Anaphylactic shock induced by a depot corticosteroid: Reflections on a clinical case

Introduction (contexte de la recherche): IgE-mediated reactions to systemic corticosteroids (CSs) are rare. Hydrocortisone and methylprednisolone succinate ester are the most frequent elicitors. Excipients of depot corticosteroids (like carmellose or macrogol) may also be involved. The involvement of the dipropionate form of betamethasone (present in the depot Diprostene) has not been studied. Objectif: To describe the case of a 40-year-old woman, who presented an anaphylactic shock reaction upon intra-articular administration of Diprostene (Betamethasone sodium phosphate and betamethasone dipropionate), associated with an iodinated radiocontrast media (ICM, Xenetix). Methodes: An allergy work-up was performed, according to recommendations for severe immediate reactions. Nine months after the reaction [hypotension (7/5 mmHg), erythema and desaturation at 94%, treated with adrenalin, methylprednisolone hemisuccinate, dexchlorpheniramine] the patient underwent skin prick tests (SPT) and intradermal tests (IDT) with ICM, bethamethasone and Diprostene (commercial molecules). Latex and chlorexidine were also studied. Resultats: The tests resulted negative for ICM, latex and chlorexidine (including serum specific IgE ImmunoCAP ThermoFisher Scientific), bethametasone phosphate (IDT 0.4 mg/mL) and carmellose (IDT 0.5 mg/mL). SPT elicited a positive reaction towards Diprostene in immediate reading, (for 5, 0.5, 0.05 mg/mL) with an erythema (10, 8, 5 mm respectively) and a wheal (of at least 3 mm for each SPT). We performed an oral drug challenge to bethametasone phosphate for a total of 8 mg and it was well tolerated. The basal tryptase was 5.5 microg/mL. Tryptasemia 30 minutes after the reaction was 26.8 microg/mL. Conclusion(s): We describe an anaphylactic reaction to Diprostene, proven by positive ST. The hypothesis of allergy to betamethasone dipropionate is under investigation. The hypothesis of allergy to macrogol, the other excipient of (which was not tested separately) is less likely, since the patient received Commirnaty SARS-CoV-2 vaccine 3 months after the reaction. The allergy work-up is ongoing (tests are programmed for betamethasone dipropionate alone).Copyright © 2023

Legionella Myocarditis Masquerading as Dual Chamber Cardiac Arrhythmia

Background Legionella pneumonia is a rare cause of myocarditis. Case 64-y.o male with CAD and PCI to LAD, DM and HTN presented to ER with mental status changes. On exam he was febrile and hypoxic.Presenting rhythm was Afib with frequent bouts of sustained and non-sustained stable posteroseptal VT treated with amiodarone and mexilitene. With right lung infiltrate on CXR and elevated WBC count, antibiotics were initiated for pneumonia. SARS COV-2 Ag and Influenza A & B was negative. Urine Ag for legionella was positive and was promptly treated with Levofloxacin. Coronary angiogram prior to discharge showed non-obstructive CAD. Decision-making Legionnaires' disease with myocarditis was suspected. Patient underwent CMR with late gadolinium enhancement (LGE) and Rest 82Rb perfusion and 18F-FDG PET/CT with high-fat dietary preparation scan for evaluation of legionella myocarditis. CMR revealed LVEF of 46%, with LGE and PET findings as described in the Figure. He was initiated on solumedrol for ongoing inflammation after completion of antibiotic therapy for Legionella pneumonia. Conclusion Our case highlights a systematic approach to differential diagnosis and use of multimodality imaging in legionella myocarditis presenting with dual chamber arrhythmia. There was good correlation between LGE inflammation/scar location and origin of VT, as well as active inflammation demonstrated by FDG PET imaging. The patient was successfully treated with antibiotics, steroids and anti-arrhythmic drugs. [Formula presented]Copyright © 2023 American College of Cardiology Foundation

A CASE OF LONG-TERM TOLERANCE AFTER KIDNEY TRANSPLANTATION.

We present a case of long-term organ functioning (ca.10 years) after allografting of a cadaveric kidney without usage of immunosuppressing drugs. In 2005, a patient suffering from a hypertensive form of chronic glomerulonephritis, have received an allogeneic graft of cadaveric kidney compatible for AB0 system, HLA antigens (A19, B07, DR04), and negative results of cross-match test. The graft function was immediately restored, with normalization of creatinine levels achieved 4-5 days after surgery. Immunosuppression with cyclosporine, solumedrol, cellcept, metypred and simulect was performed in the hospital. Pulse therapy with solumedrol was performed on the day +20 due to the development of initial rejection signs. The postoperative period proceeded without infectious complications. The patient was discharged being recommended to take cyclosporine, Cell-Sept and Metypred. Within a year after transplantation, the patient claimed for pain in the hip joint, and, therefore, metypred was completely canceled. Subsequently, the Cellcept was replaced with a Mayfortic. In 2007, the signs of coxarthrosis were revealed at computed tomography, followed by aseptic necrosis of the the right femur head. Deforming osteoarthritis of the right hip joint was detected, and the hip replacement surgery was suggested. In 2010, due to risk of side effects from ongoing immunosuppressive therapy, e.g., joint damage, the Mayfortic was canceled. In 2012, being in fear of original Sandimmun Neoral replacement by a generic drug, the patient completely refused cyclosporine therapy. In 2021, the endoprosthetics of the right hip joint was performed, and the surgical wound healed initially. Since 2012, the patient has not completely taken immunosuppressive therapy. Over this time period, the patient has never been admitted to the hospital for impaired functioning of the organ graft. Meanwhile, he monitored his graft function on regular basis undergoing biochemical analyses, clinical examination, ultrasound studies of the graft and made regular visits to the outpatient department. In 2021, a week after hip replacement, there was a slight increase in serum creatinine, followed by further increase to 230 mmol/L in 2021, and to 310 mmol/L in March 2022. In February 2022, the patient suffered mild respiratory infection (confirmed COVID-19). In March 2022, the first clinical signs of increasing nephropathy appeared, i.e., swelling of both lower extremities, with leukocytes in urine upon routine analysis, increased blood flow resistance in the main artery of the transplant shown by ultrasound study. Due to worsening of the patient's condition, he resumed taking the prescribed immunosuppressants. Copyright © 2022, SPb RAACI.

SARS-CoV-2 Antibody and T Cell Response After Vaccination with or without Intensified Immunosuppression Among Pediatric Renal Transplant Recipients

Purpose: Recent data has shown poor antibody response to SARS-CoV-2 vaccination among adult kidney transplant (tx) recipients, with seroconversion ranging between 22%-58% after two mRNA vaccine doses. Here, we evaluated the antibody and T cell response to SARS-CoV-2 vaccination and evaluate the effects of intensified immunosuppression on such response in pediatric (ped) kidney tx recipients. Method(s): Between April and November 2021, 31 ped renal tx patients (pts)aged 13-22 years old had SARS-CoV-2 spike IgG assessment after receiving 2 doses of SARS-CoV-2 mRNA or 1 dose of viral vector vaccine. Pts were evaluated by their level of immunosuppression: A) standard immunosuppression (tacrolimus, mycophenolate mofetil +/- steroids) or B) intensified immunosuppression (standard immunosuppression + solumedrol pulse, IVIG, rituximab, and/or tocilizumab within 11 months prior to and up to 5 months after SARS-CoV-2 vaccination). A subgroup of 18 pts had SARS-CoV-2 Tc assessment post-vaccination. Result(s): 23 of 31 (74.2%) pts seroconverted at a median assessment time of 83 days (IQR 43-124) post-vaccination. There was no difference in the use of steroid-based or steroid-free immunosuppression between the two groups or the type of vaccine received (Table 1). 15 of 17 (88.2%) of those who received standard immunosuppression seroconverted post-vaccination compared to 8 of 14 (57.1%) in those who received intensified immunosuppression (Table 1;p = 0.10). In a subgroup of pts who had SARS-CoV-2 spike-specific Tc testing, 7 of 7 (100%) in the standard immunosuppression group had positive Tc compared to 7 of 11 (63.6%) in the intensified immunosuppression group (Table 1, p = 0.12). There was no leukopenia or difference in the WBC count in either group at the time of Tc testing (Table 1;p = 0.97). No pts developed symptomatic SARS-CoV-2 infection. Conclusion(s): Ped renal tx recipients appear to have higher rates of seroconversion after the standard 2-dose mRNA or 1-dose viral vector SARS-CoV-2 vaccination compared to adult renal tx recipients. The intensified immunosuppression group appears to have a trend towards lower SARS-CoV-2 spike IgG and Tc conversion, however, results are limited by the small sample size. Larger studies are needed to better understand the humoral and cellular response to SARS-CoV-2 vaccination in this group. (Figure Presented).

A CASE OF ANTISYNTHETASE SYNDROME: THE IMPORTANCE OF HISTORY IN DISTINGUISHING ETIOLOGY OF INTERSTITIAL LUNG DISEASE IN A COVID-19 WORLD

SESSION TITLE: Systemic Diseases Causing Pulmonary Havoc SESSION TYPE: Rapid Fire Case Reports PRESENTED ON: 10/18/2022 10:15 am - 11:10 am INTRODUCTION: In the coronavirus disease 2019 (COVID-19) era, the etiology of interstitial lung disease (ILD) should remain broad to ensure accurate diagnosis and the proper treatment of patients. Vital to the art of medicine is taking a comprehensive history, and anchoring on a common diagnosis such as COVID-19 can result in early dismissal of alternate etiologies that physicians have an obligation to explore. CASE PRESENTATION: A 58-year-old male with a history of diabetes, hypothyroidism, and hypertension presented to the emergency department (ED) with dyspnea and fever. Initial CT chest imaging was significant for reticular and fibrotic changes with peripheral ground-glass and solid nodular opacities, some with areas of central clearing. Despite negative PCR testing, he was diagnosed with COVID-19 and discharged on oxygen with pulmonary follow-up. He continued to have arthralgias, proximal muscle weakness, low-grade fevers, and weight loss. He re-presented to the ED and was admitted for hypovolemia and further exploration into a potential autoimmune etiology of his symptoms. Labs were significant for a creatine kinase of 3,381 U/L, positive autoimmune antibodies [ANA (1:320), Jo-1 (>8.0 U), and SS-A/Ro (1.4 U)], and elevated ESR and CRP (30 mm/hr and 81 mg/L). Repeat CT revealed persistent parenchymal changes. Bronchoscopy was performed without anatomical abnormalities, and bronchoalveolar lavage (BAL) fluid was normal in appearance and negative for infectious etiologies. Though the patient was a farmer and possessed risk factors for hypersensitivity pneumonitis, lack of lymphocytic predominance on BAL, negative hypersensitivity panel, and uncharacteristic CT findings helped exclude this diagnosis. The patient was diagnosed with antisynthetase syndrome and treated with pulse dose intravenous solumedrol before transitioning to prednisone with resolution of muscle weakness and radiographic improvement in lung infiltrates. Muscle biopsy was deferred given the rapid clinical response and serum markers consistent with the diagnosis. DISCUSSION: Antisynthetase syndrome is a rare cause of ILD and often presents with myositis, arthritis, skin changes, Raynaud's phenomenon, and fever [1]. These symptoms, combined with the aminoacyl-tRNA synthetase antibody—most commonly the Jo-1 antibody—help confirm the diagnosis [2]. Due to a lack of established diagnostic criteria, muscle biopsy is often used to exclude other causes of myositis [3]. The ILD associated with antisynthetase syndrome is a significant cause of morbidity and mortality, and delay in diagnosis can lead to progression of lung injury. CONCLUSIONS: Chest imaging findings in COVID-19 are nonspecific, and post-COVID lung disease often presents similarly to other ILDs [1]. Because of this, history and physical exam remain crucial tools to reflect on alternate diagnoses for ILD and will continue to be necessary as we evolve through this COVID-19 era. Reference #1: Devi HG, Pasha MM, Padmaja MS, Halappa S. Antisynthetase Syndrome: A Rare Cause for ILD. Journal of Clinical and Diagnostic Research : JCDR. 2016;10(3):OD08. doi:10.7860/JCDR/2016/16872.7361 Reference #2: Cavagna L, Trallero-Araguás E, Meloni F, et al. Influence of Antisynthetase Antibodies Specificities on Antisynthetase Syndrome Clinical Spectrum Time Course. Journal of Clinical Medicine. 2019;8(11). doi:10.3390/jcm8112013 Reference #3: Schmidt J. Current Classification and Management of Inflammatory Myopathies. J Neuromuscul Dis. 2018;5(2):109-129. doi: 10.3233/JND-180308. PMID: 29865091;PMCID: PMC6004913. DISCLOSURES: No relevant relationships by Dustin Norton No relevant relationships by Alyssa Simon No relevant relationships by Kang Rui Xiang

DRUG-INDUCED PNEUMONITIS IN THE SETTING OF SARS-COV-2 INFECTION

SESSION TITLE: Drug-Induced and Associated Critical Care Cases Posters 1 SESSION TYPE: Case Report Posters PRESENTED ON: 10/19/2022 12:45 pm - 01:45 pm INTRODUCTION: Interstitial pneumonitis (ILD) is inflammation of lung interstitium leading to scarring and pulmonary fibrosis. Various etiologies include idiopathic, connective tissue disorders, sarcoidosis and drug induced1. Many chemotherapy agents have been implicated in drug related ILD such as bleomycin, taxanes. However, newer chemotherapeutic drugs such as molecular agents such as anti-VEGF, anti-EGFR (panitumumab) could be causative of drug induced ILD. CASE PRESENTATION: A 75-year-old female with stage IV sigmoid colon cancer treated with surgery, adjuvant FOLFOX chemotherapy and Panitumumab. She presented to the emergency department with shortness of breath and hypoxia after known COVID-19 exposure. Initial imaging with chest radiography showed bilateral ground glass opacities. A chest CT pulmonary embolism protocol was negative for pulmonary embolism but showed bilateral ground glass opacities (GGOs) and some interstitial thickening (L>R) not typical of COVID-19 infection. She was treated with remdesivir and dexamethasone, however her oxygen requirements continued to rapidly escalate. A repeat CT chest without contrast showed bilateral asymmetric interstitial thickening and GGOs. Given persistence of CT chest abnormalities, workup for interstitial lung disease was initiated. The results include ANA titer 1:80, otherwise negative ANCA profile, rheumatoid factor, anti-CCP, Scl-70, Sjogren antibodies. Given clinical history and imaging findings, diagnosis of ILD was suspected, and she was started on solumedrol 1 mg/kg. Her oxygen requirements decreased significantly over the next 2 days, and she was discharged home on oral steroid taper and pneumocystis pneumonia prophylaxis. DISCUSSION: Panitumumab is a fully humanized monoclonal antibody against EGFR. Approved by the US Food and Drug Administration in 2006 for advanced or recurrent colorectal cancer exhibiting wild-type KRAS mutation.2 ILD is rarely reported with panitumumab monotherapy, but higher incidence when used as a combination treatment such as with FOLFOX or FOLFIRI. A Japanese post-marketing surveillance study from 2010-2015 showed an ILD incidence of 1.3% but mortality rates of 51.3%.2 EGFR is expressed on basal cells and non-cilia cells of the bronchioles and type II cells of the alveolus. EGFR mediated mechanisms are important in tissue repair.3 Therefore inhibition of this pathway has been postulated to play a role in development of ILD. Another mechanism was decreased surfactant production by type II cells in pre-clinical study.4,5 ILD secondary to Panitumumab can occur at any point during therapy and up to 1 year after administration of drug.6 The role of infectious processes, in this case, COVID-19 pneumonia, could synergistically worsen ILD presentation. CONCLUSIONS: Although the incidence of ILD is low, the mortality rate is high, therefore early recognition and treatment is associated with improved clinical outcomes. Reference #1: Mudawi D, Heyes K, Hastings R, Rivera-Ortega P, Chaudhuri N. An update on interstitial lung disease. Br J Hosp Med (Lond). Jul 2 2021;82(7):1-14. Reference #2: Osawa M, Kudoh S, Sakai F, et al. Clinical features and risk factors of panitumumab-induced interstitial lung disease: a postmarketing all-case surveillance study. Int J Clin Oncol. Dec 2015;20(6):1063-1071. Reference #3: The FASEB Journal - 2000 - Puddicombe - Involvement of the epidermal growth factor receptor in epithelial repair in asthma.pdf. DISCLOSURES: No relevant relationships by Navitha Ramesh No relevant relationships by Uba Udeh

DIFFUSE ALVEOLAR HEMORRHAGE: A NOVEL ETIOLOGY?

SESSION TITLE: Pathologies of the Post-COVID-19 World SESSION TYPE: Rapid Fire Case Reports PRESENTED ON: 10/18/2022 10:15 am - 11:10 am INTRODUCTION: Diffuse Alveolar Hemorrhage (DAH) is a pathological lung condition that can result in rapid respiratory failure and death, with classic cases revolving around autoimmune pathology. However, new information regarding immune dysregulation post- covid infection continues to develop. Here we describe the case of a woman diagnosed with post-covid DAH with no prior autoimmune conditions. CASE PRESENTATION: A 49 y/o female with no history of rheumatologic or connective tissue disease history was evaluated in the ED for worsening acute hypoxic respiratory failure. She reported fever, cough without hemoptysis, and shortness of breath. She was recently discharged 7 days prior on 2L of oxygen after a 10 day ICU stay requiring high flow nasal cannula support for Covid pneumonia. A new chest computed tomography (CT) showed no pulmonary embolus, but revealed increased bilateral interstitial and alveolar opacities. Prednisone 60 mg daily and empiric antimicrobial therapy were initiated, and bacterial/fungal serologies were sent. Further deterioration occurred over 2 days resulting in need for mechanical ventilation. Bronchoscopy with bronchoalveolar lavage (BAL) was performed showing increasing bloody return through each cycle raising concerns for DAH. Extensive infectious workup and connective tissue disease/vasculitis panels were negative except for a positive ANA. A steroid burst with 1 gram of solumedrol daily for 3 days was started followed by prednisone 60mg daily with a 10mg weekly taper. Remarkable clinical improvement was seen and while repeat CT showed worsening infiltrates a repeat bronchoscopy 7 days later showed no residual blood on BAL and she was extubated and rapidly titrated down to room air over 24 hours. DISCUSSION: Diffuse alveolar hemorrhage is a rare life-threatening condition brought on by disruption of the alveolar-capillary basement membrane, and carries a high mortality rate of 46% (1). There are 3 main classifications of DAH, based upon histopathologic pattern, including pulmonary capillaritis (PC), bland pulmonary hemorrhage, and diffuse alveolar damage (DAD), as seen in acute respiratory distress syndrome (2-3). In this case, DAH was likely due to a combination PC and DAD, with the former contributing heavily given her response to pulse steroids. There is much to learn about long covid auto-immune dysregulation. Since DAH mimics pneumonia on CT, in those patients returning to the hospital post-covid infection, DAH should be considered as prompt treatment is required (3). CONCLUSIONS: DAH is a rare disease that can be difficult to recognize. Only a minority of patients present with hemoptysis and CT can be mistaken for worsening multifocal pneumonia. With a wide variety of new post-covid infection syndromes being described, auto-immune dysregulation leading to DAH may represent a small but significant proportion of covid readmissions. Reference #1: Bradna P, Manak J, Soukup T, Toms J, Kodeda M. Ab0565 diffuse alveolar hemorrhage, diagnosis, treatment and 3-year prognosis in a group of 32 cases of tertiary centre. Annals of the Rheumatic Diseases. 2016;75(Suppl 2):1098-1098. Reference #2: Franks TJ, Koss MN. Pulmonary capillaritis. Curr Opin Pulm Med. 2000;6(5):430-435. Reference #3: Lara AR, Schwarz MI. Diffuse alveolar hemorrhage. Chest. 2010;137(5):1164-1171 DISCLOSURES: No relevant relationships by Nicholas Germano No relevant relationships by Bryan Krajicek

COMPARISON OF HIGHER VERSUS LOWER DOSE STEROID ADMINISTRATION IN PATIENTS WITH COVID-19 AND ACUTE HYPOXEMIC RESPIRATORY FAILURE ON INHALED EPOPROSTENOL

SESSION TITLE: Critical Care Management of COVID-19 SESSION TYPE: Original Investigations PRESENTED ON: 10/17/2022 01:30 pm - 02:30 pm PURPOSE: Superimposed bacterial co-infection is common among patients with Coronavirus disease-19 (COVID-19) pneumonia. Incidence of any superimposed infection ranges from 0% to 40%. Up to 50% of COVID-19 patients who died, had concomitant bacterial or fungal infection. Steroids are recommended for the treatment of acute hypoxemic respiratory failure (AHRF) due to COVID-19 and are thought to mitigate inflammatory organ injury. This retrospective study explores a subset of COVID-19 patients receiving Epoprostenol (iEPO) for AHRF and compared two different steroid treatment strategies and the impact on patient outcomes. METHODS: This is a retrospective study of 101 COVID-19 patients with AHRF receiving iEPO and systemic steroids. Patients in the high dose steroid group (n=59) received a minimum of dexamethasone 20mg daily or solumedrol 100mg daily while the standard dose steroid group (n=52) were those who received any lower dose. Patients that were DNR/I were excluded from the study. The primary outcome of the study was the rate of bacterial co-infection defined by positive cultures. Secondary outcome was mortality. RESULTS: Results showed that patients treated with high dose steroids were older (66.77±11.17 vs 60.33±14.49, p0.006) and received a longer treatment course (18 days (12-25) vs 12.5 days (10-17), p 0.004). Univariate and Multivariate analysis showed that higher dose steroids were not associated with increased risk of superimposed bacterial infection (OR 0.96, CI (0.34-2.66), p0.93). The duration of steroids, regardless of the dose, was associated with increased risk of superimposed bacterial infection (OR 1.06, CI (1.01-1.13), p0.033). When adjusted for comorbidities and inflammatory state, there was no significant difference in mortality between patients treated with high dose compared to standard dose steroids (OR 3.60, CI (0.65-19.93), p0.14). A longer duration of steroids was associated with a trend towards improved mortality (OR 0.93, CI (0.87-1.00), p0.072). CONCLUSIONS: Our study suggests that the duration of steroids, rather than dosage, had an effect on patient outcomes. There was no difference in bacterial co-infection rates between the two groups, but infection rates were increased among those who received a longer course of steroid treatment. There was a trend towards lower mortality with increased steroid duration, however, this did not reach statistical significance. Given this trend towards lower mortality, future prospective studies should investigate steroid duration to determine if a longer course of treatment leads to better outcomes in patients with COVID-19 pneumonia and refractory AHRF. CLINICAL IMPLICATIONS: Based on our study, patients should not receive a higher dose or longer duration of steroid treatment given the increased risk of bacterial infection with no definitive improvement in mortality. DISCLOSURES: No relevant relationships by Natasha Garg No relevant relationships by Abhinav Hoskote No relevant relationships by Raymonde Jean No relevant relationships by Arpanjeet Kaur No relevant relationships by Sara Luby No relevant relationships by Omar Mahmoud No relevant relationships by Maria Athena Riego No relevant relationships by Edith Robin No relevant relationships by James Salonia No relevant relationships by DISHANT SHAH No relevant relationships by Venus Sharma No relevant relationships by Elizabeth Zipf

Acute Hemorrhagic Leukoencephalitis as a Primary Presentation in an Immunocompromised Patient With Cerebral Toxoplasmosis

Objective: To draw attention towards a devastating presentation of Acute Hemorrhagic Leukoencephalitis (AHLE) in an immunocompromised patient with cerebral toxoplasmosis. Background: AHLE is a rare, hyper-acute variant of Acute Disseminated Encephalomyelitis (ADEM). It is often preceded by an upper respiratory infection, and associated pathogens include influenza, Epstein Barr Virus (EBV), mycoplasma pneumonia, and SARS-CoV-2. Design/Methods: NA Results: A 27-year-old man presented to our hospital with a three day history of headaches and altered mental status. He was having seizures on arrival. He had a Glasgow Coma Scale (GCS) of 4 upon arrival. His pupils were anisocoric and sluggish to light. His brainstem reflexes were intact. Motor exam revealed extensor posturing in bilateral upper extremities and triple flexion in bilateral lower extremities in response to noxious stimuli. He received lorazepam in the emergency room with minimal improvement and was ultimately intubated for airway protection. Computed tomography (CT) head showed regions of hypoattenuation involving bilateral basal ganglia and thalami with superimposed acute hemorrhage, significant mass effect, and patchy regions of acute hemorrhage in the cerebellum. Magnetic resonance imaging (MRI) brain revealed areas of confluent FLAIR signal abnormality in the deep white matter, bilateral basal ganglia and thalami, brainstem, and throughout the cerebellum. He had a hypercellular cerebral spinal fluid (CSF) analysis that showed white blood cell count of 218 with lymphocytic predominance. Protein was elevated to 412 mg/dl and glucose was 17 mg/dl. He was found to be HIV-1 positive with a CD4 count of 6 cells per cubic centimeter. CSF specific toxoplasmosis PCR showed 730,000 copies/milliliter. He was treated with solumedrol and broad-spectrum antimicrobials with minimal improvement in his clinical picture and ultimately succumbed to his disease. Conclusions: This report highlights AHLE as a rapidly progressive hemorrhagic demyelination of white matter. It is imperative to recognize it to implement life saving therapies earlier in the course.

An Unusual Case of CLIPPERS

Objective: To present an unusual presentation of CLIPPERS that was responsive to rituximab Background: CLIPPERS (chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids) is a neuroinflammatory disorder typically affecting the brainstem and cerebellum with clinical and radiographic improvement with steroids. One reported case showed improvement with rituximab. We present a case of CLIPPERS with supra- and infratentorial involvement that improved with rituximab. Design/Methods: A 30-year-old male presented with several months of headaches, dizziness, and face and arm numbness, then developed diplopia and gait ataxia. Serial MRI's showed worsening punctate enhancing and T2-hyperintense lesions in the brainstem and supratentorial white matter over months. Workup showed normal CSF cell count, and negative CSF cytology, ACE, VDRL, oligoclonal bands, serologic IgG4, Coccidioidomycosis, Lupus, rheumatoid arthritis, and COVID. Vascular imaging showed no evidence of vasculitis. Biopsy showed a dense perivascular lymphocytic infiltrate including B and T cells, without evidence of vasculitis or lymphoma. He received IVIG and IV solumedrol, with symptom resolution and some improvement on imaging. Rituximab was started with subsequent resolution of the lesions on MRI. Results: NA Conclusions: CLIPPERS has a variable clinical presentation but typically includes gait ataxia and diplopia. MRI shows multiple punctate/curvilinear enhancing lesions in the brainstem and cerebellum, rarely in the spinal cord or supratentorially. Differential diagnoses include neurosarcoidosis, Behcet's disease, vasculitis, lymphoma, chronic infections, glioma, and demyelinating disease. It is characterized by responsiveness to steroids, and patients require long-term steroid or steroid-sparing agent treatment, at least until resolution of enhancement. Methotrexate, hydroxychloroquine, and cyclophosphamide are most commonly used. There was one report of treatment with rituximab with 4 years stability. Our case was unusual as he had supra and infratentorial lesions, and he had good response to rituximab. Rituximab should be considered in the treatment of CLIPPERS.

Late Allograft Rejection: A Case Report

Recognition of donor antigens by recipient T cells in secondary lymphoid organs initiates the adaptive inflammatory immune response leading to the rejection of allogeneic transplants. We present a unique case of a 38-year-old male with late allograft rejection due to immunosuppressive cytotoxic therapy. There is limited literature available as well as management. This case highlights the need for further investigative research of this entity and its pathogenesis.

Penile Prosthesis Now An In office Procedure: A Single Center Experience In The US

Introduction: Inflatable penile prosthesis (IPP), an implantable device for treatment of ED, historically have always been done in a hospital setting or outpatient setting. These surgeries are now done more frequently around the world as an in-office procedures. With the increase risk of COVID infections and the improvement of IPP technique we began performing this procedure in the office under local and total intravenous anesthesia. Objective: To present the nuances of office based 3 piece penile prosthesis and the outcome data for the feasibility of in-office implants while minimizing complications. Methods: A retrospective chart review was performed on the 10 IPP patients who had surgery in the office based setting in our clinic. The age ranges varied from 34-58 years of age. All pateints who opted for IPP in the office were screened for any and history of pelvic surgery, renal failure, cardiac stents or heart failure. Preoperatively, Antibiotics used were Vancomycin, Amikacin and oral Fluconazole and oral Neurontin for analgesia. All patients had a preoperative COVID nasal swab or had the vaccine prior to surgery. Intraoperatively Vancomycin, Amikacin and Fluconazole were used for irrigation and implant prep. Smaller table sets with stacking sterile field was used with headlights and loupes. IV sedation was used with the assistance of an anesthesiologist who used Propofol for sedation. A propofol bolus was given prior to entering the space of retzius. The patients also received a penile and pudendal block with a mixture of 1% Lidocaine, 0.5% Marcaine and 1mg Solumedrol for post-op pain management. Postoperatively, Neurontin and Tylenol were given PO and Toradol was given IV. Results: Of the 10 patients selected, 0 patients had infections we had even with a drain being in place 2 patients suffered a hematoma. 1 patient suffered urinary retention, resolving after 24 hours. Patients were cleared for device use between 5 to 8 weeks. 1 patient's implant was recalled;however, the patient did not have a desire for re-operation and has the device and works around the valve. The average procedure time was 53.5 minutes. Incision size range was 1.7 cm to 2.5 cm in length.Drains were placed in all patients for 24 to 48 hours with out puts of 90-160cc. Patients were discharged after 90 minutes in recovery phase. Conclusions: Office based penile prosthesis is safe and feasible in the post COVID world. Nuances such was headlights, loupes and adequate block-aid and sterile field efficiency with preloading and stacking are a necessity. With careful patient selection, in-office implantable penile prosthesis implant can be a safe feasible alternative for patients that have severe ED, have gone through alternative therapies, but either cannot afford and or insurance does not cover this procedure. Disclosure: Any of the authors act as a consultant, employee or shareholder of an industry for: Coloplast

Transverse myelitis in a pediatric patient with COVID-19

Case Report Transverse myelitis is the segmental inflammation of the spinal cord with motor and sensory abnormalities at and below the level of the lesion. Often, the etiology is unknown but may be attributed to autoimmune conditions or viruses. Here we describe a rare case of transverse myelitis secondary to severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2]/coronavirus disease (COVID-19). Case A 5-year-old male with a history of asthma presented for vomiting and altered mental status. The patient was noted to be altered, lethargic, and in respiratory distress. Intubation was performed. After family collateral was obtained, it was revealed that patient possibly ingested Sertraline and/or Risperidone at an unknown time prior to arrival. History also revealed that he had slurred speech, ataxia, and a fall with trauma to forehead 1 day prior to arrival. He tested positive for COVID-19 via PCR and chest x-ray revealed RLL consolidation. Dexamethasone was started. When sedation was weaned in hopes of extubation, patient was noted to be alert, but not moving extremities and had minimal gag and cough reflex. MRI of Brain and Spine were conducted and revealed findings suggestive of long segment transverse myelitis involving C2 to C3. LP was performed with unremarkable CSF studies and IV Solumedrol was started. In light of active COVID-19 infection, and worsening respiratory status, patient started on 5 days Remdesivir. Further, patient underwent ten sessions of plasmapheresis. Repeat MRI was consistent with previous. Physical and occupational therapy initiated at the onset of illness in hopes of achieving musculoskeletal improvement. Patient had some minimal musculoskeletal improvement, however, given his condition, decision was made for patient to undergo placement of gastrostomy and tracheostomy tubes. Patient was weaned off of sedatives and withdrawal was treated with a clonidine taper. Once stabilized, patient was transferred to neurological inpatient rehabilitation center. Discussion Neurological manifestations in children affected by SARS-CoV-2 are relatively common but are often non-specific. Worldwide data reports only 1% of children with COVID-19 present with severe symptoms of encephalopathy, seizures, and meningeal signs. Pathophysiology is multifactorial, including direct invasion of the CNS, vascular insufficiency, immune dysregulation and autoimmunity. Imaging is paramount in the diagnosis of transverse myelitis. Treatments are emerging and may include steroids, immunoglobulin, plasmapheresis, and monoclonal antibodies. Conclusion Much is unknown about COVID-19. Information is emerging and evolving daily. Cases of transverse myelitis in COVID-19 have been reported in few adult patients and minimal pediatric patients. Practitioners should keep transverse myelitis on their list of differentials for neurological complications of SARS-CoV-2 infections and initiate aggressive treatment with a multidisciplinary approach.

Mysterious cause of hypotension in MIS-C

Case Report Multisystem inflammatory syndrome (MIS-C) involves severe multi-organ inflammatory injury 2-6 weeks after COVID-19 infection. Seventy to 85% of patients have cardiovascular involvement, including diminished left ventricular ejection fraction (EF), coronary aneurysm, arrhythmias, valvular dysfunction, and pericardial effusion. Here we present a patient who arrived to the pediatric emergency department (ED) with MIS-C and suspected cardiogenic shock, though without the echocardiogram abnormalities commonly associated with MIS-C. A 7 year old African American male presented for a third time to our ED over the course of 4 days of febrile illness and was found to have MIS-C. During this time, he had no chest pain, palpitations, shortness of breath, or abnormal cardiopulmonary exam. At the first 2 ED visits, he was generally well appearing and after treating fever, had vital signs normal for his age. At his third visit, his vital signs were notable for borderline hypotension 86/48 (threshold 83/39 for his height of 1.25 meters). Troponins, chest X-ray, and EKG were normal. Bedside ultrasound was normal, with EF 55-60% so the hypotension was presumed to be secondary to hypovolemia and sepsis. However, despite 40 mL/kg of fluid boluses and maintenance fluid x1.5, his blood pressure continued to downtrend to a nadir of 79/39. He soon developed an S3 gallop and facial edema indicating fluid overload. His proBNP 4986 pg/mL also resulted at this time, suggesting cardiac injury was present. A formal cardiology echocardiogram confirmed the bedside ultrasound findings, noting normal ventricular size and motion, trivial pericardial effusion, and normal coronary artery size. However, it also detected diastolic dysfunction evident in mildly elevated E/e' of 10.86 of lateral mitral annulus, and 12.7 at medial mitral annulus. Three hours after starting solumedrol for treatment of MIS-C, his blood pressure improved to 110/52. The patient had no further episodes of hypotension, though it is unclear if steroids had resolved this by alleviating the underlying inflammation or as a secondary effect. We present a case of MIS-C that led to diastolic heart failure detected by mild hypotension, elevated proBNP, and subtle findings on formal echocardiogram. Although less common than systolic dysfunction in MIS-C, early recognition of diastolic heart failure is important for effective fluid management and initiation of vasoactive agents in criticallly 'ill patients. Diastolic heart failure with preserved systolic function has been seen on echo of MIS-C patients, and is hypothesized to be the subacute period after recovery of systolic function. However, we did not find clinical symptoms of systolic heart failure prior to the patient's development of diastolic heart failure. It is therefore essential to recognize that a patient with MIS-C may present with diastolic heart failure without preceding symptoms or echo findings of other cardiac anomalies.

A case of severe rhabdomyolysis and acute myocarditis in an adolescent female

INTRODUCTION: Rhabdomyolysis describes a condition where muscle tissue destruction occurs. Mortality and morbidity can be significant especially when multi-organ injury ensues. In very few instances, myocarditis has been described in association with this condition. DESCRIPTION: An 11-year-old previously healthy female presents with vomiting, diarrhea, tactile fever, worsening severe bilateral leg pain and gross hematuria for four days. At the Emergency Department, her ECG showed ST depression in lateral leads and abnormal Q waves. Laboratory studies were notable for significantly elevated CK >330,000 U/L. Elevated Troponin T and Troponin I at 3.60 ng/ml and 0.54 ng/mL, respectively. Elevation of CRP 23.5 mg/dl, ALT 1,966 U/L, AST 5,956 U/L, and Ferritin 712.1 ng/ml. Patient had dark brown urine, which was positive for blood, and urine myoglobin peaked at 2690 ng/mL. Her renal function was normal with blood urea nitrogen 8 mg/dl and creatinine 0.4 mg/dl. C3 and C4 levels were decreased, 45 mg/dl and 5 mg/dl, respectively. Anti-dsDNA negative, ANCA negative, and ANA negative. Nasopharyngeal PCR was negative for Mycoplasma pneumoniae, influenza A and B. Blood enterovirus PCR negative. COVID PCR and antibodies negative. Neuromuscular genetic testing was non-diagnostic. Her echocardiography showed thin rim of pericardial effusion and normal ejection fraction. Cardiac MRI demonstrated myocardial edema and regional sub-epicardial delayed enhancement consistent with acute myocarditis. Patient was started on hyperhydration therapy, Solumedrol and intravenous immunoglobulin. The rhabdomyolysis resulted in severe extremity weakness requiring prolonged rehabilitation. Her condition and biomarkers normalized and was subsequently discharged home. Follow up cardiac MRI 6 months later showed increased extracellular volume (ECV) of 38% suggestive of focal and diffuse areas of fibrosis. Patient remains under physical activity restrictions and is being followed by cardiology service. DISCUSSION: Our case highlights severe rhabdomyolysis in association with acute myocarditis and subsequent cardiac structural abnormalities. Although it remains unclear whether myocarditis evolved as a complication of rhabdomyolysis or was triggered by same inciting agent, an infectious etiology overall remains the most likely culprit.

RBC-hitchhiking chitosan nanoparticles loading methylprednisolone for lung-targeting delivery.

Hyper-inflammation associated with cytokine storm syndrome causes high mortality in patients with COVID-19. Glucocorticoids, such as methylprednisolone sodium succinate (MPSS), effectively inhibit this inflammatory response. However, frequent and chronic administration of glucocorticoids at high doses leads to hormone dependence and serious side effects. The aim of the present study was to combine nanoparticles with erythrocytes for the targeted delivery of MPSS to the lungs. Chitosan nanoparticles loading MPSS (MPSS-CSNPs) were prepared and adsorbed on the surface of red blood cells (RBC-MPSS-CSNPs) by non-covalent interaction. In vivo pharmacokinetic study indicated that RBC-hitchhiking could significantly reduce the plasma concentration of the drug and prolong the circulation time. The mean residence time (MRT) and area under the curve (AUC) of the RBC-MPSS-CSNPs group were significantly higher than those of the MPSS-CSNPs group and the MPSS injection group. Moreover, in vivo imaging and tissue distribution indicated that RBC-hitchhiking facilitated the accumulation of nanoparticles loading fluorescein in the lung, preventing uptake of these nanoparticles by the liver. Furthermore, compared with the MPSS-CSNPs and MPSS treatment groups, treatment with RBC-MPSS-CSNPs considerably inhibited the production of inflammatory cytokines such as TNF-α and IL-6, and consequently attenuated lung injury induced by lipopolysaccharide in rats. Therefore, RBC-hitchhiking is a potentially effective strategy for the delivery of nanoparticles to the lungs for the treatment of acute lung injury and acute respiratory distress syndrome.