Comparison of 1.1 GBq and 2.2 GBq Activities in Patients with Low-Risk Differentiated Thyroid Cancer Requiring Postoperative 131I Administration: A Real Life Study.

OBJECTIVES: To compare the efficacy of low and moderate 131I activities in low-risk differentiated thyroid carcinoma (DTC) patients requiring postoperative thyroid remnant ablation in a real-world clinical setting. METHODS: We retrospectively reviewed the records of 299 low-risk DTC patients (pT1-T2, Nx(0) Mx) who had undergone (near)-total thyroidectomy followed by 131I therapy, using either low (1.1 GBq) or moderate (2.2 GBq) radioiodine activities. The response to initial treatments was evaluated after 8-12 months, and patient responses were classified according to the 2015 American Thyroid Association guidelines. RESULTS: An excellent response was observed in 274/299 (91.6%) patients, specifically, in 119/139 (85.6%) and 155/160 (96.9%) patients treated with low and moderate 131I activities, respectively (p = 0.029). A biochemically indeterminate or incomplete response was observed in seventeen (22.2%) patients treated with low 131I activities and three (1.8%) patients treated with moderate 131I activities (p = 0.001). Finally, five patients showed an incomplete structural response, among which three and two received low and moderate 131I activities, respectively (p = 0.654). CONCLUSIONS: When 131I ablation is indicated, we encourage the use of moderate instead of low activities, in order to reach an excellent response in a significantly larger proportion of patients, including patients with the unexpected persistence of the disease.

Incidence and prevalence of large vessel vasculitis (giant cell arteritis and Takayasu arteritis) in northern Italy: A population-based study.

OBJECTIVES: To investigate the epidemiology of the entire spectrum of large vessel vasculitis (LVV) in a well-defined population from a Northern Italian area. METHODS: All patients with incident giant cell arteritis (GCA) diagnosed from 2005 to 2016 and all patients with incident Takayasu arteritis (TAK) diagnosed from 1998 to 2016 living in the Reggio Emilia area were identified. Only patients satisfying the modified inclusion criteria of the GiACTA trial, and the 1990 ACR classification criteria for TAK were included. The epidemiology of cranial- and LV-GCA was separately evaluated. RESULTS: 207 patients were diagnosed with GCA and 5 with TAK. 123 patients had cranial-GCA, 53 patients had LV-GCA, and the remaining 31 patients had overlapping features. The standardized annual incidence rate of GCA was 8.3 (95% CI 7.1, 9.4) per 100,000 population ages ≥50 years. The standardized annual incidence rate of cranial-GCA (6.1 [95% CI 5.1, 7.1] per 100,000 population ages ≥50 years) was double the rate of LV-GCA (3.4 [95% CI 2.7, 4.2]). The age-specific incidence rates were similar in the <70 and >90 years age groups, but they were higher in cranial-GCA than in LV-GCA in the age groups 70-79 and 80-89 years. The age- and sex-adjusted annual incidence rate of TAK was 0.5 (95% CI 0.1, 1.2) per 1,000,000 population. CONCLUSION: Incidence of GCA is higher than previously reported by study evaluating only biopsy-proven or ACR classification criteria confirmed cases. Cranial-GCA and LV-GCA have epidemiological differences. TAK is an extremely rare disease also in Italy.

Significance of inflammation restricted to adventitial/periadventitial tissue on temporal artery biopsy.

OBJECTIVE: To evaluate the characteristics and significance of inflammation restricted (RI) to the adventitial and/or periadventitial tissue on temporal artery biopsy (TAB). METHODS: We studied a retrospective cohort of 80 patients with RI, extending our earlier series of 39 patients. For comparison purposes, we collected the same data from 254 patients with transmural inflammation (TMI) and 81 TAB-negative patients. A review of the literature was also performed. RESULTS: A final diagnosis of giant cells arteritis (GCA) and/or polymyalgia rheumatica (PMR) was observed in 86% of patients with RI. Compared to TMI, GCA diagnosis was significantly less frequently observed in patients with RI and in those TAB-negative (p < 0.0001), while cranial manifestations were significantly less frequent (p = 0.001) and ESR and CRP values at diagnosis significantly reduced (p < 0.0001). PMR, permanent visual loss, and large vessel involvement at diagnosis were equally present in the 3 subgroups. The median duration of prednisone therapy, the cumulative prednisone dosages, and the relapse and long-term remission rates were similar between patients with GCA-RI and those with TMI. The positive likelihood ratios (LRs) of pathological evidence of RI at TAB for GCA or GCA/PMR diagnoses were 0.88 (CI, 0.61-1.27) and 1.15 (CI, 0.67-1.99), while that of inflammation limited to adventitia was 1.37 (CI, 0.59-3.19) and 3.77 (CI, 0.53-26.72). In the literature review, the positive LR of RI for GCA diagnosis was 0.92 (CI, 0.68-1.25). CONCLUSION: A large part of the patients with RI have GCA/PMR, however, the diagnostic value of RI for GCA diagnosis is not relevant.

Relapses and long-term remission in large vessel giant cell arteritis in northern Italy: Characteristics and predictors in a long-term follow-up study.

OBJECTIVE: To evaluate characteristics and predictors of relapses and long-term remission in an Italian cohort of patients with large-vessel (LV) giant cell arteritis (GCA). METHODS: We evaluated 87 consecutive patients with LV-GCA followed up at the Rheumatology Unit of Reggio Emilia Hospital (Italy) for at least 2 years. Patients with relapses and long-term remission were compared to those without. A group of 34 patients with biopsy proven GCA without LV vasculitis (LVV) at diagnosis was considered for comparison. PATIENTS: 37 patients (42.5%) experienced one or more relapses. Nineteen (37.2%) of the 51 relapses were experienced during the first year after diagnosis. The majority of relapses occurred with doses of prednisone (PDN) ≤ 10 mg/day (74.5%). Polymyalgia rheumatica (PMR) (41.2%) and worsening at imaging of LVV (39.2%) were the most frequently observed relapsing manifestations. The total cumulative prednisone dose was significantly higher (p < 0.0001) and the total duration of PDN treatment longer (p < 0.0001) in relapsing patients compared to those without relapses. Relapsing patients had at diagnosis more frequently fever ≥ 38°C (p = 0.03) and visual manifestations (p = 0.03), and less frequently long-term remission (p = 0.002). In the multivariate model fever ≥ 38°C (HR 2.30, 95%CI:1.11-4.78) and total cumulative PDN dose (HR 1.18, 95%CI: 1.08-1.30) were significantly associated with an increased risk of relapses, while aortic arch involvement at imaging at diagnosis (HR 0.26, 95%CI: 0.11-0.59) and long-term remission (HR 0.27, 95%CI: 0.11-0.65) with a reduced risk. 35/84 patients (41.6%) experienced long-term remission. PMR and disease relapses were less frequently observed (p = 0.04 and p = 0.002, respectively), and the total cumulative prednisone dose was lower (p < 0.001) in patients with long-term remission compared to those without. In the multivariate model the presence of relapses (HR 0.21, 95%CI: 0.07-0.62) and the total cumulative PDN dose (HR 0.85, 95%CI: 0.77-0.95) were significantly negatively associated with long-term remission. CONCLUSION: In our cohort of patients with LV GCA we identified predictors of a relapsing course and long-term remission, which were observed in around half of the patients.

Comparison of biopsy-proven giant cell arteritis in North America and Southern Europe: a population-based study.

OBJECTIVES: To compare clinical characteristics, treatment and prognosis of two population-based cohorts of patients with biopsy-proven giant cell arteritis (GCA) from Olmsted County, Minnesota, USA (Olmsted cohort) and the Reggio Emilia area, Northern Italy (Reggio cohort). METHODS: All patients residing in Olmsted County and the Reggio Emilia area with a new diagnosis of biopsy-proven GCA in 1986-2007 were retrospectively identified. Patients were followed from GCA diagnosis to death, migration or September 2011. RESULTS: The study included 110 patients in the Olmsted and 144 in the Reggio cohort. Compared with the Olmsted cohort, patients from the Reggio cohort had longer duration of symptoms prior to diagnosis (median 1.4 months vs. 0.7, p<0.001) and were younger (mean 74.6 years vs. 77.8, p=0.002), more likely to have cranial symptoms (93% vs. 86%, p=0.048), permanent vision loss (21% vs. 6%, p=0.001) and systemic symptoms (67% vs. 46%, p=0.001). ESR and CRP were higher (mean 88 mm/h vs. 73, and 89.0 mg/L vs. 35.2, both p<0.001) in the Reggio cohort. Patients from the Olmsted cohort received a higher initial prednisone dose (mean 53.6 mg/day vs. 49.5, p=0.001). There were no differences in relapse rates, cumulative glucocorticoid (GC) dosages at 1, 2 and 5 years, and time to first GC discontinuation. CONCLUSIONS: Geographical, genetic and/or environmental factors may contribute to the different clinical features at onset of GCA observed in this study.

Interleukin-6 expression in inflamed and non-inflamed temporal arteries from patients with giant cell arteritis.

OBJECTIVES: To evaluate whether interleukin-6 expression in the temporal arteries could be a more sensitive marker of active inflammation compared to the presence of an inflammatory infiltrate. METHODS: Sixty-three formalin-fixed, paraffin-embedded temporal artery biopsies performed between 2009 and 2012 from 32 patients with biopsy-proven giant cell arteritis, 8 patients with a negative biopsy but with a final diagnosis of giant cell arteritis, and 23 controls (patients with an initial clinical suspicion of giant cell arteritis in whom an alternative diagnosis subsequently was made) were examined. Biopsy specimens showing a transmural inflammatory infiltrate were considered positive for giant cell arteritis. Immunochemistry was performed to detect interleukin-6 in the temporal artery specimens. Slides of temporal artery biopsies were independently assessed by five readers. Interleukin-6 expression was graded as 0 (absent), 1 (mild), 2 (moderate) and 3 (marked). We considered anti-IL-6 staining positive if staining was of grade 2 or 3. RESULTS: Temporal artery biopsies specimens from patients with biopsy-proven giant cell arteritis, biopsy-negative giant cell arteritis and controls were positive for anti-interleukin-6 staining in 59%, 13% and 48% of cases, respectively. CONCLUSIONS: Interleukin-6 expression does not increase the sensitivity of temporal artery biopsy in patients with giant cell arteritis who have morphologically uninflamed arteries.

Survival predictors in biopsy-proven giant cell arteritis: a northern Italian population-based study.

OBJECTIVE: To evaluate the influence of disease-related findings and treatment outcomes on survival in a population-based cohort of Northern Italian patients with GCA. METHODS: A total of 281 patients with incident temporal artery biopsy (TAB)-proven GCA, diagnosed over a 26-year period (1986-2012) and living in the Reggio Emilia area, were retrospectively evaluated. We analysed clinical, imaging and laboratory findings at diagnosis, pathological patterns of TAB, CS treatment and therapeutic outcomes, and traditional cardiovascular risk factors as factors predictive of survival. RESULTS: Univariate analysis showed that increased mortality was associated with large vessel involvement at diagnosis [hazard ratio (HR) 5.84], while reduced mortality was associated with female sex (HR 0.66), PMR (HR 0.54), higher haemoglobin levels (HR 0.84) at diagnosis, long-term remission (HR 0.47) and inflammation limited to adventitia or to the adventitial vasa vasorum (HR 0.48) at TAB examination. Multivariate analysis confirmed the association between increased mortality and large vessel involvement (HR 5.14) at diagnosis, between reduced mortality and PMR (HR 0.57) at diagnosis and adventitial inflammation (HR 0.31) at TAB. CONCLUSION: PMR at diagnosis and inflammation limited to the adventitia at TAB appear to identify subsets of patients with more benign disease, while large vessel involvement at diagnosis is associated with reduced survival.

Incidence, Prevalence, and Survival of Biopsy-Proven Giant Cell Arteritis in Northern Italy During a 26-Year Period.

OBJECTIVE: To investigate the epidemiology and mortality in patients with biopsy-proven giant cell arteritis (GCA) in northern Italy. METHODS: All patients with incident temporal-artery biopsy-positive GCA, diagnosed between 1986 and 2012 and living in the Reggio Emilia area, were identified by using a pathology register and by reviewing all histopathologic specimens. For each patient, we identified 1 comparison subject from the same geographic area, matched for age and sex. Mortality rates and specific causes of death were reported. RESULTS: There were 285 incident cases of biopsy-proven GCA (210 women) during the 26-year study period. The overall age- and sex-adjusted incidence per 100,000 persons ages ≥50 years was 5.8 (95% confidence interval [95% CI] 5.1, 6.5). Incidence was significantly higher in women (7.8 [95% CI 6.7, 8.9]) than in men (3.3 [95% CI 2.6, 4.1]) (P < 0.0001). Annual age- and sex-adjusted incidence rates significantly increased by 15.9% per 3 years from 1986 to 2000, then significantly fell by -4.8% per 3 years from 2001-2012. The prevalence of GCA on December 31, 2012 was 87.9 (95% CI 75.8, 101.4). No significant differences in the mortality rates were observed between GCA patients (4.9 per 100 person-years [95% CI 4.1, 5.8]) and non-GCA subjects (5.6 [95% CI 4.7, 6.6]). No significant differences in causes of death were observed comparing GCA patients to non-GCA subjects. CONCLUSION: This large population-based study of biopsy-proven GCA confirmed the lower incidence of GCA in Mediterranean countries and did not observe any increased mortality risk.

Long-term remission in biopsy proven giant cell arteritis: A retrospective cohort study.

OBJECTIVE: To evaluate the frequency of long-term remission after glucocorticoids (GCs) suspension in an Italian cohort of patients with biopsy-proven GCA and to identify factors that may predict long-term remission. METHODS: We evaluated 131 patients with biopsy-proven transmural GCA diagnosed and followed up at the Rheumatology Unit of Reggio Emilia Hospital (Italy) for whom sufficient information was available from the time of diagnosis until at least 18 months of follow-up. Long-term remission was defined as complete clinical remission without elevation of inflammatory markers for at least one year after the GC withdrawal. RESULTS: 73 patients (56%) experienced long-term remission. Disease flares were less frequently observed in patients with long-term remission compared to those without (p = 0.002). The cumulative doses of prednisone at 1 year and for the entire followup duration were significantly lower (p < 0.0001 for both parameters) in patients with long-term remission; similarly, the duration of prednisone treatment was also significantly lower (p < 0.0001). The presence of PMR at diagnosis (HR 0.46) was significantly negatively associated with long-term remission (p = 0.008), while hemoglobin levels (HR 1.48) were significantly positively associated (p < 0.0001). Patients with long-term remission were able to reach 10 mg/day and 5 mg/day of prednisone sooner than the patients without (p = 0.02 and p < 0.0001, respectively). CONCLUSION: In our cohort of GCA patients around half of the patients were able to attain long-term remission. Recognition of findings which predict disease course may aid decisions regarding therapy.

Flares in Biopsy-Proven Giant Cell Arteritis in Northern Italy: Characteristics and Predictors in a Long-Term Follow-Up Study.

This study evaluated the frequency, timing, and characteristics of flares in a large cohort of Italian patients with biopsy-proven giant cell arteritis (GCA) and to identify factors at diagnosis able to predict the occurrence of flares. We evaluated 157 patients with biopsy-proven transmural GCA diagnosed and followed at the Rheumatology Unit of Reggio Emilia Hospital (Italy) for whom sufficient information was available from the time of diagnosis until at least 4 years of follow-up. Fifty-seven patients (36.5%) experienced ≥1 flares. Fifty-one (46.4%) of the 110 total flares (88 relapses and 22 recurrences) were experienced during the first 2 years after diagnosis. The majority of relapses occurred with doses of prednisone ≤ 10 mg/day (82.9%), whereas only 3.4% of relapses occurred for doses ≥ 25 mg/day. Polymyalgia rheumatica (46.5%) and cranial symptoms (41.9%) were the most frequent manifestations at the time of the first relapse. Cumulative prednisone dose during the first year and total cumulative prednisone dose were significantly higher in flaring patients compared with those without flares (7.8 ±â€Š2.4 vs 6.7 ±â€Š2.4 g, P = 0.02; 15.5 ±â€Š8.9 vs 10.0 ±â€Š9.2 g, P = 0.0001, respectively). The total duration of prednisone treatment was longer in flaring patients (58 ±â€Š44 vs 30 ±â€Š30 months, P = 0.0001).Patients with disease flares had at diagnosis more frequently systemic manifestations (P = 0.02) and fever ≥ 38°C (P = 0.02), significantly lower hemoglobin levels (P = 0.05), more frequent presence at temporal artery biopsy (TAB) specimens of giant cells (P = 0.04) and intraluminal acute thrombosis (P = 0.007), and more moderate/severe arterial inflammation (P = 0.009) compared with those without flares. In the multivariate model fever ≥ 38 °C (hazard ratio 2.14; 95% confidence interval, 1.06-4.32, P = 0.03) and the severity of inflammatory infiltrate (moderate/severe versus mild) (hazard ratio 5.41; 95% confidence interval, 1.64-17.87, P = 0.006) were significantly associated with an increased risk of flares. In conclusion, a flaring course is common in GCA and it is associated with prolonged GC requirements. Fever at diagnosis and severity of inflammation at TAB appear to predict the development of disease flares.

Correlations between histopathological findings and clinical manifestations in biopsy-proven giant cell arteritis.

OBJECTIVE: To correlate histopathological features of positive temporal artery biopsy (TAB) and clinical manifestations of the disease in a large single-center population-based cohort of patients with biopsy-proven giant cell arteritis (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 2013. 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. RESULTS: 274 patients had a final diagnosis of biopsy-proven GCA and were included in the study. Cranial ischemic events (CIEs) were observed in 161 (58.8%), visual manifestations in 79 (28.8%) and permanent (partial or complete) visual loss in 51 (18.6%) patients. Predictors for the development of CIEs were older age (OR = 1.057, 95% CI 1.019-1.097, p = 0.003), lower ESR values (OR = 0.990, 95% CI 0.981-0.999, p = 0.026) as well as the presence of giant cells (OR = 1.848, 95% CI 1.045-3.269, p = 0.035) and laminar necrosis at TAB (OR = 2.334, 95% CI 1.187-4.587, p = 0.014). Predictors for the development of permanent visual loss were lower CRP values (OR = 0.906, 95% CI 0.827-0.992, p = 0.033) and the presence of calcifications at TAB (OR = 3.672, 95% CI 1.479-9.121, p = 0.005). Fibrinoid necrosis was not observed in any of the TABs evaluated. CONCLUSION: Pathological features of TAB may predict some manifestations of GCA. These findings may have implications for patients' management.

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.

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.

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.

PlA1/A2 polymorphism of the platelet glycoprotein receptor IIIA and risk of cranial ischemic complications in giant cell arteritis.

OBJECTIVE: To investigate potential associations of the PlA1/A2 polymorphism of the platelet glycoprotein IIIa (GPIIIa) gene with susceptibility to, and clinical expression of, giant cell arteritis (GCA). METHODS: One hundred forty patients with biopsy-proven GCA who were residents of Reggio Emilia, Italy, and 241 population-based healthy controls from the same geographic area were genotyped for the PlA1/A2 polymorphism of the platelet GPIIIa gene by molecular methods. The patients were divided into subgroups according to the presence or absence of polymyalgia rheumatica and cranial ischemic complications. The distribution of the PlA1/A2 genotype was investigated, and odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated. RESULTS: The distribution of the PlA1/A2 genotype differed significantly between GCA patients with and those without visual loss caused by anterior ischemic optic neuritis (P = 0.016, corrected P [P(corr)] = 0.048). The PlA2 allele was found significantly more frequently in GCA patients with anterior ischemic optic neuritis than in those without anterior ischemic optic neuritis (P = 0.023, P(corr) = 0.046, OR 2.4 [95% CI 1.2-4.8]). Homozygosity for the PlA2 allele was significantly more frequent among GCA patients with anterior ischemic optic neuritis than among those without (P = 0.019, P(corr) = 0.038, OR 7.1 [95% CI 1.64-30.6]). Cranial ischemic complications occurred in 8 of 19 patients (42.1%) receiving antiplatelet therapy, compared with 22 of 118 patients (18.6%) not receiving such therapy (P = 0.03, OR 3.2 [95% CI 1.1-8.8]). CONCLUSION: Our findings show that A2/A2 homozygosity is associated with an increased risk of visual loss due to anterior ischemic optic neuritis in GCA patients. Antiplatelet therapy, however, was not effective in reducing the risk of ischemic events in this population of GCA patients.