Approach to patients with unexplained multimorbidity with sensitivities

Thanks to Drs. Campbell, Abbass and Zehr for their insightful response to the articles on unexplained multimorbidity with sensitivities (MWS).[1,2] Their letter highlights important issues which I would like to address.

What causes people to get sick?

There are many ways of being sick, but there are only a few factors that actually cause sickness. A detailed review of medical history will confirm that there are only five etiological determinants of illness: i) Genetics, ii) Deficiencies, iii) Pathogens, iv) Toxic exposures, and v) Psychological factors.[3] Furthermore, the Centers for Disease Control recently concluded that virtually all illness results from the interaction of genetic susceptibility and modifiable environmental factors.[4] Integrating these two streams, it is evident that the totality of adverse modifiable environmental factors includes toxic exposures such as chemical pollutants and radiation, pathogens, deficiency states, as well as emotional and psychological adversities. When people suggest that illness is the result of autoimmune changes, chemical imbalances, hormonal dysregulation, inflammatory states, degenerative problems, and so on, it is important to realize that these processes are epiphenomena resulting from primary underlying causes and that these processes describe pathophysiological mechanisms of illness, not etiological determinants. The five factors listed above, including psychological and emotional factors, are the root source of all illness - any or all of these can contribute to multimorbidity.

To address the major tenor of the letter: each human person could be described as a unique metaphysical ecosystem configured within a biochemical machine. When considering disease etiology, a disregard of the metaphysical component of our being (the mental, social, and spiritual as discussed in the WHO definition of health[5]) would be inappropriate indeed. As the letter writers suggest, much scientific work and experience support adverse psychological states as primary determinants of morbidity. Furthermore, it is well established that measures to address adverse emotional states can have enormous potential benefit if the underlying source of the problem is fundamentally emotional and psychological. Measures to quell emotional manifestations if the underlying problem is a chemical toxicant burden (such as bioaccumulated lead, mercury, solvents, or flame retardants in the brain), however, are usually less than successful. Furthermore, as medical trainees are often not apprised of the immense role of toxic determinants of morbidity, there is often a default to attribute inexplicable multimorbidity states to pathopsychology - a reality that frustrates many patients.

What are the causes of multimorbidity?

Sensitivity related illness (SRI) resulting from toxicant exposures is definitely NOT the sole cause of multimorbidity. The papers on MWS[1,2] were never intended to be a systematic review of all causes of multimorbidity, but rather a discussion of the emerging pandemic of unexplained multimorbidity with sensitivities - i.e. unremitting MWS in patients that cannot be attributed to any other cause and that does not respond to other interventions. The above listed primary determinants of illness can all contribute to multimorbidity states. Infection with pathogens causing Lyme disease, for example, can definitely manifest as MWS. Another area not explored in the papers was widespread deficiency states, a common etiological source of multimorbidity and a subject often neglected in medical education.[6] For example, vitamin D is involved in genetic regulation and expression, with over 2700 binding sites on the human genome.[7] Insufficiency of this vital nutrient is rampant in North America[8] and is associated with assorted conditions involving most organ systems.[9] Several other prevalent deficiencies can also present as multimorbidity including inadequate levels of nutrients such as magnesium [10] and omega-3 polyunsaturated docosahexanoic acid (DHA). [11] [12]

Furthermore, primary determinants of illness can act in concert or synergistically to facilitate multimorbidity and sensitivities. While the chemical sensitivity epidemic may be primarily related to toxicant exposures, for example, it is certainly true that stress can exacerbate immune dysfunction and thus trigger sensitivities in a susceptible host. Accordingly, it is wonderful that emotional contributors to illness are addressed in Nova Scotia, as the letter writers suggest. I have not seen literature evidence, however, to suggest that stress is the predominant etiological determinant of the escalating epidemic of sensitivities.[13] There is, on the other hand, abundant evidence in the literature to support the contention that toxicant exposures are the principal etiological factor in SRI. Recent literature about young children, for example, confirms that environmental sensitivities with documented immune dysregulation are directly related to a whole variety of prenatal chemical exposures.[14,15,16,17,18,19,20] It is unlikely that intensive short-term dynamic psychotherapy will be efficacious against sensitivity related problems in this cohort.

Moving forward

Most importantly, I believe that physicians should have the training and skills to pursue ALL etiological determinants of illness in patients with MWS in order to identify which primary factors are causing the sickness. As part of a comprehensive medical workup including a psychological assessment, it is my sincere hope that a broad toxicant panel looking for bioaccumulated chemical toxicants will soon be available. I routinely incorporate this laboratory testing tool with multimorbidity patients and often find accrued chemical pollutants as a potential reason to explain the ongoing suffering and chronic illness. This metric provides objective laboratory evidence to conclusively determine if people have a toxicant burden and allows for appropriate interventions to clear the burden, if present, in order to preclude and treat illness. Elimination of toxicant burdens that are disrupting physiology on an ongoing basis can be life changing for chronically ill people.[21,22,23] Unfortunately, such testing is not yet generally available in Canada - but such analysis at a population level has been recently carried out and published by both Health Canada[24] and the Centers for Disease Control.[25] In response to the recognized problem of widespread deficiency issues, it is also my hope that in-depth training about nutritional biochemistry with appropriate laboratory testing will also be available so that clinicians can determine the nutritional status of their patients in order to address biochemical insufficiencies.

Conclusion

While considering the letter from Drs. Campbell, Abbass and Zehr, there appears to be no major difference in opinion, but rather a difference in focus. My brief articles for Canadian Family Physician were not designed to be an expansive exposition exploring all etiological determinants of morbidity, but an introduction to SRI as one of the common sequelae of chemical toxicant bioaccumulation - a prevalent determinant of multimorbidity that is increasingly being recognized and discussed in the scientific literature. Finally, it was also my objective to emphasize the importance of looking for the etiology of disease in clinical medicine whenever possible. If a persistent noise was emanating from your car engine, you would most assuredly expect the mechanic to find and correct the cause of the noise, not to dispense ear muffs. Although we can camouflage symptoms with drugs, illness commences because of a cause, illness persists because the cause persists, and illness can only truly resolve when the cause is addressed. With tools and knowledge to identify causative determinants, appropriate interventions can be undertaken to facilitate healing and restoration for many of our patients suffering with multimorbidity. Thank you.

References:

1. Genuis SJ (2014) Pandemic of idiopathic multimorbidity. Canadian family physician Medecin de famille canadien 60: 511-514, e290-513.

2. Genuis SJ, Tymchak MG (2014) Approach to patients with unexplained multimorbidity with sensitivities. Canadian family physician Medecin de famille canadien 60: 533-538.

3. Genuis SJ (2012) What's out there making us sick? Journal of Environmental and Public Health 605137.

4. Office of Genomics and Disease Prevention: Centers for Disease Control and Prevention. Department of Health and Human S (2000) Gene- Environment Interaction Fact Sheet.

5. World Health Organization Constitution: definition of health. World Health Organization, Geneva, 1948.

6. Lo C (2000) Integrating nutrition as a theme throughout the medical school curriculum. Am J Clin Nutr 72: 882S-889S.

7. Ramagopalan SV, Heger A, Berlanga AJ, Maugeri NJ, Lincoln MR, et al. (2010) A ChIP-seq defined genome-wide map of vitamin D receptor binding: associations with disease and evolution. Genome research 20: 1352 -1360.

8. Hanley DA, Davison KS (2005) Vitamin D insufficiency in North America. J Nutr 135: 332-337.

9. Schwalfenberg G (2007) Not enough vitamin D: health consequences for Canadians. Can Fam Physician 53: 841-854.

10. Nielsen FH (2014) Effects of magnesium depletion on inflammation in chronic disease. Current opinion in clinical nutrition and metabolic care.

11. Pinel A, Morio-Liondore B, Capel F (2014) n-3 Polyunsaturated fatty acids modulate metabolism of insulin-sensitive tissues: implication for the prevention of type 2 diabetes. Journal of physiology and biochemistry 70: 647-658.

12. Abeywardena MY, Patten GS (2011) Role of omega3 long-chain polyunsaturated fatty acids in reducing cardio-metabolic risk factors. Endocrine, metabolic & immune disorders drug targets 11: 232-246.

13. Genuis SJ (2010) Sensitivity-related illness: the escalating pandemic of allergy, food intolerance and chemical sensitivity. The Science of the Total Environment 408: 6047-6061.

14. Reichrtova E, Ciznar P, Prachar V, Palkovicova L, Veningerova M (1999) Cord serum immunoglobulin E related to the environmental contamination of human placentas with organochlorine compounds. Environmental health perspectives 107: 895-899.

15. Jedrychowski W, Perera F, Maugeri U, Miller RL, Rembiasz M, et al. (2011) Intrauterine exposure to lead may enhance sensitization to common inhalant allergens in early childhood: a prospective prebirth cohort study. Environmental Research 111: 119-124.

16. Jedrychowski W, Galas A, Pac A, Flak E, Camman D, et al. (2005) Prenatal ambient air exposure to polycyclic aromatic hydrocarbons and the occurrence of respiratory symptoms over the first year of life. Eur J Epidemiol 20: 775-782.

17. Grandjean P, Poulsen LK, Heilmann C, Steuerwald U, Weihe P (2010) Allergy and sensitization during childhood associated with prenatal and lactational exposure to marine pollutants. Environmental health perspectives 118: 1429-1433.

18. Okada E, Sasaki S, Saijo Y, Washino N, Miyashita C, et al. (2012) Prenatal exposure to perfluorinated chemicals and relationship with allergies and infectious diseases in infants. Environmental Research 112: 118-125.

19. Miyashita C, Sasaki S, Saijo Y, Washino N, Okada E, et al. (2011) Effects of prenatal exposure to dioxin-like compounds on allergies and infections during infancy. Environmental Research 111: 551-558.

20. Stolevik SB, Nygaard UC, Namork E, Haugen M, Kvalem HE, et al. (2011) Prenatal exposure to polychlorinated biphenyls and dioxins is associated with increased risk of wheeze and infections in infants. Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association 49: 1843-1848.

21. Redgrave TG, Wallace P, Jandacek RJ, Tso P (2005) Treatment with a dietary fat substitute decreased Arochlor 1254 contamination in an obese diabetic male. J Nutr Biochem 16: 383-384.

22. Ross GH, Sternquist MC (2012) Methamphetamine exposure and chronic illness in police officers: significant improvement with sauna- based detoxification therapy. Toxicology and industrial health. 28(8):758- 68.

23. Genuis SJ (2011) Elimination of persistent toxicants from the human body. Human & experimental toxicology 30: 3-18.

24. Health Canada (2013) Canadian Helath Measures Survey. Second report on human biomonitoring of environmental chemicals in Canada. .Accessed on April 2,2014 at [http://www.hc-sc.gc.ca/ewh- semt/contaminants/human-humaine/chms-ecms-eng.php].

25. Centers for Disease Control and Prevention: Department of Health and Human Services (2013) Fourth National Report on Human Exposure to Environmental Chemicals. Atlanta: Georgia. Updated Tables.Accessed April 14/2014 at [ http://www.cdc.gov/exposurereport/pdf/FourthReport_UpdatedTables_Mar2013.pdf ]

Conflict of Interest:

None declared