Post-exertional malaise is associated with greater symptom burden and psychological distress in patients diagnosed with Chronic Fatigue Syndrome, by Marcella May, Sara F Milrad, Dolores M Perdomo, Sara J Czaja, Mary Ann Fletcher, Devika R Jutagir, Daniel L Hall, Nancy Klimas, Michael H Antoni in Journal of Psychosomatic Research, Volume 129, February 2020, []



  • Patients high in PEM endorse greater symptom burden than those low in PEM
  • Patients high in PEM endorse greater psychological adversity than those low in PEM
  • Results suggest the Fukuda case definition does not define a heterogeneous group
  • PEM may identify patients who would most benefit from psychological intervention

Research abstract:

Post-exertional malaise (PEM) is often considered a cardinal symptom of Chronic Fatigue Syndrome (CFS). There is no gold standard diagnostic method for CFS, however, and the Centers for Disease Control (CDC) Fukuda case definition does not require PEM. Research has identified differences in symptom burden between patients according to PEM, but whether it is associated with psychological distress has not been investigated.

The CDC CFS Inventory, Fatigue Symptom Inventory, Profile of Mood States, Center for Epidemiologic Studies Depression Scale, Perceived Stress Scale, and subscales of the Sickness Impact Profile were administered to 261 patients diagnosed with the Fukuda criteria. PEM status (loPEM/hiPEM) was determined via self-reported post-exertional fatigue severity. Analyses of covariance (ANCOVA), controlling for age and gender, assessed cross-sectional group differences, and cross-sectional linear regressions using the continuous PEM severity predictor paralleled these analyses.

hiPEM patients reported greater symptom intensity, frequency, and interference than loPEM counterparts (p’s < .001). hiPEM patients also reported greater social disruption, depressive symptoms, and mood disturbance (p’s ≤ .011). Groups did not differ in recent negative life experiences, perceived stress, or demographic variables. The results of regression analyses mirrored those of ANCOVAs.

This study replicates the association between PEM and symptom burden and additionally associates PEM with psychological distress; psychological distress could, however, be a consequence of symptom burden. Differences between hiPEM and loPEM CFS patients highlight the heterogeneity of diagnoses resulting from the Fukuda criteria. It is also possible that PEM identifies particularly distressed patients for whom psychological intervention would be most beneficial.

Pre-proof full paper

Virology blog: Trial By Error: PEM Is Bad and So Is Fukuda, New Study Finds,
24 December 2019, By David Tuller     Excerpt:

So as far as I can tell, the main message of this paper is, or should be, that the Fukuda case definition is inadequate because many of those who meet it do not appear to experience PEM as a debilitating factor, if they experience it at all. Given that PEM is already viewed as the cardinal symptom of the illness, the logical conclusion is that such patients don’t have ME, despite having been diagnosed with CFS per Fukuda. As it reads, the study’s main finding seems to be that CFS patients with PEM need psychological intervention—when in fact what they really need most is effective medical treatments for their ME.

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