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Objectives: The aim of this study was to compare the prevalence, entity and local distribution of arterial wall calcifications evaluated on CT scans in patients with large vessel vasculitis (LVV) and patients with lymphoma as reference for the population without LVV., Methods: All consecutive patients diagnosed with LVVs with available baseline positron emission tomography-CT (PET-CT) scan performed between 2007 and 2019 were included; non-LVV patients were lymphoma patients matched by age (±5 years), sex and year of baseline PET-CT (≤2013; >2013). CT images derived from baseline PET-CT scans of both patient groups were retrospectively reviewed by a single radiologist who, after setting a threshold of minimum 130 Hounsfield units, semiautomatically computed vascular calcifications in three separate locations (coronaries, thoracic and abdominal arteries), quantified as Agatston and volume scores., Results: A total of 266 patients were included. Abdominal artery calcifications were equally distributed (mean volume 3220 in LVVs and 2712 in lymphomas). Being in the LVVs group was associated with the presence of thoracic calcifications after adjusting by age and year of diagnosis (OR 4.13, 95% CI 1.35 to 12.66; p=0.013). Similarly, LVVs group was significantly associated with the volume score in the thoracic arteries (p=0.048). In patients >50 years old, calcifications in the coronaries were more extended in non-LVV patients (p=0.027 for volume)., Conclusion: When compared with patients without LVVs, LVVs patients have higher calcifications in the thoracic arteries, but not in coronary and abdominal arteries., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: The number of susceptibility loci currently associated with vasculitis is lower than in other immune-mediated diseases due in part to small cohort sizes, a consequence of the low prevalence of vasculitides. This study aimed to identify new genetic risk loci for the main systemic vasculitides through a comprehensive analysis of their genetic overlap., Methods: Genome-wide data from 8467 patients with any of the main forms of vasculitis and 29 795 healthy controls were meta-analysed using ASSET. Pleiotropic variants were functionally annotated and linked to their target genes. Prioritised genes were queried in DrugBank to identify potentially repositionable drugs for the treatment of vasculitis., Results: Sixteen variants were independently associated with two or more vasculitides, 15 of them representing new shared risk loci. Two of these pleiotropic signals, located close to CTLA4 and CPLX1 , emerged as novel genetic risk loci in vasculitis. Most of these polymorphisms appeared to affect vasculitis by regulating gene expression. In this regard, for some of these common signals, potential causal genes were prioritised based on functional annotation, including CTLA4 , RNF145 , IL12B , IL5 , IRF1 , IFNGR1 , PTK2B , TRIM35 , EGR2 and ETS2 , each of which has key roles in inflammation. In addition, drug repositioning analysis showed that several drugs, including abatacept and ustekinumab, could be potentially repurposed in the management of the analysed vasculitides., Conclusions: We identified new shared risk loci with functional impact in vasculitis and pinpointed potential causal genes, some of which could represent promising targets for the treatment of vasculitis., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose of Review: To summarize the histologic findings of vasculitis, and to give some practical considerations on biopsy samples., Recent Findings: The larger use of imaging and the discoveries of serological markers in the diagnosis of vasculitis have increased the clinical recognition of these entities. Nevertheless, biopsy remains the gold standard for diagnosis in most cases. So far, biopsies are also useful to obtain information about prognosis and to guide a more specific treatment. In recent years, less invasive diagnostic approaches have become available, lowering the risks related to the procedure and permitting a definite diagnosis in most cases. Histological examination permits a definite diagnosis of vasculitis. However, the findings may be nonspecific if not evaluated in the proper clinical setting. The interaction between clinicians and pathologists is crucial to obtain a definite diagnosis., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: To identify patients with VEXAS syndrome (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic syndrome) from a single-center cohort of Italian patients with vasculitis, using a clinically oriented phenotype-first approach., Methods: We retrospectively reviewed the clinical records of 147 consecutive male patients followed up in our vasculitis clinic from 2013 to date. All patients with a diagnosis of vasculitis and treatment-resistant manifestations of inflammation, persistently elevated inflammation markers, and hematologic abnormalities were identified. Bone marrow aspirates were examined for the presence of vacuoles. Sequencing of ubiquitin-activating enzyme E1 (UBA-1) was performed using genomic DNA from peripheral blood leukocytes or bone marrow tissue., Results: Seven patients with vasculitis and concomitant features of VEXAS syndrome were identified. A final diagnosis of VEXAS syndrome was made in 3 of the 5 patients who underwent sequencing of UBA-1 (diagnosis was made postmortem for 1 patient). In all 3 patients, examination of the bone marrow aspirate revealed vacuoles characteristic of VEXAS syndrome, and all 3 patients met the definitive World Health Organization criteria for myelodysplastic syndrome. Cytogenetic analysis showed normal karyotypes in all 3 patients., Conclusion: To our knowledge, this is the first report of VEXAS syndrome associated with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis. Our data emphasize the need to consider VEXAS syndrome when evaluating patients with various forms of systemic vasculitis. The novel association between VEXAS syndrome and ANCA-associated vasculitis reported herein warrants further investigation., (© 2021 The Authors. Arthritis & Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)

Objective: The aim was to identify any association between imaging signs of vessel wall inflammation (positron emission tomography-CT (PET-CT) score and CT/MR wall thickening) and synchronous and subsequent vascular damage (stenoses/dilations) in patients with large vessel vasculitis (LVV)., Methods: Consecutive patients with LVV referred to a tertiary centre in 2007-2020 with baseline PET-CT and morphological imaging (CT/MR angiography) performed within 3 months were included. All available PET-CT and CT/MR scans were reviewed to assess PET-CT uptake (4-point semi-quantitative score), wall thickening, stenoses and dilations for 15 vascular segments. The associations of baseline PET score and CT/MR wall thickening with synchronous and incident stenoses/dilations at CT/MR performed 6-30 months from baseline were evaluated in per-segment and per-patient analyses. Respective areas under the receiver operating characteristic curve (AUC) were calculated., Results: We included 100 patients with LVV (median age: 48 years, 22% males). Baseline PET score and wall thickening were strongly associated (Cuzick non-parametric test for trend across order groups (NPtrend) <0.001). The association with synchronous stenoses/dilations was weak for PET score (NPtrend=0.01) and strong for wall thickening (p<0.001). In per-patient analyses, sensitivity/specificity for ≥1 synchronous stenoses/dilations were 44%/67% for PET score ≥2 and 66.7%/60.5% for wall thickening. Subsequent CTs/MRs were available in 28 patients, with seven incident stenoses/dilations. Baseline PET score was strongly associated with incident stenoses/dilations (p=0.001), while baseline wall thickening was not (p=0.708), with AUCs for incident stenoses/dilations of 0.80 for PET score and 0.52 for wall thickening., Conclusion: PET score and wall thickening are strongly associated, but only baseline PET score is a good predictor of incident vessel wall damage in LVV., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Heart involvement in vasculitis is rare, but potentially severe. The ascertainment of cardiac disease in vasculitis is complex and requires an integrated multidisciplinary approach involving the Rheumatologist, Radiologist, Cardiologist, and Heart surgeon., Areas Covered: the authors searched PubMed using the keywords 'heart'[Mesh] and vasculitis"[Mesh]., Expert Opinion: Virtually any vasculitis can affect the heart, but cardiac involvement is more common in some vasculitides such as Takayasu arteritis, polyarteritis nodosa, and eosinophilic granulomatosis with polyangiitis. Immunosuppressive treatment and when indicated surgery can improve the prognosis.

Rituximab represents a milestone in the treatment of mixed cryoglobulinemic vasculitis. Despite usually well-tolerated, rituximab may induce different types of adverse drug reactions, including exacerbation of vasculitis. Rituximab biosimilar have been recently approved in Europe in the treatment of rheumatoid arthritis, but no data are available about effectiveness and safety of rituximab biosimilar in the treatment of mixed cryoglobulinemic vasculitis. We describe a severe skin vasculitis reactivation in a patient affected by rheumatoid arthritis and mixed cryoglobulinemic vasculitis treated with rituximab biosimilar. After 7 days from the first infusion, a severe purpuric rash at lower limbs appeared, that resolved in about 2 weeks with high dose-corticosteroid. Rituximab-induced vasculitis has also been described since 2001, but its pathophysiology is still controversial due to the anecdotical descriptions in literature and the variability of the time between the rituximab infusion and the onset of skin lesions. Up to date, this is the first report describing a vasculitic flare in a patient affected by mixed cryoglobulinemic vasculitis treated with rituximab biosimilar.

To develop evidence-based recommendations for the use of imaging modalities in primary large vessel vasculitis (LVV) including giant cell arteritis (GCA) and Takayasu arteritis (TAK). European League Against Rheumatism (EULAR) standardised operating procedures were followed. A systematic literature review was conducted to retrieve data on the role of imaging modalities including ultrasound, MRI, CT and [ 18 F]-fluorodeoxyglucose positron emission tomography (PET) in LVV. Based on evidence and expert opinion, the task force consisting of 20 physicians, healthcare professionals and patients from 10 EULAR countries developed recommendations, with consensus obtained through voting. The final level of agreement was voted anonymously. A total of 12 recommendations have been formulated. The task force recommends an early imaging test in patients with suspected LVV, with ultrasound and MRI being the first choices in GCA and TAK, respectively. CT or PET may be used alternatively. In case the diagnosis is still in question after clinical examination and imaging, additional investigations including temporal artery biopsy and/or additional imaging are required. In patients with a suspected flare, imaging might help to better assess disease activity. The frequency and choice of imaging modalities for long-term monitoring of structural damage remains an individual decision; close monitoring for aortic aneurysms should be conducted in patients at risk for this complication. All imaging should be performed by a trained specialist using appropriate operational procedures and settings. These are the first EULAR recommendations providing up-to-date guidance for the role of imaging in the diagnosis and monitoring of patients with (suspected) LVV., Competing Interests: Competing interests: TAB received research grants from Deutsche Forschungsgemeinschaft (DFG) and Siemens Healthineers and received consultancies and speaker fees from HeartFlow, GSK, MSD, Roche, Bayer, Bracco, Guerbet and Siemens. EB received consultancies and speaker fees from Roche, which were paid to the University Medical Center Groningen. BD has received consultancies from Roche, GSK and Munidipharma. APD received speaker fees from Roche. WS received consultancies and speakers fee from Roche and GSK. All other authors have no competing interest., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Despite the progress in the last years on the field of vasculitides, there are several unmet needs regarding classification, disease activity assessment, predictors of flares and complications, and type of treatment for the different forms. The 1990 American College of Rheumatology (ACR) classification criteria currently used to define giant cell arteritis and Takayasu arteritis were designed to discriminate between different types of vasculitides but not to differentiate vasculitis from other disorders. Recently, efforts have been made to overcome the shortcomings of the ACR criteria. The lack of an accepted definition of disease activity in large-vessel vasculitides presents a major challenge in creating useful and valid outcome tools for the assessment of disease course. Identification of predictors of flares can aid in optimizing therapeutic strategies, minimizing disease flares, and reducing treatment-related side effects. It is furthermore important to recognize and characterize the risk factor that might predict the manifestations associated with poor outcome and prognosis. Two RCTs have evidenced the efficacy of tocilizumab in addition to glucocorticoids (GCs) in the treatment of giant cell arteritis (GCA). However, the role of tocilizumab or other biological agents without GCs needs to be investigated. Recent observational studies have suggested that rituximab is also effective in patients with eosinophilic granulomatosis with polyangiitis and in antineutrophil cytoplasmic antibodies (ANCA)-negative patients with granulomatosis with polyangiitis and microscopic polyangiitis. Rituximab or anti-TNF alfa may represent a possible alternative therapy in case of refractory or difficult to treat polyarteritis nodosa (PAN) patients. The new International Criteria for Behçet's Disease have shown a better sensitivity and a better accuracy compared to the older International Study Group on Behçet's Disease criteria. The EULAR recommendations for the management of Behçet's disease (BD) have been recently updated. However, the treatment of refractory disease is still a real challenge.

Purpose of Review: The aim of this article was to review the recent contributions to the scoring methods of PET in vasculitis as well as to its role in the diagnostic work-up., Recent Findings: Both visual and semiquantitative scoring methods can be used to interpret PET scans. PET has been shown to be both sensitive and specific in the diagnosis of large-vessel vasculitis. In addition, it also has a role in predicting vascular complications., Summary: There is a need to better standardize the scoring methods used to interpret PET scans. In clinical practice, PET is useful to diagnose untreated individuals with suspected large-vessel vasculitis and contributes to identify patients at risk for vascular complications.

Objective: Polyarteritis nodosa (PAN) is a systemic necrotizing vasculitis of medium-sized visceral vessels. However, cutaneous arteritis (CA) and gastrointestinal (GI) vasculitis are forms of single-organ vasculitis having indistinguishable histopathologic findings from PAN. The aim of this study was to evaluate and compare the clinical characteristics, treatment, and outcomes of patients with systemic PAN, CA, and GI vasculitis., Methods: Retrospective cohorts were assembled, consisting of patients with PAN, CA, and GI vasculitis between 1980 and 2014. The demographics, clinical characteristics, treatment, and outcomes of patients were abstracted from medical records., Results: We included 48 patients with PAN, 41 patients with CA, and 19 patients with GI vasculitis. The disease of 1 patient evolved from CA to systemic PAN during the disease course. At diagnosis, 94% of patients with PAN, 93% of patients with CA, and 67% of patients with GI vasculitis were treated with glucocorticoids. Additional immunosuppressive agents were used in 67% of PAN, 37% of GI vasculitis, and 32% of CA cases. The 5-year cumulative relapse rate was 45.2% in CA, and only 9.6% in PAN during a followup of approximately 6 years. No deaths were observed in the CA group. The survival rate at 10 years was 66% in the PAN group and 61% in the GI vasculitis group., Conclusion: Systemic PAN, CA, and GI vasculitis take different clinical courses and therefore may be different diseases, rather than existing on a spectrum of the same disease. Progression of CA to systemic PAN is very rare. Relapse risk is low during followup in PAN. Patients with CA have a higher relapse rate than those with systemic PAN, possibly due to less use of immunosuppressive therapy in CA., (© 2016, American College of Rheumatology.)

Objective: 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 18 F-fluorodeoxyglucose-positron emission tomography ( 18 FDG-PET)., Methods: A total of 31 consecutive patients with LVV (14 with Takayasu arteritis, 17 with giant cell arteritis with large vessel involvement) underwent both PET/computed tomography and carotid artery color Doppler ultrasound (CDUS) for a total of 35 combined assessments. Right carotid artery CEUS was performed after CDUS in all assessments. Kerr's criteria, a complete clinical examination, and acute phase reactants were simultaneously evaluated. The intensity of vascular uptake and vascularization of the carotid artery wall were compared., Results: Ten 18 F-FDG/PET scans showed active vascular 18 F-FDG uptake (visual grade ≥2) in the right carotid artery. CEUS demonstrated severe vascularization (grade 2) within the right carotid artery wall in 12 examinations. The carotid CEUS vascularization grade significantly correlated with vascular 18 F-FDG uptake (P < 0.001) and maximum standardized uptake value (SUV) in the right carotid artery/mean SUV in the superior vena cava (P = 0.001). When active vascular 18 F-FDG uptake (≥2) was considered the gold standard for defining vascular inflammation, carotid CEUS had a sensitivity of 100% (95% confidence interval [95% CI] 65-100) and a specificity of 92% (95% CI 72-99). The positive likelihood ratio was 12.5 (95% CI 3.3-47.2). Severe vascularization at CEUS and active vascular 18 F-FDG uptake were significantly more frequent in active disease according to Kerr's criteria compared to inactive (P = 0.001 and P = 0.002, respectively)., Conclusion: Carotid CEUS vascularization grade and the grade of vascular inflammation on 18 F-FDG-PET were correlated in patients with LVV., (© 2016, American College of Rheumatology.)

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., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Vascular inflammation is present in a subset of patients with cerebral amyloid angiopathy (CAA) and has a major influence in determining the disease manifestations. Radiological characterization of this subset is particularly important to achieve early recognition and treatment. We conducted this study to investigate the role of imaging in differentiating CAA with and without inflammation. We reviewed neuroimaging findings for 54 patients seen at Mayo Clinic over 25 years with pathological evidence of CAA and with available neuroimaging at the time of diagnosis. Clinical data were also recorded. Patients were grouped into CAA alone (no vascular inflammation), Aβ-related angiitis or ABRA (angiodestructive inflammation), and CAA-related inflammation or CAA-RI (perivascular inflammation). Imaging findings at presentation were compared among patient subgroups. Radiological features supporting a diagnosis of ABRA or CAA-RI were identified. Radiologic findings at diagnosis were available in 27 patients with CAA without inflammation, 22 with ABRA, and 5 with CAA-RI. On MRI, leptomeningeal disease alone or with infiltrative white matter was significantly more frequent at presentation in patients with ABRA or CAA-RI compared with those with CAA (29.6% vs. 3.7%, P = 0.02; and 40.7% vs. 3.7%, P = 0.002, respectively), whereas lobar hemorrhage was more frequent in patients with CAA (62.3% vs. 7.4%, P = 0.0001). Overall, leptomeningeal involvement at presentation was present in 70.4% of patients with ABRA or CAA-RI and in only 7.4% of patients with CAA (P = 0.0001). The sensitivity and specificity of leptomeningeal enhancement to identify patients with ABRA or CAA-RI were 70.4% and 92.6%, respectively, whereas the positive likelihood ratio (LR) was 9.5. The sensitivity and specificity of intracerebral hemorrhage to identify patients with CAA were 62.9% and 92.6%, respectively, whereas the positive LR was 8.5. Microbleeds were found in 70.4% of patients with inflammatory CAA at presentation. In conclusion, leptomeningeal enhancement and lobar hemorrhage at presentation may enable differentiation between CAA with and without inflammation. The identification at initial MRI of diffuse cortical-subcortical microbleeds in elderly patients presenting with infiltrative white matter process or prominent leptomeningeal enhancement is highly suggestive of vascular inflammatory CAA.

Biological agents represent a valid therapeutic option in patients with severe and/or relapsing vasculitis. Over the last years, some of these agents have become an established therapy (such as RTX in AAV or IFX for ocular BD), and some appear to hold promise to become so. In addition, there are a number of drugs in the pipeline that may contribute to further improve the prognosis of vasculitis. As the range of medications available for vasculitis widens, the need will also increase to define the best treatment schemes as well as to identify those patients that may benefit most from biological agents., (Copyright © 2015 Elsevier Masson SAS. All rights reserved.)

In large-vessel vasculitis, imaging studies are useful to document temporal artery involvement and crucial to show large-vessel involvement. Color Doppler sonography, magnetic resonance, and computed tomography show early vasculitic lesions. Angiography delineates later vascular complications well. Color Doppler sonography, magnetic resonance angiography, and computed tomography angiography can also be used to show vascular luminal changes. Positron emission tomography is very sensitive in detecting large-vessel inflammation. Imaging procedures can also be used to monitor the course of large-vessel vasculitis. In medium-vessel vasculitis, imaging studies can be used to show both vascular changes and internal organ changes., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Purpose: We aimed to assess the impact of (18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET) on the management of patients with suspected large vessel vasculitis., Methods: An international expert panel determined diagnoses and clinical management in patients with suspected large vessel vasculitis, with and without the results of (18)F-FDG PET, respectively. The accuracy of the clinical diagnosis and the resulting clinical management with and without the (18)F-FDG PET results were compared using logistic regression models., Results: The analysis included 30 patients referred to a tertiary care centre with large vessel vasculitis and 31 controls. (18)F-FDG PET had an overall sensitivity of 73.3% [95% confidence interval (CI) 54.1-87.7%], a specificity of 83.9% (95% CI 66.3-94.5%), a positive predictive value of 81.5% (95% CI 61.9-93.7%) and a negative predictive value of 76.5% (95% CI 58.8-89.3%). The diagnostic accuracy of (18)F-FDG PET was higher in patients not receiving immunosuppressive drugs (93.3 vs 64.5%, p = 0.006). Taken in context with other available diagnostic modalities, the addition of (18)F-FDG PET increased the clinical diagnostic accuracy from 54.1 to 70.5% (p = 0.04). The addition of (18)F-FDG PET increased the number of indicated biopsies from 22 of 61 patients (36.1%) to 25 of 61 patients (41.0%) and changed the treatment recommendation in 8 of 30 patients (26.7%) not receiving immunosuppressive medication and in 7 of 31 patients (22.6%) receiving immunosuppressive medication., Conclusion: (18)F-FDG PET is a sensitive and specific imaging tool for large vessel vasculitis, especially when performed in patients not receiving immunosuppressive drugs. It increases the overall diagnostic accuracy and has an impact on the clinical management in a significant proportion of patients.

Objectives: To provide recommendations on behalf of the Italian Society for Rheumatology for the off-label use of biologic agents in the treatment of large-vessel vasculitis., Methods: A panel of experts performed a literature search and selected the evidence relevant to the topic. The following five large-vessel vasculitides were considered: giant cell arteritis, Takayasu arteritis, primary angiitis of the central nervous system, Cogan's syndrome, and Adamantiades-Behçet's disease., Results: A consensus was achieved regarding the indication of biologic agents for the treatment of large-vessel vasculitis. Levels of evidence were assigned to the papers retrieved, and the strength of the recommendations was graded according to the levels of evidence., Conclusions: These recommendations may be used for guidance in deciding which patients with large-vessel vasculitis should receive biologic therapy. Further updates of these recommendations may be published on the basis of the results of new clinical studies and of data from post-marketing surveillance.

Purpose of Review: Chronic periaortitis is characterized by a fibro-inflammatory process spreading from the abdominal aorta and the iliac arteries. Originally, chronic periaortitis was considered a localized inflammatory response to severe aortic atherosclerosis. However, subsequent studies have shown that chronic periaortitis may also involve other arteries and present with features of auto-immune diseases. This article reviews the issue of large-vessel involvement in chronic periaortitis and its implications in the pathogenesis and nosography of the disease., Recent Findings: In many reports, chronic periaortitis has been shown to involve not only the aorto-iliac axis but also other vascular segments such as the thoracic aorta, the proximal epiaortic arteries, the coronary, renal, and mesenteric arteries. Thoracic aorta involvement may manifest as thoracic periaortitis with or without aneurysmal dilatation, or simply as thoracic aorta aneurysm. Thoracic periaortitis can also be a feature of the so-called IgG4-related systemic disease, with which chronic periaortitis may sometimes be associated. Histopathologic studies of chronic periaortitis show adventitial inflammation and fibrosis, vasculitis of vasa vasorum, and adventitial lymphoid follicles with germinal centers, suggesting that chronic periaortitis could be a primary aortitis. Genetic studies have demonstrated an association with HLA-DRB1*03, a marker of auto-immunity, and with the CCR5Δ32 polymorphism, which has been mapped to a Th2 response. Taken together, these findings support the notion of a primary inflammatory or immune-mediated disorder., Summary: Chronic periaortitis is an inflammatory or immune-mediated disorder characterized histopathologically by adventitial inflammation and clinically by variable involvement of different arteries, mainly of large caliber. These findings raise the issue of whether chronic periaortitis should be considered a large-vessel vasculitis.

The term "chronic periaortitis" (CP), proposed by Mitchinson in 1984, comprises 3 main entities: idiopathic retroperitoneal fibrosis (IRF), inflammatory abdominal aortic aneurysms (IAAAs), and perianeurysmal retroperitoneal fibrosis (PRF).The presence of constitutional symptoms, high acute-phase reactants, positive autoantibodies, and associated autoimmune diseases suggests a systemic inflammatory process. Histopathologic findings show vasculitis with fibrinoid necrosis involving the aortic vasa vasorum as well as the small and medium retroperitoneal vessels.We reviewed the medical records of 608 patients with a diagnosis of vasculitis involving the gastrointestinal (GI) tract at the Mayo Clinic between January 1996 and December 2007. Only patients with biopsy-proven or typical angiographic findings of vasculitis localized to the GI tract were included.Five patients were identified with evidence of CP (1 patient with PRF, 1 with IRF, and 3 with IAAAs). Three patients were men, and the median age at diagnosis was 49 years. The diagnosis of GI vasculitis and CP was made simultaneously in 4 patients. At the time of onset, all patients had abdominal pain and constitutional manifestations; the median erythrocyte sedimentation rate was 62.5 mm/1 h (range, 20-86 mm/1 h). All patients had evidence of mesenteric vasculitis at angiography. Three patients also had associated renal artery stenoses. Abdominal computed tomography showed spleen infarcts in 2 patients, bowel wall thickening in 1, and liver infarction in 1. Two patients underwent surgical intervention for acute abdomen; there was histologic evidence of small bowel infarcts and infarction of the spleen and liver in 1. Oral prednisone was administered to all 5 patients (median starting dose, 60 mg/d; range, 25-80 mg/d). Three patients also received immunosuppressive agents, 1 tamoxifen, and 1 anti-tumor necrosis factor therapy. All patients had at least 1 relapse or recurrence of vasculitis, but at last visit, GI vasculitis and CP were in remission in all 5 patients.This study provides evidence that GI manifestations due to mesenteric vasculitis may be associated with CP. Vasculitic involvement of the renal arteries is also frequently present in these patients. Aggressive immunosuppressive treatment should be promptly initiated to forestall abdominal complications. These findings reinforce the hypothesis that a vasculitic process plays an important role in the pathogenesis of CP.

Objective: To describe the clinical features and outcomes of patients with localized vasculitis of the gastrointestinal tract (LVGT)., Methods: Medical records of 608 patients diagnosed with vasculitis involving the intra-abdominal vasculature and/or abdominal viscera between January 1996 and December 2007 were reviewed. Only patients with histopathological confirmation or typical angiographic findings of vasculitis localized to the abdomen were included., Results: We identified 18 cases with LVGT over the 12-year study period. The patients were predominantly Caucasian (89%) and female (67%) with a median age at diagnosis of 53.5 (range 17.4-83.3) years. Most of the patients presented with abdominal pain and 12 (66.6%) patients presented with an acute abdomen requiring surgical intervention. At diagnosis, the median ESR was 30.5 (range 4-77) mm/h. Autoantibody screening was generally unrevealing. Abdominal CT scan findings included: bowel wall thickening, bowel infarction and solid organ infarcts. In 14 patients, the diagnosis of vasculitis was established by abdominal angiography. Histological evidence of vasculitis was recorded in 5 (28%) patients, most commonly from gall bladder or small intestine specimens. Corticosteroid therapy was administered to 10 (56%) patients, 5 of whom also received other immunosuppressive agents. Median duration of follow-up was 10.5 (range 2-156) months. No evidence of vasculitis outside the abdomen was observed during follow-up. Seven (39%) patients died during the follow-up period. Survival of the patient cohort (compared with an age-matched US white population) was significantly reduced (P < 0.001)., Conclusion: LVGT is an uncommon form of vasculitis that can be associated with significant morbidity and mortality.

Imaging techniques play a pivotal role in securing the diagnosis of large vessel vasculitis, and in demonstrating internal organ involvement in connective tissue diseases. In large vessel vasculitis, angiography is useful in demonstrating vessel stenoses or aneurysms. However, angiography is unable to reveal initial lesions such as vessel wall oedema and thickening, and is thus not useful to make an early diagnosis. In contrast, colour Doppler ultrasonography, computerized tomography angiography, and magnetic resonance imaging/angiography are able to delineate both the vessel wall and the lumen. Therefore, they may show vessel wall alterations when the lumen is still unaffected on angiography. 18fluorodeoxyglucose positron emission tomography does not visualize the vessel wall, but is very sensitive in revealing inflamed vessels. All of these investigations have also been used to follow up patients over time and to monitor response to treatment. In connective tissue diseases, imaging techniques are particularly useful to study internal organs, especially the brain and lung. Magnetic resonance imaging is the investigation of choice to detect and monitor brain disease, while computerized tomography is the best procedure for lung disease. However, since most imaging findings are not entirely specific for any given condition, it is important to interpret the results of imaging in the broader clinical context.

Numerous human studies and animal models have implicated various infectious agents in the pathogenesis of vasculitis in susceptible hosts. However, the link between infection and vasculitis is very complex and only incompletely understood. In fact, different agents can induce the same type of vasculitis, as the case of leukocytoclastic vasculitis exemplifies. Conversely, the same agent can give rise to a panoply of host responses ranging from a clinically silent infection or localized organ involvement to devastating, widespread vasculitis.

Primary Angiitis of the Central Nervous System (PACNS) is a rare cerebrovascular disease involving the arteries of the leptomeninges, brain and spinal cord. Its diagnosis can be challenging, and the current diagnostic criteria show several limitations. Among the clinical and neuroimaging manifestations of PACNS, intracranial bleeding, particularly intracerebral hemorrhage (ICH), is poorly described in the available literature, and it is considered infrequent. This review aims to summarize the available data addressing this issue with a dedicated focus on the clinical, neuroradiological and neuropathological perspectives. Moreover, the limitations of the actual data and the unanswered questions about hemorrhagic PACNS are addressed from a double point of view (PACNS subtyping and ICH etiology). Fewer than 20% of patients diagnosed as PACNS had an ICH during the course of the disease, and in cases where ICH was reported, it usually did not occur at presentation. As trigger factors, both sympathomimetic drugs and illicit drugs have been proposed, under the hypothesis of an inflammatory response due to vasoconstriction in the distal cerebral arteries. Most neuroradiological descriptions documented a lobar location, and both the large-vessel PACNS (LV-PACNS) and small-vessel PACNS (SV-PACNS) subtypes might be the underlying associated phenotypes. Surprisingly, amyloid beta deposition was not associated with ICH when histopathology was available. Moreover, PACNS is not explicitly included in the etiological classification of spontaneous ICH. This issue has received little attention in the past, and it could be addressed in future prospective studies. [ABSTRACT FROM AUTHOR]

The role of 18F-fluorodeoxyglucose (FDG) positron emission tomography (18F-FDG PET) in the diagnosis of large vessel vasculitis (LVV) is well established. It permits us to assess the extent and the grade of vascular involvement and to rule out the other causes in clinical scenarios characterized by less specific symptoms. The advantages of 18F-FDG PET are far less clear in monitoring disease activity over time. Studies looking for the role of 18F-FDG PET as a potential biomarker had conflicting results and whether and when to repeat it during follow-up is based on clinical experience. A comprehensive assessment, including clinical, laboratory and morphological imaging is still required to monitor patients with large-vessel vasculitis over time. The aim of this review is to present more recent data about the utility of 18 F-FDG PET in the diagnosis and follow-up of LVV. [ABSTRACT FROM AUTHOR]

Central nervous system vasculitis (CNSV) is an uncommon and poorly understood form of vasculitis. Early recognition is important because medical treatment might improve the outcome. However, randomized clinical trials on CNSV treatment do not exist. Endovascular treatment has been reported in few cases, but no data exist for intracranial stenting. We report 2 cases of patients with suspected CNSV and recurrent clinical episodes, treated with intracranial stenting. A 48-year-old man had relapsing episodes of right hemiparesis. Neuroradiological exams showed severe left carotid terminus stenosis. Despite immunosuppressive therapy, neuroradiological follow-up exams showed a worsening of the aforementioned stenosis with many transient episodes of weakness in the right limbs and aphasia. A 64-year-old woman had a sudden onset of dysarthria and transient aphasia. Neuroradiological exams showed a severe arterial stenosis involving the origin of left anterior cerebral artery and middle cerebral artery (MCA). Despite dual antiplatelet therapy, she presented an acute onset of severe aphasia, due to an occlusion of the left carotid terminus and proximal MCA. In both cases, endovascular procedure and intracranial stenting was performed, with marked improvement of cerebral blood flow. No more clinical episodes were reported. Intracranial stenting may be a valid therapeutic option in selected patients with CNSV and involvement of medium or large size vessels with clinical worsening despite best medical treatment. [ABSTRACT FROM AUTHOR]

Objectives To evaluate the accuracy of PET/CT and of PET vascular activity score (PETVAS) in assessing disease activity and the ability of PETVAS in predicting relapses in a large single-centre cohort of patients with large vessel vasculitis (LVV). Methods We conducted a retrospective cohort study of prospectively collected data of consecutive patients diagnosed with LVV who underwent at least one PET/CT scan between 2007 and 2020. The nuclear medicine physician's interpretation of each PET/CT scan (active/inactive vasculitis) was compared with disease activity clinical judgement (active disease/remission). For each PET/CT scan, the PETVAS score was calculated and its accuracy in assessing disease activity was evaluated. The ability of PETVAS in predicting subsequent relapses was evaluated. Results A total of 100 consecutive LVV patients (51 large vessel GCA, 49 Takayasu arteritis) underwent a total of 476 PET/CT scans over a mean follow-up period of 97.5 months. Physician-determined PET/CT grading was able to distinguish between clinically active and inactive LVV with a sensitivity of 60% (95% CI 50.9, 68.7) and specificity of 80.1% (95% CI 75.5, 84.1); the area under the curve (AUC)was 0.70 (95% CI 0.65, 0.75). PETVAS was associated with disease activity, with an age and sex–adjusted odds ratio for active disease of 1.15 (95% CI 1.11, 1.19). A PETVAS ≥10 provided 60.8% sensitivity and 80.6% specificity in differentiating between clinically active and inactive LVV; the AUC was 0.73 (95% CI 0.68, 0.79). PETVAS was not associated with subsequent relapses, with an age and sex–adjusted hazard ratio of 1.04 (95% CI 0.97, 1.11). Conclusions The visual PET/CT grading scale and PETVAS had moderate accuracy to distinguish active LVV from remission. PETVAS did not predict disease relapses. [ABSTRACT FROM AUTHOR]

Objectives Efficacy evaluation of GCA treatment is primarily based on non-specific symptoms and laboratory markers. We aimed to assess the change in vascular inflammation in patients with large vessel (LV)-GCA under different treatments using [18F]FDG PET/CT. Methods Observational study on patients with new-onset, active LV-GCA starting treatment with either prednisolone monotherapy (PRED) or combination with MTX or tocilizumab (TOC). All patients underwent baseline and follow-up PET/CT. The aorta and its major branches were assessed using PET vascular activity score (PETVAS) by independent readers. Cumulative glucocorticoid doses and cessation of glucocorticoid treatment were documented in all patients. Results We included 88 LV-GCA patients, 27 were treated with PRED, 42 with MTX and 19 with TOC. PETVAS decreased from 18.9–8.0 units at follow-up in the overall population (P <0.001). PETVAS changes were numerically higher in patients receiving MTX (−12.3 units) or TOC (−11.7 units) compared with PRED (−8.7). Mean cumulative prednisolone dosages were 5637, 4418 and 2984 mg in patients treated with PRED, MTX and TOC (P =0.002). Risk ratios for glucocorticoid discontinuation at the time of follow-up PET/CT were 6.77 (95% CI: 1.01, 45.29; P =0.049) and 16.25 (95% CI: 2.60, 101.73; P =0.003) for MTX and TOC users compared with PRED users. Conclusion Treatment of LV-GCA inhibits vascular inflammation in the aorta and its major branches. While similar control of vascular inflammation was achieved with PRED, MTX and TOC treatments, TOC showed a strong glucocorticoid sparing effect, supporting the concept of initial combination therapy. [ABSTRACT FROM AUTHOR]

Non-infectious uveitis are intraocular inflammatory conditions caused by dysregulated activation of the immune response without any detectable infectious agents. The aim of this study was to explore potential markers and therapeutic targets for two distinct types of non-infectious uveitis associated with Behçet's disease (BD) and Vogt Koyanagi Harada (VKH) disease. Concentrations of 27 cytokines were investigated in aqueous humor (AH) samples from patients with active uveitis vs. healthy controls (HC) (n = 10 patients with BD-associated uveitis; n = 10 patients with VKH-associated uveitis; n = 10 HC) using the Bio-Plex ProTM human cytokine group I panel. Additionally, leukocytes in AH samples were counted with hemocytometers and characterized by flow cytometry. Eleven cytokines were differentially expressed between patients with uveitis and HC with a median concentration greater than 10 pg/ml. IL-6, IP-10, G-CSF, and IFNγ showed higher concentrations in AH samples from both BD and VKH patients while IL-2, IL-8, IL-13, TNFα, eotaxin, IL-1ra showed statistically significant higher concentrations only in AH samples from BD patients. GM-CSF was the sole cytokine with an opposite profile showing decreased levels in AH samples from BD patients. IL-1ra and IL-6 were detected at higher frequencies in AH samples from BD and VKH patients compared with those from HC while IFNγ and TNFα were not detected in HC. The concentrations of IL-6, IL-8, IP-10, G-CSF, IFNγ, TNFα, eotaxin, IL-1ra positively correlated with the concentrations of leukocytes in AH, suggesting that such cytokines can be produced by immune cells and/or attract and/or promote proliferation and survival of immune cells in these types of uveitis. The correlation matrix of cytokine concentrations in AH samples revealed that IFNγ, TNFα, eotaxin, IL-6, G-CSF highly correlated each other. The ratios of cytokine concentrations between AH and plasma intra-individuals showed that IL-2, IL-6, IP-10, GM-CSF were increased intraocularly. In conclusion, AH sampling followed by multiplex analysis of cytokines should be fostered in non-infectious uveitis to identify cytokines dysregulated intraocularly in each individual laying the groundwork for precision medicine. [ABSTRACT FROM AUTHOR]

To assess the efficacy and safety of Rituximab (RTX) in adult primary central nervous system vasculitis (PCNSV). We retrospectively assessed the effect of RTX in 6 patients with PCNSV. Five of the 6 were refractory to high dose glucocorticoids (GCs) and/or conventional immunosuppressants (IS). The sixth was newly diagnosed and received RTX in combination with GCs. Clinical evaluation, laboratory tests, and imaging modalities were performed at initial RTX administration and during the follow-up. Treatment response was assessed using the treating physician's global opinion regarding response and the degree of disability using the modified Rankin scale (mRS). We also performed a literature review for previous use of RTX in PCNSV using PubMed, Ovid Medline, and the Cochrane library. The six patients (3 females) had a median age at diagnosis of 50.5 years (range 17–68 years). All had active disease when RTX was started. In 4 patients, RTX administration was associated with a marked reduction in the number of flares (from 18 before starting RTX to 3 after). One patient, after an initial improvement, had 2 flares when B cells were depleted and he was not able to reduce prednisone below 20 mg/day. A 6th patient had a flare when B cells recovered and retreatment with RTX re-induced and maintained remission. The median mRS score at last visit (median: 2; range 0–4) was lower than that prior to treatment (median 3; range 1–5). The median prednisone daily dose before RTX administration was significantly higher than that at last follow-up (p =.006). In the literature review, we identified 5 papers describing 7 patients treated with RTX. Six patients responded to RTX with clinical and MRI improvement with no reported flares after RTX treatment. Our data support a potential role for RTX treatment in selected patients with PCNSV. • In PCNSV there is the need to identify effective therapeutic agents • B-cell depletion in PCNSV maintains disease remission and reduces the number of flares and GC dosage • Rituximab is effective and safe in PCNSV refractory to traditional immunosuppressive agents • Rituximab could have a role as a first line therapy for PCNSV patients with less favorable prognosis [ABSTRACT FROM AUTHOR]

Objective. Chronic periaortitis (CP) is a rare disease characterized by fibro-inflammatory tissue surrounding the abdominal aorta and the iliac arteries. Anecdotal reports have shown that CP may also involve other vascular districts, particularly the thoracic aorta. The aim of this study was to investigate the thoracic aorta and epiaortic artery involvement in CP. Methods. Patients were eligible if they had undergone imaging studies assessing inflammatory involvement of the thoracic aorta and its major branches (e.g. contrast CT, MRI or PET-CT). We explored the patterns of thoracic vessel involvement and compared the clinical characteristics of patients with and without thoracic disease. Where available, we also reviewed the thoracic vascular/perivascular tissue biopsies. Results. Of 153 CP patients seen between 1999 and 2012, 77 were eligible. Of these, 28 (36%) had thoracic involvement: 15 (54%) had thoracic periaortitis, with 7 also showing epiaortic artery involvement; 6 (21 %) had periaortitis surrounding a thoracic aortic aneurysm, 2 of them with epiaortic artery involvement; 7 (25%) had a thoracic aortic aneurysm without periaortitis. Patients with thoracic disease were more frequently female (P = 0.01), were older (P = 0.001) and had a higher frequency of pain and constitutional symptoms (P = 0.02). Thoracic (peri)vascular biopsies revealed adventitial and peri-adventitial fibro-inflammatory patterns similar to those observed in abdominal CP. Conclusion. In about one-third of patients, CP also involves the thoracic aorta and the epiaortic arteries, which supports the hypothesis of a systemic inflammatory disease of the large arteries. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objective To describe the treatment and outcomes of patients with primary central nervous system (CNS) vasculitis. Methods We retrospectively studied a cohort of 163 consecutive patients with primary CNS vasculitis who were seen at the Mayo Clinic over a 29-year period. We analyzed treatments, treatment responses, and factors predictive of outcomes. Results A favorable response was observed in 85% of patients treated with prednisone alone and in 80% of patients treated with prednisone and cyclophosphamide. Relapses were observed in 27% of patients, and 25% of patients had discontinued therapy by the time of the last followup visit. Treatment with prednisone alone was associated with more frequent relapses (odds ratio [OR] 2.90), while large vessel involvement (OR 6.14) and cerebral infarcts at the time of diagnosis (OR 3.32) were associated with a poor response to treatment. Prominent gadolinium-enhanced cerebral lesions or meninges were linked with continued treatment at the last followup encounter (OR 2.28). Higher disability scores at the last followup visit were associated with increasing age at the time of diagnosis (OR 1.44) and cerebral infarctions (OR 3.74), while lower disability scores were associated with gadolinium-enhanced cerebral lesions or meninges (OR 0.35) and cerebral amyloid angiopathy (OR 0.24). Increased mortality was associated with increasing age at diagnosis (hazard ratio [HR] 1.39), diagnosis by angiography (HR 3.28), cerebral infarction (HR 4.44), and large vessel involvement (HR 4.98), while reduced mortality was associated with gadolinium-enhanced cerebral lesions or meninges (HR 0.20). Conclusion The majority of patients with primary CNS vasculitis responded to treatment. Recognition of findings at diagnosis that predict the course or outcome may aid in decision-making regarding therapy. [ABSTRACT FROM AUTHOR]

Objective. The aim of this study was to validate the classification criteria for cryoglobulinaemic vasculitis (CV).Methods. Twenty-three centres were involved. New patients with CV (group A) and controls, i.e. subjects with serum cryoglobulins but lacking CV based on the gold standard of clinical judgment (group B) and subjects without cryoglobulins but with clinical features that can be observed in the course of CV (group C), were studied. Positivity of serum cryoglobulins was necessary for CV classification. Sensitivity and specificity of the criteria were calculated by comparing group A vs group B. The group A vs group C comparison was done to demonstrate the possible diagnostic utility of the criteria.Results. The study included 268 patients in group A, 182 controls in group B and 193 controls in group C (small vessel vasculitis, 51.8%). The questionnaire (at least 2/3 positive answers) showed 89.0% sensitivity and 93.4% specificity; the clinical item (at least 3/4 clinical involvement) showed 75.7% sensitivity and 89.0% specificity and the laboratory item (at least 2/3 laboratory data) showed 80.2% sensitivity and 62.4% specificity. The sensitivity and specificity of the classification criteria (at least 2/3 positive items) were 89.9% and 93.5%, respectively. The comparison of group A with group C demonstrated the clinical utility of the criteria in differentiating CV from CV mimickers.Conclusion. Classification criteria for CV were validated in a second, large, international study confirming good sensitivity and specificity in a complex systemic disease. [ABSTRACT FROM PUBLISHER]

The article presents information on primary central nervous system vasculitis which may include headache, strokes and altered cognition. The use of angiography for its diagnosis and the impact of the size of vessels on the outcome of the treatment are also discussed. The treatment of the disease using corticosteroids at the early stages may prevent serious outcomes. The use of differential diagnosis is also discussed. INSETS: Search strategy and selection criteria;Panel: Causes of secondary CNS vasculitis.

Primary vasculitis of the central nervous system (PCNSV) is a rare and diagnostically challenging form of vasculitis limited to the brain and/or spinal cord. It is a complex and often severe disease with multifaceted clinical and pathological appearances, suggesting multiple disease subtypes and the potential existence of multiple etiologic pathways. We describe in detail the clinical, imaging, and neuropathological findings of PCNSV summarizing literature data and our observations from a cohort of 131 patients diagnosed at Mayo Clinic over a 25-year period (1983-2007). Unlike systemic vasculitis, little is known regarding PCNSV pathogenesis and the involved immunological mechanisms. Increased recognition of the disease spectrum and in-depth characterization of its histopathologic and immunological phenotype will be critical to eventually understanding the underlying derangements and mechanisms driving PCNSV. Improved understanding of the pathogenetic mechanisms of the disease may also help determine whether the different histologic patterns and clinical subsets represent more than one disease and ultimately may permit development of novel diagnostic and therapeutic strategies for it. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM PUBLISHER]

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. [ABSTRACT FROM AUTHOR]