Epidemiological and clinical factors associated with post-exertional malaise severity in patients with myalgic encephalomyelitis/chronic fatigue syndrome, by Alaa Ghali, Paul Richa, Carole Lacout, Aline Gury, Anne-Berengere Beucher, Chadi Homedan, Christian Lavigne & Geoffrey Urbanski in Journal of Translational Medicine vol 18, no. 246 (2020) Published: 22 June 2020


Research abstract:


Post-exertional malaise (PEM), the cardinal feature of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), occurs generally after exposure to a stressor. It is characterized by the worsening of ME/CFS symptoms and results in aggravating the course of the disease and the quality of life of patients. Due to its unpredictable onset, severity, and recovery time, identifying patients with higher risk for severe PEM would allow preventing or reducing its occurrence. We thus aimed at defining possible factors that could be associated with PEM severity.


Adult patients fulfilling ME international consensus criteria who attended the internal medicine department of University hospital Angers-France between October 2011 and December 2019 were included retrospectively. All patients were systematically hospitalized for an etiological workup and overall assessment. We reviewed their medical records for data related to the assessment: epidemiological data, fatigue features, clinical manifestations, and ME/CFS precipitants.

PEM severity was appreciated by the Center for Disease Control self-reported questionnaire. The study population was classified into quartiles according to PEM severity scores. Analyses were performed with ordinal logistic regression to compare quartile groups.

The two-way link between recurrent infections and PEM in ME/CFS patients. An infectious precipitant results in impaired immune function leading to susceptibility to recurrent viral infections and some of ME/CFS manifestations such as fatigue and flu-like symptoms. Stress and mood changes can also impact the immune system. PEM will occur after a stressor (physical, cognitive, emotional and/or infectious) leading to a worsening of ME/CFS baseline symptoms, including immune/inflammatory-related symptoms and psychological disturbances. This will perpetuate the immune dysfunction with aggravation of ME/CFS symptoms, and more frequent viral infections. aME/CFS: myalgic encephalitis/chronic fatigue syndrome. bPEM: post-exertional malaise


197 patients were included. PEM severity was found to be positively associated with age at disease onset ≥ 32 years (OR 1.8 [95% CI 1.1–3.0] (p = 0.03)), recurrent infections during the course of the disease (OR 2.1 [95% CI 1.2–3.7] (p = 0.009)), and when ME/CFS was elicited by a gastrointestinal infectious precipitant (OR 5.7 [1.7–19.3] (p = 0.006)).


We identified some epidemiological and clinical features, which were positively associated with PEM severity in subsets of ME/CFS patients. This could help improving disease management and patients’ quality of life.

Excerpt from conclusion:

Given the non-homogeneity of the ME/CFS population, and knowing that PEM is associated with disability and poorer outcome, we attempted to identify patients with higher risk for severe PEM on epidemiological and clinical features. To the best of our knowledge, our study is the first to identify factors that may influence PEM severity in ME/CFS patients.

We observed more severe PEM in older patients at disease onset, and among those who were suffering from recurrent infections during their disease course. More severe PEM was also observed in patients in whom ME/CFS onset was preceded by GI infectious precipitants.

Accordingly, this will allow adapting and individualizing the disease management, especially in the absence of curative treatment. Hence older patients should be advised to adhere more strictly to pacing strategies, and specific measures against infections together with pacing should be recommended for those who display recurrent and/or persistent infections. The aim is to prevent PEM occurrence, or at least reducing its severity, to help improving disease course and patients’ quality of life.

ME Research UK: Predicting the severity of post-exertional malaise

Key findings

Three factors were found to be associated with increased PEM severity, and may help to identify patients who would benefit from pacing strategies:

  • Developing ME/CFS at the age of 32 years or older.
  • Being susceptible to recurrent viral infections.
  • Developing ME/CFS after a gastrointestinal infection.
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