Carpal tunnel syndrome in systemic sclerosis: prevalence, clinical correlates, and diagnostic performance of ultrasound compared with nerve conduction studies

Abstract

Background

Carpal tunnel syndrome (CTS) is a frequent yet under-recognized complication in systemic sclerosis (SSc), where hand symptoms may overlap with vasculopathy and musculoskeletal involvement. Consequently, diagnosis often requires nerve conduction studies (NCS), while the role of ultrasound remains incompletely defined. We aimed to determine the prevalence of CTS in SSc using NCS as the reference standard, identify associated clinical and disease-related factors, and assess the diagnostic performance of ultrasound.

Methods

We conducted a cross-sectional study including consecutive SSc patients recruited from the Rheumatology Unit of Colentina Clinical Hospital, Bucharest, Romania (January 2023-March 2025). All participants underwent standardized clinical examination, comprehensive musculoskeletal ultrasound, and NCS within a 7-day interval. The ultrasound protocol incorporated multiple structural and dynamic parameters of the median nerve, including maximal cross-sectional area (maxCSA) and complementary measurements. CTS was defined and staged electrophysiologically according to the Bland scale. Associations were analyzed using clustered generalized estimating equation models accounting for bilateral hands. Ultrasound diagnostic performance was evaluated using maxCSA thresholds and receiver operating characteristic analysis.

Results

The study included 109 patients (218 hands). NCS-defined CTS was present in 34.1% of hands and in 44.0% of patients, indicating a substantial burden of objective neuropathy in SSc. Independent associations were predominantly traditional vascular and occupational factors, particularly arterial hypertension and smoking, whereas global SSc phenotype variables were not independently associated. Median nerve maxCSA showed moderate discriminative ability (AUC 0.722) with an optimal cutoff of 10 mm². Threshold-based definitions demonstrated increasing specificity with higher cutoffs. Although sensitivity remained limited, a positive ultrasound was substantially associated with the presence of CTS.

Conclusions

CTS is common in SSc when systematically investigated and appears to be associated with general vascular vulnerability than with global disease phenotype. Ultrasound provides clinically meaningful complementary information, particularly as a confirmation and triage tool, and performs best in more advanced disease. While NCS remains important for exclusion and severity staging, ultrasound may help triage and support diagnosis in selected high-probability cases.

Supplementary Information

The online version contains supplementary material available at 10.1186/s41927-026-00645-9.

Introduction

Carpal tunnel syndrome (CTS) is the most frequent entrapment neuropathy of the upper limb and remains a clinically relevant source of pain, sensory disturbance, and functional impairment. In connective tissue diseases, CTS is particularly challenging because symptoms may overlap with vasculopathy-related paresthesia and hand disability, while objective confirmation and staging often require nerve conduction studies (NCS).

Systemic sclerosis (SSc) can involve peripheral nerves through a combination of fibrosis, edema, and microvascular dysfunction, creating a plausible substrate for median nerve (MN) compression at the wrist. NCS in SSc report a wide range of MN neuropathy and CTS frequency, with many cases being mild and sometimes asymptomatic, suggesting that CTS may be under-recognized without systematic testing [1]. The actual reported prevalence of CTS or MN neuropathy at the wrist in SSc varies widely across studies, largely depending on the diagnostic approach. Earlier reports based mainly on clinical assessment described relatively low prevalence rates, ranging from approximately 3.2% to 25% [2–6], with some studies reporting CTS in only 3.2% of patients [6]. Similarly, a systematic review identified CTS in approximately 6.5% of SSc patients [3], supporting the notion that clinically overt CTS is relatively uncommon. However, studies incorporating NCS have consistently reported higher rates of MN involvement, for example in 43.7–44% of patients, with up to 88% of them being asymptomatic [7–9]. Several studies have shown that peripheral nervous system involvement in SSc is more frequent than previously recognized, including subclinical polyneuropathy and entrapment neuropathies that may not be evident on clinical examination alone [4, 5, 10]. These findings suggest that MN involvement, including CTS, may be substantially underdiagnosed in the absence of systematic testing. In addition, ultrasound studies have demonstrated structural abnormalities of the MN across different stages of SSc, supporting the concept of early and diffuse nerve involvement [11].

Ultrasound has also been used to detect MN enlargement at the carpal tunnel in SSc, including in patients without overt symptoms, and studies suggest that peripheral nerve involvement in SSc may include altered mechanical properties (e.g., increased stiffness) even when maximal cross-sectional area (maxCSA) is not markedly increased [11]. Despite growing interest in peripheral nerve ultrasound, there is still no single consensus on the optimal site/approach or cutoff for sonographic CTS diagnosis across settings, and thresholds derived from idiopathic CTS may not transfer cleanly to SSc where tissue biomechanics and comorbid inflammatory/vascular changes may differ. Moreover, prior SSc studies have variably used symptoms, ultrasound, or NCS, and head-to-head evaluations of ultrasound diagnostic performance against NCS together with a structured assessment of SSc remain limited. A non-systematic scoping check of the literature suggests that relatively few studies focus specifically on CTS or MN neuropathy in SSc, and available reports are methodologically heterogeneous in case definitions (symptom-based vs. NCS-confirmed) and study populations [11–13]. This strikingly small and temporally skewed literature indicates that CTS in SSc has remained a niche and under-investigated topic, with most available evidence derived from older reports or small, methodologically heterogeneous studies rather than contemporary, systematically characterized cohorts. Consequently, there is limited high-quality information on the true burden of CTS in SSc at both patient and hand level using objective electrophysiological criteria, the clinical phenotype associated with NCS-confirmed CTS in SSc, and whether commonly used ultrasound maxCSA thresholds derived from idiopathic CTS populations retain adequate diagnostic performance in the distinct tissue and microvascular milieu of SSc. This gap is clinically relevant because hand symptoms are frequent in SSc and misattribution may delay appropriate CTS management, while over-diagnosis may lead to unnecessary investigations or procedures. These considerations underscore the need for studies that combine standardized clinical assessment with same-day ultrasound and NCS in well-characterized SSc patients to quantify prevalence, define associated features, and benchmark ultrasound performance against electrophysiology.

In this context, this study aims to estimate the prevalence of CTS in SSc at the patient and hand level using NCS as reference, identify clinical, serological, and SSc-related features associated with NCS-defined CTS and assess diagnostic performance of ultrasound versus NCS for CTS in SSc.

Methods

Patients and SSc

This cross-sectional study enrolled all consecutive patients diagnosed with SSc and evaluated in the Rheumatology Unit of Colentina Hospital (Bucharest, Romania) between January 2023 and March 2025. Consecutive inclusion was ensured by enrolling all eligible SSc admissions during the study period, with physician referral supplemented by systematic electronic medical record screening of all department admissions by the study coordinator. SSc was diagnosed by each treating rheumatologist, and SSc characteristics were retrieved from the physical and electronic medical records within the study timeframe. Exclusion criteria were: age < 18 years; acute CTS (defined as a rapidly developing compression of the MN within the carpal tunnel most commonly caused by trauma, hemorrhage, or acute inflammatory processes, typically representing a surgical emergency requiring urgent decompression, given that ultrasound and NCS may capture transient edema or conduction block rather than chronic compressive pathology); prior paresis or cervical radiculopathy (confirmed clinically and, when indicated, by cervical imaging); confirmed diabetic polyneuropathy; previous wrist fractures or malunited callus affecting the wrist; prior CTS decompression surgery; local glucocorticoid or anesthetic injection into the carpal tunnel or physiotherapy targeting the wrist region within the previous three months; oral contraceptive use within the prior six months; decompensated hypothyroidism; chronic kidney disease requiring hemodialysis; and overlapping inflammatory joint diseases (including rheumatoid arthritis, systemic lupus erythematosus, Sjögren’s disease, mixed connective tissue disease). Occupational exposures were assessed during the standardized clinical interview using self-reported occupational history and responses were recorded as binary (yes/no). For each participant, all study procedures (history, interview and questionnaires, general and CTS-focused examination, ultrasound, NCS, and verification of exclusion criteria) were completed within a 7-day interval. The study was conducted in accordance with the Declaration of Helsinki and was approved by the local ethics committee (2/19 January 2023). All participants provided written informed consent prior to any study-related procedure.

Clinical evaluation

All participants completed a standardized clinical assessment before ultrasound and NCS. Examinations were performed by the same investigator (senior rheumatologist) and focused on sensory abnormalities in the MN territory, including median-ulnar sensory discrimination, Tinel’s sign, and Phalen’s test, together with evaluation of thenar atrophy and motor weakness. Specifically, light touch sensation was assessed in the MN distribution using gentle tactile stimulation, performed between the thenar and hypothenar eminences and across the radial and ulnar aspects of the ring finger. Sensory perception was recorded as normal or abnormal based on patient-reported perception. Motor function was evaluated by testing thumb abduction against resistance, reflecting the function of the abductor pollicis brevis muscle, and by assessing lateral pinch strength, in which the patient was asked to grasp an object between the lateral aspect of the thumb and index finger while resistance was applied. In addition, the presence of thenar eminence atrophy was documented. Grip strength was measured using a Camry EH101 digital hand dynamometer (Zhongshan Camry Electronic Co., Ltd., Guangdong, China). Testing was performed with the arm alongside the body, the elbow flexed at 90°, and the wrist in a neutral position. Each patient completed three maximal-effort trials, and the mean value (kgf) was recorded.

Ultrasound evaluation

Ultrasound assessments were performed by a second senior rheumatologist certified in advanced musculoskeletal ultrasound by EULAR (European Alliance of Associations for Rheumatology), who was blinded to clinical data. Examinations were carried out using a MyLab Seven ultrasound system (Esaote SpA, Genoa, Italy) equipped with a 7–18 MHz linear transducer. Patients were evaluated in the seated position with the forearm supinated and the fingers maintained in a neutral posture. Power Doppler (PD) settings included a 9.1 MHz frequency and a 750 Hz pulse repetition frequency. Each wrist was scanned in both longitudinal and transverse planes, following the standardized acquisition protocols recommended by the 2017 EULAR musculoskeletal ultrasound guidelines [14]. As there is currently no consensus on the optimal site or technique for MN sonographic measurement in suspected CTS, we applied a multimodal ultrasound protocol incorporating several approaches frequently reported in the literature [15–19], in order to evaluate their diagnostic performance head-to-head against NCS in this disease context. The definition and description of ultrasound measures have been previously published by our group [20]. For each quantitative parameter, three repeated measurements were obtained and the mean value was used for analysis to minimize measurement variability. MN mobility was recorded as normal versus abnormal; abnormal mobility was defined as absent displacement of the nerve or only partial displacement limited to the radioulnar plane during active wrist and finger movement. Ultrasound CSA thresholds (> 10, > 11, >12 mm²) were prespecified based on commonly used cutoffs in the CTS ultrasound literature to capture a range from screening-oriented to higher-specificity (rule-in) definitions [21–23]. Beyond MN measurements, the wrist ultrasound examination included assessment of local musculoskeletal features that could plausibly contribute to MN compression, including wrist synovitis, flexor tendon tenosynovitis, and periarticular/soft-tissue calcifications (calcinosis) when present.

NCS evaluation

Electrophysiological confirmation of CTS was performed for each hand using a Nihon Kohden Neuropack electromyograph (Nihon Kohden Corporation, Tokyo, Japan) with surface cup recording electrodes and a surface electrical stimulator. MN sensory and motor nerve conduction studies, including F-waves, were obtained at a stimulation rate of 1 Hz. Antidromic sensory nerve action potentials (SNAPs) were recorded following wrist stimulation, with recording electrodes positioned on the index, middle, and ring fingers for comparative assessment and a fixed 14-cm stimulation-recording distance. Motor studies were performed according to standard protocols, recording compound muscle action potentials (CMAPs) with the active electrode placed over the abductor pollicis brevis. Stimulus duration was 0.2 ms at all sites. All examinations were conducted by the same neurologist, who was blinded to clinical and ultrasound findings. Skin temperature was continuously monitored, with testing performed in an air-conditioned room maintained at 23–25 °C. NCS-defined CTS (yes/no) was the primary outcome. CTS was defined electrophysiologically using the Bland scale (0 = normal to 6 = extremely severe), namely as a Bland grade ≥ 1 [24, 25]. In addition to MN sensory and motor studies, ulnar NCS were performed to assess for concomitant ulnar neuropathy, including involvement at Guyon’s canal, in order to distinguish isolated MN entrapment from possible multifocal entrapment patterns in SSc.

Statistics

General statistics

Nominal variables were reported as absolute frequency and percent of sub/group. Data distribution normality was assessed using descriptive statistics, normality, stem-and-leaf plots, and the Lilliefors corrected Kolmogorov-Smirnov test. Normally distributed continuous variables are reported as “mean ± standard deviation”, while non-normally distributed continuous variables are reported as “median (first quartile, third quartile)”. Baseline patient-level characteristics were compared between CTS groups (NCS-confirmed CTS in at least one hand) using χ²/Fisher tests for categorical variables and Mann-Whitney U tests for continuous variables. All statistical tests were considered significant if p < 0.05 and were performed using IBM SPSSc Statistics version 26.0 for Windows (IBM Corp., Armonk, NY, USA), Stata version 12 (StataCorp, College Station, TX, USA) and R version 4.5.1 (R Foundation for Statistical Computing, Vienna, Austria).

Differences and associations of CTS diagnosis

Comparisons of CTS-related symptoms and examination findings between hands with and without NCS-defined CTS were performed using hand-level univariate generalized estimating equation (GEE) models clustered by patient ID (exchangeable working correlation; robust standard errors). Binary clinical variables were analyzed with logistic GEE and reported as odds ratios (OR) with 95% confidence intervals (CI), while continuous variables were analyzed using GEE with Gaussian distribution and reported as mean differences with 95% CI.

Because each patient contributed two hands, analyses were performed at the hand level with methods that account for within-patient correlation. The primary association analyses used logistic GEE clustered by patient ID (exchangeable working correlation; robust standard errors) with NCS-defined CTS diagnosis (yes/no) as the dependent variable. To manage a large number of candidate predictors and to avoid inappropriate independence assumptions in preliminary screening, we used a two-stage strategy with distinct roles. Stage 1 (patient-level screening) was a pragmatic dimensionality-reduction step applied to variables that are inherently patient-level (demographics, comorbidities, SSc phenotype/organ involvement, serology, and treatments). A patient-level outcome was defined as NCS-defined CTS in ≥ 1 hand. Candidate variables were compared between groups using using χ² or Fisher’s exact tests for categorical variables and Mann-Whitney U tests for continuous variables. Variables meeting a liberal screening threshold (p < 0.20) and/or considered clinically relevant were prioritized for stage 2. Stage 1 results were not interpreted as final inference. Stage 2 (hand-level screening and modeling) consisted of univariate hand-level GEE models for all shortlisted patient-level predictors and for all hand-level predictors (clinical symptoms/signs and ultrasound measurements). For univariate hand-level screening of candidate predictors, each variable was entered individually, and variables showing evidence of association were retained for subsequent multivariable modeling. Multivariable GEE models were then specified a priori to address distinct predictor domains and to limit collinearity: a base model with prespecified covariates age, sex, and BMI forced in all models; a cardiovascular/lifestyle model (base + hypertension, smoking, cardiac involvement); an occupational exposure model (base + vibration exposure, lifting, repetitive activity, computer work); a combined model (base + cardiovascular/lifestyle + occupational variables + telangiectasia) to evaluate robustness across domains; and a SSc phenotype model (base + SSc subtype, disease duration, current Rodnan score, capillaroscopy pattern). Model estimates are reported as odds ratios (OR) with 95% CI. Age, sex, and BMI were forced in all multivariable models because they are established or plausible confounders of CTS and reflect baseline body size/structure. To minimize overfitting, the number of predictors per model was kept parsimonious relative to the number of CTS-positive hands, and highly correlated occupational variables were not interpreted as independent causal effects.

Ultrasound performance

Raw comparisons of ultrasound variables between CTS and non-CTS hands were performed using hand-level GEE models clustered by patient ID (Gaussian for continuous and logistic for categorical measures). Ultrasound diagnostic performance for CTS was evaluated at the hand level using NCS-defined CTS diagnosis (yes/no) as the reference standard. Binary ultrasound definitions were assessed using MN maxCSA thresholds (> 10, > 11, >12 mm²). For each definition, sensitivity, specificity, positive and negative predictive values (PPV/NPV), likelihood ratios (LR + and LR-), and Cohen’s kappa were calculated. Specifically, agreement between ultrasound and NCS for binary CTS classification was quantified using Cohen’s κ, comparing US-positive status (by prespecified maxCSA thresholds) against NCS-defined CTS diagnosis (yes/no). Because each patient contributed two hands, uncertainty was quantified using cluster bootstrap 95% CI, resampling patient identifiers with replacement and retaining both hands within each resampled patient. Receiver operating characteristic (ROC) analysis was performed for MN maxCSA as a continuous predictor to estimate area under the curve (AUC) and determine the optimal cutoff using the Youden index. Prespecified subgroup analyses included performance stratified by NCS severity stage and ROC/AUC analyses restricted to dominant versus non-dominant hands.

Results

Baseline characteristics and group comparisons

A total of 109 patients with SSc contributed 218 hands. Baseline characteristics were summarized and compared between patients with NCS-defined CTS in ≥ 1 hand and those without CTS (Table 1). In brief, CTS-positive patients tended to be older and more frequently had hypertension and smoking exposure, while SSc subtype, Rodnan score, and capillaroscopy pattern did not show clear differences.

Table 1.

Baseline characteristics of SSc patients by CTS status (patient-level)

	all (n = 109)	no CTS (n = 61)	CTS (n = 48)	p
Age, y	58.7 ± 11.6	56.6 ± 12.3	61.4 ± 10.0	0.045
BMI, kg/m2	24.2 ± 4.3	23.9 ± 3.9	24.7 ± 4.8	0.438
Rodnan score	8.5 ± 7.3	8.9 ± 8.2	8.0 ± 6.1	0.946
SSc duration, y	5.2 (1.1–12.2)	6.8 (3.2–13.8)	2.0 (0.7–7.2)	0.007
Raynaud duration, y	8.0 (4.2–17.1)	9.4 (5.8–18.0)	6.6 (3.0–16.0)	0.078
Female sex	96 (88.1%)	57 (93.4%)	39 (81.2%)	0.073
Smoking	31 (28.4%)	13 (21.3%)	18 (37.5%)	0.088
Vibration exposure	18 (16.5%)	5 (8.2%)	13 (27.1%)	0.018
Lifting exposure	58 (53.2%)	28 (45.9%)	30 (62.5%)	0.083
Repetitive activity	60 (55.0%)	29 (47.5%)	31 (64.6%)	0.119
Computer work	24 (22.0%)	18 (29.5%)	6 (12.5%)	0.037
AHT	55 (50.5%)	24 (39.3%)	31 (64.6%)	0.012
Cardiac involvement	27 (24.8%)	10 (16.4%)	17 (35.4%)	0.027
ILD	70 (64.2%)	40 (65.6%)	30 (62.5%)	1.000
GI involvement	68 (62.4%)	41 (67.2%)	27 (56.2%)	0.165
Telangiectasia	82 (75.2%)	41 (67.2%)	41 (85.4%)	0.090
Calcinosis cutis	29 (26.6%)	18 (29.5%)	11 (22.9%)	0.513
Arthritis	20 (18.3%)	14 (23.0%)	6 (12.5%)	0.211
Anti-Scl-70 positive	54 (49.5%)	29 (47.5%)	25 (52.1%)	0.990
Anticentromere positive	29 (26.6%)	16 (26.2%)	13 (27.1%)	0.992

Notes: CTS status is defined at the patient level as NCS-defined CTS in ≥ 1 hand. Continuous variables are reported as mean ± SD or as median (Q1-Q3). P-values are from two-sided Mann-Whitney U tests and χ2/Fisher’s exact tests. Abbreviations: AHT arterial hypertension; BMI body mass index; CTS carpal tunnel syndrome; GI gastrointestinal; ILD interstitial lung disease; NCS nerve conduction studies; SD standard deviation; SSc systemic sclerosis; y years

Clinical CTS-related findings (hand-level)

CTS-related symptoms and bedside tests showed limited discriminatory value between hands with and without NCS-defined CTS in SSc. Nocturnal symptoms, positional triggers (raised hand, repetitive movements, position change), relief by shaking, Tinel’s and Phalen’s signs, and the presence of MN-territory sensory loss were not significantly different between CTS and non-CTS hands in clustered analyses (all p > 0.05; Table 2). In contrast, grip strength differed modestly between groups, being lower in CTS hands compared with non-CTS hands (16.4 ± 5.9 versus 17.4 ± 6.2 kgf; p = 0.022, clustered analysis).

Table 2.

Clinical comparison of hands with or without NCS-CTS (n = 218)

	non-CTS (n = 144)	CTS (n = 74)	OR (95% CI)	p
Nocturnal symptoms	51 (35.4%)	34 (46.0%)	1.56 (0.78–3.12)	0.209
Symptoms with raised hand	49 (34.0%)	37 (50.0%)	1.83 (0.90–3.70)	0.095
Symptoms with repetitive movement	33 (22.9%)	22 (29.7%)	1.45 (0.68–3.09)	0.336
Symptoms with position change	64 (44.4%)	36 (48.6%)	1.38 (0.72–2.62)	0.329
Relief by shaking	67 (46.5%)	30 (40.5%)	0.93 (0.48–1.79)	0.828
Tinel (positive)	13 (9.0%)	8 (10.8%)	1.49 (0.63–3.49)	0.364
Phalen (positive)	23 (16.0%)	19 (25.7%)	1.39 (0.67–2.85)	0.373
Sensory loss (any; ≥1)	17 (11.8%)	9 (12.2%)	1.02 (0.42–2.47)	0.969
Thenar weakness/atrophy	25 (17.4%)	7 (9.5%)	0.45 (0.20–1.04)	0.062
Dry skin in MN territory	39 (27.1%)	20 (27.0%)	0.98 (0.47–2.05)	0.951
Morning stiffness	49 (34.0%)	23 (31.1%)	0.85 (0.42–1.71)	0.644
Grip strength (kgf)	17.4 ± 6.2	16.4 ± 5.9		0.022

Notes: Each patient contributed up to two hands. Binary variables: reported as n (%) and compared using univariate logistic GEE clustered by patient ID (exchangeable working correlation; robust standard errors), reported as OR (95% CI). Continuous variables (e.g., grip strength): compared using GEE with Gaussian distribution (identity link) clustered by patient ID; values presented as mean ± SD (descriptive) with p-values from clustered models. Sensory loss coding: “Any sensory loss” defined as sensory loss grade ≥ 1 vs. 0. Abbreviations: CI confidence interval; CTS carpal tunnel syndrome; GEE generalized estimating equations; kgf kilogram-force; NCS nerve conduction studies; MN median nerve; OR odds ratio

Ultrasound evaluation

On raw between-group comparison, CTS hands demonstrated higher MN maxCSA (11.1 ± 3.8 versus 9.1 ± 1.7 mm²; p < 0.001), and higher structural ratios reflecting focal enlargement (entry/exit MN area ratio and entry MN CSA/PT ratio; both p ≤ 0.005). Retinaculum-SP distance was also greater in CTS hands (p = 0.019), whereas PT area, retinaculum thickness, flattening ratios, and contralateral CSA ratio did not differ significantly. Categorical ultrasound signs (hypoechogenicity, Doppler, and entry decalibration) were more frequent in CTS hands (supplementary table S1).

On ultrasound evaluation (218 hands), the mean MN maxCSA was 9.77 ± 2.77 mm². Using maxCSA thresholds, ultrasound-defined CTS was present in 26.6% of hands for MN maxCSA over 10 mm², 16.1% for maxCSA over 11 mm², and in 8.7% for maxCSA above 12 mm². The mean MN area at tunnel entry was 9.27 ± 2.66 mm² with a mean flattening ratio of 3.08 ± 0.93. At the tunnel exit, mean MN area was 7.91 ± 3.49 mm² with a mean flattening ratio of 3.04 ± 2.02. Structural/dynamic abnormalities included hypoechogenicity in 33.6%, intra-/perineural Doppler signal in 14.9%, entry decalibration in 34.3%, and exit decalibration in 3.8%; altered mobility was recorded in 44.9% of cases. The MN area at the pronator teres level had a mean or 6.11 ± 1.18 mm². The ratio of maxCSA and MN area at the pronator teres averaged 1.62 ± 0.45. The retinaculum-scaphoid/pisiform line distance measured 2.45 ± 1.37 mm, while flexor retinaculum thickness had a mean of 0.60 ± 0.33 mm. A contralateral normalization metric (maxCSA/contralateral MN area ratio) averaged 1.02 ± 0.18, and the entry MN area to pronator teres MN area ratio had a mean of 1.55 ± 0.45. Structural variants were uncommon: a bifid MN was identified in 12.0% of hands, a persistent median artery in 7.0% of hands, and an accessory tendon/muscle in 2.8% of hands.

NCS evaluation

On NCS performed in 218 hands, mean SNAP amplitude was 26.2 ± 12.9 µV and mean SCV was 49.1 ± 8.2 m/s. Motor studies showed a mean motor distal latency 3.74 ± 0.76 ms, mean CMAP amplitude of 7.76 ± 2.38 mV, and mean MCV of 54.6 ± 6.3 m/s; mean F-wave latency was 27.1 ± 2.6 ms. Overall, NCS-defined CTS was present in 34.1% of evaluated hands, corresponding to 44.0% of patients with CTS in at least one hand. Severity staging (hand-level) was stage 0 (65.9%), stage 1 (3.7%), stage 2 (20.1%), stage 3 (8.4%), stage 5 (1.4%), and stage 6 (0.5%). Ulnar NCS identified ulnar neuropathy at Guyon’s canal in 21 hands (9.6%) from 14 patients (12.8%). Among affected patients, 12 patients had concomitant NCS-defined CTS together with ulnar involvement at Guyon’s canal. Notably, 23 patients (21.1%) had NCS-defined CTS in the absence of CTS-related symptoms, corresponding to 35 asymptomatic but NCS-positive hands (16.1%).

Factors associated with CTS

Patient-level pre-screening identified several candidate correlates of CTS, including older age, sex, AHT, smoking, vibration exposure, computer work, lifting/repetitive activity, cardiac involvement, higher Raynaud VAS, and telangiectasia (supplementary table S2). In the univariate GEE screening, higher odds of NCS-defined CTS were associated with older age, male sex, AHT, smoking, vibration exposure, lifting, computer work, repetitive activity, SSc cardiac involvement and larger fist circumference (supplementary table S3). The base multivariate model (M0) showed an inverse association between female sex and NCS-defined CTS (OR 0.28, 95% CI 0.08–0.89; p = 0.032; Table 3), while age and BMI were not significant (supplementary table S4). In the cardiovascular/lifestyle model (M1), smoking remained independently associated with CTS (OR 2.97, 95% CI 1.15–7.64; p = 0.024; Table 3), whereas AHT showed a borderline association (OR 2.08; p = 0.076) and SSc cardiac involvement was not significant. In the occupational exposure model (M2), computer work was independently inversely associated with CTS (OR 0.33, 95% CI 0.11-1.00; p = 0.049; Table 3), while vibration exposure was borderline (OR 2.78; p = 0.075). In the combined model (M3), AHT (OR 2.76, 95% CI 1.14–6.69; p = 0.024) and smoking (OR 3.43, 95% CI 1.28–9.19; p = 0.014) remained independently associated with higher CTS odds, and computer work retained an inverse association (OR 0.27, 95% CI 0.08–0.88; p = 0.029; Table 3); the remaining occupational variables, cardiac involvement, and telangiectasia were not significant after adjustment. Finally, in the SSc phenotype model (M4), none of the disease-specific variables were independently associated with CTS (all p > 0.05), although shorter SSc duration showed a borderline inverse association (OR 0.92 per year, 95% CI 0.83–1.01; p = 0.087; Table 3).

Table 3.

Hand-level multivariable association models (M0-M4) with the NCS-defined CTS diagnosis (n = 218)

	M0	M1	M2	M3	M4
Age(per 1 y)	1.03 (0.99–1.06) p = 0.178	1.01 (0.97–1.05) p = 0.623	1.0 (0.97–1.05) p = 0.509	0.99 (0.95–1.04) p = 0.836	1.04 (0.99–1.09) p = 0.162
Sex: female vs. male	0.28 (0.08–0.89) p = 0.032	0.51 (0.14–1.87) p = 0.311	0.56 (0.19–1.62) p = 0.283	1.15 (0.34–3.96) p = 0.821	0.36 (0.10–1.29) p = 0.116
BMI (per 1 kg/m²)	1.05 (0.96–1.15) p = 0.323	1.04 (0.95–1.15) p = 0.397	1.03 (0.94–1.13) p = 0.520	1.04 (0.95–1.14) p = 0.422	1.01 (0.91–1.13) p = 0.802
AHT: yes vs. no	-	2.08 (0.93–4.68) p = 0.076	-	2.76 (1.14–6.69) p = 0.024	-
Smoking: yes vs. no	-	2.97 (1.15–7.64) p = 0.024	-	3.43 (1.28–9.19) p = 0.014	-
SSc cardiac involvement: yes vs. no	-	1.76 (0.70–4.42) p = 0.231	-	1.76 (0.60–5.17) p = 0.300	-
Vibration exposure: yes vs. no	-	-	2.78 (0.90–8.59) p = 0.075	1.79 (0.55–5.87) p = 0.334	-
Lifting exposure: yes vs. no	-	-	1.62 (0.70–3.76) p = 0.258	1.99 (0.73–5.41) p = 0.178	-
Repetitive activity: yes vs. no	-	-	1.79 (0.71–4.48) p = 0.217	1.88 (0.75–4.72) p = 0.181	-
Computer work: yes vs. no	-	-	0.33 (0.11-1.00) p = 0.049	0.27 (0.08–0.88) p = 0.029	-
Telangiectasia: yes vs. no	-	-	-	1.98 (0.41–9.55) p = 0.395	-
SSc subtype: limited/sine vs. diffuse	-	-	-	-	1.71 (0.46–6.37) p = 0.422
SSc duration (per 1 y)	-	-	-	-	0.92 (0.83–1.01) p = 0.087
Current Rodnan score (per 1 point)	-	-	-	-	1.02 (0.95–1.10) p = 0.588
Capillaroscopy pattern (per 1 stage)	-	-	-	-	0.94 (0.60–1.49) p = 0.807
QIC	234	220	209	187	159

Notes: OR (95% CI) values are from multivariate logistic GEE models (binomial, logit) clustered by patient (2 hands per patient), reported with 95% CI, 2-sided Wald’s test p-values and QIC. M0 (base): age (continuous, years), sex (female vs. male), BMI (continuous, kg/m²). M1 (cardiovascular/lifestyle): M0 + AHT (yes/no), smoking (yes/no), SSc cardiac involvement (yes/no). M2 (occupational exposures): M0 + vibrations exposure (yes/no), lifting exposure (yes/no), repetitive activity exposure (yes/no), computer work (yes/no). M3 (combined model): M0 + AHT (yes/no), smoking (yes/no), SSc cardiac involvement (yes/no), vibrations exposure (yes/no), lifting exposure (yes/no), repetitive activity exposure (yes/no), computer work (yes/no). M4 (SSc phenotype): M0 + SSc subtype (limited/sine vs. diffuse), SSc duration (continuous, years), current Rodnan score (continuous), capillaroscopy pattern (ordinal 0–4; per + 1 stage), telangiectasia (yes/no). Abbreviations: AHT arterial hypertension; BMI body mass index; CI confidence interval; CTS carpal tunnel syndrome; GEE Generalized Estimating Equations; NCS nerve conduction study; OR odds ratio; QIC quasi-likelihood information criterion; SSc systemic sclerosis; y year

Ultrasound performance

Ultrasound definitions based on MN maxCSA demonstrated high specificity but limited sensitivity relative to NCS-defined CTS. Using maxCSA thresholds (Table 4), sensitivity/specificity were 43.7%/82.7% for > 10 mm², 32.4%/91.4% for > 11 mm², and 16.9%/94.9% for > 12 mm², with corresponding fair agreement at > 10 and > 11 (κ = 0.28 and κ = 0.27) and lower agreement at > 12 (κ = 0.15). Discrimination using maxCSA as a continuous measure was moderate, with an overall AUC of 0.722 (95% CI 0.628–0.802) and an optimal cutoff of 10.0 mm² (Fig. 1 for all hands; supplementary Figure S1 for dominant and non-dominant hands; Table 5). Additional ultrasound metrics provided lower or at best modest discrimination (AUC range 0.50–0.65; Table 5). Stage-stratified analyses showed higher ultrasound positivity with greater NCS severity, rising from 31.7% at stage 2 to 55.6% at stage 3 for the > 10 mm² definition, while false-positive rates among NCS stage 0 hands were 17.3%, 8.6%, and 5.0% for the > 10, >11, and > 12 mm² thresholds, respectively. In dominant-hand subgroup ROC analyses, AUC was 0.683 (0.572–0.782) versus 0.763 (0.643–0.865) in non-dominant hands; and the optimal cutoff of maxCSA remained approximately 10 mm² in both subsets. Additional categorical ultrasound signs showed limited diagnostic value for NCS-defined CTS in SSc (supplementary table S5), with fair-to-poor agreement overall (κ ranging from 0.07 to 0.40) and generally modest likelihood ratios. Hypoechogenicity provided the best balance (sensitivity 60.6%, specificity 79.1%, κ 0.40), whereas Doppler and exit decalibration were highly specific but insensitive (sensitivity 28.2% and 7.4%, respectively), and altered mobility demonstrated low discriminative capacity (specificity 58.3%, κ 0.07).

Table 4.

Performance of ultrasound maxCSA cut-offs compared to NCS-defined CTS

	max CSA > 10 mm2	max CSA > 11 mm2	max CSA > 12 mm2
Sensitivity, % (95%CI)	43.7 (29.9–56.9)	32.4 (18.5–45.0)	16.9 (6.7–27.8)
Specificity, % (95%CI)	81.6 (72.8–89.2)	91.5 (85.8–96.3)	95.0 (89.8–98.7)
PPV, % (95%CI)	54.4 (37.6–70.2)	65.7 (46.3–83.3)	63.2 (33.3–88.2)
NPV, % (95%CI)	74.2 (65.9–81.6)	72.9 (64.6–80.4)	69.4 (61.4–76.7)
LR+ (95%CI)	2.37 (1.43–4.12)	3.81 (1.92–8.32)	3.40 (1.13–15.55)
LR- (95%CI)	0.69 (0.52–0.88)	0.74 (0.59–0.88)	0.87 (0.75–0.98)
Cohen’s κ (95%CI)	0.27 (0.10–0.41)	0.27 (0.13–0.41)	0.15 (0.02–0.28)

Notes: Cohen’s kappa evaluates diagnostic agreement between ultrasound (threshold-based CTS classification) and NCS-defined CTS diagnosis at the hand level; it does not represent interobserver reliability. CIs were obtained using a cluster bootstrap resampling patient identifier (retaining both hands per patient). Abbreviations: CI confidence interval; CTS carpal tunnel syndrome; LN+/- positive/negative likelihood ratio; maxCSA median nerve cross-sectional area on ultrasound; NCS nerve conduction study; NPV negative predictive value; PPV positive predictive value

Fig. 1.

Receiver operating characteristic (ROC) curves showing the diagnostic performance of ultrasound (US) median nerve (MN) maximum cross-sectional area (MN maxCSA, mm²) for identifying nerve conduction study-defined carpal tunnel syndrome (CTS) in systemic sclerosis (all hands). The area under the curve (AUC) summarizes overall discrimination, and the optimal maxCSA cutoff was determined using the Youden index

Table 5.

Performance of other ultrasound MN measures compared to NCS-defined CTS diagnosis

Ultrasound measure	AUC	95%CI	Optimal	95%CI	Se	Sp
MN maxCSA (mm2)	0.722	0.628–0.802	≥ 10	10.0–10.0	73.2%	69.5%
NM area at pronator teres (mm2)	0.502	0.416–0.591	≤ 7.0	5.00–8.00	94.2%	13.5%
Entry/exit MN area ratio	0.638	0.546–0.727	≥ 1.22	1.09–1.44	61.3%	65.3%
Entry long/short ratio	0.536	0.437–0.627	≤ 3.0	2.85–4.56	60.0%	53.9%
Exit long/short ratio	0.533	0.438–0.628	≤ 2.65	1.79–4.18	45.0%	65.3%
Retinaculum-SP line distance (mm)	0.639	0.543–0.732	≥ 2.0	1.50–2.90	84.8%	44.1%
Flexor retinaculum thickness (mm)	0.522	0.432–0.617	≥ 0.5	0.37–0.77	77.1%	29.7%
Max MN area/contralateral MN area ratio	0.552	0.509–0.602	≥ 0.90	0.85–1.10	82.9%	29.3%
Entry MN area/area at pronator teres ratio	0.654	0.569–0.739	≥ 1.57	1.33-2.00	58.2%	68.6%

Notes: Optimal cutoff maximized the Youden index. CIs were obtained using a cluster bootstrap resampling of patient identifiers (1500 replicates), retaining both hands within each sampled patient. Optimal thresholds are shown as ≥ or ≤ because some metrics performed better when interpreted in the inverse direction. Abbreviations: AUC area under the curve; CI confidence interval; CTS carpal tunnel syndrome; maxCSA maximum cross-sectional area; MN median nerve; NCS nerve conduction study; Se sensitivity; Sp specificity

Discussions

CTS, its burden and clinical correlates in SSc

Using Bland grade ≥ 1 as the diagnostic threshold is appropriate for defining electrodiagnostically confirmed CTS, because grade 0 indicates no electrophysiological evidence of CTS, whereas grades 1–6 represent increasing neurophysiological abnormality [24]. This approach is widely used to standardize CTS severity reporting in clinical and research settings [26–29]. At the same time, it should be recognized that grade 1 reflects very mild CTS detectable only by the most sensitive comparative tests; therefore, a ≥ 1 threshold prioritizes sensitivity and may capture early/subclinical disease, which is particularly relevant in SSc where symptoms can be nonspecific and may overlap with vasculopathy and musculoskeletal hand involvement [1]. Bland NCS grading system has limitations, particularly regarding the definition of threshold values and the potential for overlap between severity categories, a problem shared by all existing classification systems than may not fully capture the continuous spectrum of nerve dysfunction and may result in unclassifiable or overlapping cases [30]. However, despite these limitations, the Bland scale remains one of the most widely used tools for grading CTS severity and has been extensively applied in clinical studies and practice. Its use in our study allows for comparability with previous literature and facilitates standardized assessment of disease severity.

Our findings indicate a substantial burden of objectively confirmed CTS in SSc, with NCS-defined CTS present in 34.1% of examined hands and 44.0% of patients affected in at least one hand, much higher than in the general population [31] and in professionally-predisposed populations [32]. This prevalence is clinically meaningful in a real-life SSc population, where paresthesia and functional limitation may arise from multiple competing mechanisms. The prevalence observed in our study is comparable to previous NCS reports and likely reflects the use of systematic assessment, including NCS and standardized diagnostic criteria, enabling the detection of mild and subclinical cases. The variability across studies may be explained by methodological differences, including reliance on clinical versus NCS definitions of CTS, differences in diagnostic thresholds, and heterogeneity in patient selection. These findings highlight the importance of standardized and multimodal evaluation for accurately estimating CTS prevalence in SSc. The high frequency of NCS-confirmed CTS supports a low threshold for objective testing in symptomatic SSc patients, particularly because clinical symptoms can overlap with vasculopathy-related sensory complaints and musculoskeletal hand involvement.

In SSc, classic CTS-oriented clinical features had limited ability to separate NCS-confirmed CTS from non-CTS hands. Provocative maneuvers (Tinel and Phalen), symptom patterns (nocturnal symptoms, positional provocation, relief by shaking), and MN-territory sensory loss were not clearly enriched in NCS-confirmed CTS, underscoring the overlap between compressive neuropathy and SSc-related contributors to hand discomfort (vasculopathy, skin thickening, musculoskeletal pain, and neuropathic symptoms of mixed origin). The observed difference in grip strength, with slightly lower values in CTS-positive hands, is directionally consistent with CTS-related motor impairment; however, in SSc grip force is also influenced by skin tightness, joint/tendon involvement, pain avoidance, and global disability, so grip strength is best interpreted as a nonspecific functional marker rather than a diagnostic discriminator. The limited separation of CTS and non-CTS hands by symptoms and signs supports a low threshold for objective confirmation (NCS and/or ultrasound), particularly when diagnostic certainty and NCS staging will influence management.

In non-SSc populations, particularly in idiopathic CTS, ultrasound has consistently demonstrated high diagnostic accuracy, largely reflecting MN enlargement secondary to mechanical compression. In contrast, previous studies suggest that nerve compression may not represent the primary mechanism responsible for symptoms in SSc [33]. Instead, peripheral nerve involvement has been attributed to alternative mechanisms, such as focal compression of individual nerve fascicles due to increased connective tissue within the endoneurium and perineurium, as well as microangiopathy of the vasa nervorum [34]. The MN is supplied by a complex and highly interconnected vascular network, including epineural and intrafascicular plexuses, with a particularly rich capillary distribution in the deeper perifascicular regions. These microvascular structures represent key targets of vascular damage in SSc, where microangiopathy is a hallmark feature. In addition, the nerve receives blood supply from multiple arterial sources, which may also be affected in the disease. This vascular vulnerability may contribute to ischemic nerve injury, providing a plausible explanation for the occurrence of CTS-like symptoms in the absence of clear compressive mechanisms. Consequently, early nerve involvement may be predominantly functional rather than structural. Early morphological changes of the MN in SSc, including mild enlargement, may reflect regenerative processes following ischemic injury rather than true compressive swelling. Similar mechanisms have been described in other conditions characterized by subclinical neuropathy, such as diabetes [35]. Thus, ultrasound, which primarily detects structural nerve enlargement, may underestimate CTS in SSc patients, where nerve dysfunction may occur without significant changes in CSA. This may explain the relatively limited diagnostic performance observed in our study. While maxCSA may still be useful as a supportive or triage tool, its diagnostic value appears limited when used in isolation in this specific population.

Pathophysiologically, SSc provides several other plausible substrates for MN compression, apart from microvascular dysfunction and chronic ischemia, namely tissue edema, and progressive fibrosis, which may increase intracarpal tunnel pressure, while peri-tendinous inflammation or tendon friction phenomena could further compromise nerve gliding and nerve perfusion. However, an important observation in the present study is that, when examined in multivariable clustered models, the most consistent independent correlates of NCS-defined CTS were not global SSc phenotype markers, but rather traditional CTS risk factors and occupational/behavioral proxies. Specifically, AHT and smoking showed the most stable positive associations with NCS-defined CTS after adjustment. These findings, which confirm recent published results in other populations [36, 37], can be interpreted in two complementary ways. First, they may reflect the contribution of general cardiometabolic and vascular factors to MN vulnerability, which are highly relevant in a disease already characterized by endothelial dysfunction and impaired microcirculation. Second, they may capture broader comorbidity clustering that accompanies age and long-term disease, acting as pragmatic markers of higher baseline risk. Clinically, the smoking association is particularly actionable given its established vascular effects and its plausibility as a contributor to nerve ischemia and impaired tissue repair in SSc. Occupational exposures behaved as expected in univariate screening and in exposure-focused models, with vibration exposure [38] and forceful/repetitive work [39] patterns tending toward higher CTS odds. Attenuation in the fully combined model is not unexpected, given collinearity among exposure variables and their shared variance with broader occupational profiles. This pattern suggests that in SSc patients, occupational risk should ideally be captured with either a composite “manual exposure” indicator or more granular intensity measures, rather than multiple overlapping binary variables that may compete for the same explanatory signal. The inverse association observed for “computer work”, which was also observed meta-analytically [40], warrants careful interpretation. Rather than implying a protective effect of computer use, this variable most plausibly functions as a proxy for a lower-strain occupational profile relative to vibration- and force-associated work, and/or for healthy-worker effects (patients with more severe hand disability or established CTS being less likely to remain in active employment). Socioeconomic confounding (education, urban residence, work status) and potential misclassification of what constitutes “computer work” may further contribute. Accordingly, this association should be framed as an indicator of occupational profile differences and residual confounding rather than a biologically protective exposure.

The absence of independent associations between NCS-defined CTS and global SSc phenotype variables suggests that CTS in SSc does not simply track with macro-level disease severity. This may reflect a true dissociation between global skin/vascular phenotype and local compressive neuropathy, or it may be influenced by limited power and reduced sample size in complete-case phenotype models. It also raises the possibility that more local hand-level SSc features may be more directly relevant CTS determinants, such as peri-tendinous fibrosis, structural nerve changes, calcinosis near the tunnel, and flexor tenosynovitis.

In SSc, peripheral nerve dysfunction may be multifactorial, and NCS abnormalities detected in the MN can reflect not only focal compression but also concomitant entrapment at other sites or broader neuropathic involvement. In our study sample, ulnar NCS demonstrated ulnar neuropathy at Guyon’s canal in a subset of hands, with several patients showing concurrent CTS and ulnar involvement. This supports the concept that multifocal entrapment neuropathy may occur in SSc and can contribute to overlapping or nonspecific hand symptoms. Clinically, these findings reinforce the value of objective neurophysiologic testing in SSc patients with hand complaints to avoid misattribution of symptoms and to guide targeted management.

The finding that a substantial subset of CTS cases was asymptomatic yet NCS-positive underscores the potential for clinical under-recognition in SSc, where symptom attribution is complex and mild electrophysiologic CTS may be silent.

Diagnostic performance of ultrasound versus NCS

In this study population, ultrasound assessment of the MN using maxCSA demonstrated moderate overall discrimination for NCS-defined CTS, but limited concordance with NCS when operationalized using fixed maxCSA thresholds. Across commonly used cutoffs, specificity increased as thresholds rose, yet sensitivity declined substantially, resulting in only fair agreement with NCS at > 10 and > 11 mm² and weaker agreement at > 12 mm². This pattern indicates that, in SSc, a threshold-based ultrasound definition of CTS functions better as a rule-in tool than as a stand-alone screening test: a positive result supports CTS, but a negative ultrasound does not reliably exclude NCS-confirmed disease. A key clinical observation is that ultrasound positivity increased with NCS severity stage, consistent with the expectation that more advanced CTS produces more marked structural nerve enlargement. Despite this tendency, several stages contained small numbers of observations, therefore, stage-specific differences should be interpreted cautiously and are best considered hypothesis-generating. Moreover, sensitivity remained only moderate even at intermediate severity, suggesting that in SSc a meaningful proportion of electrophysiologic CTS may occur without sufficiently large maxCSA changes to surpass standard thresholds. This has practical consequences in SSc, where sensory symptoms may be nonspecific and where missing CTS can delay targeted management; it supports retaining NCS for cases in which diagnostic certainty or severity staging is required. The modest performance of alternative ultrasound metrics reinforces the primacy of maxCSA as the single most informative measurement in this dataset. Importantly, these additional parameters did not surpass maxCSA and are therefore unlikely to provide substantial incremental value in routine practice without external validation. Thus, the data support a pragmatic ultrasound strategy in SSc: MN maxCSA remains the most useful sonographic marker, best applied as an adjunct test to increase confidence when positive, while acknowledging that ultrasound alone cannot replace NCS when the clinical aim is to exclude CTS or to characterize severity. The limited incremental value of several adjunct ultrasound parameters beyond maxCSA suggests that imaging markers validated in idiopathic CTS cannot be assumed to generalize to SSc, underscoring the importance of disease-context validation and the potential need for alternative metrics (e.g., composite models or stiffness-based approaches) in future studies.

Given the moderate discrimination of maxCSA and the limited sensitivity of threshold-based definitions in SSc, ultrasound should be interpreted as an adjunctive test rather than a substitute for electrophysiology. In practical terms, US may reasonably prioritize or expedite management in a narrow subset of patients with high clinical suspicion and clearly abnormal CSA (e.g., markedly enlarged MN at the tunnel) where the pretest probability is already high and clinical-sonographic concordance is strong, particularly in settings where NCS access is limited. However, NCS remains necessary when the aim is to exclude CTS, to stage severity, to evaluate mild or asymptomatic cases, when ultrasound is normal or borderline despite symptoms, when clinical and ultrasound findings are discordant, or when alternative neuropathic processes (including multifocal entrapment or generalized neuropathy) must be considered.

Limitation and further research

This study has several limitations that should be considered when interpreting the findings. Firstly, the cross-sectional design limits causal inference, and the sample may be affected by referral/selection bias, so prevalence estimates should be interpreted in that context. Some exposure variables relied on self-report and may not capture intensity or duration, increasing the risk of residual confounding and collinearity. Several partially overlapping multivariable GEE models were evaluated to address different predictor domains. Given the limited number of CTS-positive hands and correlated exposures, some effect estimates may be unstable and should be interpreted cautiously. Finally, small numbers in certain subgroups (e.g., males and sine scleroderma) may limit precision and generalizability. Future work should validate these findings in independent study populations, and incorporate more granular occupational metrics and local hand pathology (e.g., tenosynovitis, calcinosis). Although local wrist pathology was assessed qualitatively on ultrasound, we did not apply a standardized grading system for the severity and proximity of tenosynovitis/calcinosis to the carpal tunnel, and tendon friction rubs were not systematically quantified; therefore, residual confounding by local musculoskeletal contributors to MN dysfunction cannot be excluded. The addition of elastography assessment may further improve the sensitivity of ultrasound evaluation, and future studies should investigate whether, under these conditions, ultrasonography could potentially replace NCS.

Conclusions

NCS-defined CTS was present in 34.1% of evaluated hands, corresponding to 44.0% of patients with CTS in at least one hand, higher than other reported populations. The most consistent independent correlates of NCS-defined CTS in SSc were traditional CTS risk factors and occupational/behavioral proxies, not SSc-specific disease phenotype. Ultrasound MN maxCSA shows moderate discrimination and limited concordance for NCS-defined CTS in SSc, but its threshold-based diagnostic performance is limited by low sensitivity, with an optimal cutoff of 10 mm². This would suggest that in SSc, ultrasound maxCSA is useful as a supportive/triage tool and can help confirm CTS when positive, especially with higher maxCSA cutoffs, but it should not replace NCS when the aim is to exclude CTS or to assess severity.

Supplementary Information

Below is the link to the electronic supplementary material.

Abbreviations

AHT

Arterial hypertension

AUC

Area under the curve

BMI

Body mass index

CI

Confidence interval

CMAP

Compound muscle action potentials

CSA

Cross-sectional area

CTS

Carpal tunnel syndrome

EULAR

European Alliance of Associations for Rheumatology

GEE

Generalized estimating equation

LR

Likelihood ratios

MN

Median nerve

NCS

Nerve conduction studies

NPV

Negative predictive values

OR

Odds ratios

PD

Power Doppler

PPV

Positive predictive values

QIC

Quasi-likelihood information criterion

ROC

Receiver operating characteristic

SNAP

Sensory nerve action potentials

Se

Sensitivity

Sp

Specificity

SSc

Systemic sclerosis

Author contributions

Conceptualization, D.N.P., M.I.P., L.E. and C.C.; methodology, D.N.P. and C.C.P.; software, C.C.P.; formal analysis, C.C.P.; investigation, D.N.P., D.A., A.D. I.A.C., A.R., M.A.E.; resources, M.I.P. and D.N.P; writing of original draft, D.N.P. and C.C.P.; review and editing of draft, D.N.P., C.C.P., O.M., D.A., A.D., I.A.C., A.R., M.I.P., M.A.E., L.E. and C.C; supervision, L.E., C.C., M.I.P.; project administration, D.N.P. All authors have read and agreed to the published version of the manuscript.

Funding

This research received no external funding.

Data availability

The datasets used during the current study are available from the corresponding author on reasonable request.

Declarations

Ethics approval and consent to participate

The study was conducted in accordance with the Helsinki Declaration and was approved by the local ethics committee (number 2/January 19th, 2023). All patients signed informed consent before any study procedure.

Consent for publication

Not applicable.

Competing interests

The authors declare no competing interests.