Giuseppe Germanò

Large-vessel involvement in recent-onset giant cell arteritis: a case–control colour-Doppler sonography study

OBJECTIVES The prevalence of large-vessel vasculitis (LVV) in newly diagnosed GCA is still debated. The aim of this study was to investigate the prevalence of LVV in newly diagnosed GCA using colour-Doppler sonography (CDS) and to compare the clinical and laboratory findings of GCA patients with and without LVV. METHODS Sixty-two consecutive patients with new-onset GCA underwent CDS of the epiaortic vessels and of the aorta. The identified patients with LVV were randomly matched (1 : 2 ratio) to GCA patients without LVV. RESULTS In 18 (29%) out of 62 patients, CDS showed the characteristic halo sign indicative of vasculitis in at least one vessel examined. Three patients had insufficient documentation and were excluded from the comparative analysis. Compared with patients without LVV, those with LVV were more frequently female (100 vs 73%), less likely to have cranial manifestations (73 vs 97%) and borderline less likely to have jaw claudication (13 vs 43%, P = 0.05). The two groups had similar ages at diagnosis, prevalence of constitutional manifestations and rates of positive temporal artery biopsies. CONCLUSIONS LVV evidenced by CDS was found in 29% of patients with newly diagnosed GCA. This prevalence is similar to that found in previous studies with a similar design. GCA patients with LVV had less frequent cranial manifestations. Early diagnosis of LVV in GCA can help tailor treatment accordingly and may prevent vascular complications.

Is colour duplex sonography-guided temporal artery biopsy useful in the diagnosis of giant cell arteritis? A randomized study

OBJECTIVE The aim of this study was to assess the usefulness of colour duplex sonography (CDS)-guided temporal artery biopsy (TAB) for the diagnosis of GCA in patients with suspected GCA. METHODS From September 2009 through December 2012, 112 consecutive patients with suspected GCA were randomized to undergo CDS-guided TAB or standard TAB. All patients underwent temporal artery physical examination and temporal artery CDS prior to TAB. CDS of the temporal artery was performed by the same ultrasonographer, who was unaware of the patients clinical data, and all TABs were evaluated by the same pathologist. Seven patients in whom biopsy failed to sample temporal artery tissue were excluded from the analysis. RESULTS Fifty patients were randomized to undergo CDS-guided TAB and 55 patients to standard TAB. Except for a younger age in patients who underwent standard TAB (P = 0.026), no significant differences were observed between the two groups. There were no significant differences in the frequencies of positive TAB for classic transmural inflammation (28% vs 18.2%) or for periadventitial small vessel vasculitis and/or vasa vasorum vasculitis (6% vs 14.5%) between the two groups. No significant differences in the frequency of positive TAB in the two groups were observed when we excluded the patients treated with glucocorticoids and when we stratified the patients of the two groups for the presence or absence of the halo sign. CONCLUSION Our study showed that CDS-guided TAB did not improve the sensitivity of TAB for diagnosing GCA.

Comparison between colour duplex sonography findings and different histological patterns of temporal artery

OBJECTIVE To assess the findings of temporal artery colour duplex sonography (CDS) in GCA characterized by a histological pattern of periadventitial small vessel vasculitis (SVV) and/or vasa vasorum vasculitis (VVV) and compare it with those observed in classic GCA with transmural vasculitis. METHODS We studied 30 patients with SVV and/or VVV, 63 patients with classic GCA and 67 biopsy-negative patients identified over a 9-year period. CDS of the temporal arteries was performed in all patients by one ultrasonographer. Temporal artery biopsy was used as the reference standard. Sensitivities, specificities and likelihood ratios (LRs) were calculated. RESULTS The frequency of the halo sign on CDS was significantly lower in the patients with SVV and/or VVV compared with those with classic GCA (20% vs 82.5%, P = 0.0001). The halo sign had a sensitivity of only 20% (95% CI 8.4, 39.1%) and a specificity of 80.6% (95% CI 68.7, 88.9%) for the diagnosis of SVV and/or VVV. The negative LR was 0.992 (CI 0.824, 1.195), and the positive LR was 1.030 (CI 0.433, 2.451). The halo sign for the diagnosis of biopsy-proven classic GCA had a higher sensitivity of 82.5% (CI 70.5, 90.5%), the same specificity of 80.6% (CI 68.7, 88.9%) and a higher positive LR (4.253; CI 2.577, 7.021). CONCLUSION The halo sign is infrequently found in GCA characterized by a histological pattern of SVV and/or VVV. This limits the sensitivity of CDS in correctly identifying patients with GCA.

Contrast-enhanced ultrasound of the carotid artery in patients with large vessel vasculitis: Correlation with positron emission tomography findings.

To assess the findings of contrast‐enhanced ultrasound (CEUS) of carotid arteries in patients with large vessel vasculitis (LVV) and to compare them with those observed using 18F‐fluorodeoxyglucose–positron emission tomography (18FDG‐PET).

Histopathologic Findings of Patients With Biopsy-Negative Giant Cell Arteritis Compared to Those Without Arteritis: A Population-Based Study.

To evaluate whether there are histopathologic features of negative temporal artery biopsy (TAB) that allow differentiation between patients with giant cell arteritis (GCA) and those without.

Clinical images: PET-CT and contrast-enhanced ultrasound in Takayasu’s arteritis

35 Kelchtermans H, De Klerck B, Mitera T et al. Defective CD4+CD25+ regulatory T cell functioning in collageninduced arthritis: an important factor in pathogenesis, counter-regulated by endogenous IFN-gamma. Arthritis Res Ther 2005;7:R402 15. 36 Glant TT, Mikecz K, Arzoumanian A et al. Proteoglycan-induced arthritis in BALB/c mice. Clinical features and histopathology. Arthritis Rheum 1987;30:201 12.

FRI0472 Correlations between Different Histological Subsets of GIANT Cell Arteritis and Clinical Manifestations in A Large Monocentric Cohort of Biopsy Positive GCA Patients

Background Temporal artery biopsy (TAB) showing transmural inflammation is considered the gold standard for the diagnosis of giant cell arteritis (GCA). In some cases of GCA, inflammation is confined to the periadventitial small vessels, the vasa vasorum and/or the adventitia. These patients seem to closely resemble classic GCA, but the final significance of this more limited inflammation need more confirmation. Objectives To describe and correlate different histological subsets of GCA with demographic and clinical manifestations in a large monocentric cohort of biopsy positive GCA patients. Methods All TABs performed for suspected GCA between 1986 and 2012 were reviewed by a single pathologist. Based on the localization of the inflammation, positive TABs were classified into 4 categories: small vessel vasculitis (SVV), with inflammation limited to small periadventitial vessels devoid of muscular coat; vasa vasorum vasculitis (VVV), with inflammation surrounding the adventitial vasa vasorum; inflammation limited to adventitia (ILA), with inflammation spreading from vasa vasorum to the adventitia without extension to the media; transmural inflammation (TMI), with external elastic lamina disruption and extension of the inflammation to the media. Results 317 TABs were positive for inflammation and were classified as: 253 (79.8%) TMI, 18 (5.7%) ILA, 19 (6.%) VVV and 27 (8.5%) SVV. Compared to patients with TMI, those with SVV and VVV had a significantly lower frequency of headache (55.6% vs 77.9%, p=0.010 for SVV and 57.9% vs 77.9%, p=0.048 for VVV), jaw claudication (7.4% vs 44.7%, p<0.0001 for SVV and 15.8% vs 44.7%, p=0.015 for VVV), abnormalities of TA at physical examination (33.3% vs 71.3%, p<0.0001 for SVV and 47.1% vs 71.3%, p=0.036 for VVV), halo at TA color duplex sonography (CDS) (27.3% vs 72.4%, p<0.0001 for SVV and 16.7% vs 72.4%, p<0.0001 for VVV), systemic symptoms (only for VVV, 42.1% vs 66.8%, p=0.029), a lower levels of ESR (70.4±30.9 vs 86.5±30.1, p=0.011 for SVV and 64.9±34.7 vs 86.5±30.1, p=0.010 for VVV, mean ± DS mm/hour) and CPR (7.4±8.4 vs 8.9±6.1, p=0.027 for SVV and 3.5±3.7 vs 8.9±6.1, p<0.0001 for VVV, mean ± DS mg/dl) an higher frequency of male gender (63% vs 22.1%, p<0.0001 for SVV and 42.1% vs 22.1%, p=0.048 for VVV) and peripheral arthritis (only for SVV, 22.2% vs 6%, p=0.002) but a similar frequency of polymyalgia rheumatica, large vessel involvement and visual symptoms (including blindness). Patients with ILA were more similar to those with TMI, showing only a lower frequency of headache (55.6% vs 77.9%, p=0.031), abnormalities of TA at physical examination (40% vs 71.3%, p=0.011) and halo at TA CDS (14.3% vs 72.4%, p=0.003). Conclusions The histological spectrum of inflammatory lesions that can be found in TAB is broad and constitutes a continuum, ranging from SVV at one extreme, through VVV and the more spread ILA in the middle, to TMI at the other extreme of the spectrum. Despite the differences in cranial symptoms, halo sign at CDS and levels of acute-phase reactants, it is crucial that clinicians be aware that all different histologic TAB patterns are equally associated with a risk of visual loss, thus requiring prompt glucocorticoid treatment. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.5674

FRI0471 Negative Temporal Artery Biopsies: Pathologic Findings of Patients with Biopsy-Negative GIANT Cell Arteritis Compared to Those of Patients without Arteritis

Background Temporal artery biopsy (TAB) showing transmural inflammation is considered the gold standard for the diagnosis of giant cell arteritis (GCA). A negative TAB does not rule out GCA, and a diagnosis of biopsy-negative GCA was reported in 5-25% of patients. In the absence of active inflammation (negative TAB), other structural changes in the wall of TA are often present and some of those have been described as “healed” or quiescent arteritis, but if these histological changes are expression of GCA is still debated. Objectives To evaluate if there are histopathological features of negative TAB that allow to differentiate patients with GCA from those without. Methods 42 consecutive patients with negative TAB were retrospectively selected. All patients underwent TAB for suspected GCA between January 2009 and December 2012. Demographic, clinical and laboratory data at presentation and at each follow up visit were collected. A pathologist with expertise in vasculitis blinded to clinical data and final diagnosis reviewed all 42 negative TABs. Histopathologic features evaluated were: the presence of a focal medio-intimal scar with medial attenuation, intimal hyperplasia, fragmentation of inner elastic lamina (IEL), calcification, adventitial fibrosis and neoangiogenesis. Results After a median follow-up period of 177 days (interquartile range 38, 508), 20 of the 42 patients had a final diagnosis of GCA, while in the remaining 22 patients GCA was excluded (9 had polymyalgia rheumatica, 4 non arteritic anterior ischemic optic neuropathy, 3 fibromyalgia, 2 non-specific elevation of inflammatory markers, 1 fever of unknown origin, 1 rheumatoid arthritis, 1 ANCA associated vasculitis, 1 osteoarthitis). 1990 ACR classification criteria for GCA were satisfied in 13 of the 20 patients with GCA (65%) and in none of the 22 non-GCA patients. 12 patients (60%) with GCA and 14 patients (64%) with non-GCA were on steroid therapy when TAB was performed (p>0.05). The mean prednisone dose was (mg± SD) 23.75 ±12.95 for GCA patients and 13.57 ±11.67 for non-GCA patients (p=0.05). Mean duration of prednisone treatment was (days±SD) 30.58±44.23 for GCA patients and 144.36±162.24 for non GCA patients (p<0.05). A focal medio-intimal scar with medial attenuation was found in 15% of GCA vs 14% of non-GCA patients (p>0.05). Intimal hyperplasia was present in 45% vs 59%, fragmentation of IEL in 80% vs 91%, calcification in 30% vs 18%, adventitial fibrosis in 10% vs 5% and neoangiogenesis in 10% vs 9% of GCA vs non-GCA patients respectively (all p NS). 4 patients with GCA had visual loss. A focal medio-intimal scar with medial attenuation was not observed in these 4 patients, intimal hyperplasia was observed in 2, fragmentation of IEL in all 4, calcification in 2, adventitial fibrosis in 1 and neoangiogenesis in 1. Histological findings of GCA patients with visual loss were similar to those of patients with non-GCA. Conclusions The histological features of negative TAB evaluated in this study do not allow to differentiate between GCA and non-GCA patients. These data suggest that in the absence of mural active inflammation, other histological changes of the TA wall are not specific for GCA. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.5633

SAT0268 Comparison of Histopathological Findings with Clinical Manifestations in A Large Single Center Cohort of Patients with Biopsy-Proven GIANT Cell Arteritis

Background Giant cell arteritis (GCA) is a vasculitis that involves large and medium sized arteries in patients older than 50 years. Temporal artery biopsy (TAB) is the gold standard for the diagnosis of GCA. Cranial symptoms are the most common manifestations of the disease, while permanent visual loss is the most feared ischaemic complication of GCA and is reported in 10-20% of patients. Previous study have tried to correlate histological features of TAB with cranial and visual symptoms, but the results reported are not conclusive. Objectives To correlate histological findings of TAB with clinical manifestations in a large single center cohort of consecutive patients with biopsy-proven GCA. Methods A pathologist with expertise in vasculitis and blinded to clinical data and final diagnosis reviewed all TABs performed for suspected GCA at our hospital between January 1986 and December 2012. Positive TABs showing only small vessel vasculitis and/or vasa vasorum vasculitis without transmural inflammation were excluded from the comparison analysis. Histopathologic features evaluated were: the severity of inflammation and intimal hyperplasia, both graded on a semiquantitative scale (mild=1, moderate=2 severe=3), the presence of intraluminal acute thrombosis, calcifications, giant cells, fibrinoid necrosis and laminar necrosis, consisting in a band of coagulative necrosis sometimes bordered by palisading histiocytes and following the internal elastic lamina. Results 271 patients had a final diagnosis of biopsy-proven GCA and were included in the study. More severe inflammation on semiquantitative scale was more frequently seen in patients with any cranial symptoms (88.4% grade 3; 87.5% grade 2 and 74.7% grade 1, p=0.026), headache (80.4% grade 3; 80% grade 2 and 65.3% grade 1, p=0.038), abnormalities of TA at physical examination (82.6% grade 3; 63.5% grade 2 and 56.9% grade 1, p=0.001) and halo at TA colour duplex sonography (CDS) (75.5% grade 3; 78.4% grade 2 and 48.5% grade 1, p=0.011). The presence of laminar necrosis was more frequent in patients with visual symptoms (43.1% vs 24.8%, p=0.005), and in those with abnormalities of TA at physical examination (82.3% vs 65.3%, p=0.012). The presence of calcifications was more frequent in patients with visual symptoms (45.5% vs 25%, p=0.003), and in patients without systemic symptoms (71.3% vs 52.7%, p=0.009). More severe intimal hyperplasia on semiquantitative scale was less frequently seen in patients with polymyalgia rheumatica (PMR) (32.2% grade 3; 53.8% grade 2 and 56.3% grade 1, p=0.008). The presence of giant cells was more frequent in patients with jaw claudication (49.2% vs 30.8%, p=0.006). Fibrinoid necrosis was present only in 2 cases (0,7%), in both sparing the temporal artery and limited to a small branch. Conclusions The data of this large monocentric cohort of biopsy-proven GCA patients evidenced that visual symptoms correlate with the presence of laminar necrosis and calcifications. Cranial symptoms and halo at TA CDS correlate with the severity of mural inflammation. PMR inversely correlates with intimal hyperplasia. Fibrinoid necrosis was not a features of GCA. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.5659