Evaluation of Chronic Kidney Disease Epidemiology Collaboration equation to estimate glomerular filtration rate in scleroderma patients.

OBJECTIVE: Renal involvement in SSc is often subclinical and chronic kidney disease (CKD) develops, with slow worsening of glomerular filtration rate (GFR). The present investigation was undertaken in order to study how well the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) correlates with measured GFR (mGFR) in a group of SSc patients with serum creatinine (sCr) in the normal range. METHODS: Forty-one scleroderma patients (37 females and 4 males) with a median age of 46 years were enrolled. GFR was measured using technetium-99 m DTPA (Tc-99 m DTPA). The modified Cockroft-Gault formula, 4- and 7-variable Modification of Diet in Renal Disease (MDRD) and CKD-EPI equations were used for estimated GFR (eGFR). RESULTS: mGFR showed a median value of 84 ml/min (range 32.8-121.2 ml/min). Seven patients had reduced GFR (<60 ml/min), 19 had GFR within 60-90 ml/min and 15 had GFR >90 ml/min. The results showed mild correlation between the BSA-modified Cockroft-Gault and mGFR (P > 0.05), mild statistically significant correlation with 4-variable MDRD (P < 0.05), high statistically significant correlation with 7-variable MDRD (P = 0.01), but the greatest correlation was obtained using CKD-EPI (P = 0.002). No correlation with age, disease duration or subset of disease was found. CONCLUSIONS: In scleroderma patients with normal sCr value, CKD-EPI is a useful formula to assess GFR.

Impulse Oscillometry, Small Airways Disease, and Extra-Fine Formulations in Asthma and Chronic Obstructive Pulmonary Disease: Windows for New Opportunities.

In recent years, the perspective of management of respiratory disease has been gradually changing in light of the increasing evidence of small airways as the major site of airflow obstruction contributing to the development of both COPD and asthma already in early stages of disease. First and foremost, the evidence is redefining disease severity, identifying small airways disease phenotypes and early signs of disease, and revising prevalence and overall epidemiological data as well. Much effort has been put toward the instrumental assessment of small airways' involvement and early detection. Several clinical trials have evaluated the advantage of extra-fine formulations which can best target the small airways in uncontrolled asthma and severe COPD. Here, we briefly present a practical overview of the role of the small airways in disease, the most appropriate diagnostic methods for quantifying their impairment, and provide some insight into the costs of respiratory management in Italy, especially in sub-optimally controlled disease.

Laser Doppler perfusion imaging in systemic sclerosis impaired response to cold stimulation involves digits and hand dorsum.

OBJECTIVES: To assess by Laser Doppler perfusion imaging (LDPI) skin blood perfusion of hands in patients with SSc and primary RP (PRP) at baseline and after cold stimulation (CS). In SSc patients, the associations between skin perfusion and nailfold video capillaroscopy (NVC) patterns were also evaluated. METHODS: Forty patients with SSc, 38 patients with PRP and 32 healthy controls were recruited. Skin blood flow of the hands was detected by Lisca Laser Doppler Perfusion Imager at baseline and after CS. Further laser Doppler scanning was performed for each hand at 0 (T(1)), 3 (T(2)), 7 (T(3)) and 15 min (T(4)). RESULTS: Baseline mean perfusion is significantly (P < 0.000 l) lower in SSc patients than in healthy controls. In SSc patients, mean perfusion is reduced after CS (P < 0.0001) and skin flow recovery (significant difference between T(0) and T(4), P < 0.0001) is incomplete. In SSc patients with low vascular damage (early and active capillaroscopic groups), the abnormal microvascular response to CS involves only the digits, while the perfusion of hands dorsum is normal. With the progression of vascular damage (late capillaroscopic groups), the abnormal microvascular response to CS also appears in the hand dorsum skin. In PRP patients, baseline hand perfusion is very low and the skin flow recovery after CS is absent (P < 0.05). CONCLUSION: In early SSc, the thermoregulation of finger skin is impaired, but only in advanced stages of microangiopathy does the skin of the hand dorsum show a vasomotor control failure.

N-acetylcysteine infusion reduces the resistance index of renal artery in the early stage of systemic sclerosis.

AIM: To evaluate resistance index (RI) changes in renal artery after N-acetylcysteine infusion in patients with systemic sclerosis. METHODS: In an open-label study 40 patients with systemic sclerosis (SSc) were treated with N-acetylcysteine (NAC) iv infusion over 5 consecutive hours, at a dose of 0.015 g x kg(-1) x h(-1). Renal haemodynamic effects were evaluated by color Doppler examination before and after NAC infusion. RESULTS: NAC infusion significantly reduced RI in a group of sclerodermic patients with early/active capillaroscopic pattern, modified Rodnan Total Skin Score (mRTSS) <14 and mild-moderate score to the vascular domain of Medsger Scleroderma Disease Severity Scale (DSS). RI increased after NAC infusion in patients with late capillaroscopic pattern, mTRSS>14 and severe-end stage score to the vascular domain of DSS. In patients with reduction of RI after NAC infusion, diffusion capacity for carbon monoxide mean value was significantly higher than in those patients with an increase of RI. No significant differences in renal blood flow were found between patients with different subsets of SSc. CONCLUSION: In patients with low disease severity NAC ameliorates vascular renal function.

Intrarenal hemodynamic parameters correlate with glomerular filtration rate and digital microvascular damage in patients with systemic sclerosis.

OBJECTIVES: To evaluate intrarenal arterial stiffness by Doppler ultrasound and examine the correlation between renal Doppler indices, glomerular filtration rate, and digital microvascular damage in systemic sclerosis patients. METHODS: Thirty systemic sclerosis patients and 30 healthy controls were enrolled in this study. Doppler indices of intrarenal arterial stiffness, peak systolic flow velocity, end diastolic flow velocity, resistive index, pulsative index, and systolic/diastolic (S/D) ratio were measured on the interlobar artery of both kidneys. Glomerular filtration rate was measured using Tc(99m) diethylenetriamine pentaacetic acid (DTPA). Equation 7 from the Modification of Diet in Renal Disease was used to estimate glomerular filtration rate. Nailfold videocapillaroscopy findings were classified as early, active, and late patterns. RESULTS: The intrarenal arterial stiffness, evaluated by Doppler indices, was higher in systemic sclerosis patients than healthy controls. In systemic sclerosis patients pulsative index (r = -0.69), resistive index (r = -0.75), and S/D ratio (r = -0.74) showed a negative correlation with measured glomerular filtration rate (P < 0001). High correlation (P = 0008) was observed between measured and estimated glomerular filtration rate (r = 0.55). Pulsative index, resistive index, and S/D ratio significantly increased with progression of capillaroscopic damage. Conversely, measured glomerular filtration rate significantly decreased with capillaroscopic damage progression. CONCLUSIONS: Doppler indices of intrarenal arterial stiffness are noninvasive diagnostic tests to evaluate renal damage in SSc patients. Intrarenal arterial stiffness and glomerular filtration rate correlate with capillaroscopic microvascular damage.

Bosentan improves skin perfusion of hands in patients with systemic sclerosis with pulmonary arterial hypertension.

OBJECTIVE: Our aim was to investigate effects of bosentan on hand perfusion in patients with systemic sclerosis (SSc) with pulmonary arterial hypertension (PAH), using laser Doppler perfusion imaging (LDPI). METHODS: We enrolled 30 SSc patients with PAH, 30 SSc patients without PAH, and 30 healthy controls. In SSc patients and healthy controls at baseline, skin blood flow of the dorsum of the hands was determined with a Lisca laser Doppler perfusion imager. The dorsal surface of the hands was divided into 3 regions of interest (ROI). ROI 1 included 3 fingers of the hand from the second to the fourth distally to the proximal interphalangeal finger joint. ROI 2 included the area between the proximal interphalangeal and the metacarpophalangeal joint. ROI 3 included only the dorsal surface of the hand without the fingers. LDPI was repeated in SSc patients and controls after 4, 8, and 16 weeks of treatment. In SSc patients, nailfold videocapillaroscopy and Raynaud Condition Score (RCS) were performed at baseline and at 4, 8, and 16 weeks. RESULTS: SSc patients with PAH enrolled in the study received treatment with bosentan as standard care for PAH. In these patients with PAH, after 8 and 16 weeks of treatment, bosentan improved minimum, mean, and maximum perfusion and the perfusion proximal-distal gradient. Bosentan seems to be most effective in patients with the early and active capillaroscopic pattern than in patients with the late pattern. Bosentan improved skin blood flow principally in the ROI 1 compared to the ROI 2 and ROI 3. Bosentan restored the perfusion proximal-distal gradient in 57% of SSc patients with the early capillaroscopic pattern. No significant differences from baseline were observed in the RCS in SSc patients with PAH. CONCLUSION: Bosentan improved skin perfusion in SSc patients with PAH, although it did not ameliorate symptoms of Raynaud's phenomenon. Skin blood perfusion increased in SSc patients with PAH, particularly in the skin region distal to the proximal interphalangeal joint, and in patients with the early/active capillaroscopic pattern. Double-blind randomized clinical trials are needed to evaluate the effects of bosentan on skin perfusion of SSc patients without PAH and with active digital ulcers.

The different photoplethysmographic patterns can help to distinguish patients with primary and sclerodermic Raynaud phenomenon.

INTRODUCTION: The aim of this study is to investigate pulsatility of digital arteries of hands by means of photoplethysmography (PPG) in patients with primary Raynaud phenomenon (PRP) and systemic sclerosis (SSc) and to compare the results with those obtained in healthy controls. METHODS: One hundred five patients with SSc, 96 patients with PRP and 85 healthy controls were recruited in this study. Nailfold videocapillaroscopy and PPG were performed in healthy controls and patients. In patients with SSc, the capillaroscopic pattern was classified as early, active and late group pattern. A baseline PPG was recorded simultaneously in all 10 fingers of the hands. The photoplethysmographic curves were evaluated for morphology and amplitude of sphygmic wave. RESULTS: In healthy controls group, PPG shows the presence of photoplethysmographic homogeneous pattern and high mean value of sphygmic wave amplitude. In PRP group, PPG demonstrates homogeneous photoplethysmographic pattern and low mean value of sphygmic wave amplitude. Finally, in the SSc group, photoplethysmographic pattern is dyshomogeneous, and the mean value of sphygmic wave amplitude is intermediate between the other 2 groups. The PPG findings are different in the 3 capillaroscopic groups of patients with SSc and 2 subsets of disease. CONCLUSION: PPG represents a technique noninvasive to evaluate simultaneously in all 10 fingers of hands digital arteries pulsatility. PPG improves the evaluation of vascular damage in patients with primary and sclerodermic RP.

Dropped head syndrome and Systemic sclerosis.

The prominent or isolated weakness of cervical extensor muscles is a relatively rare clinical sign. Commonly, this is known as "dropped-head syndrome". This abnormal flexion of the head may occur in a variety of neuromuscular diseases and in a few non-neurological disorders as well. Systemic sclerosis is a clinically heterogeneous disorder which affects small arteries, microvessels and connective tissue with the involvement of multiple organs such as lung, heart, kidney and gastrointestinal tract. There is no evidence in literature of association between dropped head syndrome and rheumatic diseases, particularly systemic sclerosis. The case we describe concerns a 74-year-old woman with dropped-head syndrome associated to Systemic sclerosis and pulmonary hypertension in absence of myositis signs.

High incidence of celiac disease in patients with systemic sclerosis.

OBJECTIVE: To evaluate the presence of celiac disease in patients with systemic sclerosis (SSc). The association of autoimmune diseases with celiac disease has been reported, but few publications deal with the combination of SSc and celiac disease. METHODS: We investigated the presence of anti-tissue transglutaminase (anti-tTG) antibodies and serum antiendomysial antibodies (anti-EMA) in 50 patients with SSc. All subjects were on a gluten-containing diet. Duodenal mucosa histology and biopsy culture were performed in anti-tTG-positive patients; anti-EMA and IgA, IgG1 anti-tTG were detected in culture supernatants. RESULTS: The incidence of celiac disease in patients with SSc was found to be 8%. Serum anti-tTG antibody-positive results were detectable in 5 out of 50 patients with SSc, but only in 4 of them was the diagnosis confirmed by histological results (Marsh classification). CONCLUSION: Our data show an increased prevalence of celiac disease in patients with SSc.

Erectile dysfunction in systemic sclerosis: effects of longterm inhibition of phosphodiesterase type-5 on erectile function and plasma endothelin-1 levels.

OBJECTIVE: To investigate the effects of prolonged inhibition of phosphodiesterase type-5, using once-daily long-acting phosphodiesterase type-5 inhibitor (tadalafil) on erectile function and biomarkers of endothelial function in male patients with systemic sclerosis (SSc) and erectile dysfunction (ED). METHODS: In an open-label study, 14 nonconsecutive male patients with SSc with different degrees of ED were enrolled into the study irrespective of their clinical response to tadalafil, and received once-daily tadalafil 10 mg for 12 weeks. Primary endpoints were variations from baseline of penile arterial inflow [peak systolic velocity (PSV, cm/s); measured with dynamic color duplex ultrasound] and the erectile function domain score (measured with the International Index of Erectile Function questionnaire). Secondary endpoints were variations from baseline of morning erections (determined by modified question 13 of the Structured Interview on Erectile Dysfunction questionnaire) and plasma concentrations of endothelin-1 (ET1). RESULTS: The PSV and the erectile function domain score were significantly improved by once-daily tadalafil (from 21.3 +/- 6.4 to 30.0 +/- 7.0 cm/s and from 13.0 +/- 6.8 to 17.0 +/- 9.0 vs baseline, respectively; p <0.05). Question 13 scores decreased dramatically after treatment compared with baseline (from 2.2 +/- 0.2 to 0.8 +/- 0.5 arbitrary units; p < 0.001), and plasma ET1 levels decreased (from 24 +/- 15 to 9.8 +/- 7.4 pg/ml; p < 0.05). CONCLUSION: In men with SSc-related ED, once-daily tadalafil improved both erectile function and vascular measures of cavernous arteries. Increases in morning erections and decreases in plasma ET1 levels were found, which may play a potential role in preventing progression of penile fibrosis and erectile dysfunction.