Effect of glucocorticoid treatment on computed tomography angiography detected large-vessel inflammation in giant-cell arteritis. A prospective, longitudinal study.

Computed tomography angiography (CTA) detects signs of large-vessel vasculitis (LVV) in about 67.5% of patients with giant-cell arteritis (GCA) at the time of diagnosis and early aortic dilatation in 15%. The outcome of CTA-findings of LVV upon glucocorticoid treatment has not been prospectively evaluated. The aim of our study was to prospectively assess glucocorticoid-induced changes in CTA findings of LVV in patients with GCA. Forty biopsy-proven GCA patients evaluated by CTA at diagnosis were prospectively followed and scheduled a new CTA approximately after 1 year of treatment. Vessel wall thickening, diameter, and contrast enhancement of the aorta and its tributaries were evaluated. Results were compared to those obtained at the time of diagnosis. CTA was repeated to 35 patients after a median follow-up of 13.5 months (IQ25-75% 12.4-15.8). Arterial wall thickening was still present in 17 patients (68% of the patients who initially had LVV). The number of affected segments and wall thickness at various aortic segments significantly decreased and no patients developed new lesions, new aortic dilation or increase in previous dilation. Contrast enhancement disappeared in 15 (93.75%) of 16 patients in whom this finding could be assessed. Signs of LVV improve with treatment. While contrast enhancement resolves in the majority of patients, vessel wall thickening persists in two thirds. However, the number of affected aortic segments as well as aortic wall thickness significantly decreases. Longer follow-up is necessary to determine the clinical significance of persisting wall thickening and its relationship with relapses or subsequent development of aortic dilatation or large-vessel stenoses.

Advances in the diagnosis of large vessel vasculitis.

The diagnosis of large-vessel vasculitis has experienced substantial improvement in recent years. While Takayasu arteritis diagnosis relies on imaging, the involvement of epicranial arteries by giant-cell arteritis facilitates histopathological confirmation. When appropriately performed temporal artery biopsy has high sensitivity and specificity. However, an optimal biopsy is not always achievable and, occasionally, the superficial temporal artery may not be involved. Imaging in its various modalities including colour-duplex ultrasonography, computed tomography angiography, magnetic resonance angiography and positron emission tomography, are emerging as important procedures for the diagnosis and assessment of disease extent in large-vessel vasculitis. Recent contributions to the better performance and interpretation of temporal artery biopsies as well as advances in imaging are the focus of the present review.

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.

Prospective long term follow-up of a cohort of patients with giant cell arteritis screened for aortic structural damage (aneurysm or dilatation).

BACKGROUND: Aortic structural damage (ASD) may complicate the course of patients with giant cell arteritis (GCA). However the frequency and outcome of ASD has not been assessed in long term prospective studies. METHODS: In a previous screening of 54 biopsy proven GCA patients, significant ASD was detected in 12 (22.2%) after a median follow-up of 5.4 years. These patients were periodically evaluated (every 4 years) over a median of 10.3 years (range 4-16.6 years) in order to investigate the development of new ASD and the outcome of previously detected abnormalities. RESULTS: 18 of the 54 patients abandoned the study due to death or other reasons. The remaining 36 patients were subjected to a second screening and 14 to a third screening. 12 (33.3%) of the 36 patients re-screened and 16 (29.6%) of the initial cohort developed ASD, all but one in the thoracic aorta. Aortic diameters at the ascending and descending aorta significantly increased over time. One patient (1.9% of the initial cohort) died from aortic dissection. Surgery was advised in eight (50%) patients with ASD but could only be performed in three patients (37.7%). The development of ASD was not associated with persistence of detectable disease activity. CONCLUSIONS: The incidence of ASD is maximal within the first 5 years after diagnosis but continues developing over time, affecting up to 33.3% of individuals after long term follow-up. Once ASD occurs, dilatation increases over time, underlining the need for periodic evaluation. Surgical repair is feasible in about one-third of candidates.

Treatment with angiotensin II receptor blockers is associated with prolonged relapse-free survival, lower relapse rate, and corticosteroid-sparing effect in patients with giant cell arteritis.

OBJECTIVE: To determine whether concomitant treatment with angiotensin-converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB) is associated with changes in the outcome of patients with giant cell arteritis (GCA). METHODS: A study cohort of 106 patients with biopsy-proven GCA was longitudinally followed up for 7.8 ± 3.3 years. Patients were stratified according to their treatment with ACEI, ARB, or no ACEI/ARB. Time to first relapse, number of flares, time to achieve a stable prednisone dose <10mg/day and <5mg/day with no relapses, time required to completely discontinue prednisone, cumulative dose of prednisone received during the first year, and concentrations of acute-phase reactants at pre-defined time points (baseline, 6, 12, 18, and 24 months) were compared among the 3 groups. Cox proportional hazards models were performed to adjust for potential confounders. RESULTS: Patients receiving ARB presented a significantly longer relapse-free survival than patients treated with ACEI or patients not receiving ACEI/ARB (p = 0.02). The adjusted hazard ratio for relapses in patients treated with ARB was 0.32 (95% CI: 0.12-0.81, p = 0.017). In addition, patients who received ARB achieved a prednisone maintenance dose <10mg/day faster than all other patients (p = 0.0002). No significant differences were observed among groups in acute-phase reactant levels during follow-up. However, patients not receiving ACEI/ARB had significantly higher C-reactive protein and haptoglobin concentrations than those receiving ACEI or ARB at various time points. CONCLUSIONS: Addition of ARB to glucocorticoids is associated with lower relapse rate and more prolonged disease-free survival in patients with GCA.

Large vessel involvement in biopsy-proven giant cell arteritis: prospective study in 40 newly diagnosed patients using CT angiography.

BACKGROUND: Necroscopic and surgical studies have suggested that giant cell arteritis (GCA) may target the aorta and its main branches. Imaging techniques are able to detect large vessel vasculitis (LVV) non-invasively in patients, but the prevalence of LVV in GCA has not been clearly established. OBJECTIVE: To assess prospectively the prevalence, characteristics and topography of LVV in patients with newly diagnosed GCA and to determine the associated clinical and laboratory features. METHODS: CT angiography (CTA) was performed in 40 consecutive patients with newly diagnosed biopsy-proven GCA. Patients were treatment-naïve or had been treated with corticosteroids for <3 days. Vessel wall thickness and vessel diameter (dilation or stenoses) at four aortic segments (ascending aorta, aortic arch, descending thoracic and abdominal aorta) and at the main aortic branches were evaluated. RESULTS: LVV was detected in 27 patients (67.5%). The vessels involved were as follows: aorta (26 patients, 65%), brachiocephalic trunk (19 patients, 47.5%), carotid arteries (14 patients, 35%), subclavian arteries (17 patients, 42.5%), axillary arteries (7 patients, 17.5%), splanchnic arteries (9 patients, 22.5%), renal arteries (3 patients, 7.5%), iliac arteries (6 patients, 15%) and femoral arteries (11 patients, 30%). Dilation of the thoracic aorta was already present in 6 patients (15%). Cranial ischaemic events were significantly less frequent in patients with LVV (p=0.029). Treatment-naïve patients had a higher frequency of LVV (77% vs 29%, p=0.005). CONCLUSIONS: CTA-defined LVV occurs in two-thirds of patients with GCA at the time of diagnosis and aortic dilation is already present in 15%. Previous corticosteroid treatment may decrease CTA-detected LVV.

Central nervous system vasculitis: still more questions than answers.

The central nervous system (CNS) may be involved by a variety of inflammatory diseases of blood vessels. These include primary angiitis of the central nervous system (PACNS), a rare disorder specifically targeting the CNS vasculature, and the systemic vasculitides which may affect the CNS among other organs and systems. Both situations are severe and convey a guarded prognosis. PACNS usually presents with headache and cognitive impairment. Focal symptoms are infrequent at disease onset but are common in more advanced stages. The diagnosis of PACNS is difficult because, although magnetic resonance imaging is almost invariably abnormal, findings are non specific. Angiography has limited sensitivity and specificity. Brain and leptomeningeal biopsy may provide a definitive diagnosis when disclosing blood vessel inflammation and are also useful to exclude other conditions presenting with similar findings. However, since lesions are segmental, a normal biopsy does not completely exclude PACNS. Secondary CNS involvement by systemic vasculitis occurs in less than one fifth of patients but may be devastating. A prompt recognition and aggressive treatment is crucial to avoid permanent damage and dysfunction. Glucocorticoids and cyclophosphamide are recommended for patients with PACNS and for patients with secondary CNS involvement by small-medium-sized systemic vasculitis. CNS involvement in large-vessel vasculitis is usually managed with high-dose glucocorticoids (giant-cell arteritis) or glucocorticoids and immunosuppressive agents (Takayasu's disease). However, in large vessel vasculitis, where CNS symptoms are usually due to involvement of extracranial arteries (Takayasu's disease) or proximal portions of intracranial arteries (giant-cell arteritis), revascularization procedures may also have an important role.