Recent insights into 3 underrecognized conditions

Prevalence and costs

Data from the 2014 Canadian Community Health Survey by Statistics Canada indicate that of Canadians aged 25 years or older, 5.5% (1.3 million) reported having 1 or more of the 3 conditions: 1.6% reported ME-CFS, 2.0% reported FM, and 2.7% reported ES-MCS. Women were more than twice as likely as men were to report each disorder. Comparing respondents who reported 1 or more of the conditions with those reporting none, 16% versus 10% reported at least 10 consultations in the past year with a primary care practitioner, 53% versus 32% reported at least 1 consultation with a specialist, 15% versus 8% reported at least 1 hospitalization, and 40% versus 26% reported joblessness.³ The economic and human costs of these conditions appear considerable.

Biological mechanisms: ME-CFS and FM

Some advances have clearly been made in recognition of and research into ME-CFS and FM. Recent reviews,^4–7 including those by the US Institute of Medicine and advice for patients by the American College of Physicians, support the existence of these conditions as distinct disabling disorders affecting millions with a likely organic or physiologic basis. Infections are the suspected initial trigger of ME-CFS, with contribution from environmental and polygenetic susceptibility factors. Evidence is mounting for involvement of immunologic and inflammatory pathologies, neurotransmitter signaling disruption, microbiome perturbations, and metabolic or mitochondrial abnormalities. Regarding FM, the central nervous system is likely involved, triggered by physical trauma or infections. Twin studies indicate inheritance might contribute to half the risk of developing FM.⁷ Some studies suggest the involvement of genetic polymorphisms related to the metabolism of neurotransmitters involved in pain modulation.

Stigma and meagre funding: ES-MCS

In contrast, recognition of and research into ES-MCS in North America has remained bleak. (The exception is some early work by the University of Toronto’s Environmental Hypersensitivity Research Unit that found discriminant validity of 2 published case definitions⁸ and identified associations with genetic polymorphisms that are known to alter metabolism of some chemicals.⁹) A detailed PubMed search uncovered only 320 references specific to ES-MCS, compared with 7453 references specific to ME-CFS and 9846 references specific to FM, with relatively few describing original research. No high-level reviews of the evidence surrounding ES-MCS have occurred since a 1999 statement made by the American College of Occupational and Environmental Medicine¹⁰ and a 2001 international workshop,¹¹ both concluding that substantial research investments were needed. No such investments followed.

Research funding for all 3 conditions has been meagre or nonexistent. From 2012 to 2015, for example, the Canadian Institutes of Health Research funded 2, 11, and 0 grants for ME-CFS, FM, and ES-MCS research, respectively, with a combined total of $1.8 million—less than 10% of the funding for research on emphysema or on multiple sclerosis and epilepsy, which have lower prevalences.

Slow progress likely reflects, in part, the social stigmatization surrounding these conditions.^12,13 This is particularly severe for ES-MCS, given the common need for affected patients to avoid everyday exposures to items that trigger their symptoms, such as fragrances, cleaning products, and marking pens.¹⁴ Stigmatization also increases the risk of anxiety, depression, and other psychological symptoms that can be mistaken for causes rather than effects of the diseases themselves. Moreover, the uncertainty surrounding management strategies and, in the case of ES-MCS, the legal struggles that often occur regarding causation and avoidance issues, also arguably cast a “chill” on clinicians and scientists, deterring involvement in clinical care and research.

Future steps

But things might be turning around. For example, the Canadian Institutes of Health Research announced the results of a ME-CFS planning and dissemination grant competition,¹⁵ a harbinger for important potential future funding of basic research. The US National Institutes of Health announced 3 ME-CFS Collaborative Research Centers with more than $6 million in funding in 2017.¹⁶ With respect to ES-MCS, there is a growing body of research being published by investigators in Europe and Japan, which has provided evidence supporting the involvement of neurobiological,^17,18 metabolic,¹⁹ and genetic susceptibility factors.²⁰

Finally, in its interim report, the Ministry of Health and Long-Term Care task force proposed that concrete steps be taken to establish a foundation for an effective, patient-centred system of care in Ontario (Box 2).¹ It is also now working on convening experts on all 3 conditions to establish case definitions and subsequently to create clinical practice guidelines that will be valuable both for everyday recognition and management and for formulating a basis for research.

Given the widespread nature of these conditions and the associated burden of suffering nation-wide, it is important for all clinicians and, in particular, front-line primary care practitioners, to take note. We also call for a national effort to increase research directed at all 3 of these conditions as distinct entities, but with efficiencies associated with studying them together.