein conjugates (Thrasher et al. 1990; Fiedler et al., 1992; Heuser et al. 1992; Kipen et al. 1992; Levin and Byers, 1992; Rea et al. 1992). However, across these studies, there were no consistent findings suggestive of immunological reactivity in MCS.|access-date=2019-10-15|archive-date=2019-12-14|archive-url=https://web.archive.org/web/20191214155129/http://test.nicnas.gov.au/Media/Latest_News/MCS.asp}}</ref> In the 1980s and 1990s, some researchers hypothesized that these immune irregularities suggested that MCS was caused by a chemically induced disturbance of the immune system, which resulted in chronic immune dysfunction.<ref name="Australia2010-allergy" /><ref name="Genuis2013">{{cite journal | vauthors = Genuis SJ | title = Chemical sensitivity: pathophysiology or pathopsychology? | journal = Clinical Therapeutics | volume = 35 | issue = 5 | pages = 572–7 | date = May 2013 | pmid = 23642291 | doi = 10.1016/j.clinthera.2013.04.003 }}</ref> However, there is no consistent pattern of immunological reactivity or abnormality in MCS.<ref name="Australia2010-allergy" /><ref>{{cite journal | vauthors = Labarge XS, McCaffrey RJ | title = Multiple chemical sensitivity: a review of the theoretical and research literature | journal = Neuropsychology Review | volume = 10 | issue = 4 | pages = 183–211 | date = December 2000 | pmid = 11132100 | doi = 10.1023/a:1026460726965 | s2cid = 22976957 }}</ref> +People who are experiencing symptoms of MCS do not routinely exhibit the immune markers associated with allergies.<ref name="Australia2010-allergy">{{Cite web|title=A Scientific Review of Multiple Chemical Sensitivity: Identifying Key Research Needs.''|date=2010|publisher=National Industrial Chemicals Notification and Assessment Scheme, Australian Government|location=Canberra, Australia|pages=21–22|url=http://test.nicnas.gov.au/Media/Latest_News/MCS.asp|url-status=dead|quote=A classical allergic reaction involves a specific cell or antibody-mediated response that alerts the body to the allergen and results in changes to some immunological parameters (such as increased serum IgE, IgG, complement levels or lymphocyte counts) that can be measured biochemically. Early immunological testing of MCS patients did not find levels of immunoglobulins, complement, B-cell, T-cell or T-cell subsets in MCS subjects outside normal limits that would indicate either allergic sensitisation or aberrant immune reactivities (Terr, 1986). Subsequent studies have reported out of range values in individual MCS patients for immunoglobulins, complement components, peripheral blood lymphocyte subsets, activated T cells or abnormal serum antibodies to tissue antigens and chemical-protein conjugates (Thrasher et al. 1990; Fiedler et al., 1992; Heuser et al. 1992; Kipen et al. 1992; Levin and Byers, 1992; Rea et al. 1992). However, across these studies, there were no consistent findings suggestive of immunological reactivity in MCS.|access-date=2019-10-15|archive-date=2019-12-14|archive-url=https://web.archive.org/web/20191214155129/http://test.nicnas.gov.au/Media/Latest_News/MCS.asp}}</ref> In the 1980s and 1990s, some researchers hypothesized that these immune irregularities suggested that MCS was caused by a chemically induced disturbance of the immune system, which resulted in chronic immune dysfunction.<ref name="Australia2010-allergy" /><ref name="Genuis2013" /> However, there is no consistent pattern of immunological reactivity or abnormality in MCS.<ref name="Australia2010-allergy" /><ref>{{cite journal | author = Labarge XS, McCaffrey RJ | year = 2000 | title = Multiple chemical sensitivity: a review of the theoretical and research literature | journal = Neuropsychol Rev | volume = 10 | issue = 4| pages = 183–211 | doi=10.1023/a:1026460726965| pmid = 11132100 | s2cid = 22976957 }}</ref> -There is also evidence that people with MCS are more likely than controls to have [[Allergy|allergies]]<ref name="Valderrama2015">{{Cite web|title=Actualizacion de la Evidencia Cientifica sobre Sensibilidad Quimica Multiple (SQM)|trans-title=Review of the scientific evidence on Multiple Chemical Sensitivity|url=https://www.sergas.es/Asistencia-sanitaria/Documents/953/Actualizaci%C3%B3n%20de%20la%20evidencia%20cient%C3%ADfica%20sobre%20sensibilidad%20qu%C3%ADmica%20m%C3%BAltiple.pdf|location=Madrid: Ministerio de Sanidad, Servicios Sociales e Igualdad|vauthors=Valderrama Rodríguez M, Revilla López MC, Blas Diez MP, Vázquez Fernández del Pozo S, Martín Sánchez JI|type=pdf}}</ref>{{Rp|16}} <ref name=Hybenova2010>{{cite journal | vauthors = Hybenova M, Hrda P, Procházková J, Stejskal V, Sterzl I | title = The role of environmental factors in autoimmune thyroiditis | journal = Neuro Endocrinology Letters | volume = 31 | issue = 3 | pages = 283–9 | year = 2010 | pmid = 20588228 }}</ref><ref>{{cite journal | vauthors = Ziem G, McTamney J | title = Profile of patients with chemical injury and sensitivity | journal = Environmental Health Perspectives | volume = 105 | issue = Suppl 2 | pages = 417–36 | date = March 1997 | pmid = 9167975 | pmc = 1469804 | doi = 10.2307/3433348 | jstor = 3433348 }}</ref><ref>{{cite journal | vauthors = Nogué S, Fernández-Solá J, Rovira E, Montori E, Fernández-Huerta JM, Munné P | title = [Multiple chemical sensitivity: study of 52 cases] | journal = Medicina Clinica | volume = 129 | issue = 3 | pages = 96–8; quiz 99 | date = June 2007 | pmid = 17594860 | doi = 10.1157/13107370 }}</ref> +There is also evidence that people with MCS are more likely than controls to have [[Allergy|allergies]]<ref name="Valderrama2015">{{Cite web|title=Actualizacion de la Evidencia Cientifica sobre Sensibilidad Quimica Multiple (SQM)|trans-title=Review of the scientific evidence on Multiple Chemical Sensitivity|url=https://www.sergas.es/Asistencia-sanitaria/Documents/953/Actualizaci%C3%B3n%20de%20la%20evidencia%20cient%C3%ADfica%20sobre%20sensibilidad%20qu%C3%ADmica%20m%C3%BAltiple.pdf|location=Madrid: Ministerio de Sanidad, Servicios Sociales e Igualdad|vauthors=Valderrama Rodríguez M, Revilla López MC, Blas Diez MP, Vázquez Fernández del Pozo S, Martín Sánchez JI|type=pdf}}</ref>{{Rp|16}} <ref name=Hybenova2010>{{cite journal |vauthors=Hybenova M, Hrda P, Prochazkova J, Stejskal V, Sterzl I | year = 2010 | title = The role of environmental factors in autoimmune thyroiditis | journal = Neuro Endocrinol Lett | volume = 31 | issue = 3| pages = 283–9 | pmid = 20588228 }}</ref><ref>{{cite journal |vauthors=Ziem G, McTamney J | year = 1997 | title = Profile of patients with chemical injury and sensitivity | journal = Environ Health Perspect | volume = 105 | issue = Suppl 2| pages = 417–36 | doi=10.2307/3433348| jstor = 3433348 | pmid = 9167975 | pmc = 1469804 }}</ref><ref>{{cite journal |vauthors=Nogue S, Fernandez-Sola J, Rovira E, Montori E, Fernandez-Huerta JM, Munne P | year = 2007 | title = Multiple chemical sensitivity: study of 52 cases | journal = Med Clin (Barc) | volume = 129 | issue = 3| pages = 96–8 | doi = 10.1157/13107370 | pmid = 17594860 }}</ref> === Psychological === -Several mechanisms for a psychological etiology of the condition have been proposed, including theories based on misdiagnoses of an underlying mental illness, stress, or [[classical conditioning]].{{Citation needed|date=October 2019}} Many people with MCS also meet the criteria for [[major depressive disorder]] or [[anxiety disorder]].<ref name="Lax">{{cite journal | vauthors = Lax MB, Henneberger PK | title = Patients with multiple chemical sensitivities in an occupational health clinic: presentation and follow-up | journal = Archives of Environmental Health | volume = 50 | issue = 6 | pages = 425–31 | year = 1995 | pmid = 8572720 | doi = 10.1080/00039896.1995.9935978 }}</ref>{{primary source inline|date=June 2019}} Other proposed explanations include [[somatic symptom disorder]],<ref name="pmid16314597">{{cite journal | vauthors = Bailer J, Witthöft M, Paul C, Bayerl C, Rist F | title = Evidence for overlap between idiopathic environmental intolerance and somatoform disorders | journal = Psychosomatic Medicine | volume = 67 | issue = 6 | pages = 921–9 | year = 2005 | pmid = 16314597 | doi = 10.1097/01.psy.0000174170.66109.b7 | s2cid = 43197074 }}</ref>{{primary source inline|date=June 2019}} [[panic disorder]],<ref>{{cite journal | vauthors = Binkley KE, Kutcher S | title = Panic response to sodium lactate infusion in patients with multiple chemical sensitivity syndrome | journal = The Journal of Allergy and Clinical Immunology | volume = 99 | issue = 4 | pages = 570–4 | date = April 1997 | pmid = 9111504 | doi = 10.1016/s0091-6749(97)70086-1 }}</ref>{{primary source inline|date=June 2019}} [[migraine]], [[chronic fatigue syndrome]], or [[fibromyalgia]] and brain fog. Through behavioral conditioning, it has been proposed that people with MCS may develop real, but unintentionally psychologically produced, symptoms, such as anticipatory nausea, when they encounter certain odors or other perceived triggers.<ref>{{cite journal | vauthors = Hetherington L, Battershill J | title = Review of evidence for a toxicological mechanism of idiopathic environmental intolerance | journal = Human & Experimental Toxicology | volume = 32 | issue = 1 | pages = 3–17 | date = January 2013 | pmid = 23060407 | doi = 10.1177/0960327112457189 | s2cid = 37072673 }}</ref><ref name="pmid16314597" />{{primary source inline|date=June 2019}} It has also been proposed in one study that individuals may have a tendency to "catastrophically misinterpret benign physical symptoms"<ref name="Medscape">{{cite web |url=http://www.medscape.com/viewarticle/411615 |title= Idiopathic Environmental Intolerance May Have Psychological Component|publisher=Medscape.com |access-date=2008-01-13 }}</ref><ref name="pmid16314597" />{{primary source inline|date=June 2019}} or simply have a disturbingly acute sense of smell.{{medical citation needed|date=June 2019}} The personality trait [[Absorption (psychology)|absorption]], in which individuals are predisposed to becoming deeply immersed in sensory experiences, may be stronger in individuals reporting symptoms of MCS.<ref>{{cite journal | vauthors = Witthöft M, Rist F, Bailer J | title = Evidence for a specific link between the personality trait of absorption and idiopathic environmental intolerance | journal = Journal of Toxicology and Environmental Health. Part A | volume = 71 | issue = 11–12 | pages = 795–802 | year = 2008 | pmid = 18569578 | doi = 10.1080/15287390801985687 | s2cid = 32122169 }}</ref><ref name="pmid16314597" />{{primary source inline|date=June 2019|reason=Bailer 2005 and Whitthoft 2008}} In the 1990s, behaviors exhibited by MCS sufferers were hypothesized by some to reflect broader sociological fears about industrial pollution and broader societal trends of [[technophobia]] and [[chemophobia]].<ref name="Shorter1997">{{cite journal | vauthors = Shorter E | title = Multiple chemical sensitivity: pseudodisease in historical perspective | journal = Scandinavian Journal of Work, Environment & Health | volume = 23 | issue = Supplement 3 | pages = 35–42 | date = 1997 | pmid = 9456064 }}</ref><ref name="pmid16314597" /> +Several mechanisms for a psychological etiology of the condition have been proposed, including theories based on misdiagnoses of an underlying mental illness, stress, or [[classical conditioning]].{{Citation needed|date=October 2019}} Many people with MCS also meet the criteria for [[major depressive disorder]] or [[anxiety disorder]].<ref name="Lax">{{cite journal|vauthors=Lax MB, Henneberger PK|year=1995|title=Patients with multiple chemical sensitivities in an occupational health clinic: presentation and follow-up|journal=Arch. Environ. Health|volume=50|issue=6|pages=425–31|doi=10.1080/00039896.1995.9935978|pmid=8572720}}</ref>{{primary source inline|date=June 2019}} Other proposed explanations include [[somatic symptom disorder]],<ref name="pmid16314597">{{cite journal |vauthors=Bailer J, Witthöft M, Paul C, Bayerl C, Rist F |title=Evidence for overlap between idiopathic environmental intolerance and somatoform disorders |journal=[[Psychosom Med]] |volume=67 |issue=6 |pages=921–9 |year=2005 |pmid=16314597 |doi=10.1097/01.psy.0000174170.66109.b7 |s2cid=43197074 |url=http://www.psychosomaticmedicine.org/cgi/pmidlookup?view=long&pmid=16314597}}</ref>{{primary source inline|date=June 2019}} [[panic disorder]],<ref>{{cite journal |vauthors=Binkley KE, Kutcher S | year = 1997 | title = Panic response to sodium lactate infusion in patients with multiple chemical sensitivity syndrome | journal = J Allergy Clin Immunol | volume = 99 | issue = 4| pages = 570–4 | doi=10.1016/s0091-6749(97)70086-1| pmid = 9111504 }}</ref>{{primary source inline|date=June 2019}} [[migraine]], [[chronic fatigue syndrome]], or [[fibromyalgia]] and brain fog. Through behavioral conditioning, it has been proposed that people with MCS may develop real, but unintentionally psychologically produced, symptoms, such as anticipatory nausea, when they encounter certain odors or other perceived triggers.<ref>{{Cite journal|title = Review of evidence for a toxicological mechanism of idiopathic environmental intolerance|journal = Human & Experimental Toxicology|date = 2013-01-01|issn = 1477-0903|pmid = 23060407|pages = 3–17|volume = 32|issue = 1|doi = 10.1177/0960327112457189|first1 = Lh|last1 = Hetherington|first2 = Jm|last2 = Battershill|s2cid = 37072673}}</ref><ref name="pmid16314597" />{{primary source inline|date=June 2019}} It has also been proposed in one study that individuals may have a tendency to "catastrophically misinterpret benign physical symptoms"<ref name="Medscape">{{cite web |url=http://www.medscape.com/viewarticle/411615 |title= Idiopathic Environmental Intolerance May Have Psychological Component|publisher=Medscape.com |access-date=2008-01-13 }}</ref><ref name="pmid16314597" />{{primary source inline|date=June 2019}} or simply have a disturbingly acute sense of smell.{{medical citation needed|date=June 2019}} The personality trait [[Absorption (psychology)|absorption]], in which individuals are predisposed to becoming deeply immersed in sensory experiences, may be stronger in individuals reporting symptoms of MCS.<ref>{{cite journal |vauthors=Witthöft M, Rist F, Bailer J |title=Evidence for a specific link between the personality trait of absorption and idiopathic environmental intolerance |journal=J. Toxicol. Environ. Health Part A |volume=71 |issue=11–12 |pages=795–802 |year=2008 |pmid=18569578 |doi=10.1080/15287390801985687 |s2cid=32122169 }}</ref><ref name="pmid16314597" />{{primary source inline|date=June 2019|reason=Bailer 2005 and Whitthoft 2008}} In the 1990s, behaviors exhibited by MCS sufferers were hypothesized by some to reflect broader sociological fears about industrial pollution and broader societal trends of [[technophobia]] and [[chemophobia]].<ref name="Shorter1997">{{cite journal |last1=Shorter |first1=E |title=Multiple chemical sensitivity: pseudodisease in historical perspective |journal=Scandinavian Journal of Work, Environment, and Health |date=1997 |volume=23 |issue=Supplement 3 |pages=35–42 |pmid=9456064}}</ref><ref name="pmid16314597" /> -These theories have attracted criticism.<ref name=":7">Task Force on Environmental Health (2017). ''[http://www.health.gov.on.ca/en/common/ministry/publications/reports/environmental_health_2017/task_force_on_environmental_health_report.pdf Time for leadership: recognizing and improving care for those with ME/CFS, FM and ES/MCS]''. Phase 1 report. Toronto, Ontario: Ministry of Health and Long-Term Care; 2017.</ref><ref>{{cite journal | vauthors = Tuuminen T | title = Multiple Chemical Sensitivity: Review of the State of the Art in Epidemiology, Diagnosis, and Future Perspectives | journal = Journal of Occupational and Environmental Medicine | volume = 60 | issue = 8 | pages = e429 | date = August 2018 | pmid = 29851734 | doi = 10.1097/JOM.0000000000001369 | s2cid = 46918964 }}</ref> +These theories have attracted criticism.<ref name=":7" /><ref>{{Cite journal | doi=10.1097/JOM.0000000000001369| pmid=29851734| title=Multiple Chemical Sensitivity| journal=Journal of Occupational and Environmental Medicine| volume=60| issue=8| pages=e429| year=2018| last1=Tuuminen| first1=Tamara}}</ref> In Canada, in 2017, following a three-year government inquiry into environmental illness, it was recommended that a public statement be made by the health department.<ref>Task Force on Environmental Health (2017). [http://www.health.gov.on.ca/en/common/ministry/publications/reports/environmental_health_2017/task_force_on_environmental_health_report.pdf Time for leadership: recognizing and improving care for those with ME/CFS, FM and ES/MCS. Phase 1 report.] Toronto, Ontario: Ministry of Health and Long-Term Care; 2017.p.17</ref>{{Update inline|date=June 2020|type=was a statement made?}} @@ -65,88 +37,17 @@ A 2018 systematic review concluded that the evidence suggests that abnormalities in sensory processing pathways combined with peculiar personality traits best explains this condition.<ref name="pmid30088144" /> -== Pathomechanism == -There are two toxicological approaches to explain the pathomechanism of MCS: the model of neurogenic inflammation and the model of chemical inflammation. +== Diagnosis == +In practice, diagnosis relies entirely upon the [[Self-report study|self-reported]] claim that symptoms are triggered by exposure to various substances.<ref name=":0" /> -=== Neurogenic inflammation === -Chemical exposure can occur in patients without them perceiving an unpleasant odor.<ref name = "Hill_2010">{{cite book | vauthors = Hill HU, Huber W, Müller KE | title=Multiple Chemikalien-Sensitivität (MCS): Ein Krankheitsbild der chronischen Multisystemerkrankungen (CMI). Umweltmedizinische, toxikologische und sozialpolitische Aspekte – Ein Blick auf den aktuellen Forschungsstand|edition=3rd |publisher=Shaker|publication-place=Aachen |isbn=978-3-8322-9046-7 |date=2010 |language=German}}</ref>{{rp|62}} This leads to changes in brain functions: There is a reduced blood flow to the [[temporal lobe]], the two temporal regions and the prefortal areas of the cerebral cortex. This disorder is permanent in chronically ill patients. Further exposure to triggering substances leads to an additional reduced blood flow to the [[olfactory brain]] in the right and left [[hippocampus]], in the right [[Parahippocampal gyrus]], in the right [[amygdala]], in the right [[thalamus]] and in the right lower cerebral cortex. In healthy patients, other regions are affected by decreased blood flow.<ref name = "Hill_2010" />{{rp|82}} +Many other tests have been promoted by various people over the years, including testing of the immune system, [[porphyrin metabolism]], provocation-neutralization testing, [[autoantibodies]], the [[Epstein–Barr virus]], testing for evidence of exposure to pesticides or heavy metals, and challenges involving exposure to chemicals, foods, or inhalants.<ref name=":0" /> None of these tests correlate with MCS symptoms, and none are useful for diagnosing MCS.<ref name=":0" /> -Volatile, organic compounds also lead to prolonged reaction and reflex times, a disturbed sense of balance, a decline in the ability to differentiate between colors and cognitive performance.<ref name = "Hill_2010" />{{rp|66}} +The stress and [[Anxiety disorder|anxiety]] experienced by people reporting MCS symptoms are significant.<ref name=":0" /> [[Neuropsychological assessment]]s do not find differences between people reporting MCS symptoms and other people in areas such as verbal learning, memory functioning, or [[psychomotor learning|psychomotor performance]].<ref name=":0" /> Neuropsychological tests are [[Sensitivity and specificity|sensitive but not specific]], and they identify differences that may be caused by unrelated medical, neurological, or neuropsychological conditions.<ref name=":0" /> -A direct transport of chemicals via the [[olfactory system]] has been demonstrated in rats.<ref>{{cite journal | vauthors = Sorg BA, Swindell S, Tschirgi ML | title = Repeated low level formaldehyde exposure produces enhanced fear conditioning to odor in male, but not female, rats | journal = Brain Research | volume = 1008 | issue = 1 | pages = 11–9 | date = May 2004 | pmid = 15081377 | doi = 10.1016/j.brainres.2004.02.015 | s2cid = 40180809 }}</ref> There, Harmful substance act directly on the brain, since the [[blood–brain barrier]] is circumvented: from the olfactory mucosa to the [[olfactory bulb]] / [[Olfactory nerve| 1. Cranial nerve]], on to the amygdala and finally into the limbic system and via the thalamus to the frontal cortex.<ref name = "Hill_2010" />{{rp|68–59}} - -Repeated excitation of this nervous system leads to sensitization, especially in the [[limbic system]], as a result of which the threshold for subsequent reactions to chemicals is lowered. This in turn leads to an unspecific readiness to react to substances to which someone has not yet been exposed.<ref name = "Hill_2010" />{{rp|70–71}} - -After exposure of MCS patients to volatile, organic compounds, the values of [[nerve growth factor]] and of [[Vasoactive intestinal peptide|vasoactive peptide]] rise above the already increased base value.<ref>{{cite journal | vauthors = Kimata H | title = Effect of exposure to volatile organic compounds on plasma levels of neuropeptides, nerve growth factor and histamine in patients with self-reported multiple chemical sensitivity | journal = International Journal of Hygiene and Environmental Health | volume = 207 | issue = 2 | pages = 159–63 | date = February 2004 | pmid = 15031958 | doi = 10.1078/1438-4639-00262 }}</ref> This is not the case in patients with [[Dermatitis|allergic eczema]] or allergic dermatitis. This enables the distinction between neurogenic inflammation and atopic or allergic forms.<ref name = "Hill_2010" />{{rp|77}} - -==== TRP receptors ==== -The binding of certain foreign substances or pollutants to chemo- or nociceptors of sensitive [[Nociceptor|C-fibers]] in the skin, internal organs and mucous membranes of the airways leads to their excitation and the transmission of this signal to the central nervous system. The most important nociceptors are the [[Vanilloid receptor|vanilloid]] and the [[TRP channels|TRP receptors]]. These are activated by [[capsaicin]], reactive oxygen compounds, volatile fungal toxins of the [[dialdehyde]] type (e.g. [[Isovaleraldehyde|isovalleral]]) or volatile organic emissions. The receptors are therefore jointly responsible for the triggering in phase II and for the development of the symptoms in phase I.<ref name = "Hill_2010" />{{rp|73}} The C-fibers excited by the receptors send the signal to the [[spinal cord]] and the [[medulla oblongata]]. As a result,[[ Glutamate]] is released and the [[NMDA receptor]] is activated. It is phosphorylated and thus permanently switched to an activated state, so that there is an increased sensitivity to stimuli with the same stimulus. Some of the nerve cells activated in this way release [[Substance P]] into the [[Central nervous system|CNS]] and the periphery. Substance P is in turn responsible for triggering inflammatory and pain reactions.<ref name = "Hill_2010" />{{rp|73}} - -The clinical picture of [[Fibromyalgia]] is partly caused by the same mechanism.<ref name = "Hill_2010" />{{rp|73–74}} - -The TRPA1 receptor, a subgroup of the TRP receptors, is a chemoreceptor that is activated by substances such as [[allicin]] [[gingerol]], [[mustard oil]], [[cinnamaldehyde]], [[allyl isothiocyanate]] and by [[Isovaleraldehyde| isovalleral]] is irritated. In addition, it binds pollutants such as [[acrolein]], [[isothiocyanates]], other organic irritants in exhaust gases and various aldehyde components in cigarette smoke, but also metabolites of various drugs and [[4-hydroxynonenal]].<ref>{{cite journal | vauthors = Macpherson LJ, Dubin AE, Evans MJ, Marr F, Schultz PG, Cravatt BF, Patapoutian A | title = Noxious compounds activate TRPA1 ion channels through covalent modification of cysteines | journal = Nature | volume = 445 | issue = 7127 | pages = 541–5 | date = February 2007 | pmid = 17237762 | doi = 10.1038/nature05544 | bibcode = 2007Natur.445..541M | s2cid = 4344572 }}</ref> It is assumed that the isocyanates evaporating from [[polyurethane foam]]s act via the TRP receptor.<ref name = "Hill_2010" />{{rp|74}} Animal experiments have shown that the covalent bond to the TRPA1 receptor causes inflammation and pain reactions.<ref>{{cite journal | vauthors = McNamara CR, Mandel-Brehm J, Bautista DM, Siemens J, Deranian KL, Zhao M, Hayward NJ, Chong JA, Julius D, Moran MM, Fanger CM | display-authors = 6 | title = TRPA1 mediates formalin-induced pain | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 104 | issue = 33 | pages = 13525–30 | date = August 2007 | pmid = 17686976 | pmc = 1941642 | doi = 10.1073/pnas.0705924104 | bibcode = 2007PNAS..10413525M }}</ref> The covalent bond comes about because electrophilic substances interact with a [[SH group|SH-group]] of a [[cysteine]] residue on the TRPA1 receptor. Such substances are increasingly found in cigarette smoke, smog but also fire smoke and are the cause of life-threatening shortness of breath in the case of smoke poisoning. This group of substances also includes all products of [[oxidative stress]] and [[lipid peroxidation]].<ref name = "Hill_2010" />{{rp|74}} As a result of the covalent bond, the receptor remains in its activated state even after the substances have acted, which in turn leads to a lowering of the sensitivity threshold. The symptoms of this sensitivity reaction, especially to organic solvents and some pesticides,<ref>{{cite journal | vauthors = Bradberry SM, Cage SA, Proudfoot AT, Vale JA | title = Poisoning due to pyrethroids | journal = Toxicological Reviews | volume = 24 | issue = 2 | pages = 93–106 | date = 2005 | pmid = 16180929 | doi = 10.2165/00139709-200524020-00003 | s2cid = 32523158 }}</ref> are due to the function of the TRP receptors and are reminiscent of [[rhinitis]] or [[Bronchial asthma|asthma]]. Therefore one speaks of a "[[Reactive airways dysfunction syndrome|Reactive Airway Dysfunction Syndrome]]" (RADS).<ref>{{cite journal | vauthors = Meggs WJ | title = RADS and RUDS--the toxic induction of asthma and rhinitis | journal = Journal of Toxicology. Clinical Toxicology | volume = 32 | issue = 5 | pages = 487–501 | date = 1994-01-01 | pmid = 7932908 | doi = 10.3109/15563659409011053 }}</ref> However, allergen-specific antibodies or [[T lymphocyte|T lymphocytes]] are missing in this form of asthma: activated effector cells of the immune system (e.g. [[mast cell|mast cells]]) are detectable.<ref name = "Hill_2010" />{{rp|75–76}} - -In addition to the TRPA1 receptor, chemical substances can also act directly in the brain on [[TRPV1]]. The resulting increased release of glutamate leads in turn to the activation of the NMD-receptors and thus ultimately to the development of inflammatory processes.<ref>{{cite journal | vauthors = Steenland HW, Ko SW, Wu LJ, Zhuo M | title = Hot receptors in the brain | journal = Molecular Pain | volume = 2 | pages = 34 | date = November 2006 | pmid = 17092351 | pmc = 1647269 | doi = 10.1186/1744-8069-2-34 }}</ref> Such chronic inflammations induce genes for synthesis new TRPV1 receptors on sensory nerve fibers of the airways and thus lead in turn to increased sensitivity to chemical substances.<ref>{{cite journal | vauthors = Zhang G, Lin RL, Wiggers M, Snow DM, Lee LY | title = Altered expression of TRPV1 and sensitivity to capsaicin in pulmonary myelinated afferents following chronic airway inflammation in the rat | journal = The Journal of Physiology | volume = 586 | issue = 23 | pages = 5771–86 | date = December 2008 | pmid = 18832423 | pmc = 2655410 | doi = 10.1113/jphysiol.2008.161042 }}</ref> - -==== NMDA receptors ==== -The activation of the [[NMDA receptor]] caused by glutamate leads to the increased formation of [[nitrogen monoxide]] (NO), a trigger of inflammatory reactions.<ref>{{cite journal | vauthors = Zhang G, Lin RL, Wiggers M, Snow DM, Lee LY | title = Altered expression of TRPV1 and sensitivity to capsaicin in pulmonary myelinated afferents following chronic airway inflammation in the rat | journal = The Journal of Physiology | volume = 586 | issue = 23 | pages = 5771–86 | date = December 2008 | pmid = 18832423 | pmc = 2655410 | doi = 10.1113/jphysiol.2008.161042 }}</ref> Therefore, with MCS or also [[Chronic fatigue syndrome|CFS]], increased parameters of the NO metabolism such as [[Citrulline]], citrulline-bound peptides or increased NO concentrations in the exhaled air.<ref name = "Hill_2010" />{{rp|87}} - -Three [[Nitric oxide synthase|Nitric oxide synthases]] are involved in the development of MCS: the neutral NOS (nNOS), the [[Endothelial nitric oxide synthase|endothelial NOS]] (eNOS) and the inducible NOS (iNOS). They are all activated, among other things, by calcium that has flowed into the cell through the activated NMDA receptor. In particular the iNOS shows a much increased activity in inflammation.<ref name = "Hill_2010" />{{rp|88}} - -Nitric oxide reacts with superoxide radicals and other reactive oxygen compounds to form [[peroxynitrite]], a strong [[oxidant]] that inhibits [[superoxide dismutase]] (SOD) in particular. As a result, the enrichment of the ROS leads to an increased formation of nitric oxide. Functionally restricted [[Mitochondrion|Mitochondria]] as well as structural damage and inflammation in the brain and nervous system arise.<ref name = "Hill_2010" />{{rp|88}} The increased chemical sensitivity in the limbic system is limited to the brain regions in which NMDA receptors occur.<ref>{{cite journal | vauthors = Hillert L, Musabasic V, Berglund H, Ciumas C, Savic I | title = Odor processing in multiple chemical sensitivity | journal = Human Brain Mapping | volume = 28 | issue = 3 | pages = 172–82 | date = March 2007 | pmid = 16767766 | pmc = 6871299 | doi = 10.1002/hbm.20266 }}</ref> The disturbance of the energy metabolism caused by the NO peroxynitrite cycle causes the NMDA receptors to be over-sensitive to other stimuli. This is done by lowering the [[membrane potential]].<ref>{{cite journal | vauthors = Novelli A, Reilly JA, Lysko PG, Henneberry RC | title = Glutamate becomes neurotoxic via the N-methyl-D-aspartate receptor when intracellular energy levels are reduced | journal = Brain Research | volume = 451 | issue = 1–2 | pages = 205–12 | date = June 1988 | pmid = 2472189 | doi = 10.1016/0006-8993(88)90765-2 | s2cid = 34328175 }}</ref><ref>{{cite journal | vauthors = Pall ML | title = NMDA sensitization and stimulation by peroxynitrite, nitric oxide, and organic solvents as the mechanism of chemical sensitivity in multiple chemical sensitivity | journal = FASEB Journal | volume = 16 | issue = 11 | pages = 1407–17 | date = September 2002 | pmid = 12205032 | doi = 10.1096/fj.01-0861hyp | s2cid = 7360200 }}</ref> - -The SH group of cysteine is the main target of nitric oxide;<ref>{{Cite journal| vauthors = Stamler JS |date=1994|title=Redox signaling: Nitrosylation and related target interactions of nitric oxide|url=https://linkinghub.elsevier.com/retrieve/pii/0092867494902690|journal=Cell|language=en|volume=78|issue=6|pages=931–936|doi=10.1016/0092-8674(94)90269-0|pmid=7923362|s2cid=44589529}}</ref> the formation of these nitrosyl compounds is mostly reversible. Peroxynitrite, on the other hand, reacts with the OH group from [[tyrosine]] to [[nitrotyrosine]] in an irreversible process.<ref>{{cite journal | vauthors = Groves JT | title = Peroxynitrite: reactive, invasive and enigmatic | journal = Current Opinion in Chemical Biology | volume = 3 | issue = 2 | pages = 226–35 | date = April 1999 | pmid = 10226050 | doi = 10.1016/S1367-5931(99)80036-2 }}</ref> The blockade of tyrosine leads to functional disorders of the [[thyroid]] and thus to the blockage of the formation of [[thyroid hormones]]. In many chronic, inflammatory diseases such as[[Atherosclerosis| arteriosclerosis]], [[multiple sclerosis]], [[Amyotrophic lateral sclerosis| amyotropic lateral sclerosis]] or [[Parkinson's disease]], the nitro and nitrotyrosine concentrations are increased. Melatonin is also nitrosated.<ref>{{cite journal | vauthors = Pall ML | title = Elevated, sustained peroxynitrite levels as the cause of chronic fatigue syndrome | journal = Medical Hypotheses | volume = 54 | issue = 1 | pages = 115–25 | date = January 2000 | pmid = 10790736 | doi = 10.1054/mehy.1998.0825 }}</ref> Furthermore, peroxynitrite [[SH group]] oxidizes enzymes.<ref>{{cite journal | vauthors = Kuhn DM, Aretha CW, Geddes TJ | title = Peroxynitrite inactivation of tyrosine hydroxylase: mediation by sulfhydryl oxidation, not tyrosine nitration | journal = The Journal of Neuroscience | volume = 19 | issue = 23 | pages = 10289–94 | date = December 1999 | pmid = 10575026 | pmc = 6782408 | doi = 10.1523/JNEUROSCI.19-23-10289.1999 }}</ref> The activated NMDA receptor and the iNOS induced thereby lead to an increased formation of Peroxynitrite with the associated nitration of tyrosine and oxidation of SH groups in proteins.<ref name = "Hill_2010" />{{rp|90}} An example of this would be [[Glutathione S-transferase|Glutathione ''S''-transferase]], the active center of which is inhibited by nitration of the tyrosine.<ref>{{cite journal | vauthors = Wong PS, Eiserich JP, Reddy S, Lopez CL, Cross CE, van der Vliet A | title = Inactivation of glutathione S-transferases by nitric oxide-derived oxidants: exploring a role for tyrosine nitration | journal = Archives of Biochemistry and Biophysics | volume = 394 | issue = 2 | pages = 216–28 | date = October 2001 | pmid = 11594736 | doi = 10.1006/abbi.2001.2532 }}</ref> As a result, detoxification reactions can only take place to a reduced extent. Furthermore, enzymes for the biosynthesis of [[dopamine]], [[serotonin]], [[tyrosine hydroxylase]] and [[tryptophan hydroxylase]] are inhibited.<ref>{{cite journal | vauthors = Kuhn DM, Aretha CW, Geddes TJ | title = Peroxynitrite inactivation of tyrosine hydroxylase: mediation by sulfhydryl oxidation, not tyrosine nitration | journal = The Journal of Neuroscience | volume = 19 | issue = 23 | pages = 10289–94 | date = December 1999 | pmid = 10575026 | pmc = 6782408 | doi = 10.1523/JNEUROSCI.19-23-10289.1999 }}</ref> The resulting lack of dopamine and serotonin causes key symptoms of MCS and CFS, such as depression and chronic fatigue. The lack of [[melatonin]] caused by the inhibited synthesis of serotonin leads to sleep disorders.<ref name = "Hill_2010" />{{rp|90}} +Another major goal for diagnostic work is to identify and treat any other medical conditions the person may have.<ref name=":0" /> People reporting MCS-like symptoms may have other health issues, ranging from common conditions, such as [[Depression (mood)|depression]] or [[asthma]], to less common circumstances, such a documented chemical exposure during a [[work accident]].<ref name=":0" /> These other conditions may or may not have any relationship to MCS symptoms, but they should be diagnosed and treated appropriately, whenever the [[patient history]], [[physical examination]], or routine [[medical test]]s indicates their presence.<ref name=":0" /> The [[differential diagnosis]] list includes [[solvent exposure]], [[occupational asthma]], and allergies.<ref name=":0" /> -Peroxynitrite plays a central role in a number of cell-damaging processes in acute and chronic diseases such as [[stroke]],[[Heart attack| myocardial infarction]],[[Heart failure| chronic heart failure]],[[Diabetes mellitus| diabetes]], [[cancer]], neurodegenerative diseases and chronic inflammatory diseases.<ref>{{cite journal | vauthors = Pacher P, Beckman JS, Liaudet L | title = Nitric oxide and peroxynitrite in health and disease | journal = Physiological Reviews | volume = 87 | issue = 1 | pages = 315–424 | date = January 2007 | pmid = 17237348 | pmc = 2248324 | doi = 10.1152/physrev.00029.2006 }}</ref> It oxidizes important metabolic substances such as[[Ascorbic acid| vitamin C]], [[glutathione]],[[ unsaturated fatty acids]], [[cholesterol]], [[tocopherol]], [[lycopene]], [[coenzyme Q10]] and makes them ineffective. This leads to [[oxidative stress]]. When the brain is still in the stage of development and differentiation, the maturation of the nerve cells and their growth are inhibited. This can lead to permanent impairment of mental performance in children.<ref name = "Hill_2010" />{{rp|92}} +=== Definitions === +Different researchers and proponents use different definitions, which complicates research and can affect diagnosis.<ref name=":3">{{Cite web|last=International Programme on Chemical Sensitivity|date=February 1996|title=Report of Multiple Chemical Sensitivities Workshop|url=https://apps.who.int/iris/bitstream/handle/10665/63109/PCS_96.29.pdf|access-date=11 June 2020|location=Berlin, Germany}}</ref> For example, the 1987 definition that requires symptoms to begin suddenly after an identifiable, documented exposure to a chemical,<ref name=":2">{{Cite journal|last1=Rossi|first1=Sabrina|last2=Pitidis|first2=Alessio|date=February 2018|title=Multiple Chemical Sensitivity: Review of the State of the Art in Epidemiology, Diagnosis, and Future Perspectives|journal=Journal of Occupational and Environmental Medicine|language=en-US|volume=60|issue=2|pages=138–146|doi=10.1097/JOM.0000000000001215|pmid=29111991|issn=1076-2752|pmc=5794238}}</ref> but the 1996 definition by the WHO/ICPS says that the cause can be anything, including other medical conditions or psychological factors.<ref name=":1">{{Cite journal|last=Katoh|first=Takahiko|date=2018|title=Multiple Chemical Sensitivity (MCS): History, Epidemiology and Mechanism|trans-title=Multiple Chemical Sensitivity (MCS): History, Epidemiology and Mechanism|journal=Nihon Eiseigaku Zasshi (Japanese Journal of Hygiene)|language=ja|volume=73|issue=1|pages=1–8|doi=10.1265/jjh.73.1|issn=1882-6482|pmid=29386440|doi-access=free}}</ref><ref name=":2" /> -The binding of glutamate to the NMDA receptor increases the formation of ROS, nitric oxide, peroxynitrite and damages the cell membrane through lipid peroxidation, which leads to the triggering of [[apoptosis]].<ref name = "Mattson_1998">{{cite journal | vauthors = Mattson MP | title = Free radicals, calcium, and the synaptic plasticity-cell death continuum: emerging roles of the transcription factor NF kappa B | journal = International Review of Neurobiology | volume = 42 | pages = 103–68 | date = 1998 | pmid = 9476172 | doi = 10.1016/s0074-7742(08)60609-1 | publisher = Elsevier | isbn = 978-0-12-366842-4 }}</ref> The result is functional disorders in the brain, muscles, the [[retina]] of the eyes, [[intestinal mucosa]] and [[immune system]].<ref name = "Hill_2010" />{{rp|92}} - -Both nitric oxide and peroxynitrite inhibit respiratory metabolism and energy balance in the mitochondria.<ref>{{cite journal | vauthors = Sherer TB, Kim JH, Betarbet R, Greenamyre JT | title = Subcutaneous rotenone exposure causes highly selective dopaminergic degeneration and alpha-synuclein aggregation | journal = Experimental Neurology | volume = 179 | issue = 1 | pages = 9–16 | date = January 2003 | pmid = 12504863 | doi = 10.1006/exnr.2002.8072 | s2cid = 12851989 }}</ref> Nitric oxide inhibits the iron-sulfur centers of complexes I, II and IV of the [[respiratory chain]] and thus their function in electron transport.<ref>{{cite book | vauthors = Forfia PR, Hintze TH, Wolin MS, Kaley G | chapter = Role of Nitric Oxide in the Control of Mitochondrial Function|date=1999 | title =Oxygen Transport to Tissue XXI| series = Advances in Experimental Medicine and Biology|volume=471|pages=381–388| veditors = Eke A, Delpy DT |place=Boston, MA|publisher=Springer US|doi=10.1007/978-1-4615-4717-4_46| pmid = 10659170|isbn=978-1-4613-7137-3 }}</ref> Due to the lack of [[Adenosine triphosphate]] leads to the "energy deficiency syndrome" or "mitochondrial disease", because ATP-dependent ion pumps (e. g.[[Sodium-Potassium Pump | Na-K-ATPase]]) of the nerve cells can only work to a limited extent or are even completely inhibited.<ref name = "Mattson_1998" /> There can also be disturbances in the transmission of nerve impulses along the axon fibers. This results in the symptoms of peripheral and central [[Polyneuropathy|polineuropathy]] and [[encephalopathy]]. The energy deficiency syndrome itself manifests itself in symptoms such as extreme tiredness, short-term, coma-like deep sleep after meals in connection with uncontrolled salivation and heavy snoring, rapid exhaustion during mental and physical activity and muscle weakness with [[lactic acidosis]]. The syndrome is characterized by aerobic [[glycolysis]]: Damage to the mitochondrial enzymes means that the hydrogen split off from the glucose can no longer be oxidized. The electron is therefore transferred directly to oxygen without the participation of [[Nicotinamide adenine dinucleotide|NADH]], so that more oxygen radicals and superoxides are formed. This leads to genotoxic and inflammatory reactions such as radical chain reactions with unsaturated fatty acids in the membrane ([[lipid peroxidation]]).<ref name = "Hill_2010" />{{rp|92}} [[Parkinson's disease|Parkinson]] and [[Huntington's disease]] are typical representatives of diseases as a result of the energy deficiency syndrome.<ref>{{cite journal | vauthors = Sherer TB, Kim JH, Betarbet R, Greenamyre JT | title = Subcutaneous rotenone exposure causes highly selective dopaminergic degeneration and alpha-synuclein aggregation | journal = Experimental Neurology | volume = 179 | issue = 1 | pages = 9–16 | date = January 2003 | pmid = 12504863 | doi = 10.1006/exnr.2002.8072 | s2cid = 12851989 }}</ref> - -Ppesticides of [[Organophosphate|organophosphates]] have a neurotoxic effect<ref>{{cite journal | vauthors = Abou-Donia MB | title = Organophosphorus ester-induced chronic neurotoxicity | journal = Archives of Environmental Health | volume = 58 | issue = 8 | pages = 484–97 | date = August 2003 | pmid = 15259428 | doi = 10.3200/AEOH.58.8.484-497 | s2cid = 6720069 }}</ref> and inhibit the enzyme [[acetylcholinesterase]] in the nervous system and brain. As a result, the neurotransmitter [[acetylcholine]] is no longer broken down, so that acetylcholine increases [[Muscarinic acetylcholine receptor|muscarinic]] and [[Nicotinic acetylcholine receptor|nicotinic]] receptors in the nervous system and the brain. This leads to increased glutamate release and NMDA receptor activation.<ref name = "Hill_2010" />{{rp|99}} Organophosphates are also contained in [[plasticizers]], [[flame retardants]], or plastic building materials such as [[soundproofing]] and thermal insulation panels, in upholstery and assembly foams and in electronic devices. As a result of this broad application, the pollutants get into the indoor air, accumulate in house dust and from there finally get into the human organism.<ref name = "Hill_2010" />{{rp|100}} - -Pesticides of the group of [[pyrethroids]] attack the sodium ion channels in the membranes of nerve cells in the brain, which also carry the NMDA receptor. After the cell has been excited, they slow down the closing of the sodium channels, so that the NMDA receptors are strengthened.<ref>{{Cite journal| vauthors = Valentine WM |date=1990|title=Pyrethrin and Pyrethroid Insecticides |journal=Veterinary Clinics of North America: Small Animal Practice|language=en|volume=20|issue=2|pages=375–382|doi=10.1016/S0195-5616(90)50031-5|pmid=2180183}}</ref> - -==== GABA receptors ==== -Nerve toxins, especially chlorinated hydrocarbon insecticides such as [[hexachlorocyclohexane]], [[lindane]], [[chlordane]],[[Dieldrin| deildrin]], [[aldrin]] and [[toxaphene]], but also various [[active ingredient|active ingredients]] ensure [[non-competitive inhibition]] at the GABAa receptors.<ref>{{Cite book|url=https://www.worldcat.org/oclc/249397277|title=Lehrbuch der Toxikologie mit 342 Tabellen|date=2004| vauthors = Marquardt H |isbn=978-3-8047-1777-0|edition=2., völlig neu bearb. Aufl|location=Stuttgart|language=de|oclc=249397277}}</ref><ref>{{cite journal | vauthors = Corrigan FM, MacDonald S, Brown A, Armstrong K, Armstrong EM | title = Neurasthenic fatigue, chemical sensitivity and GABAa receptor toxins | journal = Medical Hypotheses | volume = 43 | issue = 4 | pages = 195–200 | date = October 1994 | pmid = 7838000 | doi = 10.1016/0306-9877(94)90065-5 }}</ref><ref>{{cite journal | vauthors = Halaris AE, Belendiuk KT, Freedman DX | title = Antidepressant drugs affect dopamine uptake | journal = Biochemical Pharmacology | volume = 24 | issue = 20 | pages = 1896–7 | date = October 1975 | pmid = 19 | doi = 10.1016/0006-2952(75)90412-8 }}</ref> With repeated exposure to low concentrations, neurotoxic insecticides such as [[Endosulfan]], [[Chlordimeform]], [[Amitraz]], [[Chlorpyrifos]] and Lindane it can cause [[Epilepsy|epilepsy-like]] seizures. The concentration threshold of a new seizure falls with each exposure.<ref name = "Hill_2010" />{{rp|102}} By administering NMDA antagonists, this can be reduced or completely prevented.<ref name = "Hill_2010" />{{rp|103}} - -Binding to the picrotoxin binding site of the [[GABA receptor]] by pesticides such as lindane or [[dieldrin]] leads to an influx of chloride and thus to the functional inhibition of the GABA receptor.<ref>{{cite journal | vauthors = Llorens J, Tusell JM, Suñol C, Rodríguez-Farré E | title = On the effects of lindane on the plus-maze model of anxiety | journal = Neurotoxicology and Teratology | volume = 12 | issue = 6 | pages = 643–7 | date = 1990 | pmid = 1701517 | doi = 10.1016/0892-0362(90)90078-Q }}</ref> - -By inhibiting the GABA receptors, the regulation of nerve activity is blocked by negative feedback, so that there is increased nerve activity and thus the release of glutamate.<ref name = "Hill_2010" />{{rp|102}} - -=== Chemical ignition === -When people with MCS are exposed to chemicals - especially fragrances - [[Basophil|basophils]] release increased amounts of histamine.<ref name = "Hill_2010" />{{rp|109}} The basophilic granulocytes have the above-mentioned TRPV1 receptors and other TRP receptors.<ref>{{cite journal | vauthors = Planells-Cases R, Garcìa-Sanz N, Morenilla-Palao C, Ferrer-Montiel A | title = Functional aspects and mechanisms of TRPV1 involvement in neurogenic inflammation that leads to thermal hyperalgesia | journal = Pflugers Archiv | volume = 451 | issue = 1 | pages = 151–9 | date = October 2005 | pmid = 15909179 | doi = 10.1007/s00424-005-1423-5 | s2cid = 29016595 }}</ref> - -Furthermore, after exposure to volatile chemicals, MCS sufferers developed symptoms of severe [[rhinitis]] with increased mucus secretion. In this nasal wash, in contrast to healthy test persons, [[histamine]] and some inflammation markers such as [[cytokine|cytokines]], [[interferons]] and [[nitric oxide]] could be detected.<ref>{{cite journal | vauthors = Koren HS, Devlin RB | title = Human upper respiratory tract responses to inhaled pollutants with emphasis on nasal lavage | journal = Annals of the New York Academy of Sciences | volume = 641 | issue = 1 Sources of In | pages = 215–24 | date = April 1992 | pmid = 1580472 | doi = 10.1111/j.1749-6632.1992.tb16545.x | bibcode = 1992NYASA.641..215K | s2cid = 29387298 }}</ref><ref>{{Cite journal|date=1990-01-01|title=Nasal lavage as a tool in assessing acute inflammation in response to inhaled pollutants |journal=Toxicology|language=en|volume=60|issue=1–2|pages=15–25|doi=10.1016/0300-483X(90)90159-E|issn=0300-483X|last1=Koren |first1=Hillel S. |last2=Hatch |first2=Gary E. |last3=Graham |first3=Delores E. |pmid=2315937 }}</ref><ref>{{cite journal | vauthors = Koren HS, Graham DE, Devlin RB | title = Exposure of humans to a volatile organic mixture. III. Inflammatory response | journal = Archives of Environmental Health | volume = 47 | issue = 1 | pages = 39–44 | date = 3 August 2010 | pmid = 1540001 | doi = 10.1080/00039896.1992.9935942 }}</ref> Similar reactions could be demonstrated in cell cultures through exposure to substances from fungi and microorganisms.<ref>{{cite journal | vauthors = Hirvonen MR, Ruotsalainen M, Savolainen K, Nevalainen A | title = Effect of viability of actinomycete spores on their ability to stimulate production of nitric oxide and reactive oxygen species in RAW264.7 macrophages | journal = Toxicology | volume = 124 | issue = 2 | pages = 105–14 | date = December 1997 | pmid = 9458000 | doi = 10.1016/S0300-483X(97)00141-8 }}</ref> - -==== Reactive Oxygen Species (ROS) ==== -Reactive oxygen species can arise from the effects of foreign substances and pollutants. For example, there is a connection between the effect of [[7,12-Dimethylbenz(a)anthracene|7,12-Dimethylbenz(''a'')anthracene]] and an increase in the ROS in rat follicle cells before they lead to [[apoptosis]]. Adding [[glutathione]] can prevent apoptosis in the cell cultures.<ref>{{cite journal | vauthors = Tsai-Turton M, Nakamura BN, Luderer U | title = Induction of apoptosis by 9,10-dimethyl-1,2-benzanthracene in cultured preovulatory rat follicles is preceded by a rise in reactive oxygen species and is prevented by glutathione | journal = Biology of Reproduction | volume = 77 | issue = 3 | pages = 442–51 | date = September 2007 | pmid = 17554082 | doi = 10.1095/biolreprod.107.060368 | s2cid = 23914562 }}</ref> - -In the lung tissue, particulate matter can cause the formation of reactive oxygen species. In particular, inhalation of dust containing [[heavy metals]] leads to a significantly increased formation of oxygen radicals in the immune cells of the lungs compared to the control group.<ref>{{cite journal | vauthors = Dellinger B, Pryor WA, Cueto R, Squadrito GL, Hegde V, Deutsch WA | title = Role of free radicals in the toxicity of airborne fine particulate matter | journal = Chemical Research in Toxicology | volume = 14 | issue = 10 | pages = 1371–7 | date = October 2001 | pmid = 11599928 | doi = 10.1021/tx010050x }}</ref><ref>{{cite journal | vauthors = Gilmour PS, Ziesenis A, Morrison ER, Vickers MA, Drost EM, Ford I, Karg E, Mossa C, Schroeppel A, Ferron GA, Heyder J, Greaves M, MacNee W, Donaldson K | display-authors = 6 | title = Pulmonary and systemic effects of short-term inhalation exposure to ultrafine carbon black particles | journal = Toxicology and Applied Pharmacology | volume = 195 | issue = 1 | pages = 35–44 | date = February 2004 | pmid = 14962503 | doi = 10.1016/j.taap.2003.10.003 }}</ref><ref name=":9">{{citation|title=Aerosolforschung der GSF|url=https://www.helmholtz-muenchen.de/fileadmin/GSF/pdf/publikationen/broschueren/aerosolforschung/Aerosolbroschuere.pdf|archive-url=https://web.archive.org/web/20210210111434/https://www.helmholtz-muenchen.de/fileadmin/GSF/pdf/publikationen/broschueren/aerosolforschung/Aerosolbroschuere.pdf|archive-date=2021-02-10|editor-surname1=GSF-Forschungszentrum für Umwelt und Gesundheit, Mitglied der Helmholtzgemeinscha|language=de}}</ref> Substances bound to the surface of the particles, such as [[quinones]], can cause [[oxidative stress]] further promote.<ref name=":9" /> In animal experiments with rats, these fine dust particles could be detected in the liver, heart and brain.<ref name=":9" /> Through the action of c[[Cyclooxygenase|yclooxygenases]] as a result of fine dust such as [[diesel soot]] or carbon particles, eventually reactive oxygen species arise.<ref>{{cite journal | vauthors = Hofer TP, Bitterle E, Beck-Speier I, Maier KL, Frankenberger M, Heyder J, Ziegler-Heitbrock L | title = Diesel exhaust particles increase LPS-stimulated COX-2 expression and PGE2 production in human monocytes | journal = Journal of Leukocyte Biology | volume = 75 | issue = 5 | pages = 856–64 | date = May 2004 | pmid = 14966191 | doi = 10.1189/jlb.0803387 | s2cid = 29601177 }}</ref> This is done by activating the gene for the cyclooxigenase-2 in macrophages in the tissue of the [[Pulmonary alveolus|alveoli]]. The increased formation of ROS now intensifies inflammatory reactions in the lungs via the induction factor [[NF-κB]].<ref name=":9" /> - -In the immune system, the physiological function of the ROS is to kill pathogens and trigger inflammation via NF-κB. If the inflammation is chronic, however, ROS attacks cells and tissues in your own body.<ref>{{Cite book|url= https://www.worldcat.org/oclc/249397277 |title=Lehrbuch der Toxikologie mit 342 Tabellen|date=2004| vauthors = Marquardt J |isbn=978-3-8047-1777-0|edition=2., völlig neu bearb. Aufl|location=Stuttgart|language=de|oclc=249397277}}</ref> - -In animal models it was shown that a reduction in ROS led to a decrease in [[8-hydroxyguanine]], an indicator of oxidative damage to DNA. Furthermore, compared to the control group, there was less heart damage or arteriosclerotic vascular changes - even in advanced age.<ref>{{cite journal | vauthors = Schriner SE, Linford NJ, Martin GM, Treuting P, Ogburn CE, Emond M, Coskun PE, Ladiges W, Wolf N, Van Remmen H, Wallace DC, Rabinovitch PS | display-authors = 6 | title = Extension of murine life span by overexpression of catalase targeted to mitochondria | journal = Science | volume = 308 | issue = 5730 | pages = 1909–11 | date = June 2005 | pmid = 15879174 | doi = 10.1126/science.1106653 | bibcode = 2005Sci...308.1909S | s2cid = 38568666 }}</ref><ref>{{cite journal | vauthors = Arai T, Kelly VP, Minowa O, Noda T, Nishimura S | title = High accumulation of oxidative DNA damage, 8-hydroxyguanine, in Mmh/Ogg1 deficient mice by chronic oxidative stress | journal = Carcinogenesis | volume = 23 | issue = 12 | pages = 2005–10 | date = December 2002 | pmid = 12507922 | doi = 10.1093/carcin/23.12.2005 }}</ref> Membrane proteins accumulate due to the oxidation of SH groups under the action of ROS. Because of the now existing covalent disulfide bridges, the membrane proteins are restricted in their mobility.<ref>{{cite journal | vauthors = Dünschede F, Zwicker K, Ackermann H, Zimmer G | title = ADP- and oligomycin-sensitive redox behavior of F0 b thiol in ATPsynthase depends on neighbored primary structure: investigations using 14-C-labeled alpha lipoic acid | journal = BioFactors | volume = 19 | issue = 1–2 | pages = 19–32 | date = 2003 | pmid = 14757974 | doi = 10.1002/biof.5520190104 }}</ref> The lipid molecules of the [[lipid bilayer]] now have a less ordered arrangement,<ref>{{cite journal | vauthors = Balakirev MY, Zimmer G | title = Gradual changes in permeability of inner mitochondrial membrane precede the mitochondrial permeability transition | journal = Archives of Biochemistry and Biophysics | volume = 356 | issue = 1 | pages = 46–54 | date = August 1998 | pmid = 9681990 | doi = 10.1006/abbi.1998.0738 }}</ref> so the membrane is more permeable to ions such as hydrogen or potassium.<ref name = "Hill_2010" />{{rp|117}} - -[[Nitric oxide synthase|Nitric oxide synthases]] induced by ROS form increasingly [[nitrogen monoxide]] and, together with ROS, [[peroxynitrite]]. Peroxynitrite triggers the chain reaction of [[lipid peroxidation]]. This process is known as [[nitrosative stress]].<ref name = "Hill_2010" />{{rp|113}} In addition to peroxynitrite, other oxygen radical formers such as [[adriamycin]], [[paraquat]],[[Nitrofurantoin| nitrufurantoin]] or [[paracetamol]] trigger lipid peroxidation. During the metabolism of paracetamol to[[N-acetyl-p-benzoquinone imine|'' N''-acetyl-''p''-benzoquinone imine]] the [[superoxide anion]] ^•O₂⁻ is formed. When [[carbon tetrachloride]] is metabolized, the trichloromethyl radical (^•CCl₂) or the trichloromethyl peroxy radical (CCl₂OO^•).<ref name = "Hill_2010" />{{rp|117}} - -Lipid peroxidation can cause great damage, especially in the brain. This is because the brain has a relatively low antioxidant capacity<ref name=":10">{{Cite journal| vauthors = Vardarajan S, Yatin S, Aksenova M, Butterfield DA |date=2000|title=Review: Alzheimer's Amyloidb-Peptide-Associated Free RadicalOxidative Stress and Neurotoxicity |url= http://hs.as.uky.edu/sites/default/files/Varadarajan%20et%20al%202000%20J%20Struct.%20biol%20130%20%20184-208.pdf|journal=Journal of Structural Biology|volume=130|issue=2–3|pages=184–208|doi=10.1006/jsbi.2000.4274|pmid=10940225}}</ref> and has a high oxygen demand. This need is associated with a higher production of oxygen radicals in the mitochondria.<ref name = "Hill_2010" />{{rp|118}} The polyunsaturated fatty acids present in the membranes of the nerve cells of the brain are particularly susceptible to lipid peroxidation.<ref>{{Cite book| vauthors = Halliwell B, Gutteridge MC |url=https://www.worldcat.org/oclc/915560715|title=Free radicals in biology and medicine|date=2015 |isbn=978-0-19-102698-0|edition=|location=Oxford|oclc=915560715}}</ref> If this mechanism of oxidative stress is no longer prevented with glutathione, this contributes to degenerative processes, which can ultimately lead to [[dementia]] and [[Alzheimer's disease]].<ref name=":10" /> - -A protein domain of the p66Shc protein produces [[hydrogen peroxide]] with the help of copper. In addition, in the event of cellular stress, four p66Shc molecules combine via [[Protein-protein interaction|cysteine-cysteine interactions]] to form a stable [[Protein complex|complex]], which causes the mitochondria to burst and thus triggers apoptosis. Both glutathione and [[thioredoxin]] can inhibit the activity of p66Shc.<ref>{{cite journal | vauthors = Gertz M, Fischer F, Wolters D, Steegborn C | title = Activation of the lifespan regulator p66Shc through reversible disulfide bond formation | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 105 | issue = 15 | pages = 5705–9 | date = April 2008 | pmid = 18413607 | pmc = 2311372 | doi = 10.1073/pnas.0800691105 | bibcode = 2008PNAS..105.5705G }}</ref> - -The apoptosis of a nerve cell in the brain also ensures the apoptosis of the presynaptic (upstream) nerve cell. The reason for this is that the life-sustaining reaction of the postsynaptic cell on the presynaptic cell is no longer given by growth hormones.<ref name = "Mattson_1998" /> As a result, degeneration processes spread far beyond the once affected cell.<ref name = "Hill_2010" />{{rp|133}} - -In the human organism there is a delicate relationship between reducing and oxidizing substances. Oxidative stress shifts this redox equilibrium in the direction of oxidation, which leads to a reversal in the direction of pathogenic processes. Due to an excess of oxidizing substances, about [[lymphocytes]] are more easily attached to the [[endothelial cells]] of the blood vessels and promote inflammatory processes there.<ref name = "Hill_2010" />{{rp|115}} The cellular [[redox potential]] shifts from about −0.24 V on the mitochondrial membrane to positive values. The value in [[blood plasma]] saturated with oxygen is 0.22 V. Due to the close connection with inflammation, this is also referred to as inflammation syndrome.<ref name = "Hill_2010" />{{rp|118}} - -In order to compensate for the lack of reducing SH groups as in [[cysteine]] or glutathione, the cell metabolism tries to compensate for the cysteine deficiency through new synthesis from methionine. However, since the mitochondrial function is disturbed, there is too little NADH, so that [[Tetrahydrofolic acid|methyl-tetrahydrofolic acid]] cannot be regenerated from [[folic acid]]. Due to the lack of methyl tetrahydrofolic acid, [[homocysteine]] cannot be converted to [[methionine]]; homocysteine accumulates and is therefore a sign of chronic inflammatory processes or oxidative stress.<ref>{{cite journal | vauthors = Bottiglieri T, Laundy M, Crellin R, Toone BK, Carney MW, Reynolds EH | title = Homocysteine, folate, methylation, and monoamine metabolism in depression | journal = Journal of Neurology, Neurosurgery, and Psychiatry | volume = 69 | issue = 2 | pages = 228–32 | date = August 2000 | pmid = 10896698 | pmc = 1737050 | doi = 10.1136/jnnp.69.2.228 }}</ref> ROS are considered to be the trigger for the formation of factors such as [[heat shock proteins]]. Pollutants and foreign substances induce the HSP group 60/65, which normally act as a protective system against physical and chemical stress stimuli.<ref name = "Hill_2010" />{{rp|131}} In mononuclear cells of the peripheral blood of MCS patients, a strong increase in HSP-60-[[Gene expression|expression]] was demonstrated.<ref>{{Cite journal|date=2002|title=Die Rolle von oxidativem Stress in der Pathogenese von MCS|journal=Zeitschrift für Umweltmedizin|language=de|volume=4|pages=198–205}}</ref> - -==== [[NF-κB]] and [[Cytokine|cytokines]] ==== -Oxidative and nitrosative stress, especially ROS, activate the transcription factor NF-κB, which sets numerous inflammatory mechanisms in motion. In animal experiments it could be proven that - after 6 hours of administration of coal dust with a concentration of 300 µg/m³ via the breath - the oxidative stress increased and the migration of the NF-κB subunits B50 and B65 into the cell nucleus began. These subunits ensure an increased synthesis of [[mRNA]] at the sites in the DNA that code for pro-inflammatory cytokines ([[Interferon-γ]], [[TNF-α]], [[Interleukin-6]]).<ref>{{cite journal | vauthors = Shukla A, Timblin C, BeruBe K, Gordon T, McKinney W, Driscoll K, Vacek P, Mossman BT | display-authors = 6 | title = Inhaled particulate matter causes expression of nuclear factor (NF)-kappaB-related genes and oxidant-dependent NF-kappaB activation in vitro | journal = American Journal of Respiratory Cell and Molecular Biology | volume = 23 | issue = 2 | pages = 182–7 | date = August 2000 | pmid = 10919984 | doi = 10.1165/ajrcmb.23.2.4035 }}</ref> - -The synthesis of NF-κB is up to 10 times higher in the cells of the immune system in MCS patients compared to control persons.<ref>{{citation|title=MCS ein NF-κB-getriggerter Entzündungsprozess. Hrsg.: Organ des Deutschen Berufsverbandes der Umweltmediziner ; Organ der Deutschen Gesellschaft für Umwelt- und Humantoxikologie.|date=2003|volume=11|pages=80–86|editor-surname1=|language=de|id=}}</ref> In addition, NF-κB remains permanently active due to the ROS leads to an excess of proinflammatory cytokines.<ref name = "Hill_2010" />{{rp|121}} Interferon-γ-values are already increased in MCS patients before a provocation load; there is a further increase upon exposure. The secretion of [[Interleukin-10]] by peripheral lymphocytes, however, is reduced by more than half both before and after a challenge. Interleukin-10 normally reduces inflammatory responses via [[negative feedback]].<ref name = "Hill_2010" />{{rp|124}} - -== Definitions == -Different researchers and proponents use different definitions, which complicates research and can affect diagnosis.<ref name=":3">{{Cite web|last=International Programme on Chemical Sensitivity|date=February 1996|title=Report of Multiple Chemical Sensitivities Workshop|url=https://apps.who.int/iris/bitstream/handle/10665/63109/PCS_96.29.pdf|access-date=11 June 2020|location=Berlin, Germany}}</ref> For example, the 1987 definition that requires symptoms to begin suddenly after an identifiable, documented exposure to a chemical,<ref name=":2">{{cite journal | vauthors = Rossi S, Pitidis A | title = Multiple Chemical Sensitivity: Review of the State of the Art in Epidemiology, Diagnosis, and Future Perspectives | language = en-US | journal = Journal of Occupational and Environmental Medicine | volume = 60 | issue = 2 | pages = 138–146 | date = February 2018 | pmid = 29111991 | pmc = 5794238 | doi = 10.1097/JOM.0000000000001215 }}</ref> but the 1996 definition by the WHO/ICPS says that the cause can be anything, including other medical conditions or psychological factors.<ref name=":1">{{cite journal | vauthors = Katoh T | title = [Multiple Chemical Sensitivity (MCS): History, Epidemiology and Mechanism] | language = ja | journal = Nihon Eiseigaku Zasshi. Japanese Journal of Hygiene | volume = 73 | issue = 1 | pages = 1–8 | date = 2018 | pmid = 29386440 | doi = 10.1265/jjh.73.1 | trans-title = Multiple Chemical Sensitivity (MCS): History, Epidemiology and Mechanism | doi-access = free }}</ref><ref name=":2" /> - -In 1996, an expert panel at WHO/ICPS was set up to examine MCS.<ref name=":5">{{cite journal | vauthors = Schwenk M | title = Multiple Chemical Sensitivity (MCS) - Scientific and Public-Health Aspects | journal = GMS Current Topics in Otorhinolaryngology, Head and Neck Surgery | volume = 3 | pages = Doc05 | year = 2004 | pmid = 22073047 | pmc = 3199799 }}</ref> The panel accepted the existence of "a disease of unclear pathogenesis", rejected the claim that MCS was caused by chemical exposure, and proposed these three diagnostic requirements for what they re-named ''idiopathic environmental intolerances'' (IEI): +In 1996, an expert panel at WHO/ICPS was set up to examine MCS.<ref name=":5">Schwenk, Michael (2004). [https://pubmed.ncbi.nlm.nih.gov/22073047/ "Multiple Chemical Sensitivity (MCS) - Scientific and Public-Health Aspects".] ''GMS current topics in otorhinolaryngology, head and neck surgery''. ISSN 1865-1011. PMC 3199799 . <nowiki>PMID 22073047</nowiki>.  </ref> The panel accepted the existence of "a disease of unclear pathogenesis", rejected the claim that MCS was caused by chemical exposure, and proposed these three diagnostic requirements for what they re-named ''idiopathic environmental intolerances'' (IEI): # the disease was acquired (not present from birth) and must produce multiple relapsing symptoms; @@ -155,81 +56,9 @@ In Japan, MCS is called ''chemical hypersensitivity'' or ''chemical intolerance'' (<span dir="ltr" lang="ja">化学物質過敏症</span>; kagaku bushitsu kabinsho), and the 1999 Japanese definition requires one or more of four major symptoms – headaches; malaise and fatigue; muscle pain; joint pain – combined with laboratory findings and/or some minor symptoms, such as mental effects or skin conditions.<ref name=":1a">{{cite web|title=Safety and Health Topics: Multiple Chemical Sensitivities|url=https://www.osha.gov/multiple-chemical-sensitivities|access-date=2021-01-06|publisher=Osha.gov}}</ref> The defined lab findings are abnormalities in [[Parasympathetic nervous system|parasympathetic nerves]], [[Cerebral cortex|cerebral cortical]] dysfunction diagnosed by [[SPECT]] testing, [[visuospatial]] abnormalities, abnormalities of [[Eye movement disorder|eye movement]], or a positive [[provocation test]].<ref name=":1" /> -== Diagnosis == -In practice, diagnosis relies entirely upon the [[Self-report study|self-reported]] claim that symptoms are triggered by exposure to various substances.<ref name=":0" /> - -Many other tests have been promoted by various people over the years, including testing of the immune system, [[porphyrin metabolism]], provocation-neutralization testing, [[autoantibodies]], the [[Epstein–Barr virus]], testing for evidence of exposure to pesticides or heavy metals, and challenges involving exposure to chemicals, foods, or inhalants.<ref name=":0" /> None of these tests correlate with MCS symptoms, and none are useful for diagnosing MCS.<ref name=":0" /> - -The stress and [[Anxiety disorder|anxiety]] experienced by people reporting MCS symptoms are significant.<ref name=":0" /> [[Neuropsychological assessment]]s do not find differences between people reporting MCS symptoms and other people in areas such as verbal learning, memory functioning, or [[psychomotor learning|psychomotor performance]].<ref name=":0" /> Neuropsychological tests are [[Sensitivity and specificity|sensitive but not specific]], and they identify differences that may be caused by unrelated medical, neurological, or neuropsychological conditions.<ref name=":0" /> - -Another major goal for diagnostic work is to identify and treat any other medical conditions the person may have.<ref name=":0" /> People reporting MCS-like symptoms may have other health issues, ranging from common conditions, such as [[Depression (mood)|depression]] or [[asthma]], to less common circumstances, such a documented chemical exposure during a [[work accident]].<ref name=":0" /> These other conditions may or may not have any relationship to MCS symptoms, but they should be diagnosed and treated appropriately, whenever the [[patient history]], [[physical examination]], or routine [[medical test]]s indicates their presence.<ref name=":0" /> The [[differential diagnosis]] list includes [[solvent exposure]], [[occupational asthma]], and allergies.<ref name=":0" /> - -=== General === -The diagnostics in [[environmental medicine]] consists of the following three sections: - -==== 1. Social history of environmental medicine ==== -Here, the entire environment of the patient is examined more closely with regard to exposure to harmful substances. This includes the living, working or training environment, tooth materials in the dental field (including implants and root filling materials), consumption of luxury goods (smoking, alcohol), eating habits, leisure behavior or sport / physical activity and other factors such as social conditions, income, family or possible stress factors.<ref name = "Hill_2010" />{{rp | 252}} - -==== 2. Exclusion diagnostics ==== -Symptoms that have a cause other than environmental must be advised by appropriate specialists (e.g. [[internist |internists]],[[neurology | neurologists]], [[psychiatrists]],[[cardiology | cardiologists]], [[Otorhinolaryngology|otorhinolaryngologists]],[[urology | urologists]] etc.). Only when environmental factors cannot be excluded as the cause, environmental medical [[laboratory diagnostics]] hat to be used; to assess the overall clinical picture, the results of other medical specialties are nevertheless important and necessary.<ref name = "Hill_2010" />{{rp | 252/253}} - -==== 3. Environmental medical monitoring and laboratory diagnostics ==== -This point is divided into several sub-areas: <ref name = "Hill_2010" />{{rp | 253–256}} - -* '''external exposure''': analytics / [[environmental monitoring]]; qualitative and quantitative detection of pollutants in the patient's environment -* '''internal exposure''': analysis / [[biomonitoring]]: detection of foreign substances and pollutants including their metabolites in the patient's body samples (blood, serum, saliva, urine, hair, fatty tissue, etc.) <br /> Unfortunately, biomonitoring often does not provide any meaningful results. There are mutliple reasons for this: -** [[Metabolites]] are often only detectable a few days after exposure. Therefore, attempts are made to detect chemically altered proteins, which is still possible months after exposure. Longer past exposure can no longer be recorded. -** Fat-soluble substances can accumulate in high concentrations in adipose tissue and / or brain without being detectable in blood or urine -** Analysis methods are not yet available for many pollutants (e.g. around 50% of the pesticides used in agriculture). Due to the lack of evidence, a mental illness can be incorrectly diagnosed instead of MCS. -** Even if toxicological limit and guide values are not exceeded, chronic exposure to pollutants can lead to lasting disruptions in functional control loops. - -: For these reasons - if there is reasonable suspicion of chronic long-term exposure to chemicals - priority should be given to effect monitoring. -* '''Biological effect monitoring''': Proof of effects or the effects of pollutants on the patient <br />This includes physiological, immunological, neurological, endocrine or metabolic changes such as [[Antibodies]], changes in the hormonal balance, sensitized [[lymphocytes]], changes in the [[Peripheral nervous system|peripheral]] and[[central nervous system]], systemic inflammatory reactions including their markers ([[cytokine |cytokines]]), immunological sensitization type I and type IV. -* '''Susceptibility monitoring''':Using biochemical laboratory diagnostics, the individual sensitivity to environmental factors can be determined. These include, among other things, genetic [[Gene polymorphism|polymorphism]]s for enzymes of phase I and II of the detoxification system ([[cytochrome P450]]-[[Monooxygenase|monooxygenases]], [[glutathione transferase|glutathione transferases]], [[N-acetyltransferase|N-acetyltransferases]], [[Catechol-O-methyltransferase|Catechol-O-methyltransferases]], [[UDP-glucuronosyltransferase|UDP-glucuronosyltransferases]]). <br />Detection of disorders of the blood-brain barrier is also to be classified here. - -=== Provocation tests === -In the provocation tests, patients are exposed to low levels of chemicals and compared with non-sensitized control subjects. Alternatively, you can measure [[neuropeptides]] and cytokines that are detectable in the blood as a result of chemical exposure. In affected patients, the blood count is significantly higher than in control persons. For example, volatile organic compounds show an increase in the serum concentration of the inflammatory markers [[substance P]], [[vasoactive intestinal peptide]],[[nerve growth factor]] and [[histamine]].<ref>{{Cite journal|last=Kimata|first=Hajime|date=2004|title=Effect of exposure to volatile organic compounds on plasma levels of neuropeptides, nerve growth factor and histamine in patients with self-reported multiple chemical sensitivity|url=https://linkinghub.elsevier.com/retrieve/pii/S143846390470276X|journal=International Journal of Hygiene and Environmental Health|language=en|volume=207|issue=2|pages=159–163|doi=10.1078/1438-4639-00262}}</ref> - -However, the procedure for this type of test is to be viewed critically from a medical ethical point of view, since damage must be added to the participants in the examination.<Ref name = "Hill_2010" />{{rp | 256}} - -=== Immunological in vitro test systems === -Compared to the provocation tests, these test systems have the advantage that the reaction of cells of the immune system can be analyzed without having to expose the patient to the harmful substances himself. There are different types of tests, the [[Immune Tolerance Test]] (ITT) and the [[Lymphocyte Transformation Test]] (LTT).<Ref name = "Hill_2010" />{{rp | 256/257}} - -In the immune tolerance test, the reaction of a patient's immune cells to various stressors is tested by exposing them to a mixture of pollutants as a marker. An influenza virus antigen and the amount of the cytokines [[Interferon-γ|IFN-𝛾]],[[Interleukin-10 | Il-10]],[[TNF-α | TNF-𝞪]] and [[Interleukin-1β|IL-1β]], which are released thereby, are used as control. MCS patients show a significant increase in IFN-𝛾 and / or TNF-𝞪. The ITT is therefore suitable as a basic test for the detection of an immune regulatory disorder. MCS can also be differentiated from CFS: MCS has a high concentration of IFN-and a low concentration of II-2; with CFS exactly the other way round.<ref name = "Hill_2010" />{{rp | 257}} - -The lymphocyte transformation test is recommended for differential diagnosis. If the ITT and LTT show positive results for a certain chemical, a chronic allergic type IV sensitization can be assumed. However, if only the ITT is positive, MCS is the disease.<Ref name = "Hill_2010" />{{rp | 257}} - -=== Stage diagnostics and immune status === -By applying step-by-step diagnostics, MCS can be differentiated from various allergies and infectious diseases using clinical-internal and inflammatory parameters. The stages include: -# Level: [[white blood cell differential]], [[erythrocyte sedimentation rate]], [[immunoelectrophoresis]] of serum proteins, quantitative immunoglobulins with [[Immunoglobulin E|IgE]] and [[Urine test|urine status]] -# Level: [[C-reactive protein]] (CRP), [[malondialdehyde]], [[homocysteine]],[[immunoglobulin G | IgG subclasses]] and TNF-𝞪 -# Level: LTT, ITT, [[cytokine]]s, [[autoantibodies]] and [[neopterin]] -# Level: Further tests for more detailed clarification, see: [[#Clinical laboratory diagnostics |Clinical laboratory diagnostics]] - -Levels 1 and 2 are used to differentiate between acute and chronic inflammation and bacterial or viral infection. If a corresponding infection is suspected, bacteria or virus-specific pathogen detection must be carried out. Level 3 limits the clinical picture of environmental medicine.<Ref name = "Hill_2010" />{{rp | 259}} - -The laboratory parameters mentioned above can be determined in the context of an immune status; the investigation can be carried out to different extents. Examples are: immunophenotyping of the T-cell subclasses CD4-TH1 and CD4-TH2, ratio of CD4-T helper cells to cytotoxic CD8-T cells or the CD4 / CD8 quotient, number / concentration of NK and B cells, determination of the activation markers on the T lymphocytes ([[CD25]], [[Integrin beta 1|CD29]], [[CD69]], [[Transferrin receptor 1|CD71]], [[HLA-DR]]) for findings on the activation status of the cellular immune system, determination of the regulatory T cells to recognize an overactive immune system, determination of the cytokine pattern in the serum or IgE determinations to exclude type 1 sensitization.<Ref name = "Hill_2010 "/>{{rp | 259/260}} - -The following immunological tests are recommended for the immune status: Determination of the ratio of immunologically imprinted CD4 memory cells to naive CD4 helper cells and the CD8 effector cells to native CD8 cell production. In chronic inflammatory multisystem diseases, both quotients increase to 1.5 times the normal value. Furthermore, the proportion of T8 lymphocytes no longer capable of dividing with the surface antigen CD57 should be determined in relation to the total number of T8 lymphocytes. After specific activation, these cells can trigger [[apoptosis]], are signs of a chronic activation of the immune system and indicate the end stage of degenerative diseases.<Ref name = "Hill_2010" />{{rp | 261}} - -=== Clinical laboratory diagnostics === -There are several markers for MCS and other environmental diseases. In the following, the parameters to be determined are divided into detoxification capacity, stress parameters, parameters for oxidative and nitrosative stress, antioxidative capacity and stress hormone status. - -* Detoxification capacity:<ref name = "Hill_2010" />{{rp | 263}} content of [[Glutathione|reduced glutathione]],[[superoxide dismutase]],[[glutathione peroxidase]], [[Glutathione S-transferase|Glutathione-S-transferase]] in erythrocytes, caffeine saliva test -* Exercise parameters:<ref name = "Hill_2010" />{{rp | 264/265}} Heat shock protein [[HSP60]] (increased in MCS patients), [[mercapturic acid|mercapturic acids]], [[NF-κB|NF-kB]] activation, 37 kDa RNase-L protein, stress status see below, [[homocysteine]], [[neopterin]]. [[Substance P]],[[ nerve growth factor]] and the vasoactive intestinal peptide are permanently elevated in patients with chronic MCS. When provoked with [[Volatile organic compounds|VOC]]-substances, there is a significant increase compared to allergy patients. -* Parameters for oxidative and nitrosative stress:<ref name = "Hill_2010" />{{rp | 265/266}} Determination of [[Nitrogen monoxide|NO]] and[[peroxynitrite]] as well as the activity and enzyme concentration of the nNOS and iNOS (NO synthases), [[8-Oxo-2'-deoxyguanosine]], intracellular [[adenosine triphosphate]], determination of the S100 brain barrier protein,[[lactic acid| lactate]] / [[Pyruvate]] ratio, the cellular redox potential and the oxidative stress or the antioxidant status as well as [[malondialdehyde]] (in the urine) including [[nitrotyrosine | 3-nitrotyrosine]], nitrophenylacetic acid, [[citrulline]] and [[methylmalonic acid]] -* Parameters of the antioxidant capacity:<ref name = "Hill_2010" />{{rp | 266/267}}[[tocopherol | vitamin E]],[[ascorbic acid | vitamin C]], [[Beta-Carotene|beta-carotenes]], [[coenzyme Q10]], [[selenium]]. These antioxidant vitamins or enzyme components serve as[[radical (chemistry) | radical scavengers]] or [[reducing agents]] to detoxify [[Reactive oxygen species|oxygen radical compounds]] (ROS). In the case of chronic environmental diseases, these parameters are usually reduced. -* Stress hormone status:<ref name = "Hill_2010" />{{rp | 267}} [[cortisol]]-day profile (morning peak is missing in chronic multisystem and CFS sufferers), [[melatonin]]-day-and night profile (nocturnal peak is absent in sick people), [[dehydroepiandrosterone]] - -=== Imaging procedures === -Imaging methods are used to determine functional disorders of the brain or functional brain centers. [[Single photon emission computed tomography]] (SPECT) and [[positron emission tomography]] (PET) are two widely used methods in environmental medicine. Using SPECT it was shown that exposure to [[formaldehyde]], solvents,[[pentachlorophenol | pentachlorophenone]], [[Organophosphate|organophosphate pesticides]] and [[mercury (element)|mercury]] results damage of dopaminergic [[Dopamine receptors|D₂-receptors]] in [[basal ganglia]]. This in turn leads to limitations in procedural memory, motor coordination and fine motor skills.<Ref name = "Hill_2010" />{{rp | 268}} - -=== Psychological test procedures === -Psychological and psychometric test procedures and questionnaires can provide information about disorders of brain functions. An example of this would be the [[Chemical Odor Sensitivity Scale]], also known as the COSS test.<Ref name = "Hill_2010" />{{rp | 269}} - -== International Statistical Classification of Diseases == -The [[International Statistical Classification of Diseases and Related Health Problems]] (ICD), maintained by the [[World Health Organization]], is a [[medical coding]] system used for [[medical billing]] and statistical purposes – not for deciding whether any person is sick, or whether any collection of symptoms constitutes a single disease. The ICD does not list MCS as a [[wikt:discrete|discrete]] disease.<ref name="Sears">Sears, Margaret E. 2007. [http://www.chrc-ccdp.gc.ca/sites/default/files/envsensitivity_en.pdf "The Medical Perspective on Environmental Sensitivities."] Note: The opinions expressed in this report are those of the author and do not necessarily reflect the views of the [[Canadian Human Rights Commission]].</ref> However, this does not mean that people with MCS-related symptoms cannot be treated or billed for medical services. For example, the public health service in Germany permits healthcare providers to bill for MCS-related medical services under the ICD-10 code T78.4, which is for idiosyncratic reactions, classified under the heading T78, <span dir="ltr" lang="de">Unerwünschte Nebenwirkungen, anderenorts nicht klassifiziert</span> ("adverse reactions, not otherwise specified").<ref name=":4">{{cite journal | vauthors = Harter K, Hammel G, Fleming M, Traidl-Hoffmann C | title = Multiple chemical sensitivity (MCS) - a guide for dermatologists on how to manage affected individuals | journal = Journal der Deutschen Dermatologischen Gesellschaft = Journal of the German Society of Dermatology | volume = 18 | issue = 2 | pages = 119–130 | date = February 2020 | pmid = 32026633 | doi = 10.1111/ddg.14027 | doi-access = free }}</ref> Being able to get paid for medical services and collect statistics about unspecified, idiosyncratic reactions does not mean that MCS is recognized as a specific disease or that any particular cause has been defined by the German government. Healthcare providers can also bill for MCS-related services under the ICD-10 codes of F45.0 for [[somatization disorder]].<ref name=":4" /> MCS is named in [[Evidence-based medicine|evidence-based]] ("S3") [[Medical guideline|guidelines]] for the management of patients with nonspecific, functional, and somatoform physical symptoms.<ref name=":4" /> +=== International Statistical Classification of Diseases === +The [[International Statistical Classification of Diseases and Related Health Problems]] (ICD), maintained by the [[World Health Organization]], is a [[medical coding]] system used for [[medical billing]] and statistical purposes – not for deciding whether any person is sick, or whether any collection of symptoms constitutes a single disease. The ICD does not list MCS as a [[wikt:discrete|discrete]] disease.<ref name="Sears">Sears, Margaret E. 2007. [http://www.chrc-ccdp.gc.ca/sites/default/files/envsensitivity_en.pdf "The Medical Perspective on Environmental Sensitivities."] Note: The opinions expressed in this report are those of the author and do not necessarily reflect the views of the [[Canadian Human Rights Commission]].</ref> However, this does not mean that people with MCS-related symptoms cannot be treated or billed for medical services. For example, the public health service in Germany permits healthcare providers to bill for MCS-related medical services under the ICD-10 code T78.4, which is for idiosyncratic reactions, classified under the heading T78, <span dir="ltr" lang="de">Unerwünschte Nebenwirkungen, anderenorts nicht klassifiziert</span> ("adverse reactions, not otherwise specified").<ref name=":4">{{Cite journal|last1=Harter|first1=Katharina|last2=Hammel|first2=Gertrud|last3=Fleming|first3=Megan|last4=Traidl‐Hoffmann|first4=Claudia|date=February 2020|title=Multiple chemical sensitivity (MCS) – a guide for dermatologists on how to manage affected individuals|journal=JDDG: Journal der Deutschen Dermatologischen Gesellschaft|language=en|volume=18|issue=2|pages=119–130|doi=10.1111/ddg.14027|pmid=32026633|issn=1610-0379|doi-access=free}}</ref> Being able to get paid for medical services and collect statistics about unspecified, idiosyncratic reactions does not mean that MCS is recognized as a specific disease or that any particular cause has been defined by the German government. Healthcare providers can also bill for MCS-related services under the ICD-10 codes of F45.0 for [[somatization disorder]].<ref name=":4" /> MCS is named in [[Evidence-based medicine|evidence-based]] ("S3") [[Medical guideline|guidelines]] for the management of patients with nonspecific, functional, and somatoform physical symptoms.<ref name=":4" /> ==Management== -There is no single proven treatment for MCS.<ref name=":7" /> The goal of treatment is to improve [[Quality of life (healthcare)|quality of life]], with fewer distressing symptoms and the ability to maintain employment and social relationships, rather than to produce a permanent cure.<ref name=":0" /> +There is no single proven treatment for MCS.<ref name=":7" /> The goal of treatment is to improve [[Quality of life (healthcare)|quality of life]], with fewer distressing symptoms and the ability to maintain employment and social relationships, rather than to produce a permanent cure.<ref name=":0" /> A [[multidisciplinary]] treatment approach is recommended.<ref name="pmid30088144" /> It should take into account the uncommon personality traits often seen in affected individuals and physiological abnormalities in sensory pathways and the limbic system.<ref name="pmid30088144" /> There is also no scientific consensus on supportive therapies for MCS, "but the literature agrees on the need for patients with MCS to avoid the specific substances that trigger reactions for them and also on the avoidance of [[xenobiotic]]s in general, to prevent further sensitization."<ref name=":7" /><ref name =Valderrama2015 />{{Rp|17}}<ref name=":6">''A Scientific Review of Multiple Chemical Sensitivity: Identifying Key Research Needs.'' Published in 2010 by the National Industrial Chemicals Notification and Assessment Scheme, Australian Government. Canberra, Australia http://test.nicnas.gov.au/Media/Latest_News/MCS.asp</ref> @@ -237,5 +66,5 @@ Common [[self-care]] strategies include avoiding exposure to known triggers, [[Detoxification (alternative medicine)|detoxification]], and emotional self-care.<ref name=":0" /> Healthcare providers can provide useful education on the body's natural ability to eliminate and excrete toxins on its own and support positive self-care efforts.<ref name=":0" /> Avoiding triggers, such as by removing smelly cleaning products from the home, can reduce symptoms and increase the person's sense of being able to reclaim a reasonably normal life.<ref name=":0" /> However, for other people with MCS, their efforts to avoid suspected triggers will backfire, and instead produce harmful emotional side effects that interfere with the overall goal of reducing distress and disability.<ref name=":0" /> -Some studies suggest a special focus on correcting any nutritional deficiencies may be beneficial.<ref name="pmid30088144">{{cite journal | vauthors = Viziano A, Micarelli A, Pasquantonio G, Della-Morte D, Alessandrini M | title = Perspectives on multisensory perception disruption in idiopathic environmental intolerance: a systematic review | journal = International Archives of Occupational and Environmental Health | volume = 91 | issue = 8 | pages = 923–935 | date = November 2018 | pmid = 30088144 | doi = 10.1007/s00420-018-1346-z | s2cid = 51936485 }}</ref> +Some studies suggest a special focus on correcting any nutritional deficiencies may be beneficial.<ref name="pmid30088144">{{Cite journal|last1=Viziano|first1=A.|last2=Micarelli|first2=A.|last3=Pasquantonio|first3=G.|last4=Della-Morte|first4=D.|last5=Alessandrini|first5=M.|date=November 2018|title=Perspectives on multisensory perception disruption in idiopathic environmental intolerance: a systematic review.|url=https://www.researchgate.net/publication/326880068|journal=Int Arch Occup Environ Health|volume=91|issue=8|pages=923–935|doi=10.1007/s00420-018-1346-z|pmid=30088144|s2cid=51936485}}</ref> == Epidemiology == @@ -246,20 +75,20 @@ A 2014 study by the Canadian Ministry of Health estimated, based on its survey, that 0.9% of Canadian males and 3.3% of Canadian females had a diagnosis of MCS by a health professional.<ref name=":7" />{{Rp|37}}<ref>Canadian Community Health Survey (CCHS) 2014, Ministry of Health and Long-Term Care Share File, Statistics Canada.</ref> -While a 2018 study at the University of Melbourne found that 6.5% of Australian adults reported having a medical diagnosis of MCS and that 18.9 per cent reported having adverse reactions to multiple chemicals.<ref>Pigatto PD, Guzzi G. Prevalence and Risk Factors for MCS in Australia. ''Preventive Medicine Reports'' 2019.</ref><ref name=":21">{{Cite news|url=https://about.unimelb.edu.au/newsroom/news/2018/july/common-chemical-products-making-australians-sick-study-finds|title=Common chemical products making Australians sick, study finds|date=2 July 2018|work=The University of Melbourne Newsroom|access-date=20 November 2019}}</ref><ref>{{cite journal | vauthors = Steinemann A | title = Prevalence and effects of multiple chemical sensitivities in Australia | journal = Preventive Medicine Reports | volume = 10 | pages = 191–194 | date = June 2018 | pmid = 29868366 | pmc = 5984225 | doi = 10.1016/j.pmedr.2018.03.007 | doi-access = free }}</ref> The study also found that for 55.4 per cent of those with MCS, the symptoms triggered by chemical exposures could be disabling.<ref name=":21" /> +While a 2018 study at the University of Melbourne found that 6.5% of Australian adults reported having a medical diagnosis of MCS and that 18.9 per cent reported having adverse reactions to multiple chemicals.<ref>Pigatto PD, Guzzi G. Prevalence and Risk Factors for MCS in Australia. ''Preventive Medicine Reports'' 2019.</ref><ref name=":21">{{Cite news|url=https://about.unimelb.edu.au/newsroom/news/2018/july/common-chemical-products-making-australians-sick-study-finds|title=Common chemical products making Australians sick, study finds|date=2 July 2018|work=The University of Melbourne Newsroom|access-date=20 November 2019}}</ref><ref>{{cite journal | author = Steinemann A | year = 2018 | title = Prevalence and effects of multiple chemical sensitivities in Australia | journal = Prev Med Rep | volume = 10 | pages = 191–4 | doi=10.1016/j.pmedr.2018.03.007| pmid = 29868366 | pmc = 5984225 | doi-access = free }}</ref> The study also found that for 55.4 per cent of those with MCS, the symptoms triggered by chemical exposures could be disabling.<ref name=":21" /> ===Gulf War syndrome=== -Veterans of the Gulf War attributed to [[Gulf War syndrome]] are similar to those reported for MCS, including headache, fatigue, muscle stiffness, joint pain, inability to concentrate, sleep problems, and gastrointestinal issues.<ref>{{cite journal | vauthors = Gray GC, Gackstetter GD, Kang HK, Graham JT, Scott KC | title = After more than 10 years of Gulf War veteran medical evaluations, what have we learned? | journal = American Journal of Preventive Medicine | volume = 26 | issue = 5 | pages = 443–52 | date = June 2004 | pmid = 15165662 | doi = 10.1016/j.amepre.2004.02.006 }}</ref> +Veterans of the Gulf War attributed to [[Gulf War syndrome]] are similar to those reported for MCS, including headache, fatigue, muscle stiffness, joint pain, inability to concentrate, sleep problems, and gastrointestinal issues.<ref>{{cite journal |vauthors=Gray GC, Gackstetter GD, Kang HK, Graham JT, Scott KC | year = 2004 | title = After more than 10 years of Gulf War Veteran medical evaluations, what have we learned? | journal = American Journal of Preventive Medicine | volume = 26 | issue = 5| pages = 443–452 | doi=10.1016/j.amepre.2004.02.006| pmid = 15165662 }}</ref> -A population-based, cross-sectional epidemiological study involving American veterans of the Gulf War, non-Gulf War veterans, and non-deployed reservists enlisted both during Gulf War era and outside the Gulf War era concluded the prevalence of MCS-type symptoms in Gulf War veterans was somewhat higher than in non-Gulf War veterans.<ref name="pmid10789611">{{cite journal | vauthors = Black DW, Doebbeling BN, Voelker MD, Clarke WR, Woolson RF, Barrett DH, Schwartz DA | title = Multiple chemical sensitivity syndrome: symptom prevalence and risk factors in a military population | journal = Archives of Internal Medicine | volume = 160 | issue = 8 | pages = 1169–76 | date = April 2000 | pmid = 10789611 | doi = 10.1001/archinte.160.8.1169 | doi-access = free }}</ref> After adjusting for potentially confounding factors (age, sex, and military training), there was a robust association between individuals with MCS-type symptoms and psychiatric treatment (either therapy or medication) before deployment and, therefore, before any possible deployment-connected chemical exposures.<ref name="pmid10789611"/> +A population-based, cross-sectional epidemiological study involving American veterans of the Gulf War, non-Gulf War veterans, and non-deployed reservists enlisted both during Gulf War era and outside the Gulf War era concluded the prevalence of MCS-type symptoms in Gulf War veterans was somewhat higher than in non-Gulf War veterans.<ref name="pmid10789611">{{cite journal |vauthors=Black DW, Doebbeling BN, Voelker MD, Clarke WR, Woolson RF, Barrett DH, Schwartz DA |title=Multiple chemical sensitivity syndrome: symptom prevalence and risk factors in a military population |journal=Arch. Intern. Med. |volume=160 |issue=8 |pages=1169–76 |date=April 2000 |pmid=10789611 |doi= 10.1001/archinte.160.8.1169|doi-access=free }}</ref> After adjusting for potentially confounding factors (age, sex, and military training), there was a robust association between individuals with MCS-type symptoms and psychiatric treatment (either therapy or medication) before deployment and, therefore, before any possible deployment-connected chemical exposures.<ref name="pmid10789611"/> -The odds of reporting MCS or chronic multiple-symptom illness was 3.5 times greater for Gulf War veterans than non-Gulf veterans.<ref>{{cite journal | vauthors = Thomas HV, Stimpson NJ, Weightman AL, Dunstan F, Lewis G | title = Systematic review of multi-symptom conditions in Gulf War veterans | journal = Psychological Medicine | volume = 36 | issue = 6 | pages = 735–47 | date = June 2006 | pmid = 16438740 | doi = 10.1017/s0033291705006975 | s2cid = 35677845 }}</ref> Gulf War veterans have an increased rate of being diagnosed with multiple-symptom conditions compared to military personnel deployed to other conflicts.<ref>{{cite journal | vauthors = Ismail K, Lewis G | title = Multi-symptom illnesses, unexplained illness and Gulf War Syndrome | journal = Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences | volume = 361 | issue = 1468 | pages = 543–51 | date = April 2006 | pmid = 16687260 | pmc = 1569616 | doi = 10.1098/rstb.2006.1815 }}</ref> +The odds of reporting MCS or chronic multiple-symptom illness was 3.5 times greater for Gulf War veterans than non-Gulf veterans.<ref>{{cite journal |vauthors=Thomas HV, Stimpson NJ, Weightman AL, Dunstan F, Lewis G | year = 2006 | title = Systematic review of multi-symptom conditions in Gulf War veterans." Multi-symptom illnesses, unexplained illness, and Gulf War Syndrome" | url =http://orca.cf.ac.uk/6803/1/Systematic_review.pdf | journal = Psychological Medicine | volume = 36 | issue = 6| pages = 735–747 | doi=10.1017/s0033291705006975| pmid = 16438740 }}</ref> Gulf War veterans have an increased rate of being diagnosed with multiple-symptom conditions compared to military personnel deployed to other conflicts.<ref>{{cite journal |vauthors=Ismail K, Lewis G | year = 2006 | title = Multi-symptom illnesses, unexplained illness, and Gulf War Syndrome | journal = Philosophical Transactions of the Royal Society B | volume = 361 | issue = 1468| pages = 543–551 | doi=10.1098/rstb.2006.1815| pmc = 1569616 | pmid=16687260}}</ref> == Prognosis == -About half of those who claim to be affected by MCS get better over the course of several years, while about half continue to experience distressing symptoms.<ref name=":0">{{Cite book|title=Current Occupational & Environmental Medicine| vauthors = Harrison R |publisher=McGraw-Hill Education/Medical|year=2014|isbn=978-0-07-180816-3|edition=Fifth|location=New York|pages=819–826|chapter=Multiple Chemical Sensitivity|oclc=898477589}}</ref> +About half of those who claim to be affected by MCS get better over the course of several years, while about half continue to experience distressing symptoms.<ref name=":0">{{Cite book|title=Current Occupational & Environmental Medicine|last=Harrison|first=Robert|publisher=McGraw-Hill Education/Medical|year=2014|isbn=978-0-07-180816-3|edition=Fifth|location=New York|pages=819–826|chapter=Multiple Chemical Sensitivity|oclc=898477589}}</ref> == History == MCS was first proposed as a distinct disease by [[Theron Randolph|Theron G. Randolph]] in 1950. In 1965, Randolph founded the [[Society for Clinical Ecology]] as an organization to promote his ideas about symptoms reported by his patients. As a consequence of his insistence upon his own, non-standard definition of ''allergy'' and his unusual theories about how the immune system and toxins affect people, the ideas he promoted were widely rejected, and [[clinical ecology]] emerged as a non-recognized medical specialty.<ref name=":0" /> -In the 1990s, an association was noted with chronic fatigue syndrome, fibromyalgia, and Gulf War syndrome.<ref name="Donnay">{{cite journal| vauthors = Donnay AH |date=1999|title=On the Recognition of Multiple Chemical Sensitivity in Medical Literature and Government Policy|journal=International Journal of Toxicology|volume=18|issue=6|pages=383–392|doi=10.1080/109158199225099|s2cid=72141513}}</ref> +In the 1990s, an association was noted with chronic fatigue syndrome, fibromyalgia, and Gulf War syndrome.<ref name="Donnay">{{cite journal|author=Donnay|first=Albert H|date=1999|title=On the Recognition of Multiple Chemical Sensitivity in Medical Literature and Government Policy|journal=International Journal of Toxicology|volume=18|issue=6|pages=383–392|doi=10.1080/109158199225099|s2cid=72141513}}</ref> In 1994, the AMA, [[American Lung Association]], [[United States Environmental Protection Agency|US EPA]] and the US [[Consumer Product Safety Commission]] published a booklet on [[Indoor air quality|indoor air pollution]] that discusses MCS, among other issues. The booklet further states that a pathogenesis of MCS has not been definitively proven, and that symptoms that have been self-diagnosed by a patient as related to MCS could actually be related to allergies or have a psychological basis, and recommends that physicians should counsel patients seeking relief from their symptoms that they may benefit from consultation with specialists in these fields.<ref name="urlIndoor Air Pollution: An Introduction for Health Professionals | Publications | Indoor Air | Air | US EPA">{{cite book|title=Indoor Air Pollution: An Introduction for Health Professionals|year=1994|publisher= Co-sponsored by: The American Lung Association (ALA), The Environmental Protection Agency (EPA), The Consumer Product Safety Commission (CPSC), and The American Medical Association (AMA)|url=http://www.epa.gov/iedweb00/pubs/hpguide.html#faq1|quote=[D]efinition of the phenomenon is elusive and its pathogenesis as a distinct entity is not confirmed....The current consensus is that in cases of claimed or suspected MCS, complaints should not be dismissed as psychogenic, and a thorough workup is essential. Primary care givers should determine that the individual does not have an underlying physiological problem and should consider the value of consultation with allergists and other specialists.|access-date=2008-06-30}}</ref> @@ -269,5 +98,5 @@ The different understandings of MCS over the years have also resulted in different proposals for names.<ref name=":1" /> For example, in 1996 the International Programme on Chemical Safety proposed calling it ''idiopathic environmental illness'', because of their belief that chemical exposure may not the sole cause,<ref name=":3" /> while another researcher, whose definition includes people with allergies and acute poisoning, calls it ''chemical sensitivity''.<ref name=":1" />{{Clarify|reason=Who? Text is in Japanese so different source needed.|date=June 2020}} -== See also == +==See also== * [[Electromagnetic hypersensitivity]] * [[Sick building syndrome]] @@ -277,18 +106,5 @@ == References == -{{Reflist}} - -== Further reading == -{{refbegin}} -* NICNAS (Australian Government Department of Health and Aging): A scientific review of multiple chemical sensitivity: Working Draft report, November 2008. {{Webarchiv|url=https://web.archive.org/web/20100120040642/http://www.nicnas.gov.au/Current_Issues/MCS/MCS_Report_PDF.pdf |text=Online }} -* N. A. Ashford, C. S. Miller: ''Chemical exposures. Low levels and high stakes.'' 2. Auflage. Van Nostrand Reinhold, New York 1998. -* S. M. Caress, A. C. Steinemann, C. Waddick: ''Symptomatology and etiology of multiple chemical sensitivities in the southeastern United States.'' In: ''Archives of Environmental and Occupational Health.'' (2002); 57, S. 429–436. -* S. Reid, M. Hotopf, L. Hull, K. Ismail, C. Unwin, S. Wessely: ''Multiple Chemical Sensitivity and Chronic Fatigue Syndrome in British Gulf War Veterans.'' In: ''American Journal of Epidemiology.'' (2001); 153, S. 604–609. -* R. Kreutzer, R. R. Neutra, N. Lashuay: ''Prevalence of people reporting sensitivities to chemicals in a population based survey.'' In: ''American Journal of Epidemiology.'' (1999); 150, S. 1–12. -* W. J. Meggs, K. A. Dunn, R. M. Bloch u. a.: ''Prevalence and nature of allergy and chemical sensitivity in a general population.'' In: ''Archives of Environmental and Occupational Health.'' (1996); 51, S. 275–282. -* A. L. Davidoff, P. M. Keyl, W. Meggs: ''Development of multiple chemical sensitivities in laborers after acute gasoline fume exposure in an underground tunneling operation.'' In: ''Archives of Environmental and Occupational Health.'' (1998); 53, S. 183–189. -* Martin L. Pall: ''Explaining „Unexplained Illnesses“. Disease Paradigm for Chronic Fatigue Syndrome, Multiple Chemical Sensitivity, Fibromyalgia, Post-Traumatic Stress Disorder, Gulf War Syndrome, and Others.'' Harrington Park Press/Haworth Press, New York/ London 2007, ISBN 978-0-7890-2388-9. -* William J. Rea: ''Chemical Sensitivity.'' Volume 1–4, Lewis Publishers; Volume 1, ISBN 0-87371-541-1; Volume 2, ISBN 0-87371-963-8; Volume 3, ISBN 0-87371-964-6; Volume 4, ISBN 0-87371-965-4. -{{refend}} +<references /> == External links == @@ -301,4 +117,2 @@ [[Category:Ailments of unknown cause]] [[Category:Sensitivities]] -[[Category:Intoxication]] -[[Category:Neurological disorders]] '