Na+ deposition in the fibrotic skin of systemic sclerosis patients detected by 23Na-magnetic resonance imaging

Abstract

Objective: Skin fibrosis is the predominant feature of SSc and arises from excessive extracellular matrix deposition. Glycosaminoglycans are macromolecules of the extracellular matrix, which facilitate Na + accumulation in the skin. We used 23 Na-MRI to quantify Na + in skin. We hypothesized that skin Na + might accumulate in SSc and might be a biomarker for skin fibrosis.

Methods: In this observational case-control study, skin Na + was determined by 23 Na-MRI using a Na + volume coil in 12 patients with diffuse cutaneous SSc and in 21 control subjects. We assessed skin fibrosis by the modified Rodnan skin score prior to 23 Na-MRI and on follow-up 12 months later.

Results: 23 Na-MRI demonstrated increased Na + in the fibrotic skin of SSc patients compared with skin from controls [mean ( s . d .): 27.2 (5.6) vs 21.4 (5.3) mmol/l, P < 0.01]. Na + content was higher in fibrotic than in non-fibrotic SSc skin [26.2 (4.8) vs 19.2 (3.4) mmol/l, P < 0.01]. Furthermore, skin Na + amount was correlated with changes in follow-up modified Rodnan skin score (R 2 = 0.68).

Conclusions: 23 Na-MRI detected increased Na + in the fibrotic SSc skin; high Na + content was associated with progressive skin disease. Our findings provide the first evidence that 23 Na-MRI might be a promising tool to assess skin Na + and thereby predict progression of skin fibrosis in SSc.

Keywords: 23Na-MRI; extracellular matrix; fibrosis; skin Na+; systemic sclerosis.

Fig. 1

²³Na-MRI detects increased Na⁺ in fibrotic SSc skin and discriminates between affected and non-affected skin (A–C) Skin Na⁺ (A) and water content (B) of SSc patients (n = 12) and age-matched controls (n = 21) quantified by ²³Na-MRI and ¹H-MRI. (C) Representative²³Na-MRI detects increased Na⁺ in fibrotic SSc skin and discriminates between affected and non-affected skin. ²³Na- and ¹H-magnetic resonance images of healthy (left) and fibrotic skin (right). Calibration tubes are placed below the forearm. Arrows indicate the site of measurement. (D) Skin Na⁺ content in fibrotic forearm vs non-involved lower leg in the same patients (n = 11). (E) Skin Na⁺ content of non-affected SSc skin vs healthy control patients (both lower leg). (F) Representative ²³Na-magnetic resonance images of the forearm vs lower leg of an SSc patient.

Fig. 2

Skin Na⁺ correlates with change of the modified Rodnan skin score and EULAR Scleroderma Trials and Research Disease Activity Score (A) The mRSS was assessed at the time of ²³Na-MRI and 12 months later at a follow-up visit in 11 out of 12 patients. The initial mRSS was substracted from the follow-up mRSS (ΔmRSS) to describe the course of the fibrotic skin disease. (B) The EUSTAR DAS was determined at the first visit together with ²³Na-MRI in all SSc patients. The amount of Na⁺ in the forearm skin assessed by ²³Na-MRI was positively correlated with the EUSTAR DAS. EUSTAR: EULAR Scleroderma Trials and Research; mRSS: modified Rodnan skin score.