Scientists search for reliable biomarkers in Multiple Chemical Sensitivity

Written by Matthew Hogg BSc (Hons)

Tuesday, 30 August 2011 11:48

After years out in the medical and scientific wilderness, researchers are starting to take a serious look at the underlying pathological mechanisms at work in multiple chemical sensitivity in seach of a reliable biomarker that would revolutionise diagnosis and treatment.

Italian researchers examined all available evidence regarding scientific, medical and social aspects of multiple chemical sensitivity (MCS) and related environmental Illnesses (EI) with an emphasis on the biological abnormalities thus far uncovered which might point the way to the development of a biomarker that could be used clinically.

Among the biological dysfunctions noted by other researchers and discussed in this review are immunological dysregulation, neurogenic inflammation, limbic kindling and neural sensitisation, toxicant-induced loss of tolerance (TILT), altered xenobiotic metabolism, altered nitric oxide/peroxynitrite cycle (NO/ONOO-). Those familiar with MCS research will recognise these to be the key experiemental findings and leading hypotheses for explaining the pathogenesis and ongoing pathophysiology in the condition.

In addition to discussing the important findings and hypotheses of the likes of Professor Martin Pall PhD and Dr. Claudia S. Miller MD, MS, the scientists behind this review of the current state of evidence also report on their own findings in studies with MCS patients that add to the overall picture of current research and medical and public perception of the illness.

In a case history of 620 Italian patients with symptoms attributable to MCS, admitted to the Redox Marker Diagnostic Service at the Dermatological Research Institute, Rome, 35% of cases reported concomitant electrical hypersensitivity (EHS), approximately 10% of chronic fatigue syndrome (CFS) and of fibromyalgia (FM) co-morbidities, and 5% of cases reported intolerance to multiple dental amalgam fillings.

The scientists note that "Some authors view this as a proof of the functional somatic syndrome hypothesis, where symptoms or diagnostic criteria overlap to indicate a prevailing common psychosocial denominator of the disorders." However, they believe the opposite is in fact the case, stating that "...from the biological perspective, the marked similarity of symptoms may also support the expectations for a possible identification of common organic etiological biomarkers of disease."

They go on to suggest that the high level of comorbidities among this group of illnesses does not necessarily suggest they are slightly different manifestations of the same disease but that it is likely they share dysfunctions in some common molecular pathways, mainly relating to detoxification, redox homeostasis, and neuroimmune signaling.

According to the authors of this paper there are a number of important reasosn why MCS as a disease entity and those affected by it are often ignored. These being:

The wide array of symptoms and signs allegedly linkable to environmental triggers exposure.
The diversity of the subjects affected, reacting on the basis of individual sensitivity and possibly genetic predisposition.
The mere absence of proven pathogenic mechanisms and consequently of clear-cut diagnostic criteria.
The wide spectrum of possible triggers.
Absence of clear dose-dependent reactions, generating methodological difficulties and bias in provocation studies.

Point 5, the absence of clear dose-dependent reactions, is an important issue as it produces studies that conclude there is no evidence for MCS - yet these studies are based on flawed traditional toxicology-based designs. As such the deck is stacked hugely against MCS as being legitimate from the start.

The authors of the current paper argue that our idea of toxicology needs revising before the reason so many people are affected by MCS and other multi-system illnesses becomes clear.

"There exist conceptual difficulties in attributing a disease status to the paradoxical reaction observed in MCS to chemico-physical stimuli delivered in concentrations far below threshold levels established for environmental compounds by the conventional toxicology approach. The general assumption of a hormetic (biphasic) behaviour for xenobiotics on biological systems may allow new scenarios, overcoming the threshold dose-response model, and introducing the concept that an environmental toxicant may induce the opposed effects of stimulation/adaptation or toxicity, respectively at very low or high concentrations. The complex network of hormetic response pathways might be altered at some unknown point(s) in MCS subjects, through mechanisms still to be investigated."

The researchers also bravely suggest that, besides the methodological research difficulties, the vested interests of the industrial and pharmaceutical world are contributing significantly to the persisting general scarce attention of public health systems worldwide to the large numbers of people suffering symptoms of chemical exposure and liviing with MCS.

In terms of treatment, the researchers conclude that: "Today, the only therapeutic approach with demonstrated beneficial effects is exposure avoidance, with the consequent complex task of removing putative indoor triggers from the living environment, often impossible in working and public places. Based on present available information, selected therapeutic proposals based on active antioxidant/chelator/gene- and immune-modulating principles, able to selectively prevent formation and release of excess reactive species or hydro- or lipid-peroxides, and to enhance specific detoxification pathways through ROS/RNS modulation, are to be taken into consideration for future clinical trials, which will be possible only if and when appropriate medical infrastructures with specific environmental requirements will be provided for these patients on the large scale.

After reading this paper it is clear that the data supporting an organic, biological explanation for the symptoms experienced by those suffering from MCS far outweighs that suggesting a psychogenic explanation. However, problems with current views of toxicology and other methodological issues make conclusive research difficult and this is compounded by interference from vested commercial interests and lack of political will. Still, it is heartening for MCS sufferers that more and more researchers are taking an active interest in explaining MCS, which presents a substantial intellectual challenge. Hopefully, this will lead to the development of a reliable biomarker and diagnostic criteria sooner rather than later.

The paper is published in International Journal of Environmental Research and Public Health and the full text is available online for free here.

Reference: De Luca C Raskovic D Pacifico V Thai JC Korkina L (2011) The search for reliable biomarkers of disease in multiple chemical sensitivity and other environmental intolerances International Journal of Environmental Research and Public Health 8(7):2770-97