Autoimmune pulmonary alveolar proteinosis in an adolescent girl with rapidly progressive dyspnea

Autoimmune pulmonary alveolar proteinosis (PAP) is a rare disease, especially in pediatrics, but important to consider, as it may avoid unnecessary and/or invasive investigations and delayed diagnosis. This case report highlights an adolescent girl with rapid onset dyspnea but an unremarkable physical exam and initial testing. However, due to a high index of suspicion, a chest computed tomography (CT) scan was done, revealing a "crazy paving" pattern, which then prompted expedited assessment. This finding, however, is not as specific as often discussed and has a broad differential diagnosis, which will be reviewed in detail as part of this case. Furthermore, this report demonstrates a diagnostic approach for PAP that avoids lung biopsy, previously considered to be required for diagnosis of PAP, but is increasingly becoming unnecessary with more advanced blood tests and understanding of their sensitivity and specificity. Additionally, management strategies for PAP will be briefly discussed.Copyright © 2022 Canadian Thoracic Society.

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

Hypereosinophilic Syndrome Following the BNT162b2 (BioNTech/Pfizer) Vaccine Successfully Treated with Mepolizumab: A Case Report and Review of the Literature.

Although an increasing number of real-life data confirm large-scale clinical trial findings on the efficacy and safety of SARS-CoV-2 vaccines, rare but severe adverse reactions have begun to emerge. Here, we report a full-blown hypereosinophilic syndrome (HES) following a BNT162b2 (BioNTech/Pfizer) vaccine. A 48-year-old man developed, 5 days after the first shot of the SARS-CoV-2 vaccine, erythematous and painful nodular lesions in the lower and upper limbs accompanied by widespread itching, acrocyanosis with gangrenous lesions at the tips of the first and fourth fingers of the right hand, as well as paresthesia in the right hand and foot. Investigations revealed isolated eosinophilia, occlusion of the right ulnar artery, and electromyography alteration compatible with multifocal sensory neuropathy, as well as minimal accentuation of the interstitial texture with some ground glass appearance. Despite treatment with prednisone in combination with warfarin, he developed thrombosis of the left ulnar artery. Therefore, therapy with an IL-5 inhibitor and acetylsalicylic was successfully added. Given the time interval between the onset of clinical manifestations and the vaccine shot, we believe that the mRNA vaccine triggered the eosinophilic response. This case evidences a possible link between HES and the SARS-CoV-2 vaccination. Mepolizumab, an IL-5 inhibitor, might be considered in steroid refractory cases.

Colitis with Hypereosinophilia following the Second Dose of the BNT162b2 mRNA COVID-19 Vaccine: A Case Report with a Literature Review.

A 61-year-old man presented with a 7-day history of watery diarrhea and loss of appetite after receiving the second dose of the Pfizer-BioNTech COVID-19 vaccine. Laboratory studies showed significant eosinophilia and an elevated IgE level (white cell count, 18.4×109/L; eosinophil count, 9.5×109/L; and IgE level, 540 IU/L). Symptoms resolved 10 days after vaccination without any steroids or antiallergic medications, and the eosinophil count had also returned to within normal limits 2 months later. Several cases of eosinophilic disorders following receipt of any type of injectable COVID-19 vaccine have been reported, so the etiology should be examined.

DYSPNEIC AFTER EVERY COVID-19 SHOT: SUSPECTED BNT162B2 MRNA VACCINE-RELATED, DRUG-INDUCED PULMONARY EOSINOPHILIA

SESSION TITLE: Issues After COVID-19 Vaccination Case Posters SESSION TYPE: Case Report Posters PRESENTED ON: 10/19/2022 12:45 pm - 01:45 pm INTRODUCTION: Eosinophilia is the most commonly reported adverse event following administration of the Pfizer/BioNTech vaccine, accounting for 237 of 372 events (63.7%). Eosinophilic pneumonia has been described noted in 3 of all reported cases. CASE PRESENTATION: We present the case of a 73 year-old male presented to his PCP with a 3 week history of nonproductive cough and wheezing. He completed a 2-shot series of BNT162b2 mRNA (Pfizer/BioNTech) COVID vaccine 1 week prior to symptom onset. He had no history of respiratory symptoms, smoking, sick contacts, recent travel, chemical or biological exposures. On presentation, he was afebrile, tachycardic and required 3LPM supplemental oxygen to maintain peripheral oxygen saturation (SpO2) above 94%. Laboratory findings noted leukocytosis (13,200/mL) and eosinophilia at 5% (Absolute Eosinophil Count (AEC): 580 cells/L). Respiratory viral panel, procalcitonin, ESR and D-dimer were negative. Chest CT scan was unremarkable. He was treated with azithromycin, prednisone and inhaled bronchodilators with improvement in hypoxia. 2 weeks later, he reported intermittent dyspnea during a pulmonary clinic visit. Pulmonary function testing was normal (FEV1/FVC: 76%;FVC: 3.67L (90% predicted);FEV1: 2.80L (88% predicted). IgE level was normal and eosinophilia had resolved. 6 months after initial symptom onset, the patient received his third BNT162b2 mRNA vaccine dose. 2 weeks after vaccination, he presented to the ED with severe dyspnea, wheezing and cough with yellow sputum. He also noted a new itchy, erythematous bilateral forearm rash and painless oral ulcers. On exam, he was afebrile, tachypneic with SpO2 of 93% on 4LPM supplemental oxygen and audibly wheezing with a prolonged expiratory phase. Laboratory studies noted elevated creatinine and leukocytosis (23,100/mL) with marked eosinophilia (29.5 %, AEC: 6814 cells/L). Chest CT scan revealed a 2 cm rounded ground-glass opacity in the right upper lobe. (Figure 1.) Further workup revealed a weakly positive antihistone antibody (1:4 titer). IgE, ANA, ANCA, SS-A/B, anti-CCP, and complement levels were normal. Intravenous methylprednisolone treatment was initiated with rapid improvement in dyspnea, eosinophilia and renal function. A transbronchial biopsy (Figure 2.) of the RUL lung lesion revealed organizing pneumonia with mixed inflammatory infiltrate. Bronchoalveolar lavage analysis revealed elevated WBC (432 cells/L) with neutrophilic predominance (85%). Patient was discharged home on a prednisone taper with resolution of symptoms. DISCUSSION: Subsequent allergy work up did not indicate any apparent etiology of hypereosinophilia. Testing for strongyloides, coccidiosis and aspergillosis were also negative. A final diagnosis of BNT162b2 mRNA vaccine related pulmonary eosinophilia was made. CONCLUSIONS: Additional study is warranted into eosinophilic disease associated with the BNT162b2 mRNA vaccine. Reference #1: 1. United States Department of Health and Human Services (DHHS), Public Health Service (PHS), Centers for Disease Control (CDC) / Food and Drug Administration (FDA), Vaccine Adverse Event Reporting System (VAERS) 1990 - 03/11/2022, CDC WONDER On-line Database. Accessed at http://wonder.cdc.gov/vaers.html on Mar 11, 2022 1:18:37 PM DISCLOSURES: No relevant relationships by Matthew Haltom No relevant relationships by Nikky Keer No relevant relationships by Thekrayat Khader No relevant relationships by Muthiah Muthiah

DUPILUMAB-INDUCED SEVERE HYPEREOSINOPHILIA COMPLICATED WITH EOSINOPHILIC PNEUMONIA

SESSION TITLE: Challenges in Asthma SESSION TYPE: Rapid Fire Case Reports PRESENTED ON: 10/18/2022 10:15 am - 11:10 am INTRODUCTION: Dupilumab is one of the recently developed biological anti-asthma medications which is a human IgG4 monoclonal antibody. Dupliumab inhibits the biological effects of both IL-4 and IL-13. In 2018, Dupilumab was approved for treating moderate to severe asthma with an eosinophilic phenotype or with oral corticosteroid-dependent asthma. Transient, laboratory eosinophilia is a common side effect of Dupilumab, but clinical consequences are hardly ever reported. CASE PRESENTATION: We present a 66-year-old female patient with history of severe persistent asthma with an eosinophil's baseline of 1403 cells/mm3. She was started on Dupilumab a month prior to presenting to our hospital with shortness of breath, facial rash, recurrent fever and fatigue. Upon further investigations, patient was found to have severe peripheral eosinophilia (35%, absolute eosinophil count of 6100 cells/mm3), imaging studies that included CT scan of the chest showed patchy pulmonary consolidations, ground glass opacification and mediastinal lymphadenopathy. Non-invasive infectious work up including COVID-19 was negative. Then, patient underwent fiberoptic bronchoscopy with bronchoalveolar lavage (BAL), transbronchial biopsy, ultrasound guided lymph node fine needle aspiration and endobronchial biopsy (for diffuse endobronchial nodular lesions). Infectious work up from the BAL was negative but the BAL cytology showed eosinophilic alveolitis (31%). Histopathologic examination of the above biopsies showed significant interstitial inflammation with predominant eosinophils. Subsequently, Dupilumab was discontinued, and patient was started on prednisone 60 mg daily with remarkable eosinophils count reduction from a peak of 11,232 to 84 cells/mm3 along with significant improvement in her symptoms. CT chest 8 weeks later showed near complete resolution of pulmonary opacities. DISCUSSION: Dupilumab is an effective treatment for moderate to severe persistent asthma, by lowering rates of asthma exacerbation, as well as better lung function and asthma control. However, it has been reported that dupilumab can rarely cause a state of significant hyper-eosinophilia, which can rarely lead to complications such as eosinophilic pneumonia. Our patient was treated with dupilumab for her severe persistent asthma and after an intensive work up, we reached a diagnosis of severe Dupilumab induced hyper–eosinophilia leading to eosinophilic pneumonia and skin rash. CONCLUSIONS: We believe that this unique report is an important add to the reports in literature as it describes this rare entity in the differential diagnosis. Monitoring serum eosinophils count closely for the first few weeks of treatment with dupilumab should be considered, particularly for patients with unusual high level of eosinophils at baseline, to prevent severe complications. We believe that more studies are needed to better describe dupilumab induced severe hyper–eosinophilia Reference #1: Pelaia, Corrado, et al. "Dupilumab for the treatment of asthma.” Expert opinion on biological therapy 17.12 (2017): 1565-1572 Reference #2: Castro, Mario, et al. "Dupilumab efficacy and safety in moderate-to-severe uncontrolled asthma.” New England Journal of Medicine 378.26 (2018): 2486-2496 Reference #3: Menzella, Francesco, et al. "A case of chronic eosinophilic pneumonia in a patient treated with dupilumab.” Therapeutics and clinical risk management 15 (2019): 869 DISCLOSURES: No relevant relationships by Hamza Alsaid No relevant relationships by Mark Cowan No relevant relationships by Kamel Gharaibeh no disclosure on file for Kathryn Robinett;Consultant relationship with Medtronic Please note: 1 year Added 04/04/2022 by Ashutosh Sachdeva, value=Consulting fee Consultant relationship with Intuitive Inc Please note: Intermittent Added 04/04/2022 by Ashutosh Sachdeva, value=Consulting fee Consultant relationship with MErit Please note: 2 years Added 04/04/2022 by Ashutosh Sa hdeva, value=Consulting fee Scientific Medical Advisor relationship with AMBU Please note: 6 months Added 04/04/2022 by Ashutosh Sachdeva, value=Consulting fee

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.

POS-009 CAPTOPRIL-INDUCED ACUTE INTERSTITIAL NEPHRITIS: A RARE ASSOCIATION

Introduction: Acute interstitial nephritis (AIN) is an important reversible cause of acute kidney injury (AKI). Its prevalence is about 6-8% in histologically proven AKI.Early diagnosis of drug-induced AKI is vital because the discontinuation of the causal treatment facilitates recovery of the renal function. Methods: We report a case of captopril-induced AIN. Results: We report the case of a 82-year-old woman with a history of untreated hypertension. She was admittedin our department for AKI. Two days before admission, Captopril was initiated for high blood pressure (BP) as well as vitamin therapy for suspicion of a sars covid 19 infection, which was ruled out by a negative pcr covid test and a normal thoracic scan. The initial physical examination showed asthenia and a BP of 160/90 mmHg. Urinary labstix was negative. The biological analysis showed AKI: creatinine rose from 80 to 230 and then to 530 µmol/l, anemia at 7 g/dl and moderate hyper eosinophilia at 700 elements/ml. A renal biopsy was not performed because of the presence of cysts, and the diagnosis of interstitial nephritis was suspected. The drug-induced origin was confirmed after having eliminated infectious and tumoral origin. The pharmacovigilance investigation incriminated captopril. Captopril was stopped and the patient was put on corticosteroids 0.5 mg/kg/d. The evolution was favorable with an improvement of the renal function (creatinine at 120 µmol/l one month later). Conclusions: Angiotensin-converting enzyme (ACE) inhibitors can cause an increase in serum creatinine or potassium levels in patients with renal failure, renal artery stenosis, heart failure, or hypovolemia, but are rarely reported to be involved as an etiology of AIN. We report one of the rare cases of captopril-induced AIN. No conflict of interest

Neurologic complications of myocarditis.

Myocarditis, a nonischemic acquired cardiomyopathy, is an uncommon condition with multiple presentation patterns which may be initially difficult to recognize and may simulate other conditions such as acute myocardial infarction, pericarditis, septicemia, etc. There are four distinct clinical presentation patterns that include: (1) low-grade nonspecific symptoms such as fatigue; (2) symptoms that resemble an acute myocardial infarction, especially in younger individuals; (3) a heart failure presentation which may be acute, subacute, or chronic and may be associated with cardiac conduction system defects and arrhythmias; and (4) an arrhythmia presentation that may produce sudden cardiac death, especially in young athletes with minimal or no prodromal symptoms. This chapter will provide a brief overview of various myocarditis etiologies and diagnostic modalities. The ultimate focus will be directed toward neurologic manifestations of myocarditis and its subtypes, complications of specific therapies including extracorporeal membrane oxygenation (ECMO) for refractory heart failure, and review the current literature regarding the appropriate use of therapeutic anticoagulation in myocarditis and heart failure for stroke prevention. Covid-19 infection has been discovered to cause myocarditis. The emerging science will be discussed. Nuances of brain death (BD) determination in patients receiving venoarterial ECMO for heart failure refractory to standard medical therapies will be discussed.