34 HOW TO TREAT: MYALGIC ENCEPHALOMYELITIS / CHRONIC FATIGUE SYNDROME
34 HOW TO TREAT: MYALGIC ENCEPHALOMYELITIS / CHRONIC FATIGUE SYNDROME
18 JULY 2025 ausdoc. com. au burnetti) and Mycoplasma pneumoniae. The most commonly reported infectious agent is EBV, with about 9-13 % of patients with EBV developing an ME / CFS-like presentation six months post infection.
13, 14
No causal role has been established between a specific infectious agent and ME / CFS, and while many report a post-viral onset, antiviral medications are not successful in treating ME / CFS in the chronic or post-infectious stage. 5
Onset is associated with a genetic predisposition, with several generations in a family reporting ME / CFS. 15 Despite this, there have been limited genome-wide association studies that have yielded consistent and reproducible data, and no risk loci have been identified. 16 Genetic phenotypes for five cellular processes or biological systems have been identified in ME / CFS. They are, first, susceptibility to infection; second, autoimmune and chronic inflammation development; third, metabolic dysfunction; fourth, increased vulnerability to stress; and fifth, sleep disturbances. 17
Features of susceptibility may not only involve genetic susceptibility but also personal medical history and underlying conditions, culminating in a trigger event and a chronic inflammatory response. A relationship has been reported between the quantification of micro ribonucleic acids and the pathomechanism of ME / CFS; however,
16, 18 results vary.
Adapted using BioRender. com
EPIDEMIOLOGY
ME / CFS affects individuals of all ages, socioeconomic, racial and ethnic groups. The condition is estimated to have a prevalence of 17-24 million people worldwide. 19 Around 190,000-240,000 Australians have been diagnosed with or report symptoms of ME / CFS. 20 This estimate was determined before the COVID-19 pandemic, which is believed to have increased the prevalence. The average age of onset is between early 30s and late 40s; however, ME / CFS can also occur in adolescents. 21 Some authors report a slight increase in relative risk among women, while others report a larger
21 – 23 female-to-male ratio of 6:1.
ME / CFS manifests along a spectrum of severity, ranging from mild to severe. Those with mild ME / CFS often report decreased capacity to sustain employment and interpersonal relationships but can typically manage daily activities. Moderately severe ME / CFS is associated with a significant reduction in activity, restricted mobility and an inability to consistently perform activities of daily living. Patients classified as having moderate ME / CFS are mostly housebound. A patient with severe ME / CFS is typically bedbound and will be dependent on mobility aids and a carer. About 25 % of patients have severe ME / CFS. 24
DIAGNOSIS
A REVIEW of ME / CFS case criteria revealed 25 case definitions. 25 With the overlapping diagnostic criteria and clinical presentation, this poses a significant diagnostic challenge. The Royal Australasian College of Physicians published the Chronic Fatigue Syndrome Clinical Practice Guidelines in 2002. 26 These guidelines placed a high emphasis on the
Figure 1. A representation of symptoms reported by individuals with ME / CFS. Symptom categories align with commonly used case criteria, including the Canadian Consensus Criteria for ME.
Table 1. Overview of symptom criteria according to diagnostic definition Guideline CDC‘ Fukuda’ CCC ICC IOM NICE Terminology CFS ME / CFS ME ME / CFS ME / CFS Symptom criteria Post-exertional malaise X X X X X Fatigue X X X X Cognitive disturbances(‘ brain fog’) X X X X X Body pain X X X Sleep disturbances X X X X X Neurosensory, perceptual and motor disturbances X X Recurrent flu-like symptoms X X X Susceptibility to viral infections Sensitivity to food, medications and odours X X Cardiovascular X X X Respiratory Gastrointestinal and genitourinary X X Loss of thermostatic stability X X
X denotes symptoms included within the criteria.
use of the early 1994 Fukuda criteria for CFS, which is now no longer recommended. These guidelines are considered outdated, and their use is not encouraged. Importantly, many physicians and researchers recognise the limitations of using these criteria as they are considered too broad for a definitive diagnosis.
Alternative international guidelines for ME / CFS can be used( see table 1). The UK National Institute of Health and Care Excellence( NICE) published the ME / CFS: Diagnosis and Management Clinical Guidelines in 2021. 27 These guidelines highlight key symptoms of ME / CFS, including debilitating chronic fatigue not
X
X
relieved by rest( lasting six months or longer), post-exertional malaise( PEM) with delayed onset, unrefreshing sleep, and neurocognitive impairments.
Alternative diagnostic criteria include the ICC and Canadian Consensus Criteria( CCC) for ME / CFS. The 2003 CCC emphasises key symptoms overlapping with the NICE guidelines and also highlights the importance of autonomic, neuroendocrine and immune dysfunction symptom categories to capture the diverse multisystemic nature of ME / CFS. 28 The ICC, published in 2011, identifies many of the aforementioned symptoms highlighted by the NICE guidelines and the CCC; however, it has removed the traditional six-month waiting period required for diagnosis. 29 The terminology regarding PEM evolved to post-exertional neuroimmune exhaustion to encompass the multisystemic nature of post-exertional exacerbation of symptoms. Further, the ICC is more stringent when delineating additional impairments, categorised into gastrointestinal, genitourinary and energy metabolism or ion transport impairments.
In 2015, the Institute of Medicine( IOM)— now the National Academy of Medicine— proposed new diagnostic criteria for ME / CFS and introduced the term‘ systemic exertion intolerance disease’( SEID). 30 A diagnosis of SEID requires a substantial reduction in pre-illness activity levels, PEM and unrefreshing sleep, accompanied by cognitive impairment or orthostatic intolerance. The term‘ SEID’ is less commonly used in practice and research.
Differential diagnoses, or diagnoses of exclusion, include any active or previous medical conditions that may explain the presence of chronic