Abstract
This cross-sectional study assesses the prevalence and risk of excessive sweating and joint hypermobility in Israeli adolescents aged 16 to 19 years.
Primary focal hyperhidrosis is excessive sweating and occurs in 1% of the Israel population to 4.8% of the US population.1,2 Hypermobility spectrum disorder (HSD) and hypermobile Ehlers-Danlos Syndrome (hEDS) are complex noninflammatory connective-tissue disorders manifested by joint hypermobility, musculoskeletal symptoms, and autonomic dysregulation. While autonomic dysregulation may play a role in the pathophysiological processes of hyperhidrosis and HSD or hEDS,1,3 data on the association between them are scarce.4 We assessed the association between hyperhidrosis and HSD or hEDS in a nationwide study.
Methods
This cross-sectional study included Israeli adolescents aged 16 to 19 years who were evaluated before compulsory military service between 1998 and 2020. Assessment included a health summary by a primary care physician, medical interview, and physical examination. The Israeli Defense Forces Medical Corps Institutional Review Board approved this study and waived informed consent to protect the anonymity of the patients. We followed the STROBE reporting guideline.
Hyperhidrosis was diagnosed by a board-certified dermatologist. We included adolescents with focal excessive sweating for at least 6 months without apparent cause and with impairment in daily activities. Diagnosis of HSD or hEDS was confirmed by a board-certified rheumatologist or orthopedic surgeon and required the presence of generalized joint hypermobility (Beighton score, ≥6 of 9),4 with chronic musculoskeletal symptoms or recurrent joint dislocations unrelated to trauma. Adolescents with hereditary connective-tissue disorder other than HSD or hEDS were excluded.
Socioeconomic status was reported by residence locality at the time of examination.5 Sociodemographic differences between adolescents with hyperhidrosis and the control group were evaluated using 2-sample, 2-tailed t tests (continuous variables) and χ2 tests (categorical variables). Logistic regression models were used to calculate the odds ratio (OR) and 95% CIs for HSD or hEDS with or without hyperhidrosis. Multivariable models were adjusted for sociodemographic and anthropometric variables. Sex-stratified analysis and an analysis restricted to adolescents with unimpaired health were also conducted.
Two-sided P < .05 indicated statistical significance. Data analysis was performed between July and September 2023 using R 4.0.2 (R Core Team).
Results
Of 1 626 407 adolescents included (945 519 males [58%], 680 888 females [42%]; mean [SD] age, 17.2 [0.5] years), 2% were diagnosed with hyperhidrosis and 0.3% were diagnosed with HSD or hEDS. Characteristics of the study population are presented in the Table.
Table. Characteristics of the Study Population by Hyperhidrosis Diagnosis .
| Characteristic | Patients, No. (%) | |
|---|---|---|
| Control (n = 1 593 697) | Hyperhidrosis (n = 32 710) | |
| Age, mean (SD), y | 17.2 (0.5) | 17.3 (0.5) |
| Sex | ||
| Male | 922 831 (58) | 22 688 (69) |
| Female | 670 866 (42) | 10 022 (31) |
| BMI, mean (SD) | 21.9 (4.1) | 22.5 (4.4) |
| Socioeconomic status | ||
| Low | 430 298 (27) | 7 196 (22) |
| Medium | 828 723 (52) | 18 318 (56) |
| High | 334 676 (21) | 7 196 (22) |
| Completed 11 y of education | 1 514 012 (95) | 30 747 (94) |
| Israeli born | 1 338 705 (84) | 28 131 (86) |
Abbreviation: BMI, body mass index (calculated as weight in kilograms divided by height in meters squared).
Prevalence of HSD or hEDS in adolescents with hyperhidrosis was significantly higher than in adolescents without hyperhidrosis (0.5% vs 0.3%; P < .001) (Figure). Similarly, prevalence of hyperhidrosis was significantly higher in those with than without HSD or hEDS (3.6% vs 2.0%; P < .001). An unadjusted logistic regression model confirmed these findings (OR, 1.84; 95% CI, 1.57-2.14), which persisted in a multivariable model (OR, 1.83; 95% CI, 1.56-2.13). The association was consistent in both sexes and persisted in adolescents with unimpaired health.
Figure. Adjusted Odds Ratios (AORs) for Hypermobility Spectrum Disorder and Hypermobile Ehlers-Danlos Syndrome in Adolescents With Hyperhidrosis vs the Control Group.
The AORs were adjusted for age at time of medical evaluation, sex, socioeconomic status, educational level, and immigration status. Dashed line indicates no effect. Error bars represent 95% CIs.
Discussion
We found that adolescents with hyperhidrosis had almost 2-fold increased odds of HSD or hEDS, with no differences by sex or comorbidities. Prevalence of hyperhidrosis was significantly higher in adolescents with HSD or hEDS.
Since autonomic dysregulation is believed to be a factor in the pathogenesis of both conditions, shared mechanistic pathways might explain the association between hyperhidrosis and HSD or hEDS.1,3 Parvaneh et al6 assessed 130 children with benign joint hypermobility syndrome and 160 healthy controls and observed hyperhidrosis in 56.2% of patients and 16.3% of controls. However, that study assessed a relatively small number of patients in a tertiary center, and the reported hyperhidrosis prevalence was exceptionally high.1,3
A study limitation is the observational design. Moreover, due to the rarity of HSD or hEDS, the clinical utility of screening patients with hyperhidrosis is limited. Study strengths include use of a nationwide sample with systemic screening and confirmation of all diagnoses by board-certified specialists.
We found an association between hyperhidrosis and HSD or hEDS. In the appropriate clinical context, clinicians should consider a concomitant diagnosis of hyperhidrosis and HSD or hEDS. Future study is needed to examine the underlying mechanisms of these conditions.
Data Sharing Statement
References
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Supplementary Materials
Data Sharing Statement