Positron emission tomography assessment of large vessel inflammation in patients with newly diagnosed, biopsy-proven giant cell arteritis: a prospective, case-control study

BACKGROUND: Positron emission tomography (PET) scan is emerging as a promising imaging technique to detect large-vessel inflammation in giant cell arteritis (GCA). However, the lack of a standardised definition of arteritis based on (18)fluorodeoxyglucose (FDG) uptake is an important limitation to the use of PET scan for diagnostic purposes. OBJECTIVE: To prospectively assess the intensity and distribution of FDG uptake at different vascular territories in patients with newly diagnosed GCA compared with controls. METHODS: 32 consecutive, biopsy-proven, GCA patients treated with glucocorticoids for ≤3 days were included. The control group consisted of 20 individuals, who underwent PET/CT for cancer staging. Maximal standardised uptake value (SUVm) was calculated at four aortic segments, supraaortic branches and iliac-femoral territory. Sensitivity and specificity was calculated by receiver-operator characteristic curves (ROC) analysis. RESULTS: Mean SUVm was significantly higher in patients than in controls in all vessels explored and correlated with acute-phase reactants and serum IL-6. Mean of the SUVm at all the vascular territories had an area under the curve (AUC) of 0.830, and a cut-off of 1.89 yielded a sensitivity of 80% and a specificity of 79% for GCA diagnosis. There were no significant differences in AUC among the vascular beds examined. CONCLUSIONS: FDG uptake by large vessels has a substantial sensitivity and specificity for GCA diagnosis

Early- versus late-onset systemic sclerosis. Differences in clinical presentation and outcome in 1037 patients

Peak age at onset of systemic sclerosis (SSc) is between 20 and 50 years, although SSc is also described in both young and elderly patients. We conducted the present study to determine if age at disease onset modulates the clinical characteristics and outcome of SSc patients. The Spanish Scleroderma Study Group recruited 1037 patients with a mean follow-up of 5.2 ± 6.8 years. Based on the mean ± 1 standard deviation (SD) of age at disease onset (45 ± 15 yr) of the whole series, patients were classified into 3 groups: age ≤ 30 years (early onset), age between 31 and 59 years (standard onset), and age ≥ 60 years (late onset). We compared initial and cumulative manifestations, immunologic features, and death rates. The early-onset group included 195 patients; standard-onset group, 651; and late-onset, 191 patients. The early-onset group had a higher prevalence of esophageal involvement (72% in early-onset compared with 67% in standard-onset and 56% in late-onset; p = 0.004), and myositis (11%, 7.2%, and 2.9%, respectively; p = 0.009), but a lower prevalence of centromere antibodies (33%, 46%, and 47%, respectively; p = 0.007). In contrast, late-onset SSc was characterized by a lower prevalence of digital ulcers (54%, 41%, and 34%, respectively; p < 0.001) but higher rates of heart conduction system abnormalities (9%, 13%, and 21%, respectively; p = 0.004). Pulmonary hypertension was found in 25% of elderly patients and in 12% of the youngest patients (p = 0.010). After correction for the population effects of age and sex, standardized mortality ratio was shown to be higher in younger patients. The results of the present study confirm that age at disease onset is associated with differences in clinical presentation and outcome in SSc patients

Persistence of inflammatory activity in giant cell arteritis:Role of the angiotensin II system

[spa] La arteritis de células gigantes (ACG) es una vasculitis sistémica idiopática que afecta principalmente arterias de mediano y gran calibre. La calidad de vida de estos pacientes puede verse seriamente afectada debido a múltiples complicaciones inmediatas y tardías. Esta tesis es un compendio de cuatro artículos que evalúan características clínicas e inmunopatológicas de la persistencia de la inflamación crónica en la ACG. En la primera publicación, se describen las características y la evolución de la enfermedad en una pequeña serie de pacientes latinoamericanos, concluyéndose que las manifestaciones y el comportamiento de esta vasculitis es similar a la reportada en otras cohortes, principalmente de origen caucásico. En el segundo artículo se describe la prevalencia, características y factores asociados con las recaídas o rebrotes, una manifestación de la constante actividad inflamatoria de la ACG. Nuestro estudio demostró que los pacientes con esta vasculitis sufren recaídas de manera frecuente, lo que se asoció a largo plazo con mayor requerimiento de esteroides sistémicos y mayor prevalencia de efectos adversos. La tercera publicación tuvo como punto de partida la necesidad de identificar tratamientos alternativos para lograr un mejor control de la ACG. El punto de partida de este estudio fueron los efectos anti-inflamatorios vinculados a los antagonistas de los receptores de angiotensina (ARA). Los resultados mostraron que la adición de ARA al tratamiento habitual de la ACG estaba asociado con un menor número de recaídas y un efecto ahorrador de corticoesteroides (CE). A partir de esta observación clínica, investigamos si la angiotensina II (ATll) podría desempeñar un papel en el mantenimiento de la actividad inflamatoria crónica de la ACG. En el cuarto manuscrito mostramos que el sistema de la ATll está sobre-expresado en las arterias temporales de pacientes con esta vasculitis. Además, corroboramos que la ATll es capaz de inducir citoquinas pro-inflamatorias en un sistema de co-cultivo de linfocitos, monocitos y células musculares lisas vasculares derivadas de arteria temporal, efecto inhibido mediante el bloqueante del receptor de angiotensina II, losartán.[eng] Giant cell arteritis (GCA) is a systemic vasculitis of unknown aetiology that affects medium-sized and large arteries. GCA may deeply impair the patient's quality of life as a result of systemic smouldering activity, disease progression or adverse effects related to therapy. The present thesis is a compendium of four articles assessing clinical and immunopathological characteristics associated with persistence of chronic inflammation in GCA patients. In the first publication, we described the clinical course of a small series of GCA patients derived from Latin America, a geographic area where data regarding this disease were virtually absent. We found that major features observed in this population were similar to those reported in series of Caucasian origin. The second article described the prevalence, predictors, and main features of relapses, one of the many faces of the persistent inflammatory activity that characterizes GCA. This study, performed in a large cohort of patients uniformly treated and followed, demonstrated that disease flares are frequent and, importantly, that a relapsing course was associated with higher and prolonged GC requirements and increased morbidity. The third publication was oriented to the need of identifying adjuvant therapies for GCA and deals with the potential benefit of adding angiotensin II receptor blockers (ARB) to standard prednisone treatment. The study rationale was based on the pleiotropic anti-inflammatory effects recently described for this drug class. Our results suggest that ATII receptor blockade may help to maintain remission, reduce the relapse rate, and spare glucocorticoids in patients with GCA. Following this clinical observation, we further investigated a potential contribution of the angiotensin II (ATII) system in the maintenance of inflammatory activity in GCA. In the fourth paper we showed that ATII system is overexpressed in GCA inflammatory lesions. In addition, we confirmed that ATII exhibited pro-inflammatory properties in co-cultures of Iymphocytes, monocytes and temporal artery-derived vascular smooth muscle cells which were reversed by the angiotensin II receptor blocker losartan