Explore the vast range of titles available.

Background Nailfold videocapillaroscopy (NVC) is a feasible method that allows the observation of the microvascular changes that mark the course of systemic sclerosis (SSc). In previous studies, we demonstrated that the NEMO score, i.e. the cumulative number of microhaemorrhages and microthromboses, is a good indicator of the steady-state level and overtime changes of disease activity (DA) in SSc. Objectives To verify whether high NEMO scores, which mirror a very active microvascular derangement in the fingers, may be associated with the subsequent development of ischaemic digital ulcers (IDUs). Methods The NEMO score was assessed at baseline (T0) in 98 patients with SSc, all classified according to the ACR-EULAR criteria. Of them, 90 were females, 48 had the limited and 50 had the diffuse cutaneous variant of SSc. Afterwards, the patients were closely followed up for 2 years, and the appearance of new IDUs recorded at any time of the follow-up. The T0-NEMO score values of patients who developed IDUs were compared to those of patients who did not. A receiver operating curve (ROC) was constructed, and the area under the curve (AUC) calculated by plotting the sensitivity and 1-specificity of the different NEMO score values in predicting the subsequent development of IDUs. Results During the follow-up, 38 out of 98 patients developed one or more IDUs. The NEMO score at T0 was significantly higher in those who developed IDUs with respect to those who did not [median 14.5 (95% CI 11.0–21.5) and 4.5 (95% CI 4.0–6.0), respectively, p  < 0.0001]. The ROC curve derived from different T0-NEMO score values had an AUC of 0.79 (95% CI 0.69–0.86, p  < 0.0001). A NEMO score of ≥ 12 had a sensitivity of 83.3% (95% CI 71.5–91.7) and a specificity of 63.2% (95% CI 46.0–78.2), with positive (P) and negative (N) predictive (PV) values of 58.9% (95% CI 44.7–72.2) and 85.6% (71.8–94.4), respectively. A NEMO score of ≥ 16 had a sensitivity of 95.0% (95% CI 86.1–99.0) and a NPV of 93.4% (77.5–99.2). Conclusions Being a valid tool to measure DA levels in SSc, the NEMO score also appears to be closely related to the subsequent development of IDUs in this disease.

The aim of the present study was to retrospectively evaluate response to therapy in 73 patients affected by systemic sclerosis (SSc) who underwent long-term cyclic treatment with intravenous iloprost for peripheral vascular involvement (average duration of treatment 54.12±41.04 months). Seventy-three SSc patients were enrolled. Data were collected by reviewing clinical records and by phone or direct interview. Patients underwent a thorough physical examination at the end of follow up. The incidence of severe vascular manifestations was also assessed. Statistical analysis was performed by Wilcoxon's signed rank test and descriptive statistics using Statview software. In this study cohort, 55 of 73 (75.2%) patients had a history of ischemic digital ulcers (DUs); 28 patients (38.4%) had active DUs at the beginning of treatment. Skin ulcers healed completely in 25 of 28 patients (89.3%) at the end of the first treatment. However, 40 of 55 patients (72.6%) relapsed after an average of 24 months. There was a significant correlation between relapse rate and/or number of ulcers and clinical factors (diffuse subset, changes in results of Allen's test, NT-pro BNP levels). The annual incidence of pulmonary arterial hypertension (PAH) was 2.34 (95%CI: 0.94-4.83) per 100 person years, the rate of gangrene was 2.7%, and no cases of scleroderma renal crisis were recorded. The incidence of PAH and of digital gangrene was higher than that observed in unselected SSc case series. These data suggest that our patients treated with iloprost have a higher vascular involvement than large case series of unselected SSc patients. A number of clinical factors are correlated to the severity of vascular involvement and could have an impact on the response to therapy. The clinical significance of these findings requires clarification and further investigation is needed.

Systemic sclerosis (SSc, scleroderma) is a complex connective tissue disease whose earliest clinical manifestations are microvascular tone dysregulation and peripheral microcirculatory abnormalities. Following previous evidence of an association between circulating neurovascular guidance molecules and SSc disturbed angiogenesis, here, we measured the levels of soluble neuropilin 1 (sNRP1), semaphorin 3E (Sema3E), and Slit2 by enzyme-linked immunosorbent assay in serum samples from a large case series of 166 SSc patients vs. 110 healthy controls. We focused on their possible correlation with vascular disease clinical features and applied logistic regression analysis to determine which of them could better reflect disease activity and severity. Our results demonstrate that, in SSc: (i) sNRP1 is significantly decreased, with lower sNRP1 serum levels correlating with the severity of nailfold videocapillaroscopy (NVC) abnormalities and the presence of ischemic digital ulcers (DUs); (ii) both Sema3E and Slit2 are increased, with Sema3E better reflecting early NVC abnormalities; and (iii) higher Sema3E correlates with the absence of DUs, while augmented Slit2 associates with the presence of DUs. Receiver operator characteristics curve analysis revealed that both circulating sNRP1 and Sema3E show a moderate diagnostic accuracy. Moreover, logistic regression analysis allowed to identify sNRP1 and Sema3E as more suitable independent biomarkers reflecting the activity and severity of SSc-related peripheral microvasculopathy.

Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatic condition in childhood and an important cause of short and long term disability. Oligoarthritis is defined as an arthritis that affects four o fewer joints during the first 6 months of disease. The large majority of patients within this category belongs to a quite well defined disease which is not observed in adults. It is characterized by an early onset (before 6 years of age), an asymmetric arthritis involving mainly large joints, a female predilection, a high frequency of positive antinuclear antibodies (ANA), a high risk for developing chronic iridocyclitis and consistent HLA associations. We describe 3 clinical cases who presented monoarthritis of the elbow as early sign of oligoarticular JIA. All patients showed inflammatory markers elevation and 2/3 were ANA positive. MRI showed the presence of synovial inflammation without bone involvement. Intraarticular triamcinolone hexacetonide, led to remission in one case, while in the other two there was a re-activation of the disease treated with NSAIDs and/or MTX. The reported cases represent 0.6% of 490 patients with JIA followed by our unit in the last 10 years. Cases of exclusive involvement of the elbow at onset of JIA in literature are rare. Therefore, we report 3 cases of monoarthritis of the elbow as initial sign of oligoarticular JIA, a very atypical onset of this disease.

This chapter contains sections titled: Characteristics Treatment References

IntroductionAlthough there is abundant evidence of vascular perturbation from studies of peripheral blood in systemic sclerosis (SSc), there are few data about the ability to use biomarkers of vascular injury and growth factors to predict vascular outcomes and response to therapy. We sought to explore the association between candidate vascular biomarkers and digital ulcerations (DU) in a clinical trial context.MethodsWe examined 19 circulating vascular, angiogenic, and inflammatory biomarkers in 124 patients with scleroderma and DU who participated in a randomized controlled trial of oral treprostinil diolamine (ClinicalTrials.gov identifier NCT00775463). Correlation, regression, and random forest analyses were conducted to assess biomarker relationships in response to drug treatment.ResultsOver the 20-week trial, 82 (66%) patients had their cardinal ulcer completely heal, 54 (44%) developed new ulcers, and 72 (58%) had complete healing of all ulcers; mean change in ulcer burden comparing week 20 with baseline was − 0.36 ± 1.70. Nineteen biomarkers were analyzed for their association and ability to predict clinical DU outcomes. After adjusting for multiple comparisons, no individual biomarker (baseline level, week 20 level, or change over time) was significantly associated with any of the clinical outcomes, suggesting that traditional vascular, angiogenic or inflammatory drivers are not predictive of ulcer fate.ConclusionsThe lack of strong response to any of the vascular, angiogenic, or inflammatory markers suggest that these pathways are not primary drivers in the development of DU clinical outcomes in a SSc population with prevalent DU.Key Points:• Currently we lack robust biomarkers to predict vascular outcomes or response to therapy in scleroderma patients with Raynaud’s phenomenon.• Longitudinal assessment of vascular biomarkers in a clinical trial setting provides a unique opportunity to define biomarkers that predict vascular outcomes.• In a randomized controlled trial of oral treprostinil diolamine for treatment of scleroderma-associated digital ulcers, biomarkers involved in several vascular, inflammatory, and angiogenic pathways did not predict short-term clinical response to therapy or digital ulcer outcomes.• Further study of these and other biomarkers should be considered in Raynaud’s clinical trials in scleroderma patients without prevalent digital ulcers.