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1.
Diagn Interv Imaging ; 105(4): 137-143, 2024 Apr.
Article En | MEDLINE | ID: mdl-38284342

PURPOSE: The purpose of this in vivo animal study was to compare the acute histological effects on the arterial vessel wall of free-flow vs. blocked-flow embolization with metacryloxysulfolane-n­butyl cyanoacrylate (MS-NBCA) in several concentrations. MATERIALS AND METHODS: A total of 42 rabbit renal arteries were embolized using MS-NBCA mixed with ethiodized oil. The MS-NBCA concentration was 12.5%, 25%, or 50%. All mixtures were injected under both free-flow and blocked-flow conditions. The rabbits were euthanised 30 min after arterial embolization. Arterial-lumen distension, intimal inflammation and necrosis, peri­arterial edema, and distality of MS-NBCA penetration were assessed histologically. Multivariable regression analyses were performed using a manual backward procedure, with linear, ordinal and logistic regression to search for factors associated with these outcomes RESULTS: Marked or severe dilatation was observed in 36 out of 42 arteries (86%) and marked or transmural intimal arteritis in all 42 arteries (42/42; 100%). Lumen dilatation caused focal vessel-wall flattening, which resulted in intimal necrosis. Multifocal necrosis extending from the intima to the media occurred in 23 out of 42 kidneys (55%) and peri­arterial edema with multifocal vascular leakage in 19 out of 42 kidneys (45%). At multivariable analysis, blocked-flow MS-NBCA injection was associated with greater severity of vessel-wall lesions, including intimal arteritis (P = 0.003) and intimal necrosis (P = 0.014), compared to free-flow injection. Blocked-flow injection was also associated with peri­arterial edema (P = 0.008) and greater distality of MS-NBCA penetration (P = 0.001). CONCLUSION: Blocked-flow MS-NBCA injection during renal artery embolization is significantly associated with more acute arterial-wall damage and greater distality of glue penetration compared to free-flow injection in a rabbit model. These preliminary findings may have clinical implications, as blocked-flow injection is routinely used to treat specific vascular diseases or malformations in human.


Arteritis , Embolization, Therapeutic , Enbucrilate , Animals , Humans , Rabbits , Cyanoacrylates , Renal Artery , Embolization, Therapeutic/methods , Arteritis/drug therapy , Edema , Necrosis , Treatment Outcome
2.
PLoS One ; 19(1): e0295268, 2024.
Article En | MEDLINE | ID: mdl-38241272

In steroid-responsive meningitis-arteritis (SRMA), inflammatory dysregulation is driven by neutrophilic granulocytes resulting in purulent leptomeningitis. Neutrophils can generate neutrophil extracellular traps (NET). Uncontrolled NET-formation or impaired NET-clearance evidently cause tissue and organ damage resulting in immune-mediated diseases. The aim of the study was to verify that NET-formation is detectable in ex vivo samples of acute diseased dogs with SRMA by visualizing and measuring NET-markers in serum and cerebrospinal fluid (CSF) samples. CSF-samples of dogs with acute SRMA (n = 5) and in remission (n = 4) were examined using immunofluorescence (IF)-staining of DNA-histone-1-complexes, myeloperoxidase and citrullinated Histone H3 (H3Cit). Immunogold-labeling of H3Cit and neutrophil elastase followed by transmission electron microscopy (TEM) were used to determine ultrastructural NET-formation in the CSF of one exemplary dog. H3Cit-levels and DNase-activity were measured in CSF and serum samples using an H3Cit-ELISA and a DNase-activity-assay, respectively in patients with the following diseases: acute SRMA (n = 34), SRMA in remission (n = 4), bacterial encephalitis (n = 3), meningioma with neutrophilic inflammation (n = 4), healthy dogs (n = 6). NET-formation was detectable with IF-staining in n = 3/5 CSF samples of dogs with acute SRMA but were not detectable during remission. Vesicular NET-formation was detectable in one exemplary dog using TEM. DNase-activity was significantly reduced in dogs suffering from acute SRMA compared to healthy control group (p < 0.0001). There were no statistical differences of H3Cit levels in CSF or serum samples of acute diseased dogs compared to dogs under treatment, dogs suffering from meningioma or bacterial encephalitis or the healthy control group. Our findings demonstrate that NET-formation and insufficient NET-clearance possibly drive the immunologic dysregulation and complement the pathogenesis of SRMA. The detection of NETs in SRMA offers many possibilities to explore the aetiopathogenetic influence of this defence mechanism of the innate immune system in infectious and non-infectious canine neuropathies.


Arteritis , Dog Diseases , Encephalitis , Extracellular Traps , Meningeal Neoplasms , Meningioma , Meningitis , Humans , Dogs , Animals , Meningitis/drug therapy , Meningitis/veterinary , Arteritis/drug therapy , Arteritis/veterinary , Steroids , Deoxyribonucleases
3.
Mod Rheumatol Case Rep ; 8(1): 182-194, 2023 Dec 29.
Article En | MEDLINE | ID: mdl-37947034

Coronary periarteritis is a dangerous manifestation of IgG4-related disease, because it forms coronary artery aneurysms, which may cause sudden cardiac death. We report the case of a 78-year-old woman with IgG4-related coronary periarteritis and a coronary aneurysm, which showed progressive enlargement despite maintenance therapy for Type 1 autoimmune pancreatitis. This case was unique, in that coronary periarteritis was the only active lesion that recurred. Low-dose glucocorticoids suppressed the progression of periarterial lesions but led to rapid thinning of the aneurysmal wall and an increase in the size of mural thrombi, which pose a risk of myocardial infarction. Our systematic literature review including 98 cases of 86 articles was performed to examine its treatment strategies and complications. Among the cases in which the effect of immunosuppressive therapy could be followed radiologically, 33 of 37 (89.1%) cases showed improvement in wall thickening/periarterial soft tissue, while 6 of 13 (46.2%) showed worsening increase in the outer diameter of the coronary aneurysms. We propose a draft treatment algorithm and suggest that immunosuppressive therapy for IgG4-related coronary periarteritis with coronary aneurysms should be conducted only after the therapeutic benefit has been determined to outweigh the risks. Because coronary periarteritis can occur without other organ involvement, as in our case, all cases of IgG4-related disease require careful monitoring of coronary artery lesions.


Arteritis , Coronary Aneurysm , Immunoglobulin G4-Related Disease , Female , Humans , Aged , Coronary Aneurysm/diagnosis , Coronary Aneurysm/etiology , Coronary Aneurysm/therapy , Immunoglobulin G4-Related Disease/complications , Immunoglobulin G4-Related Disease/diagnosis , Immunoglobulin G4-Related Disease/drug therapy , Immunoglobulin G , Arteritis/drug therapy , Arteritis/pathology , Glucocorticoids/therapeutic use
4.
Vet J ; 300-302: 106030, 2023.
Article En | MEDLINE | ID: mdl-37704169

Steroid-responsive meningitis-arteritis (SRMA) occurs as an immune-mediated, inflammatory, and non-infectious disorder of juvenile and young-adult dogs. In principle, SRMA is divided into two clinical courses: during the typical acute form, dogs are presented with fever, cervical hyperaesthesia, and reluctance to move. The more protracted form most probably emerges after insufficient immunosuppressive treatment or relapses, with additional neurologic deficits localized in the cervical and thoracolumbar spinal cord or multifocally. The trigger leading to SRMA still remains an unsolved riddle for immunologists and clinical neurologists. In the past, many attempts have been made to clarify the etiology of this disease without success. The purpose of writing this narrative review about SRMA is to summarize new insights on the pathogenesis of SRMA with a focus on immunologic dysregulation. Furthermore, unusual manifestations of the disease, new diagnostic approaches using possible laboratory biomarkers or diagnostic imaging tools, and potential innovative treatment strategies are discussed.


Arteritis , Dog Diseases , Meningitis , Animals , Dogs , Meningitis/drug therapy , Meningitis/veterinary , Arteritis/drug therapy , Arteritis/veterinary , Biomarkers , Steroids/therapeutic use , Dog Diseases/drug therapy
5.
J Clin Lipidol ; 17(5): 694-699, 2023.
Article En | MEDLINE | ID: mdl-37598001

Elevated lipoprotein(a) [Lp(a)] is a causal risk factor for atherosclerotic cardiovascular disease. However, there are no approved and effective treatments for lowering Lp(a) and the associated cardiovascular risks. Omega-3 fatty acids (ω-3FAs), primarily eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), have both triglyceride-lowering and anti-inflammatory properties. This pilot study investigated the effect of high dose ω-3FAs (3.6 g/day) on arterial inflammation in 12 patients with elevated Lp(a) (> 0.5 g/L) and stable coronary artery disease (CAD) receiving cholesterol-lowering treatment. Arterial inflammation was determined using 18F-fluorodexoyglucose positron emission tomography/computed tomography before and after 12-weeks intervention. ω-3FAs significantly lowered plasma concentrations of triglycerides (-17%, p < 0.01), Lp(a) (-5%, p < 0.01) as well as aortic maximum standardized uptake value (SUVmax) (-4%, p < 0.05). The reduction in SUVmax was significantly inversely associated with average on-treatment EPA (r = -0.750, p < 0.01), but not DHA and triglyceride, concentrations. In conclusion, high dose ω-3FAs decrease arterial inflammation in patients with elevated Lp(a) and stable CAD, which may involve a direct arterial effect of EPA.


Arteritis , Coronary Artery Disease , Fatty Acids, Omega-3 , Humans , Eicosapentaenoic Acid/therapeutic use , Pilot Projects , Fatty Acids, Omega-3/therapeutic use , Docosahexaenoic Acids/therapeutic use , Coronary Artery Disease/drug therapy , Triglycerides , Arteritis/drug therapy , Lipoprotein(a)
6.
Transpl Infect Dis ; 25(5): e14108, 2023 Oct.
Article En | MEDLINE | ID: mdl-37504382

BACKGROUND: Aspergillus spp. is an uncommon and life-threatening cause of transplantrenal artery pseudoaneurysm after kidney transplantation. CASE: We report the case of a 62-year-old woman who underwent kidney transplantation 10 months before and presented a 7-cm asymptomatic transplant renal artery pseudoaneurysm. Transplanted kidney and pseudoaneurysm were surgically removed in emergency. Renal graft, urine, and pseudoaneurysm cultures grew Aspergillus flavus. She recovered after 12 months of antifungal therapy. LITERATURE REVIEW: To date 14 cases of Aspergillus spp. renal arteritis after kidney transplantation have been published, including 50% Aspergillus flavus arteritis. Vast majority were diagnosed within 90 days after transplantation (73%). Despite allograft nephrectomy and antifungal therapy, mortality rate was high (33%).


Aneurysm, False , Arteritis , Kidney Transplantation , Female , Humans , Middle Aged , Aneurysm, False/etiology , Aneurysm, False/microbiology , Antifungal Agents/therapeutic use , Arteritis/drug therapy , Arteritis/microbiology , Aspergillus , Aspergillus flavus , Kidney , Kidney Transplantation/adverse effects
7.
Ann Rheum Dis ; 82(3): 324-330, 2023 03.
Article En | MEDLINE | ID: mdl-36450449

OBJECTIVE: Recent large-scale randomised trials demonstrate that immunomodulators reduce cardiovascular (CV) events among the general population. However, it is uncertain whether these effects apply to rheumatoid arthritis (RA) and if certain treatment strategies in RA reduce CV risk to a greater extent. METHODS: Patients with active RA despite use of methotrexate were randomly assigned to addition of a tumour necrosis factor (TNF) inhibitor (TNFi) or addition of sulfasalazine and hydroxychloroquine (triple therapy) for 24 weeks. Baseline and follow-up 18F-fluorodeoxyglucose-positron emission tomography/CT scans were assessed for change in arterial inflammation, an index of CV risk, measured as an arterial target-to-background ratio (TBR) in the carotid arteries and aorta. RESULTS: 115 patients completed the protocol. The two treatment groups were well balanced with a median age of 58 years, 71% women, 57% seropositive and a baseline disease activity score in 28 joints of 4.8 (IQR 4.0, 5.6). Baseline TBR was similar across the two groups. Significant TBR reductions were observed in both groups-ΔTNFi: -0.24 (SD=0.51), Δtriple therapy: -0.19 (SD=0.51)-without difference between groups (difference in Δs: -0.02, 95% CI -0.19 to 0.15, p=0.79). While disease activity was significantly reduced across both treatment groups, there was no association with change in TBR (ß=0.04, 95% CI -0.03 to 0.10). CONCLUSION: We found that addition of either a TNFi or triple therapy resulted in clinically important improvements in vascular inflammation. However, the addition of a TNFi did not reduce arterial inflammation more than triple therapy. TRIAL REGISTRATION NUMBER: NCT02374021.


Antirheumatic Agents , Arteritis , Arthritis, Rheumatoid , Cardiovascular Diseases , Humans , Female , Middle Aged , Male , Antirheumatic Agents/adverse effects , Cardiovascular Diseases/prevention & control , Cardiovascular Diseases/chemically induced , Tumor Necrosis Factor-alpha , Risk Factors , Arthritis, Rheumatoid/diagnostic imaging , Arthritis, Rheumatoid/drug therapy , Arthritis, Rheumatoid/chemically induced , Methotrexate/therapeutic use , Immunologic Factors/therapeutic use , Heart Disease Risk Factors , Arteritis/chemically induced , Arteritis/drug therapy , Treatment Outcome
8.
Pediatr Rheumatol Online J ; 20(1): 119, 2022 Dec 22.
Article En | MEDLINE | ID: mdl-36550471

BACKGROUND: Kawasaki disease (KD) is usually treated with high-dose intravenous immunoglobulin (IVIg) as severe infectious and other diseases. Due to issues that are associated with immunoglobulin preparation, such as the risk of possible contamination by infectious agents and limited blood banking resources, recombinant immunoglobulins are required. We developed a novel recombinant antibody drug candidate, "VasSF," based on the therapeutic effects it exerted on a mouse spontaneous crescentic glomerulonephritis model (SCG/Kj). Apolipoprotein A-2 (ApoA2) has been identified as one of VasSF's target molecules. METHODS: Here, we tested the potential of anti-apolipoprotein A-2 antibodies (anti-ApoA2) as a new therapeutic drug against KD by examining its effect on a mouse model, in which KD was induced via Candida albicans water-soluble fraction (CAWS). CAWS (2 mg/mouse) was injected intraperitoneally into C57BL/6NCrSlc mice for five consecutive days. The incidence and histological severity of vasculitis in CAWS-induced coronary arteritis in mice administered anti-ApoA2 was examined. The following experimental groups were tested: solvent (only PBS (-) injection); anti-ApoA2 antibodies at dosages of 0.05 mg, 0.1 mg, and 0.5 mg/kg/day; human IgG at 0.1 mg/kg/day. RESULTS: The group treated with anti-ApoA2 0.5 mg/kg/day showed a lower incidence of panvasculitis induced by CAWS, less inflammation of the coronary arteries and aortic roots, and lower levels of serum IL-6, M-CSF, and MIP-1α and 32 cytokines/chemokines compared with those in the solvent group. CONCLUSIONS: The anti-ApoA2 treatment suppressed the development of coronary arteritis in an animal KD model and anti-ApoA2 shows potential as an effective therapeutic candidate for the treatment of KD vasculitis. The use of specific antibodies that display higher vasculitis-suppressing effects, such as anti-ApoA2, may attenuate KD as well as other infectious diseases, with less severe adverse side effects than treatment with IVIg.


Arteritis , Coronary Artery Disease , Mucocutaneous Lymph Node Syndrome , Vasculitis , Humans , Mice , Animals , Mucocutaneous Lymph Node Syndrome/complications , Mucocutaneous Lymph Node Syndrome/drug therapy , Immunoglobulins, Intravenous/therapeutic use , Mice, Inbred C57BL , Vasculitis/etiology , Coronary Artery Disease/complications , Disease Models, Animal , Coronary Vessels/pathology , Arteritis/drug therapy , Arteritis/etiology , Solvents/adverse effects
9.
Molecules ; 27(23)2022 Nov 22.
Article En | MEDLINE | ID: mdl-36500227

Cardiovascular disease caused by atherosclerosis (AS) seriously affects human health. Photothermal therapy (PTT) brings hope to the diagnosis and treatment of AS, with the development of nanotechnology. To improve treatment efficiency, self-assembled CuCo2S4 nanocrystals (NCs) were developed as a drug-delivery nanocarrier, triggered by near-infrared (NIR) light for efficient chemophotothermal therapy of arterial inflammation. The as-prepared self-assembled CuCo2S4 NCs exhibited excellent biocompatibility and a very high chloroquine (CL)-loading content. In addition, the self-assembled CuCo2S4 NCs/CL nanocomposites showed good photothermal performance, due to strong absorption in the NIR region, and the release of CL from the NCs/CL nanocomposites was driven by NIR light. When illuminated by NIR light, both PTT from the NCs and chemotherapy from the CL were simultaneously triggered, resulting in killing macrophages with a synergistic effect. Moreover, chemo-photothermal therapy with CuCo2S4 NCs/CL nanocomposites showed an effective therapeutic effect for arterial inflammation, in vivo. Our work demonstrated that chemo-photothermal therapy could be a promising strategy for the treatment of arterial inflammation against atherosclerosis.


Arteritis , Hyperthermia, Induced , Nanoparticles , Neoplasms , Humans , Phototherapy/methods , Photothermal Therapy , Nanoparticles/chemistry , Drug Delivery Systems/methods , Arteritis/drug therapy , Doxorubicin/therapeutic use , Neoplasms/drug therapy
10.
Intern Med ; 61(3): 351-356, 2022.
Article En | MEDLINE | ID: mdl-35110514

Immunoglobulin-G4-related disease (IgG4-RD) is a multi-organ systemic inflammatory disorder. The ideal treatment of coronary artery involvement in IgG4-RD remains uncertain due to its rarity. We herein report a case of coronary artery involvement with IgG4-RD, wherein mass lesions surrounded the coronary arteries with a moderate stenosis lesion in the right coronary artery (RCA). The fractional flow reserve (FFR) of the RCA was 0.76. After steroid therapy, the mass lesions around the coronary arteries improved. The FFR of the RCA also improved from 0.76 to 0.86. These findings suggest the efficacy of using steroid therapy for coronary artery involvement with IgG4-RD.


Arteritis , Fractional Flow Reserve, Myocardial , Arteritis/drug therapy , Coronary Vessels/diagnostic imaging , Humans , Immunoglobulin G , Steroids/therapeutic use
11.
J Vasc Res ; 59(3): 176-188, 2022.
Article En | MEDLINE | ID: mdl-34929700

INTRODUCTION AND OBJECTIVE: Kawasaki disease (KD) is associated with diffuse and systemic vasculitis of unknown aetiology and primarily affects infants and children. Intravenous immunoglobulin (IVIG) treatment reduces the risk of developing coronary aneurysms, but some children have IVIG-resistant KD, which increases their risk of developing coronary artery injury. Here, we investigated the effect of recombinant human soluble thrombomodulin (rTM), which has anticoagulant, anti-inflammatory, and cytoprotective properties on the development of coronary arteritis in a mouse model of vasculitis. METHODS: An animal model of KD-like vasculitis was created by injecting mice with Candida albicans water-soluble fraction (CAWS). This model was used to investigate the mRNA expression of interleukin (IL)-10, tumour necrosis factor alpha (TNF-α), and tissue factor (TF), in addition to histopathology of heart tissues. RESULTS: rTM treatment significantly reduces cardiac vascular endothelium hypertrophy by 34 days after CAWS treatment. In addition, mRNA expression analysis revealed that rTM administration increased cardiac IL-10 expression until day 27, whereas expression of TNF-α was unaffected. Moreover, in the spleen, rTM treatment restores IL-10 and TF expression to normal levels. CONCLUSION: These findings suggest that rTM suppresses CAWS-induced vasculitis by upregulating IL-10. Therefore, rTM may be an effective treatment for KD.


Arteritis , Mucocutaneous Lymph Node Syndrome , Thrombomodulin , Vasculitis , Animals , Arteritis/drug therapy , Arteritis/pathology , Candida albicans/metabolism , Coronary Vessels/metabolism , Disease Models, Animal , Humans , Immunoglobulins, Intravenous , Interleukin-10 , Mice , Mucocutaneous Lymph Node Syndrome/drug therapy , RNA, Messenger , Recombinant Proteins/therapeutic use , Thrombomodulin/therapeutic use , Tumor Necrosis Factor-alpha/metabolism , Vasculitis/drug therapy , Vasculitis/prevention & control
12.
Nuklearmedizin ; 61(1): 33-41, 2022 Feb.
Article En | MEDLINE | ID: mdl-34918332

PURPOSE: Resveratrol has shown promising anti-inflammatory effects in in vitro and animal studies. We aimed to investigate this effect on arterial inflammation in vivo. METHODS: This was an additional analysis of a double-blind randomized crossover trial which included eight male subjects with decreased insulin sensitivity who underwent an 18F-fluoroxyglucose (18F-FDG) PET/CT after 34 days of placebo and resveratrol treatment (150 mg/day). 18F-FDG uptake was analyzed in the carotid arteries and the aorta, adipose tissue regions, spleen, and bone marrow as measures for arterial and systemic inflammation. Maximum target-to-background ratios (TBRmax) were compared between resveratrol and placebo treatment with the non-parametric Wilcoxon signed-rank test. Median values are shown with their interquartile range. RESULTS: Arterial 18F-FDG uptake was non-significantly higher after resveratrol treatment (TBRmax all vessels 1.7 (1.6-1.7)) in comparison to placebo treatment (1.5 (1.4-1.6); p=0.050). Only in visceral adipose tissue, the increase in 18F-FDG uptake after resveratrol reached statistical significance (p=0.024). Furthermore, CRP-levels were not significantly affected by resveratrol treatment (p=0.091). CONCLUSIONS: Resveratrol failed to attenuate arterial or systemic inflammation as measured with 18F-FDG PET in subjects at risk of developing type 2 diabetes. However, validation of these findings in larger human studies is needed.


Arteritis , Diabetes Mellitus, Type 2 , Arteritis/diagnostic imaging , Arteritis/drug therapy , Cross-Over Studies , Diabetes Mellitus, Type 2/drug therapy , Fluorodeoxyglucose F18 , Humans , Inflammation/drug therapy , Male , Positron Emission Tomography Computed Tomography , Radiopharmaceuticals , Resveratrol/therapeutic use
14.
Int J Rheum Dis ; 24(8): 1004-1013, 2021 Aug.
Article En | MEDLINE | ID: mdl-34138520

OBJECTIVE: Immunoglobulin G4-related disease (IgG4-RD) is a newly recognized fibro-inflammatory disease which affects many systems, as well as the cardiovascular system. Identifying the coronary involvement like periaortitis, coronary periarteritis and pericarditis is important, as they often cause unfavorable outcomes. METHODS: Eighty-one patients with IgG4-RD were retrospectively evaluated for symptomatic coronary artery involvement from Hacettepe University Vasculitis Research Center (HUVAC) database. The demographic, laboratory, radiologic and clinical characteristics of the patients were assessed. RESULTS: Among 81 patients with IgG4-RD, 6 patients (M/F:5/1) had coronary artery involvement. The patients' median age was 57 and serum IgG4 levels were above normal except for one case. All patients with coronary arteritis revealed an increased coronary vessel wall thickening and stenotic lesions. The coronary aneurysm and pericarditis were observed in half of the patients. Immunosuppressive treatments were given to all the patients and most of them followed in stable condition. CONCLUSION: Coronary arteritis is a rare but notable manifestation of IgG4-RD. Although coronary periarteritis can cause significant morbidity and mortality, it seems better results can be achieved with early diagnosis and treatment.


Arteritis/immunology , Coronary Artery Disease/immunology , Immunoglobulin G4-Related Disease/immunology , Immunoglobulin G/blood , Adult , Aged , Aged, 80 and over , Arteritis/blood , Arteritis/diagnosis , Arteritis/drug therapy , Biomarkers/blood , Coronary Artery Disease/blood , Coronary Artery Disease/diagnosis , Coronary Artery Disease/drug therapy , Databases, Factual , Female , Humans , Immunoglobulin G4-Related Disease/blood , Immunoglobulin G4-Related Disease/diagnosis , Immunoglobulin G4-Related Disease/drug therapy , Immunosuppressive Agents/therapeutic use , Male , Middle Aged , Retrospective Studies , Treatment Outcome , Turkey , Up-Regulation
15.
Arthritis Rheumatol ; 73(2): 286-294, 2021 02.
Article En | MEDLINE | ID: mdl-32951354

OBJECTIVE: Temporal arteritis (TA) is a typical manifestation of giant cell arteritis (GCA). Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAVs) are rarely revealed by TA manifestations, leading to a risk of misdiagnosis of GCA and inappropriate treatments. This study was undertaken to describe the clinical, biologic, and histologic presentations and outcomes in cases of TA revealing AAV (TA-AAV) compared to controls with classic GCA. METHODS: In this retrospective case-control study, the characteristics of patients with TA-AAV were compared to those of control subjects with classic GCA. Log-rank test, with hazard ratios (HRs) and 95% confidence intervals (95% CIs), was used to assess the risk of treatment failure. RESULTS: Fifty patients with TA-AAV (median age 70 years) were included. Thirty-three patients (66%) presented with atypical symptoms of GCA (ear, nose, and throat involvement in 32% of patients, and renal, pulmonary, and neurologic involvement in 26%, 20%, and 16% of patients, respectively). Blood samples were screened for ANCAs at the time of disease onset in 33 patients, and results were positive in 88%, leading to a diagnosis of early TA-AAV in 20 patients. The diagnosis of AAV was delayed a median interval of 15 months in 30 patients. Compared to controls with GCA, patients with TA-AAV were younger (median age 70 years versus 74 years), were more frequently men (48% versus 30%), and had high frequencies of atypical manifestations and higher C-reactive protein levels (median 10.8 mg/dl versus 7.0 mg/dl). In patients with TA-AAV, temporal artery biopsy (TAB) showed fibrinoid necrosis and small branch vasculitis in 23% of patients each, whereas neither of these characteristics was evident in controls with GCA. Treatment failure-free survival was comparable between early TA-AAV cases and GCA controls, whereas those with delayed TA-AAV had a significantly higher risk of treatment failure compared to controls (HR 3.85, 95% CI 1.97-7.51; P < 0.0001). CONCLUSION: TA-AAV should be considered diagnostically in cases of atypical manifestations of GCA, refractoriness to glucocorticoid treatment, or early relapse. Analysis of TAB specimens for the detection of small branch vasculitis and/or fibrinoid necrosis could be useful. Detection of ANCAs should be performed in cases of suspected GCA with atypical clinical features and/or evidence of temporal artery abnormalities on TAB.


Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/physiopathology , Giant Cell Arteritis/physiopathology , Temporal Arteries/physiopathology , Aged , Aged, 80 and over , Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/diagnosis , Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/drug therapy , Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/pathology , Arteritis/diagnosis , Arteritis/drug therapy , Arteritis/pathology , Arteritis/physiopathology , Asthenia/physiopathology , Case-Control Studies , Cough/physiopathology , Delayed Diagnosis , Diagnosis, Differential , Diplopia/physiopathology , Female , Fever/physiopathology , France , Giant Cell Arteritis/diagnosis , Giant Cell Arteritis/drug therapy , Giant Cell Arteritis/pathology , Glucocorticoids/therapeutic use , Headache/physiopathology , Humans , Jaw , Male , Middle Aged , Pain/physiopathology , Polymyalgia Rheumatica/physiopathology , Proportional Hazards Models , Retrospective Studies , Scalp , Sweating , Temporal Arteries/pathology , Treatment Failure , Vision Disorders/physiopathology , Weight Loss
16.
J Am Anim Hosp Assoc ; 57(1): 1-7, 2021 Jan 01.
Article En | MEDLINE | ID: mdl-33260200

Treatment with high corticosteroid dosages for steroid-responsive meningitis-arteritis (SRMA) is correlated with severe adverse effects and worse quality of life. In order to improve immunosuppression and decrease dosage and duration of glucocorticoid treatment, a second immunosuppressive drug is commonly used in most of the immune-mediated diseases. The objective of this retrospective study was to evaluate the efficacy, tolerability, and occurrence of relapse for the combination of prednisolone and azathioprine. All dogs received azathioprine 2 mg/kg q 24 hr for 1 mo and then 2 mg/kg every other day for 2 mo; prednisolone was started at an immunosuppressive dosage and tapered off gradually during a mean of 3 mo. Twenty-six dogs met inclusion criteria. Twenty-one dogs (81%) were in clinical remission with no relapse observed within the 2 yr follow-up period. Treatment was well tolerated in all dogs and side effects were most of the time mild and self-limiting. The relapse rate (19%) was lower than most published rates. A prednisolone and azathioprine combination appeared to be effective for primary treatment of dogs with SRMA and allows a quicker tapering in prednisolone dosage, a decrease in long-term side effects of steroids, a shorter duration of treatment, and a low relapse rate.


Arteritis/veterinary , Azathioprine/therapeutic use , Dog Diseases/drug therapy , Meningitis/veterinary , Prednisolone/therapeutic use , Animals , Arteritis/drug therapy , Dogs , Female , Glucocorticoids , Immunosuppressive Agents , Male , Meningitis/drug therapy , Quality of Life , Retrospective Studies
17.
BMC Vet Res ; 16(1): 437, 2020 Nov 11.
Article En | MEDLINE | ID: mdl-33176763

BACKGROUND: We report the first case of canine Salmonella meningoencephalomyelitis and second case of canine Salmonella bacteriuria, as well as the first reported case of Salmonella enterica subspecies houtenae in a dog. CASE PRESENTATION: Immunosuppressive treatment in a dog for a relapse of steroid-responsive meningitis and arteritis (SRMA) allowed for the opportunistic establishment of a bacteremia with Salmonella enterica subsp. houtenae, ultimately causing meningoencephalomyelitis and subclinical bacteriuria. The bacterial infections were treated with a four-month course of amoxicillin; clinical treatment success was determined by serial negative urine cultures and lack of clinical signs correlated to the meningoencephalomyelitis. CONCLUSIONS: Both the bacteriuria and meningoencephalomyelitis represented opportunistic infections in a dog immunosuppressed for SRMA. The clinical course of this infectious meningoencephalitis emphasizes the importance of differentiating relapse of initial disease from opportunistic infection occurring in a compromised central nervous system. The novel Salmonella species identified in this case acts as a reminder that infectious disease diagnostics should not be curbed by anecdotal prediction of routine pathogenic suspects.


Bacteriuria/veterinary , Dog Diseases/microbiology , Encephalomyelitis/veterinary , Salmonella/isolation & purification , Amoxicillin/therapeutic use , Animals , Anti-Bacterial Agents/therapeutic use , Arteritis/drug therapy , Arteritis/veterinary , Bacteriuria/drug therapy , Bacteriuria/microbiology , Dog Diseases/drug therapy , Dogs , Encephalomyelitis/drug therapy , Encephalomyelitis/microbiology , Female , Immunosuppressive Agents/therapeutic use , Meningitis/drug therapy , Meningitis/veterinary , Opportunistic Infections/veterinary , Steroids/therapeutic use
19.
J Cutan Pathol ; 47(9): 854-859, 2020 Sep.
Article En | MEDLINE | ID: mdl-32338386

Cutaneous vasculitis can be classified into two types based on the affected vessel size: small vessel vasculitis predominantly affecting dermal venules, and muscular vessel vasculitis as found in cutaneous arteritis predominantly affecting arteries located at the dermal-subcutaneous junction. We describe two cases with a novel small vessel vasculitis disorder, which exclusively affected arterioles in the mid-dermis, and show clinical and pathological difference distinct from cutaneous polyarteritis nodosa and cutaneous venulitis. Both patients were male, and presented with painful infiltrative plaques, involving the palms, soles, and thighs without extracutaneous involvement except for fever and arthralgia. Histopathological examination revealed vasculitis in the mid-dermis characterized by a predominant infiltration of neutrophils with vessel wall fibrinoid necrosis and leukocytoclasia identical to the features of leukocytoclastic vasculitis, except that the affected vessels were arterioles rather than venules. Serological examinations showed normal levels of serum complements, immune complexes, and antineutrophil cytoplasmic antibodies, and vasculitis disorders associated with systemic diseases were excluded in both patients. The patients showed a good response to short-term treatment with prednisolone up to 30 mg. This novel cutaneous arteriolitis clinicopathologically different from both cutaneous venulitis and cutaneous arteritis appears to be a skin-limited disorder.


Arterioles/pathology , Arteritis/diagnosis , Skin Diseases, Vascular/pathology , Skin/blood supply , Adult , Arteritis/drug therapy , Arteritis/pathology , Arthralgia/diagnosis , Arthralgia/etiology , Diagnosis, Differential , Fever/diagnosis , Fever/etiology , Glucocorticoids/administration & dosage , Glucocorticoids/therapeutic use , Humans , Male , Neutrophils/pathology , Polyarteritis Nodosa/diagnosis , Prednisolone/administration & dosage , Prednisolone/therapeutic use , Skin/pathology , Treatment Outcome , Vasculitis/pathology , Vasculitis, Leukocytoclastic, Cutaneous/diagnosis , Young Adult
20.
Rev. bras. oftalmol ; 79(2): 134-137, Mar.-Apr. 2020. graf
Article Pt | LILACS | ID: biblio-1137940

Resumo Apresentamos um caso de neurosífilis em um homem jovem, com queixa de baixa acuidade visual (BAV) em olho esquerdo. Cursou com lesões eritemato-descamativas nas palmas das mãos, plantas dos pés e úlceras orais, sem lesões genitais. O exame oftalmológico revelou arterite em arcada nasal superior no olho afetado. Apresentou VDRL (1:4096) e FTA-Abs positivos. O exame do líquor cefalorraquidiano foi negativo. O tratamento foi realizado com ceftriaxona 2g/ dia por 14 dias, associado à prednisona 0,5mg/kg oral 48h após início do antibiótico. Após 15 dias de tratamento, houve melhora da AV, regressão da vasculite e redução da titulação do VDRL para 1:128.


Abstract We present a case of neurosyphilis in a young man with a complaint of low visual acuity in the left eye. He had erythematous-scaly lesions on the palms of the hands, soles of the feet and oral ulcers, without genital lesions. The ophthalmic examination revealed arteritis in the upper nasal arcade in the affected eye. He presented VDRL (1: 4096) and FTA-Abs positive. The cerebrospinal fluid cerebrospinal fluid test was negative. The treatment was performed with ceftriaxone 2g / day for 14 days, associated with prednisone 0.5mg / kg oral 48h after antibiotic onset. After 15 days of treatment, there was improvement of AV, regression of vasculitis and reduction of VDRL titration to 1: 128.


Humans , Male , Adult , Arteritis/drug therapy , Treponema pallidum , Ceftriaxone/therapeutic use , Visual Acuity , Anti-Inflammatory Agents/therapeutic use , Anti-Bacterial Agents/therapeutic use , Neurosyphilis/drug therapy
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