Evaluation of estimated glomerular filtration rate and clinical variables in systemic sclerosis patients.

OBJECTIVES: The most important renal complication of systemic sclerosis (SSc) is scleroderma renal crisis (SRC). Many patients demonstrate less severe renal complications, most likely associated with reduced renal blood flow and a consequent reduction in glomerular filtration rate (GFR). The mechanism of this slowly progressive form of chronic renal disease is unclear. The aim of this study was to evaluate GFR by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) and the 7-variable Modification of Diet and Renal Disease (MDRD) equations in SSc patients and to correlate estimated GFR (eGFR) with clinical variables of the disease. METHODS: 105 unselected and consecutive patients with SSc were enrolled. Serum creatinine was measured in all patients and GFR was estimated by 7-variable MDRD and CKD-EPI equations. Nailfold videocapillaroscopy was performed in all patients. RESULTS: The mean value of eGFR evaluated by both 7-variable MDRD and CKD-EPI was significantly different (p < 0.0001) in the three capillaroscopic groups and correlated negatively with the severity of capillaroscopic damage (early: 95 ± 16 mL/min and 101 ± 12 mL/min, active: 86 ± 25 mL/min and 95 ± 17 mL/min, late: 76 ± 21 mL/min and 82 ± 21 mL/min). The mean value of eGFR evaluated by 7-variable MDRD (97 ± 23 mL/min vs. 74 ± 15 mL/min, p < 0.0001) and CKD-EPI< (0.83 ± 0.20 mL/min vs. 0.68 ± 0.10 mL/min, p < 0.0001) was significantly higher in SSc patients without history of digital ulcers than in those with. CONCLUSION: We can conclude that in SSc patients without renal involvement, eGFR decreases with the progression of digital vascular damage.

Three-dimensional echocardiography and 2D-3D speckle-tracking imaging in chronic pulmonary hypertension: diagnostic accuracy in detecting hemodynamic signs of right ventricular (RV) failure.

BACKGROUND: Our aim was to compare three-dimensional (3D) and 2D and 3D speckle-tracking (2D-STE, 3D-STE) echocardiographic parameters with conventional right ventricular (RV) indexes in patients with chronic pulmonary hypertension (PH), and investigate whether these techniques could result in better correlation with hemodynamic variables indicative of heart failure. METHODS AND RESULTS: Seventy-three adult patients (mean age, 53±13 years; 44% male) with chronic PH of different etiologies were studied by echocardiography and cardiac catheterization (25 precapillary PH from pulmonary arterial hypertension, 23 obstructive pulmonary heart disease, and 23 postcapillary PH from mitral regurgitation). Thirty healthy subjects (mean age, 54±15 years; 43% male) served as controls. Standard 2D measurements (RV-fractional area change-tricuspid annular plane systolic excursion) and mitral and tricuspid tissue Doppler annular velocities were obtained. RV 3D volumes and global and regional ejection fraction (3D-RVEF) were determined. RV strains were calculated by 2D-STE and 3D-STE. RV 3D global-free-wall longitudinal strain (3DGFW-RVLS), 2D global-free-wall longitudinal strain (GFW-RVLS), apical-free-wall longitudinal strain, basal-free-wall longitudinal strain, and 3D-RVEF were lower in patients with precapillary PH (P<0.0001) and postcapillary PH (P<0.01) compared to controls. 3DGFW-RVLS (hazard ratio 4.6, 95% CI 2.79 to 8.38, P=0.004) and 3D-RVEF (hazard ratio 5.3, 95% CI 2.85 to 9.89, P=0.002) were independent predictors of mortality. Receiver operating characteristic curves showed that the thresholds offering an adequate compromise between sensitivity and specificity for detecting hemodynamic signs of RV failure were 39% for 3D-RVEF (AUC 0.89), -17% for 3DGFW-RVLS (AUC 0.88), -18% for GFW-RVLS (AUC 0.88), -16% for apical-free-wall longitudinal strain (AUC 0.85), 16 mm for tricuspid annular plane systolic excursion (AUC 0.67), and 38% for RV-FAC (AUC 0.62). CONCLUSIONS: In chronic PH, 3D, 2D-STE and 3D-STE parameters indicate global and regional RV dysfunction that is associated with RV failure hemodynamics better than conventional echo indices.

Increased intrarenal arterial stiffness may predict the occurrence of new digital ulcers in systemic sclerosis.

OBJECTIVE: Patients with systemic sclerosis (SSc; scleroderma) are at high risk for the development of ischemic digital ulcers (DUs), which occur in 35-60% of SSc patients. The aim of this study was to assess the correlation between intrarenal arterial stiffness and DUs in SSc patients and to evaluate the prognostic value of Doppler indices to predict new DU occurrence. METHODS: Seventy unselected, consecutive patients with SSc (58 women and 12 men, mean ± SD age 49.5 ± 13.8 years) were enrolled. In all patients, Doppler ultrasound examination was performed. The following Doppler indices of intrarenal stiffness were measured: peak systolic velocity (PSV), end diastolic velocity (EDV), resistive index (RI), pulsatile index (PI), and systolic/diastolic ratio (S/D). RESULTS: In total, 30 (42%) of 70 patients experienced new DUs. RI, S/D, and PI were significantly higher in SSc patients with new DUs than in SSc patients without new DUs. The receiver operating characteristic (ROC) curves demonstrated a good accuracy of new DU prediction for RI (0.94, P < 0.0001), S/D (0.92, P < 0.0001), and PI (0.88, P < 0.0001). Conversely, the ROC curve showed no performance for PSV (0.58, P > 0.05) and EDV (0.28, P > 0.05). Using a cutoff value of 0.70 for RI and 3.25 for S/D, the positive predictive value was 90.6% and 92.9%, respectively. CONCLUSION: We can conclude that Doppler indices of intrarenal stiffness are reliable markers of new DU occurrence. Doppler indices could be used in association with the capillaroscopic and clinical findings or serologic tests for the identification of patients at high risk of developing DUs.

Nutritional status measured by BMI is impaired and correlates with left ventricular mass in patients with systemic sclerosis.

OBJECTIVE: Systemic sclerosis (SSc) is a multisystemic chronic disease that is complicated by protein-energy malnutrition (PEM). Considering that PEM also may influence left ventricular mass (LVM), the aim of this study was to evaluate whether LVM is related to patients' nutritional status and to determine clinically relevant features of SSc. METHODS: Adult patients referring to our institution were considered. Body weight, height, body mass index (BMI), involuntary weight loss, and the presence of gastrointestinal symptoms were recorded. Echocardiography was performed to assess LVM, using the Devereux regression formula. Results were then normalized by body surface area. Pattern, skin thickening, disease activity and severity, and duration were assessed to characterize SSc. RESULTS: Ninety-four patents with SSc (81 women and 13 men; median duration of disease 7 y) were studied. The prevalence of PEM as assessed by BMI < 20 kg/m(2) was 19%, whereas 15% of patients reported involuntary weight loss of any degree. Patients who lost weight reported gastrointestinal symptoms more frequently (P < 0.05). PEM was not associated with disease activity. LVM (g/m(2)) correlated with patients' BMI (r = 0.32; P < 0.01), and the vascular domain of disease severity (DDS; r = 0.21; P < 0.05), but it showed a negative correlation with skin thickening (r = -0.21 P = 0.01). Patients with ulcers had a significantly greater LVM than patients without skin lesions. CONCLUSIONS: Our study shows that LVM correlates with patients' BMI, skin thickening, and the vascular domain of DSS. Therefore, LVM could serve as a marker of nutritional status and fibrosis in patients with SSc.

Clitoral blood flow in systemic sclerosis women: correlation with disease clinical variables and female sexual dysfunction.

OBJECTIVES: The objectives of this study were to investigate clitoral blood flow in SSc women compared with healthy controls and to correlate it with microvascular damage and disease clinical variables. We also evaluated the correlation between clitoral blood flow and sexual dysfunction. METHODS: Twenty-two SSc women and 20 healthy controls matched for sex and age were enrolled in this study. Baseline Doppler indices of the clitoral artery were measured. Peak systolic velocity, end diastolic velocity, resistive index (RI), pulsatile index (PI) and systolic/diastolic (S/D) ratio were measured. The female sexual function index (FSFI) was used to assess sexual function. RESULTS: The RI and S/D ratio were higher (P < 0.0001) in SSc women compared with healthy controls. The PI, RI and S/D ratio increased with progression of capillaroscopic damage. The RI and S/D ratio were higher (P < 0.01) in women with digital ulcers than in women without digital ulcers. No correlation exists between Doppler indices of the clitoral artery and age or clinical variables of disease. The FSFI was reduced in 7 (32%) of 22 SSc women. A negative correlation was observed between both the FSFI and RI (R = -0.74, P < 0.0001) and the S/D ratio (R = -0.68, P < 0.0001). A negative correlation exists between the RI and all domains of the FSFI score except for desire. CONCLUSION: Clitoral blood flow was reduced in SSc women compared with healthy controls. Clitoral blood flow was reduced in SSc women with digital ulcers and it correlated with capillaroscopic damage progression. A negative correlation exists between the RI and S/D ratio and all domains of the FSFI score except for desire.

Autoantibodies to estrogen receptor α in systemic sclerosis (SSc) as pathogenetic determinants and markers of progression.

Systemic sclerosis (SSc) is a multisystem autoimmune disease of unknown etiology characterized by inflammation, autoantibody production, and fibrosis. It predominantly affects women, this suggesting that female sex hormones such as estrogens may play a role in disease pathogenesis. However, up to date, the role of estrogens in SSc has been scarcely explored. The activity of estrogens is mediated either by transcription activity of the intracellular estrogen receptors (ER), ERα and ERß, or by membrane-associated ER. Since the presence of autoantibodies to ERα and their role as estrogen agonists interfering with T lymphocyte homeostasis were demonstrated in other autoimmune diseases, we wanted to ascertain whether anti-ERα antibodies were detectable in sera from patients with SSc. We detected anti-ERα antibody serum immunoreactivity in 42% of patients with SSc (30 out of 71 analyzed). Importantly, a significant association was found between anti-ERα antibody values and key clinical parameters of disease activity and severity. Fittingly, anti-ERα antibody levels were also significantly associated with alterations of immunological features of SSc patients, including increased T cell apoptotic susceptibility and changes in T regulatory cells (Treg) homeostasis. In particular, the percentage of activated Treg (CD4(+)CD45RA(-) FoxP3(bright)CD25(bright)) was significantly higher in anti-ERα antibody positive patients than in anti-ERα antibody negative patients. Taken together our data clearly indicate that anti-ERα antibodies, probably via the involvement of membrane-associated ER, can represent: i) promising markers for SSc progression but, also, ii) functional modulators of the SSc patients' immune system.

Erectile dysfunction, endothelium dysfunction, and microvascular damage in patients with systemic sclerosis.

INTRODUCTION: Erectile dysfunction (ED) prevalence in men with systemic sclerosis (SSc) is high and can be considered a manifestation of endothelium damage. AIM: This study aims to correlate ED with endothelial dysfunction and digital vascular damage in SSc patients. MAIN OUTCOME MEASURES: The main outcome measures were erectile function, Doppler indices of cavernous arteries, flow-mediated dilation (FMD), capillaroscopic damage, skin perfusion, and digital pulsatility. METHODS: In 23 SSc patients, erectile function was investigated using the International Index of Erectile Function-5 (IIEF-5). Doppler indices of cavernous arteries, peak systolic velocity (PSV), end-diastolic velocity (EDV), and resistive index (RI) were measured at the penoscrotal junction before and after pharmacostimulation with 20 mg prostaglandin E1. FMD and nailfold videocapillaroscopy (NVC) were used to evaluate endothelial dysfunction and capillaroscopic damage. Skin perfusion and digital sphygmic waves were measured by laser Doppler perfusion imaging (LDPI) and digital photoplethysmography (PPG), respectively. RESULTS: IIEF-5 score was reduced in 83% of patients. PSV was reduced in 96%, while EDV was increased in 48% of patients. A positive correlation was observed between IIEF-5 score and FMD (r = 0.71, P < 0.0001) and between the former and PSV (r = 0.76, P < 0.0001). A negative correlation was observed between EDV and FMD (r = -0.509, P < 0.01). FMD and Doppler indices were reduced with capillaroscopic damage progression. A positive correlation exists between LDPI perfusion and IIEF-5 score (r = 0.743, P < 0.0001) and between the former and PSV (r = 0.714, P < 0.0001), while a negative correlation is observed between LDPI perfusion and EDV (r = -0.677, P < 0.0001). A positive correlation exists between PPG pulsatility and IIEF-5 score (r = 0.752, P < 0.0001) and between the former and PSV (r = 0.747, P < 0.0001), while negative correlation is observed between PPG pulsatility and EDV (r = -0.689, P < 0.0001). CONCLUSION: In SSc patients, ED correlates with endothelial dysfunction and digital microvascular damage.

Red blood cell alterations in systemic sclerosis: a pilot study.

AIMS: The aim of this work was to investigate whether systemic oxidative imbalance that occurs in patients with systemic sclerosis affects red blood cell integrity. METHODS: Reactive oxygen species, intracellular content of total thiols and molecules involved in red blood cell aging (e.g., glycophorin A, band 3, CD47 and phosphatidylserine externalization), have been analyzed in erythrocytes from 39 patients with systemic sclerosis and 30 healthy donors by using flow and static cytometry. Analyses were carried out taking into account the two clinical subsets of scleroderma: diffuse cutaneous sclerosis and limited cutaneous sclerosis. RESULTS: A significant reduction (p<0.05) of intracellular total thiols and a significant loss (p<0.01) of glycophorin A, band 3 and CD47 was found in red blood cells from patients with limited cutaneous sclerosis. Conversely, a significant increase (p<0.01) of reactive oxygen species levels and CD47 expression was found in red blood cells from patients with diffuse cutaneous sclerosis. Phosphatidylserine externalization was significantly increased both in patients with limited and diffuse disease. Importantly, this increase was related with disease severity and nailfold capillaroscopy. CONCLUSIONS: Altogether these results suggest a reappraisal of the red blood cells as useful markers in the clinical management of the disease.

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.

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.

Long-term N-acetylcysteine therapy in systemic sclerosis interstitial lung disease: a retrospective study.

Systemic sclerosis (SSc) is associated with interstitial lung diseases. The primary endpoints of this study were changes between baseline and month 24 in single-breath carbon monoxide diffusing capacity (DLco). The secondary endpoints were: vital capacity (VC), forced expired volume in 1 sec (FEV1), total lung capacity (TLC), scores of high resolution computed tomography (HRCT) of the chest, number of adverse effects. In this study, we retrospectively investigated data from SSc patients who had undergone therapy with high-dose intravenous N-acetylcysteine (NAC) at a dosage of 15 mg/Kg/h for 5 consecutive hours every 14 days. After NAC therapy median values of DLco (69.5 vs 77.7%), VC (99 vs 101.3%) and TLC (93 vs 98.3%) significantly increased. We did not observe any significant changes from baseline in FEV1 value and HRTC score. The improvement in lung function was more evident in SSc patients without radiological signs of pulmonary fibrosis than in patients with pulmonary fibrosis. In SSc patients with mild-moderate pulmonary fibrosis intravenous NAC administration slows the rate of deterioration of DLco, VC and TLC. In conclusion, this retrospective study demonstrates that long-term therapy with intravenous NAC ameliorates pulmonary function tests in SSc patients.

In systemic sclerosis macrovascular damage of hands digital arteries correlates with microvascular damage.

OBJECTIVE: To assess morphology and blood flow of the proper palmar digital arteries (PPDA) by color Doppler ultrasonography (CDUS) and its relationship with nailfold videocapillaroscopy (NVC), skin blood perfusion and digital arteries pulsatility of hands in SSc patients and healthy controls. METHODS: CDUS, NVC, laser Doppler perfusion imaging (LDPI) and photoplethysmography (PPG) were performed in 36 systemic sclerosis (SSc) patients and 20 healthy controls. RESULTS: CDUS was pathologic in 69% of patients with SSc and in none of healthy controls (p<0.0001). SSc patients with low vascular damage (early capillaroscopic pattern) have a normal morphology of PPDA, but the blood flow, evaluated by peak systolic velocity (PSV) and end diastolic velocity (EDV), is reduced and vascular resistance, measured by resistive index (RI) and pulsatility index (PI), increased. At this stage the LDPI mean perfusion and digital artery pulsatility, evaluated by PPG, were reduced. The US changes appear with microvascular damage progression (active and late capillaroscopic patterns), while the PPDA blood flow progressively decreases (PSV and EDV decreased, RI and PI increased). The macrovascular damage correlates with disease duration. Anti-topoisomerase I represents an independent predictive factor for macrovascular damage. We not observed any association between digital ulcer history, pulmonary fibrosis and US findings. CONCLUSION: PPDA blood flow dysfunction is already present in early disease. Structural macrovascular damage progresses with worsening of SSc microangiopathy.

Erectile dysfunction of sclerodermic patients correlates with digital vascular damage.

BACKGROUND: The prevalence of erectile dysfunction (ED) in men with systemic sclerosis (SSc) can be considered a manifestation of endothelium damage. Aim of the study is to investigate ED in SSc patients by color Doppler ultrasound examination and to correlate it with disease severity and digital vascular damage. METHODS: In 20 males SSc patients blood flow velocity in the cavernous artery was determined with Duplex ultrasonography. Naifold videocapillaroscopy, Sexual Health Inventory for Men (SHIM) and Medsger Disease Severity Scale (DSS) were performed. Arteriogenic ED was defined by the presence of a reduced peak systolic velocity (PSVs), while diastolic velocity (EDV) and the resistive index (RI) were estimated to evaluate venocclusive dysfunction. SSc patients are classified by capillaroscopic pattern and vascular domain of DSS into two groups: low vascular damage (early or active capillaroscopic pattern and score of vascular domain of DSS≤2) and high vascular damage (late capillaroscopic pattern and score of vascular domain of DSS≥3). RESULTS: In all SSc patients a reduction of SHIM is present (mean 13.5±6.3). Patients with less vascular damage have a significantly (p<0.001) higher score of SHIM than patients with greater vascular damage (19.2±2.4 vs 7.9±2.7). No significant difference (p>0.5) between the two groups of vascular damage was found in PSVs. Venocclusive dysfunction was present only (p<0.001) in the group with high vascular damage. CONCLUSION: We can assert that there is a relationship between SSc vascular digital damage and ED.

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.

Digital ulcers as an initial manifestation of systemic lupus erythematosus.

Digital ulcers (DUs) and gangrene are common skin manifestations of connective tissue diseases, especially systemic sclerosis. Raynaud's phenomenon (RP) is an almost universal manifestation of systemic sclerosis, with 95% of all patients being affected, and resulting in DUs in approximately 30% of the patients each year. Although RP may be present in approximately 25-50% of the patients, DUs are relatively rare in systemic lupus erythematosus (SLE) and never present as an initial manifestation of disease. In this case report DUs appear as the initial manifestation of SLE in a young woman with a capillaroscopic scleroderma pattern and elevated systolic pulmonary arterial pressure.

Penile involvement in Systemic Sclerosis: New Diagnostic and Therapeutic Aspects.

Systemic Sclerosis (SSc) is a connective tissue disorder featuring vascular alterations and an immunological activation leading to a progressive and widespread fibrosis of several organs such as the skin, lung, gastrointestinal tract, heart, and kidney. Men with SSc are at increased risk of developing erectile dysfunction (ED) because of the evolution of early microvascular tissutal damage into corporeal fibrosis. The entity of penile vascular damage in SSc patients has been demonstrated by using Duplex ultrasonography and functional infra-red imaging and it is now clear that this is a true clinical entity invariably occurring irrespective of age and disease duration and constituting the ''sclerodermic penis". Once-daily phosphodiesterase type-5 (PDE5) inhibitors improve both sexual function and vascular measures of cavernous arteries by improving surrogate markers of endothelial dysfunction, that is, plasma endothelin-1 and adrenomedullin levels, which may play a potential role in preventing progression of penile fibrosis and ED. Also, the beneficial effect of long-term PDE5i add-on therapy to SSc therapy in the treatment of Raynaud's phenomenon is described.

Echocardiographic myocardial imaging reveals segmental cardiomyopathy in Churg-Strauss syndrome.

Cardiovascular involvement is the leading cause of morbidity and death in Churg-Strauss syndrome. Herein, we describe the case of a 47-year-old man with Churg-Strauss syndrome, in whom the use of novel echocardiographic techniques revealed segmental cardiomyopathy. Tissue Doppler and speckle-tracking imaging showed that both longitudinal and radial strain were impaired at the septal level and that the impairment of circumferential strain affected left ventricular torsion. Our case shows that advanced echocardiography with myocardial strain imaging in multiple vectors can identify systolic-diastolic abnormalities in a patient with myocardial infiltration and a normal left ventricular ejection fraction.

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.