High-frequency ultrasound of the skin in systemic sclerosis: an exploratory study to examine correlation with disease activity and to define the minimally detectable difference

Abstract

Background: Thickened skin is a major clinical feature in patients with systemic sclerosis (SSc). We investigated changes of skin thickness in patients with SSc using both high frequency ultrasound (HFU) and the modified Rodnan skin score (mRSS) to evaluate the feasibility of application of HFU in skin involvement and the relationship between HFU and clinical profiles.

Methods: We recruited 31 consecutive patients with SSc and 31 age-matched and sex-matched healthy controls in this prospective, cross-sectional study. Skin thickness was measured by an 18-MHz ultrasonic probe at five different skin sites. Total skin thickness (TST) and skin thickness using categorical mRSS scores were recorded and compared to HFU. The European Scleroderma Trial and Research (EUSTAR) group Disease Activity Index (EUSTAR-DAI) and other clinical manifestations were assessed and analyzed.

Results: TST in patients with SSc was thicker than in healthy controls (P < 0.001), and correlated positively with total mRSS and the EUSTAR-DAI and correlated negatively with disease duration (P < 0.05). Patients with higher TST had higher EUSTAR-DAI, mRSS, C-reactive protein (CRP) and lower diffusing capacity of the lung for carbon monoxide (DLCO) (P < 0.05). Even in patients who on clinical assessment were assigned an mRSS that suggested the skin thickness was normal. This was also true to mRSS locally of 1 and 2 (P < 0.01). The area under the receiver operator characteristic (ROC) curve was 0.831 and yielded sensitivity of 77.4% and specificity of 87.1% at the predicted probability of 7.4 mm as the optimal cutoff point to access skin thickness.

Conclusions: In the study, HFU was able to measure skin thickness, it correlated quantitatively with a valid measure of SSc activity, and a minimal detectable difference was identified.

Keywords: Disease activity; High frequency ultrasound; Minimal detectable difference; Skin thickness; Systemic sclerosis.

Fig. 1

High-frequency ultrasound, 18-MHz echograms (vertical images) highlight the epidermis and dermis at the forearm in a healthy control and a patient with systemic sclerosis. The skin thickness was 1.3 mm (between the plus sign) in the control (a), and 2.0 mm (between the plus sign) in the patient (b)

Fig. 2

Total skin thickness (TST) evaluated by high-frequency ultrasound in patients with systemic sclerosis (SSc) and healthy controls (Ctrl) (SSc vs Ctrl, P < 0.001), and patients with diffuse SSc (dSSc) and patients with limited SSc (lSSc) (dSSc vs lSSc, P > 0.05)

Fig. 3

Local skin thickness evaluated by high-frequency ultrasound in patients with systemic sclerosis (SSc) and healthy controls (Ctrl) (SSc vs Ctrl, P < 0.05 for all, with the exclusion of the leg). Data are presented for different skin areas, showing the 25th and 75th percentiles of measures as boxes, the median (line within the box) and the minimum and maximum values (whiskers)

Fig. 4

Comparisons of total skin thickness (TST) evaluated by high-frequency ultrasound in healthy control and patients with systemic sclerosis (SSc) with scales of the modified Rodnan skin score (mRSS). Boxes represent the 25th and 75th percentile of measures, and the median (line within the box) and the minimum and maximum values (whiskers) are shown. TST with mRSS = 0, mRSS = 1 and mRSS = 2 in the patients were all significantly higher than in the controls (P = 0.0012, P <0.0001 and P < 0.0001, respectively). No significant difference was found between patients with mRSS = 3 and the controls (P = 0.0578)