Francesco Muratore

Large-vessel giant cell arteritis: a cohort study

OBJECTIVE The aim of this study was to compare baseline variables, treatment and outcomes in patients with large-vessel GCA (LV-GCA), primarily of the upper extremities, with those with cranial disease (C-GCA). METHODS All patients >50 years of age with radiographic evidence of subclavian LV-GCA diagnosed between 1 January 1999 and 31 December 2008 were identified and compared with those with biopsy-positive C-GCA diagnosed in the same period. RESULTS The study included 120 LV-GCA patients and 212 C-GCA patients. Compared with C-GCA, patients with LV-GCA were younger [68.2 years (s.d. 7.5) vs 75.7 (7.4), P < 0.001] and had longer duration of symptoms at GCA diagnosis (median 3.5 vs 2.2 months, P < 0.001). A history of PMR was more common in LV-GCA patients (26% vs 15%, P = 0.012), but a smaller proportion had cranial symptoms (41% vs 83%, P < 0.001) and vision loss (4% vs 11%, P = 0.035). ACR classification criteria for GCA were satisfied in 39% of LV-GCA patients and 95% of C-GCA patients (P < 0.001). Compared with C-GCA, patients with LV-GCA had more relapses (4.9 vs 3.0/10 person-years, P < 0.001), higher cumulative corticosteroid (CS) doses at 1 year [11.4 g (s.d. 5.9) vs 9.1 (s.d. 3.7), P < 0.001] and required longer treatment (median 4.5 vs 2.2 years, P < 0.001). CONCLUSION Although patients with LV-GCA had a lower rate of vision loss, they had a higher relapse rate and greater CS requirements. The ACR criteria for GCA are inadequate for the classification of patients with LV-GCA.

Inflamed temporal artery: histologic findings in 354 biopsies, with clinical correlations.

We reviewed 888 temporal artery biopsies (TAB) performed in 871 patients in a single institution from January 1986 to December 2013. Forty-four biopsies (4.9%) were inadequate, 490 (55.2%) were devoid of inflammation and were considered negative, and 354 (39.9%) showed inflammation and were considered positive. On the basis of the localization of the inflammation, positive TABs were further classified into 4 categories: small vessel vasculitis (SVV), in which inflammation was limited to small periadventitial vessels devoid of muscular coat, with sparing of the temporal artery (32 cases, 9% of the positive biopsies); vasa vasorum vasculitis (VVV), in which inflammation was limited to the adventitial vasa vasorum (23 cases, 6.5% of the positive biopsies); inflammation limited to adventitia (ILA), in which inflammation extended from a strictly perivascular localization to the surrounding adventitia, without medial involvement (25 cases, 7% of the positive biopsies); and transmural inflammation (TMI), in which inflammation crossed the external elastic lamina and extended to the media (274 cases, 77.5% of the positive biopsies). In TMI, inflammation was generally more prominent between media and adventitia and mostly consisted of T lymphocytes and macrophages, with occasionally a significant number of plasma cells. Numerous eosinophils or neutrophils (with or without leucocytoclasia and suppurative necrosis), fibrinoid necrosis (limited to small branches of the temporal artery), and acute thrombosis were unusual, being present in 8%, 1.8%, 0.7%, and 9.5% of our biopsies with TMI, respectively. Giant cells, laminar necrosis, and calcifications prevailed along the internal elastic lamina and were present in 74.8%, 25.2%, and 20% of the biopsies with TMI, respectively. Among the 322 patients with positive TAB on whom we obtained clinical information, 317 had giant cell arteritis and 5 had a different disease: 3 (with SVV at histology) had ANCA-associated vasculitis, 1 (with SVV with amyloid deposits) had primary systemic amyloidosis, and 1 (with TMI limited to a small branch) had polyarteritis nodosa. In none of these cases the biopsy showed fibrinoid necrosis or significant numbers of eosinophils or neutrophils. Considering the 317 patients with giant cell arteritis, those with SVV and VVV compared with those with TMI had a significantly lower frequency of cranial manifestation (including headache, jaw claudication, and abnormalities of temporal arteries), lower serum levels of acute-phase reactants, and a reduced frequency of prednisone therapy at the time of TAB, of the “halo sign” at color duplex sonography of temporal arteries, and of systemic symptoms (for VVV). Polymyalgia rheumatica and blindness were equally represented in all patients groups, whereas there was a higher frequency of male sex and peripheral arthritis in patients with SVV. Patients with ILA were more similar to those with TMI, having a lower frequency of headache, of abnormalities of temporal arteries, and of a positive “halo sign” at color duplex sonography of temporal arteries. In conclusion, the histologic spectrum of inflammatory lesions that can be found in TAB is broad, and the differences have clinical implications.

Small-vessel vasculitis surrounding an uninflamed temporal artery and isolated vasa vasorum vasculitis of the temporal artery: Two subsets of giant cell arteritis

OBJECTIVE To evaluate the frequency and clinical characteristics of periadventitial small-vessel vasculitis (SVV) and isolated vasa vasorum vasculitis (VVV). METHODS We identified 455 temporal artery biopsies performed in residents of Reggio Emilia, Italy between 1986 and 2003. Slides of temporal artery biopsy specimens were reviewed by a pathologist who was blinded with regard to clinical data. SVV was defined as inflammation of the small vessels external to the temporal artery adventitia, and VVV was defined as isolated inflammation of temporal artery vasa vasorum. Medical records of patients with SVV and/or VVV were reviewed, and demographic, clinical, laboratory, and followup data were collected. For comparison purposes, we collected the same data from an equal number of randomly selected patients with evidence of classic giant cell arteritis (GCA). RESULTS Sixteen patients had SVV, 18 had isolated VVV, and 5 had both SVV and VVV. Compared with patients with classic GCA, the frequencies of headache, scalp tenderness, abnormalities of temporal arteries, jaw claudication, anorexia, and weight loss, the levels of acute-phase reactant at diagnosis, and the initial and cumulative doses prednisone were significantly lower and the frequency of peripheral synovitis was higher in the patients with SVV, and the frequency of cranial ischemic events was similar in the 2 groups. In contrast, the clinical characteristics and erythrocyte sedimentation rate at diagnosis of patients with isolated VVV were similar to those of patients with classic GCA. CONCLUSION Our findings indicate that isolated VVV and SVV should be considered part of the histopathologic spectrum of GCA.

Statin use in giant cell arteritis: a retrospective study.

Objective. (1) To examine the association between statin use and giant cell arteritis (GCA); (2) to compare the clinical features and disease course of GCA among statin users and nonusers. Methods. For this retrospective study, we reviewed the medical records of all patients with biopsy-positive GCA diagnosed between 1998 and 2008. Using a case-control design, we compared the frequency of statin use in GCA patients to non-GCA population-based subjects who were randomly selected and individually matched by sex, age, and calendar year to the GCA cases. Statin use at diagnosis or index date and during followup was abstracted. In subjects with GCA, clinical information at diagnosis and followup was collected. Results. We included 594 patients, 297 with GCA (73% female), mean age at diagnosis 75 years. The rate of statin exposure at index date was 18.1% for GCA patients versus 33.3% for controls (p < 0.001). Patients using statins were less likely to develop GCA compared with patients not using statins (OR 0.31, 95% CI 0.15–0.6, p < 0.001), even after adjustment for cardiovascular risk factors. Among patients with GCA, the presenting clinical features and acute-phase reactants were similar in patients receiving statins compared to those not on statin therapy. These 2 groups were also similar with regard to relapse rate, prednisone tapering, and overall survival. Conclusion. Patients using statins may be less likely to develop GCA compared to patients who are not using statins. Statin use does not appear to modify the clinical presentation or the course of the disease.

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.

Imaging of vasculitis: State of the art.

The increasing availability and improvement of imaging techniques are making a profound impact in the evaluation and management of patients with vasculitis, particularly for those with large vessel vasculitis, and will most likely play an ever more important role in the future. Deep, large vessels can be examined by CT or MRI, while ultrasound is the method of choice for the evaluation of superficial vessels (such as temporal, carotid, and axillary arteries). PET is very sensitive in detecting large vessel inflammation, but it does not delineate the vessel wall. Imaging studies can also be used to monitor the disease course and the development of late vascular complication. This review will focus on the role of imaging studies in diagnosing and monitoring LVV, but will also mention their principal applications in medium and small-sized vessel vasculitis. Indications and limitations of the available imaging modalities will be discussed as well.

Extra-cranial giant cell arteritis and Takayasu arteritis: How similar are they?

OBJECTIVE To compare clinical and imaging characteristics of patients with giant cell arteritis (GCA) and upper extremity (UE) arterial involvement to patients with Takayasu arteritis (TAK). METHODS A cohort of patients seen at the Mayo Clinic with TAK diagnosed between 1984 and 2009 and a cohort of patients with GCA and UE arterial involvement diagnosed between 1999 and 2008 were studied. RESULTS The TAK cohort consisted of 125 patients (91% female); the mean age (±SD) at diagnosis was 30.9 (±10) years. The cohort of patients with GCA and UE involvement comprised of 120 patients (80% female); the mean age (±SD) at diagnosis was 67.8 (±7.5) years. The mean time from onset of symptoms to diagnosis was significantly longer in TAK (3.2 years) than GCA (0.5 years), p < 0.001. UE claudication was reported in 40% with TAK and 53% with GCA, p = 0.04. UE blood pressure discrepancy was present in 65% with TAK versus 28% with GCA, p < 0.001. Involvement of the thoracic aorta, abdominal aorta, carotid arteries, innominate artery, mesenteric artery, and left renal artery was more frequently observed in TAK (p < 0.05). Among patients with luminal changes of the thoracic aorta, stenotic/occlusive lesions were predominant in TAK (81% compared to 0% in GCA), whereas aneurysmal disease was more common in GCA (100% compared with 19% in TAK, p < 0.001). CONCLUSION Patients with GCA and UE involvement differ from patients with TAK in clinical and imaging characteristics. Aortic aneurysms were more common in GCA, while stenotic changes of the aorta were more common in TAK, suggesting different pathophysiologic mechanisms or vascular response to injury.

MicroRNA markers of inflammation and remodelling in temporal arteries from patients with giant cell arteritis

Objectives There is increasing evidence that microRNAs (miRNAs) are deregulated in autoimmune and cardiovascular diseases. The present study aimed to identify if miRNAs are deregulated in giant cell arteritis (GCA), a vasculitis affecting large-sized and medium-sized arteries, and to determine if miRNA levels might allow to discriminate between patients with GCA and those without. Methods 58 patients who had temporal artery biopsy (TAB) for suspected GCA were included in the study and divided into three groups: patients with TAB-positive GCA showing a transmural inflammation (n=27), patients with TAB-negative GCA (n=8) and TAB-negative non-GCA patients with a final diagnosis different from GCA (n=23). To identify candidate miRNAs deregulated in GCA, we profiled the expression of 1209 miRNAs in inflamed TABs and normal TABs. Selected miRNAs were then validated by real-time PCRs and in situ hybridisation (ISH). Results MiR-146b-5p, -146a, -155, -150, -21 and -299-5p were significantly more expressed in inflamed TABs from patients with GCA. miRNAs were mainly deregulated at the tissue level because peripheral blood mononuclear cells and polymorphonuclear cells from the three groups of patients and age-matched healthy controls had similar levels of miRNAs. ISH showed that miR-21 was mainly expressed by cells in the medial and intimal layers of inflamed TABs. Patients with TAB-negative GCA had a miRNA profile similar to TAB-negative non-GCA patients. Conclusions MiR-146b-5p, -146a, -21, -150, -155, -299-5p are overexpressed in the presence of inflammation in TABs from patients with GCA.

Mycophenolate mofetil in primary central nervous system vasculitis

OBJECTIVE To evaluate the efficacy and safety of mycophenolate mofetil (MMF) in adult primary central nervous system vasculitis (PCNSV). METHODS We studied a cohort of 163 patients with PCNSV who were seen at the Mayo Clinic from 1983 to 2011. We compared patients treated with MMF and those receiving other therapies. RESULTS We identified 16 patients treated with MMF. MMF in combination with GCs achieved a favorable response in most patients. A significant proportion of patients treated with MMF had a less severe disability at last follow-up compared to those receiving other therapies (p = 0.023) and cyclophosphamide and prednisone (p = 0.017). No statistically significant differences were observed regarding relapses and ability to discontinue therapy at last follow-up. A trend to a more favorable treatment response was observed in patients treated with MMF compared to those treated with other therapies (p = 0.075). Only 1 patient suspended MMF for severe leukopenia. CONCLUSION MMF seems to be an effective and safe therapy for adult PCNSV.