Validation of the suction device Nimble for the assessment of skin fibrosis in systemic sclerosis

Abstract

Objectives: Skin fibrosis is a main hallmark of systemic sclerosis (SSc). Clinical assessment is done semi-quantitatively using the modified Rodnan skin score (mRSS). Objective measurements for quantifying skin fibrosis could complement the mRSS to achieve higher reproducibility. The aim of this study was to explore the potential of suction measurements to detect structural changes in the skin that are associated with skin fibrosis.

Methods: This clinical trial included 30 SSc patients and 30 healthy volunteers (HC). We validated a novel suction device-the Nimble-to quantify skin stiffness in comparison to the Cutometer using the OMERACT filter.

Results: A significant difference (p < 0.05) between the skin stiffness of HC and SSc patient groups was found for each location measured. The correlation between the measurements of forearm skin stiffness and the mRSS values was high for the Nimble (r = 0.82) and moderate for the Cutometer (r = 0.58). A ROC analysis showed good ability for the Nimble to distinguish between SSc patients with and without skin involvement (AUC = 0.82). Both suction devices provided excellent reliability in all measurements on HC and SSc patients and proved face validity and feasibility.

Conclusion: Suction devices assessing skin stiffness, such as the Nimble, show clear potential to objectively quantify skin fibrosis in SSc patients and might be promising outcome measures complementing established methods such as the mRSS.

Trial registration: Clinicaltrials.gov, NCT03644225, Registered 23 August 2018-Retrospectively registered, http://www.clinicaltrials.gov.

Keywords: Skin fibrosis; Skin stiffness; Suction measurement; Systemic sclerosis.

Fig. 1

Schemes of the working principles of the Nimble (a) and Cutometer (b) suction devices. The Nimble operates in a displacement-controlled fashion, with negative pressure drawing the skin into the probe opening until it reaches a defined height (h). The outcome measure is the pressure (p_cl) needed for the specific tissue elevation. The Cutometer operates in a load-controlled fashion, with negative pressure drawing the skin into the probe opening until a maximum pressure is reached. The outcome measure is the elevation corresponding to a specific suction load. We extracted the maximum elevation (R0 in mm) for our study

Fig. 2

a Finite element (FE) simulation of suction experiment using a neo-Hookean material model with Young’s modulus E. The 2D cross-sectional geometry is depicted. b Estimated k^Nimble and k^R0 for two materials, M1 and M2, with FE analysis (FE stiffness) and mean (n = 3) of k^Nimble and k^R0 (experimental stiffness). The dotted line indicates the linear relationship between k^Nimble or k^R0 and the Young’s modulus of the material

Fig. 3

Mean and SEM for HC (white) and SSc (gray) measured with the Nimble (a) and the Cutometer (b) for the four body locations, n = 30 for each group. For all locations and both devices, significant differences were found with a paired t-test (p < 0.0)

Fig. 4

Skin stiffness score of suction measurements correlated with mRSS values of SSc patients. a Correlation of kSS^Nimble with mRSS⁴_total of the four measured locations. The first group includes the kSS^Nimble for the HC group, the second the kSS^Nimble for the SSc patients with total mRSS⁴_total = 0 and the following grouped in mRSS ranges of: 1 ≤ mRSS⁴_total ≤ 3, 4 ≤ mRSS⁴_total ≤ 6, 7 ≤ mRSS⁴_total ≤ 9 and 10 ≤ mRSS⁴_total ≤ 12. b Correlation of kSS^R0 with mRSS⁴_total of the four measured locations

Fig. 5

a Skin stiffness score (kSS) of Nimble measurements grouped into SSc patients with mRSS⁴_total = 0 and mRSS⁴_total > 0. b Skin stiffness score (kSS) of Cutometer measurements grouped into SSc patients with mRSS⁴_total = 0 and mRSS⁴_total > 0. c Receiver operating characteristic (ROC) curve tests for sensitivity and specificity of suction measures. Nimble measurements showed a larger area under the ROC curve (AUC) compared to Cutometer measurements, indicating a better ability to distinguish between SSc patients with a total mRSS⁴_total = 0 and SSc patients with a total mRSS⁴_total > 0. Cut-off values were evaluated by the Youden’s index, indicated in red