SARS-CoV- 2 vaccine-induced Eosinophilic Granulomatosis with PolyAngiitis (EGPA)

Case report: A 63 y.o. man with known allergic rhinoconjunctivitis and mild asthma, sensitized to house dust mites, cat dander and grass and pellitory pollens, presented at the Emergency Department (ED) of our Hospital for diplopia, left temporo-parietal headache, fleeting knurled scotoma, and impaired color vision, associated with dry cough, occurring the day after the booster dose of the anti-SARS- CoV- 2 vaccine (mRNA-1273). Collecting clinical history, it emerged that 6 months before, just after the first vaccine dose (BNT162b2), he developed a progressive worsening of asthma, becoming severe and uncontrolled despite high dose inhaled corticosteroids plus long-acting beta2-agonists, montelukast and tiotropium bromide, and requiring maintenance oral corticosteroid treatment: any attempt to withdraw systemic corticosteroid was associated with exacerbations of asthma. During the access to the emergency room and the subsequent hospitalization, the following emerged: severe hypereosinophilia (12400 cells/mcl), left third cranial nerve palsy, elevated serum troponin, echocardiographic signs of acute myopericarditis with interventricular septal thickening, MRI signs of cardiac interventricular septal hypokinesia, and multiple pulmonary consolidations on CT scan. Serum ANCA was negative. The clinical presentation (asthma, third cranial nerve mononeuropathy, myopericarditis with signs of interventricular septal distress, typical lung involvement) associated with the finding of severe hypereosinophilia was suggestive of eosinophilic granulomatosis with polyagioitis (EGPA). Already in the emergency room, the patient was promptly treated with 3 boluses of methylprednisolone 1 g i.v. (1 bolus per dey). During the hospitalization he underwent the first cycle (out of 6 planned) of i.v. cyclophosphamide 1000 mg and initiated therapy with oral prednisone 75 mg/day (1 mg/kg/day). After the initiation of systemic corticosteroid therapy there was depletion of blood eosinophils, progressive reduction of serum troponin, resolution of cough and almost complete regression of 3rd cranial nerve palsy. At the time of submission, the patient was discharged and taken on an outpatient basis to continue therapy with cyclophosphamide and possibly associate mepolizumab as a steroid-sparing strategy. In conclusion, this is a case of EGPA arising after SARS-CoV- 2 vaccination. It has been described that vasculitis can be triggered by infectious episodes or vaccinations: to date only two other EGPA cases likely induced by anti-SARS- CoV- 2 mRNA vaccines have been described in the literature.

A flare of EGPA after vaccination for COVID-19, description and follow-up of a clinical case

Background: Although rarely, vaccines can stimulate the immunological mechanisms underlying immune-mediated inflammatory diseases. in patients with COVID-19 there is also evidence that high titers of autoantibodies, with variable clinical relevance, can be detected. Method(s): We describe the case of a 71-year- old lady diagnosed with eosinophilic granulomatosis with polyangiitis (EGPA) in 2010 with paraesthesia, myalgia, eosinophilia and severe asthma. After induction of remission, the patient has shown regression of the vasculitis but persistence of the uncontrolled asthma. For this reason, since February 2019 she started Mepolizumab 100 mg/month. In December 2020 she tested positive for the SARS-CoV- 2 virus, manifesting a mild form then she tested negative in January 2021. In April 2021 she was vaccinated with a single dose of BNT162b2 mRNA vaccine. After about 10 days, she started to complain arthromyalgia and after a week of gait alteration, paraesthesia, dyspnoea and worsening cough associated with chest pain. Blood tests showed an increase in creatinephosphokinase (CPK 955 U/L) and hypereosinophilia (4.3x10

Spotting the Needle Amongst the Haystack - When Asthma Isn't Asthma

Introduction/Background: Eosinophilic granulomatosis with polyangiitis (EGPA), previously known as Churg-Strauss Syndrome, is a rare, small to medium vessel ANCA associated vasculitis. Hallmarks of EGPA include asthma, chronic rhinosinusitis, and peripheral neuropathy. EGPA is characterized by a prodrome of asthma and allergic rhinitis, followed by peripheral blood hyper-eosinophilia and accumulation of extravascular eosinophils, and finally systemic vasculitis. Extrapulmonary involvement is common, sometimes with fatal outcomes. The onset of EPGA is typically between 25-50 years;however, EGPA also occurs during childhood and has a significant morbidity and mortality. Description/Method: Our patient presented to the emergency department with a 2-week history of lethargy, wheeze and left sided neck swelling. After testing COVID-19 positive eight months prior to this, she developed wheezy episodes and was subsequently diagnosed with asthma which was managed with bronchodilators as required. She was reviewed by an allergist who confirmed a dust mite allergy and prescribed Montelukast. She remained well during the summer months however during winter she had 3 distinctive episodes of wheeze and cough which were managed by antibiotics and prednisolone. In the emergency department, an echocardiogram was performed which showed a cardiac tamponade. She was transferred to CICU where she had a pericardial drain inserted. The fluid was abundant with inflammatory cells. Multiple investigations were performed as follows: Hb: 135g/L, wbc: 20.30 x 10 9/L, Eosinophils: 12.77 x 10 9/L, CRP: 51 mg/L, ESR: 75 mm/hr, LDH: 1188 IU/L, IgE: 8000 UI/ml, ANA, ANCA: negative. CT chest showed mediastinal lymphadenopathy and patchy bilateral infiltrate and cardiac MRI showed myopericarditis and LV fibrosis. BMA showed no malignant cells and sinusitis was confirmed by CT. On examination, she was underweight. Her nasal mucosa looked inflamed. Otherwise systemic examination was unremarkable. In the context of poor ejection fraction (20%) with LV fibrosis, urgent MDT was arranged and concluded that our working diagnosis was EGPA. The decision was made to start IV methylprednisolone 10mg/kg/day for 3 days and Ivermectin. That night our patient had a VF arrest which required a single shock conversion 4J/kg. There was 7-minute downtime. Treatment was escalated to include cyclophosphamide, rituximab and plasmapheresis. The patient made a remarkable recovery, extubated and transferred to a normal ward. Her eosinophils count and inflammatory markers improved dramatically following treatment. However, she developed severe neuropathic left leg pain and NCS confirmed peripheral neuropathy Discussion/Results: EGPA is a very rare disease and diagnosis can be challenging especially with the absence of histopathology diagnosis. Early empirical treatment especially in a very ill child in intensive care unit can save lives and divert the progress of the disease. This patient has fulfilled the American College of Rheumatology criteria to diagnose EGPA including asthma, eosinophil count > 10% of upper normal, peripheral neuropathy, pulmonary infiltrates on CT thorax and paranasal sinuses abnormalities. Cardiac biopsy of the fibrotic mass may be a useful tool for diagnosis;however, this invasive procedure may expose this patient with high risk of fatal arrhythmias. Since other causes of eosinophilia were ruled out including parasitic infections, lymphoproliferative disorders, and rare primary immunodeficiency syndromes (hyper-IgE syndrome due to STAT3 or DOCK8 deficiency and Omenn syndrome) and the patient responded well to treatment, the diagnosis of EGPA was supported. Key learning points/Conclusion: Asthma not responding to bronchodilator could be another diagnosis Eosinophilia should be interpreted with caution. Defer the need for histopathology diagnosis in critically ill children Cardiac involvement is a life-threatening marker Early diagnosis prevents life threatening complications.

Safety of ANCA-associated vasculitis patients receiving covid-19 vaccination

Background: The Covid-19 vaccines administration programs implemented in most countries, WHO showed 5.22 billion persons vaccinated at least one dose up to June 29th 2022. EULAR and ACR guidelines suggested autoimmune and inflammatory rheumatic diseases (AIIRDs) patients with stable or low disease activity should receive Covid-19 vaccination. ANCA-associated vasculitis (AAV) patients are AIIRDs subgroup during pandemic, the safety of Covid-19 vaccination has not been reported in large scale study. We analyzed publications of patients with AAV who had relapse post-vaccination and further discussed the challenges for AAV patients under B-depleting therapy with appropriate vaccination recommendations. Method(s): We used descriptive thematic analysis to find out the flare features including severity, organ involvement, therapy strategy in AAV patients after Covid-19 vaccination. This article conforms with the Scale for Assessment of Narrative Review Articles (SANRA) guidelines. After eligibility criteria and selection process, there were 6 matched articles which had 10 individual cases. Result(s): AAV could involve several organs throughout the body, most cases involved kidney and lung injury. Among the 10 cases, there were 2 cases of EGPA, 3 of MPA and 1 RLV patient with clearly written diagnosis and all patients were assessed as being in disease remission prior to vaccination. The cases were special in age characteristic with 71-85 years old. Seven patients had anti-ANCA type test in 3 cases were anti-PR3 type and another 4 cases were anti-MPO type both with higher titers than during remission. Four had new onset organ involvements rather than the recurrence of the original organ relapse after vaccination. Among them, the 74-year- old male suspended rituximab for 6 months interval before vaccination, he developed diffuse alveolar hemorrhage and infection followed under restart rituximab treatment and eventually died of respiratory failure. Another same age male was diagnosed with new crescentic pauci-immune glomerulonephritis and discharged with creatine level as 307umol/L. Conclusion(s): Patients with AAV in remission rarely experienced severe relapse after vaccination, and some involved new-onset organ while others are worsened of the original involvement. Pulmonary new onset involvement might be triggered by neutrophil extracellular traps promotion. The elderly receiving B-cell depleting therapy who are at infection risk with low humoral response should be under careful evaluation between last dose of rituximab and next dose of vaccination. Kidney injury presented mostly with good clinical treatment response. However, longer observation should be considered whether those patients received kidney replacement therapy earlier than expected. (Figure Presented).

ATYPICAL VARIANT OF GRANULOMATOSIS WITH POLYANGIITIS WITH EOSINOPHILIA

SESSION TITLE: Critical Systemic Disease Case Report Posters SESSION TYPE: Case Report Posters PRESENTED ON: 10/19/2022 12:45 pm - 01:45 pm INTRODUCTION: Granulomatosis with polyangiitis (GPA) is a necrotizing granulomatous vasculitis affecting small-to-medium sized blood vessels. GPA is highly associated with antineutrophil cytoplasmic antibodies (ANCAs) and often triggered by environmental factors such as medications and infectious agents. Tracheobronchial stenosis and diffuse alveolar hemorrhage are serious complications of GPA. CASE PRESENTATION: A 35-year-old Caucasian male with a history of chronic sinusitis requiring balloon sinuplasty and recent tympanostomy had presented multiple times to the emergency room due to dyspnea and cough with pinkish sputum production. This was associated with sore throat and fever, which were attributed to his COVID-19 infection and treated with supportive care. Due to persistent drainage through his tympanostomy he was prescribed levofloxacin by his ENT specialist. After the second dose of levofloxacin, he developed Raynaud's phenomenon, diffuse purpuric lesions and swelling over his lower extremity, eyelids, and elbows. Four days later he developed worsening hemoptysis and dyspnea for which he was admitted for further evaluation. Laboratory findings were remarkable for peripheral eosinophilia, elevated ESR 19mm/hr, CRP 9.2mg/dl, c-ANCA 1:320 titer, positive proteinase-3 antibodies and normal p-ANCA titers. Urinalysis with microscopic hematuria. Chest CT scan showed ground glass opacity, consolidative infiltrate with subpleural sparing and minimal left bronchial stenosis. Bronchoscopy suggestive of diffuse alveolar hemorrhage. Limited lung biopsy showed ulcer and granulation tissue with abundant eosinophils, but no granulomatous inflammation noted. Pulse dose steroids and Rituximab were initiated, and rapid clinical improvement was noted. Patient was discharged on prednisone taper and Pneumocystis jiroveci prophylaxis. DISCUSSION: We believe that GPA may have been triggered by recent COVID-19 infection and levofloxacin use. Mild peripheral blood and tissue eosinophilia (<12%) has been described in GPA, however it is a rare finding. GPA and eosinophilic granulomatosis with polyangiitis (EGPA) are both ANCA vasculitis that involve lungs and kidneys. GPA presents with sinusitis, alveolar hemorrhage and high titers of PR-3 antibodies. EGPA presents with a history of atopic, asthma and high titers of myeloperoxidase-ANCA along with abundant peripheral eosinophils. Our patient best fits the diagnostic criteria for GPA with eosinophilia variant rather than EGPA. Our patient had no history of asthma or atopic disease and p-ANCA was normal, which also points away from EGPA. CONCLUSIONS: Clinicians should recognize the differential diagnosis for eosinophils in ANCA vasculitis. Early diagnosis of ANCA vasculitis and initiation of appropriate treatment is important to decrease morbidity and mortality. Reference #1: Potter MB, Fincher RK, Finger DR. Eosinophilia in Wegener's Granulomatosis. Chest 116: 1480-1483, 1999 Reference #2: Krupsky, Meir et al. Wegener's Granulomatosis With Peripheral Eosinophilia. CHEST, Volume 104, Issue 4, 1290 - 1292 Reference #3: Kitching AR, Anders HJ, et al. ANCA-associated vasculitis. Nat Rev Dis Primers. 2020 Aug 27;6(1):71. doi: 10.1038/s41572-020-0204-y. PMID: 32855422. DISCLOSURES: No relevant relationships by Afoma King No relevant relationships by Joshuam Ruiz Vega No relevant relationships by Krishna Shah no disclosure on file for Milos Tucakovic;

DOES VACCINATION and VARIANTS AFFECT the COURSE of the COVID-19 in INFLAMMATORY RHEUMATIC DISEASE?

Background: Although there have been expansion of knowledge about the course of COVID-19 in rheumatologic diseases, it still remains unclear the effect of vaccination status and variants on the disease course. Objectives: We aimed to investigate the general clinical characteristics of our patients with infammatory rheumatic disease (IRD) who had COVID-19 disease, their vaccination status and the time periods in which different variants were dominant during the disease. Methods: During the routine follow-up of our patient's with IRD, whether the patients had COVID-19 disease, when they were vaccinated (Pfzer/Biontech or Sinovac in our Country) and main clinical characteristics and their comor-bid diseases were recorded. The last patient was included in the study on January 25, 2022. They were divided into those who received insufficient or no vaccine and those who received a full dose of vaccine. The patients were divided into 3 groups according to the period they had the disease: Those who had the disease between March 2020 and June 2021accepted as '1st period patietns', the period when the Alpha and Beta variants, the initial forms of the disease, were dominant variants in populations;those who had the disease between July 2021 and November 2021, when the Delta variant dominated the World and in our country accepted as '2nd period patients';and those who had the disease in December 2021 and later, when the Omicron variant was dominant throughout the world and in our country, was accepted as ' 3rd period' patients. Results: Total 463 (294 woman) IRD patients enrolled to the study. Distrubution of these patients included Behcet's syndrome:15;familial mediterranean fever: 5 7, rheumatoid arthritis:134, Sjogren's syndrome:24, systemic lupus erythema-tosus:26, Spondyloarthritis:141, necrotising vasculitis:6 and Others:50 cases. Mean age of patients were 46±13,2 (18-83) years. 354 (77%) of our patients got sick in the 1st period, 80 (17%) in the 2nd period and 28 (6%) in the 3rd period. When patients were compared in terms of their clinical complaints in these periods, dyspnea was signifcantly higher in patients in the 1st period (1st. period 36% vs 3rd period 18%;p:0.039), but there was no difference between other complaints including lung involvement and the frequency of hospitalization (p>0.05). 53% of patients had received at least 2 doses of mRNA vaccine. 84% of the patient has had COVID19 before full vaccination with any valid vaccine. When the patients who were full vaccinated and those who were not vaccinated or inadequately vaccinated at the time of illness were compared in terms of clinical features, lung involvement frequency and hospitalization frequency, no difference was found between them. (p>0.05, for all). However, hospitalization and lung involvement were less in those who received a booster dose of any valid vaccine (p: 0.03). While the average hospitalization rate was 17% for all groups, this rate was 50% for necrotizing vasculitis and was signifcantly higher (p:0,005). The probability of lung involvement and hospitalization were found to be sig-nifcantly higher in patients using prednisolone 5mg (or equivalents) or more;(p:0.008 and p:0.000, respectively). Pulmonary involvement was signifcantly higher among patients receiving sulphasalasine (p:0.008). Among the patients on Rituximab, the probability of hospitalization was higher than those who did not (p: 0.01). There was no statistical difference in terms of hospitalization and pulmonary involvement between patients who took other drugs (p>0.05, for all). A total of 5 cases died, including 2 GPA, 1 EGPA, 1 RA and 1 FMF patients. Only 8 patients had a second history of COVID19. Conclusion: The frequency of COVID-19 among IRD cases seems to decrease over time. Full vaccination seems effective for the prevention of COVID-19. It should be recommended that IRD patients have the full dose of vaccines and boosters. The risk of lung involvement and hospitalization increases in patients using certain drugs, such as corticosteroids, sulphasalasine and ituximab. These patients should be followed more closely.

COVID-19 in PATIENTS with ANCA ASSOCIATED VASCULITIS

Background: In patients with ANCA associated vasculitis (AAV) a higher mortality rate due to COVID-19 has been observed compared to general population1. Objectives: We aimed to evaluate the frequency and severity of COVID-19 in a well-defned AAV cohort. Methods: Medical records of AAV cases diagnosed at our secondary/tertiary rheumatology center between January 2010 and February 2020 and followed during the COVID-19 pandemic between March 2020 and November 2021 were analyzed. Results: During the 122-month period, AAV was newly diagnosed in 117 patients. Fifteen patients died before the beginning of COVID-19 pandemic. Of the remaining 102 patients (68.8% females, 42 (41.2%) GPA;32 (31.4%) MPA;19 (18.6%) EGPA and 8 (7.8%) not further clinically subclassifed AAV), SARS-CoV-2 infection was documented by PCR test in 11 (10.8%) patients (9 (81.8%) females;mean (SD) patient age at COVID-19 65.3 (±20.4) years;7 GPA and 4 MPA). Five patients had mild COVID-19 symptomatically treated at home, and 6 patients had severe infection. Clinical features of COVID-19 are presented in Table 1. Three patients (27.3%) died due to COVID-19. There were 5 additional deaths of AAV patients during pandemic period, all these related to cancer progression. At the time of diagnosed COVID-19, AAV was in remission in 10 patients and relapsed 2 months prior in one patient. All patients except one were receiving immunomodulatory treatment (steroids only 2;DMARDs only 4;steroids + DMARDs 4). Of the 97 patients eligible for vaccination against COVID-19 (5 AAV patients died before vaccines against SARS-CoV-2 were available), 79 (81.4%) received by the end of November 2021 at least one dose, including 2 patients that later developed COVID-19 (both fully vaccinated;2.5% breakthrough rate). Conclusion: Our study shows that COVID-19 heralds a poor prognosis in AAV, with over 50% patients having severe disease and 25% deaths.

Case presentation: Initiation of dupilumab therapy for severe CRSwNP and severe reduced quality of life in post-covid syndrome

Introduction The use of biologics has been described as an effective therapy in phase 3 studies in severe CRSwNP. Relatively unexplored is the post-covid syndrome in CRSwNP patients. Method Case presentation. Results Presentation of a 75-year-old patient with CRSwNP, asthma, ASA intolerance and eosinophilic granulomatosis with polyangiitis. Drug therapy with daily 1-5 mg prednisolone oral and inhalation therapy with formoterol/ beclomethasone. In February 2021, the patient was diagnosed with SARS-CoV-2 infection. For four days, the patient was admitted to a hospital with pronounced physical weakness without respiratory insufficiency. Anosmia has long been known because of CRSwNP. After Covid-19 illness, the patient reported severe sleep impairment and a severe state of exhaustion compatible with a post-covid syndrome. In addition, the patient was impaired by a severe nasal obstruction. At presentation in the rhinological consultation 7 months after Covid-19 illness, severe nasal polyps (NP overall score 8) and anosmia were detected. Dupilumab therapy (anti IL-4/IL-13 antibody) was initiated for severe CRSwNP. In the course of 2 months, an improved quality of life with less nasal obstruction as well as a reduced NP overall score of 6 were shown. Furthermore, the sleep impairment and exhaustion of the patient did not improve. Conclusion Dupilumab therapy improves quality of life in patients with severe CRSwNP, which may be especially important in post-covid syndrome.

Eosinophilic Granulomatosis with Polyangiitis in a Twelve-Year-Old BoyReceiving Montelukast: A Case Report

Introduction: Eosinophilic granulomatosis with polyangiitis (EGPA) is a multisystem disorder characterized by asthma, prominent peripheral blood eosinophilia, and small-vessel vasculitis. We report a case of EGPA in an adolescent with uncontrolled asthma who was receiving montelukast. Case: A 12-year-old boy who is known to have asthma and allergic rhinitis which were previously controlled on ICS, intranasal steroids, and prolonged use of montelukast for 4 years. He presented with cough and nasal blockage for 2 months. He also reported an increase in the frequency of asthma attacks and received multiple courses of systemic steroids. Subsequently, his asthma controller medications were upgraded to ICS/LABA few weeks prior to admission. His symptoms were also associated with weight loss, diarrhoea and haematochezia. He was vitally stable and maintained oxygen saturation on room air. Physical examination revealed nasal polyps, purple skin flat lesions on palms and feet (Figure1), and bilateral crackles on chest auscultation. His blood investigations were significant for leukocytosis with marked eosinophilia (11x103/uL, (51%)), high inflammatory markers and total-IgE (1975 kU/L). Initial chest XR showed bilateral interstitial thickening and small pleural effusions (Figure2). Chest CT showed centrilobular nodules and peripheral ground-glass opacities, tree-in-bud appearance with no peripheral sparing in addition to moderate pericardial effusion and bilateral mild pleural effusion (Figure3). Sinus CT showed extensive sino-nasal polyposis with pansinusitis (Figure4). Initial echocardiography showed moderate pericardial effusion with normal biventricular function. Patient was started on IV furosemide. During his hospitalization, patient developed chest pain. His serial troponin was rising and LV contractility was depressed. ECG showed ST-segment depression. Therefore, EGPA with cardiac involvement was suspected. Cardiac MR showed features of a peri-myocarditis. IVIG was commenced for suspicion of coronary artery involvement, which was later disputed by cardiac cath. He was also started on IV pulse steroids at a dose of 30 mg/kg for 3 days which resulted in dramatic decrease in troponin level, eosinophil count and CRP. Skin biopsy, which was later performed after administration of steroids, showed perivascular non-necrotizing granulomas. His ANA, ANCA and COVID-19 PCR came negative. Serum chemistries and urine microscopy were unremarkable. Patient was later started on Rituximab with significant clinical, serological and radiological (Figure5,6) improvement after 10-months of follow-up. Discussion: EGPA is rare but should be considered in children with uncontrolled asthma, eosinophilia and rhino-sinusitis. This case shows the importance of being aware that montelukast could cause EGPA, in spite of the uncertainty about its mechanism. (Figure Presented).

A late diagnosis of eosinophilic granulomatosis with polyangiitis

Background: Eosinophilic granulomatosis with polyangiitis (EGPA) is a medium and small vessel vasculitis. Discussion: A 58-years man was admitted to the Emergency Department in January 2022 for myalgia and weakness of lower limbs in recent COVID-19 infection. He had a clinical history of allergic asthma and eosinophilic pneumonia (ANCA negative) diagnosed as secondary to sensitization work-related in 2001. Blood test showed a severe hypereosinophilia (absolute eosinophil count: 9875/microL) and elevated creatine kinase (CK: 7555 U/L). He was hospitalized in HUB COVID. During hospitalization reported paraesthesia of upper and lower limbs and fever;blood test showed elevation of inflammation markers. Autoimmune screening showed a antineutrophil cytoplasmic antibodies positivity (ANCA anti-MPO 178UI/mL). A sinus CT showed nasal polyposis. A neurological evaluation and electromyography were performed with the evidence of polyneuropathy. Muscle biopsy showed eosinophil-associated vascular occlusion and eosinophilassociated tissue damage. The investigation excluded renal, cardiac, pulmonary and gastro-intestinal involvement. A steroid therapy (Prednisone 1 mg/kg/die) was started with clinical improvement. Conclusions: EGPA is a multisystemic disorder, typically suspected based on a combination of clinical findings, such as asthma, nasal and sinus symptoms, peripheral neuropathy, and eosinophilia ≥1500/microL. ANCA antibodies are positive in around 40% of patients and diagnosis can often be challenging and delayed.

Pancarditis as the Clinical Presentation of Eosinophilic Granulomatosis with Polyangiitis: A Multimodality Approach to Diagnosis

Eosinophilic pancarditis (EP) is a rare, often unrecognized condition caused by endomyocardial infiltration of eosinophil granulocytes (referred as eosinophilic myocarditis, EM) associated with pericardial involvement. EM has a variable clinical presentation, ranging from asymptomatic cases to acute cardiogenic shock requiring mechanical circulatory support (MCS) or chronic restrictive cardiomyopathy at high risk of progression to dilated cardiomyopathy (DCM). EP is associated with high in‐hospital mortality, particularly when associated to endomyocardial thrombosis, coronary arteries vasculitis or severe left ventricular systolic dysfunction. To date, there is a lack of consensus about the optimal diagnostic algorithm and clinical management of patients with biopsy‐proven EP. The differential diagnosis includes hypersensitivity myocarditis, eosinophil granulomatosis with polyangiitis (EGPA), hypereosinophilic syndrome, parasitic infections, pregnancy‐related hypereosinophilia, malignancies, drug overdose (particularly clozapine) and Omenn syndrome (OMIM 603554). To our knowledge, we report the first case of pancarditis associated to eosinophilic granulomatosis with polyangiitis (EGPA) with negative anti‐neutrophil cytoplasmic antibodies (ANCA). Treatment with steroids and azathioprine was promptly started. Six months later, the patient developed a relapse: treatment with subcutaneous mepolizumab was added on the top of standard therapy, with prompt disease activity remission. This case highlights the role of a multimodality approach for the diagnosis of cardiac involvement associated to systemic immune disorders.

Management of PIMS-TS in children from a low-income country: A single center experience

Introduction: PIMS-TS features a toxic shock-like syndrome or Kawasaki-like syndrome in the setting of SARS-CoV-2 positive diagnostic testing. The main cause is a severe cytokine storm resulting in a wide spectrum of clinical phenotypes, ranging from mild selfresolving to severe life-threatening presentations. Objectives: To report the experience of a single center from a lowincome country, in the management of PIMS-TS. Methods: A retrospective descriptive study of 9 cases with PIMS-TS. Results: We had 4 boys and 5 girls. The mean age was of 11-yearold, with extremes of 7 and 15-yesr-old. Medical history was marked by one case of Churg and Strauss syndrome under steroids, one case of recurrent idiopathic pancreatitis under steroids and azathioprine, one case of sarcoidosis under steroids and mycophenolate mofetil, and one case of nephrosis. All cases had history of contact with a COVID-19 positive case. SARS-CoV-2 RT-PCR was positive in 5 cases, while SARS-CoV-2 IgM antibodies were positive in one case and SARS-CoV-2 IgG antibodies were positive in all cases. Telltale symptoms were acute fever in one case, protracted fever in 4 cases, respiratory tract infection (rhinitis, caught, polypnea) in one case, Kawasaki -like symptoms (cheilitis, conjunctivitis, cervical lymphadenopathies and rush) in 2 cases, myocarditis in 3 cases, gastrointestinal symptoms (abdominal pain, vomiting, diarrhea) in 3 cases, toxic shock in one case, uveitis in one case, acute kidney injury in 8 cases, and liver failure in 4 cases. All patients had high acute phase reactants (ESR, CRP, ferritin). Hematological involvement was in the form of microcytic anemia in 3 cases, hemolytic anemia in 2 cases, polynuclear neutrophils' leukocytosis in 4 cases, leucopenia in 4 cases, lymphopenia in 3 cases, thrombocytosis in 5 cases, and thrombocytopenia in 3 cases. Two children had hepatic cytolysis, while 6 had high D-dimers and LDH levels, 5 had high fibrinogen level, and 3 had high triglycerides level. Management was based on steroids in all cases (3 pulses of methylprednisolone at 1g/1.73 m2/ day, followed by oral prednisone for a mean time of 3 weeks). Meanwhile, one case was put under tocilizumab and one case was put under intravenous immunoglobulins. Hemodialysis was needed in the acute phase in 4 children. Two cases were put under intravenous noradrenaline, while 3 cases were treated by antibiotics. Anticoagulation was prescribed in 3 cases. Evolution was marked by complete remission in 8 cases and in a mean time of 2 weeks. We deplore one death from multiple organ dysfunction Syndrome following septic choc. Conclusion: In our experience, PIMS-TS was more prevalent in immunocompromised children. Steroids were effective as a first line treatment. Complete remission with no sequela is the rule.

Mepolizumab for severe eosinophilic asthma-real-life data

Background: Mepolizumab, a humanized monoclonal antibody against IL-5, is a therapeutic option in patients with severe eosinophilic asthma. Its efficacy has been shown in clinical trials. Our aim is to present data from our center to corroborate this evidence in the complexity of real-life patients. Method: A retrospective study of patients with severe eosinophilic asthma treated with mepolizumab in our center was performed. We collected data regarding demographics, eosinophilic blood count, FEV 1 , fractional exhaled nitric oxide (FeNO), clinically significant exacerbations [need to start or increase oral corticosteroids (OCS), emergency department visit and/or hospitalization], OCS and safety profile, before and after patients started mepolizumab. Results: A total of 12 patients were included (9 female, mean age 53.7 ± 8.9 years old);10 patients had concomitant chronic rhinosinusitis with nasal polyps. Mepolizumab was administered in a dose of 100 mg every 4 weeks, except for 2 patients diagnosed with eosinophilic granulomatosis with polyangiitis (EGPA) (300 mg every 4 weeks). The mean duration of treatment was 13.75 months [3 - 28 months]. Due to COVID-19 pandemics restriction it was not possible to assess absolute eosinophilic count in 2 patients, as well as FeNO and FEV 1 in 2 different patients after treatment. The mean value before and after treatment for each outcome were the following: absolute eosinophilic blood count, from 537.5/μl to 116/μl ( p = 0.005);FEV 1 , from 1.44L to 1.84L ( p = 0.036);FeNO, from 62.27ppm to 41.8ppm ( p = 0.260);clinically significant exacerbations, from 2.83 in the previous year to 0.25 ( p = 0.007). Prior to treatment, 8 patients were treated with daily OCS, and after starting mepolizumab 3 of them were able to stop OCS and the others reduced daily dose (mean dose reduction 64.7%, ranging from 25% to 98.5%). The only side effect reported was sporadic headache, and no one discontinued treatment. Conclusion: In our sample, we observed a significant reduction in eosinophilic blood count, clinically significant exacerbations and OCS use, as well as improvements in FEV 1 , in patients with severe eosinophilic asthma treated with mepolizumab, with a good safety profile. This information supports data from clinical trials and early real-life experience in other populations.

Eosinophils and COVID-19-clinical case of COVID-19 infection in a patient with eosinophilic granulomatosis with polyangiitis

Coronavirus disease (COVID-19) is an infectious disease caused by a newly discovered coronavirus. COVID-19 is caused by a virus called severe acute respiratory syndrome coronavirus 2 or SARS-CoV-2. The impact of the pandemic has led to significant research on all aspects of the disease, including diagnostic biomarkers, related risk factors and strategies that could be used for its treatment and prevention. To this end, eosinopenia has been identified as one of many factors that could facilitate diagnosis and have prognostic value in cases of severe COVID-19. While eosinophil-associated conditions have been misdiagnosed as COVID-19 and others are among the reported complications, patients with pre-existing eosinophil-associated diseases (e.g. asthma, eosinophilic gastrointestinal diseases) do not appear to be at increased risk of severe disease. Interestingly, several recent studies have shown that a diagnosis of asthma may be associated with some degree of protection. We present a 42-year-old patient with eosinophilic granulomatosis with polyangiitis (Church-Strauss vasculitis) known for 4 years, who in March 2021 was diagnosed with COVID-19 infection. The disease was presented with manifestations of acute viral infection, with observed post-COVID transient migrating nodules of subcutaneous adipose tissue on the limbs, percentage of eosinophils over 50 and complete recovery.

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

Case report-IntroductionCOVID-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 descriptionA 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-DiscussionThis 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 intr ducing 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 pointsDespite 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 and eosinophilic granulomatosis with polyangiitis or COVID-19 mimicking eosinophilic granulomatosis with polyangiitis?

Coronavirus disease 2019 (COVID-19) and eosinophilic granulomatosis with polyangiitis (EGPA) share similarities in clinical, imaging findings and may present with respiratory distress. Differentiating a new-onset EGPA from COVID-19 during the current pandemic is a diagnostic challenge, particularly if other EGPA symptoms are overlooked. Here in this study we reviewed the literature regarding EGPA patients with COVID-19 and patients who diagnosed with EGPA or suffered an EGPA flare mimicking COVID-19. We conducted a literature survey in PUBMED database using meshed keywords "COVID-19" and "EGPA", "COVID-19" and "eosinophilic granulomatosis with polyangiitis", "COVID-19" and "Churg Strauss Syndrome", to reveal previously reported cases involving EGPA patients who had COVID-19 infection, patients who suspected to have COVID-19 but eventually diagnosed with EGPA and patients with a known diagnosis of EGPA who suffered a flare but a COVID-19 infection was suspected initially. A total of 11 cases (6 literature cases, 5 cases from our clinic) were included in our study. Seven (63.6%) of the cases were defined as COVID-19 mimicker and 4 (36.4%) were EGPA with COVID-19. All of the cases in EGPA with COVID-19 group had a history of asthma. All of them had a positive PCR result and ground-glass opacities in thorax CT. In COVID-19 mimicker group, six (85.7%) patients had a history of asthma and other EGPA features that were observed were eosinophilia in 6 (85.7%). Our study provided clues regarding the EGPA/COVID-19 diagnostic challenge which may be useful in the current pandemic. Since none of the findings in COVID-19 are disease-specific, other conditions like EGPA should not be overlooked particularly in PCR negative patients and clinical, laboratory and imaging findings should be interpreted carefully. Furthermore, we did not observe poor outcomes in EGPA patients who had COVID-19.