Spontaneous Improvement of Aortitis Associated with Severe COVID-19 Infection-A Case Report.

Aortitis is a rare complication of the coronavirus disease 2019 (COVID-19) and is often treated empirically with steroids. We present a case of spontaneous resolution of aortitis without treatment. A 65-year-old man was admitted to our intensive care unit for severe COVID-19 pneumonia and underwent rehabilitation in the general ward. On day 12, he developed fever, and on day 13, he developed right cervical pain and increased inflammatory markers. On day 16, a cervical echocardiogram showed vasculitis in the right common carotid artery, and on day 17, computed tomography (CT) of the neck showed thickening of the arterial wall of the right common to the internal carotid arteries. A retrospective assessment of the CT scan on day 12 showed wall thickening from the thoracic aorta to the abdominal aorta, and a diagnosis of aortitis was made. Autoantibody analysis, culture, and magnetic resonance imaging (MRI) of the head and neck showed no abnormalities. During the investigation of the cause of aortitis, the fever and inflammatory reaction spontaneously resolved and the right cervical pain gradually improved. Therefore, the patient was diagnosed with transient COVID-19-related aortitis. To our knowledge, this is the first report describing the spontaneous resolution of COVID-19-related aortitis.

Time-related aortic inflammatory response, as assessed with 18F-FDG PET/CT, in patients hospitalized with severely or critical COVID-19

Aim: Arterial involvement has been implicated in the coronavirus disease of 2019 (COVID-19). Fluorine 18-fluorodeoxyglucose positron emission tomography/ computed tomography (18F-FDG PET/CT) imaging is a valuable tool for the assessment of aortic inflammation and is a predictor of outcome. We sought to prospectively assess the presence of aortic inflammation and its time-dependent trend in patients with COVID-19. Method(s): Between November 2020 and May 2021, in this pilot, casecontrol study, we recruited 20 patients with severe or critical COVID-19 (mean age of 59+/-12 years), while 10 age and sex-matched individuals served as the control group. Aortic inflammation was assessed by measuring 18F-FDG uptake in PET/CT performed 20-120 days post-admission. Global aortic target to background ratio (GLA-TBR) was calculated as the sum of TBRs of ascending and descending aorta, aortic arch, and abdominal aorta divided by 4. Index aortic segment TBR (IAS-TBR) was designated as the aortic segment with the highest TBR. Result(s): There was no significant difference in aortic 18F-FDG PET/CT uptake between patients and controls (GLA-TBR: 1.46 [1.40-1.57] vs. 1.43 [1.32-1.70], respectively, p=0.422 and IAS-TBR: 1.60 [1.50-1.67] vs. 1.50 [1.42-1.61], respectively, p=0.155). There was a moderate correlation between aortic TBR values (both GLA and IAS) and time distance from admission to 18F-FDG PET-CT scan (Spearman's rho=-0.528, p=0.017 and Spearman's rho=-0.480, p=0.032, respectively), Figure 1. Patients who were scanned less than or equal to 60 days from admission (n=11) had significantly higher GLA-TBR values compared to patients that were examined more than 60 days post-admission (GLA-TBR: 1.53 [1.42-1.60] vs. 1.40 [1.33-1.45], respectively, p=0.016 and IAS-TBR: 1.64 [1.51-1.74] vs. 1.52 [1.46-1.60], respectively, p=0.038). There was a significant difference in IAS-TBR between patients scanned <=60 days and controls (1.64 [1.51-1.74] vs. 1.50 [1.41-1.61], p=0.036), Figure 2. Conclusion(s): This is the first study suggesting that aortic inflammation, as assessed by 18F-FDG PET/CT imaging, is increased in the early post-COVID phase in patients with severe or critical COVID-19 and largely resolves over time. Our findings may have important implications for the understanding of the course of the disease and for improving our preventive and therapeutic strategies.

Recurring episodes of bundle branch reentry ventricular tachycardia due to aortitis preceded by SARS-CoV-2 infection: a case report.

BACKGROUND: SARS-CoV-2 may trigger both vasculitis and arrhythmias as part of a multisystem inflammatory syndrome described in children as well as in adults following COVID-19 infection with only minor respiratory symptoms. The syndrome denotes a severe dysfunction of one or more extra-pulmonary organ systems, with symptom onset approximately 2-5 weeks after the COVID-19 infection. In the present case, a seemingly intractable ventricular tachycardia preceded by SARS-CoV2 infection was only managed following the diagnosis and management of aortitis. CASE PRESENTATION: A 69-year-old woman was hospitalized due to syncope, following a mild COVID-19 infection. She presented with paroxysmal atrial fibrillation and intermittent ventricular tachycardia interpreted as a septum-triggered bundle branch reentry ventricular tachycardia, unaffected by amiodaron, lidocaine and adenosine. A CT-scan revealed inflammation of the aortic arch, extending into the aortic root. In the following days, the tachycardia progressed to ventricular storm with intermittent third-degree AV block. A temporary pacemaker was implanted, and radiofrequency ablation was performed to both sides of the ventricular septum after which the ventricular tachycardia was non-inducible. Following supplemental prednisolone treatment, cardiac symptoms and arrythmia subsided, but recurred after tapering. Long-term prednisolone treatment was therefore initiated with no relapse in the following 14 months. CONCLUSION: We present a rare case of aortitis complicated with life-threatening ventricular tachycardia presided by Covid-19 infection without major respiratory symptoms. Given a known normal AV conduction prior to the COVID-19 infection, it seems likely that the ensuing aortitis in turn affected the septal myocardium, enabling the reentry tachycardia. Generally, bundle branch reentry tachycardia is best treated with radiofrequency ablation, but if it is due to aortitis with myocardial affection, long-term anti-inflammatory treatment is mandatory to prevent relapse and assure arrhythmia control. Our case highlights importance to recognize the existence of the multisystem inflammatory syndrome in adults (MIS-A) following COVID-19 infection in patients with alarming cardiovascular symptoms. The case shows that the early use of an CT-scan was crucial for both proper diagnosis and treatment option.

A Case of Bilateral Sequential Optic Neuropathies With Pachymeningitis and Aortitis: Difficulty in Differentiating Erdheim-Chester Disease From IgG4-Related Disease

Objective We describe a case of bilateral sequential optic neuropathies with pachymeningitis and aortitis, with findings that raised suspicion of Erdheim-Chester disease versus IgG-4 related disease. Background Erdheim-Chester disease (ECD) is a rare histiocytic neoplasm characterized by tissue infiltration by foamy histiocytes, and chronic, uncontrolled inflammation. IgG4-related disease (IgG4-RD) is an insidiously progressive immune-mediated fibrotic disease typified by tumour-likemass formation in many affected organs. Neurologic manifestations are diverse. Design/Methods A 58-year-old male was transferred to our centre for acute onset sequential optic neuropathies. His visual acuity was light perception for the right eye and 20/50 in the left eye. Results Enhanced MRI of the brain and orbits showed focal pachymeningeal thickening and enhancement in the anterior cranial fossa and over the left frontal lobe with eccentric enhancement of the right optic nerve sheath. CRP was elevated (23 mmol/L to 62 mmol/L);extensive CSF and serum infectious and inflammatory investigations were unrevealing. PET body demonstrated aortitis and CT angiography suggested coronary artery vasculitis. Bone scan showed symmetric involvement of the long bones. Dural biopsy was delayed due to the Covid-19 pandemic and was completed following a protracted steroid course and a 15 mg/kg dose of cyclophosphamide. Pathology showed mixed inflammatory infiltrate and increased expression of IgG4 neutrophils.Clusters ofCD68+,CD1a, and S100-negative macrophages were seen in all layers of dura. No BRAF mutation was identified. Conclusions This case demonstrates classic imaging findings of ECD including pachymeningitis, symmetric long bone involvement and aortitis. Pathology in ECD may show characteristic foamy histiocytes, that were absent in this case. This case demonstrates the challenge of biopsy interpretation following immunosuppressive and cytotoxic therapy and the difficulty of differentiating ECD from IgG4-RD.

A rare case of COVID-19 associated aortitis

Background: There has been a myriad of vascular manifestations associated with the coronavirus disease 2019 (COVID-19) pandemic, including reports of associated small- and medium-vessel vasculitis. However, there are limited reports of large vessel vasculitis, specifically aortitis, related to the COVID-19 infection. Case presentation: A 62-year-old female with history notable for peripheral artery disease, chronic obstructive pulmonary disease, hypertension, and hyperlipidemia presented for evaluation of abdominal pain. She was hospitalized two weeks prior with a COVID-19 infection causing respiratory failure. At presentation, she endorsed one week of progressive lower abdominal pain with anorexia. Vitals were notable for a blood pressure of 185/93 mmHg and heart rate of 94. Labs were notable for white blood cell count 8.1, CRP 85.4, and ESR of 96. A CT abdomen/pelvis with IV contrast demonstrated circumferential wall thickening of the infrarenal aorta with surrounding inflammatory stranding, suggestive of aortitis (Panel A). Additional evaluation included negative blood cultures, non-reactive RPR, normal IgG subclass 4, negative ANA screen, negative myeloperoxidase and proteinase-3 antibodies, and negative cryoglobulin. Given her recent COVID-19 infection, it was felt that her aortitis was COVID-19 related. For this, the patient was initiated on prednisone 60mg daily after her negative infectious work up with subsequent resolution of her abdominal pain. Repeat imaging and labs at 2 weeks demonstrated resolution of aortic findings (Panel B) and normalization of inflammatory markers. Her prednisone was tapered over a 6-week course without recurrence of symptoms. Conclusion(s): Aortitis should be recognized as a potential complication related to COVID-19 infections. While aortitis is associated with significant morbidity and mortality, early initiation of corticosteroids can lead to favorable outcomes.

Society for Vascular Medicine Vascular Scientific Sessions

The proceedings contain 83 papers. The topics discussed include: Aortobronchial fistula in a 75-year-old male presenting with hemoptysis- a case report;a rare case of COVID-19 associated aortitis;complications of vascular Ehlers-Danlos Syndrome;good things don't always come in small packages: Idiopathic small-vessel vasculitis;kissing carotids: A case of incidental found bilateral retropharyngeal carotid arteries;downhill esophageal varices: Rare cause of esophageal varices;acute upper limb ischemia and a large cardioembolic infarct in an elderly female presenting with multiple intracardiac thrombi;acute upper limb ischemia as initial presentation of COVID-19 infection in a 49-year-old male: A case report;a missed ruptured abdominal aortic aneurysm in a paraplegic patient;rare adverse event following cyanoacrylate closure of greater saphenous vein;and vascular Ehlers-Danlos Syndrome: A case of leaking intracranial and intraabdominal aneurysms.

Aortitis as a Sequela from COVID-19 Infection

Case Diagnosis: Aortitis from COVID-19 infection. Case Description or Program Description: 74-yearold male with prior MI s/p 2 vessel CAB, and known COVID-19 infection prior to arrival who presented to the local acute care hospital with complaints of worsening shortness of breath and ataxia. He was medically stabilized but found to have continued deficits in selfcare, mobility, and cognition for which he was transferred to an acute inpatient rehabilitation. On his 3rd rehab day he was found to have ongoing fatigue and sustained tachycardia concerning for pulmonary embolism (PE). CT angiogram of the chest revealed no signs of PE, but found evidence suggesting aortitis. Setting(s): Acute Inpatient Rehab Hospital Assessment/Results: Rheumatology was consulted and confirmed aortitis with elevated inflammatory and immunologic markers. He was started the patient on oral prednisone, and had rapid improvement in symptoms in 6 days. He was discharged home with a long-term course of oral steroids and follow up with Rheumatology. Discussion (relevance): We present a rare complication from COVID-19 infection presenting with sustained tachycardia concerning for pulmonary embolism, but found to have aortitis. At the time of diagnosis this was only the third documented case of COVID-19 induced aortitis in the world. Conclusion(s): This case reports a rare and atypical sequela of COVID-19 infection, as it helps illustrate another unique cell-mediated immune response to COVID-19 infection. It highlights the role of a multidisciplinary approach to COVID patients even after the acute infection has resolved.

Interdisciplinary Approach Is Essential for Sufficient Diagnosis and Therapy in Igg4-Related Disease Involving Multiple Organs

Introduction: IgG4-related disease (IgG4-RD) is a systemic, chronic inflammatory syndrome, with enlargement of involved organs, elevated serum levels of IgG4, dense lymphoplasmocytic infiltrates, rich in IgG4-positive plasma cells, and fibrosis in involved organs. The most frequently involved organs are the pancreato-hepatobiliary tract, salivary and lacrimal glands, the retroperitoneum, kidneys, lungs, and aorta. Often multiple organ systems are involved. As an initial treatment, glucocorticoids are recommended. In patients with relapse along with glucocorticoid dose reduction, various immunosuppressive agents have been reported. Aims & Methods: We reviewed 98 patients (2019-now) who were treated in the special outpatient unit for IgG4-RD at the University Hospital of Essen and identified 10 patients with IgG4-RD involving multiple organ systems. Result(s): The first patient is a 65-year-old male diagnosed with an IgG4- RD involving parotitis, lymphadenitis, sialadenitis with orbitopathy and elevated IgG4 serum level (7400 mg/l). Clinically response to therapy with steroids was documented. The second patient is a 63-year-old man with an IgG4-positive pancreatitis, sialadentis, lymphadenopathy, and elevated IgG4 serum level (3960 mg/l). Immunosuppression with tacrolimus leaded to clinical benefit. As the third patient, we report a 48-year-old man with IgG4-related inflammatory condition in pancreas and kidneys with high IgG4 serum levels. The patient was successfully treated with azathioprine and prednisolone. As the fourth patient, we demonstrate a 34-year-old man with IgG4-related autoimmune hepatitis, lymphadenitis, and pancreatitis. After treatment with tacrolimus in combination with rituximab, a significant decrease of IgG4-level was detected. The fifth patient, a 65-year-old man, was diagnosed with IgG4-related fibro- inflammatory pseudotumors in the liver, esophagitis, and lymphadenopathy combined with high serum levels of IgG4 (12000 mg/l). Clinically response to therapy with steroids and azathioprine was reported. As the sixth patient we demonstrate a 29-year-old male with IgG4-related lymphadenopathy, recurrent myocarditis, and pancreatitis. The patient has symptom-free episodes under low-dose prednisolone. We also found an IgG4-RD with multiple organ involvement in our seventh patient. A 54-year-old man with IgG4-related cholangitis, pancreatitis, prostatitis, and very high serum level of IgG4 (26700 mg/l) were treated with steroids and azathioprine. As our eight case, we present a 23-year-old man with congenital hepatic fibrosis, after living-donor liver transplantation, who developed an IgG4- related disease with high IgG4 serum levels (45300 mg/l) after infection with SARS-CoV-2. Pathologically enlarged lymph nodes were detected. In a biopsy of retroperitoneal lymph nodes, IgG4-positive plasma cells were detectable. Intestinal biopsies have shown numerous positive plasma cells in the IgG4-staining (40 IgG4 positive plasma cells/HPF). Treatment with rituximab is planned. The ninth patient is a 56-year-old woman with lymphadenitis and cholangitis, who clinically responded to a treatment with budesonide. As the last patient we present a 59-year-old man with an IgG4-related aortitis, cardiac fibrosis, cholangitis, hepatitis, exocrine pancreatic insufficiency and Hashimoto's thyroiditis responding very sufficient to rituximab. Conclusion(s): An interdisciplinary approach is essential for a sufficient diagnosis and therapy in IgG4-RD involving multiple organs. This collective is extremely heterogeneous, and treatment is often based on individual concepts.

A RARE CASE OF COVID-19-INDUCED AORTITIS

SESSION TITLE: Post-COVID-19 Infection Complications SESSION TYPE: Case Report Posters PRESENTED ON: 10/17/2022 12:15 pm - 01:15 pm INTRODUCTION: Aortitis is a type of vasculitis that refers to inflammation of the aortic wall. Most common causes are rheumatologic disorders and bacterial infection. Here, we report a viral cause of aortitis induced by COVID-19. CASE PRESENTATION: A 73 year old female with history of coronary artery disease, chronic kidney disease, COPD, hypertension, pulmonary embolism on Eliquis and abdominal aortic aneurysm (AAA) status post repair presented with acute hypoxemia secondary to Covid-19 pneumonia. Of note, patient was vaccinated against COVID-19. CT abdomen at admission demonstrated a known infrarenal AAA with increased degree aortic wall thickening, concerning for aortitis. Aortitis was initially thought to be due to endovascular infection from possible bacteremia rather than surgical site infection as the patient had the AAA repair almost a year prior. Given that bacterial aortitis could result in death, blood cultures were obtained and she was started on Vancomycin and Rocephin. Rapid Plasma Reagin was ordered to rule out syphilis. She had titer of 1-2 which was thought to be false positive as fluorescent treponemal antibody absorption test was negative. After blood cultures and inflammatory markers were negative, antibiotics were discontinued. Aortitis was attributed to COVID. Patient was treated with DEXA-ARDS protocol. Repeat CT abdomen after 8 days no longer showed gross evidence of aortitis. Patient was discharged home with home healthcare. DISCUSSION: Aortitis, a rare complication of COVID-19, has been reported. A proposed mechanism of this pathogenesis involves acute endotheliitis, where endothelial cells infected by virions become infiltrated by neutrophils and mononuclear cells, leading to apoptosis and lymphocytic endotheliitis [1]. Later, these arteries move through the stages of an accelerated karyolysis, accumulation of apoptotic bodies, caspase granules, and fibrinoid substances, leading to leukocytoclastic vasculitis [1]. This inflammatory reaction is followed by deposition of polyclonal antigen-antibody immune complexes, which is a type III hypersensitivity acute vasculitis [2]. Our patient's history of AAA repair predisposed her to increased endothelial dysfunction. After other bacterial infectious causes and post-surgical complications were ruled out, patient was treated with steroids. Most cases of COVID induced aortitis have been treated with prednisone that required treatment for around 1 month [3]. Here, we present a patient treated with DEXA-ARDS with resolution of aortitis. CONCLUSIONS: Due to the novelty, the understanding of exact pathogenesis and long term effects of COVID-19 induced aortitis is limited. However, our case does serve to support prior case reports of COVID-19 aortitis that showed clinical and radiologic response to steroids. Further research is warranted to diagnose and treat aortitis in order to avoid life threating complications. Reference #1: Varga, Zsuzsanna, et al. "Endothelial cell infection and endotheliitis in COVID-19.” The Lancet 395.10234 (2020): 1417-1418. Reference #2: Roncati, Luca, et al. "Type 3 hypersensitivity in COVID-19 vasculitis.” (2020): 108487-108489. Reference #3: Dhakal, Pravash et al. "Aortitis in COVID-19.” IDCases vol. 24 (2021): e01063. doi:10.1016/j.idcr.2021.e01063 DISCLOSURES: No relevant relationships by Jessica Lee No relevant relationships by Thong Ngo No relevant relationships by Marrian Sedrak No relevant relationships by Hena Yagnik

Tuberculosis and Cardiovascular Complications: An Overview.

Tuberculosis (TB) is a dominant cause of mortality from a single infectious disease agent. It is a global health issue that has been tagged as a public health emergency for decades. The disease process, which is caused by Mycobacterium tuberculosis (MTB), affects the respiratory system as well as many other organ systems in the body, such as the lymphatic system, central nervous system (CNS), gastrointestinal system, and cardiovascular system (CVS). Generally, cardiovascular diseases are the leading cause of death worldwide, with most of the mortality in low and middle-income countries. Also, the high mortality rate of TB is skewed to these regions, making the mortality of TB with CVS involvement exceptionally high. The multisystemic involvement of TB impacts the cardiovascular system in various forms. While pericarditis caused by TB is quite common, other complications like myocarditis, coronary artery disease, and aortitis are rarer, necessitating a high index of suspicion and holistic management. This article reviews the pathophysiology of cardiovascular complications in TB, highlighting mechanisms of occurrence, common complications, management protocols, and prognostic factors. Our review highlights some of the gaps in understanding cardiovascular complications in TB, necessitating further research to investigate causal mechanisms and treatment.

THE COURSE of NOVEL CORONAVIRUS DISEASE 2019 (COVID-19) in PATIENTS with IGG4-RELATED DISEASE TREATED with RITUXIMAB

Background: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease 2019 (COVID-19) raised many questions and concerns about the safety of different immunosuppressive agents in patients (pts) with rheumatic diseases during the pandemic. There is some data that anti-B-cell depletion strategies could lead to more severe disease course. Rituximab (RTM) is one of the most effective, safe and well tolerated agents in IgG4-related disease (IgG4-RD) treatment. Information about the course of COVID-19 in pts with IgG4-RD is lacking. Objectives: To examine clinical course of COVID-19 in pts with IgG4-RD treated with anti-CD20 monoclonal antibody (RTM). Methods: Single center observational study. We searched in our clinical base from 2019 to 2021 years for pts with IgG4-RD, treated with RTM within this period. Diagnosis of IgG4-RD was based on comprehensive diagnostic criteria (H. Umehara, 2011). COVID-19 infection was registered when PCR test results were positive. RTM was administered in two 1000 mg infusions 14 days apart for the 1st course, then 500 mg every 6 months. We used mean ± standard deviation and median values with interquartile range of 25-75 percentile to characterize quantitative data. Results: Fifteen pts, 6 women and 9 men, mean age 53.2 ± 12 years, receiving RTM monotherapy were included. The majority of patients (80%) had multiple organ involvement, mean number 2,3 (from 1 to 5): dacryadenitis-11 pts, sialadenitis-10 pts, AIP 1-4 pts, lung disease-3 pts, sclerosing cholangiris-2 pts, kidney disease-2 pts, retroperitoneal fbrosis-1 pt, aortitis-1 pt, prostatitis-1 pt. Median duration of IgG4-RD before COVID-19 onset was 48 [27;72] months, median duration of RTM treatment was 22 [11,5;30,5] months and median time from the last dose of RTM was 2 [1;4,5] months. Three pts had arterial hypertension or coronary heart disease anamnesis, 4 pts had asthma, 2 pts were overweight and 1 had class 3 obesity. No pts were vaccinated against SARS-CoV-2. Six patients (40%) required hospitalization and 4 of them received IL-6 inhibitors, only 1 required mechanical lung ventilation, 6 patients (40%) had only minor symptoms and didn't require any specifc treatment, glucocorticoids were administered to 8 patients. All patients, except one, were older than 50, but they didn't have severe comorbidities. One patient, a 46 year-old man with a long anamnesis of IgG4-related dacryo-and sialad-enitis, bronchial asthma, arterial hypertension class 3 and class 3 obesity, died. Due to small number of studied pts no statistical correlations could be established. Conclusion: The proportion of hospitalized pts with IgG4-RD and RTM treatment was surprisingly high. The worst course was in patient with severe comorbidity. It appears that RTM can have negative impact on susceptibility to COVID-19 and its disease course.

EXCELLENT PROGNOSIS of RHEUMATIC MANIFESTATIONS FOLLOWING COVID-19 VACCINATION: 7 MONTHS FOLLOW-UP DATA

Background: It is well established that severe forms of SARS-CoV2 infection can induce a massive cytokine storm, which may disrupt the immune system stability and conceivably stimulate the development of reactive manifestations through a molecular mimicry process. Likewise, anti-COVID-19 vaccines, which have so far proved an excellent tolerability and safety profile, are able boost the immune response via different biologic technologies and adjuvant combinations possibly facilitating, in predisposed subjects, the onset of infammatory or even autoimmune manifestations. Objectives: We report a case series of suspected rheumatic adverse events following immunization (AEFI) associated with anti-COVID-19 vaccine. We focused our attention on the prognosis of these patients by analysing their available follow-up data. Methods: We included patients evaluated at frst-aid rheumatologic consultancy and at rheumatologic outpatient and inpatient clinic at Padua University Hospital between May and September 2021 presenting with new-onset rheumatic manifestation or a fare of an underlying rheumatic disease within 30 days after receiving an anti-COVID-19 vaccine dose. Inclusion and exclusion criteria were in accordance with the World Health Organization guidelines for AEFI surveillance. All patients were re-evaluated in January 2022: telemedicine or face-to-face visit. Response to therapy was classifed as complete, good or absent according to the clinician's judgment based on clinical examination, patient's reporting and analysis of laboratory data. Results: We identifed 30 cases of suspected rheumatic AEFI reported in Table 1. Comprehensively the most common manifestations were infammatory arthritis (40.0%), rheumatic polymyalgia (26.7%) and adult-onset Still disease (13.3%). Among patients with an underlying rheumatic disease we recorded an AOSD fare, a rheumatoid arthritis fare with involvement of hands proximal inter-phalangeal joints, one case of wrist arthritis in a patient with psoriatic arthritis, one of aortitis in a patient with large vessels vasculitis, one case of polyarthritis in undifferentiated connective tissue disease and a nephritis fare in a patient with systemic lupus erythematosus. Treatment for the suspected AEFI was based on systemic glucocorticoids (GC) alone (63.3%), systemic GC plus IL-1R antagonists (13.3%), non-steroidal autoinfammatory drugs (13.3%), intra-articular GC (6.6%), colchicine (3.3%) and non-steroidal anti-infammatory drugs (13.3%). At last follow-up contact (7.8±1.5 months) 26 patients (89.6%) were classified as complete responders. Eleven of them (42.3%) withdrew therapy without experiencing recurrence of disease manifestation. One patient with lupus nephritis had a proteinuric flare after the first BNT162b dose;he showed an initial good response to increased glucocorticoid therapy but had a new 24h proteinuria increase at second follow-up visit three months later requiring implementation of immunosuppressive therapy. Another patient with AOSD was in remission at last FU visit in December 2021 but required hospitalization in January 2022 for disease relapse due to a suspected gastrointestinal infection. Finally, one patient hospitalized for a seronegative polyarthritis after the first BNT162b dose achieved complete remission at last available contact (one month after hospital discharge) but was then lost in follow-up. Conclusion: After a mean follow-up of 7.8±1.5 months nearly all of patients showed a complete/good response to standard therapy and about half of them withdrew the treatment without losing the remission status.

COVID-19 Aortitis: A Review of Published Cases.

Coronavirus disease 2019 (COVID-19) has a myriad of different presentations and various complications. Aortitis is one of the less explored pathologies associated with COVID-19 infections. In this review, we searched PubMed/Medline, Web of Science, Google Scholar, and Scopus for case series and case reports involving adults patients who presented with aortitis and COVID-19. We found and reviewed four published case reports of aortitis in a setting of COVID-19 infection. The mean age of the four adult patients was 69 ± 1.732 years (range = 63-71 years), and all patients were males. Most of the patients (75%) did not have any preexisting comorbidities. All patients were treated conservatively and recovered with excellent outcomes.

More difficult still: Treating severe rapidly progressive glomerulonephritis in the context of COVID-19 pneumonia.

We present the case of a male patient with severe SARS-CoV-2 pneumonia, with simultaneous onset of p-ANCA positive rapidly progressive glomerulonephritis. We discuss the different therapeutic possibilities, emphasising the appropriateness of their administration according to the time in the course of the infection.

Mimickers of Large Vessel Giant Cell Arteritis.

Giant cell arteritis (GCA) is a large-vessel granulomatous vasculitis occurring in patients over 50-year-old. Diagnosis can be challenging because there is no specific biological test or other diagnoses to consider. Two main phenotypes of GCA are distinguished and can be associated. First, cranial GCA, whose diagnosis is usually confirmed by the evidence of a non-necrotizing granulomatous panarteritis on temporal artery biopsy. Second, large-vessel GCA, whose related symptoms are less specific (fever, asthenia, and weight loss) and for which other diagnoses must be implemented if there is neither cephalic GCA nor associated polymyalgia rheumatica (PMR) features chronic infection (tuberculosis, Coxiella burnetti), IgG4-related disease, Erdheim Chester disease, and other primary vasculitis (Behçet disease, relapsing polychondritis, or VEXAS syndrome). Herein, we propose a review of the main differential diagnoses to be considered regarding large vessel vasculitis.

COVID-19 associated aortitis

Case report-IntroductionSince the emergence of Coronavirus disease 2019 (COVID-19) there has been increasing recognition of the potential associated cardio-vascular manifestations. There have been reports of Kawasaki like disease in children. However, in adults there are very few reports of non-cutaneous vasculitis. Here we report the case of an adult male presenting with an inflammatory aortitis associated with COVID-19 infection.Case report-Case descriptionA 71-year-old Caucasian male with a background of cholecystectomy and rotator cuff repair presented to hospital in May 2020 with a 3-month history of feeling generally unwell, weight loss and worsening thoraco-lumbar back pain. Prior to the onset of these symptoms he had had a 2-week illness in March 2020 clinically consistent with COVID-19 infection comprising fevers, hot sweats, dry cough, and chest tightness for which he had not sought medical attention. He had no recent travel history. Physical examination was unremarkable.On admission, COVID-19 tests revealed evidence of prior infection with negative SARS-CoV-2 polymerase chain reaction test but positive SARS-CoV-2 antibodies. Blood tests revealed a marked inflammatory state with a C-reactive protein of 122mg/L, plasmas viscosity of 2.76, Ferritin 777ug/L, Interleukin-6 of 25 ng/L and normocytic anaemia with a Haemoglobin of 77g/L. Immunology tests were negative for anti-neutrophil cytoplasmic antibody, anti-glomerular basement antibodies, HLA-B27, anti-citrullinated protein antibody, rheumatoid factor, and nuclear antibodies, with normal IgG 4 subclasses. Microbiology workup showed negative blood cultures, syphilis screen and Hepatitis B and C serology. Temporal artery ultrasound was unremarkable. Troponin-T, pro-B-type natriuretic peptide, electrocardiogram and echocardiogram were normal. CT thorax abdomen pelvis revealed inflammatory change surrounding the aortic arch extending all the way down the aorta in keeping with a florid inflammatory aortitis with no aneurysms seen.Rapid resolution of symptoms was seen with commencement of Prednisolone 40mg once daily, with normalisation of CRP one week later and subsequent normalisation of haemoglobin and plasma viscosity. A repeat CT aorta 2 weeks after commencement of prednisolone demonstrated a reduction in the thickness of the inflammatory rind over the aorta from 6mm to 2mm. The patient now continues a reducing regime of prednisolone and remains in clinical remission.Case report-DiscussionIn children, Kawasaki like disease associated with COVID-19 is well described and can result in coronary artery inflammation and aneurysm. In adults, COVID-19 associated cutaneous vasculitis is well recognised however there are only a small number of case reports of organ specific vasculitis including the central nervous system, retina, and small bowel. To our knowledge this is the first reported case of aortitis associated with COVID-19 infection in an adult patient.The mechanisms underlying the development of COVID-19 associated vasculitis are not established but may be secondary to endothelial inflammation. Findings from a histological case series suggest that SARS-CoV-2 can infect endothelial cells directly, possibly via endothelial ACE2 receptors, leading to inflammation in the endothelium. Another postulated mechanism is that endothelial cell dysfunction and inflammation is caused by the cytokine storm that can be seen in some patients with COVID-19 infection.Our patient responded very well to corticosteroid treatment. However, in case of a relapse his cytokine profile could be helpful in directing further therapeutic options. IL-6 levels were elevated in our patient. Studies show that IL-6 appears to play a dominant role in the cytokine storm. In a report of 150 patients IL-6 was found to be significantly higher in the group with severe disease and possibly predictive of mortality. The IL-6 antagonist, Tocilizumab, has also been used with promising results. The first report of its use was in China in 21 critically ill COVID-19 patients with significant improvements Since this first report, further clinical trials are underway investigating the efficacy and tolerability of IL-6 antagonists in patients with COVID-19 disease. Expanding our understanding of the pathogenesis of COVID-19 associated vasculitis is a critical area for future research to identify other immune targets for novel/existing therapeutic agents.Case report-Key learning points Vasculitis including aortitis can be a complication of COVID-19 infection.Endothelial cell inflammation is likely to play key role in the pathogenesis of COVID-19 associated vasculitis.In addition to corticosteroids, other immune-modulating drugs presently used in rheumatology may be effective therapeutic agents.

Large vessel vasculitis related to COVID-19 infection

Case report-IntroductionBy June 2020, 175,000 cases of COVID-19 had been identified in London alone. The most common symptoms include fever, headache, loss of smell, cough, myalgia, and sore throat. The major complication is acute respiratory distress syndrome (ARDS) but systemic complications such as cardiomyopathy, acute kidney injury, encephalopathy and coagulopathy are being identified. A delayed multi-system inflammatory syndrome in children has also been recognised and further complications are likely to be identified as our experience increases. Here, we report the case of a patient with large vessel vasculitis who initially presented with symptoms highly likely to be due to COVID-19 infection.Case report-Case descriptionA 36-year-old black African nurse presented in May 2020, with acute onset 7 days prior of high-grade fevers, rigors, nights sweats, generalised myalgia, sore throat, headache with photophobia, anosmia, dysgeusia and a widespread rash. She was a smoker with no other relevant medical, travel nor sexual history, and no drug use. A COVID-19 swab on day 2 had been negative and she had taken a course of Doxycycline.Examination revealed firm palpable subcutaneous nodules on lower limbs, upper back and forehead and cervical lymphadenopathy. She was photophobic with no meningism. The rest of her physical examination was normal. BP was 116/97 mmHg, heart rate 109 bpm and satO2 100%. Investigations demonstrated C-reactive protein 330mg/L, erythrocyte sedimentation rate 140, Ferritin 479, lymphopaenia 0.7x109, eGFR 54 with no haematoproteinuria, D-dimer 3.05 mg/L with INR 1.1, aPTT 1.3, fibrinogen 8.8 g/L. Hb, WCC, liver function, CK, serum ACE and triglycerides were normal. Infectious screen revealed negative blood cultures, HIV, Hepatitis B and C, EBV, CMV and Treponema pallidum serology. CT brain and CSF analysis were normal including bacterial culture and viral PCR. ANA, ENA, dsDNA, ANCA and aPL antibodies were negative with normal complement levels. Throat swab grew group A streptococcus and she was treated with broad spectrum antibiotics for 7 days maintaining fevers up to 39oC. Skin biopsy was non-specific with negative direct immunofluorescence but showed microvascular thrombi in the papillary dermis. COVID-19 PCR tests (three naso-pharyngeal swabs and one stool PCR) and IgG test (day 38) were negative. CT showed no pneumonitis but non-specific retroperitoneal stranding with medium/large vessel vasculitis involving both proximal renal arteries and a 6 cm segment of mid abdominal aorta on PET-CT. We started oral prednisolone 40mg with immediate resolution of her fevers, myalgia, and inflammatory markers, remaining well a month later.Case report-DiscussionTakayasu's arteritis is the most common autoimmune large vessel vasculitis (LVV) affecting young females and involves inflammation of the arterial wall ultimately resulting in stenosis and obstruction of the vessel. However, it is rare in patients with African heritage and usually presents with a prolonged prodromal phase. Given the atypical presentation and symptoms consistent with COVID-19 infection we feel that this patients' LVV may have been a complication of COVID-19 infection. The relationship between infections and vasculitis is complex. TB and syphilis cause aortitis and a relationship between infection and vasculitis has been proven in HBV associated PAN and HCV associated cryoglobulinemia.Experimental data supports a possible association between CMV and herpes virus and Takayasu arteritis. It could, therefore, be hypothesised that COVID-19 infection can trigger LVV. Our patient had a throat swab positive for Streptococcus pyogenes which is an uncommon cause of infective endocarditis and mycotic aneurism, but this patient had no evidence of either endocarditis or aneurism formation and so it was felt the throat swab finding was incidental. Our patient had repeated negative COVID-19 nasopharyngeal swabs and a negative antibody test at day 38.Although this argues against a diagnosis of COVID-19 related illness, the relative lack of inform tion we currently have regarding sensitivities of the tests, at what point COVID-19 PCR becomes negative in the illness and when/if patients develop antibodies, means these negative tests in the presence of typical symptoms cannot exclude the diagnosis. We believe this case is extremely important to highlight a possible novel inflammatory complication of COVID-19 infection. We decided to treat this patient in line with guidance for the management of LVV, including the introduction of methotrexate, but it will be interesting to observe her long-term outcome.Case report-Key learning points Increasing numbers of COVID-19 related systemic inflammatory conditions are likely to be recognised over the coming months. We present the case of patient with large vessel vasculitis who initially presented atypically with symptoms consistent with COVID-19 infectionTo identify these complications, COVID-19 symptoms questioning should be part of any routine medical historyMore information is required regarding the sensitivity of COVID-19 PCR and antibody tests to aid the diagnosis of these conditionsThe long-term management of inflammatory conditions associated with COVID-19 infection is not clear and a discussion is warranted as to whether DMARDs should be initiated.

Post-COVID myocarditis diagnosed by endomyocardial biopsy and/or magnetic resonance imaging 2-9 months after acute COVID-19

Purpose: To study clinical features of myocarditis and its possible mechanisms (including persistence of SARS-Cov-2 in the myocardium) in the long-term period after acute COVID-19. Methods: Fifteen patients (8 male and 7 female, mean age 47.8±13.4, 24-65 years) diagnosed with postcovid myocarditis were included in the study. The diagnosis of COVID-19 was confirmed by positive PCR results in 40%, and seroconversion in all patients. The average time of admission after COVID-19 was 4 [3;7] months, from 2 to 9 months. The diagnosis of myocarditis was confirmed by cardiac MRI in 10 patients and by right ventricular endomyocardial biopsy (EMB) in 6 patients. The PCR for cardiotropic viruses and PCR with immunohistochemical study for SARSCov2 detection were used. All patients had study for anti-heart antibodies (AHA), EchoCG, and Holter ECG. Coronary atherosclerosis was excluded in all patients over 40 years (7 coronary angiography, 4 cardiac CT). Results: A clear association of the cardiac symptoms with a previous new coronavirus infection was noted in all patients. The symptoms started 1-5 months following COVID-19. MRI showed subepicardial and intramyocardial LGE, signs of hyperemia, increased T1 relaxation time, edema. AHA levels were increased 3-4-fold in 73%. Two variants of postcovid myocarditis were observed. 1. Arrhythmic variant (n=6) - newly developed frequent supraventricular or ventricular extrasystole, recurrent atrial fibrillation in the absence of systolic dysfunction. 2. Decompensated variant with biventricular heart failure (n=9): the mean LV EF was 34.1±7.8% (23 to 46%), LV EDD 5.8±0.7 cm, EDV 153.8±46.1 ml, pulmonary artery systolic pressure 40.7±11.2 mmHg. In one case, myocarditis was accompanied by IgG4- and ANCA-negative aortitis. SARS-Cov-2 RNA was detected in 4 of 5 myocardial biopsies (in one case the material in the study). The longest period of virus persistence after COVID-19 was 9 months. By using spike and nucleocapsid antibodies, coronavirus was detected in cardiomycytes and macrophages. Data of patients with morphologically proved myocarditis are presented in Table 1. Lymphocytic myocarditis was diagnosed and confirmed immunohistochemically (n=5);giant cell myocarditis with atrial standstill was detected in one more case (Fig. 1). Three patients had also signs of endocarditis, in two cases with parietal thrombosis. Conclusions: COVID-19 can lead to the subacute and chronic myocarditis of varying severity. Post-COVID myocarditis manifests itself in two main clinical forms - isolated arrhythmias and systolic dysfunction with heart failure. Post-COVID myocarditis is characterized by prolonged persistence of coronavirus (up to 9 months in this study, in most patients with decompensated variant) in combination with high immune activity (high titers of AHA), which should be considered as the main mechanisms of its longterm course. Treatment approaches for such myocarditis require investigation. (Figure Presented).

Association of Large Vessel Aneurysm/Pseudo-Aneurysm/Aortitis and Deep Vein Thrombosis in Patients with Behçet's Disease: A Case Report.

BACKGROUND: Behçet's disease (BD) is a complex vasculitis with some vascular manifestations including venous thrombosis, arterial thrombosis/aneurysm/pseudoaneurysm, and co-associated venous thrombosis and arterial lesions. We present two patients with Behçet's disease came with progressive both arterial and venous involvement. CASE PRESENTATION: The first patient was a young man with recurrent oral aphthosis and skin folliculitis and referred with complaint of new abdominal pain and 2 months severe headache. He had not referred to a physician due to COVID-19 pandemic until that time. In addition, he gradually developed a lower extremity edema and eventually was diagnosed with BD complicated with brain sagittal sinus vein thrombosis, abdominal aortic aneurysms and aortitis and deep vein thrombosis (DVT) of femoral vein. The second patient was a young woman with previous history of uveitis, DVT and recurrent oral and genital aphthosis presented with a large inguinal mass due to large iliac artery pseudoaneurysm impending to rupture, and after the operation, due to poor follow-up, developed a new femoral DVT. CONCLUSION: It seems the same inflammatory process is responsible for arterial and venous involvement in patients with BD, so it should be considered that involvement in one side (venous/arterial) can be a risk factor for the other side (venous/arterial) and early immunosuppressive treatment should always be considered to improve the prognosis.