POS1338 INCIDENCE, PREVALENCE, AND MORTALITY OF CHRONIC PERIAORTITIS: A POPULATION-BASED STUDY

Background:Chronic periaortitis is an inflammatory condition that typically involves the infrarenal portion of the abdominal aorta. Few studies are available to outline the epidemiology of this rare condition. To date, no epidemiologic studies on periaoritis have been performed in North America.Objectives:To evaluate the epidemiology, presentation and outcomes of patients with chronic periaortitis from 1998 through 2018.Methods:An inception cohort of patients with incident chronic periaortitis from January 1, 1998 through December 31, 2018, in Olmsted County, Minnesota, USA, was identified based on comprehensive individual medical record review utilizing the Rochester Epidemiology Project medical record linkage system. Inclusion required radiographic and/or histologic confirmation of periarterial soft tissue thickening around at least part of the infra-renal abdominal aorta or the common iliac arteries. Data were collected on demographic characteristics, clinical presentation, renal and radiographic outcomes, and mortality. Incidence rates were age and sex adjusted to the 2010 United States white population.Results:Eleven incident cases of chronic periaortitis were identified during the study period. Mean±SD age at diagnosis was 61.8±13.4 years. The cohort included 9 men (82%) and 2 women (18%). The most common presenting symptom was pain with 55% (6/11) reporting abdominopelvic-pelvic pain, 36% (4/11) back pain, and 18% (2/11) flank pain. Obstructive uropathy was present in 73% (8/11) subjects: 3 (27%) unilateral left, 1 (9%) unilateral right, and 4 (36%) bilateral. Mean creatinine at presentation was 2.7±3.4 mg/dL. Ureteral stenting was required at diagnosis in seven patients: unilateral left in 2, unilateral right in 1 and bilateral in 4. All 11 patients received glucocorticoids with a median (IQR) dose of 40 (30, 60) mg/day. Additional non-glucocorticoid therapeutics were used in 10 patients.Renal function stage at last follow up declined in 2 patients, remained the same in 3 patients and improved in 6 patients. Mean creatinine at last follow-up was 1.2±0.2 mg/dL. Among the seven patients requiring baseline indwelling ureteral stent placement only two required ongoing ureteral stenting at last follow up. None of the four patients without ureteral stenting at diagnosis progressed to require stenting during the follow-up period. No patient underwent ureterolysis surgery in this cohort. Periarterial soft tissue thickening at last follow up had increased in thickness in 1 (9%), was unchanged in 2 (18%), decreased in size but did not resolve in 6 (55%), and fully resolved in 18%.Age- and sex-adjusted incidence rates per 100,000 population were 0.26 for females, 1.56 for males and 0.87 overall. Overall prevalence on January 1, 2015 was 8.98 per 100,000 population. Median (IQR) length of follow-up was 10.1 (2.5, 13.8) years. Overall mortality was similar to the expected age, sex, and calendar estimates of the Minnesota population with standardized mortality ratio (95% CI) for the entire cohort 2.07 (0.67, 4.84).Conclusion:This study reports the first epidemiologic data on chronic periaortitis in the United States. In this cohort of patients with chronic periaortitis, men were approximately 4 times more commonly affected than women. Mortality was not increased compared to the general population.Disclosure of Interests:None declared

Bile Acids Elevated in Chronic Periaortitis Could Activate Farnesoid-X-Receptor to Suppress IL-6 Production by Macrophages

Chronic periaortitis (CP) is a rare autoimmune disease without effective treatment. By analyzing the serum bile acid spectrum in 28 CP patients with the ultra-performance liquid chromatography-tandem mass spectrometry, we found that the bile acids were significantly altered in CP patients, with significant increases in chenodeoxycholic acid (CDCA) and glycochenodeoxycholic acid (GCDCA) and decrease in deoxycholic acid (DCA). Signaling pathway enrichment analysis from the RNA sequencing results suggested that the altered gene sets in PBMC of CP patients were associated with bile acid metabolism. Furthermore, we found that pathological concentration of CDCA could significantly inhibited IL-6 expression in RAW 264.7 cells after LPS stimulation. Since CDCA is a well-known natural high-affinity ligand for the bile acid receptor farnesoid-x-receptor (FXR) while GW4064 is the synthetic specific agonist of this receptor, we then revealed that GW4064 significantly decreased IL-6 expression in RAW 264.7 cells and bone marrow-derived macrophages but not in FXR-/- macrophages upon LPS stimulation. The western blot results with the anti-FXR antibody showed significantly increased expression in the nuclear proportion, suggesting that FXR agonist promoted the transportation of FXR into the nucleus but did not increase the FXR expression in macrophages. Dual-luciferase report assay and ChIP assay demonstrated that upon activation, FXR could directly bind to the promoter site of IL-6, leading to the decreased expression of IL-6. Thus, bile acids, especially CDCA, may operate to damp inflammation via FXR-mediated downregulation of IL-6 in mononuclear cells and provide a protective mechanism for CP patients.

Chronic Periaortitis – Review and Presentations

Chronic periaortitis is a rare inflammatory condition predominantly affecting the abdominal segment of the aorta. This can present as IgG4 related inflammatory disease, idiopathic retroperitoneal fibrosis, perianeurysmal retroperitoneal fibrosis and inflammatory abdominal aortic aneurysm (IAAA). Aortitis can also be a manifestation of a number of rheumatological large vessel vasculitides such as Takayasu arteritis and giant cell arteritis (GCA). We present three interesting cases of chronic periaortitis and a literature review. The first case shows a classic picture of IgG4 periaortitis. The second case illustrates periaortitis with retroperitoneal fibrosis, ureteric involvement and hydronephrosis, following abdominal aortic aneurysmal stenting. The final case presents as widespread periaortitis due to Takayasu's disease involving the entire aorta including the arch and root of the subclavian artery.