High-resolution ultrasound of peripheral nerves in systemic sclerosis: a pilot study of computer-aided quantitative assessment of nerve density.

OBJECTIVES: To quantitatively evaluate and compare nerve density in patients with limited cutaneous systemic sclerosis (lcSSc) and control subjects using high-resolution ultrasound (US) with a computer-aided assessment. METHODS: Forty patients and 40 age- and sex-matched control subjects were prospectively enrolled. Ultrasound (US) examination (17-5 MHz probe) of the median nerve at the elbow was performed bilaterally by one radiologist. A software quantified the ratio between the hypoechoic and hyperechoic areas of peripheral nerves on ultrasound. Two observers set the threshold in the images acquired, and three observers performed the digital analysis of nerve density. Statistical analysis included Mann-Whitney U-test of patients versus control subjects and subgroup analysis of symptomatic and non-symptomatic patients. Intra and inter-observer agreement of the three observers were assessed with the kappa statistic. RESULTS: In all, 160 median nerves were evaluated. According to the US, nerve density was significantly reduced in lcSSc patients compared to control subjects (mean and standard deviation: 41 ± 3 vs 56 ± 4, p < 0.01). Subgroup analysis showed that symptomatic patients (n = 15) had reduced nerve density compared to non-symptomatic (n = 25) patients (39 ± 5 vs 43 ± 4, p < 0.01). Intra-observer agreement was very good (K = 0.82). Inter-observer agreements were good: reader 1 vs reader 2: k = 0.78 (95% confidence interval 0.65 to 0.91); reader 2 vs reader 3: k = 0.72 (95% confidence interval 0.65 to 0.82); reader 3 vs reader 1: k = 0.71 (95% confidence interval 0.64-0.81). CONCLUSIONS: In lcSSc patients, nerve density was reduced, especially in the symptomatic group, compared to control subjects.

Alteration of Th17 and Treg cell subpopulations co-exist in patients affected with systemic sclerosis.

Aim of the study has been to understand the relationship between TH17 and Treg cell subsets in patients affected with systemic sclerosis (SSc). Phenotypes and functions of Th17 and Treg cell subsets were analyzed in a series of 36 SSc patients. Th17 cell concentration in the peripheral blood was found to be increased in SSc patients with respect to healthy controls independently from type or stage of disease. After PBMC stimulation with a polyclonal stimulus or Candida albicans antigens the frequency of Th17 T cell clones was significantly higher in SSc patients with respect to controls suggesting the skewing of immune response in SSc patients toward Th17 cell generation/expansion. Concerning the Treg compartment, both CD4+CD25+ and CD8+CD28- Treg subsets showed quantitative and qualitative alteration in the peripheral blood of SSc patients. Collectively, these data highlight the existence of an imbalanced ratio between Th17 and Treg cell subsets in SSc patients.

The role of ultrasound imaging in the evaluation of peripheral nerve in systemic sclerosis (scleroderma).

BACKGROUND: Patients affected by scleroderma may complain of sensory disturbances especially in the hands. PURPOSE: To study the imaging features of upper limb nerves in patients affected by scleroderma (SSc). MATERIALS AND METHOD: Twenty-five patients affected only by SSc were prospectively evaluated with high-resolution US and magnetic resonance (MRI) or computer tomography (CT) when necessary (2 patients). Median and ulnar nerves were evaluated bilaterally. Nerve conduction studies were performed in the symptomatic patients (n = 10). Results of imaging studies were correlated with disease duration, autoimmunity and immunosuppression. Nerves of SSc patients were compared with a control group of 90 patients matched for age and body mass index. RESULTS: The prevalence of sensory disturbances revealed by clinical examination was 40%. In symptomatic SSc patients (n = 10) US evaluation revealed nerve abnormalities in 70% of cases (n = 7/10). n = 2 had a carpal tunnel syndrome. n = 5 had cubital tunnel syndrome. In two of them CT and MR were necessary to identify the compressed nerve at the level of the elbow due to the presence of calcifications. There was no association between the presence of an entrapment neuropathy and disease duration, autoantibodies and immunosuppression. CONCLUSION: Ultrasound, CT and MR may detect nerve abnormalities in 70% of SSc patients complaining of neurologic disturbances in the hands. The results of imaging studies support the hypothesis of a vascular dependent neuropathy in SSc.

The thickness of the A1 pulleys reflects the disability of hand mobility in scleroderma. A pilot study using high-frequency ultrasound.

BACKGROUND: Hand involvement in scleroderma is a serious concern. Clinical tests to asses hand dysfunction are based on the experience of the clinician. OBJECTIVE: To asses if utrasonographic (US) measurement of A1 pulley thickness may be used as an indicator of hand mobility in scleroderma. MATERIALS AND METHODS: Institutional review board approval and patient informed consent was obtained. Twenty-eight patients affected suffering from scleroderma and 40 healthy controls were prospectively evaluated by two blinded radiologists with US, with a transducer operating at 17MHz. A1 pulley thickness was measured and correlated with the Hand Mobility in Scleroderma Test (HAMIS) and disease duration. RESULTS: The thickness of the A1 pulley was greater in sclerodermic patients than in controls (p < 0.05). Intra and inter-observer agreement were better for ultrasound (0.94;0.88) than for HAMIS tests (0.71;0.70). A good correlation between pulley thickness, hand mobility and disease duration was found (r = 0.78, p < 0.018; r = 0.54, p < 0.05). CONCLUSION: A1 pulley thickness measured on ultrasound correlates with hand mobility and disease duration. Ultrasound is an useful tool to evaluate hand disability in scleroderma.

Brachial artery endothelial-dependent flow-mediated dilation identifies early-stage endothelial dysfunction in systemic sclerosis and correlates with nailfold microvascular impairment.

OBJECTIVE: To assess possible correlations between endothelial-dependent flow-mediated dilation (FMD) of the brachial artery and nailfold videocapillaroscopy (NVC) in patients with systemic sclerosis (SSc). Evidence has shown that vascular impairment in SSc may be a sign of endothelial dysfunction involving both microvascular and macrovascular systems, although the pathological mechanisms of the dysfunction are poorly understood. METHODS: Forty-three consecutive patients (mean age 51 +/- 11 yrs) with SSc were studied. Thirty patients had limited cutaneous SSc, 13 had diffuse cutaneous SSc. Twenty-seven healthy subjects (mean age 48 +/- 8 yrs) were recruited as controls. Ultrasound assessment of FMD was performed on all subjects in order to evaluate macrovascular function. Patients were divided into 3 patterns of microvascular damage on the basis of NVC (early, active, and late), and the microangiopathy evolution score was calculated, as reported elsewhere. RESULTS: FMD was significantly reduced in patients with SSc compared to healthy subjects [median 8.0% (3.0%-9.0%) vs 15.0% (12.0%-16.0%), respectively; p < 0.0001]. Patients with an early pattern of microangiopathy showed reduced FMD values compared to controls (p = 0.0001). FMD was significantly reduced in patients with SSc who had the late NVC pattern of microangiopathy compared to active and early patterns (p = 0.003 and p = 0.001, respectively). FMD was inversely correlated with the microvascular damage rate in patients with SSc (p < 0.0001). CONCLUSION: We demonstrated the simultaneous presence of macrovascular and microvascular impairment in patients with SSc, which was already present in the early phase of the vascular disease.

Cardiac magnetic resonance imaging detects subclinical right ventricular impairment in systemic sclerosis.

OBJECTIVE: To assess myocardial involvement in patients with systemic sclerosis (SSc) with no signs or symptoms of cardiac impairment (New York Heart Association functional class I). METHODS: Fifty patients (45 women, 5 men, age 53.3 +/- 12.9 yrs) who did not complain of serious diseases other than SSc were recruited out of 119 consecutive patients with SSc. Thirty-three were found to have limited cutaneous SSc (lSSc) and 17 diffuse SSc (dSSc). All underwent cardiovascular magnetic resonance imaging (MRI) to determine right and left systolic and diastolic volumes and ventricular ejection fractions (RVEF and LVEF). Thirty-one healthy subjects matched for sex, age, and body surface area (BSA) were studied as controls. Diffusion lung capacity test (DLCO) and high resolution computed tomography were performed to evaluate lung involvement. RESULTS: Disease duration between patients with lSSc (14.1 +/- 11.4 yrs) and those with dSSc (6.9 +/-4.4yrs) was found to be significantly different (p < 0.003). lSSc patients were older than those with dSSc (54.8 +/- 13.7 yrs vs 50.4 +/- 9.9 yrs, respectively; p < 0.04). Anticentromere antibodies and Scl-70 were positive in 23 (46%) and 17 patients (34%). Except for the left and right systolic volumes, all unadjusted cardiac MRI measures were significantly reduced in SSc compared to the controls (p < 0.001 and p < 0.009). These differences persisted after adjustment for subjects' height and BSA. Raw RVEF data and RVEF data matched for height and BSA were significantly reduced in dSSc patients in comparison to lSSc (p < 0.03). CONCLUSION: Compromised RVF was found in patients with asymptomatic SSc. Unlike standard diagnostic techniques, cardiac MRI appears to be a rapid and noninvasive means of determining subclinical right myocardial involvement that is otherwise undetected in patients with SSc.