A. d’Ascanio

Vascular reactivity in patients with undifferentiated connective tissue diseases

INTRODUCTION Endothelial dysfunction is an early event in the development of atherosclerotic disease. We investigated endothelial function in the peripheral circulation of patients with undifferentiated connective tissue diseases (UCTDs), in comparison to healthy controls. METHODS In 15 young UCTD patients (mean age 39 years) with inactive disease and without cardiovascular risk factors and in 15 age-matched controls we evaluated endothelial function in the brachial conduit artery and in the forearm microcirculation. The first district was assessed by flow mediated dilation (FMD) and response to glyceryl trinitrate, and forearm microcirculation by blood flow changes (strain-gauge venous plethysmography) in response to intra-arterial acetylcholine (Ach) and sodium nitroprusside (SNP). Nitric oxide (NO) availability was evaluated by repeating Ach in the presence of intraarterial N(G)-monomethyl-l-arginine (l-NMMA), an NO synthase inhibitor. RESULTS FMD and response to GTN were similar in UCTD patients and controls. UCTD patients showed a reduced response to Ach (P<0.001) and SNP (P<0.01) as compared to controls. In healthy controls l-NMMA infusion significantly (P<0.001) reduced the vascular response to Ach, while in UCTD patients l-NMMA failed to affect vasodilation to Ach. In UCTD patients, vascular responses were unrelated to clinical manifestations or autoantibody profile. CONCLUSIONS Young UCTD patients are characterized by reduced endothelium-dependent and -independent vasodilation in the forearm microcirculation, but not in peripheral conduit arteries. Reduced NO availability was indirectly observed. These results suggest that in the absence of traditional risk factors, inactive systemic autoimmune diseases impair NO-dependent but also endothelium-independent vasodilation selectively in the microcirculation.

Rate of serious infections in Behçet’s disease patients receiving biologic therapies: a prospective observational study

Behçet’s disease (BD) is a systemic, chronic relapsing vasculitis, typically characterized by recurrent oro-genital ulcers, ocular inflammation, and skin manifestations [1, 2]. The clinical profile of BD is extremely variable; while prevalent mucocutaneous involvement and arthritis represent the only clinical features in patients with a benign disease subset, there are other patients who develop potentially sightor lifethreatening manifestations, due to ocular, neurological, or major vascular involvement [3]. Literature shows growing data reporting effectiveness of tumor necrosis factor (TNF)alpha blockers in inducing remission for sightand lifethreatening involvement in BD [4–6]. Since TNF plays an important role in host defense and tumor growth control, antiTNF antibody therapies may increase the risk of serious infections.

Epidemiology and Management of Neuropsychiatric Disorders in Behçet’s Syndrome

Behçet’s syndrome (BS) is a systemic, chronic, relapsing vasculitis, typically characterized by recurrent orogenital ulcers, ocular inflammation and skin manifestations; articular, vascular, gastroenteric and neurological involvement may also occur. Besides the other clinical features of BS, it seems relatively frequent that patients with BS develop a neurobehavioural syndrome, characterized by euphoria, bipolar disorders and paranoid attitudes, loss of insight/disinhibition, and indifference to their disease, defined as ‘neuro-psycho-BS’. To date, the pathogenetic mechanism underlying neuro-psycho-BS has not been determined. It may be secondary to organic neurological involvement, or it may be related to poor quality of life and the relapsing course of the disease. Another engaging theory suggests that it could be related to the frequent observation of psychiatric symptoms during relapses or, in some cases, in the phases preceding reactivation of the disease; these elements suggest that psychiatric disorders in BS could represent a crucial element, whether a psychiatric subset or a distinct clinical feature of the disease. Moreover, it has been reported that cognitive impairment in BS can be seen with or without central nervous system involvement. Globally, psychiatric symptoms have been described as being multifaceted, ranging from anxiety disorders to depressive–bipolar disorders or to psychotic ones. In addition, some psychological characteristics of BS patients seem to predispose them to maladaptive stress management, which may lead to stress-related disorders, including anxiety and depression. Therefore, the aims of this review are to explore the epidemiology of neuro-psycho-BS by evaluating the relationship between the stress system and the multifaceted psychiatric manifestations in BS, and to summarize the therapeutic strategy used.

High sensitivity troponin might be a marker of subclinical scleroderma heart involvement: a preliminary study

Introduction Although often asymptomatic, cardiac involvement is common in systemic sclerosis (SSc), and is associated with an increased morbidity and mortality. The aim of this study is to investigate whether high-sensitivity troponin (HSTn) might represent a useful tool to detect subclinical scleroderma heart involvement (SHI) in SSc. Methods We enrolled 65 consecutive SSc patients who performed HSTn test, electrocardiogram and an echocardiogram within six months of HSTn test. We acquired also data about N-terminal segment of proBNP (NT-proBNP) and cardiac magnetic resonance imaging (cMRI). We excluded patients with overt pulmonary arterial hypertension. We defined as subclinical SHI the presence of the following conditions: diastolic dysfunction, pericardial effusion, conduction abnormalities/arrhythmias, oedema and/or T2 weighted non-ischemic pattern showed by cMRI. Results Twelve patients showed SHI, and 23 and 29, respectively, had high levels of HSTn and of NT-proBNP. SHI is correlated with high levels of HSTn (p = 0.02) with a significant difference between HSTn values in patients with or without SHI (59 vs. 13 ng/mL; p = 0.0097). Moreover, among patients with abnormal NT-proBNP, 18 also had out of range HSTn (Spearman rank correlation 0.5; p<0.0001). According to ROC curve analysis, the best HSTn cut-off value in distinguishing between patients with and patients without SHI was 16 ng/mL (sensitivity 66.7%, specificity 83%; area under the curve: 0.77 (95% CI: 0.65-0.87) p<0.001. Conclusions Our data show a close relationship between HSTn and NT-proBNP in SSc patients with SHI. HSTn might be a marker of SHI while NT-proBNP seems to be less specific for heart dysfunction.

Post-occlusive reactive hyperaemia (POHR) in systemic sclerosis: very early disease (VEDOSS) represents a separate entity compared to established disease

Objectives: Vascular involvement is a key feature of systemic sclerosis (SSc). Vascular changes are central to the pathogenesis of the disease and the assessment of vascular involvement has a prognostic value. This assessment therefore has a pivotal role in the management of SSc patients. The aim of our study was to evaluate post-occlusive reactive hyperaemia (PORH) in consecutive SSc patients and to test whether a PORH test might be a useful tool for the early diagnosis of SSc. Method: Between April 2011 and April 2015, 60 consecutive SSc patients (mean age 56 ± 15 years, females:males = 18:1) were enrolled in the study. The patients were divided into those with full-blown SSc (n = 50) and those with very early diagnosis of SSc (VEDOSS) (n = 10) according to the literature. Laser speckle contrast analysis (LASCA) was used to assess PORH. Results: A statistically significant difference was detected in the post-ischaemic hyperaemic peak flow between VEDOSS and established SSc (424% vs. 137%, p = 0.0011). PORH peak flow decreased according to the capillaroscopic pattern (early = 419%, active = 163%, late = 145%, p = 0.0027). Moreover, a correlation between capillary density and peak flow was revealed (rho = 0.33, p < 0.01). Conclusions: These data show a different pattern of vascular involvement in VEDOSS compared to established disease that mirrors capillaroscopic changes. Functional features of very early and established disease seem to be the physiological counterpart of abnormalities detected by capillaroscopy. The POHR test might be a useful aid for further characterization of vascular involvement in SSc. In particular, blunted POHR might prove a tool to separate pre-clinical from full-blown SSc.

The use of rituximab in idiopathic inflammatory myopathies: description of a monocentric cohort and review of the literature

Rituximab (RTX), a chimeric monoclonal antibody targeted against CD20, has been used to treat refractory inflammatory myopathies (IIM). The primary objective of this study was to retrospectively assess the efficacy of RTX in reducing disease activity in patients with IIM refractory to conventional therapy. Secondary aim was the evaluation of adverse events (AE) during the treatment period. We examined 26 patients with a diagnosis of IIM, referred to our Rheumatology Unit and treated with RTX for active refractory disease. Patients were treated with RTX 1000 mg i.v., twice, with a 2-week interval. RTX treatment was associated with a significant reduction of creatine kinase (p=0.001) after six months compared to the baseline, an improved muscular strength measured with MMT8 (p<0.001) and a reduction of the extramuscular activity of the disease measured with MYOACT (p<0.001). In particular, RTX improved DM skin rash, arthritis and pulmonary manifestations. Autoantibody positivity (in particular antisynthetase, anti- SRP and antiRo/SSA), and a disease duration <36 months at the moment of the treatment are associated with a better response rate. Treatment with RTX was also associated with a reduction of the mean daily dose of steroids needed to control disease activity (p=0.002). Our results have confirmed that RTX is efficacious in the treatment of refractory IIM. Ad hoc controlled trials are needed to better clarify the specific subset of patients who may better respond to the treatment and the optimal therapeutic schedule.

SAT0543 Quality of life in behÇet’s syndrome: the role of patient reported outcome

Background Behçet’s syndrome (BS) is a systemic vasculitis, typically characterised by recurrent oro-genital ulcers, ocular inflammation and skin manifestations; articular, vascular, gastro-enteric and neurological involvement may also occur.The complex pattern of BS profile can effect negatively on patients‘ quality of life. Objectives The primary aim of this study was to explore the role of quality of life in BD patients by means of patient reported outcome (PRO); the secondary aim was to study any correlation between disease activity and quality of life. Methods The study enrolled 130 patients (71 M, 59 F), all fulfilling the International Study Group (ISG) criteria for BS. Their mean age was 42±8 years, 18–77 while the mean age at disease onset was 11±4 years 5–18 and the mean follow-up of 8±2 years. Disease activity was evaluated by means of the Behçet’s Disease Current Activity Form (BDCAF), while Short-form-36 (SF-36) was used to evaluate quality of life. Disease activity was compared with the global SF-36 score and with each dimension, that includes: physical functioning, physical disability, body pain, general health, vitality, social functioning, emotional disability, mental health. The statistical analysis was performed using Student t-test, Mann-Whitney-U test, ANOVA and Pearson correlation Results At time of evaluation, according BDCAF, 51 BS patients (39%) had clinically active disease (36 muco-cutaneous involvement, 21 ocular involvement 10 joint involvement, 6 neurological involvement, 4 gastro-enteric). As expected, the overall SF-36 scores were significantly lower in patients with clinically active disease. Moreover, female BS patients had statistically significant lower scores in all SF-36 domains compared with male patients. When each domain of SF-36 was evaluated, we found that physical disability (p=0.004), body pain (p=0.006), general health (p=0.001), and vitality (p=0.001) were significantly lower in patients with disease activity. Notably, vitality (p=0.001), physical disability(p=0.004), social functioning (p=0.001), emotional disability (p=0.003) and mental health (p=0.001) were significantly lower in patients with muco-cutaneous active disease, compared with the other patients with active disease. Conclusions The clinicians who take care of any chronic disease would like to correctly know the current status of a patient to manage him properly. In this regard, the combination data of PRO measures and disease activity have been demonstrated to add more information compared to the evaluation of disease activity alone. These consideration suggest that the correct assessment of BS needs a multi-dimensional approach, that fairly includes disease activity, disease damage and quality of life Disclosure of Interest None declared

Muscular vasculitis confined to lower limbs: description of two case reports and a review of the literature

Muscular involvement is common during systemic vasculitides, such as polyarteritis nodosa. However, in rare cases, muscular involvement can be the only clinically evident feature of the disease. The clinical pattern of isolated muscular vasculitis may mimic several other inflammatory muscle disorders, such as idiopathic inflammatory myositis, and may represent a challenge in differential diagnosis. Herewith, we present two clinical cases as examples of peculiar clinical and histopathological characteristics of isolated muscular vasculitis. Our patients were successfully treated with steroids and immunosuppressive agents. Moreover, we provide a review of the recent existing medical literature. Our cases suggest the importance of performing muscle biopsy in patients with muscular symptoms to guide the diagnosis and the treatment.

Prognosis and Disease Activity

Behcet’s disease (BD) is globally characterized by a variable spectrum of disease profile: while prevalent mucocutaneous lesions and arthritis represent the only clinical features in patients with a benign disease subset, there are other patients who develop potentially sight or life-threatening manifestations, due to ocular, neurological, or major vascular involvement. Beside the organ involvement, demographic factors could considerably influence the long-term and short-term outcomes of BD: age at disease onset, duration of disease, gender, and sex. Younger men patients are more suitable to have a more severe disease, due to an increased frequency both of morbidity and mortality, related to ocular, vascular, and neurological involvement. Eye involvement represents one of the most serious manifestation of BD and occurs in half of the patients. It seems more frequent and more severe among young males and, unluckily, it still remains one of the most significant causes of morbidity. Usually, ocular disease develops within the first years of disease onset and it seems to be more severe in this period; moreover, growing data suggest that the prognosis of BD patients with ocular involvement is mainly dependent upon the severity of visual acuity at presentation. Although not included in the ISG criteria for BD, neurological involvement represents the second main cause of mortality, preceded by large vessel disease. Parenchymal CNS involvement represents a serious morbidity of disease, often leading to disability and, if not treated early, to mortality, while dural sinus thrombosis is associated with a more favorable outcome than parenchymal involvement. The prevalence of vascular involvement varies from 20 to 35 % of BD patients and it may involve all types of vessels within the arterial and venous system. It is characterized by a clear male preponderance. Vascular involvement in BD represents a serious risk for multiple vessel-related complications, including thromboses, stenoses, occlusions, and aneurysms. Since there are no established laboratory findings to define BD and the diagnosis remains mainly dependent on the identification of the typical clinical pictures, to a certain extent, there are no optimal measures that would simplify the evaluation of the disease. Unluckily, there are no validated biomarkers that could reflect disease activity over time.

AB0839 Evaluation of serum levels of N-terminal prob-type natriuretic peptide (NT-PROBNP) in patients with polymyositis and dermatomyositis (PM/DM): Preliminary data

Background symptomatic clinically cardiac involvement in PM/DM is rare but seems to be one of the most important cause of death1. High Nt-proBNP levels are commonly considered a marker of heart failure and were recently detected in rheumatic diseases without clinically evident heart involvement. Some authors hypothesize that high Nt-proBNP values can be likely considered indicators of subclinical cardiac damage2. Objectives evaluation Nt-proBNP levels in a group of patients with PM/DM compared with normal healthy subjects. Methods we enrolled consecutive PM/DM patients (Bohan and Peter criteria) hospitalized in our Unit from 2006 to 2010; in all of them we measured Nt-proBNP serum levels (normal values <125 pg/ml) and performed an echocardiographic evaluation. We excluded patients with reduced left ventricular function (EF<55%), kidney failure, ischemic cardiomyopathy, arrhythmias and clinical history for other cardiovascular diseases. The most common cardiovascular risk factors as hypertension, hypercholesterolemia, diabetes, smoke were evaluated. Results we enrolled 34 patients (21 PM and 13 DM); 26 female and 8 male, mean age 54 years [24-76]; mean disease duration 24 month [0-24], and a group of 32 healthy subjects, comparable for age and sex. Mean value of Nt-proBNP levels was 352 pg/ml in PM/DM patients (440 pg/ml in PM, 217 pg/ml in DM) and 51 pg/ml in control group (p<0.001). We also subdivided PM/DM and the control group according to the presence of cardiovascular risk factors and compared Nt-proBNP levels in 4 groups. Data are reported in the table Group Subgroups No. patients Mean Nt-proBNP values [range] 1 PM/DM with risk factors 19 536 [10-4955]°* 2 PM/DM without risk factors 15 103 [10-378]° 3 Normal subjects with risk factors 15 60 [16-192]* 4 Normal subjects without risk factors 17 41 [4-100] °p=0.006, *p=0.005. In PM/DM patients, the presence of cardiovascular risk factors increased widely Nt-proBNP levels (536 vs 103 pg/ml; p=0.006) while in the controls group the values were only lowly increased (60 vs. 41). In the subgroups without cardiovascular risk factors (2 and 4), Nt-proBNP mean values, even if in the normal range, were higher in PM/DM group than in healthy subjects (p=0.074). In presence of cardiovascular risk factors, Nt-proBNP mean values were higher in the subgroup 1 compared with subgroup 3 (p=0005). Conclusions This data suggests that, even without evident cardiac involvement, in presence of cardiovascular risk factors, patients with PM/DM have higher Ntpro-BNP levels and probably an higher risk to develop heart involvement. This intriguing aspect needs to be studied in detail in a larger amount of patients and controls, to establish the weight of the single cardiovascular risk factor. References Lundberg I: The heart in dermatomyositis and polymyositis. Rheumatology (Oxford) 2006; 45 Suppl 4: iv 18-21. Giannoni A, Tani C et al: When the heart is burning: amino-terminal pro-brain natriuretic peptide as an early marker of cardiac involvement in active autoimmune rheumatic disease. Int J Cardiol. 2011;148(2):161-7. Disclosure of Interest None Declared