UNASSIGNED: Kawasaki disease (KD), an acute febrile illness and systemic vasculitis, is the leading cause of acquired heart disease in children in industrialized countries. KD leads to the development of coronary artery aneurysms (CAA) in affected children, which may persist for months and even years after the acute phase of the disease. There is an unmet need to characterize the immune and pathological mechanisms of the long-term complications of KD.
UNASSIGNED: We examined cardiovascular complications in the Lactobacillus casei cell wall extract (LCWE) mouse model of KD-like vasculitis over 4 months. The long-term immune, pathological, and functional changes occurring in cardiovascular lesions were characterized by histological examination, flow cytometric analysis, immunofluorescent staining of cardiovascular tissues, and transthoracic echocardiogram.
UNASSIGNED: CAA and abdominal aorta dilations were detected up to 16 weeks following LCWE injection and initiation of acute vasculitis. We observed alterations in the composition of circulating immune cell profiles, such as increased monocyte frequencies in the acute phase of the disease and higher counts of neutrophils. We determined a positive correlation between circulating neutrophil and inflammatory monocyte counts and the severity of cardiovascular lesions early after LCWE injection. LCWE-induced KD-like vasculitis was associated with myocarditis and myocardial dysfunction, characterized by diminished ejection fraction and left ventricular remodeling, which worsened over time. We observed extensive fibrosis within the inflamed cardiac tissue early in the disease and myocardial fibrosis in later stages.
UNASSIGNED: Our findings indicate that increased circulating neutrophil counts in the acute phase are a reliable predictor of cardiovascular inflammation severity in LCWE-injected mice. Furthermore, long-term cardiac complications stemming from inflammatory cell infiltrations in the aortic root and coronary arteries, myocardial dysfunction, and myocardial fibrosis persist over long periods and are still detected up to 16 weeks after LCWE injection.

UNASSIGNED: Chest pain is a frequent reason patients seek medical attention. The broad spectrum of potential etiologies makes determining the underlying cause of chest pain complex. Among cardiovascular etiologies, aortitis is a rare but life-threatening possibility that should be considered in the differential diagnosis.
UNASSIGNED: A 53-year-old female with a history of smoking presented with progressively worsening chest and epigastric pain over several weeks. She had seen multiple physicians previously for the same symptoms with unremarkable work-ups. Physical examination was notable for severe tenderness upon palpation of her lower abdomen. The electrocardiogram and troponins were unremarkable. Computed tomography of the abdomen revealed aneurysmal dilatation of the abdominal aorta, soft tissue thickening, and surrounding inflammatory stranding, consistent with aortitis. Infectious and autoimmune work-ups were unremarkable. Intravenous steroids were initiated, and her symptoms improved significantly. Her aortitis was attributed to inflammation secondary to chronic smoking.
UNASSIGNED: Aortitis is a rare condition with varied clinical presentations. Etiologies of aortitis include infection and non-infectious inflammation. Diagnosis of aortitis requires a thorough clinical assessment and prompt imaging of the aorta, with computed tomography being the preferred imaging modality.
UNASSIGNED: Evaluation for cardiovascular chest pain must extend beyond an electrocardiogram and troponin level. Imaging should be considered in patients with atypical symptoms. Aortitis is a rare but important diagnosis requiring immediate treatment.

UNASSIGNED: The long isoform of the Wnk1 (with-no-lysine [K] kinase 1) is a ubiquitous serine/threonine kinase, but its role in vascular smooth muscle cells (VSMCs) pathophysiology remains unknown.
UNASSIGNED: AngII (angiotensin II) was infused in Apoe-/- to induce experimental aortic aneurysm. Mice carrying an Sm22-Cre allele were cross-bred with mice carrying a floxed Wnk1 allele to specifically investigate the functional role of Wnk1 in VSMCs.
UNASSIGNED: Single-cell RNA-sequencing of the aneurysmal abdominal aorta from AngII-infused Apoe-/- mice revealed that VSMCs that did not express Wnk1 showed lower expression of contractile phenotype markers and increased inflammatory activity. Interestingly, WNK1 gene expression in VSMCs was decreased in human abdominal aortic aneurysm. Wnk1-deficient VSMCs lost their contractile function and exhibited a proinflammatory phenotype, characterized by the production of matrix metalloproteases, as well as cytokines and chemokines, which contributed to local accumulation of inflammatory macrophages, Ly6Chi monocytes, and γδ T cells. Sm22Cre+Wnk1lox/lox mice spontaneously developed aortitis in the infrarenal abdominal aorta, which extended to the thoracic area over time without any negative effect on long-term survival. AngII infusion in Sm22Cre+Wnk1lox/lox mice aggravated the aortic disease, with the formation of lethal abdominal aortic aneurysms. Pharmacological blockade of γδ T-cell recruitment using neutralizing anti-CXCL9 antibody treatment, or of monocyte/macrophage using Ki20227, a selective inhibitor of CSF1 receptor, attenuated aortitis. Wnk1 deletion in VSMCs led to aortic wall remodeling with destruction of elastin layers, increased collagen content, and enhanced local TGF-β (transforming growth factor-beta) 1 expression. Finally, in vivo TGF-β blockade using neutralizing anti-TGF-β antibody promoted saccular aneurysm formation and aorta rupture in Sm22 Cre+ Wnk1lox/lox mice but not in control animals.
UNASSIGNED: Wnk1 is a key regulator of VSMC function. Wnk1 deletion promotes VSMC phenotype switch toward a pathogenic proinflammatory phenotype, orchestrating deleterious vascular remodeling and spontaneous severe aortitis in mice.

An 81-year-old man with prostate cancer (cT3aN0M0), who had been undergoing hormonal therapy for 4 years and had maintained low prostate specific antigen levels, developed metastasized pelvic lymph nodes. A tissue biopsy revealed neuroendocrine differentiation of prostate cancer in the metastatic lymph nodes. Consequently, chemotherapy with carboplatin＋etoposide was initiated. During the first course, filgrastim was administered for 2 days due to a drop in his neutrophil count to 230/μl. During the second course, pegfilgrastim was administered as prophylaxis on day 4. However, on day 10 of the second course, he started to develop a fever and fatigue. Suspecting infection, antibiotics were administered, but failed to ameliorate his symptoms. On day 14, plain computed tomography revealed signs of aortic inflammation. Given the lack of improvement even after one week of antibiotic therapy, steroid treatment was initiated on the suspicion of granulocyte colony-stimulating factor (G-CSF) -induced aortitis, which rapidly improved his symptoms. Therefore, when encountering a case in which a fever remains unresponsive to antibiotics during chemotherapy with G-CSF agents, a differential diagnosis of aortic inflammation caused by G-CSF agents needs to be considered.

Immune-checkpoint inhibitors (ICIs) are considered as the novel treatment modality in certain cancers. They may soon be used widely even as the first-line option for cancer treatment due to their remarkable efficacies and impacts on survival rates, particularly in cases of advanced metastatic cancer. Of note, these agents might unveil new autoimmune diseases as well as causing flare-ups of a pre-existing autoimmune disease. Data in this field have been accumulated during recent years. Early detection and a collaborative approach are, therefore, crucial in the management of a patient who presents with any of these conditions. Herein, we report a patient with a diagnosis of metastatic renal cell cancer presented with vasculitis involvement in the aorta during nivolumab treatment. Our aim with this case is to increase the awareness of ICI-related vasculitis involvement among rheumatologists in the light of literature.

OBJECTIVE: Aortitis in Giant Cell Arteritis (GCA-aortitis) is a frequent complication that may lead to aneurysms. Tocilizumab (TCZ) was approved in GCA, but the efficacy in GCA-aortitis and aneurysms has not been analyzed to date. Our aim was to assess the effectiveness and safety of TCZ in a wide series of GCA-aortitis and aneurysms.
METHODS: Multicentre observational study with GCA-aortitis treated with TCZ. GCA was diagnosed by: a) ACR criteria, b) temporal artery biopsy, and/or c) imaging techniques. Aortitis was diagnosed mainly by PET/CT. Main outcomes were EULAR and imaging remission. Others were clinical remission, analytical normalization, corticosteroid-sparing effect, and the prevention and improvement of aneurysms.
RESULTS: 196 patients with GCA-aortitis treated with TCZ. After 6 months, 72.2% reached EULAR remission but only 12% an imaging remission; increasing up-to 81.4% and 31.8%, respectively, at 24 months. A rapid clinical remission, ESR and CRP normalization was observed in 47.4%, 84.3% and 55.6%, at 1 month, increasing to 89.6%, 85.3% and 80.3% at 24 months, respectively. Aneurysms were present in 10 (5%) patients. Five of them required early surgery, while 3 others enlarged. No patient on TCZ therapy developed aneurysms during follow-up.
CONCLUSIONS: In patients with GCA-aortitis treated with TCZ, a rapid and maintained clinical and analytical improvement was observed. However, there was an uncoupling between clinical and EULAR remission with imaging remission.

OBJECTIVE: Systematic review of current evidence to analyze the prevalence of extracranial large vessel vasculitis (LVV) using 18F-FDG PET/CT in patients with polymyalgia rheumatica (PMR) or giant cell arteritis (GCA).
METHODS: PubMed and EMBASE were searched and the results were screened by two reviewers. Study quality was assessed using a modified version of the Newcastle-Ottawa scale. Heterogeneity between studies was assessed using the I2 statistic and the Q test. Further subgroup analyses were performed by disease type, study quality, and 18F-FDG PET/CT uptake criteria. Publication bias was assessed by funnel plot and Egger\'s test.
RESULTS: 268 publications were identified, of which 17 met the selection criteria and were included in the meta-analysis. The overall pooled prevalence of extracranial LVV by 18F-FDG PET/CT was 54.5% [95% CI: 42.6%-66.1%]. In patients with GCA the prevalence was significantly higher than in patients with PMR (60.1% vs. 41.8%, P = 0.006). Likewise, studies with a lower risk of bias reported a higher prevalence of extracranial LVV (61.1% vs. 46.9%; P = 0.010). No publication bias was observed.
CONCLUSIONS: The 18F-FDG PET/CT test may be useful in the detection of extracranial LVV, both in patients with PMR or GCA. Such involvement is more frequent in patients with GCA, and may vary depending on the quality of the studies.

A 54-year-old woman with a diagnosis of Erdheim-Chester disease under therapy with dabrafenib presents with clinical signs of heart failure. After discontinuing the offending medication and initiating guideline-directed medical therapy for heart failure with reduced ejection fraction, the clinical picture improved.

OBJECTIVE: Giant cell arteritis (GCA) is one of the most common large vessel (LVV) vasculitis and is associated with a high risk of relapse and cardiovascular complications. Improving risk stratification remains a significant issue in this patient population. We aimed to perform a cluster analysis among GCA to identify clusters and evaluate their prognostic value.
METHODS: In a multicenter cohort study, we performed hierarchical cluster analysis on the factor analysis of mixed data coordinates results with 283 GCA patients\' characteristics to generate clusters and assess incidence of relapse, cardiovascular events and death.
RESULTS: Three clusters were identified: \"Vascular relapsing profile\" (23.0%), \"Typical GCA profile\" (47.7%), and \"Ophthalmologic elderly profile\" (29.3%). The \"Vascular relapsing profile\" cluster included younger patients with more frequent relapses and cardiovascular events, particularly thoracic aortic aneurysms. The \"Typical GCA profile\" was the largest, with classic cranial manifestations and frequently associated polymyalgia rheumatica. The \"Ophthalmologic elderly profile\" had the oldest patients with more visual loss and the highest mortality rate.
CONCLUSIONS: Our findings underline the varied prognostic landscape within GCA, emphasizing the poor cardiovascular prognosis of younger patients with LV involvement and the higher mortality among elderly patients. This reinforces the need for further research regarding the screening of aortic abnormalities and whether those patients might benefit from intensive treatment with biotherapy and cardiovascular risk factors management.

Syphilitic aortitis is a rare disease caused by Treponema pallidum affecting the aorta and leading to inflammation. Syphilitic aortitis is one of the causes of aortic aneurysms. This article presents surgical treatment of a patient with syphilitic aortitis and thoracic aortic aneurysm. This clinical case confirms the difficulties of surgical treatment.
Сифилитический аортит является редким заболеванием, вызванным инфекцией Treponema pallidum, которая воздействует на аорту и приводит к ее воспалению и повреждению. Сифилитический аортит является одной из причин формирования аневризмы аорты. В данной статье представлен клинический случай хирургического лечения пациента с сифилитическим аортитом и аневризмой грудной аорты. Клинический случай подтверждает сложности хирургического лечения.