O05 Active Bechet's with life threatening arterial disease, complicated by concurrent COVID-19 infection at the peak of the COVID-19 pandemic: did immunosuppression help or hinder?

Abstract Case report - Introduction Behcet’s disease is a rare chronic multi-organ inflammatory disorder characterized by oral aphthous and genital ulceration, often associated with several systemic manifestations. These include skin lesions, arthritis, ocular disease, CNS, GI, and vascular involvement. Arterial disease can affect medium and large sized arteries, leading to aneurysm development with the potential to rupture. We report a case of Behcet’s disease presenting in such a manner, with multiple aneurysms at imminent risk of arterial rupture. The presentation occurred at the peak of the COVID-19 pandemic, in April 2020 with the patient contracting the virus complicating cyclophosphamide immunosuppression therapy post operatively. Case report - Case description A 54-year-old man had been under rheumatology follow up for numerous years. He reported recurrent oral ulcers, and episodic fevers. He previously had confirmed cerebral sinus thrombosis, aseptic endocarditis, multiple pulmonary emboli and was investigated for inflammatory bowel disease. He presented acutely to AE with a painful, tender left calf and a large pulsatile mass in the calf. He reported paraesthesia in his left leg/foot suggestive of nerve compression. CT angiogram performed, revealed a large 6.5cm x 4cm left tibioperoneal trunk (TPT) pseudoaneurysm (Fig.1), and 1.2cm right anterior tibial (ATA) pseudoaneurysm (Fig 2). There was also a 3.8cm infrarenal inflammatory abdominal aortic pseudoaneurysm (Fig 3), and finally a 2.3cm right lower lobe pulmonary artery aneurysm. Laboratory investigations revealed raised inflammatory markers, with ESR of 120 and CRP 73. A diagnosis of vascular Behcet’s was suspected. Urgent surgical intervention was deemed necessary to prevent limb and life-threatening complications of arterial rupture. He underwent open surgical decompression and graft repair of the left TPT aneurysm. Endovascular stenting of infrarenal AAA was performed and the right ATA aneurysm was ligated and excised. The pulmonary artery aneurysm was managed conservatively, but interval CT Imaging post immunosuppression treatment showed complete resolution. This undoubtedly was due to immunosuppression therapy. The first cyclophosphamide and methylprednisolone infusion were given day 1 post-op. The following day he developed a fever and a dry cough. He subsequently tested positive for SARS-COV-2. This was at the height of the COVID-19 pandemic. He required supplementary oxygen, but his condition did not deteriorate further, and he made a complete recovery. A difficult dilemma was posed between immunosuppression and the risk of infection having been diagnosed with COVID-19. An MDT approach was adopted, and input was sought from the Birmingham Bechet’s centre of excellence. He continued immunosuppressive treatment once recovered from the virus. Case report - Discussion Bechet’s disease is considered a form of systemic vasculitis and is unique in its ability to involve blood vessels of all sizes from the arterial and venous systems. Vascular manifestations in Bechet’s disease are associated with increased mortality and morbidity with manifestations more common in men. Arterial rupture is the leading cause of sudden death in patients with Bechet’s disease. Endovascular and perivascular inflammation of large vessels can lead to haemorrhage, aneurysm formation with risk of rupture, stenosis, and thrombus development. To prevent potential life-threatening complications of vascular Bechet’s, a combination of surgical/radiological and medical management is often required. High dose corticosteroids and cyclophosphamide infusions are typically used, with aim to achieve disease remission. It is recommended that if surgical/radiological interventions are indicated, it should ideally be performed when the disease is quiescent. However, urgent intervention is required if the aneurysm is at high risk of rupture, rapidly enlarging or if there is organ threatening ischemia. This was the approach used in this patient. Potent immunosuppression with cyclophosphamide and high dose corticosteroids is indicated in arterial disease of Bechet’s. The inherent risk of infection with these agents, being used at the peak of a global pandemic created a challenging clinical dilemma. To complicate matters further, the patient developed fever and cough following the 1st cyclophosphamide/steroid treatment and tested positive for COVID-19. His condition was relatively mild however and made a full recovery from the virus. Behcet’s disease can be a difficult and challenging condition to diagnose. There is often a delay in diagnosis. Our patient was previously referred to a tertiary Bechet’s centre but felt there was insufficient clinical grounds to make the diagnosis at that stage. Case report - Key learning points This case provides a rare example of an immunosuppressed patient with rheumatic disease contracting COVID-19 after extensive vascular intervention. A poor outcome may have been expected but in contrary the patient’s disease course was mild. This perhaps supports the theory that immunosuppression may play a protective role during COVID-19. The role of immunosuppression in a hyperinflammatory COVID-19 state is an area of much research interest. Suppression of the cytokine storm with immune therapy has been hypothesised as a potential therapy target for some COVID-19 patients. However, this is still unproven. Corticosteroid treatment with dexamethasone has been shown to reduce mortality in COVID-19 patients in hospital, through the Recovery Trial. In addition, encouraging evidence continues to emerge for the role of IL1 and IL6 inhibitors in the cytokine storm. It is rare for a patient to present with such extensive aneurysmal disease. Vascular complications of Bechet’s although rare need to be considered. The management for vascular manifestations of Bechet’s disease requires co-ordination and collaborative work between Rheumatologists, Vascular surgery, and Radiologists. Guidance from expert centres is highly recommended. Prompt medical and surgical intervention is needed to prevent serious limb and life-threatening complications of arterial Bechet’s disease. Our case raises the clinical conundrum of immunosuppression therapy in serious organ threatening rheumatic disease with concomitant COVID-19 infection. A patient-centred approach with patient involvement in clinical decisions is required. Patients and clinicians alike should balance the risks associated with organ threatening rheumatic disease and infection risks. The current global coronavirus pandemic makes such decisions more difficult with an additional communicable disease prevalent in the community. With few clinically proven therapies and no vaccine available for COVID-19, Rheumatologists will have to grapple with this dilemma for the foreseeable future.

and she was treated with broad spectrum antibiotics for 7 days maintaining fevers up to 39 o C. 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 -Discussion: Takayasu'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 presentationand symptoms consistent with COVID-19infection 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-19nasopharyngeal swabs and a negative antibody test at day 38. Although this argues against a diagnosis of COVID-19 related illness, the relative lack of information 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 thiscase isextremely important tohighlight apossiblenovelinflammatory 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 learningpoints . 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 infection . To identify these complications, COVID-19 symptoms questioning should be part of any routine medical history . More information is required regarding the sensitivity of  PCR and antibody tests to aid the diagnosis of these conditions . The 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 Case report -Introduction: Behcet's disease is a rare chronic multiorgan inflammatory disorder characterized by oral aphthous and genital ulceration, often associated with several systemic manifestations. These include skin lesions, arthritis, ocular disease, CNS, GI, and vascular involvement. Arterial disease can affect medium and large sized arteries, leading to aneurysm development with the potential to rupture. We report a case of Behcet's disease presenting in such a manner, with multiple aneurysms at imminent risk of arterial rupture. The presentation occurred at the peak of the COVID-19 pandemic, in April 2020 with the patient contracting the virus complicating cyclophosphamide immunosuppression therapypost operatively.
Case report -Case description: A 54-year-old man had been under rheumatology follow up for numerous years. He reported recurrent oral ulcers, and episodic fevers. He previously had confirmed cerebral sinus thrombosis, aseptic endocarditis, multiple pulmonary emboli and was investigated for inflammatory boweldisease. HepresentedacutelytoAE withapainful,tenderleftcalf andalargepulsatile mass in the calf. He reported paraesthesia in his left leg/foot suggestive of nerve compression. CT angiogram performed, revealed a large 6.5cm x 4cm left tibioperoneal trunk (TPT) pseudoaneurysm ( Fig.1), and 1.2cm right anterior tibial (ATA) pseudoaneurysm (Fig 2). There was also a 3.8cm infrarenal inflammatory abdominal aortic pseudoaneurysm (Fig 3), and finally a 2.3cm right lower lobe pulmonary artery aneurysm. Laboratory investigations revealed raised inflammatory markers, with ESR of 120 and CRP 73. A diagnosis of vascular Behcet's was suspected. Urgent surgical intervention was deemed necessary to prevent limb and life-threatening complicationsof arterial rupture. He underwent opensurgical decompression and graft repair of the left TPT aneurysm. Endovascular stenting of infrarenal AAA was performed and the right ATA aneurysm was ligated and excised. The pulmonary artery aneurysm was managed conservatively, but interval CT Imaging post immunosuppression treatment showed complete resolution. This undoubtedly was due to immunosuppression therapy. The first cyclophosphamide and methylprednisolone infusion were given day 1 post-op. The following day he developed a fever and a dry cough. He subsequently tested positive for SARS-COV-2. This was at the height of the COVID-19 pandemic. He required supplementary oxygen, but his condition did not deteriorate further, and he made a complete recovery. A difficult dilemma was posed between immunosuppression and the risk of infection having been diagnosed with COVID-19. An MDT approach was adopted, and input was sought from the Birmingham Bechet's centre of excellence. He continued immunosuppressive treatment once recovered from the virus. Case report -Discussion: Bechet's disease is considered a form of systemic vasculitis and is unique in its ability to involve blood vessels of all sizes from the arterial and venous systems. Vascular manifestations in Bechet's disease are associated with increased mortality and morbidity with manifestations more common in men. Arterial rupture is the leading cause of sudden death in patients with Bechet's disease. Endovascular and perivascular inflammation of large vessels can lead to haemorrhage, aneurysm formation with risk of rupture, stenosis, and thrombus development.
To prevent potential life-threatening complications of vascular Bechet's, a combination of surgical/radiological and medical management is often required. High dose corticosteroids and cyclophosphamide infusions are typically used, with aim to achieve disease remission. It is recommended that if surgical/radiological interventions are indicated, it should ideally be performed when the disease is quiescent. However, urgent intervention is required if the aneurysm is at high risk of rupture, rapidly enlarging or if there is organ threatening ischemia. This was the approach used in this patient. Potent immunosuppression withcyclophosphamide andhighdosecorticosteroids is indicated in arterial disease of Bechet's. The inherent risk of infection with these agents, being used at the peak of a global pandemic created a challenging clinical dilemma. To complicate matters further, the patient developed fever and cough following the 1st cyclophosphamide/steroid treatment and tested positive for COVID-19. His condition was relatively mild however and made afull recovery from the virus. Behcet's disease can be adifficult and challenging condition to diagnose. There is often a delay in diagnosis. Our patient was previously referred to a tertiary Bechet's centre but felt there was insufficient clinical grounds to make the diagnosis at that stage. Case report -Key learning points: This case provides a rare example of an immunosuppressed patient with rheumatic disease contracting COVID-19 after extensive vascular intervention. A poor outcome may have been expected but in contrary the patient's disease course was mild. This perhaps supports the theory that immunosuppression may play aprotectiverole during COVID-19. The role of immunosuppression in a hyperinflammatory COVID-19 state is an area of much research interest. Suppression of the cytokine storm with immune therapy has been hypothesised as a potential therapy target for some COVID-19 patients. However, this is still unproven. Corticosteroidtreatmentwithdexamethasone hasbeenshown toreduce mortality in COVID-19 patients in hospital, through the Recovery Trial. In addition, encouraging evidence continues to emerge for the role of IL1 and IL6 inhibitorsin the cytokine storm. It is rare for a patient to present with such extensive aneurysmal disease. Vascular complications of Bechet's although rareneed tobe considered. The management for vascular manifestations of Bechet's disease requires co-ordination and collaborative work between Rheumatologists, Vascular surgery, and Radiologists. Guidance from expert centres is highly recommended. Prompt medical and surgical intervention is needed to prevent serious limb and life-threatening complications of arterial Bechet'sdisease. Our case raises the clinical conundrum of immunosuppression therapy in serious organ threatening rheumatic disease with concomitant COVID-19 infection. A patient-centred approach with patient involvement in clinical decisions is required. Patients and clinicians alike should balance the risks associated with organ threatening rheumatic disease and infection risks. The current global coronavirus pandemic makes such decisions more difficult with an additional communicable disease prevalent in the community. With few clinically proven therapies and no vaccine available for COVID-19, Rheumatologists will have to grapple with this dilemma for the foreseeablefuture.

Southend University Hospital NHS Foundation Trust, Southend, United Kingdom
Case report -Introduction: COVID-19 is an infectious disease caused by a newly discovered b-coronavirus, named Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2), resulted in a recent pandemic of COVID-19. As a novel pathogen, the nature and degree of risk of COVID-19 to individuals with rheumatic diseases were unknown, as was its ability to induce musculoskeletal and autoimmune disease. Concerns were related to the chronic autoimmune or inflammatory disease and immune suppressive medications to treat it. The consequences of this infection are currently not fully understood, including the autoimmune sequelae. Here we present two cases of inflammatory arthritis with a temporal link to COVID-19. Case report -Case description: Case 1: A 37-year-old Caucasian male was referred to Rheumatology with severe joint pains. He developed flulike symptoms in early April 2020, with myalgia, fever, sore throat, anosmia, and fatigue. SARS-CoV-2 PCR swab was positive. He recovered from these initial symptoms, however 4 weeks later, he developed pain and swelling in his hands, feet, ankles, and knee joints with early morning stiffness. On examination, there was marked synovitis of hands, wrists, knees, and ankle joints. Systemic examination was otherwise normal. Case 2: A 70-year-old lady developed sore throat and cough started in lateMarch2020. 3weeks later,shebecamegenerally unwell withlethargy and fatigue. Her cough gradually improved, but she continued to experience breathlessness on minimal exertion. In early May 2020, she developed excruciating pain in her hands, wrists, and right knee joints with morning stiffness. On examination she had synovitis in the wrists, small joints of the hands and right knee. Systemic examinationotherwise was unremarkable. Given the severe inflammatory arthritis, both patients were commenced on oral prednisolone with remarkableimprovement 4 weekslater. Case report -Discussion: We present 2 cases of acute inflammatory arthritis, which were suspected to have been triggered by COVID-19 viral infection without any musculoskeletal complications with good prognosis. COVID-19 is anew disease and our understanding of it is continuingto grow. The initial concern was that COVID-19 -19 infection may lead to severe illness in immunocompromised patients, including those and with rheumatic conditions. However, this was not seen in large numbers. To our knowledge, COVID-19-related inflammatory arthritis has not previously been reported in the literature. Our current understanding of the COVID-19 pathogenic mechanisms is limited. However, it is likely that the disease may evolve in overlapping phases. Case report -Key learning points: In both cases, it was suggested that COVID-19 19 may be a triggering factor for inflammatory arthritis with good prognosis and settled with steroid therapy. It was suggested that arthritis may occur in patients with COVID-19, in previously fit and well patients without any underlying co-morbidities and autoimmune rheumatic disease and warrants urgent Rheumatology review. However, all COVID-19 suspected cases should be investigated on an individual basis to exclude other diagnosis to avoid missing other common reversible illnesses.