Ivone Silva

Impaired angiogenesis as a feature of digital ulcers in systemic sclerosis

Impaired angiogenesis in systemic sclerosis has a major role in tissue injury pathogenesis. Our objective was to determine whether angiogenic biomarkers (vascular endothelial growth factor (VEGF), endoglin, and endostatin) are related to microvascular damage and to determine their predictive value for new digital ulcers (DU). The main outcome of the study was the occurrence of a new digital ulcer during 3-year follow-up. This prospective longitudinal study was performed between October 2011 and December 2014. Seventy-seven patients definitely diagnosed with systemic sclerosis where divided into two groups: those with active DU at baseline and those with no DU until enrollment. Patients were matched by sex and age with healthy controls. Serum levels of VEGF, endoglin, and endostatin were measured at enrollment, and several nailfold videocapillaroscopies were performed during the 3-year follow-up. Serum levels of VEGF were lower (245.06, 158.68–347.33; p < 0.001) and those of endoglin were higher (3.013, 1.463–7.023; p < 0.001) in patients with active DU than those with no DU history (339.49, 202.00–730.93/1.879, 0.840–3.280), and they were higher than those found in controls (178.030, 101.267–222.102)/0.277, 0.154–0.713), respectively. No differences in endostatin levels were found between groups (p = 0.450). Endoglin was the only biomarker significantly different (p = 0.031) between patients with diffuse versus limited systemic sclerosis and between early, active, and late patterns (p = 0.020). VEGF was identified as an independent predictor for the development of new DU. Our study confirmed the relationship between angiogenic vascular biomarkers and the occurrence of DU. Endoglin and VEGF serum levels are potential risk factors, and VEGF has a predictive value for the occurrence of new DU.

Endothelial dysfunction, microvascular damage and ischemic peripheral vasculopathy in systemic sclerosis

OBJECTIVE To evaluate endothelial dysfunction and microvascular damage in secondary Raynaud Phenomenon (SRP) and Systemic sclerosis (SSc)-associated patients as possible predictors of ischemic fingertip digital ulcers (DU) in a 3-year clinical follow-up. METHODS Flow-mediated dilatation (FMD), nailfold videocapillaroscopy (NVC), endothelin-1 (ET-1) and asymmetric dimethylarginine (ADMA) were analysed in a 3-year observational cohort study of 77 SRP patients with systemic sclerosis. The primary outcome was the occurrence of a new DU. RESULTS Risk factors for DU at baseline were low FMD% (p < 0.001), NVC pattern (p < 0.001), high microangiopathy evolution score (MES) (p < 0.001), increased ET-1 (p < 0.001) and increased ADMA serum levels (p = 0.001). Median time to the occurrence of a new DU was 4.50 (1.25-16.25) months. The risk factors for the occurrence of at least one new DU episode in follow-up included a history of at least one DU before enrolment (p < 0.001), autoantibody anti-scleroderma-70 (p = 0.012), NVC late pattern (p < 0.001), high MES score (p < 0.001), low FMD% (p < 0.001) and increased ET-1 serum levels (p < 0.001).We used univariate Cox regression analysis to show that FMD >9.41% (HR: 0.37 95% CI: 0.14-0.99) and ET-1 >11.85 pmol/L (HR: 3.81 95% CI: 1.41-10.26) and NVC (HR: 2.29 95% CI: 0.97-5.38) were predictors of DU recurrence. In terms of first DU event in naïve DU patients at baseline, late NVC pattern (HR: 12.66 95% CI: 2.06-77.89) and MES score (HR: 1.693 95% CI: 1.257-2.279) were independent predictors. CONCLUSION This study identified endothelium dysfunction biomarkers (FMD and ET-1) and severe microvascular damage in NVC as strong predictors of new DU in SSc patients.

Digital ulcers in systemic sclerosis: role of flow-mediated dilatation and capillaroscopy as risk assessment tools

AimThe aim of this study was to evaluate macrovascular endothelial dysfunction and microvascular damage as clinical markers of peripheral microangiopathy in patients with Raynaud’s phenomenon (RP).Patients and methodsSeventy-seven secondary RP with systemic sclerosis, 32 primary RP and 34 healthy controls were included in our study. Secondary RP patients were divided into two subgroups: 39 with digital ulcers (DU) and 38 without digital ulcers (non-DU).ResultsPatients with DU had significantly lower flow-mediated dilatation values (5.34 ± 7.49%) compared to non-DU patients (16.21 ± 11.31%), primary RP (17.96 ± 12.78%) and controls (20.17 ± 8.86%), p<0.001, favouring macrovascular endothelium dysfunction. Regarding microvascular damage, the DU group had a predominately capillaroscopic late pattern (71.1%) whereas non-DU patients had an active pattern (56.4%). The microangiopathy evolution score was significantly higher in the DU group compared to the non-DU group (4.79 ± 1.82 vs. 1.79 ± 1.56, p<0.001). Flow-mediated dilation was significantly lower in late pattern (6.13 ± 7.09%) compared to active (12.58 ± 10.66%) and early patterns (17.72 ± 14.90%), p = 0.016 and p = 0.044 respectively.ConclusionsLow flow-mediated dilatation and microvascular damage in capillaroscopy are early clinical markers of DU risk in RP patients.

Aneurysmal Degeneration of the Brachial Artery after Vascular Access Creation: Surgical Treatment Results

Abstract True peripheral artery aneurysms proximal to a longstanding arteriovenous fistula is a well‐recognized complication. Late aneurysmal degeneration is rare. This study analyzed the characteristics, therapeutic options, and outcomes of true donor brachial artery aneurysms (DBAA) after arteriovenous fistula (AVF) for hemodialysis. We retrospectively collected the data of patients with DBAA after AVF creation, surgically repaired between January 2001 and September 2015. We excluded patients with pseudoaneurysms, anastomotic aneurysms, and infected aneurysms. We recorded patients demographics, type of access, aneurysm characteristics, symptoms, treatment, and follow‐up. Ten patients were treated for aneurysmal degeneration of the brachial artery. Average aneurysm diameter was 37.5 mm. All cases had, at least, one previous distal AVF, ligated or thrombosed, at the time of diagnosis. The first access was created in mean 137 months before the diagnosis of DBAA. Nine patients had previous medical history of renal transplant and were under immunosuppressive therapy. All patients were symptomatic at the time of diagnosis. In all cases, the treatment was aneurysmectomy followed by interposition bypass. One patient developed a postoperative hematoma with the need of surgical drainage. At 50 months of follow‐up, one patient was submitted to percutaneous angioplasty due to an anastomotic stenosis. No other complications occurred during the entire follow‐up period (mean: 69 months). The pathogenesis underlying DBAA remains unclear. Increased blood flow after AVF creation, immunosuppressive therapy, and ligation/thrombosis of the AVF may contribute to aneurysm formation. Surgical treatment by aneurysmectomy and bypass, with autogenous conducts, is a safe and effective option.

Raynaud and digital ulcers in patients with juvenile systemic sclerosis: ambulatory iloprost protocol. A single center experience

Results: Since 2007 we treated three patients with jSSc and active digital ulcers: two girls, 12 and 13 years, and a boy of 18 months old at time of first treatment. A total of 19 treatments of iv. iloprost were done, 15 of these in ambulatory basis with the elastomeric pump. Outcomes were good with a reduced number and severity of RP attacks in all patients, and reduced pain associated with RP and DU. No disabling or severe side effects were observed. Two patients, the girls, had no more active digital ulcers after the second treatment with a follow-up of 2 and 3 years respectively. One patient, male, has recurrent digital ulcers, but number has decreased from 4 to 1 not interfering with daily activities. Conclusion: Iloprost iv. perfusion with the elastomeric pump at ambulatory is a safe and effective treatment for patients with refractory RP to calcium channel blockers and in patients with digital ulcers. The authors suggest two treatments in the winter season with reduction of number and severity of R and ulcer healing.

PReS-FINAL-2122: Autologous stem cell transplantation in a patient with severe systemic sclerosis in Portugal

Systemic sclerosis (SSc) is a progressive disease, whose pathogenesis includes early immunological events and vascular alterations. There is a subgroup of patients with a rapidly progressive disease or refractory to conventional treatment which can benefit from intensive immunosuppression and rescue with transplant of haematopoietic progenitors (TPH).