A case of anaphylaxis to the BNT162b2 mRNA COVID-19 vaccine in a patient with confirmed polyethylene glycol allergy

Case report The Food and Drug Administration (FDA) provided emergency use authorization (EUA) for the Pfizer/BioNTech (BNT162b2) COVID-19 vaccine in December 2020. Implementation of COVID-19 mass vaccination efforts were implemented soon after. However, following the FDAs EUA, COVID-19 vaccine allergic reactions were reported. These findings led to concerns about vaccine hesitancy and the possible avoidance of future doses. The Texas Children's Hospital COVID-19 Vaccine Hypersensitivity Clinic was established in December 2020 to help address these concerns and to evaluate both pediatric and adult patients with immediate allergic reactions to the COVID-19 vaccines, as well as evaluating patients with polyethylene glycol (PEG) or polysorbate (PS) allergy. We present the case of an 18yo female who experienced anaphylaxis following her second Pfizer mRNA COVID-19 vaccine. The patient developed symptoms of generalized hives, chest tightness and dyspnea 17 minutes after receiving the Pfizer mRNA COVID-19 vaccine. She was treated in the emergency department with IM prednisone and PO diphenhydramine. Of note, in 2018, she had a similar response to her HPV9 vaccine (containing PS 80). Tryptase wasn't obtained at the time of her COVID-19 or HPV9 vaccine reactions, but she did have a baseline that was normal around 4ng/mL. Skin testing was performed to the following: PEG 3350, PS 20 and PS 80. Skin testing (skin prick and intradermal) were negative for PS20 and PS80. PEG 3350 skin prick was negative but methylprednisone acetate (PEG 3350) was positive at the 4mg/mL intradermal testing strength. She underwent a Miralax (PEG 3350) oral challenge. Within 20 minutes of ingesting 0.17grams PEG 3350 she developed an itchy macular rash on neck and upper chest, nausea and a globus throat sensation. She was treated with PO cetirizine and symptoms improved. Tryptase level was obtained 30 min after the start of her reaction and was 4ng/mL. Given the patient's reaction, she was advised to avoid PEG containing products and will return to undergo a graded-step challenge to the Janssen (J&J) COVID-19 vaccine. The prevalence of COVID-19 mRNA vaccine anaphylaxis and PEG allergies is rare. However, allergy referral is warranted in cases of immediate reactions to the COVID-19 vaccine or history of PEG or polysorbate allergies.

Misuse of prescription and over-the-counter drugs to obtain illicit highs: how pharmacists can prevent abuse

There have been increasing reports of misuse of a range of prescription and over-the-counter (OTC) drugs for recreational purposes. The use of psychoactive pharmaceuticals and 'pharming' are new, widespread phenomena involving the non-medical use of prescription and OTC drugs, which are recreationally used to achieve psychoactive effects either on their own or in combination with other substances. This article provides an overview of the topic, focusing on a range of medicines (e.g. prescription medicines such as quetiapine, gabapentinoids, Z-drugs, bupropion, venlafaxine and over-the-counter medicines such as loperamide, dextromethorphan, benzydamine, promethazine, chlorphenamine, diphenhydramine and hyoscine butylbromide) that have emerged as misused and diverted, or are already described through the literature, as well as recorded by drug users' online websites reporting new trends and experimentations of drug abuse. This rapidly changing drug scenario represents a challenge for pharmacy, psychiatry, public health and drug control policies. Moreover, possibly resulting from the COVID-19 pandemic, drug use habits and availability have changed, causing a shift in behaviours relating to both prescription and OTC medicines. Healthcare professionals should be aware of potential prescription drugs diversion, recognise misuse cases, consider the possibility of polydrug misuse, and prevent it where possible. Pharmacists can prevent and reduce drug abuse, and should be involved in evidence-based actions to detect, understand and prevent drug diversion activities and the adverse effects of drug misuse. Copyright © 2020 Pharmaceutical Press. All rights reserved.

A HARD PILL TO SWALLOW

SESSION TITLE: COVID-19 Case Report Posters 3 SESSION TYPE: Case Report Posters PRESENTED ON: 10/19/2022 12:45 pm - 01:45 pm INTRODUCTION: Epiglottitis is an inflammation of the epiglottis which can be life-threatening in the absence of prompt intervention. Although primarily a pediatric condition, streptococcus pneumonia has been identified as a common pathogen in adults. SARS-CoV 2 has been known to affect a multitude of systems including the upper respiratory tract, but rarely the epiglottis. CASE PRESENTATION: A 66-year-old female with a past history of hypertension, and hypothyroidism presented with acute onset pharyngodynia and dysphagia with a feeling of throat closing up due to swelling and difficulty speaking. She had a recent COVID-19 diagnosis and was doing well except for mild fatigue. Upon presentation, she was hemodynamically stable. Physical exam revealed posterior pharyngeal edema without any exudate, mildly edematous uvula, and no stridor. Laboratory data was pristine except for elevated inflammatory markers. Rapid streptococcal test and MRSA swab were negative. Sputum culture showed usual respiratory flora and blood cultures were negative. A neck CT showed diffuse edema without any evidence of abscess. Laryngoscopy performed by the ENT surgeon revealed diffuse edema including epiglottitis. Emergent intubation revealed supra and epiglottis edema sparing the vocal cords. The patient was given Decadron and Benadryl to help with the edema along with clindamycin and subsequently transferred to ICU for further care. She was treated with Ceftriaxone for 7 days due to a chest X-ray finding of pneumonia. As for COVID 19 treatment, she received a course of Remdesivir and Decadron. Decadron was given at an increased interval to reduce edema around the epiglottis. Her ICU course was complicated with hypotension requiring intermittent vasopressor support, and acute kidney injury from ischemic acute tubular necrosis which slowly improved. Repeat CT chest showed bibasilar consolidations with peripheral ground-glass opacities. In view of hospital-acquired pneumonia, she was started on Ertapenem. Her clinical condition improved and she was successfully extubated. She was shifted to the floors from where she was discharged without any further complications. DISCUSSION: There are only two other reported cases of COVID 19 epiglottitis. The patient's advanced age and obesity were non-modifiable risk factors, but the COVID-19 infection played a role. The virus can lead to excessive upregulation of the host inflammatory response through repeat epithelial and endothelial damage leading to a cytokine storm, which may be responsible for this presentation. A great level of attention is to be maintained while attending to these patients given the multitude of systems that can be affected. CONCLUSIONS: COVID-19 is a potential cause of life-threatening acute epiglottitis. Early suspicion and direct visualization of the epiglottis is the key to success for early management. Reference #1: Emberey J, Velala SS, Marshall B, et al. Acute Epiglottitis Due to COVID-19 Infection. Eur J Case Rep Intern Med. 2021;8(3):002280. Published 2021 Mar 3. doi:10.12890/2021_002280 Reference #2: Smith C, Mobarakai O, Sahra S, Twito J, Mobarakai N. Case report: Epiglottitis in the setting of COVID-19. IDCases. 2021;24:e01116. doi: 10.1016/j.idcr.2021.e01116. Epub 2021 Apr 7. PMID: 33842206;PMCID: PMC8025537. DISCLOSURES: No relevant relationships by Arunava Saha

NOT THE VACCINE, BUT ANAPHYLAXIS TO THE COVID-19 VIRUS ITSELF

SESSION TITLE: Poster Cases in Asthma and Allergy SESSION TYPE: Case Report Posters PRESENTED ON: 10/17/2022 12:15 pm - 01:15 pm INTRODUCTION: Anaphylaxis is an acute, potentially life-threatening, systemic allergic reaction that presents as a multitude of manifestations after exposure to an allergen. It is rare to have an anaphylactic reaction to the SARS-Cov-2 vaccine, however, we present a patient who had a prolonged anaphylactic reaction to the SARS-CoV-2 virus itself. CASE PRESENTATION: A 23-year-old female with past medical history of chronic idiopathic urticaria and dermatographism presented with fatigue, rash, rhinitis, and lip swelling in the setting of being COVID-19 positive. She had received two doses of the Pfizer-BioNTech COVID-19 vaccine nine months prior without any adverse affects. During the SARS-CoV-2 Omicron variant surge, the patient was exposed to a family member who had contracted COVID-19 infection. Two days prior to presentation, she started having a diffuse rash throughout her body. In the Emergency Department, she was given IM epinephrine x2, IV Solu-Medrol and IV Benadryl with temporary improvement in her symptoms. She developed hypotension that required initiation of a continuous epinephrine infusion and was admitted to the Medical Intensive Care Unit. Each time the epinephrine was held, generalized urticaria recurred and she would become hypotensive with her systolic blood pressure decreasing below 80 mmHg. The urticaria completely resolved and her blood pressure improved when the epinephrine infusion was restarted. The patient was treated with remdesivir, Solu-Medrol, loratadine, and famotidine. She was able to be weaned off the epinephrine infusion over the course of four days. Immunological workup was unremarkable apart from elevation of IL-10 on her cytokine panel. DISCUSSION: The symptoms and syndromes associated with COVID-19 infection remain diverse and while urticaria has been a documented manifestation of the virus, it is uncommon (1). There is a single case report of an anaphylactic reaction in response to COVID-19 (2). Given our patient's symptoms were temporally related to the COVID-19 infection, we believe the SARS-COV-2 virus was the trigger. She did not have any other exposure during this time. This case is unique in that the virus not only triggered the urticaria, but that her symptoms persisted for four days. After receiving antiviral therapy plus steroids and antihistamines, her symptoms finally resolved. The SARS-COV-2 virus itself is primarily attacked by immune cells, including mast cells, which release an array of proinflammatory cytokines (3). We postulate that in our patient, her history of chronic urticaria predisposed her to an exaggerated inflammatory response. CONCLUSIONS: SARS-CoV-2 has clinically presented itself in a multitude of ways across many disciplines. In a patient with a history of urticaria, prolonged anaphylactic symptoms can be triggered by the virus itself. Reference #1: Adeliño R., Andrés-Cordón J.F., De la Cruz Martínez C.A. Acute urticaria with angioedema in the setting of coronavirus disease 2019. J Allergy Clin Immunol Pract. 2020;8(7):2386–2387. Reference #2: Alvarez-Perea A, Baeza ML. Anaphylactic shock following the diagnosis of coronavirus disease 2019. Ann Allergy Asthma Immunol. 2020;125(4):477-478. Reference #3: Kritas SK, Ronconi G, Caraffa A, Gallenga CE, Ross R, Conti P. Mast cells contribute to coronavirus-induced inflammation: new anti-inflammatory strategy. J Biol Regul Homeost Agents. 2020 January-February,;34(1):9-14. DISCLOSURES: No relevant relationships by Brianne Navetta-Modrov No relevant relationships by Azzam Paroya Speaker/Speaker's Bureau relationship with Bayer Please note: current Added 03/30/2022 by Paul Strachan, value=Honoraria Speaker/Speaker's Bureau relationship with United Therapeutics Please note: more than 5 years Added 03/30/2022 by Paul Strachan, value=Honoraria Speaker/Speaker's Bureau relationship with Gilead Please note: $1001 - $5000 by Paul Strachan, value=Honoraria Removed 03/30/2022 by Pau Strachan Speaker/Speaker's Bureau relationship with Genentech Please note: $5001 - $20000 by Paul Strachan, value=Honoraria Removed 03/30/2022 by Paul Strachan Speaker/Speaker's Bureau relationship with Boehringer Ingelhein Please note: More than 5 years Added 03/30/2022 by Paul Strachan, value=Honoraria Stock Ownership relationship with Pfizer Please note: Purchased in 2000-2002 Added 03/30/2022 by Paul Strachan, value=nothing, I purchased stock Speaker/Speaker's Bureau relationship with Portola Please note: $1001 - $5000 by Paul Strachan, value=Honoraria Removed 03/30/2022 by Paul Strachan Stock Ownership relationship with Portola Please note: $5001 - $20000 by Paul Strachan, value=nothing, I purchased stock Removed 03/30/2022 by Paul Strachan Stock Ownership relationship with La Jolla Pharmaceuticals Please note: Purchased a few years back Added 03/30/2022 by Paul Strachan, value=nothing, I purchased stock Stock Ownership relationship with Seatle Genetics Please note: Purchased more than 5 years ago Added 03/30/2022 by Paul Strachan, value=nothing, I purchased stock PI relationship with United Therapeutics Please note: Current Added 03/30/2022 by Paul Strachan, value=Grant/Research Support PI relationship with Actelion/Janssen Please note: Current Added 03/30/2022 by Paul Strachan, value=Grant/Research Support PI for clinicial trial relationship with Roche Please note: Current Added 03/30/2022 by Paul Strachan, value=Grant/Research PI for clinicial trial relationship with Bellerophon Please note: Current Added 03/30/2022 by Paul Strachan, value=Grant/Research Support Speaker/Speaker's Bureau relationship with Actelion/Janssen Please note: Current Added 03/30/2022 by Paul Strachan, value=Honoraria

Eco-friendly resolution of spectrally overlapping signals of a combined triple-action over-the-counter pharmaceutical formulation for symptomatic management of COVID-19 pandemic: application to content uniformity testing.

Currently, all researchers are concentrating their efforts on countering the COVID-19 pandemic. The majority of patients are managed at home, according to recent statistics. An OTC triple action combination comprising paracetamol (PAR), aspirin (ASP), and diphenhydramine (DIPH) is commonly given for pain relief, fever control, and as a night-time sleep aid. This combination is currently recommended for COVID-19 patients as part of symptomatic treatment and management. In this work, three smart, simple, accurate, eco-friendly, and cost-effective spectrophotometric methods are developed for simultaneous determination of PAR, ASP, and DIPH in their combined over-the-counter caplet dosage form without any prior separation steps. The first method is the first derivative spectrophotometry (D1) which determined PAR at 259.7 nm. The second one is the dual-wavelength in ratio spectra (DWRS) for determination of ASP at 214.1 and 220.1 nm after using 10.0 µg/mL of PAR as a divisor, where PAR was a constant, and the wavelengths difference equal to zero for DIPH. The third method is the double divisor-ratio difference spectrophotometric one (DD-RD) which was based on using the sum of 15.0 µg/mL of each of PAR and ASP as a double divisor, and the difference in amplitudes was measured at two wavelengths ∆P(214.5-226.0) for determination of DIPH. The developed methods have been validated as per ICH guidelines. Furthermore, the three suggested methods were employed successfully to assay marketed pharmaceutical formulation and to investigate the content uniformity of the dosage units in accordance with the United States Pharmacopeia's guidelines. Finally, the greenness profile of the proposed methods was assessed and compared with the reported method using the analytical eco-scale system, national environmental method index (NEMI), green analytical procedure index (GAPI), and analytical greenness (AGREE) metric. The results from the proposed methods statistically agreed with those obtained by the reported one, with no significant differences in accuracy and precision.

Kratom-induced cholestatic liver injury: A pandemic within a pandemic?

Objectives: Mitragyna speciosa (commonly known as kratom) has both opioid and stimulant-like effects. Recently, Thailand decriminalized the possession and sale of kratom, led to people in many areas earned income selling Kratom at a time of widespread unemployment due to COVID-19. Here, we report a patient with post-Covid syndrome who developed mixed cholestatic-hepatocellular liver injury secondary to kratom. Materials and Methods: A 23-year-old Thai man was seen for evaluation of fatigue and nausea, followed soon after with pruritus, dark urine and jaundice. The patient had no known underlying disease but had been treated with mild COVID-19 pneumonia in the past 2 months. He reported taking kratom recreationally for 2 weeks as a treatment for his post-COVID insomnia. Kratom was bought from his friend and used as a homemade iced cocktail called ''4 9 100'' that consists of Coca-Cola, tea made from boiled kratom leaves, and diphenhydramine-containing cough syrup which has been popular in Southernmost provinces of Thailand. On workup, his total bilirubin was noted to be 10.6 mg/dL, aspartate aminotransferase was 642 U/L, alanine aminotransferase 1,635 U/L. Extensive workups including viral etiologies was negative. Abdominal ultrasound revealed only fatty liver without cirrhosis. Results: The patient had been managed conservatively for 5 days in the hospital. Urine toxicology screening confirmed the presence of only mitragynine. At two weeks later, serum total bilirubin was decreased to 1.5 mg/dL, aspartate aminotransferase was 112 U/L, alanine aminotransferase 404 U/L. He was in a stable condition and normalized liver function tests at 3 months after discharge. Conclusion: There is growing evidence that kratom is safe if used as pure kratom products or brewed herbal decoction in small doses and for a limited period of time. However, the polydrug patterns of kratom use could lead to severe liver injury.

SWEET SYNDROME IN ACUTE MYELOGENOUS LEUKEMIA- A CASE REPORT

CASE: Patient is a 63 y/o F with PMH of relapsed AML on treatment with Gilteritinib, Meniere's Disease, asthma, GERD, PRA positive, CKD Stage 3. She was on cycle 1 day + 20 of Gilteritinib when she presented with a neutropenic fever of 101.9. She reported congestion and headache. She was pan cultured and started on empiric Cefepime. Her blood cultures, COVID test and CXR were all negative for sources of infection. Eventually, Cefepime was stopped, and she was transited to PO Cefdinir and Cipro but redeveloped fevers and a maculopapular rash. Repeat pan-cultures were negative. Antibiotics were broadened to Merrem, Linezolid and Cresemba and her fevers improved. However, the rash continued to worsen. There was concern that nodular rash was secondary to infection or possible drug reaction from her antibiotics. Her rash showed no improvement with Benadryl or withholding drugs. She underwent skin punch biopsy before discharge. Biopsy showed florid superficial inflammation with benign ulcer that was highly suggestive of Sweet Syndrome given history of AML. IMPACT/DISCUSSION: Sweet syndrome (SS), or acute febrile neutrophilic dermatosis is a rare inflammatory condition characterized by painful cutaneous nodules and neutrophilic infiltrate in the dermis, in the absence of vasculitis. This syndrome is associated with malignancies with AML and MDS being the most reported. Malignancy associated Sweet Syndrome accounts for 15-20% of cases of SS. The atypical production of both pro-inflammatory cytokines (IL - 6, TNF - alpha) and signaling molecules demonstrated in AML is suspected to affect neutrophil function leasing to dermal clumping of the mature neutrophils. In our patient the fever presented prior to the rash with sudden onset of nodular as it has been commonly reported in literature review. Glucocorticoids, either topical or systemic, together with antibiotics and wound care, represent the mainstays of SS therapy. The rash heals without scarring if no ulcerations are present. The signs and symptoms of Sweet syndrome can mimic infection and be treated inaccurately, thus, it is important to make a correct diagnosis. Our patient's tissue cultures were negative for microorganisms. She was started on glucocorticoid with good response in regards to her rash but did have some scars and hyperpigmentation. Unfortunately due to her aggressive AML and complications patient elected to go to Hospice. CONCLUSION: When SS is established, the physician should keep a high index of suspicion to search underlying malignancies. Sweet Syndrome generally responds promptly to treatment with glucocorticoid.

TREATMENT SUCCESS IN A RESISTANT CASE OF INSOMNIA WITH AN IRREGULAR CIRCADIAN RHYTHM DISORDER

Introduction: A 19-year-old non-verbal male with history of CHARGE syndrome, severe autism, intellectual disability, coloboma with blindness OD and severely imparied vision OS, deafness, self-injurious and aggressive behavior, Tetralogy of Fallot status post repair, pulmonary valve replacement, hypertension, hypothyroidism, megacolon, gastrostomy tube dependence, eosinophilic esophagitis and chronic kidney disease with an irregular sleep cycle who has failed multiple medications for insomnia has shown treatment success with suvorexant. Report of Cases: This patient's sleep schedule ranges from 1.5 to 5 hour segments at various times of day or night including naps at school with occasional longer periods of sleep up to 10 hours and longer periods of wakefulness up to 22 hours who has been treated with the following medications: trazodone, clonidine, hydroxyzine, diphenhydramine, quetiapine, gabapentin, mirtazapine, eszopiclone, melatonin and ramelteon. His behavioral problems have been treated with olanzapine. He continued to be aggressive and difficult to direct. His parents reported exhaustion. Then, suvorexant 5mg was added at bedtime while the following sleep medications were continued: gabapentin total daily dose of 1500mg (300mg in morning and 3pm;900mg at bedtime, 300mg one hour later if still awake), ramelteon 8mg, mirtazapine 7.5mg and olanzapine 10mg at bedtime and bid prn aggressive behavior. He also takes the following daily medications: bisacodyl, polyethylene glycol, simethicone, hyoscyamine, cholecalciferol, aspirin, levothyroxine, hypoallergenic nutritional formula, starch and albuterol prn. With the addition of suvorexant 5mg, he had been able to get 9.5 hours of consolidated sleep at night with improvement in his behavior until he contracted Covid-19 and regressed. The suvorexant dose was increased to 10mg which again improved his insomnia and behavior. Conclusion: Various medications have either not worked at all or have worked suboptimally for insomnia in this medically complex patient who has an irregular Circadian rhythm disorder. Adding an orexin receptor antagonist as a novel mechanism to his regimen has shown promise. At this time, this patient has been stable for one month with suvorexant 10mg at bedtime after regression on the 5mg dose that coincided with a Covid-19 infection. We are proceeding with cautious optimism.

The Role of Cetirizine in the Changing Landscape of IV Antihistamines: A Narrative Review.

Since 1955, the only available H1 antihistamines for intravenous administration have been first-generation formulations and, of those, only intravenously administered (IV) diphenhydramine is still approved in the USA. Orally administered cetirizine hydrochloride, a second-generation H1 antihistamine, has been safely used over-the-counter for many years. In 2019, IV cetirizine was approved for the treatment of acute urticaria. In light of this approval, this narrative review discusses the changing landscape of IV antihistamines for the treatment of histamine-mediated conditions. Specifically, IV antihistamines will be discussed as a treatment option for acute urticaria and angioedema, as premedication to prevent infusion reactions related to anticancer agents and other biologics, and as an adjunct treatment for anaphylaxis and other allergic reactions. Before the development of IV cetirizine, randomized controlled trials of IV antihistamines for these indications were lacking. Three randomized controlled trials have been conducted with IV cetirizine versus IV diphenhydramine in the ambulatory care setting. A phase 3 trial of IV cetirizine 10 mg versus IV diphenhydramine 50 mg was conducted in 262 adults who presented to the urgent care/emergency department with acute urticaria requiring antihistamines. For the primary efficacy endpoint, defined as change from baseline in a 2-h patient-rated pruritus score, non-inferiority of IV cetirizine to IV diphenhydramine was demonstrated (score - 1.6 vs - 1.5, respectively; 95% CI - 0.1, 0.3). Compared with IV diphenhydramine, IV cetirizine demonstrated fewer adverse effects including less sedation, a significantly shorter length of stay in the treatment center, and fewer returns to the treatment center at 24 and 48 h. Similar findings were demonstrated in another phase 2 acute urticaria trial and in a phase 2 trial assessing IV cetirizine for pretreatment for infusion reactions in the oncology/immunology setting. IV cetirizine is associated with similar patient outcomes, fewer adverse effects, and increased treatment center efficiency than IV diphenhydramine.

Acute food refusal in 12 year old with anorexia nervosa requiring sedation and mechanical ventilation for enteral feedings

Case Report Anorexia Nervosa is a mental health disorder with significant morbidity and mortality. Acute food refusal is one of the indications for admission. We present a patient who went to extreme lengths to restrict food intake, requiring intensive care sedation and ventilation to enable enteral feedings. 12 year old male, was admitted with symptoms of anorexia nervosa and BMI of 12.0, (<1%ile) with baseline BMI of 16 (25%ile), K of 3.3 and glucose of 54. He was treated with supervised eating on an inpatient pediatric floor with no need for enteral feeding. Psychiatry consultation confirmed the diagnosis of anorexia nervosa and recommended the addition of Olanzapine to his Sertraline. He was discharged pending placement in an eating disorder center after 21 days of hospitalization with discharge BMI of 14. He was followed as an outpatient by his pediatrician, dietician and counselor but unfortunately, he required readmission 11 days after discharge due to acute food refusal, with BMI that had dropped to 13.1. Patient was readmitted and started on nasogastric (NG) feeds but he became severely agitated, pulling NG out multiple times and continued to lose weight with BMI dropping to 12. Sedation was attempted to facilitate maintenance of NG feedings, with Benadryl, Haldol and Ativan, but was ineffective at levels deemed safe without compromising his airway and breathing. Due to severe malnourishment and unsuccessful NG feeds he was transferred to PICU for sedation, endotracheal intubation and continuous nasoduodenal (ND) tube feedings on two separate occasions while inpatient. He was able to wean from the ventilator but once awake he found ways to manipulate delivery of his calories, even finding scissors and cutting the ND tube. The patient ultimately agreed to eat in order to avoid replacement of the feeding tube. He was finally transferred to an eating disorder facility, with a BMI of 13.9 and persistent anorexia thinking with restriction of eating anything but pizza. Patient completed three months of an inpatient program and had significant improvement in BMI to 19.3 (70%ile). He was subsequently discharged for continued outpatient follow-up and since discharge from the eating disorder center, his BMI has shown steady improvement in outpatient follow-up. He shows no signs of food refusal and is doing well with Family Based Therapy. This case highlights several unique characteristics in management of eating disorder patients. The age and being male along with extreme food refusal and resistance to enteral feeding that led to the requirement of deep sedation are quite unusual and not well described in the medical literature. The severity of his illness was a significant barrier to inpatient placement. In addition, despite a nationwide attempt to find an inpatient facility for him, which took several weeks, we identified shortages in eating disorder beds that have been exacerbated by the COVID-19 pandemic.

Relapsed Refractory Acquired Thrombotic Thrombocytopenic Purpura (aTTP) Following COVID-19 Vaccination

Introduction: Acquired thrombotic thrombocytopenic purpura (aTTP) due to an acquired deficiency in the enzyme ADAMTS13 leads to ultra-large von Willebrand multimers, thrombocytopenia and microangiopathic hemolytic anemia. Complications include microvascular and macrovascular thrombosis. We present an unusual case of a patient with a history of refractory aTTP who experienced relapsed aTTP following COVID-19 vaccine. Case Description: A 57-year-old African-American male with a history of refractory aTTP experienced a relapse following 3 years of remission after receiving COVID-19 vaccination. The patient was initially diagnosed with aTTP in 2016, after presenting with symptoms of dark urine, mild headaches and transient episodes of aphasia and paresthesia. Due to symptoms and persistently low ADAMTS13 levels, he required prolonged and extensive treatment including over 5 weeks of daily therapeutic plasma exchange (TPE), followed by gradual reduction in frequency of TPE sessions, as well as trials of rituximab, eculizumab, steroids, mycophenolate mofetil and bortezomib. Ultimately, he achieved remission after 9 months of intermittent TPE, 3 months of weekly bortezomib 1 mg/m 2, mycophenolate mofetil up-titrated to 1,750 mg twice daily, and then slowly tapered off over a 2-year period. The patient was doing well for 3 years without manifestations of aTTP (2 years off all therapeutics), until he developed a petechial rash 7 weeks after receiving the second dose of the Moderna COVID-19 vaccine. He was found to have acute thrombocytopenia with platelets of 38 x 10 9/L (normal range 135-317 x 109/L), from a baseline of 200-300 x 10 9/L. He was referred to the emergency department, where additional labs were notable for mildly elevated LDH of 508 U/L (normal range 122-222 U/L), hemoglobin of 12.4 g/dL (normal range 13.2-16.6 g/dL), creatinine at baseline, and peripheral blood smear showing 1-3 schistocytes per high-powered field. ADAMTS13 activity level was t <5% (normal >/= 70%), with positive ADAMTS13 inhibitor screen and titer of 1.5 (normal <0.4), consistent with relapsed aTTP. The patient was admitted to the hospital, and initiated on daily TPE, with steroids and diphenhydramine prior to each TPE session. He quickly improved with TPE alone, but given his history of refractory aTTP, he was discharged on weekly rituximab for 4 weeks and caplacizumab 11 mg daily for 30 days. His platelets remained stable within the upper limit of normal during his 30 day course of caplacizumab. However, 3 weeks after completion of caplacizumab, he had an acute drop in his platelets to 23 x 10 9/L. His ADAMTS13 level was again found to be <5%, and inhibitor level was the highest that it had ever been at 11.4. He was again hospitalized and underwent 8 sessions of daily TPE, as well as re-initiation of caplacizumab, mycophenolate mofetil 500 mg bid (with increasing taper), and a prednisone taper. Intravenous Cyclophosphamide 750 mg/m 2 was also added every 3 weeks. With this regimen, patient's platelet count normalized and remain stable, and his ADAMTS13 activity level has reached 52-59%. Discussion: Cases of vaccine-induced immune thrombotic thrombocytopenia (VITT) have been described as a complication following vaccination with formulations containing replication-defective adenoviral vectors (AstraZeneca-Oxford and Johnson&Johnson COVID-19 vaccines)(Arepally and Ortel 2021, Simpson, Shi et al. 2021). VITT and aTTP are both immune-mediated, however, VITT is distinct and pathogenically linked to autoimmune heparin-induced thrombocytopenia (HIT), given the presence of anti-platelet factor 4 antibodies in these patients, whereas aTTP is due to reduction in ADAMTS13 level, secondary to an antibody inhibitor of ADAMTS13 (Arepally and Ortel 2021). Recently, cases have been reported of de novo aTTP developing shortly after COVID-19 vaccination with all available vaccines, except the Moderna (mRNA-1273) vaccine (Al-Ahmad, Al-Rasheed et al. 2021, de Bruijn, Maes et al. 2021, Maayan, Kirgner et al. 2021, Ruhe, Schnetzke et al. 2021, Waqar, Khan et a . 2021, Yocum and Simon 2021). Additionally, cases of relapsed aTTP have been described following only the BNT162B2 (Pfizer-BioNTech) vaccine (Maayan, Kirgner et al. 2021, Sissa, Al-Khaffaf et al. 2021). This is the first case, to our knowledge, reported in the literature of aTTP following vaccination with Moderna's mRNA-1273 vaccine. Disclosures: No relevant conflicts of interest to declare.

Early Evaluation of the Use of Crizanlizumab in Sickle Cell Disease: A National Alliance of Sickle Cell Centers Study

Background: Vaso-occlusive crises (VOC) are the most common acute complication of sickle cell disease (SCD). Crizanlizumab, an anti-P-selectin monoclonal antibody, is an FDA-approved disease-modifying therapy (DMT) for SCD patients (pts) aged ≥16 yrs to reduce the frequency of VOC. To better understand its use and impact, the National Alliance for Sickle Cell Centers (NASCC) conducted a retrospective study of pts prescribed crizanlizumab from 11/2019-6/30/2021. NASCC is a non-profit organization formed to support SCD centers in delivering quality comprehensive care by setting and adopting specific standards and advocating for improved health outcomes in SCD. This study describes the largest real-world cohort of pts treated with crizanlizumab. Methods: This is a two-part study. Part 1 was to evaluate NASCC center crizanlizumab practice and to summarize data on insurance approval and the frequency of drug discontinuation. Part 2 includes pt level data to evaluate reasons for discontinuation and acute care utilization pre and post therapy. Acute care use includes day hospital/infusion, emergency department visits, and hospitalizations for VOC (excluding COVID-19). The index date for each pt is defined as the 1st crizanlizumab infusion date. Chart review (electronic health records) was used to identify all acute care visits 12 months pre-index and ≤12 months post index. Acute care data will be analyzed in aggregate. Evaluation of center-specific use of crizanlizumab, time to initial site level formulary approval and drug discontinuation were analyzed. Pt level data collection is ongoing to include sufficient time post index date. VOC characteristics will be summarized using medians, median differences (pre/post treatment), and 95% confidence intervals. Additional evaluation of effectiveness of crizanlizumab will include analysis based on number of doses received, pre-treatment VOC burden, concomitant hydroxyurea (HU) use and genotype. Results: Data includes pts prescribed crizanlizumab at 11 NASCC centers. Site- formulary approvals to use crizanlizumab varied from 12/2019-12/2020. As a result, the 1st pt to receive treatment at each site varied from 1/15/2020-1/20/2021. Mean time from site-level approval to first infusion was 77 days (range: 0-394). Over 50% of sites received insurance denials mainly due to “insufficient medical necessity” or “medication not covered by the prescription plan.” Sites were able to successfully appeal denials for 71% of pts (Table 1). Treatment Delivery: Each site gives infusions over 30 minutes and the majority (64%) do not use pre-medication unless pts had reactions. Some sites use diphenhydramine/acetaminophen (3) or normal saline and ketorolac (1). All sites prescribe crizanlizumab to pts of all SCD genotypes. Pts Treated: 297 pts were prescribed crizanlizumab of whom 238 received ≥ 1 infusion. There was variation in number of pts/site (range 6-73, mean 21) due to time to site-level approval, insurance and pt population. Of these 238, 75 pts (32%) discontinued treatment (0-17 pts/site). Sites reported pts perceived lack of improvement or feeling their overall pain was increased, transportation issues and infusion related reactions (IRRs) characterized by pain as some of the reasons for discontinuation. Evaluation of real-world efficacy measured by changes in acute care utilization, including sub-analysis by genotype, pre-treatment VOC burden and concomitant HU use, are pending sample size dependent feasibility. Discussion: This is the first multi-center real-world analysis of crizanlizumab. Findings demonstrate some insurance barriers to therapy. The majority of pts who initiated crizanlizumab have remained on therapy;however, 1/3 of pts had lack of effect or barriers to care. Pt level data will include characteristics related to treatment failure or IRR. Improving the understanding of phenotype-specific response to novel therapies is essential in SCD. Conclusion: Post-approval therapies for rare diseases must undergo real-world evaluation to ensure study results transla e to the community. NASCC uses defined criteria for multidisciplinary care for Alliance inclusion and findings reflect the use of DMT in such centers. This is the first NASCC study of DMT in SCD. Part 2 of the study will give early insights into the effectiveness of crizanlizumab;long term follow-up is needed for a full understanding of its utility in SCD. [Formula presented] Disclosures: Kanter: Fulcrum Therapeutics, Inc.: Consultancy;Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees;Forma: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees;Agios: Honoraria, Membership on an entity's Board of Directors or advisory committees;Beam: Honoraria, Membership on an entity's Board of Directors or advisory committees;Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees;Graphite Bio: Consultancy;GuidePoint Global: Honoraria;Fulcrum Tx: Consultancy. Manwani: Novartis: Consultancy. Idowu: Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding;Pfizer: Research Funding;Global Blood Therapeutics: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau;Forma Therapeutics, Inc.: Research Funding;Ironwood: Research Funding. Treadwell: National Alliance of Sickle Cell Centers: Other: Early Evaluation of the Use of Crizanlizumab in Sickle Cell Disease. Clay: GBT: Membership on an entity's Board of Directors or advisory committees;Novartis: Honoraria. Little: Hemex Health, Inc.: Patents & Royalties;Biochip Labs: Patents & Royalties. Desai: Global Blood Therapeutics: Honoraria, Research Funding;Novartis: Research Funding, Speakers Bureau;Pfizer: Other: Publication Fee, Research Funding;Forma: Consultancy;Foundation for Sickle Cell Research: Honoraria. Lanzkron: Shire: Research Funding;Pfizer: Current holder of individual stocks in a privately-held company;Bluebird Bio: Consultancy;Teva: Current holder of individual stocks in a privately-held company;Novo Nordisk: Consultancy;GBT: Research Funding;Imara: Research Funding;CSL Behring: Research Funding;Novartis: Research Funding.

Pharmacotherapy of rhino-orbital-cerebral mucormycosis

The aim of this study is Recently there is an alarming increase in the incidence of mucormycosis in patients diagnosed with Covid-19. In this short review, we will discuss the basic principles of mucormycosis treatment, antifungal agents used along with update on pharmacotherapeutic guidelines recommended for management of mucormycosis. Searching the Pubmed with the key words “mucormycosis and covid 19 ”, “ Treatment of mucormycosis”, “ antifungal used in Mucormycosis revealed many articles, and the relevant articles were screened. Mucormycosis is an aggressive disease which is difficult to diagnose in early stage with high morbidity and mortality. Multimodal therapeutic approach consisting of early diagnosis, urgent surgical and medical intervention and elimination of predisposing factors is key to successful management of this condition. First-line antifungal agent is high-dose liposomal amphotericin B although amphotericin B deoxycholate may be the viable option in resource limited settings.