Zielinski, Mark R, Systrom, David M, Rose, Noel R · Frontiers in immunology · 2019 · DOI
Severe fatigue is one of the most disabling symptoms reported by people with autoimmune diseases, including ME/CFS. This review examines how inflammation and the brain contribute to fatigue in these conditions. The authors explain that fatigue involves multiple body systems—including energy supply, metabolism, mood, and sleep—all of which can be disrupted by inflammation.
This review provides a comprehensive framework for understanding why ME/CFS patients experience profound, disproportionate fatigue and why this symptom is so difficult to treat. By highlighting inflammation and CNS dysfunction as central mechanisms, it validates patient experiences and suggests multiple potential therapeutic targets for future research and clinical intervention.
This review does not establish specific biomarkers or prove causal mechanisms of fatigue in any single disease. As a narrative/systematic review, it synthesizes existing literature rather than providing new experimental data, and it does not determine whether inflammation causes CNS dysfunction in fatigue or vice versa. The study also does not quantify the relative contribution of each proposed mechanism to overall fatigue severity.
About the PEM badge: “PEM required” means post-exertional malaise was an explicit required diagnostic criterion for participant inclusion in this study — not that PEM was studied, observed, or discussed. Studies using criteria that do not require PEM (e.g. Fukuda, Oxford) are tagged “PEM not required”. How the atlas works →
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Primary citation
Zielinski, Mark R, Systrom, David M, & Rose, Noel R (2019). Fatigue, Sleep, and Autoimmune and Related Disorders.. Frontiers in immunology. https://doi.org/10.3389/fimmu.2019.01827
BibTeX
@article{mecfsatlas-zielinski-2019-fatigue-sleep,
author = {Zielinski, Mark R and Systrom, David M and Rose, Noel R},
title = {Fatigue, Sleep, and Autoimmune and Related Disorders.},
journal = {Frontiers in immunology},
year = {2019},
doi = {10.3389/fimmu.2019.01827},
note = {PubMed: 31447842},
url = {https://www.mecfsatlas.com/evidence/zielinski-2019-fatigue-sleep},
}Atlas snapshot reference
ME/CFS Atlas. Generator v1 / Scanner v1.4 / policy v0.1. Accessed 2026-05-29. https://www.mecfsatlas.com/evidence/zielinski-2019-fatigue-sleep
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