Myalgic encephalomyelitis / chonic fatigue syndrome: what is the fuss about?

Rea Tschopp, Daniel Paris, Rahel König, Milo Puhan, Marcel Tanner

The COVID-19 pandemic that started late in 2019 is a global devastating viral disease, causing worldwide a recorded 262 million cases and 5.2 million deaths as of November 2021. But COVID-19 also led to chronic post-COVID syndrome, whose symptoms resemble those seen in patients with myalgic encephalomyelitis / chronic fatigue syndrome (ME/CFS). Post-COVID syndrome has quickly drawn attention from scientists and governments alike (launch a long COVID task force in Switzerland). Myalgic encephalomyelitis / chronic fatigue syndrome , on the other hand, tells a different story. Unlike post-COVID syndrome, myalgic encephalomyelitis / chronic fatigue syndrome  is not a recent disease, but yet remained neglected for many decades despite being officially classified by the World Health Organization as a neurological disease in 1969. In the late 1980s, the US Centers for Disease Control and Prevention (CDC) introduced the term chronic fatigue syndrome, and in 1994 myalgic encephalomyelitis / chronic fatigue syndrome was redefined as “clinically evaluated unexplained persistent fatigue lasting longer than 6 months, accompanied by at least four out of eight symptoms”. The case-definition of myalgic encephalomyelitis / chronic fatigue syndrome has since then been updated, revised and refined multiple times.

Myalgic encephalomyelitis / chronic fatigue syndrome is not a rare disease. The global prevalence ranges from 0.2% to 2.8%, and it affects people from all races, all socioeconomic groups and all age groups. Its specific aetiology(ies) is still not known. Hypotheses include viral and non-viral infections, genetic disorders, cell receptor dysfunction, energy production alterations, toxins, immune system disorders, and psychological traumata. Although several infections have long been associated with long-term fatigue, there has been no single infective agent systematically associated with myalgic encephalomyelitis / chronic fatigue syndrome. It also  shares features with some autoimmune diseases: autoantibodies against β2-adrenergic receptors were detected in patients with myalgic encephalomyelitis / chronic fatigue syndrome, and many pathophysiological similarities have been found between these patients and patients with multiple sclerosis. In recent years, two major research directions are starting to crystalise in the search for diagnostic bio-markers: (1) cytokine/immunological anomalies and (2) cell receptor anomalies.

Myalgic encephalomyelitis / chronic fatigue syndrome is a multi-systemic physical disease, with abnormalities found in the immune, neurological, metabolic and endocrine systems. It is characterised, among others, by inflammation at cellular and biochemical levels in muscles, brain and spinal cord, metabolic dysfunctions and  haemorheological changes. Symptoms always worsen with physical and/or mental exercise and typically recovery is slow.

What does the disease mean for patients? Myalgic encephalomyelitis / chronic fatigue syndrome is a complex chronic – often life-long –medical condition that affects every organ system in the body. Only a small  percentage of cases have been reported to have recovered. The most common symptoms include pathological fatigue / post-exertional malaise, pain, unrefreshing sleep, cognitive dysfunction, immune dysfunction, autonomic dysfunction, neurological, sensory and motor disturbances, neuroendocrine and immune symptoms. The disease can severely impair the patient’s ability to conduct a normal life (school attendance and performance, work, social life) and can result in food insecurity. Patients often learn over time to know their disease and develop coping mechanisms, avoiding or mitigating triggers causing severe episodes. These coping mechanisms however, can also lead to marginalisation, which in addition to poor social and medical recognition and support, as well as misdiagnosis, can have negative reactive psychological consequences such as depression, sadness, anxiety, hopelessness – up to suicidal tendencies. Major functional and emotional impacts that impair quality of life and school performances are observed in children and adolescents, who usually have poorer coping mechanism than adults.

In recent years, the scientific community has received an exponential increase in research funding for myalgic encephalomyelitis / chronic fatigue syndrome to identify aetiologies, develop potential diagnostic biomarkers and test new experimental drugs. It was on the agenda of the summer session of the Brussels parliament in June 2020, who called for an urgent increase in research funding. A myalgic encephalomyelitis / chronic fatigue syndrome biobank has been established in the UK, the first in Europe. A multi-disciplinary European network (EUROMENE) was established with the aim of coordinating research across member states. Still, despite the rapidly increasing scientific knowledge, a striking discrepancy between science and practice remains globally and in Switzerland particularly.

Switzerland is one of the rare countries in Europe that has no scientific data on myalgic encephalomyelitis / chronic fatigue syndrome, has still not listed it as a disease and has no data about the treatment situation in Switzerland. The disease is hardly known and recognised by society. It is not taught in medical schools; hence, knowledge among physicians is likely to be poor, with subsequent devastating effects for patients. There are currently only a handful of physicians who specialise in chronic diseases that include myalgic encephalomyelitis / chronic fatigue syndrome. Health insurances, as well as the disability insurances, rarely recognise it) as a medical entity. Further reasons for poor patient diagnosis and care is the current lack of diagnostic markers. In 2021, in the context of the newly emerged Post-COVID syndrome and its similar exhaustion symptomatology, the Swiss association ME/CFS Verein Schweiz launched a national petition calling for a national strategy for myalgic encephalomyelitis / chronic fatigue syndrome and post-COVID syndrome (ME/CFS Schweiz 2021).

Besides causing much physical pain and loss of functionality in patients, myalgic encephalomyelitis / chronic fatigue syndrome is als costly to patients, healthcare systems and society. Annual economic costs were estimated at 14.5 and 24 billion USD in Australia and the USA, respectively. On average the patients generate 3–4 times higher medical costs than the general population and 50% higher medical costs than lupus or multiple sclerosis.

On the basis of global reported disease prevalence data, any numbers between 17,000 to over 100,000 people could be affected in Switzerland. Even if the most conservative prevalence data are used (0.2–0.4%), an estimated 17,000 to 40,000 people in Switzerland could have myalgic encephalomyelitis / chronic fatigue syndrome, which exceeds the number with multiple sclerosis. Literature shows that, of these, 25% are bedbound at one stage of their life and up to 60% are unable to work.

Myalgic encephalomyelitis / chronic fatigue syndrome poses a challenge for diagnostics and disease management. Awareness and knowledge of the disease are of paramount importance, considering there is currently no available treatment. Early diagnosis of patients and initiating adequate management and support may reduce the healthcare costs while improving the patient’s physical and mental well-being and functionality, thus avoiding increased severity of the disease and risk of long-term complications. Of paramount importance, however, is the trust, the mutual understanding, respect and the long-term close collaboration that has to be developed between patient and physician. There is an urgent need in Switzerland to include myalgic encephalomyelitis / chronic fatigue syndrome in the national health agenda in order to provide an adequate framework for appropriate care of patients. The emergence of post-COVID syndrome with similar symptomatology is an opportunity for the condidtion to be finally recognised as a disease in its own right.

 

Rea Tschopp, Swiss Tropical and Public Health Institute, Basel, Switzerland, University of Basel, Switzerland

Armauer Hansen Research Institute, Jimma Road, Addis Ababa, Ethiopia, rea.tschopp@swisstph.ch

Daniel Paris, Swiss Tropical and Public Health Institute, Basel, Switzerland, University of Basel, Switzerland

Rahel König, University of Basel, Switzerland

Milo Puhan, Epidemiology, Biostatistics and Prevention Institute, University of Zürich, Switzerland

Marcel Tanner, Swiss Tropical and Public Health Institute, Basel, Switzerland, University of Basel, Switzerland