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This is a Quantitative Study study.

September 18, 2025Open Access

Analysis of ME/CFS Patient Clusters in Vaes Data Reveals Distinct Subgroups

Key Points

Separating the 13 symptom clusters into two groups reduced heterogeneity within each subgroup.
Group one exhibited consistent symptom amplification with increased post-exertional malaise severity.
A second subgroup showed selective amplification of pain and neurocognitive symptoms with stable immune symptoms.
The profile of the selective subgroup resembles that of fibromyalgia, indicating potential overlap in mechanisms.

Abstract

Background: Vaes et al. (2023)@vaes2023 identified 13 symptom clusters in a large cohort of ME/CFS patients. Symptom intensity is broadly correlated with post-exertional malaise (PEM) severity, with variation across clusters that seems heterogeneous. Despite this research, no broadly accepted organizing principle has emerged from this paper or other attempts at phenotyping ME/CFS. We identified two groups of patient clusters with distinct symptom-domain profiles. Separating the 13 clusters into these subgroups reduced heterogeneity within each. The first group showed a consistent amplification pattern across all symptom domains as PEM increased, whereas the second group exhibited selective amplification: pain and neurocognitive symptoms escalated more rapidly with PEM, while immune and sleep symptoms remained relatively flat. This subgroup's profile resembles that of fibromyalgia.

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