Supplementary Material for: Cluster analysis identifies clinical phenotypes of primary hyperhidrosis

Introduction
Identifying subgroups of patients with primary hyperhidrosis (PHH) can improve the understanding of the disease pathophysiology. The study objective is to determine the naturally occurring subgroups of patients with PHH based on clinical characteristics.

Methods
In this retrospective cohort study, data was collected from participants included in a clinical trial. The data was collected between January 2020 and June 2021 from outpatients with PHH attending a dermatologic department in Denmark. Overall, 84 patients with PHH were screened for inclusion in the clinical trial. Of these, 41 met the eligibility criteria. Four participants were excluded because of missing data. The main outcome was the identification of subgroups of patients with PHH using an unsupervised hierarchical cluster analysis.

Results
Overall, 37 patients were included (28 [76.7%] females; median age at inclusion 28.0 [interquartile range (IQR) 24.0–38.3]; median body mass index 24.9 [IQR 20.9–27.4); median age of onset 13.0 [IQR 9.5–18.5]; and 26 [70.3%] had a familial disposition towards PHH). Two clusters of 18 and 17 patients were identified. The first cluster had, when compared to the second, a younger age of onset (median age 11.0 [IQR 0–13.0] vs. 17.0 [IQR 15.0–21.0], p=0.003) and higher sweat rates on gravimetry (median 175.0 [IQR 121.2–252.5] vs. 40.0 [IQR 20.0–60.0] milligrams of sweat/5 minutes, p<0.001) and transepidermal water loss (median 93.7 [IQR 91.2–97.8] vs. 59.0 [IQR 44.4–73.2] grams/meter2/hour, p<0.001). No differences were observed for the other variables.

Conclusions
This study identifies two subgroups of patients with PHH. The patients with an onset of PHH during childhood had a substantially higher sweat and evaporation rate in adulthood than those with an onset during adolescence. These findings may imply a changed understanding of the pathophysiology of PHH, by indicating that an early disease onset can lead to a worse disease course.