Symptom-based clusters in people with ME/CFS: an illustration of clinical variety in a cross-sectional cohort

BackgroundMyalgic encephalomyelitis (ME)/chronic fatigue syndrome (CFS) is a complex, heterogenous disease. It has been suggested that subgroups of people with ME/CFS exist, displaying a specific cluster of symptoms. Investigating symptom-based clusters may provide a better understanding of ME/CFS. Therefore, this study aimed to identify clusters in people with ME/CFS based on the frequency and severity of symptoms.MethodsMembers of the Dutch ME/CFS Foundation completed an online version of the DePaul Symptom Questionnaire version 2. Self-organizing maps (SOM) were used to generate symptom-based clusters using severity and frequency scores of the 79 measured symptoms. An extra dataset (n = 252) was used to assess the reproducibility of the symptom-based clusters.ResultsData of 337 participants were analyzed (82% female; median (IQR) age: 55 (44-63) years). 45 clusters were identified, of which 13 clusters included >= 10 patients. Fatigue and PEM were reported across all of the symptom-based clusters, but the clusters were defined by a distinct pattern of symptom severity and frequency, as well as differences in clinical characteristics. 11% of the patients could not be classified into one of the 13 largest clusters. Applying the trained SOM to validation sample, resulted in a similar symptom pattern compared the Dutch dataset.ConclusionThis study demonstrated that in ME/CFS there are subgroups of patients displaying a similar pattern of symptoms. These symptom-based clusters were confirmed in an independent ME/CFS sample. Classification of ME/CFS patients according to severity and symptom patterns might be useful to develop tailored treatment options. This study did not receive any funding for its design, analysis, and interpretation of data, or for writing the manuscript. Ethical approval for this study was waived by the medical ethics committee of Maastricht University because the Medical Research Involving Human Subjects Act (WMO) did not apply to this study (METC 2021-2797). Digital informed consent was obtained from all respondents at the start of the survey. Without providing informed consent, participants were unable to start the questionnaire.