Abstract
Background/Aim: Carpal tunnel syndrome (CTS) and hidradenitis suppurativa (HS) are chronic inflammatory conditions that significantly affect quality of life. While both disorders have distinct manifestations, they share common risk factors such as obesity and systemic inflammation. This study aimed to evaluate whether CTS is associated with an increased risk of HS.
Patients and Methods: We conducted a retrospective cohort study using data from the TriNetX Global Health Research Network. Adults diagnosed with CTS were matched 1:1 with controls without CTS, based on age, sex, race, body mass index (BMI), comorbidities, socioeconomic status, and healthcare utilization. Individuals with prior HS or cancer were excluded. The primary outcome was new-onset HS, identified by ICD-10 codes. Hazard ratios (HRs) with 95% confidence intervals (CIs). Sensitivity analyses incorporated varied wash-out periods, alternative CTS definitions, and different follow-up durations.
Results: After matching, 493,181 patients were included in each group. Over a 15-year follow-up period, patients with CTS showed a significantly higher risk of HS (HR=1.739; 95%CI=1.617-1.871). Sensitivity analyses validated the robustness of the results, with HRs ranging from 1.647 (95%CI=1.572-1.726) to 2.142 (95%CI=1.979-2.318) across different models. In stratified analyses, the association remained significant across all subgroups. Among males, the HR was 1.249 (95%CI=1.042-1.498), whereas among females, it was 1.739 (95%CI=1.606-1.884). Patients aged 18-64 years had an HR of 1.772 (95%CI=1.642-1.913), while those aged ≥65 years had an HR of 1.479 (95%CI=1.146-1.907).
Conclusion: CTS is significantly associated with an increased risk of HS. These findings suggest a possible shared inflammatory pathway, and dermatologic comorbidities in CTS patients should be carefully considered.
Introduction
Carpal tunnel syndrome (CTS), as a peripheral nerve entrapment neuropathy arises from compression of the median nerve at the wrist, causes numbness, and weakness in patients’ hand (1). CTS predominantly affects middle-aged individuals and is more frequent in women (2). Known risk factors span both local mechanical and systemic factors, including repetitive hand movements, vibration exposure, and underlying conditions such as diabetes, obesity, hypothyroidism, and musculoskeletal diseases (3-5). Beyond the hand symptoms, patients often struggle with fine motor tasks and sleep disruption, resulting in a marked reduction in health-related quality of life (6). CTS is associated with significant healthcare costs and lost productivity, underscoring its impact on patients’ lives and the healthcare system.
Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease with a multifactorial pathogenesis. It is proposed to be initiated by the occlusion and rupture of hair follicles, which trigger an exaggerated immune response involving neutrophil infiltration and abscess formation (7). Immunologically, HS lesions are rich in pro-inflammatory cytokines such as tumor necrosis factor (TNF)-α, interleukins (e.g., IL-1β, IL-17), and other mediators, which are elevated in skin lesions (7, 8). To date, these findings regarding the immunologic pathophysiology of HS have driven promising potential therapeutic targeting of the TNF-α and IL-17 pathways. HS is highly comorbid with diseases affecting various organ systems, including endocrinological (9, 10), dermatological (11, 12), and even infectious diseases (13). According to epidemiological studies, although the estimated prevalence of HS is approximately 0.5-1% of the population, it is frequently underdiagnosed or misdiagnosed, which may lead to an underestimated disease burden (14).
CTS and HS are both debilitating conditions with significant comorbid associations, yet an intersection between the two has not been explored. There are plausible mechanistic overlaps that support investigating a link. Systemic inflammation is a unifying theme, as underlying immune dysregulation could predispose individuals to both peripheral neuropathy and chronic skin inflammation. We hypothesized that patients with CTS might have a higher risk of developing HS, reflecting a common pathophysiological link. Understanding whether CTS is associated with HS is clinically relevant because it could alert clinicians regarding the dermatological comorbidities in patients with CTS and prompt management of shared risk factors such as obesity or smoking. Therefore, we conducted a large-scale observational study to evaluate the association between CTS and HS.
Patients and Methods
This research was structured as a retrospective cohort study utilizing the TriNetX Global Collaborative Network, a globally federated platform aggregating de-identified, dynamically updated electronic health records from a broad consortium of healthcare institutions worldwide. The analysis specifically relied on the Global Collaborative Network component, which integrates clinical data from more than 145 healthcare organizations located across North and South America, Europe, and Asia, encompassing a dataset exceeding 144 million patient data. TriNetX has been extensively employed in epidemiologic and outcomes studies in the field of dermatology (15, 16). In the current study, ethical compliance was ensured in alignment with the Declaration of Helsinki, and the study protocol received Institutional Review Board (IRB) exemption for informed consent from Chung Shan Medical University Hospital (approval number CS1-25004).
Patient selection was based on structured administrative data, including diagnostic and therapeutic coding systems, as detailed in Table I. The study population included individuals diagnosed with CTS, defined by the presence of at least two documented medical visits. The reference cohort was assembled from individuals undergoing routine health assessments. Exclusion criteria encompassed subjects below 18 years of age, those with oncological diagnoses, deceased individuals, and any patient diagnosed with hidradenitis suppurativa prior to or on the index date of inclusion (Figure 1).
Utilized proxy codes.
Patient selection process.
To minimize selection bias and enhance comparability between groups, we implemented 1:1 propensity score matching (PSM), aligning baseline demographic and clinical variables. Matching covariates included age at index event, biological sex, racial category, body mass index, major comorbidities (including: diabetes mellitus, hypertension, dyslipidemia), psychiatric and substance-related conditions, socioeconomic and environmental determinants of health, and patterns of healthcare utilization (outpatient visits and hospital admissions). To assess potential confounding and ensure analytic rigor, we performed matched cohort analyses supplemented with alternative PSM techniques and incorporated temporal washout periods to address possible reverse causality. Further subgroup analyses stratified participants by age and sex background.
All statistical evaluations were conducted using built-in analytic modules within the TriNetX interface. Risk estimates were derived using hazard ratios (HRs) and 95% confidence intervals (CIs) to quantify associations between CTS and HS incidence. Covariate balance post-matching was verified using standardized mean differences (SMDs), with values below 0.1 interpreted as indicating acceptable equivalence between groups.
Results
Baseline characteristics. Table II summarizes baseline characteristics of patients with CTS and matched controls. Before matching, patients with CTS (n=496,927) were older (mean 50.3±15.5 vs. 35.8±20.5 years; SMD=0.79), included fewer males (33.6% vs. 43.5%; SMD=0.20), and more females (63.5% vs. 52.8%; SMD=0.22). Racial distributions differed modestly as 60.1% of patients with CTS were White compared with 56.1% of controls (SMD=0.08). Patients with CTS had higher prevalence of essential hypertension (22.4% vs. 10.5%; SMD=0.33), hyperlipidemia (13.7% vs. 6.3%; SMD=0.25), diabetes mellitus (10.6% vs. 4.1%; SMD=0.25), and BMI ≥25 kg/m2 (35.9% vs. 18.3%; SMD=0.41). In addition, patients with CTS had more ambulatory visits (76.3% vs. 62.5%; SMD=0.30) and inpatient encounters (21.0% vs. 11.5%; SMD=0.26). Substance use disorders were also more common (11.5% vs. 4.3%; SMD=0.27). After 1:1 matching (n=493,181 each), all covariates achieved balance (SMDs ≤0.10).
Baseline characteristics.
Sensitivity analyses. In the 15-year follow-up, patients with CTS had a 1.74-fold higher risk of new-onset hidradenitis suppurativa compared to CTS-free controls (HR=1.739, 95%CI=1.617-1.871) (Figure 2). Under various analytic configurations, patients with CTS consistently exhibited elevated risk of new-onset hidradenitis suppurativa (HS) compared to non-CTS controls. In crude and various propensity matched models, HR was 1.647 (95%CI=1.572-1.726) in Model 1a (crude model without proceeding propensity score matching), 2.142 (95%CI=1.979-2.318) in Model 2b (propensity score matching performed on age at index and sex), and 1.925 (95%CI=1.785-2.077) in Model 3c (propensity score matching performed on age at index, sex and body mass index). When applying washout periods of 12, 24, and 36 months, patients with CTS exhibited a consistently elevated risk of developing HS, with HRs of 1.758 (95%CI=1.628-1.899), 1.788 (95%CI=1.647-1.941), and 1.752 (95%CI=1.604-1.913), respectively, compared to matched controls without CTS. Similarly, follow-up durations of 5 and 10 years post-index date yielded HRs of 1.881 (95%CI=1.716-2.062) and 1.762 (95%CI=1.634-1.901), respectively. Additionally, when employing more stringent definitions of CTS, the risk remained significantly elevated: an HR of 2.076 (95%CI=1.873-2.300) was observed using a non-steroidal anti-inflammatory drug (NSAID)-based definition, and an HR of 1.734 (95%CI=1.388-2.166) was observed using a surgical neuroplasty-based definition, relative to CTS-free individuals (Table III).
Cumulative probability of hidradenitis suppurativa in patients with carpal tunnel syndrome (CTS) and CTS-free individuals.
Sensitivity analyses: hazard ratio of hidradenitis suppurativa in different analytic models.
Stratification analysis. When stratified by sex, male patients with CTS had a hazard ratio (HR) of 1.249 (95%CI=1.042-1.498) for developing HS compared to CTS-free males, while female patients demonstrated a higher HR of 1.739 (95%CI=1.606-1.884) compared to CTS-free females. Age-stratified analysis revealed an HR of 1.772 (95%CI=1.642-1.913) for individuals aged 18-64 years and an HR of 1.479 (95%CI=1.146-1.907) for those aged ≥65 years, relative to age-matched controls without CTS (Table IV).
Age and sex stratification of hidradenitis suppurativa (HS) risk in patients with and without carpel tunnel syndrome (CTS).
Discussion
In this large, real-world data study, we found a significant association between CTS and HS, with an increased risk of 1.739-fold compared to CTS-free controls (95%CI=1.617-1.871) under a 15-year follow-up model. This observation appears to be the first study extending the spectrum of known CTS comorbidities to include a chronic inflammatory skin disorder.
Our results add to a growing body of literature highlighting links between chronic inflammatory diseases and neuropathies. It is well established that systemic inflammatory disorders can manifest with entrapment neuropathies. For example, rheumatoid arthritis (RA) and psoriatic arthritis frequently lead to CTS through chronic synovitis of the wrist flexor tendons (17). CTS is reported as the one of the most common neurological complication in RA, and integrated evidence have shown that patients with RA have an 1.96-fold risk of having CTS (18). Likewise, patients with psoriatic arthritis often experience tenosynovitis and enthesitis in the hands, which can be associated with CTS (17, 19). Intriguingly, recent studies have noted that among individuals with psoriasis, those who develop CTS or peripheral neuropathy were more likely to have underlying psoriatic arthritis, suggesting that CTS in a psoriasis patient may be an indication of systemic inflammatory joint disease (20). These observations underscore that chronic inflammation in the musculoskeletal system can impinge on peripheral nerves, aligning with our finding that inflammatory skin diseases could be epidemiologically linked to CTS.
Beyond clinical observations, emerging mechanistic data support shared inflammatory pathways in CTS and HS. A key insight is the role of systemic low-grade inflammation in idiopathic CTS. Recent evidence indicates that patients with more severe or widespread CTS symptoms exhibit elevated circulating inflammatory markers (21). For instance, a recent cross-sectional study found that patients with CTS with symptom radiation proximal to the wrist had significantly higher serum C-reactive protein (CRP) and interleukin-6 levels than those with localized symptoms (22). This suggests that even in CTS with less severe clinical expression, there may be a systemic inflammatory milieu contributing to nerve injury or pain amplification. Notably, obesity, a risk factor common to both CTS and HS, is also associated with chronic low-grade elevation of CRP and cytokines such as IL-6 (23), which could biologically link to nerve compression via swelling of synovial tissue or enhanced pain sensitivity. On the other side, HS, as a prototypical autoinflammatory skin disorder driven by immune dysregulation, is characterized by lesions with massive infiltration of neutrophils and T cells, along with elevated levels of cytokines including TNF-α, IL-1β, and IL-17 (7). These cytokines are central to the pathogenesis of HS and have become therapeutic targets. TNF-α inhibitors (e.g., infliximab, adalimumab) were the first successful biologics for HS, and more recently IL-17 pathway blockers (secukinumab, bimekizumab) have shown efficacy clinical in trials (24). The TNF-α/IL-17 axis appears to be a crucial point of convergence. TNF-α not only drives inflammation in HS but also upregulates IL-17 activity; accordingly, blocking TNF-α in patients with HS can lead to downstream reductions in IL-17 and other inflammatory mediators (25). This is notable because TNF-α and IL-17 are likewise pivotal in the immunopathology of rheumatoid and psoriatic arthritis (26, 27), which are diseases that have been reported to have a significant association with CTS in recent years. Given that HS and CTS have overlapping immunologic pathways, we hypothesize that patients with HS could have a tendency for TNF/IL-17-driven inflammation and be prone to develop both HS and inflammatory changes in peri-neural tissues. Our findings support the view of CTS and HS are not merely as isolated organ-specific ailments, but conditions that can be connected through systemic inflammatory mechanisms.
The strengths of our study include its large sample size and the use of a broad, multi-institutional electronic health record network, which enhances the evidence power of the findings. The study population drawn from diverse healthcare organizations increases confidence that the CTS-HS link is not an artifact of one region or practice pattern. Nevertheless, our work has important limitations inherent to retrospective analyses based on electronic health record. First, causality cannot be established. While we demonstrate a statistical association, the observational nature of our data made us unable to firmly determine temporal sequencing of the association. Second, there is potential for detection bias and underdiagnosis. Patients with one painful chronic condition may be more closely monitored by physicians, increasing the chance that the other condition is detected. Third, our reliance on diagnostic codes (ICD codes) for identifying CTS and HS is another source of uncertainty; misclassification is possible if codes were entered incorrectly or if conditions were managed without proper coding. Though we attempted to minimize this by requiring multiple diagnostic codes to validate each diagnosis, the potential bias caused by misclassification should still be prudently considered.
In conclusion, this study provides new evidence of a link between an CTS and HS, highlighting the interplay between musculoskeletal and dermatologic health. The discovery of an elevated HS risk in patients with CTS broadens the understanding of CTS’s comorbidity profile and suggests that nerve compression syndromes may contribute to systemic inflammation and dermatological comorbidities.
Footnotes
Authors’ Contributions
All the Authors were involved in drafting or revising the article and approved the submitted version. Study conception and design: Wu CL, Su YJ, Chang HC, Wu YH, Jhang YS, Wu MC, Chen SJ, Gau SY; Data acquisition: Wu CL, Chang HC, Gau SY; Data analysis and demonstration: Wu CL, Gau SY; Original draft preparation: Wu CL, Su YJ, Chang HC, Wu YH, Jhang YS, Wu MC, Chen SJ, Gau SY.
Conflicts of Interest
The Authors have no conflicts of interest to declare in relation to this study.
Funding
This study was funded by Chung Shan Medical University Hospital (CSH-2025-A-007).
Artificial Intelligence (AI) Disclosure
During the preparation of this manuscript, a large language model (ChatGPT 4o, OpenAI) was used solely for language editing and stylistic improvements in select paragraphs. No sections involving the generation, analysis, or interpretation of research data were produced by generative AI. All scientific content was created and verified by the authors. Furthermore, no figures or visual data were generated or modified using generative AI or machine learning-based image enhancement tools.
- Received June 23, 2025.
- Revision received July 9, 2025.
- Accepted July 14, 2025.
- Copyright © 2025 The Author(s). Published by the International Institute of Anticancer Research.
This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY-NC-ND) 4.0 international license (https://creativecommons.org/licenses/by-nc-nd/4.0).
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