Database : MEDLINE
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[PMID]: 25891759
[Au] Autor:Grayson PC; Carmona-Rivera C; Xu L; Lim N; Gao Z; Asare AL; Specks U; Stone JH; Seo P; Spiera RF; Langford CA; Hoffman GS; Kallenberg CG; St Clair EW; Tchao NK; Ytterberg SR; Phippard DJ; Merkel PA; Kaplan MJ; Monach PA; Rituximab in ANCA-Associated Vasculitis-Immune Tolerance Network Research Group
[Ad] Address:National Institute of Arthritis and Musculoskeletal and Skin Diseases, NIH, Bethesda, Maryland....
[Ti] Title:Neutrophil-Related Gene Expression and Low-Density Granulocytes Associated With Disease Activity and Response to Treatment in Antineutrophil Cytoplasmic Antibody-Associated Vasculitis.
[So] Source:Arthritis Rheumatol;67(7):1922-32, 2015 Jul.
[Is] ISSN:2326-5205
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:OBJECTIVE: To discover biomarkers involved in the pathophysiology of antineutrophil cytoplasmic antibody-associated vasculitis (AAV) and to determine whether low-density granulocytes (LDGs) contribute to gene expression signatures in AAV. METHODS: The source of clinical data and linked biologic specimens was a randomized controlled treatment trial in AAV. RNA sequencing of whole blood from patients with AAV was performed during active disease at the baseline visit and during remission 6 months later. Gene expression was compared between patients who met versus those who did not meet the primary trial outcome of clinical remission at 6 months (responders versus nonresponders). Measurement of neutrophil-related gene expression was confirmed in peripheral blood mononuclear cells (PBMCs) to validate the findings in whole blood. A negative-selection strategy isolated LDGs from PBMC fractions. RESULTS: Differential expression between responders (n = 77) and nonresponders (n = 35) was detected in 2,346 transcripts at the baseline visit (P < 0.05). Unsupervised hierarchical clustering demonstrated a cluster of granulocyte-related genes, including myeloperoxidase (MPO) and proteinase 3 (PR3). A granulocyte multigene composite score was significantly higher in nonresponders than in responders (P < 0.01) and during active disease than during remission (P < 0.01). This signature strongly overlapped an LDG signature identified previously in lupus (false discovery rate by gene set enrichment analysis <0.01). Transcription of PR3 measured in PBMCs was associated with active disease and treatment response (P < 0.01). LDGs isolated from patients with AAV spontaneously formed neutrophil extracellular traps containing PR3 and MPO. CONCLUSION: In AAV, increased expression of a granulocyte gene signature is associated with disease activity and decreased response to treatment. The source of this signature is likely LDGs, a potentially pathogenic cell type in AAV.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1506
[Cu] Class update date: 150627
[Lr] Last revision date:150627
[Js] Journal subset:AIM; IM
[St] Status:In-Data-Review
[do] DOI:10.1002/art.39153

  2 / 33519 MEDLINE  
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[PMID]: 25999375
[Au] Autor:Specks U
[Ad] Address:Division of Pulmonary and Critical Care Medicine, Mayo Clinic, Rochester, MN, USA.
[Ti] Title:Pro: Should all patients with anti-neutrophil cytoplasmic antibody-associated vasculitis be primarily treated with rituximab?
[So] Source:Nephrol Dial Transplant;30(7):1083-7, 2015 Jul.
[Is] ISSN:1460-2385
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:Randomized controlled trials have shown that rituximab is non-inferior to cyclophosphamide followed by azathioprine (CYC/AZA) for remission induction in severe granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA). The efficacy of rituximab is on par with CYC/AZA for 18 months, for patients with GPA and MPA alike, and for patients with any degree of renal impairment. The Rituximab in ANCA-associated Vasculitis (RAVE) trial also showed superiority of rituximab for patients presenting with a severe disease relapse. An exploratory analysis of the RAVE data further suggests that rituximab may be preferable for PR3-ANCA-positive patients as superiority was also achieved in that subset. When considering treatment options for patients with disease presentations for which only non-inferiority has been documented, safety concerns, compliance issues, the overall cost of each treatment approach to the patient, to society and to insurers, as well as individual patient preferences all should affect the decision-making process. The trials failed to uncover any difference in adverse events between rituximab and CYC/AZA. However, daily oral cyclophosphamide given for 3-6 months has measurable negative effects on fertility. Rituximab has certain compliance and convenience advantages. When assessing cost, the overall cost of a treatment, the societal context of the individual patient and not merely the sticker price of the drug should be considered. For all of these reasons, the author believes that CYC/AZA should be reserved for patients with newly diagnosed, MPO-ANCA-positive disease who raise no fertility, compliance or malignancy concerns.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1506
[Cu] Class update date: 150627
[Lr] Last revision date:150627
[Js] Journal subset:IM
[St] Status:In-Data-Review
[do] DOI:10.1093/ndt/gfv217

  3 / 33519 MEDLINE  
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[PMID]: 26106958
[Au] Autor:Nishimura WE; Sachetto Z; Costallat LT; Yazbek MA; Londe AC; Guariento EG; Marques SB; Bertolo MB
[Ad] Address:Department of Rheumatology, University of Campinas (UNICAMP), Campinas, SP, Brazil....
[Ti] Title:The role of KIR2DL3/HLA-C*0802 in Brazilian patients with rheumatoid vasculitis.
[So] Source:Clinics (Sao Paulo);70(6):408-12, 2015 Jun.
[Is] ISSN:1980-5322
[Cp] Country of publication:Brazil
[La] Language:eng
[Ab] Abstract:OBJECTIVES: Rheumatoid arthritis is a polygenically controlled systemic autoimmune disease. Rheumatoid vasculitis is an important extra-articular phenotype of rheumatoid arthritis that can result in deep cutaneous ulcers. The objective of this study was to establish a correlation between the frequency of major histocompatibility complex class I/II alleles and killer immunoglobulin-like receptor genotypes in patients with cutaneous rheumatoid vasculitis. METHODS: Using the Scott & Bacon 1984 criteria to diagnose rheumatoid vasculitis and after excluding any other causes such as diabetes, atherosclerosis, adverse drug reactions, infection, and smoking, patients who met the criteria were selected. All of the selected rheumatoid vasculitis patients presented deep cutaneous ulcers. Identification of the major histocompatibility complex class I/II and killer immunoglobulin-like receptor genotypes was performed by polymerase chain reaction assays of samples collected from the 23 rheumatoid vasculitis patients as well as from 80 controls (40 non-rheumatoid vasculitis RA control patients and 40 healthy volunteers). RESULTS: An association between the presence of the HLA-DRB1*1402 and HLA-DRB1*0101 alleles and cutaneous lesions in rheumatoid vasculitis patients and a correlation between the inhibitor KIR2DL3 and the HLA-C*0802 ligand in rheumatoid vasculitis patients were found. CONCLUSION: An association was found between the presence of the HLA-DRB1*1402 and HLA-DRB1*0101 alleles and the development of cutaneous lesions in rheumatoid vasculitis patients. Additionally, the HLA-C*0802 ligand protects these individuals from developing cutaneous lesions.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1506
[Cu] Class update date: 150627
[Lr] Last revision date:150627
[Js] Journal subset:IM
[St] Status:In-Data-Review

  4 / 33519 MEDLINE  
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[PMID]: 26062541
[Au] Autor:de Souza AW; van der Geest KS; Brouwer E; Pinheiro FA; Oliveira AC; Sato EI; Andrade LE; Bijl M; Westra J; Kallenberg CG
[Ad] Address:Department of Rheumatology and Clinical Immunology, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9700, RB, Groningen, The Netherlands. alexandre_wagner@uol.com.br....
[Ti] Title:High mobility group box 1 levels in large vessel vasculitis are not associated with disease activity but are influenced by age and statins.
[So] Source:Arthritis Res Ther;17:158, 2015.
[Is] ISSN:1478-6362
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:INTRODUCTION: Takayasu arteritis (TA) and giant cell arteritis (GCA) are large vessel vasculitides (LVV) that usually present as granulomatous inflammation in arterial walls. High mobility group box 1 (HMGB1) is a nuclear protein that acts as an alarmin when released by dying or activated cells. This study aims to evaluate whether serum HMGB1 can be used as a biomarker in LVV. METHODS: Twenty-nine consecutive TA patients with 29 healthy controls (HC) were evaluated in a cross-sectional study. Eighteen consecutive GCA patients with 16 HC were evaluated at the onset of disease and some of them during follow-up. Serum HMGB1 levels were measured by enzyme-linked immunosorbent assay. RESULTS: In GCA patients at disease onset mean serum HMGB1 levels did not differ from HC (5.74 ± 4.19 ng/ml vs. 4.17 ± 3.14 ng/ml; p = 0.230). No differences in HMGB1 levels were found between GCA patients with and without polymyalgia rheumatica (p = 0.167), ischemic manifestations (p = 0.873), systemic manifestations (p = 0.474) or relapsing disease (p = 0.608). During follow-up, no significant fluctuations on serum HMGB1 levels were observed from baseline to 3 months (n = 13) (p = 0.075), 12 months (n = 6) (p = 0.093) and at the first relapse (n = 4) (p = 0.202). Serum HMGB1 levels did not differ between TA patients and HC [1.19 (0.45-2.10) ng/ml vs. 1.46 (0.89-3.34) ng/ml; p = 0.181] and no difference was found between TA patients with active disease and in remission [1.31 (0.63-2.16) ng/ml vs. 0.75 (0.39-2.05) ng/ml; p = 0.281]. HMGB1 levels were significantly lower in 16 TA patients on statins compared with 13 patients without statins [0.59 (0.29-1.46) ng/ml vs. 1.93 (0.88-3.34) ng/ml; p = 0.019]. Age was independently associated with higher HMGB1 levels regardless of LVV or control status. CONCLUSIONS: Patients with TA and GCA present similar serum HMGB1 levels compared with HC. Serum HMGB1 is not useful to discriminate between active disease and remission. In TA, use of statins was associated with lower HMGB1 levels. HMGB1 is not a biomarker for LVV.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1506
[Cu] Class update date: 150627
[Lr] Last revision date:150627
[Js] Journal subset:IM
[St] Status:In-Data-Review
[do] DOI:10.1186/s13075-015-0672-8

  5 / 33519 MEDLINE  
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[PMID]: 26098644
[Au] Autor:He X; Yin W; Ding Y; Cui SJ; Luan J; Zhao P; Yue X; Yu C; Laing X; Zhao Y
[Ad] Address:Clinical research center, Wuhan Children's Hospital, No. 100 Hongkong Rd,Wuhan, China....
[Ti] Title:Higher Serum Angiotensinogen Is an Indicator of IgA Vasculitis with Nephritis Revealed by Comparative Proteomes Analysis.
[So] Source:PLoS One;10(6):e0130536, 2015.
[Is] ISSN:1932-6203
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:IgA vasculitis (IgAV), previously named as Henoch-Schönlein purpura, is the most common systematic vasculitis with unknown etiology. Lack of appropriate study system and/or animal model limits the understanding of its molecular pathogenesis and hinders the identification of targets for rational therapy, especially for its long-term complication, IgAV nephritis (IgAVN). In this study, we applied comparative analysis of serum proteomes to obtain an insight about disease pathogenesis. This study has utilized high sensitivity nanoscale ultra performance liquid chromatography-mass spectrometry (nanoLC-MS/MS) to investigate the alterations in serum proteomic profiles in patients with IgAV (n=6), IgAVN (n=6) and healthy subjects (n=7). The differentially expressed proteins were subjected to functional pathway analysis by PANTHER and DAVID software. We identified 107 differentially expressed proteins among three different groups, and functional analysis suggested that, in addition to earlier reported pathways, such as acute phase response, immune response, complement and blood coagulation pathways, hemostasis and Wnt signaling pathway were probably involved in pathogenesis of IgAV. A few differentially abundant proteins identified, such as C4a, serum amyloid A, angiotensinogen, and kininogen 1, were further validated by ELISA. More importantly, we found that angiotensinogen concentration is correlated with IgAVN and could be used as a potential marker for the progression of IgAV. This is the first report of analyzing the proteomic alterations in IgAV patients and the differentially proteins identified in this study may enhance understanding of the pathology of IgAV and a few of them may be used to monitor disease progression.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1506
[Cu] Class update date: 150627
[Lr] Last revision date:150627
[Js] Journal subset:IM
[St] Status:In-Data-Review
[do] DOI:10.1371/journal.pone.0130536

  6 / 33519 MEDLINE  
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[PMID]: 26069144
[Au] Autor:Park JY; Chung YR; Lee K; Song JH; Lee ES
[Ad] Address:Ozhean Skin Clinic, Seoul, Korea....
[Ti] Title:Clinical Experience of Interferon Alfa-2a Treatment for Refractory Uveitis in Behçet's Disease.
[So] Source:Yonsei Med J;56(4):1158-62, 2015 Jul.
[Is] ISSN:1976-2437
[Cp] Country of publication:Korea (South)
[La] Language:eng
[Ab] Abstract:Behçet's disease (BD) involves multisystem vasculitis of unknown origin. Ocular manifestations of BD mostly include bilateral panuveitis and retinal vasculitis, which are very challenging to treat. Interferon alfa-2a (IFN) has been recently introduced for treating refractory Behçet uveitis, mainly in Germany and Turkey. Nonetheless, there is so far no consensus about the ideal treatment regimen of IFN for Behçet uveitis. We report our experience of IFN treatment in five Korean BD patients with refractory uveitis. All patients complained of oral ulcers; one patient had a positive pathergy test and 2 showed the presence of HLA-B51. Immunosuppressive agents used prior to IFN treatment included cyclosporine and methotrexate. The IFN treatment was commenced with a dose of 6-9 MIU/day for 7 days, adjusted according to individual ocular manifestations, tapered down to 3 MIU three times in a week, and then discontinued. All patients showed positive response to IFN treatment; 50% of them showed complete response without additional major ocular inflammation during the follow-up period. Other BD symptoms also improved after IFN treatment in most cases. After treatment, the relapse rate and the required dose of oral corticosteroid were decreased in most cases, showing a significant steroid-sparing effect. However, the visual acuity was not improved in most cases due to irreversible macular sequelae. Despite the small sample size of this study, we suggest that, in Korean patients, IFN is an effective treatment modality for BD uveitis as was observed in German and Turkish patients.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1506
[Cu] Class update date: 150627
[Lr] Last revision date:150627
[Js] Journal subset:IM
[St] Status:In-Data-Review
[do] DOI:10.3349/ymj.2015.56.4.1158

  7 / 33519 MEDLINE  
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[PMID]: 26069134
[Au] Autor:Kim M; Kwon HJ; Choi EY; Kim SS; Koh HJ; Lee SC
[Ad] Address:Department of Ophthalmology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea....
[Ti] Title:Correlation between Fluorescein Angiographic Findings and Visual Acuity in Behçet Retinal Vasculitis.
[So] Source:Yonsei Med J;56(4):1087-96, 2015 Jul.
[Is] ISSN:1976-2437
[Cp] Country of publication:Korea (South)
[La] Language:eng
[Ab] Abstract:PURPOSE: To identify significant fluorescein angiographic (FA) characteristics associated with visual acuity (VA) in Behçet retinal vasculitis. MATERIALS AND METHODS: Retrospective review of 86 eyes of 48 patients (age: 35.6±10.2 years) with Behçet retinal vasculitis were performed. VA and FA findings as well as correlation between them were assessed. RESULTS: The mean initial VA of eyes with posterior pole-involved vasculitis (63 eyes; 73.3%) was significantly worse than that of those with peripheral vasculitis (23 eye; 26.7%) (logarithm of the minimum angle of resolution VA: 0.554±0.572 vs. 0.078±0.148; p<0.0001). Subgroup analysis revealed a more severe and diffuse pattern of vascular leakage in posterior pole-involved vasculitis compared to peripheral vasculitis (p<0.0001). Retinal vascular leakage (ß=0.345; p<0.0001), optic disc hyperfluorescence (ß=0.147; p=0.032), and macular leakage (ß=0.107; p=0.047) were significantly associated with worse initial VA. During the follow up (mean: 33.3±17.9 months), the change of leakage showed no significant correlation with change of VA in posterior pole-involved vasculitis (Ï„=0.199, p=0.092). CONCLUSION: Posterior pole involvement, the degree of retinal vascular leakage, optic disc hyperfluorescence, and macular leakage are significantly associated with VA in Behçet retinal vasculitis.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1506
[Cu] Class update date: 150627
[Lr] Last revision date:150627
[Js] Journal subset:IM
[St] Status:In-Data-Review
[do] DOI:10.3349/ymj.2015.56.4.1087

  8 / 33519 MEDLINE  
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[PMID]: 26065913
[Au] Autor:Malyavantham K; Weinstock-Guttman B; Suresh L; Zivadinov R; Shanahan T; Badgett D; Ramanathan M
[Ad] Address:Immco Diagnostics, Buffalo, NY, United States of America....
[Ti] Title:Humoral Responses to Diverse Autoimmune Disease-Associated Antigens in Multiple Sclerosis.
[So] Source:PLoS One;10(6):e0129503, 2015.
[Is] ISSN:1932-6203
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:METHODS: The study analyzed 969 serum samples from 315 HC, 411 relapsing remitting MS (RR-MS), 128 secondary progressive MS (SP-MS), 33 primary progressive MS (PP-MS) and 82 patients with other neurological diseases for autoantibodies against two putative MS antigens CSF114(Glc) and KIR4.1a and KIR4.1b and against 24 key endogenous antigens linked to diseases such as vasculitis, systemic sclerosis, rheumatoid arthritis, Sjogren's syndrome, systemic lupus erythematosus, polymyositis, scleroderma, polymyositis, dermatomyositis, mixed connective tissue disease and primary biliary cirrhosis. Associations with disability and MRI measures of lesional injury and neurodegeneration were assessed. RESULTS: The frequencies of anti-KIR4.1a and anti-KIR4.1b peptide IgG positivity were 9.8% and 11.4% in HC compared to 4.9% and 7.5% in RR-MS, 8.6% for both peptides in SP-MS and 6.1% for both peptides in PP-MS (p = 0.13 for KIR4.1a and p = 0.34 for KIR4.1b), respectively. Antibodies against CSF114(Glc), KIR4.1a and KIR4.1b peptides were not associated with MS compared to HC, or with MS disease progression. HLA DRB1*15:01 positivity and anti-Epstein Barr virus antibodies, which are MS risk factors, were not associated with these putative MS antibodies. CONCLUSIONS: Antibody responses to KIR4.1a and KIR4.1b peptides are not increased in MS compared to HC nor associated with MS disease progression. The frequencies of the diverse autoreactive antibodies investigated are similar in MS and HC.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1506
[Cu] Class update date: 150627
[Lr] Last revision date:150627
[Js] Journal subset:IM
[St] Status:In-Data-Review
[do] DOI:10.1371/journal.pone.0129503

  9 / 33519 MEDLINE  
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[PMID]: 26016754
[Au] Autor:Pagnoux C; Carette S; Khalidi NA; Walsh M; Hiemstra TF; Cuthbertson D; Langford C; Hoffman G; Koening CL; Monach PA; Moreland L; Mouthon L; Seo P; Specks U; Ytterberg S; Westman K; Hoglund P; Harper L; Flossman O; Luqmani R; Savage CO; Rasmussen N; de Groot K; Tesar V; Jayne D; Merkel PA; Guillevin L; french Vasculitis Study Group (FVSG), European Vasculitis Society (EUVAS) and Vasculitis Clinical Research Consortium (VCRC)
[Ad] Address:Division of Rheumatology, University of Toronto, Canada, and Department of Internal Medicine, National Referral Center for Necrotising Vasculitides and Systemic Sclerosis, Department of Internal Medicine, Hôpital Cochin, University of Paris, France....
[Ti] Title:Comparability of patients with ANCA-associated vasculitis enrolled in clinical trials or in observational cohorts.
[So] Source:Clin Exp Rheumatol;33(2 Suppl 89):S-77-83, 2015 Mar-Apr.
[Is] ISSN:0392-856X
[Cp] Country of publication:Italy
[La] Language:eng
[Ab] Abstract:OBJECTIVES: To analyse the differences between patients with granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA) entered into randomised clinical trials (RCTs) and those followed in large observational cohorts. METHODS: The main characteristics and outcomes of patients with generalised and/or severe GPA or MPA with a five-factor score ≥ 1 enrolled in the French Vasculitis Study Group (FVSG) or the US-Canadian-based Vasculitis Clinical Research Consortium cohorts were compared to those enrolled in one of 2 FVSG clinical RCTs (WEG91, WEGENT) or 3 European Vasculitis Society clinical trials (CYCLOPS, CYCAZAREM, IMPROVE). RESULTS: 657 patients (65.3% with GPA) in RCTs were compared to 437 in cohorts (90.6% with GPA). RCT patients were older at diagnosis than the cohort patients (56.6 ± 13.9 vs. 46.8 ± 17.3 years), had higher Birmingham vasculitis activity score (19.5 ± 9.1 vs. 16.9 ± 7.4), and more frequent kidney disease (84.0% vs. 54.9%) but fewer ear, nose, and throat symptoms (56.8% vs. 72.2%). At 56 months post-diagnosis, mortality and relapse rates, adjusted for age and renal function, were higher for patients with GPA in RCTs vs. cohorts (10.7% vs. 2.5% [p=0.001] and 22.5% vs. 15.6% [p=0.03], respectively) but similar for patients with MPA (6.2% vs. 6.6% [p=0.92] and 16.6% vs. 10.1% [p=0.39], respectively). CONCLUSIONS: Patients with GPA or MPA in RCTs and those in observational cohorts show important differences that should be remembered when interpreting results based on these study populations.
[Pt] Publication type:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T
[Em] Entry month:1505
[Cu] Class update date: 150627
[Lr] Last revision date:150627
[Js] Journal subset:IM
[St] Status:In-Process

  10 / 33519 MEDLINE  
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[PMID]: 25975436
[Au] Autor:Tullus K
[Ad] Address:Karolinska Institute, Stockholm, Sweden, Kjell.Tullus@gosh.nhs.uk.
[Ti] Title:Management of the renovascular disease in children with Takayasu arteritis.
[So] Source:Pediatr Nephrol;30(8):1213-6, 2015 Aug.
[Is] ISSN:1432-198X
[Cp] Country of publication:Germany
[La] Language:eng
[Ab] Abstract:Takaysu arteritis (TA), together with fibromuscular dysplasia, is the most common cause for renovascular hypertension. The diagnosis of vasculitis is important to make as these children benefit from immunosuppressive treatment. In many cases, however, it is more difficult than commonly realised to differentiate between these two diagnoses. Imaging which allows the inflamed arterial wall to be outlined, such as magnetic resonance or positron emission tomography scans, can be very helpful in this context. Revascularisation, either with angioplasty or surgery, seems to be effective and safe, also in children with TA. Patients with inactive disease have a more successful outcome and experience fewer complications from the intervention than those with active on-going inflammation.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1506
[Js] Journal subset:IM
[St] Status:In-Data-Review
[do] DOI:10.1007/s00467-015-3093-7


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