ME/CFS: the biology of a neglected disease
A group of South African and British researchers have reviewed the literature and described ME/CFS in terms of symptoms, severity and burden, diagnostic criteria, causes and triggers; followed by an overview of the complex pathophysiology and management of the condition. They conclude by listing research priorities for the future.
They emphasise the necessity of a holistic approach to diagnosing, researching, and treating ME/CFS, urging the scientific community to reconsider the disease’s complexity and the multifaceted approach required for its study and management.
ME/CFS symptoms
Patients display varying symptoms and several body systems are impacted: Immunological impairments; pain; gastrointestinal problems; autonomic dysfunction; respiratory issues. Although many of the symptoms overlap with other diseases, one feature that sets ME/CFS apart is a worsening of symptoms in response to relatively minor physical, cognitive, orthostatic or even emotional exertion. This phenomenon is known as post-exertional malaise (PEM) or PESE (post exertional symptom exacerbation).
The researchers find that research confirms our understanding of the range of severity of the disease and that despite its high prevalence, there are still no universally accepted clinical criteria to characterise ME/CFS, making early and accurate diagnosis difficult.
Probable causes of ME/CFS
The researchers conclude that “ME/CFS is likely to have a multifactorial origin, with multiple physiological processes implicated” in the way the disease develops. They discuss genetic presdisposition, viral triggers and reactivation, toxin and drug exposure.
The complex pathophysiology of ME/CFS
“As a consequence of infection and other stressors, such as poly-trauma for example, a state of acute inflammation and aberrant immune activation may occur. A compensatory anti-inflammatory mechanism then typically follows), causing an imbalance in immune responses combined with hypothesised autoimmunity. This may lead to subsequent physiological abnormalities including gut dysbiosis and systemic inflammation, eventually resulting in a pathological clotting system, chronic endothelialitis, vasoconstriction, and hypoxia, as found in similar conditions such as heat stroke. Additionally, dysfunctional energy metabolism along with oxidative stress are also hypothesised in the development of ME/CFS. It is hypothesised that these mechanisms occur in a spiralling, progressive way, toppling the host’s homeostatic equilibrium.” A detailed discussion is included.
Management of ME/CFS
No effective therapies and few established non-pharmacological treatments for ME/CFSwere found. Hence current advice is aimed at symptom management and lifestyle changes. The current available treatments/lifestyle modifications are summarised in the illustration.
The researchers conclude by making suggestions for future research and calls for increased support for the ME/CFS community. They also list some potential treatments for furhter investigation: Rintatolimod; steroids; mitochondrial nutraceutical; PPAR agonists; Activators of AMPK; Immunostimulative therapy; Antivirals; Antioxidants; Immunomodulators; B-cell depleting therapy; Immunoadsorption therapy.
Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: the biology of a neglected disease, by Hayley E Arron, Benjamin D Marsh, Douglas B. Kell, M Asad Khan, Beate R Jaeger, Etheresia Pretorius in Front Immunol. 2024; 15: 1386607 2024 Jun 3. [doi:10.3389/fimmu.2024.1386607]
See also:
ME Research UK: An overview of ME/CFS
Whilst not necessarily providing added information about ME/CFS, this review pools together information from multiple sources to provide a helpful overview of this complex disease.
