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CASE REPORT
Large Vessel Vasculitis After the Administration of Oxford-AstraZeneca COVID-19 Vaccine
Olga K. Katsouli1 , Vasileios G. Lainis1 , Gerasimos G. Kapellos2 , Panayiotis G. Vlachoyiannopoulos1
department of Pathophysiology, School of Medicine, National and Kapodistrian University of Athens, and Institute for Autoimmune Systemic and Neurologic Diseases, Athens, Greece, 2Haematology Department, Athens Medical Center, Athens, Greece
ABSTRACT
We report a case of a 52-year-old female with Large Vessel Vasculitis (LVV) after vaccination with Oxford-AstraZeneca COVID-19 vaccine. She was presented with fever, started two weeks after the second dose of vaccine. Laboratory values, revealed elevated inflammatory markers and chronic disease anaemia. All the infectious causes were excluded, and immunology tests were negative. Computed Tomography (CT) demonstrated concentric wall thickening of ascending and descending aorta. Positron Emission Tomography (PET) scan showed increased vascular fluorodeoxyglucose (FDG), compatible with LVV. Within one month of treatment with high dose glucocorticoids and iv cyclophosphamide, laboratory findings normalised, and fever resolved.
Mediterr J Rheumatol 2023;34(1):97-100 https://doi.org/10.31138/mjr.34.1.97
Article Submitted: 20 Dec 2022; Revised Form: 30 Jan 2023; Article Accepted: 05 Feb 2023; Available Online: 31 Mar 2023
Keywords: vasculitis, COVID-19, vaccination
INTRODUCTION
The high rate of transmission of the Coronavirus Disease 2019 (COVID-19) and the lack of effective treatment led to a rapid development of vaccines. By the end of 2020, several vaccines were available for use in many countries, over 40 candidate vaccines were under assessment in clinical trials and over 150 undergoing preclinical studies. To date, the European Medicines Agency (EMA)
authorized four
COVID-19 vaccines: BNT162 b2 vaccine (Pfizer and BioNTech, Comirnaty®), mRNA-1273 vaccine (Moderna Therapeutics, SpikeVax®), ChAdOx1 nCoV-19 (AstraZeneca and Oxford University, Vaxzevria®) and Ad26. COV2.S (Janssen
COVID19 vaccine, Jcovden®). Although these vaccines are the most powerful weapon against COVID-19 disease and are generally well-tolerated, various adverse events have been observed and reported, including several types of vasculitis.
Herein, we report a case of Large Vessel Vasculitis in a 52-year-old female, 2 weeks after the administration of Oxford-AstraZeneca COVID-19 vaccine (Vaxzevria®).
CASE PRESENTATION
A previously healthy 52-year-old female presented in our Rheumatology Department with evening fever up to 38.2°C, accompanied by fatigue, that started 5 months ago. The symptoms began two weeks, after the administration of the second dose of AstraZeneca vaccine. Previously, the patient had visited several doctors, who after a rapid work-up to rule out common infections, gave unsuccessful treatments with non-steroid anti-inflammatory drugs. On physical examination, she was alert, awake, but she was ill-appearing. Her vital signs were within normal
Corresponding Author:
Panayiotis G. Vlachoyiannopoulos Professor, MD, Department of Pathophysiology, School of Medicine National and Kapodistrian University of Athens
75 Mikras Asias Str., Athens 11527, Greece
Tel.: +30 210 746 2561 E-mail: pvlah@med.uoa.gr
Cite this article as: Katsouli OK, Lainis VG, Kapellos GG, Vlachoyiannopoulos PG. Large Vessel Vasculitis After the Administration of Oxford- 97 AstraZeneca COVID-19 Vaccine. Large Vessel Vasculitis After the Administration of Oxford-AstraZeneca COVID-19 Vaccine. Mediterr J Rheumatol 2023;34(1):97-100.
limits and the rest of examination was unremarkable. In particular, there was no tenderness upon palpation of the temporal region, arteries were evenly palpated on all extremities and the auscultation of the subclavian and axillary regions was normal.
Complete blood count showed mild anaemia (haemoglobin 10.3 g/dL) with normal differential, ESR=111 mm/ hr (ref. range: < 20 mm/hr), C-reactive protein=104 mg/L (ref. range: 0 to 7 mg/L), ferritin levels 560 ng/mL (ref. range: 24 to 307 ng/mL) and plasma fibrinogen levels 773 mg/d (ref. range: 200 to 400 mg/dL). Blood biochemistry was within normal limits. Viral hepatitis panel, blood and urine cultures, ELISA test for HIV, Wright test, VDRL, serology for EBV, CMV, Quantiferon-TB and PCR test for SARS-CoV2 were all negative. Furthermore, immunology tests including antinuclear antibodies (ANA), antibodies to extractable nuclear antigens (ENAs), anti-mitochondrial (AMA), anti-phospholipid (aPL), and anti-neutrophil cytoplasmic antibodies (ANCAs) were negative. IgG4 serum levels were also normal. Heart ultrasound revealed mild pericardial effusion with no evidence of valvular vegetations, intramural thrombi, or solid tumours. Contrast-enhanced Computed Tomography (CT) of thorax/abdomen, demonstrated concentric wall thickening of ascending aorta, aortic arch, and descending aorta. Due to these findings, a Positron Emission Tomography (PET) scan was performed, which
showed increased fluorodeoxyglucose (FDG) uptake throughout aortic arch, thoracic and abdominal aorta, subclavian, carotid, and axillary arteries, compatible with LVV (Figure 1, Figure 2). She was diagnosed as LVV related to vaccination.
According to the 2018 update of the EULAR recommendations for the management of LVV,1 we administered to the patient high doses of glucocorticoids (50 mg/day prednisone-equivalent). Due to the extensive vascular damage and the need for approval of tocilizumab administration for LVV treatment by the Hellenic Food and Drug Organization lasting 4 to 8 weeks, the patient was also placed on induction therapy with 6 monthly intravenous pulses of 1g cyclophosphamide, followed by maintenance treatment with subcutaneous tocilizumab 162 mg weekly. The patient did not present any complication during the induction and maintenance treatment. Within the first month, fever resolved, and the inflammatory markers normalised. Eight months later, the patient remains asymptomatic, receiving treatment with Tocilizumab 162 mg weekly, while the tapering of gluco-corticoids is still ongoing.
DISCUSSION
LVV is defined as the inflammation of the aorta and its major branches. The clinical presentation presents a wide range of symptoms, ranging from general symp-
LARGE VESSEL VASCULITIS AFTER THE ADMINISTRATION OF OXFORD-ASTRAZENECA COVID-19 VACCINE
toms to potentially life-threatening conditions, such as aortic rupture. The symptoms and signs depend on the underlying cause, whereas the non-specific nature of them requires a high index of suspicion by the clinician to make an early diagnosis.2
The aetiological classification of LVV includes various non-infectious and infectious causes. Giant cell arteritis (GCA) and Takayasu's arteritis are the most common representatives of non-infectious causes, although LVV is also associated with other rheumatic diseases.3 As far as the infectious LVV is concerned, the colonisation of damaged endothelium due to haematogenous dissemination of microbes leads to activation of collag-enolytic and elastolytic enzymes, resulting in aneurysm formation within weeks of infection. Among the most prevalent causative pathogens are Streptococcus pyogenes, Streptococcus pneumoniae, Salmonella and Staphylococcus species.3-
Vasculitis can be also triggered by some drugs. Several types of vasculitic disorders have been reported after the administration of various vaccines. The dominant responsible vaccine is the influenza vaccine.4 Nowadays, several cases of vasculitis have been described in the literature,5-8 after both COVID-19 disease or SARS-CoV-2 vaccination (Table 1).
Abdelmaksoud et al. reported 40 cases with vasculitis post SARS-CoV2 vaccination, the most common types of them were IgA and Leukocytoclastic vasculitis, while 3 cases of lymphocytic vasculitis, 2 cases of ANCA-associated vasculitis, 3 cases of urticarial vasculitis and 1 case of immune complex vasculitis were also observed. Most cases occurred about 6.2 days after vaccination with mRNA vaccines, while 12 cases had received the ChAdOxl nCoV-19 AstraZeneca vaccine.9 Gilio et al. reported a case of LVV in a 63-year-old patient after the first dose of BNT162b2—Pfizer-BioNTech vaccine. The PET scan performed, showed increased vascular fluorodeoxyglucose (FDG) uptake compatible with LVV, with a picture similar to our patient.10
In the period from January 6th, 2021, until August 7th, 2021 the Netherlands Pharmacovigilance Centre Lareb received 68 reports of vasculitic events occurred between 0 and 26 days after the administration of COVID-19 vaccines. The vast majority of cases involved vasculitis limited to the skin, but 11 cases of GCA were also reported.11 Furthermore, on October 27th, 2022, an analysis of all yellow cards with adverse events that occurred after vaccination with AstraZeneca vaccine during the period 4/1/21 to 26/10/22 was published in the UK. The author emphasises that the adverse reactions are not necessarily due to the vaccine, but the reporter suspected that there is a possible causal and temporal association. Sixty-nine cases of GCA and three cases of aortitis, the type of which was not specified, reported in this analysis print.12
The pathophysiologic explanation of the association of LVV with the SARS-CoV-2 vaccine has not been fully established, but is based on the following evidence: The vaccine induces Toll Like Receptor (TLR) activation,13 which in turn activates the production of IL-6 linked to disease pathogenesis.14 In addition, vaccination-induced antibodies against the spike protein of SARS-CoV-2 cross-react with many human proteins and form immune complexes that disrupt the endothelium.15 Finally, there is evidence that patients carrying the HLA-DRB1 gene are more prone to develop LVV or polymyalgia rheumatica after influenza vaccination, suggesting a coordination of genetic makeup and environmental factors in the induction of vasculitis.16 LVV is treated by corticosteroids and tocilizumab, as both induction and maintenance therapy.1 Regarding the therapeutic option followed in our case, we have to point out that the administration of tocilizumab for LVV needs approval by the Hellenic Food and Drug Administration which takes one to two months. Therefore, we administered cyclophosphamide based on previous reports.17-19
CONCLUSION
We report a case of development of a large vessel vascu-litis, 2 weeks after the administration of the second dose of ChAdOx1 nCoV-19, Oxford-AstraZeneca vaccine. Interestingly, the patient exhibited an extensive vascular inflammation, involving the aorta and its major branches, without presenting symptoms of vascular damage, but only general symptoms, such as fever. We are convinced that, this case will guide the clinicians to be more aware of this complication, without discouraging the vaccination program, the value of which is indisputable.
CONFLICT OF INTEREST
The authors declare no conflict of interest.
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Table 1. Cases of vasculitis after SARS-CoV-2 vaccination, which have been described in the literature.
Author year Age/Gender Type of vasculitis Time of onset (days) Dose Type of vaccine
Hines et al., 2021 40/F IgA Vasculitis 20 2nd Pfizer-BioNTech BNT16B2b2
Sirufo et al., 2021 76/F IgA Vasculitis 7 1st Oxford-AstraZeneca ChaAdOxl nCoV-19
Naitlho et al., 2021 62/M IgA Vasculitis 8 1st Oxford-AstraZeneca ChaAdOxl nCoV-19
Vassallo et al., 2021 51/F Lymphocytic vasculitis 7 1st Pfizer-BioNTech BNT16B2b2
Kharkar et al., 2021 31/F Lymphocytic vasculitis 1 2nd Inactivated viral vaccine COVAXIN®
Ungari et al., 2021 64/M Lymphocytic vasculitis 1 2nd Oxford-AstraZeneca ChaAdOxl nCoV-19
Badier et al., 2021 72/M IgA Vasculitis 3 1st Oxford-AstraZeneca ChaAdOxl nCoV-19
Bostan et al., 2021 33/M Leukocytoclastic vasculitis 15 1st Inactivated COVID-19 vaccine (CoronaVac)
Maye et al., 2021 23/F IgA Vasculitis 3 2nd Pfizer-BioNTech BNT16B2b2
Obeid et al., 2021 78/F IgA Vasculitis 2 1st Moderna mRNA-1273 vaccine
Grossmanet al., 2021 94/M IgA Vasculitis 7 2nd Moderna mRNA-1273 vaccine
Iwata et al., 2021 70/F IgA Vasculitis 10 2nd Pfizer-BioNTech BNT16B2b2
HakroushandTampe., 2021 79/F ANCA-associated vasculitis 2 2nd Pfizer-BioNTech BNT16B2b2
Okuda et al., 2021 37/F ANCA-associated vasculitis 14 1st Pfizer-BioNTech BNT16B2b2
Fritzen et al., 2021 60/F Leukocytoclastic vasculitis 12 2nd Oxford-AstraZeneca ChaAdOx1 nCoV-19
Cohen et al., 2021 46/F Leukocytoclastic vasculitis 13 2nd Pfizer-BioNTech BNT16B2b2
Ball-Burack et al., 2021 22/M Leukocytoclastic vasculitis 2 1st Johnson & Johnson SARS-CoV-2 vaccine
Nastroet al., 2021 84/M Leukocytoclastic vasculitis 2 1st Pfizer-BioNTech BNT16B2b2
Sandhu et al., 2021 55/F Leukocytoclastic vasculitis 5 1st Oxford-AstraZeneca ChaAdOx1 nCoV-19
Sandhu et al., 2021 48/M Leukocytoclastic vasculitis 5 1st Oxford-AstraZeneca ChaAdOx1 nCoV-19
Bostan et al., 2021 57/F Leukocytoclastic vasculitis 7 1st Pfizer-BioNTech BNT16B2b2
Dickset al., 2021 65/M Leukocytoclastic vasculitis 2 3rd Pfizer-BioNTech BNT16B2b2
Bencharattanaphakhi et al., 2021 23/F Leukocytoclastic vasculitis 2 1st Inactivated COVID-19 vaccine (CoronaVac)
Bencharattanaphakhi et al., 2021 26/F Leukocytoclastic vasculitis 2 1st Inactivated COVID-19 vaccine (CoronaVac)
Kar et al., 2021 46/F Leukocytoclastic vasculitis 5 1st Inactivated viral vaccine COVAXIN®
Jin et al., 2021 68/F Leukocytoclastic vasculitis 2 1st Oxford-AstraZeneca ChaAdOx1 nCoV-19
Cavalliet al., 2021 57/M Leukocytoclastic vasculitis 6 1st Oxford-AstraZeneca ChaAdOx1 nCoV-19
Liang et al., 2021 62/F Leukocytoclastic vasculitis 7 1st Oxford-AstraZeneca ChaAdOx1 nCoV-19
Guzman-Perez et al., 2021 57/F Leukocytoclastic vasculitis 1 1st Oxford-AstraZeneca ChaAdOx1 nCoV-19
Shahrigharahkoshanet al., 2021 77/F Leukocytoclastic vasculitis 10 1st Pfizer-BioNTech BNT16B2b2
Erler et al., 2021 42/F Leukocytoclastic vasculitis 4 1st Pfizer-BioNTech BNT16B2b2
Colia et al., 2021 22/F Leukocytoclastic vasculitis 7 2nd Pfizer-BioNTech BNT16B2b2
Dash et al., 2021 27/M Urticarial vasculitis 7 2nd Inactivated COVID-19 vaccine (CoronaVac)
Muckeet al., 2021 76/M Immune Complex Vasculitis 12 2nd Pfizer-BioNTech BNT16B2b2
Larson et al., 2021 83/F Leukocytoclastic vasculitis 7 2nd Pfizer-BioNTech BNT16B2b2
Larson et al., 2021 35/F Urticarial vasculitis 1 1st Moderna mRNA-1273 vaccine
Altun et al., 2021 38/M Leukocytoclastic vasculitis 4 1st Pfizer-BioNTech BNT16B2b2
Nazzaro et al., 2021 27/F Urticarial vasculitis 10 1st Moderna mRNA-1273 vaccine
Abdelmaksoud et al., 2022 17/F IgA Vasculitis 10 1st Pfizer-BioNTech BNT16B2b2
Abdelmaksoud et al., 2022 48/M Leukocytoclastic vasculitis 4 2nd Pfizer-BioNTech BNT16B2b2
Gilio et al., 2022 63/F Large-vessel vasculitis 1 1st Pfizer-BioNTech BNT16B2b2
Our case 52/F Large-vessel vasculitis 14 2nd Oxford-AstraZeneca ChaAdOx1 nCoV-19
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