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Disease Biomarkers Characterizing and Identifying EHS and MCS
28 nov. 2015
Reliable Disease Biomarkers Characterizing and Identifying Electrohypersensitivity and Multiple Chemical Sensitivity as Two Etiopathogenic Aspects of a Unique Pathological Disorder
''Here, we present our own experiences based on the preliminary analysis of a series of 1216 consecutive investigated cases of self-claimed EHS and/or MCS, in the framework of an ongoing prospective clinical study aiming at identifying and characterizing EHS and MCS both clinically and biologically; through the use of biomarkers detected and measured in the peripheral blood and the urine of patients. Our data clearly shows that EHS and MCS should be recognized as genuine somatic pathological entities; that patients with EHS and/or MCS are nonpsychosomatic nor psychiatric patients; and probably that EHS and MCS are two etiopathogenic aspects of a single pathological disorder.''
Dominique Belpomme1, 2 / Christine Campagnac2, 3 / Philippe Irigaray2, 4
1Paris V University Hospital, France
2European Cancer and Environment Research Institute (ECERI), Brussels, Belgium
3Hospital Director, seconded from Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France
4Association for Research and Treatments Against Cancer (ARTAC), F-75015 Paris, France
Corresponding author: Philippe Irigaray, PhD, ARTAC, 57-59 rue de la convention, 75015 Paris, Phone: +33 (0)1 45 78 53 54, Fax: +33 (0)1 45 78 53 50, E-mail: (email); Association for Research and Treatments Against Cancer (ARTAC), F-75015 Paris, France; and European Cancer and Environment Research Institute (ECERI), Brussels, Belgium
Citation Information: Reviews on Environmental Health. Volume 30, Issue 4, Pages 251–271, ISSN (Online) 2191-0308, ISSN (Print) 0048-7554, DOI: 10.1515/reveh-2015-0027, November 2015
Publication History Received:2015-09-11 Accepted:2015-11-02 Published Online:2015-11-27
Much of the controversy over the causes of electro-hypersensitivity (EHS) and multiple chemical sensitivity (MCS) lies in the absence of both recognized clinical criteria and objective biomarkers for widely accepted diagnosis. Since 2009, we have prospectively investigated, clinically and biologically, 1216 consecutive EHS and/or MCS-self reporting cases, in an attempt to answer both questions. We report here our preliminary data, based on 727 evaluable of 839 enrolled cases: 521 (71.6%) were diagnosed with EHS, 52 (7.2%) with MCS, and 154 (21.2%) with both EHS and MCS. Two out of three patients with EHS and/or MCS were female; mean age (years) was 47. As inflammation appears to be a key process resulting from electromagnetic field (EMF) and/or chemical effects on tissues, and histamine release is potentially a major mediator of inflammation, we systematically measured histamine in the blood of patients. Near 40% had a increase in histaminemia (especially when both conditions were present), indicating a chronic inflammatory response can be detected in these patients. Oxidative stress is part of inflammation and is a key contributor to damage and response. Nitrotyrosin, a marker of both peroxynitrite (ONOO°-) production and opening of the blood-brain barrier (BBB), was increased in 28% the cases. Protein S100B, another marker of BBB opening was increased in 15%. Circulating autoantibodies against O-myelin were detected in 23%, indicating EHS and MCS may be associated with autoimmune response. Confirming animal experiments showing the increase of Hsp27 and/or Hsp70 chaperone proteins under the influence of EMF, we found increased Hsp27 and/or Hsp70 in 33% of the patients. As most patients reported chronic insomnia and fatigue, we determined the 24 h urine 6-hydroxymelatonin sulfate (6-OHMS)/creatinin ratio and found it was decreased (<0.8) in all investigated cases. Finally, considering the self-reported symptoms of EHS and MCS, we serially measured the brain blood flow (BBF) in the temporal lobes of each case with pulsed cerebral ultrasound computed tomosphygmography. Both disorders were associated with hypoperfusion in the capsulothalamic area, suggesting that the inflammatory process involve the limbic system and the thalamus. Our data strongly suggest that EHS and MCS can be objectively characterized and routinely diagnosed by commercially available simple tests. Both disorders appear to involve inflammation-related hyper-histaminemia, oxidative stress, autoimmune response, capsulothalamic hypoperfusion and BBB opening, and a deficit in melatonin metabolic availability; suggesting a risk of chronic neurodegenerative disease. Finally the common co-occurrence of EHS and MCS strongly suggests a common pathological mechanism.
In 1962, Randolph first described clinically (1) what is today commonly called multiple chemical sensitivity (MCS) (2); a human pathological disorder that has been identified and defined in 1999 during an international consensus meeting on the basis of the six following criteria: “1. The symptoms are reproducible with (repeated chemical) exposure; 2. The condition is chronic; 3. Low levels of exposure (lower than previously or commonly tolerated) result in manifestations of the syndrome; 4. The symptoms improve or resolve when the inciting agents are removed; 5. Responses occur to multiple chemically unrelated substances; 6. (Added in 1999): Symptoms involve multiple organ systems” (3). Although the precise worldwide prevalence of MCS remains unclear, it is expected that due to the vastly increased number of the various chemical products that have been put on the market during the last few decades, MCS is becoming an increasing prevalent pathological disorder (4).
The recent rise of wireless telecommunication worldwide also confronts scientists with the question of whether anthropogenic electromagnetic fields (EMFs) such as emitted by cell phones, wireless internet, and high voltage power lines, can cause adverse health effects as it is the case for chemicals. In 1991 Rea first described what he called electromagnetic field sensitivity (5). Six years later, Bergqvist et al., in a report prepared by a European group of experts for the European Commission coined the term electrohypersensitivity (EHS) to encompass in a unique concept the clinical conditions in which EHS self-reporting patients complain of symptoms they attribute to EMF exposure (6). Since 1998, Santini et al. in France, reported symptoms experienced by users of digital cellular phones and the health risk of people living near cellular phone base stations (7, 8).
In 2004, because of the increasing worldwide prevalence of EHS, the World Health Organization (WHO) organized an international scientific workshop in Prague (Czech Republic) in order to define and characterize EHS. Although not acknowledging EHS as being caused by EMF exposure, the Prague working group defined EHS as “a phenomenon where individuals experience adverse health effects while using or being in the vicinity of devices emanating electric, magnetic, or electromagnetic fields … whatever its cause, EHS is a real and sometimes a debilitating problem for the affected persons” (9). However, following this meeting, WHO proposed to use the alternative term “idiopathic environmental intolerance (IEI) attributed to electromagnetic fields” (IEI – EMF), indicating there is no proven causality between the occurrence of IEI – EMF (formerly EHS) and EMF exposure (9).
In view of the poor knowledge of pathogenesis and etiology of EHS and MCS, most mainstream medical, sanitary and societal bodies maintain there is not sufficient scientific proof to support the concept that clinical symptoms experienced by EHS and/or MCS self-reporting patients are really caused by EMF and/or chemical exposure, respectively. This is particularly the case for EHS patients, for whom in comparison to sham controls, the reproduction of clinical symptoms in the presence of EMFs have globally failed to demonstrate a causal link, in blind or double-blind studies (10).
Moreover, the lack of recognized disease biomarkers objectively characterizing EHS and MCS has resulted in clinical symptoms being dismissed as psychogenic; and/ or EHS and MCS are conflated with psychosomatic or psychiatric diseases, and not recognized as true organic disorders caused by the environment (11–16). This is particularly the case for radiofrequency EMF, for which some scientists believe that EHS is an uncertain and confusing concept (17); whereas some others, on the basis of their own clinical experience agree that excessive exposure may cause EHS (5, 18, 19).
Here, we present our own experiences based on the preliminary analysis of a series of 1216 consecutive investigated cases of self-claimed EHS and/or MCS, in the framework of an ongoing prospective clinical study aiming at identifying and characterizing EHS and MCS both clinically and biologically; through the use of biomarkers detected and measured in the peripheral blood and the urine of patients. Our data clearly shows that EHS and MCS should be recognized as genuine somatic pathological entities; that patients with EHS and/or MCS are nonpsychosomatic nor psychiatric patients; and probably that EHS and MCS are two etiopathogenic aspects of a single pathological disorder.
The growing worldwide health problem
Whatever the causal origin of EHS and/or MCS, there is compelling evidence that EHS and/or MCS self-reporting patients constitute an unsolved, large and growing health problem worldwide.
As far as EHS is concerned, about 1%–10% of the investigated population, e.g. 5% in Switzerland (13), 5% in Ireland, 9% in Sweden, 9% in Germany and 11% in England are presently estimated to be EHS self-reporting persons (201). Given the seven billion persons worldwide using cordless and/or mobile phone it is expected these percentages may increase in the 50 next years. However, because at the time these estimations were made there was no objective criteria for identifying EHS (21), these data require confirmation by more objective investigations.
By using the battery of biomarkers we have investigated in this study it now seems possible to objectively characterize and identify EHS and MCS. Although termed “idiopathic”, IEI has been defined as abnormal responses possibly triggered by exposure to organic chemicals and/ or metals. It is believed that in addition, to MCS several pathological disorders such as fibromyalgia and chronic fatigue syndrome, because they may share a similar environment-related intolerance condition, could be part of IEI. We have shown multiple lines of evidence that EHS and MCS share a similar pathogenesis and so might be the same pathological disorder whatever their putative causal stressors. This strongly reinforces the concept that both EHS and MCS must be part of the so called IEI syndrome.
Since the WHO publication in 1993 on EMFs (202), much progress have been made in the identification and understanding of EMF effects on the organism, while EHS has still not been clearly characterized and acknowledged by WHO.
Present research vainly focus on the causal role of EMFs and chemicals as possible triggers of EHS and MCS, respectively and not enough on the actually unmet health care needs at a socioeconomic and public health setting for persons with environmental sensitivity (203), as it is particularly the case for EHS and/or MCS persons.
We therefore, strongly propose that whatever their proofs for their causal origins, EHS and MCS should clearly be added to the next version of the WHO international classification of diseases (ICD) on the basis on their clinical and pathological description; as has been the case for many other diseases.
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Dit is een belangrijk artikel. Het beschrijft een uitbreiding van de bestaande diagnose technieken, nl. het meten van evt. verminderde bloedstroom in delen van de hersenen als indicatie van EHS en/of MCS, naast bloed- en urineonderzoek.
Prof. Belpomme onderzoekt patiënten, waaronder uit Nederland, geeft ze een certificaat waarin staat dat ze EHS en/of MCS zijn, indien dat uit het onderzoek blijkt, en schrijft medicatie voor. Dat leidt veelal tot een verbetering van hun toestand, al blijft hun gevoeligheid (EHS en/of MCS) bestaan.
Alleen is de wachttijd voor het aannemen van nieuwe patiënten nu wel één jaar.
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