# Hand function impairment in Systemic Sclerosis: determinants through investigations of clinical, radiographic and ultrasonographic features

Giulia Franchi, Elena Marazzi, Alain Lescoat, Sophie Hecquet, Sandrine

Carvès, Guillaume Coiffier, Marine Tas, Veronica Codullo, Carlomaurizio

Montecucco, Jérôme Avouac, et al.

► To cite this version:

Giulia Franchi, Elena Marazzi, Alain Lescoat, Sophie Hecquet, Sandrine Carvès, et al. Hand function impairment in Systemic Sclerosis: determinants through investigations of clinical, radiographic and ultrasonographic features. Seminars in Arthritis and Rheumatism, 2025, 76, pp.152901. 10.1016/j.searthrit.2025.152901. hal-05456405

HAL Id: hal-05456405

https://hal.science/hal-05456405v1

Submitted on 15 Jan 2026

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and impairment of hand function remains one of the most challenging aspects in the long-term management of the disease [2]. Despite advances in therapeutic approaches, approximately half of SSc patients experience a progressive decline in hand function over time [3].

Although previous studies have shown that cutaneous, vascular, and musculoskeletal involvement contribute to hand disability in SSc, several key aspects remain insufficiently explored, including the relative weight of these domains on patient-reported outcomes (PROs), the contribution of subclinical ultrasonographic (US) abnormalities—particularly tenosynovitis and sclerosing pattern—to patients’ perceived disability, and the lack of externally validated, real-world data linking US findings to PROs. Addressing these gaps, the present study aimed to investigate the impact of cutaneous, vascular, and MSK involvement on hand function by integrating clinical, radiographic, and US features in a real-life cohort of patients with SSc.

## Methods

### Patient populations and study design

We conducted an observational, cross-sectional, multi-center study including a discovery cohort (Paris and Pavia) and an external validation cohort (Rennes). For the discovery cohort, between November 2022 and June 2023, consecutive patients were prospectively enrolled among those attending the Day Hospital unit of the Rheumatology department at Hôpital Cochin in Paris and at Fondazione IRCCS Policlinico San Matteo in Pavia. No pre-selection of patients based on severity or imaging findings was applied. Secondarily, we used as an external validation cohort, patients consecutively admitted to the Day Hospital unit of the Internal Medicine department from Rennes CHU with in-depth joint investigations already published [4]. To be eligible for participation, patients from the two cohorts (i) needed to meet the 2013 ACR/EULAR classification criteria for SSc [5], (ii) be at least 18 years old, (iii) proficient in either French or Italian and (iv) capable of completing questionnaires. Patients meeting the classification criteria for rheumatoid arthritis (RA) [6] were excluded. Participation in the study did not influence treatment decisions, which followed international and national guidelines [7].

The study was conducted in compliance with the Helsinki Declaration and approved by CPP Ile de France in Paris (prot. n. 3. SC 2561), by Comitato Etico Territoriale Lombardia 6 in Pavia (prot. N 20,100,000,356), and by Comité d'éthique du CHU in Rennes (prot. n. 23.142 and 15.09). All patients signed an informed consent form.

### Clinical assessment

GF (Paris), EM (Pavia) and AL (Rennes) collected patients' clinical history through interviews and review of medical records. Concomitant immunosuppressive and vasoactive treatments were recorded (Supplementary Material). Clinical examination was performed, assessing the presence of skin fibrosis via modified Rodnan Skin Score (mRSS), puffy hands, digital ulcers (DUs), pitting scars, telangiectasias, calcinosis, flexion contractures (defined as a fixed bending of proximal and/or distal interphalangeal joints in at least one finger), and tendon friction rubs. Synovitis and tenosynovitis were recorded according to the presence of swollen and tender radiocarpal, radioulnar, metacarpal or interphalangeal joints or tendons.

### Ultrasonographic (US) and radiographic assessment

Ultrasonography of the fingers, hands, and wrists was performed in all patients to assess synovitis, tenosynovitis, and the presence of a sclerosing pattern [8]. Synovitis was evaluated using gray-scale (GS) and Power Doppler (PD) according to OMERACT definitions [9], while tenosynovitis was defined as hypoechoic or anechoic peritendinous fluid and/or tendon sheath thickening, with or without PD signal. A

"sclerosing pattern" was defined as tenosynovial thickening with increased echogenicity and reduced compressibility or tendon sliding, suggestive of fibrotic change, as previously described [8] (Fig. 1).

All US examinations were performed by operators with more than three years of experience in musculoskeletal ultrasonography (GF, EM, GC), using high-frequency linear probes on commercially available machines, following a shared protocol (Supplementary Material).

Hand and wrist radiographs were obtained in all patients to document joint space narrowing, erosions, acro-osteolysis, and calcinosis [10]. Radiographic assessments were performed by a single physician per center (GF, EM, MT). Examiners were partially aware of patients' clinical history as part of standard care; however, PROs were collected independently and were not available to the investigators at the time of image scoring.

### Patient-reported outcomes' measures

For the purposes of this study, PROs included the assessment of joint pain intensity, Raynaud's phenomenon (RP) activity, and patient global assessment (PtGA), each measured on a 0–10 numerical rating scale (NRS), as well as the scleroderma Health Assessment Questionnaire (sHAQ) [11]. Hand-specific activity limitation was assessed using two instruments: the Cochin Hand Function Scale (CHFS) and the HAnd scleroDerma lived Experience (HAnDE) scale. The CHFS was originally developed to evaluate hand function RA [12] and hand osteoarthritis [13,14], and its concurrent and construct validity have been extensively confirmed in SSc [15–19]. It measures patient-reported difficulty in performing daily hand-related activities, such as cooking, dressing, hygiene, and writing or typing. Each item is scored on a 0–5 Likert scale (0 = no difficulty, 5 = impossible), and the total score (range 0–90) reflects the overall degree of limitation. The HAnDE scale, developed in 2021, explores the lived experience of hand involvement in SSc across multiple domains, including functional, aesthetic, relational, existential, and emotional aspects, with scores ranging from 0 (no influence) to 64 (maximum impact) [20]. Although the patient acceptable symptom state (PASS) and the minimal clinically important difference (MCID)

<figure><img src="image_2.png" /><figcaption>**Fig. 1.** Schematic drawing (a) and ultrasonographic appearance (b) of tenosynovitis with sclerosing pattern. Adapted from Freire et al. Radiology 2013; 269(3):824–30.</figcaption></figure>
have been validated [21], no predefined thresholds exist for CHFS or HANDE to categorize disability levels. All the above-mentioned PROs were collected in the original cohort, while only CHFS and HAQ were collected in the Rennes cohort.

## Statistical analysis

All statistical analyses were conducted using statistical packages of Python v3.10.7. Categorical variables were reported as numbers and percentages. Continuous variables as mean ± SD for normal distributed data or median and interquartile range [IQR] for skewed data. Separate analyses were performed for the discovery and validation cohorts. Pooled analyses were limited to variables consistently collected across centres.

Pearson's or Spearman's correlation coefficients were adopted to explore the relationship between CHFS or HANDE scale and continuous variables as appropriate. Acceptable thresholds included Spearman's (rS) or Pearson's rho (r) ≥ 0.30 [22]. Mann-Whitney's, Kruskal-Wallis' and Welch's tests were adopted to explore the relationship between CHFS or HANDE score and categorical variables as appropriate. A p-value of <0.05 was considered statistically significant.

For the multivariate analysis, we carried out a multivariable linear regression with CHFS and HANDE scores as dependent variables.

To reduce the risk of overfitting given the moderate sample size, we performed an initial reduction of the candidate variable set by retaining variables showing univariate associations (p < 0.05) and variables considered clinically relevant based on prior literature. Variables with >10% missing data were excluded from the model. For variables with <10% missing data, multiple imputation by chained equations (MICE) was performed. These candidate covariates were then entered into a LASSO penalized regression to perform shrinkage and data-driven variable selection. Lambda was selected using 10-fold cross-validation optimizing mean squared error (MSE); specifically, we used the “one-standard-error” rule (largest lambda within one standard deviation of the minimum CV error) to favour parsimony.

## Results

The final set of variables retained by LASSO consisted of acro-osteolysis, calcinosis, pitting scars, mRSS at evaluation, US-detected tenosynovitis, US-detected tenosynovitis with PD, past and current Ilo-prost treatment.

### The Paris-Pavia discovery cohort

#### Study population

A total of 73 eligible SSc patients were consecutively included (59 women, 14 men). The mean ± SD age was 60.6 ± 12.5 years and the mean ± SD disease duration was 9.6 ± 7.1 years. Patients' characteristics are shown in Table 1.

#### Hand disability and PROs

Median (IQR) values were as follows: PtGA 4 (3.0–5.5), RP NRS 5 (2.0–7.0), CHFS 6 (1.5–20.5), HANDE 23.5 (10.5–35.25), and sHAQ 0.75 (0.33–1.11). sHAQ, CHFS, and HANDE provided consistent and concordant descriptions of hand disability in our cohort. In univariate analysis, HANDE scores showed a statistically significant association with all other PROs (p < 0.01). Similar results were observed for CHFS scores, which correlated significantly with all PROs (p < 0.01), except for the RP NRS. A correlation was also found between CHFS and HANDE (r = 0.61, p < 0.001), with higher scores in one scale corresponding to higher scores in the other (Table 2). No association emerged between PRO scores and clinical characteristics such as age and disease duration (Table 3a).

<table><caption>**Table 1**

Characteristics of the study population.</caption><thead><tr><th></th><th>Discovery cohort<br>n = 73)</th><th>Validation cohort<br>(n = 67)</th></tr></thead><tbody><tr><td>Women, n, %</td><td>59 (81)</td><td>47 (70)</td></tr><tr><td>Never smoker, n, %</td><td>49 (67)</td><td>35 (52)</td></tr><tr><td>Active smoker, n, %</td><td>7 (9.6)</td><td>17 (25)</td></tr><tr><td>Former smoker, n, %</td><td>17 (23)</td><td>15 (22)</td></tr><tr><td>Age at evaluation, years, mean (SD)</td><td>60.58 (12.51)</td><td>57.5 (12.4)</td></tr><tr><td>Disease duration, years, mean (SD)</td><td>9.59 (7.13)</td><td>11.4 (11.1)</td></tr><tr><td>Laboratory</td><td></td><td></td></tr><tr><td>Anti-centromere, n, %</td><td>24 (33)</td><td>27 (40)</td></tr><tr><td>Anti-Scl70, n, %</td><td>34 (47)</td><td>23 (34)</td></tr><tr><td>Anti-RNA polymerase III, n, %</td><td>4 (5)</td><td>4 (6)</td></tr><tr><td>Cutaneous domain</td><td></td><td></td></tr><tr><td>lcSSc, n, %</td><td>36 (49)</td><td>34 (51)</td></tr><tr><td>dcSSc, n, %</td><td>22 (30)</td><td>29 (43)</td></tr><tr><td>sine scleroderma, n, %</td><td>15 (21)</td><td>4 (6)</td></tr><tr><td>mRSS at evaluation, median [IQR]</td><td>4 [1; 9]</td><td>7 [3; 13]</td></tr><tr><td>Vascular domain</td><td></td><td></td></tr><tr><td>puffy hands, n, %</td><td>25 (34)</td><td>20 (30)</td></tr><tr><td>past DUs, n, %</td><td>37 (51)</td><td>36 (54)</td></tr><tr><td>current DUs, n, %</td><td>5 (6.8)</td><td>12 (18)</td></tr><tr><td>pitting scars, n, %</td><td>34 (47)</td><td>37 (55)</td></tr><tr><td>telangiectasias, n, %</td><td>44 (60)</td><td>48 (72)</td></tr><tr><td>clinically detected calcinosis, n, %</td><td>19 (26)</td><td>26 (41)</td></tr><tr><td>acro-osteolysis, n, %</td><td>22 (30)</td><td>20 (31)</td></tr><tr><td>Musculoskeletal domain</td><td></td><td></td></tr><tr><td>history of arthralgia/arthritis, n, %</td><td>40 (65)</td><td>18 (27)</td></tr><tr><td>TJC ≥ 1, n, %</td><td>6 (8)</td><td>na</td></tr><tr><td>SJC ≥ 1, n, %</td><td>4 (5)</td><td>na</td></tr><tr><td>tendon friction rubs, n, %</td><td>2 (2.7)</td><td>na</td></tr><tr><td>flexion contractures, n, %</td><td>19 (26)</td><td>na</td></tr><tr><td>PROs</td><td></td><td></td></tr><tr><td>CHFS, median [IQR]</td><td>6.00 [1.50; 20.5]</td><td>10 [2.5;24.5]</td></tr><tr><td>HANDE, median [IQR]</td><td>23.5 [10.5; 35.2]</td><td>na</td></tr><tr><td>sHAQ, median [IQR]</td><td>0.75 [0.33; 1.11]</td><td>na</td></tr><tr><td>PtGA, median [IQR]</td><td>4.00 [3.00; 5.50]</td><td>na</td></tr><tr><td>RP NRS, median [IQR]</td><td>5.00 [2.00; 7.00]</td><td>na</td></tr></tbody></table>

SD: standard deviation; lcSSc: limited cutaneous systemic sclerosis; dcSSc: diffuse cutaneous systemic sclerosis;

mRSS: modified Rodnan Skin Score; IQR: interquartile range; DUs: digital ulcers; TJC: tender joint count; SJC: swollen joint count;

CHFS: Cochin Hand Function Scale; HANDE: HAnd scleroDerma lived Experience; sHAQ: systemic sclerosis Health Assessment Questionnaire; PtGA: patient global assessment; NRS: numeric rating scale; RP: Raynaud's phenomenon.

<table><caption>**Table 2**

Univariate analysis between PROs in the discovery cohort.</caption><thead><tr><th>PRO</th><th>median [IQR]</th><th>CHFS<br>r</th><th>CHFS<br>p-value</th><th>HANDE<br>r</th><th>HANDE<br>p-value</th></tr></thead><tbody><tr><td>CHFS</td><td>6.00 [1.50; 20.5]</td><td>-</td><td>-</td><td>0.61</td><td><strong>&lt;0.001</strong></td></tr><tr><td>HANDE</td><td>23.5 [10.5; 35.2]</td><td>0.61</td><td><strong>&lt;0.001</strong></td><td>-</td><td>-</td></tr><tr><td>sHAQ</td><td>0.75 [0.33; 1.11]</td><td>0.667</td><td><strong>&lt;0.001</strong></td><td>0.52</td><td><strong>&lt;0.001</strong></td></tr><tr><td>PtGA</td><td>4.00 [3.00; 5.50]</td><td>0.38</td><td><strong>&lt;0.01</strong></td><td>0.67</td><td><strong>&lt;0.001</strong></td></tr><tr><td>RP NRS</td><td>5.00 [2.00; 7.00]</td><td>0.06</td><td>0.69</td><td>0.37</td><td><strong>0.01</strong></td></tr></tbody></table>

SD: standard deviation; IQR: interquartile range; CHFS: Cochin hand function scale;

HANDE: HAnd scleroDerma lived Experience; sHAQ: systemic sclerosis Health Assessment Questionnaire;

PtGA: patient global assessment; NRS: numeric rating scale; RP: Raynaud's phenomenon.

#### Cutaneous involvement and PROs

In the discovery cohort, 36 patients (49%) had lcSSc, 22 (30%) had dcSSc, and 15 (21%) were sine scleroderma. The median mRSS was 7/51 at diagnosis and 4/51 at the time of evaluation. Both CHFS and HANDE scores showed significant correlation with mRSS at the time of evaluation in univariate analysis (rS = 0.34, p < 0.01; rS = 0.50, p < 0.001, respectively), whereas CHFS scores lost significance in multivariate analysis (p = 0.054). No association was observed between
<caption>**Table 3a**</caption>

Univariate analysis between continuous variables and PROs score in the discovery cohort.

<table><thead><tr><th></th><th>mean (SD) or<br>median [IQR]</th><th>CHFS<br>r</th><th>CHFS<br>p-value</th><th>HAnDE<br>r</th><th>HAnDE<br>p-value</th></tr></thead><tbody><tr><td>mRSS at<br>diagnosis</td><td>7 [0; 14]</td><td>0.20</td><td>0.11</td><td>0.22</td><td>0.08</td></tr><tr><td>mRSS at<br>evaluation</td><td>4 [1; 9]</td><td>0.34</td><td>&lt;0.01</td><td>0.50</td><td>&lt;0.001</td></tr><tr><td>Age at<br>evaluation,<br>years</td><td>60.58 (12.51)</td><td>-0.002</td><td>0.98</td><td>-0.13</td><td>0.31</td></tr><tr><td>Disease duration,<br>years</td><td>9.59 (7.13)</td><td>-0.06</td><td>0.61</td><td>-0.08</td><td>0.5</td></tr></tbody></table>

SD: standard deviation; IQR: interquartile range; CHFS: Cochin Hand Function Scale;

HAnDE: HAnd scleroDerma lived Experience; mRSS: modified Rodnan Skin Score.

either score and the pattern of skin fibrosis (limited vs diffuse) (Tables 3a and 3b).

### Vascular involvement and PROs

In univariate analysis, CHFS scores differed significantly according to the presence of telangiectasias (p = 0.01) and clinically detected calcinosis (p < 0.01), while HAnDE scores were associated with pitting scars (p = 0.01), clinically detected calcinosis (p = 0.05), acro-osteolysis (p = 0.02), and current (p < 0.01) or past Iloprost treatment (p = 0.01) (Tables 3a and 3b). Multivariate analysis confirmed that CHFS scores remained significantly associated with clinically detected calcinosis (p = 0.01), whereas HAnDE scores were significantly associated with acro-osteolysis (p = 0.01) and current (p < 0.01) or past Iloprost treatment

(p < 0.01) (Table 4). No associations were observed with current or past DUs.

### MSK involvement and PROs

Sixty-five percent of patients reported arthralgias or arthritis, with 8 % showing ≥1 tender joint and 5 % ≥1 swollen joint. Tendon friction

<caption>**Table 4**</caption>

Association of CHFS and HAnDE scores with clinical, radiographic and ultra-sonographic features in multivariate analysis in the discovery cohort.

<table><thead><tr><th></th><th>CHFS<br>regression<br>coefficient (95 %<br>CI)</th><th>CHFS<br>p</th><th>HAnDE<br>regression<br>coefficient (95 %<br>CI)</th><th>HAnDE<br>p</th></tr></thead><tbody><tr><td>Acro-osteolysis</td><td>-1.81 [-11.4; 6.20]</td><td>0.6</td><td>7.63 [1.76; 13.5]</td><td><strong>0.01</strong></td></tr><tr><td>Calcinosis</td><td>10.2 [1.44; 19.4]</td><td><strong>0.01</strong></td><td>1.43 [-5.49; 8.35]</td><td>0.68</td></tr><tr><td>Pitting scars</td><td>3.04 [-5.63; 11.6]</td><td>0.44</td><td>5.69 [-2.93; 14.3]</td><td>0.19</td></tr><tr><td>mRSS at evaluation</td><td>0.50 [-0.48; 0.94]</td><td>0.054</td><td>1.65 [-8.25; 11.6]</td><td>0.74</td></tr><tr><td>US-detected<br>tenosynovitis</td><td>4.48 [-5.36; 9.33]</td><td><strong>0.04</strong></td><td>2.13 [-2.37; 6.63]</td><td>0.35</td></tr><tr><td>US-detected<br>tenosynovitis with<br>PD</td><td>17.6 [4.18; 45.2]</td><td><strong>0.02</strong></td><td>26.6 [11.0; 42.2]</td><td>&lt;0.01</td></tr><tr><td>Past Iloprost<br>treatment</td><td>-0.447 [-10.2; 11.0]</td><td>0.93</td><td>8.33 [2.76; 13.9]</td><td>&lt;0.01</td></tr><tr><td>Current Iloprost<br>treatment</td><td>9.47 [-0.912; 19.5]</td><td>0.07</td><td>8.18 [2.17; 14.2]</td><td>&lt;0.01</td></tr></tbody></table>

The regression (or correlation) coefficient indicates the average change in PRO scores associated with the variable.

mRSS: modified Rodnan skin score; US: ultrasound; PD: Power Doppler; CHFS: Cochin Hand Function Scale; HAnDE: HAnd scleroDerma lived Experience Scale.

<caption>**Table 3b**</caption>

Univariate analysis between categorical variables and PROs in the discovery cohort.

<table><thead><tr><th></th><th>n (%) of<br>patients w/</th><th>CHFS median [IQR] in<br>patients w/</th><th>CHFS median [IQR] in<br>patients w/o</th><th>p</th><th>HAnDE median [IQR]<br>in patients w/</th><th>HAnDE median [IQR] in<br>patients w/o</th><th>p</th></tr></thead><tbody><tr><td>Clinical cutaneous features</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>lcSSc</td><td>36 (49)</td><td>6.00 [1.75 - 23.2]</td><td>6.00 [1.50 - 19.0]</td><td>0.72</td><td>24.0 [10.0 - 34.0]</td><td>23.0 [11.0 - 36.0]</td><td>0.91</td></tr><tr><td>dcSSc</td><td>22 (30)</td><td>13.0 [6.00 - 18.0]</td><td>5.00 [1.00 - 22.5]</td><td>0.30</td><td>26.5 [17.8 - 40.5]</td><td>21.5 [6.00 - 32.2]</td><td>0.07</td></tr><tr><td>sine scleroderma</td><td>15 (21)</td><td>1.50 [0.00 - 20.0]</td><td>7.00 [3.00 - 20.0]</td><td>0.10</td><td>6.00 [3.00 - 24.0]</td><td>24.0 [12.0 - 36.5]</td><td>0.08</td></tr><tr><td>Clinical vascular features</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>puffy hands</td><td>25 (34)</td><td>6.00 [2.00 - 23.0]</td><td>6.00 [1.25 - 19.5]</td><td>0.61</td><td>24.0 [12.0 - 36.0]</td><td>23.0 [10.0 - 32.0]</td><td>0.44</td></tr><tr><td>past DUs</td><td>37 (51)</td><td>6.00 [3.00 - 18.0]</td><td>8.00 [0.25 - 22.5]</td><td>0.66</td><td>24.0 [19.8 - 37.5]</td><td>18.5 [5.50 - 32.0]</td><td>0.07</td></tr><tr><td>current DUs</td><td>5 (6.8)</td><td>6.00 [2.00 - 13.0]</td><td>6.00 [1.25 - 21.0]</td><td>0.52</td><td>29.0 [23.0 - 40.0]</td><td>23.0 [9.00 - 34.0]</td><td>0.30</td></tr><tr><td>pitting scars</td><td>34 (47)</td><td>10.0 [4.25 - 22.2]</td><td>4.00 [0.00 - 20.0]</td><td>0.10</td><td>27.0 [20.0 - 40.0]</td><td>19.0 [6.00 - 27.5]</td><td><strong>0.01</strong></td></tr><tr><td>telangiectasias</td><td>44 (60)</td><td>14.0 [4.00 - 22.0]</td><td>2.50 [0.00 - 11.0]</td><td><strong>0.01</strong></td><td>25.0 [15.8 - 37.5]</td><td>20.5 [5.75 - 27.2]</td><td>0.09</td></tr><tr><td>calcinosis</td><td>19 (26)</td><td>18.0 [5.50 - 27.5]</td><td>5.50 [0.75 - 18.5]</td><td><strong>&lt;0.01</strong></td><td>24.0 [21.0 - 41.0]</td><td>21.0 [6.00 - 31.0]</td><td><strong>0.05</strong></td></tr><tr><td>past Iloprost treatment</td><td>26 (36)</td><td>6.50 [2.25 - 18.0]</td><td>6.00 [1.00 - 21.0]</td><td>0.63</td><td>26.5 [21.2 - 39.8]</td><td>19.5 [6.00 - 31.0]</td><td><strong>0.01</strong></td></tr><tr><td>current Iloprost treatment</td><td>20 (27)</td><td>9.00 [3.75 - 23.5]</td><td>6.00 [1.00 - 20.0]</td><td>0.21</td><td>31.0 [21.8 - 42.0]</td><td>20.0 [6.00 - 31.0]</td><td>&lt;0.01</td></tr><tr><td>Clinical MSK features</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>history of arthralgia/arthritis</td><td>40 (65)</td><td>6.00 [2.00 - 20.0]</td><td>5.00 [0.00 - 19.2]</td><td>0.39</td><td>26.0 [6.75 - 35.8]</td><td>21.0 [14.5 - 24.0]</td><td>0.39</td></tr><tr><td>TJC ≥ 1</td><td>6 (8)</td><td>12.0 [5.25 - 19.5]</td><td>6.00 [1.00 - 21.0]</td><td>0.47</td><td>22.5 [6.75 - 38.2]</td><td>23.5 [11.2 - 32.8]</td><td>0.84</td></tr><tr><td>SJC ≥ 1</td><td>4 (5)</td><td>3.50 [1.00 - 17.0]</td><td>6.00 [2.00 - 20.5]</td><td>0.88</td><td>9.00 [7.50 - 20.8]</td><td>24.0 [11.8 - 35.2]</td><td>0.44</td></tr><tr><td>tendon friction rubs</td><td>2 (2.7)</td><td>22.0 [20.0 - 24.0]</td><td>6.00 [1.00 - 20.0]</td><td>0.17</td><td>42.0 [42.0 - 42.0]</td><td>23.0 [9.50 - 32.8]</td><td>0.056</td></tr><tr><td>flexion contractures</td><td>19 (26)</td><td>18.0 [8.50 - 23.0]</td><td>5.00 [0.00 - 18.5]</td><td><strong>&lt;0.01</strong></td><td>31.0 [23.5 - 42.0]</td><td>21.0 [6.00 - 31.0]</td><td><strong>0.01</strong></td></tr><tr><td>Radiographic features</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>acro-osteolysis</td><td>22 (30)</td><td>11.0 [4.00 - 23.0]</td><td>6.00 [0.25 - 20.0]</td><td>0.19</td><td>27.0 [23.0 - 40.0]</td><td>20.0 [6.00 - 31.0]</td><td><strong>0.02</strong></td></tr><tr><td>calcinosis</td><td>29 (40)</td><td>7.00 [3.00 - 23.0]</td><td>6.00 [1.00 - 20.0]</td><td>0.34</td><td>24.0 [12.0 - 39.0]</td><td>23.0 [9.00 - 31.0]</td><td>0.27</td></tr><tr><td>joint space narrowing</td><td>12 (16)</td><td>5.50 [1.00 - 18.2]</td><td>14.0 [3.00 - 21.0]</td><td>0.37</td><td>22.0 [6.00 - 31.2]</td><td>24.5 [11.8 - 39.0]</td><td>0.12</td></tr><tr><td>erosions</td><td>3 (4)</td><td>23.0 [18.0 - 29.5]</td><td>6.00 [1.00 - 20.0]</td><td>0.11</td><td>40.0 [26.0 - 42.0]</td><td>23.0 [9.00 - 33.0]</td><td>0.29</td></tr><tr><td>US features</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>synovitis ≥ 1</td><td>39 (53)</td><td>7.00 [3.00 - 20.0]</td><td>6.00 [0.50 - 21.5]</td><td>0.84</td><td>24.0 [11.2 - 35.8]</td><td>23.0 [6.00 - 29.0]</td><td>0.58</td></tr><tr><td>synovitis with PD ≥ 1</td><td>23 (31.5)</td><td>6.50 [2.25 - 17.8]</td><td>6.00 [1.00 - 21.5]</td><td>0.85</td><td>23.0 [9.50 - 31.8]</td><td>23.0 [11.0 - 35.0]</td><td>0.54</td></tr><tr><td>tenosynovitis ≥ 1</td><td>21 (29)</td><td>23.0 [15.0 - 38.5]</td><td>6.00 [1.00 - 19.5]</td><td><strong>0.03</strong></td><td>36.5 [23.2 - 45.2]</td><td>23.0 [9.00 - 32.5]</td><td><strong>0.04</strong></td></tr><tr><td>tenosynovitis with PD ≥ 1</td><td>4 (5)</td><td>26.0 [22.0 - 38.0]</td><td>6.00 [1.00 - 20.0]</td><td><strong>0.04</strong></td><td>42.0 [42.0 - 49.0]</td><td>23.0 [9.00 - 32.2]</td><td><strong>0.01</strong></td></tr><tr><td>tenosynovitis with sclerosing<br>pattern ≥ 1</td><td>18 (25)</td><td>20.0 [18.0 - 26.0]</td><td>6.00 [1.00 - 20.0]</td><td>0.20</td><td>31.0 [27.0 - 42.0]</td><td>23.0 [9.00 - 34.5]</td><td>0.36</td></tr></tbody></table>

CHFS: Cochin Hand Function Scale; IQR: interquartile range; HAnDE: HAnd scleroDerma lived Experience; lcSSc: limited cutaneous SSc; dcSSc: diffuse cutaneous SSc; DUs: digital ulcers; MSK: musculoskeletal; TJS: tender joints count; SJC: swollen joints count; US: ultrasound; PD: Power Doppler.
rubs were observed in 2 patients (2.7 %) and flexion contractures in 19 (26 %). Ultrasonography detected synovitis in 39 patients, compared to 10 on clinical examination, and tenosynovitis in 21 (29 %), including 5 % with a Power Doppler signal and 25 % with a sclerosing pattern. CHFS and HANDE scores were higher in patients with flexion contractures, but not in those with tender or swollen joints. US-detected tenosynovitis and peritendinous Doppler signal were associated with higher PRO scores in both univariate (Table 3b) and multivariate analyses (Table 4), whereas US-detected synovitis showed no association.

## The Rennes validation cohort

We validated our findings in an independent cohort from a third center, focusing on the variables found significant in the original cohort. A total of 67 eligible SSc patients were included (Table 1), according to the criteria described in the Methods section. CHFS scores correlated significantly with mRSS ($r = 0.46, p < 0.001$) and were significantly associated with US-detected tenosynovitis ($p = 0.05$), particularly the fibrosing form exhibiting a sclerosing pattern ($p = 0.05$) (Table 5).

## The pooled cohort

To assess the robustness of our findings, we analysed the pooled cohort of 140 patients - 73 from the discovery cohort and 67 from validation cohort. In both univariate and multivariate analyses (Table 5), CHFS scores remained significantly correlated with mRSS ($r = 0.36, p < 0.001$ for both) and with US-detected tenosynovitis ($p < 0.01$ for both). Trends were observed for tenosynovitis with a sclerosing pattern and calcinosis, reaching statistical significance in univariate analysis ($p = 0.01$ and 0.02, respectively) but not in multivariate analysis ($p = 0.06$ and 0.055, respectively).

## Discussion

Although hand involvement is a hallmark of SSc and a key element for its diagnosis and classification, impairment of hand function is often overlooked in clinical research.

Given that digital vascular disease contributes to pain and disability in SSc [23], clinically relevant vascular features were consistently collected across all cohorts (Table 1). In line with previous reports [24, 25], higher RP NRS scores were associated with both higher CHFS and HANDE scores, suggesting that RP affects not only hand function but also psychological well-being (explored by HANDE). The low prevalence of active DUs may explain the absence of a significant association with

hand disability, potentially reflecting the mitigating effect of sustained vasodilator therapy on the clinical impact of vascular disease in SSc [26–31]. Standardized functional vascular assessments could be addressed in future studies.

Calcinosis and acro-osteolysis, markers of digital vascular damage and severe systemic disease [32–36] were associated with higher CHFS and HANDE scores in univariate and multivariate analyses in the discovery cohort, with similar trends observed in the pooled cohort. However, causal relationships cannot be inferred from these cross-sectional data.

Skin involvement also contributes to hand disability [37], with mRSS consistently emerging as an independent correlate of impaired function across cohorts, despite relatively low median values. The lack of association between hand function and skin subset (limited vs diffuse SSc) likely reflects the long mean disease duration (~10 years), with most patients beyond the peak severity phase [38,39]. Both subsets affect the extremities and can lead to sclerodactyly, highlighting the importance of addressing hand function as a therapeutic target regardless of skin involvement.

MSK involvement affects a large proportion of SSc patients (46–97 %) [40–42] but is frequently underrecognized [8,43–45]. Ultrasonography is more sensitive than clinical examination for detecting synovitis and tenosynovitis [46]. Consistent with published data [47,48], in the discovery cohort, clinical examination identified synovitis or tenosynovitis in only 5.5 % of patients, whereas ultrasonography detected synovitis in 53 % and tenosynovitis in 29 % of patients.

To our knowledge, this is the first study to demonstrate an association between US-detected tenosynovitis and hand disability in SSc, as measured by PROs, particularly CHFS, and this was confirmed in both univariate and multivariate analyses across all cohorts.

Tenosynovitis may reflect active musculoskeletal inflammation potentially affecting tendon gliding and hand function, but it could also result from altered biomechanics in patients with flexion contractures. Larger and/or longitudinal studies are needed to clarify whether flexion contractures confound the relationship between US findings and PROs, and whether tenosynovitis represents a modifiable marker of disease activity or primarily a consequence of mechanical stress.

Given its non-invasive, safe, low-cost, and dynamic nature, ultrasonography may serve as a complementary tool for assessing MSK disease severity and activity [8] in SSc evaluation.

Our study has some limitations. The cross-sectional design allows only the identification of associations and precludes causal inference; the tertiary-care setting may limit generalizability; center effects were not modelled to preserve parsimony; reliance on validated PROs without

<caption>**Table 5**</caption>

Association of CHFS scores with clinical, radiographic and ultrasonographic features in univariate and multivariate analyses across all cohorts.

<table><thead><tr><th rowspan="2"></th><th rowspan="2">Cohort</th><th rowspan="2">CHFS<br>median [IQR]</th><th colspan="2">Univariate</th><th colspan="2">Multivariate</th></tr><tr><th>r</th><th>p</th><th>regression coefficient (95 % CI)</th><th>p</th></tr></thead><tbody><tr><td rowspan="3">mRSS at evaluation</td><td>Discovery</td><td>4 [1; 9]</td><td>0.34</td><td><strong>&lt;0.01</strong></td><td>0.50 [-0.48; 0.94]</td><td>0.054</td></tr><tr><td>Validation</td><td>7 [3; 13]</td><td>0.46</td><td><strong>&lt;0.001</strong></td><td>0.427 [-0.03; 0.87]</td><td><strong>0.03</strong></td></tr><tr><td>Pooled</td><td>5 [2; 10]</td><td>0.36</td><td><strong>&lt;0.001</strong></td><td>0.66 [0.08; 1.07]</td><td><strong>&lt;0.001</strong></td></tr><tr><td rowspan="3">Calcinosis</td><td>Discovery</td><td>19 (26)</td><td>-</td><td><strong>&lt;0.01</strong></td><td>10.2 [1.44; 19.4]</td><td><strong>0.01</strong></td></tr><tr><td>Validation</td><td>26 (41)</td><td>-</td><td>0.52</td><td>2.35 [-4.93; 9.97]</td><td>0.54</td></tr><tr><td>Pooled</td><td>45 (33)</td><td>-</td><td><strong>0.02</strong></td><td>4.98 [-1.08; 10.4]</td><td>0.055</td></tr><tr><td rowspan="3">US-detected tenosynovitis ≥ 1</td><td>Discovery</td><td>21 (29)</td><td>-</td><td><strong>0.03</strong></td><td>4.48 [-5.36; 9.33]</td><td><strong>0.04</strong></td></tr><tr><td>Validation</td><td>15 (22)</td><td>-</td><td><strong>0.05</strong></td><td>7.71 [0.42; 18.9]</td><td><strong>0.05</strong></td></tr><tr><td>Pooled</td><td>36 (25.7)</td><td>-</td><td><strong>&lt;0.01</strong></td><td>9.31 [2.24; 17.5]</td><td><strong>&lt;0.01</strong></td></tr><tr><td rowspan="3">US-detected tenosynovitis with PD ≥ 1</td><td>Discovery</td><td>4 (5)</td><td>-</td><td><strong>0.04</strong></td><td>17.6 [4.18; 45.2]</td><td><strong>0.02</strong></td></tr><tr><td>Validation</td><td>2 (3)</td><td>-</td><td>0.6</td><td>7.59 [0.72; 18.3]</td><td>0.06</td></tr><tr><td>Pooled</td><td>6 (4.3)</td><td>-</td><td>0.051</td><td>9.50 [-10.6; 28.8]</td><td>0.14</td></tr><tr><td rowspan="3">US-detected tenosynovitis with sclerosing pattern ≥1</td><td>Discovery</td><td>17 (23)</td><td>-</td><td>0.12</td><td>-8.98 [-31.2; 8.10]</td><td>0.2</td></tr><tr><td>Validation</td><td>15 (22)</td><td>-</td><td><strong>0.05</strong></td><td>7.71 [0.42; 18.9]</td><td><strong>0.05</strong></td></tr><tr><td>Pooled</td><td>32 (22.8)</td><td>-</td><td><strong>0.01</strong></td><td>6.64 [-0.60; 16.5]</td><td>0.06</td></tr></tbody></table>

The regression (or correlation) coefficient indicates the average change in PRO scores associated with the variable.

mRSS: modified Rodnan skin score; US: ultrasound; PD: Power Doppler; sclerosing pattern.
objective performance measures, potential treatment effects and unmeasured confounders (e.g. analgesic use, neuropathy, digital perfusion), limited power for less frequent features, and the absence of intra- and inter-observer reliability assessment represent additional limitations.

## Conclusion

Our study highlights the multifactorial origin of hand function impairment in SSc, with contributions primarily from cutaneous (skin fibrosis) and musculoskeletal (US-detected tenosynovitis) involvement. While the impact of cutaneous manifestations has been widely reported, our findings provide initial evidence of an association between US-detected MSK involvement and hand function impairment, as measured by PROs such as the CHFS.

Larger prospective studies are warranted to determine whether hand and wrist ultrasound at baseline and follow-up can improve understanding of hand involvement, guide therapeutic strategies, and be explored as an outcome measure in clinical trials.

Because SSc hand disability has a multifactorial origin, reversing its progression remains challenging, and identifying a single effective disease-modifying therapy - or combination of therapies - may be difficult.

In conclusion, a comprehensive assessment and management of cutaneous and MSK manifestations is important to support hand function and quality of life in patients with SSc.

## Funding

No specific funding was received from any funding bodies in the public, commercial or not-for-profit sectors to carry out the work described in this manuscript.

## Data availability

Original data will be sent upon reasonable request to the corresponding author.

## CRediT authorship contribution statement

**Giulia Franchi:** Conceptualization, Data curation, Formal analysis, Writing – original draft, Writing – review & editing. **Elena Marazzi:** Data curation, Investigation, Writing – original draft. **Alain Lescoat:** Conceptualization, Data curation, Investigation, Writing – original draft, Writing – review & editing. **Sophie Hecquet:** Conceptualization, Data curation. **Sandrine Carvès:** Conceptualization, Data curation. **Guillaume Coiffier:** Investigation, Resources. **Marine Tas:** Investigation, Resources. **Veronica Codullo:** Conceptualization, Supervision. **Carlomaurizio Montecucco:** Conceptualization, Supervision. **Jérôme Avouac:** Conceptualization, Supervision, Writing – original draft, Writing – review & editing. **Yannick Allanore:** Conceptualization, Supervision, Writing – original draft, Writing – review & editing.

## Declaration of competing interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

## Acknowledgements

The authors gratefully acknowledge all patients involved in this study.

## Supplementary materials

Supplementary material associated with this article can be found, in the online version, at doi:10.1016/j.semarthrit.2025.152901.

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