EP07 Eosinophilic granulomatosis with polyangiitis: diagnostic and therapeutic challenges during COVID-19 pandemic

Abstract Case report - Introduction COVID-19 pandemic affected medical practise significantly and caused difficulties in accessing necessary investigations at the appropriate time. As of March 2020, NHS England issued measures to redirect staffs and resources in preparation for the rising cases of coronavirus. As a result of this, non-urgent tests/treatments were put on hold. We present a new case of EGPA admitted to our district general hospital during the COVID-19 pandemic to highlight the challenges faced. The diagnosis was reached based on clinical judgment in the absence of some confirmatory tests as well as the decision of starting immunosuppressant treatment during the pandemic. Case report - Case description A 41-years-old lady with a background of well-controlled asthma, presented with five days history of paraesthesia and swelling in both legs. She also reported mild pleuritic chest pain, which radiated to her left arm. Physical examination revealed left foot drop. She had reduced sensation on the L5-S1 dermatomal distribution with absent ankle reflex and reduced knee reflex of her left leg. Her left calf was swollen and tender. The rest of her examination was unremarkable. Baseline blood revealed raised WCC of 19.3 with significant eosinophilia (10). CRP and ESR were 135 mg/L and 48mm/hr, respectively. Electrocardiogram showed new T-wave inversion in the anterolateral leads with significantly raised troponin levels. There was ground glass appearance in both lungs, keeping with suspected COVID-19 and no evidence of pulmonary embolus was found on CTPA. MRI spine confirmed no evidence of cauda equina compression. Deep vein thrombosis was also excluded with US doppler. She was treated as myocarditis and pneumonia secondary to probable COVID-19 infection. Echocardiogram revealed severe LVSD (EF < 35%) with no LV hypertrophy. Three days later, she became acutely breathless and required high flow oxygen. New bilateral basal crackles were found on auscultation. Her antibiotic regimes were escalated to intravenous infusion. A revised CT report suggested the findings may correlate with eosinophilic pneumonia or EGPA. MRI of lower legs proved muscular oedema in bilaterally, which was suggestive of myositis with fasciitis. There was no significant change on the thigh musculature. CK level was slightly elevated (403 IU/L). Urinalysis was positive for blood (3+). Given the strong clinical suspicion of EPGA, a decision to start high dose steroid therapy was made, despite the pending immunology results. After the third dose of the methylprednisolone, pulsed cyclophosphamide was started along with high dose oral prednisolone. The patient was discharged home following significant clinical improvement. Case report - Discussion This patient has fulfilled 4 out of 6 criteria of ACR 1990 classification for EGPA, which are eosinophilia, bronchial asthma, mononeuritis multiplex and pulmonary infiltrates on radiological images. However, in the context of current pandemic, these changes on chest CT findings could also be suggestive of COVID-19 pneumonitis. At present, there is no reliable test for COVID-19. Even though RT-PCR testing has been the gold standard for diagnosing suspected cases, the clinical sensitivity and specificity of these tests are variable. A negative test may not rule out infection. In our case, the patient was tested twice at separate times to rule out the possibility of COVID-19 infection. During the pandemic, there is extremely limited access to some confirmatory tests. We were not able to perform nerve conduction studies on our patient as the service was suspended, instead, we sought neurologist’s review to confirm the mononeuritis multiplex. We also sought advice from haematologist to rule out the possibility of hyper-eosinophilic syndrome as bone marrow biopsy was unavailable. The screen for atypical pneumonia, aspergillosis, viruses, and tuberculosis were negative. By excluding the alternative diagnoses related to eosinophilia, we concluded that this was likely to be a case of first presentation EGPA. Our next obstacle was introducing remission–induction regimens during COVID-19 pandemic. BSR does not recommend starting new treatment due to the increased risk of infection. We had to weigh out the benefits and risks of initiating immunosuppression. Our patient was made aware of the potential risks involved which include severe infection with COVID-19. She was also shifted to a side room with strict infection control precautions and PCP prophylaxis prescribed before starting pulsed methylprednisolone and cyclophosphamide. Fortunately, her neurological symptoms resolved after three days of steroid therapy. Eosinophils count dropped within 1 day to zero, after the first dose of IV methylprednisolone. Case report - Key learning points Despite the rising cases of COVID-19 infection, it is essential to keep an open mind and consider alternative diagnosis if a patient did not respond to conventional treatment. As EGPA and COVID-19 pneumonia share similar clinical and radiological presentation, clinical judgement is essential when making the diagnosis as the treatments for both conditions are vastly different. When EGPA is suspected, a multidisciplinary team should be involved in the evaluation of different organ involvements as well as ruling out other causes of eosinophilia. The role of specialists’ inputs is extremely important in reaching the diagnosis, especially with limited access to the usual confirmatory tests due to reduced services during the pandemic. In addition, when there is an increased risk of infection such as during the COVID-19 pandemic, it is essential to weigh up the benefits and risks of commencing immunosuppressant treatment carefully. Patients need to be involved in the decision-making process as well as take precautions to minimise the risk of infection. The decision to start remission induction regimes should not be delayed if there is a presence of life or organ threatening disease manifestations in EGPA patients. Our patient has had a life-threatening disease because of multi-organ involvements (cardiac, pulmonary, and neurological systems).

COVID-19 is a multi-system illness which can cause significant extrapulmonary as well as pulmonary pathology, with emerging reports that the biliary tract and pancreas are frequently affected. Evidence to inform accurate prediction of which patients with rheumatic diseases are at highest risk of acquiring severe COVID-19 disease remains insufficient, with current shielding guidelines based on expert consensus. This case highlights the importance of widespread testing for COVID-19 in hospital patients, as not all patients carrying the SARS-CoV-2 virus will demonstrate classical respiratory features of the disease at the point of admission.

Alexa José Escudero Siosi, Hudaifa Al Ani and Antoni Chan
Royal Berkshire Hospital, Reading, United Kingdom Case report -Introduction: Coronavirus (SARS-COV-19) typically targets the respiratory tract; however extra-respiratory manifestations such as myositisand myopericarditis may be the only presenting feature. We present a patient with myopericarditis who developed sudden onset muscle weakness. CT thorax showed typical appearance of COVID-19 with anabsence ofrespiratorysymptoms. MRIofboth thighs revealed diffuse symmetrical myositis. Her clinical and paraclinical abnormalities improved with the aid of steroids. We present our approach to the case and highlight that clinicians should consider myositis as another COVID-19 manifestation when reviewing the differentials. Case report -Case description: A 50-year-old female, non-smoker, presented with few days history of central chest pain radiating to her back. This was exacerbated by lying down and inspiration. Associated with mild shortness of breath on exertion. She denied upper respiratory tract symptoms. Her past medical history included hypertension and myopericarditis in 2012 and 2013 requiring pericardiocentesis. In 2017 she presented with post-streptococcal erythemanodosum and reactive arthritisin left ankle. On auscultation her heart sounds were normal, and chest was clear. Initial investigations revealed a mild lymphopenia 0.63, a C-reactive protein of 11mg/L,and a raised troponin 77 and 103 on repeat. D-dimer, Chest x-ray were normal. ECHO showed trivial anterior pericardial effusion, good biventricular function. Treatment included colchicine 500 micrograms four times a dayand Ibuprofen 400 mg three timesaday. On her second day of admission she developed hypotensive episodes BP 75/49 mm/Hg and mild pyrexia of 37.5 degrees. Her chest pain continued. Electrocardiogram was normal, repeat echocardiogram showed stable 1.40 cm pericardial effusion. CT thorax revealed no dissection or features suggesting pulmonary sarcoidosis but ground-glass opacity changes in keeping with COVID-19. Her COVID-19 swab test came back positive.
On the 4th day of admission, she complained of sudden onset of severe pain affecting her thighs, shoulders, and arms, with marked proximal lower limbs and truncal weakness. Because of this, she struggled to mobilise. There was a rapid rise in her creatine kinase from 6.423U/L (day 5) to 32.230 U/L (day 7). ALT increased to 136. MRI showed diffuse myositis with symmetrical appearances involving the anterior, medial, and posterior muscle compartments of both thighs. In view of her previous and current presentation, autoimmune screen and extended myositis immunoblot were sent and were negative. Interestingly, her clinical and paraclinical abnormalities improved dramatically after few dayswith no steroids initially.
Case report -Discussion: The identification of extra-pulmonary manifestations neurological, cardiac, and muscular have recently increased as the number of COVID-19cases grow. This case highlights cardiac and skeletal muscle involvement could perhaps representearly or only manifestation of COVID-19. Cardiac involvement in COVID-19 commonly manifests as acute cardiac injury (8-12%), arrhythmia (8.9-16.7%) and myocarditis. In our case the cardiac MRI demonstrated evidence of myocarditis in the basal inferoseptum and apex. Myalgia and muscle weakness are among the symptoms described by patients affected by COVID-19. Some studies report the prevalence of myalgia to be between 11%-50%. The onset of symptoms and the fact that her symptoms improved rapidly led us to consider a viral myositis as the underlying cause, the viral component being COVID-19. We also considered other potential causes. There are reported cases of colchicine myopathy however this is more common in patients with renal impairment, which was absent inthis case. On further examination she did not have other clinical signs or symptoms of connective tissue disease or extra muscular manifestation of autoimmune myositis. Her abnormal ALT may be derived from damaged muscle, and therefore in this context is not necessarily a specific indicator of liver disease. Interestingly abnormal liver function tests have been attributed in 16 -53% of COVID-19cases.
Little is known about the multiple biologic characteristics of COVID-19 and there are no established clinic serological criteria for COVID-19 related myositis nor useful values/cut offs to exclude cardiac involvement in myositis, further research is therefore warranted.
In conclusion, clinicians should be aware of the rare manifestation of COVID-19 and consider this in the differentials. Of course, it is important in the first instant to rule out any serious underlying disease or overlap disorder before attributing symptoms to COVID-19.

Case report -Key learningpoints
Myositis is a rare manifestation of COVID-19 that clinicians should be aware of. Detailed medical history, examination and investigations identifies the most likely underlying cause. In the right clinical context, COVID-19 -19 testing should be included in baseline tests of patients presenting with myositis.

Furness General Hospital, Barrow, United Kingdom
Case report -Introduction: COVID-19 pandemic affected medical practise significantly and caused difficulties in accessing necessary investigations at the appropriate time. As of March 2020, NHS England issued measuresto redirect staffs and resources inpreparationfor the rising cases of coronavirus. As a result of this, non-urgent tests/treatments were put on hold. We present a new case of EGPA admitted to our district general hospital during the COVID-19 pandemic to highlight the challenges faced. The diagnosis was reached based on clinical judgment in the absence of some confirmatory tests as well as the decision of starting immunosuppressant treatment during the pandemic. Case report -Case description: A 41-years-old lady with a background of well-controlled asthma, presented with five days history of paraesthesia and swelling in both legs. She also reported mild pleuritic chest pain, which radiated to her left arm. Physical examination revealed left foot drop. She had reduced sensation on the L5-S1 dermatomal distribution with absent ankle reflex and reduced knee reflex of her left leg. Her left calf was swollen and tender. The rest of her examination was unremarkable. Baseline blood revealed raised WCC of 19.3 with significant eosinophilia (10). CRPandESRwere135 mg/Land48mm/hr,respectively.Electrocardiogram showed new T-wave inversion in the anterolateral leads with significantly raised troponin levels. There was ground glass appearance in both lungs, keeping with suspected COVID-19 and no evidence of pulmonary embolus was foundonCTPA. MRIspine confirmed noevidence ofcaudaequina compression.DeepveinthrombosiswasalsoexcludedwithUSdoppler. She was treated as myocarditis and pneumonia secondary to probable COVID-19 infection. Echocardiogram revealed severe LVSD (EF < 35%) with no LV hypertrophy. Three days later, she became acutely breathless and required high flow oxygen. New bilateral basal crackles were found on auscultation. Her antibiotic regimes were escalated to intravenous infusion. A revised CT report suggested the findings may correlate with eosinophilic pneumonia or EGPA. MRI of lower legs proved muscular oedema in bilaterally, which was suggestive of myositis with fasciitis. There was no significant change on the thigh musculature. CK level was slightly elevated (403 IU/L). Urinalysis was positive for blood (3þ). Given the strong clinical suspicion of EPGA, a decision to start high dose steroid therapy was made, despite the pending immunology results. After the third dose of the methylprednisolone, pulsed cyclophosphamide was started along with high dose oral prednisolone. The patient was discharged home following significant clinical improvement. Case report -Discussion: This patient has fulfilled 4 out of 6 criteria of ACR 1990 classification for EGPA, which are eosinophilia, bronchial asthma, mononeuritis multiplex and pulmonary infiltrates on radiological images. However, in the context of current pandemic, these changes on chest CT findings couldalso besuggestive of COVID-19 pneumonitis. At present, there is no reliable test for COVID-19. Even though RT-PCR testing has been the gold standard for diagnosing suspected cases, the clinical sensitivity and specificity of these tests are variable. A negative test may not rule out infection. In our case, the patient was tested twice at separatetimesto rule out the possibility of COVID-19infection. During thepandemic,thereis extremely limitedaccess tosome confirmatory tests. We were not able to perform nerve conduction studies on our patient as the service was suspended, instead, we sought neurologist's review to confirm the mononeuritis multiplex. We also sought advice from haematologist to rule out the possibility of hyper-eosinophilic syndrome as bonemarrow biopsy was unavailable.The screen foratypical pneumonia, aspergillosis, viruses, and tuberculosis were negative. By excluding the alternative diagnoses related to eosinophilia, we concluded that this was likely to be acase of first presentationEGPA. Our next obstacle was introducing remission-induction regimens during COVID-19 pandemic. BSR does not recommend starting new treatment due to the increased risk of infection. We had to weigh out the benefits and risks of initiating immunosuppression. Our patient was made aware of the potential risks involved which include severe infection with COVID-19. She was also shifted to a side room with strict infection control precautions and PCP prophylaxis prescribed before starting pulsed methylprednisolone and cyclophosphamide. Fortunately, her neurological symptoms resolved after three days of steroid therapy. Eosinophils count dropped within 1 dayto zero,after the first dose of IV methylprednisolone. Case report -Key learning points: Despite the rising cases of COVID-19 infection, it is essential to keep an open mind and consider alternative diagnosis if a patient did not respond to conventional treatment. As EGPA and COVID-19 pneumonia share similar clinical and radiological presentation, clinical judgement is essential when making the diagnosis as the treatments for both conditions are vastly different. When EGPA is suspected, a multidisciplinary team should be involved in the evaluation of different organ involvements as well as ruling out other causes of eosinophilia. The role of specialists' inputs is extremely important in reaching the diagnosis, especially with limited access to the usual confirmatory tests due to reduced services during the pandemic. In addition, when there is an increased risk of infection such as during the COVID-19 pandemic, it is essential to weigh up the benefits and risks of commencing immunosuppressant treatment carefully. Patients need to be involved in the decision-making process as well as take precautions to minimise the risk of infection. The decision to start remission induction regimes should not be delayed if there is a presence of life or organ threatening disease manifestations in EGPA patients. Our patient has had a lifethreatening disease because of multi-organ involvements (cardiac, pulmonary, and neurological systems).

Hanaa Rajabally, Catherine Morley and Shalabh Srivastava
South Tyneside and Sunderland NHS Foundation Trust, Sunderland, United Kingdom Case report -Introduction: Granulomatosis with Polyangiitis (GPA) is a rare small-to medium-vessel vasculitis associated with anti-neutrophil cytoplasmic autoantibody (ANCA). Its multi-systemic features include pulmonary, ear, nose, and throat (ENT), renal, and neurological manifestations. Its incidence is estimated to be 10.2 cases per million population. It is challenging to diagnose when its symptoms are treated in isolation from one another. This case highlights the difficulty in diagnosing GPA in a patient with respiratory symptoms during the Coronavirus Disease 2019 (COVID-19) pandemic and describes the challenges of managing it in the context of a subsequent COVID-19 infection as the mainstay of treatment remains immunosuppression. Case report -Case description: A 78-year-old female non-smoker with a historyoflegulcersdevelopeda3-monthhistoryofcoughandhaemoptysis and was treated in primary care for suspected sinus and chest infections. She then presented to Accident and Emergency twice for the same symptomsandwasdischargedafterhavingherantibioticschanged. 2 weeks later, she presented for the third time with cough, ongoing haemoptysis, conjunctivitis in the right eye, pain over the right side of her head, and discharge from her right ear. She was admitted as she was pyrexical,tachycardic and her CRP was 60. COVID-19 swabs were negative. ENT team recommended IV ceftriaxone and metronidazole for suspected orbital cellulitis. Blood cultures remained negative. CT sinuses with contrast showed right sided thrombosis of transverse sinus and bilateral mastoid effusion of the middle ear. Following neurology review, she was anticoagulated with dalteparin. A day later, she was transferred to the Respiratory ward and dropped her Haemoglobin level to 70. Her chest radiograph showed diffuse alveolar haemorrhage and CT images showed widespread bilateral peri-hilar consolidation. A rheumatology opinion was sought and vasculitic screen showed ANCA 268, and PR3 >177. Her urinary protein/creatinine ratio was elevated at 90. Rheumatology team confirmed multi-systemic GPA and recommended starting oral Prednisolone 60 mg daily. After the renal team was consulted, she was moved to a side-room and started on IV Methylprednisolone (pulsed with three doses), along with cyclophosphamide and rituximab. Dalteparin was discontinued. 2 days later, she desaturated, and became pyrexical. Repeat COVID-19 swabs were positive. Three Consultants agreed that Plasma Exchange and Non-Invasive Ventilation (NIV) would be inappropriate. A Do Not Attempt Resuscitation form was signed, and prognosis was discussed with the patient and her 78-year-old husband who requested to visit. Patient deteriorated and unfortunately died 6 days later.
Case report -Discussion: This case is interesting because it highlights the diagnostic challenge of GPA. Retrospectively, it may be noted that doctors persisted in treating suspected infection although the patient continued to deteriorate. However, a diagnosis should be re-considered if the patient does not respond to treatment and it is important to consider vasculitis as a cause of haemoptysis. Anticoagulation was started since the benefits were considered to outweigh the risks as her haemoptysis was of small volume. The patient soon developed pulmonary haemorrhage, so the risks of anticoagulation should not be underestimated in vasculitis. The Rheumatology team's cautious approach to immunosuppression was in stark contrast to the renal team's aggressive approach. The Renal team believed that concerns about protecting the patient from COVID-19 when she was negative from this infection should not take precedence over appropriate immunosuppression from a potentially fatal vasculitis. The patient was admitted at the start of the COVID-19 pandemic and was negative for COVID-19 on admission. She was nursed in a bay on the Respiratory ward where she later became COVID-19 positive. This raises questions about whether the earlier test was a false negative result or whether her infection was hospital-acquired. Infection control guidelines were changing rapidly at the start of the COVID-19 pandemic. The decision to avoid plasma exchange was based on the findings of the PEXIVAS trial. NIV was avoided as it required a full-face mask to minimize particle dispersion but would pose an asphyxiation risk as patient was coughing up blood. Finally, the team learntto be flexible in these extraordinary circumstances when dealing with the end-of-life decisions of the COVID-19 positive patient. Although her husband was a vulnerable person because of his age, he was given the opportunity to visit while wearing Personal Protective Equipment and agreed toself-isolate fortwo weeks. Case report -Key learning points: This case helped me appreciate the complexity of deciding to immunosuppress an already severely ill patient in the context of the COVID-19 pandemic. I recognised that the patient had a poor prognosis with or without immunosuppression and our role as healthcare professionals was to give her the best chance of recovery. The conference will allow me to interact with other colleagues and discuss whattheywoulddointhissituation asourRheumatology andRenalteams had different approaches. After further reading on false negative results, we found that Johns Hopkins researchers found that testing people for SARS-CoV2 too early in the course of infection is likely to result in a false negative test even though they may eventually test positivefor the virus. I have also learnt about the PEXIVAS trial which found that the addition of plasma exchange to standard therapy does not reduce the risk for allcause mortality among patients with severe ANCA-associated vasculitis. Moreover, a reduced-dose regimen of glucocorticoids is non-inferior to a standard-dose protocol, while reducing the risk forserious infections.