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.
Erik Squires (Tue,) studied this question.