Mild Transaminitis Research Articles

12475 Revisiting Myxedema Coma

Abstract Disclosure: M.H. Islam: None. D.R. Jimenez Corado: None. S. Siddiqui: None. M.F. Aquino Camey: None. S. Yeasmin: None. Background: Myxedema coma is a rare and life-threatening complication of hypothyroidism.Although it is rare in the era of better diagnostics and treatment modalities, its life-threatening nature mandates its timely recognition and better understanding. Case:81-year-old female with a history of hypothyroidism (unclear medication compliance) and alcohol use disorder was admitted due to alcohol withdrawal and treated with benzodiazepines. A few days prior to the presentation, she was found to have worsening confusion, unsteady gait, and multiple falls. On presentation, she was hemodynamically stable, tremulous, anxious, and oriented to person only. Blood work was remarkable for mild transaminitis. CT scan of the head revealed sequelae of microvascular disease. The day after admission, she was noted to be lethargic, and benzodiazepines were held. Later, she became hypothermic, hypotensive, bradycardic, and hyponatremic. Further investigation was pursued, revealing a TSH of 55 (normal 0.27 to 4.2 mlU/L), free T4 of <0.10 ng/dL (normal 0.8-1.7 ng/dL), free T3 of <1.0 pg/mL (normal 2.2-4 pg/mL), and cortisol of 10.7 ug/dL. Due to concerns of myxedema coma, she was started on stress dose steroids and IV levothyroxine. She was transferred to the ICU as her mental status continued to deteriorate; she underwent endotracheal intubation and received additional doses of IV levothyroxine and liothyronine. After a few days, her clinical condition and her cortisol, free T4, and free T3 levels improved; she was extubated and later discharged with an adjusted levothyroxine dose. Conclusion: It is of absolute importance to keep myxedema coma as a differential diagnosis when evaluating encephalopathic elderly patients, especially those with a history of thyroid disorders.There is a paucity of evidence to suggest a clear benefit of combining levothyroxine-liothyronine over levothyroxine alone. Treating initially with intravenous levothyroxine over oral is beneficial, as GI absorption and bioavailability are likely variable and unpredictable. In this case, oral liothyronine was used with IV levothyroxine to speed up clinical and biochemical recovery.Adrenal insufficiency often coexists with hypothyroidism, with considerable overlap in clinical features like hypotension, hypoglycemia, and hyponatremia. Administration of levothyroxine before steroids can lead to a rapid increase in metabolic rate and subsequent depletion of the existing reserves. Considering this, it can be said with fair confidence that patients need prior or concomitant stress doses of corticosteroids on an emergent basis. Later, biochemical testing can be done to evaluate the functioning of the hypothalamic-pituitary-adrenal axis and then adjust steroid doses accordingly. Presentation: 6/1/2024

Unveiling the Unconventional: Exploring Atypical Manifestations of Scrub Typhus

Scrub typhus is a rickettsial illness caused by Orientia tsutsugamushi. It is a common cause of undifferentiated febrile illness, especially in the Indian subcontinent, usually with multiorgan involvement, though central nervous involvement is rare. Here, we demonstrate a case of a young female who presented with fever, headache, vomiting, and seizures. Her examination was remarkable for generalized blanchable macular rash, opsoclonus–myoclonus along with neck rigidity and mild epigastric tenderness. Contrast-enhanced magnetic resonance imaging brain was suggestive of leptomeningitis. She also had mild pancreatitis, transaminitis, thrombocytopenia, and transaminitis. Given the ongoing tropical fever burden in Northern India, further workup was done and enzyme-linked immunosorbent assay anti-scrub typhus immunoglobulin M came as positive. Doxycycline along with supportive treatment was started, and all signs and symptoms improved gradually.

Safety of remdesivir in the treatment of acute SARS-CoV-2 infection in pediatric patients

BackgroundTransaminase and creatinine elevations have been well described in adults treated with remdesivir for COVID-19. It is hypothesized that a similar safety profile exists in children with COVID-19 treated with remdesivir, but available data are limited, especially in children < 12 months. The primary aim of this study was to determine the prevalence and timing of elevations in transaminases and creatinine in children with COVID-19 who were treated with remdesivir.MethodsThis was a retrospective, observational cohort study including all pediatric patients admitted to a single, freestanding children’s hospital who were positive for COVID-19 and received at least 1 dose of remdesivir between 1/1/2020 and 5/31/2022. Available baseline and peak transaminase and creatinine concentrations were evaluated. Multivariable logistic regression analysis was performed to identify risk factors for transaminase elevation.ResultsA total of 180 patients met inclusion criteria. Creatinine elevation of any grade was noted in 16% and remained elevated only in those with underlying chronic kidney disease. Transaminase elevation of any grade was noted in 58% of patients and remained elevated in only 1%. Older age and critical respiratory disease were associated with higher risk of significant transaminase elevation, whereas non-Hispanic ethnicity was strongly associated with protection against significant transaminase elevation.ConclusionsIn our cohort of hospitalized children with COVID-19 who were treated with remdesivir, most patients experienced only mild transaminitis and normal creatinine concentrations. A limited number of patients experienced laboratory abnormalities which were transient, suggesting a favorable safety profile for remdesivir use in pediatrics.

211At-Labeled Anti-CD45 Antibody as a Nonmyeloablative Conditioning for Canine DLA-Haploidentical Stem Cell Transplantation.

The α-emitter 211At deposits a high amount of energy within a few cell diameters, resulting in irreparable DNA double-strand breaks while minimizing off-target toxicity. We investigated the use of the 211At-labeled anti-CD45 monoclonal antibody (mAb) 211At-CD45-B10 as a nonmyeloablative conditioning regimen for dog-leukocyte-antigen-haploidentical hematopoietic cell transplantation. Methods: Seventeen healthy dogs were injected with either a 0.50 (n = 14) or 0.75 (n = 3) mg/kg dose of anti-CD45 mAb labeled with 211At (8.436-23.199 MBq [0.228-0.627 mCi/kg]) on day -3. Peripheral blood stem cells from dog-leukocyte-antigen-haploidentical donors were given on day 0. Peripheral blood chimerism was calculated by polymerase chain reaction assays, and blood clearance of the radioimmunoconjugate was studied using enzyme-linked immunosorbent assay and radioactivity measurements of serial blood samples. Results: All dogs achieved donor chimerism by day 28 (range, 27%-100%). The hematopoietic engraftment rate was 100%, though engraftment durability was variable. No difference in absorbed dose to blood was seen for the 2 mAb dosing levels studied. Neutropenia (0-29 cells/μL), lymphocytopenia (36-130 cells/μL), and thrombocytopenia (1.5-9 × 103/μL) with prompt recovery were observed. The main adverse nonhematologic event related to 211At-CD45-B10 was mild reversible transaminitis. Graft-versus-host disease was not seen. Twelve of the 17 dogs survived over 30 d, with donor chimerism ranging from 3% to 99%. Conclusion: The results suggest that nonmyeloablative conditioning with 211At-CD45-B10 could be used in haploidentical hematopoietic cell transplantation though with variable engraftment.

Efficacy and Safety of Andrographolide and Favipiravir Versus Favipiravir Monotherapy in Patients with Mild COVID-19 Infection: A Multicenter Randomized Controlled Trial

Reports indicate that Andrographolide inhibits viral replication and reduces COVID-19 symptoms. This study aimed to determine Andrographolide's additional effect and safety in mild COVID-19 patients treated with favipiravir. A multicenter, open-labeled, randomized controlled trial was conducted from October 2021 to February 2022. The patients were randomized to receive a combination of Andrographolide and favipiravir or favipiravir monotherapy. The primary outcome was the occurrence rate of severe pneumonia. The secondary outcomes were symptom improvement, inflammatory biomarkers, and adverse events on days 7 and 14. 82 mild COVID-19 patients were enrolled; 43 and 39 patients received either combination therapy or favipiravir alone. Baseline characteristics were comparable. None developed severe pneumonia, requiring a mechanical ventilator. The Andrographolide group had a significant reduction of cough compared to the controlled group; 13 (30.2%) vs. 22 (56.4%), p = 0.017 on day 7 and 4 (9.3%) vs. 7 (17.9%), p = 0.025 on day 14. Moreover, the Andrographolide group had significantly lower levels of inflammatory markers on day 7, CRP (5.8 vs. 18.4 mg/L; p = 0.019) and IL-6 (2.0 vs. 21.8 pg/mL; p = 0.001) but not on day 14. Regarding safety outcomes, the Andrographolide group had significantly higher AST levels on day 7 (40.3 vs. 32.2 U/L; p = 0.030) and both AST and ALT levels on day 14 (55.3 vs. 32.0; p = 0.014 and 63.8 vs. 40.0; p = 0.022, respectively). In mild COVID-19 patients, the combination of Andrographolide and favipiravir did not demonstrate additional benefits over favipiravir alone in preventing severe pneumonia. However, Andrographolide significantly reduced cough symptoms, especially during the first week. Furthermore, despite mild transaminitis, patients treated with Andrographolide showed improvements in inflammatory markers.

Hepatitis B Reactivation without Hepatitis Is a Common Event in Adolescent/Adult Patients of Acute Lymphoblastic Leukemia with Occult Hepatitis B (OHBI) Treated on Pediatric Protocols and Warrants Prophylactic Antivirals: A Prospective Cohort Study

Introduction: Patients with occult Hepatitis B infection(OHBI) (HBsAg negative but HBcIgG &amp;/or anti-HBs positive in the absence of immunization) are at an increased risk of Hepatitis B(HBV) reactivation while on and after chemotherapy. It can present over a spectrum ranging from asymptomatic or mild transaminitis to fatal hepatitis, affect the dose intensity of chemotherapy and compromise outcomes. The reported risk of reactivation is variable (1-24%, Yeo, 2009), and depends on the type of therapy and the method used to detect reactivation. Antiviral prophylaxis is recommended in patients with OHBI who are treated with antiCD20 monoclonal antibodies and those who undergo allogeneic stem-cell transplant, however this has not been evaluated in patients treated on pediatric-inspired ALL protocols comprising of several immunosuppressive drugs.. Methods: This was a prospective longitudinal cohort study conducted at a single tertiary care center in India between October 2017 to July 2021 (CTRI/2017/01/007747). The primary objective was to study the incidence of HBV reactivation in patients with OHBI on ALL protocol, and secondary objectives were to study the incidence of OHBI, HBV related hepatitis and its impact on chemotherapy intensity. Newly diagnosed patients with ALL/LBL, aged ≥15 years were screened for the presence of OHBI. Patients with OHBI were considered for enrollment into the prospective part of the study if they were treated on intense protocol (modified BFM-90 ALL protocol), had normal liver function tests, and no co-infection with HCV, HIV or history of HBV vaccination. Liver functions were monitored twice weekly during the induction/reinduction phase, prior to the early and delayed intensification and once every 2-3 months during the maintenance phase. HBV DNA copies by quantitative PCR (threshold for detection 20 units/ml), were measured at baseline, week 4, week 8, week 20, 32, week 48, completion of maintenance and every 3-6 months for 1 year. If a patient developed hepatitis, serum was collected for HBV DNA levels, HBsAg, HB core IgM antibody, IgM HAV antibody, IgM HEV, HCV and CMV DNA levels. HBV reactivation was defined as- either increase in serum HBV DNA level to more than 1 log higher than that of baseline or any copy numbers if it was negative at baseline. Seventy five patients with OHBI were to be studied to detect a true incidence of &amp;gt;10% HBV reactivation at a one-sided significance level of 5% and 90% power (Fleming's design) Results: A total of 566 patients were screened for the study, and 172(30.4% (95% C.I. (26.6-34.4)) patients were diagnosed with OHBI. 74 patients were enrolled in the prospective part of the study (Fig 1). The baseline characteristics of the study population are summarized in Table 1. HBV DNA was detectable at baseline in only 2(2.3%) patients. 51 patients (68.9%) completed all phases of treatment. The median follow-up was 21.6 months (range 0.03-53.5 months). A total of 402 HBV DNA tests were done in this cohort with an average of 5 tests per patient. HBV reactivation occurred in 5 patients ((6.7% 95% C.I.(1.03-12.47)), none of these patients developed hepatitis during HBV reactivation. In all the patients, reactivation occurred during the maintenance phase. All of these patients were started on antivirals (Entecavir). Overall 15(20.3%) patients developed hepatitis during the study period and CMV viremia was the cause for hepatitis in 4(26.7%) patients and HCV infection was the cause in 1 (6.6%) patient. Median AST, ALT during the episodes of hepatitis were 363 and 459 respectively (range AST 150-3490, range ALT 218-1950). Two(2.7%) patients had a delay in administration of chemotherapy due to hepatitis and median duration of delay was 21 days (range 18-24). Conclusion: We conclude that the risk of HBV reactivation is significant in adolescent/adult ALL patients with OHBI treated on pediatric inspired ALL protocols. HBV related hepatitis is a late event, and monitoring with liver function tests alone is not sufficient. The use of prophylactic antivirals is justified in patients with ALL.

THU384 Too Sweet To Digest; A Case Of Persistent Lactic Acidosis Secondary To Glycogenic Hepatopathy

Abstract Disclosure: T. Ayub: None. L.A. Robles: None. F. Sami: None. S. Saleem: None. S. Guntupalli: None. Glycogenic hepatopathy (GH) is an under-recognized cause of persistent lactic acidosis and hepatomegaly in patients with uncontrolled DM and diabetic ketoacidosis (DKA). A 19-year-old female with history of type 1 DM with recurrent DKA presented with complaints of nausea, vomiting and abdominal pain for 1 week. Physical exam showed normal vitals and lower abdominal tenderness. Her initial labs showed glucose 250 mg/dl, high anion gap metabolic acidosis with beta hydroxy butyrate of 11.3 mmol/l, lactic acid 3.2mm/l, and mild transaminitis. She was diagnosed with DKA and started on insulin drip. Anion gap responded to IV insulin and fluid therapy and was transitioned to SQ insulin. However, she had increase in her lactic acid (8.2mm/l), without hemodynamic compromise, despite fluid resuscitation. Secondary work up including blood, urine, sputum cultures were non diagnostic for an infectious etiology. Abdominal imaging showed a liver span of 26 cm. There were no signs of end organ hypoperfusion, medication or toxin mediated insult as evident by normal transthoracic echo, iron studies, urine drug screen, alcohol level and negative hepatitis panel. Review of prior hospitalizations showed recurrent episodes of DKA with similar uptrend in lactic acid levels with negative secondary work up. Prior imaging revealed hepatomegaly during DKA episodes with resolution after strict glycemic control. Given uncontrolled DM type 1 with reversible and recurrent hepatomegaly, transaminitis, hyperlipidemia and elevated lactic acid, a clinical diagnosis of glycogenic hepatopathy was made. Patient declined liver biopsy due to concerns for complications. She was discharged on home insulin regimen with outpatient follow up. GH or hepatic glycogenosis is a reversible cause of lactic acidosis and hepatomegaly seen in uncontrolled DM type 1. Pathogenesis involves presence of fluctuating levels of hyperglycemia and insulin, concomitantly, that leads to glycogen storage. Insulin inhibits gluconeogenesis resulting in decreased conversion of pyruvate to glucose and high lactic acid levels, in the absence of any infectious, metabolic and hypoxic etiology. Lactic acidosis can be worsened when treated with high dose Insulin. Definite diagnosis of GH requires liver biopsy or gradient dual-echo MRI but can be made clinically in the setting of uncontrolled DM1, hepatomegaly, transaminitis and elevated lactic acid levels. Prompt recognition of GH can prevent unnecessary diagnostic testing and can decrease the duration of hospital stay. Treatment is strict glycemic control with resolution of condition and no long-term complications. Presentation: Thursday, June 15, 2023

PA24 Abnormal interferon signature in a patient with chilblain lupus

Abstract A 5-year-old girl of Sri Lankan ancestry with no history of parental relatedness presented with the clinical features of chilblain lupus. This was particularly florid over her dorsal fingers, toes and the soles of her feet with areas in keeping with panniculitis on her calves and an epidermal naevus on the right side of her trunk. There was no ulceration or necrosis. Her parent reported occasional fevers and palpable lymph nodes in her neck. She also has bilateral astigmatism and mild valvular and supravalvular pulmonary stenosis. Blood tests showed a persisting mild transaminitis, an antinuclear antibody of 1 in 160 and a negative double-stranded DNA. She had a skin biopsy that showed supporting features for chilblain lupus. A lymph node biopsy showed nonspecific changes. The clinical suspicion was of a mild form of Aicardi–Goutières syndrome (AGS), and a genetic panel was performed that included TREX1, RNASEH2B, TMEM173 and SAMHD1 (all negative). The common mechanism behind these conditions is a type I interferonopathy. We sent blood on a research basis for RNA extraction and testing of her interferon (IFN) gene signature (IGS), which came back as abnormal (11.895; cutoff score of 2.758); she had normal expression of neutrophil-associated genes. This IFN score is on par with patients who have confirmed AGS or STING-associated vasculopathy with onset in infancy. An IGS is derived from the expression of IFN-regulated genes. A raised IGS has not only been reported to be useful as a biomarker in many rheumatic diseases, but is also used to help identify type I interferonopathies where genetic testing has not identified any clear pathogenic mutations (Crow YJ, Stetson DB. The type I interferonopathies: 10 years on. Nat Rev Immunol 2022; 22:471–83). National Institute for Health and Care Excellence guidelines allow for treatment of interferonopathies with baricitinib in patients with two documented high IFN gene signatures, which is our current plan for this patient.

A Profile Study of Japanese Encephalitis in an Industrial Hospital in Eastern India.

Introduction Japanese encephalitis (JE), caused by a Flavivirus, is one of the common causes of mosquito-borne encephalitis the world over including India. The disease is endemic in many states of India, including Jharkhand. Mortality ranges from 30 to 40% in different studies and a large number of patients survive with permanent neuropsychiatric sequelae. Aim The study aimed to evaluate the clinical spectrum, laboratory (including radiological) features and outcomes of cases of JE admitted in our hospital. Methods and materials This is a retrospective observational study consisting of confirmed cases of JE admitted to the medical wards and critical care unitof Tata Main Hospital (TMH) from January to December 2022. The case records of patients were retrieved from Hospital Management System (HMS) and analysed for demographic characteristics, clinical presentationsand treatment details along with outcome measures, which included length of stay (LOS), complications, and mortality. Observation Of the 14 confirmed cases, six (43.9%) were males and eight (57.1%) were females. The average age of male and female patients was 41.8 ± 23.1 and 35.1 ± 20.5 years respectively. A total of 35.7% of the patients were in the age group of 21 to 30 years. The clinical manifestations in the decreasing frequency were altered sensorium in 11 (78.6%) patients, headache in six (42.8%) patients, generalised convulsions in four (28.6%) cases, vomiting in three (21.4%) cases and weakness in all limbs and of the right half of the body in one (7.1%) case each. Objective neurological findings noted were neck stiffness (3, 21.4%), cog-wheel rigidity (3, 21.4%), tremors (2, 14.3%), delirium (2,14.3%), quadriparesis, facio-brachial dystonia and hemiparesis (1, 7.14%) patient each. Neutrophilic leucocytosis was observed in five (35.7%) patients and mild thrombocytopenia in two (14.3%) patients. The average C-reactive protein (CRP) level was 7.3 ± 6.6 mg/dL. Three (21.4%) patients had mild transaminitis. Cerebrospinal fluid analysis was abnormal in all patients with varying degrees of elevated protein and cell count, while adenosine deaminase (ADA) levels and sugar were normal in all patients. Magnetic resonance imaging (MRI) brain revealed bilateral thalamic T2FLAIR (fluid-attenuated inversion recovery) hyperintensities in 11 patients (78.6%). The average length of hospital stay was 9.6 ± 4.7 days. Ten patients (71.4%) needed treatment in the critical care unit. Complications seen were acute respiratory distress syndrome (2, 14.3%), sepsis with multiorgan failure (2, 14.3%) and ventilator-associated pneumonia (1, 7.1%). The case fatality rate was one (7.1%). Six patients (42.9%) had residual neuropsychiatric sequelae. Conclusion JE continues to be a major health-related problem. Most cases are concentrated during the post-monsoon period, coinciding with a higher vector density. Patients from rural backgrounds were seen to be more susceptible. JE may present with varying severities of acute encephalitic syndrome. As there is no specific treatment, timely diagnosis is important to reduce the morbidity and mortality associated with this disease. Clinicians must be aware of the wide spectrum of presentation of this disease. A high degree of suspicion along with thorough clinical examination and appropriate investigations are needed to diagnose this condition early and prevent complications.

Liver manifestations of tick-borne diseases.

Liver manifestations of tick-borne diseases.

Neonatal Dengue- A Case Series

Dengue is one of the commonest arboviral infections seen in children but in neonates, it is a disregarded entity. It can be acquired either through vertical (transplacental) or horizontal transmission (mosquito bite). It usually presents with fever, lethargy, poor feeding, and thrombocytopenia which can be accompanied by hepatosplenomegaly, transaminitis, fluid leak, petechiae, bleeding, Acute Respiratory Distress Syndrome (ARDS), shock and Acute Kidney Injury (AKI). Dengue shock in neonates responds well to dopamine if used early. A retrospective review of case records of five neonates admitted with dengue fever from October 2021 to October 2022 showed the neonates average age was 10 days and male:female ratio of 3:2. Three cases had horizontal and two cases had vertical transmission. All neonates presented with fever and were admitted within one week of illness. Petechial rashes and refusal of feeds were observed in two cases. Four cases had leukopenia whereas, all cases had thrombocytopenia. Sepsis was ruled out. Dengue Nonstructural protein 1 (NS1) antigen was positive in four cases. IgM antibody was positive in all while IgG was negative in all cases. None of the cases had hepatic derangement except for mild transaminitis in three cases. Only two cases had severe thrombocytopenia requiring platelet transfusion, but none developed bleeding, plasma leakage, shock requiring inotropes or fluid overload. Mortality due to neonatal dengue was nil and the duration of hospital stay ranged between 6-12 days. In the vertically transmitted cases, isolation of the virus from the breast milk or cord blood was not done due to logistics. Therefore, dengue fever can be suspected as one of the differentials in any neonate presenting with fever, leukopenia, and thrombocytopenia mimicking sepsis, especially during the epidemic season.

382: EHRLICHIOSIS-INDUCED MYOCARDITIS

Introduction: Myocarditis caused by Ehrlichiosis is a rare manifestation. The following case emphasizes the significance of early detection and its treatment. Description: A previously healthy 77-year-old female presented with a two-day history of generalized weakness and altered mental status. On arrival, she had a fever of 101.5°F, a heart rate of 110 beats per minute, a respiratory rate of 26 breaths per minute, a blood pressure of 80/70 mmHg, and an oxygen saturation of 92% on low-flow nasal cannula oxygen therapy. She was disoriented without a focal neurologic deficit, and the remainder of the examination was unremarkable. Laboratory evaluation revealed leukocytosis at 22000 /mm3, thrombocytopenia at 34000 /mm3, troponins at 6300 ng/mL, creatinine of 3.0 mg/dL, and mild transaminitis. Her hepatitis panel, toxicology screen, urine, and blood cultures were negative. A lumbar puncture was not performed because of thrombocytopenia. Her pan-computed tomography (CT) scans were also unremarkable. Echocardiography revealed severe diffuse hypokinesia with a left ventricle ejection fraction of 20%. Cardiac catheterization was deferred due to renal dysfunction. Her empiric antibiotics regimen was de-escalated to doxycycline after peripheral smear, and a PCR test confirmed Ehrlichiosis. Her symptoms improved, and she was discharged to inpatient rehabilitation. An echocardiogram in 6 months showed an improved ejection fraction of 45%. Discussion: Ehrlichiosis usually manifests with symptoms of fever, myalgias, and malaise mimicking influenza-like illness. However, severe sequelae are more traditionally encountered at extreme ages. Myocarditis is a rare and fatal occurrence. The pathogenic mechanism driving cardiac involvement is still partially understood. It may cause cardiac damage or produce immunosuppression and inflammatory cell dysfunction, leading to nonspecific myocyte damage. We believe our patient had ehrlichiosis-related myocarditis, as evidenced by peripheral smear testing, profoundly raised cardiac enzymes, new-onset congestive heart failure, and recovery of cardiac function after treatment. In endemic locations, especially during the summer, it is prudent to keep suspicion of ehrlichiosis-associated myocarditis.

A PATIENT WITH KABUKI SYNDROME AND HYPOGAMMAGLOBULINEMIA DEVELOPS BURKITT LYMPHOMA

<h3>Introduction</h3> Kabuki syndrome (KS) is a rare genetic disorder characterized by congenital abnormalities, autoimmunity, intellectual disability, distinctive facial abnormalities, and hypogammaglobulinemia. <h3>Case Description</h3> A 24-year-old male with KS and hypogammaglobulinemia presented to the emergency department (ED) with lower back pain and extremity paralysis. His previous genetic diagnosis of KS had a heterozygous novel variant causing a premature translational stop signal p.Pro235Alafs*6 in the KMT2D gene. The patient also has a history of congenital heart disease, autoimmune cytopenias, and longstanding hypogammaglobulinemia on/off replacement immunoglobulin with baseline IgG 300-400 mg/dL, low IgA 10-20 mg/dL, normal IgM 50-60 mg/dL, normal lymphocyte subsets, and absent protein and polysaccharide vaccine responses consistent with common variable immunodeficiency. On arrival at the ED, spinal imaging revealed a compression fracture and underlying mass. Right-axillary and bone marrow biopsies confirmed Burkitt lymphoma. He was treated with chemotherapy, radiation, and replacement immunoglobulin. He has suffered from pneumonia, adenovirus, ileus<b>,</b> heart failure, and stroke. Routine immunologic testing performed at time of diagnosis revealed normal complete blood cell count, mild transaminitis from baseline (AST/ALT 61/71 U/L), baseline immunoglobulins, and normal lymphocyte subsets. <h3>Discussion</h3> While KS is a well-known cause of hypogammaglobulinemia, the authors have identified only two other published cases of Burkitt lymphoma in KS. This case emphasizes the importance of oncological screening and that routine immunologic testing of lymphocyte subsets and immunoglobulins may not have abnormalities from baseline in patients with active lymphoma. A mild transaminitis, however, might be concerning for malignancy in these patients.

ODP524 Thyroid Storm Precipitated by COVID-19 Infection: A Case Report

Abstract Background Thyroid storm is an endocrinological emergency caused by severe thyrotoxicosis. COVID-19, caused by the novel coronavirus SARS-CoV-2, is known to cause thyroid-related complications of subacute thyroiditis but the occurrence of thyroid storm is rare. The use of first line therapies for thyrotoxicosis/thyroid storm, such as thioamides, radioactive iodine, and surgery, may be precluded by leukopenia, hemodynamic instability, and liver failure, which are commonly seen in severe COVID-19 infection. The necessity for isolation creates a challenge for surgical intervention for these patients. Here we present a unique case of thyroid storm secondary to Graves’ disease, reactivated by COVID-19 infection and managed with therapeutic plasma exchange (TPE). Clinical Case A 56-year-old African American female with history of hyperthyroidism for the past 13 years, presented to the emergency department with sore throat and fatigue for one week prior. On arrival, she was febrile with temperature of 101.1° Fahrenheit, tachycardic with heart rate of 163 bpm and tachypenic with respiratory rate of 41 rpm. Patient had bilateral orbitopathy, tender thyromegaly, thyroid bruit and fine tremors. She also had atrial fibrillation, right-sided heart failure, acute liver failure. Nasopharyngeal COVID-19 testing was positive; laboratory tests revealed TSH &amp;lt;0. 01 uIU/mL (n 0.450 - 5.330), free T4 &amp;gt;5.60 ng/dL (n 0.45 - 1.8), direct bilirubin 1.8 (n 0.1-0.3 mg/dl), mild transaminitis and INR 2.21 (n 0.9-1.1). White blood cell count was 5.4 K/uL (n 4.5-11.5) with 50.8% neutrophils (n 31-76%). Ultrasound of abdomen revealed decompensated cirrhosis with ascites. The Burch-Wartofsky score was 75 points, indicative of thyroid storm. Acute liver failure precluded the use of thioamides; due to the severity of the hyperthyroidism, ablation was not considered. The use of Lugol's iodine was held pending surgical clearance due to active COVID-19 infection. Eventually, patient underwent a total of four sessions of TPE. With each session free T4 levels decreased: 4.12 ng/dl, 2.73 ng/dl, 2.52 ng/dl, and 1.53 ng/dl, respectively. Six days after the last TPE, patient developed complications related to COVID-19 infection and expired before undergoing total thyroidectomy. Conclusion This is a complicated case of a patient with thyroid storm, acute liver failure in the setting of COVID-19 infection. SARS-CoV-2 virus may not only be a trigger for thyroid storm but also represents a challenge in the management of thyroid disease. During TPE, patients’ plasma is extracted from the components of the blood and a colloid replacement solution is infused back. Thyroxine binding globulin bound to thyroid hormones is removed with plasma and colloid replacement provides new binding sites for circulating free thyroid hormone. TPE is effective but rarely used in the past and can be considered as therapeutic for thyrotoxic patients with COVID-19 infection, in whom conventional methods of treatment are not feasible options. Presentation: No date and time listed

BRIGATINIB INDUCED PHOTOSENSITIVITY

<h3>Introduction</h3> Drug-induced photosensitivity is suspected when dermatitis develops in a sun-exposed distribution. Reactions occur by phototoxic, photoallergic, or immune-mediated mechanisms. Brigatinib is an oral tyrosine kinase inhibitor used in the treatment of non-small cell lung cancer. It causes skin rash in 24-40% of patients but is rarely linked with photosensitivity. We present a case of blistering dermatitis suspected secondary to brigatinib. <h3>Case Description</h3> A 65-year-old female with metastatic non-small cell lung cancer on brigatinib for one month presented with a pruritic maculopapular rash without systemic findings. She denied other symptoms or recent illnesses. Vitamin D supplement was the only other medication. Exam was notable for a maculopapular erythematous, partially blanchable rash in a malar distribution, a "V" pattern on the upper chest, flexor surface of arms, dorsal surface of hands with vesicular changes, and erythema of the vaginal labia. Laboratory workup was unremarkable including unchanged chronic mild transaminitis and no peripheral eosinophilia. The rash resolved with brigatinib cessation and mild to moderate potency topical corticosteroids over 2-3 weeks. A month later, brigatinib was reintroduced with sun exposure precautions and without recurrence of rash. <h3>Discussion</h3> We describe a case of suspected photosensitivity drug rash temporally related to use of brigatinib. Photosensitivity has been reported with signal transduction inhibitors, but only one other report is found in literature for brigatinib currently. Given the importance of treatment for this patient, brigatinib was reintroduced at full dose one month following the episode, with careful instructions regarding sun exposure, without rash recurrence.

Letermovir as Cytomegalovirus Prophylaxis in a Pediatric Cohort: A Retrospective Analysis

Letermovir is an attractive cytomegalovirus (CMV) prophylactic agent, but published data in children are scarce. This retrospective chart review aimed to describe our experience using letermovir as CMV prophylaxis in pediatric hematopoietic cell transplantation (HCT) recipients. Pediatric patients (age <20 years) undergoing allogeneic HCT and receiving letermovir prophylaxis in the Mayo Clinic Pediatric Bone Marrow Transplant Program were eligible for inclusion in this retrospective chart review. Medical records were reviewed to evaluate letermovir dosing, CMV levels, laboratory values, and reports of adverse effects. Between October 2020 and April 2022, 9 patients age 4 to 19 years undergoing allogeneic HCT in the Pediatric Bone Marrow Transplant Program received letermovir prophylaxis, either 240 mg or 480 mg daily at a mean and median dose of 10 mg/kg/day. Letermovir was crushed and administered via nasogastric tube in 4 of 9 patients. Two patients received letermovir for secondary CMV prophylaxis after initial treatment with ganciclovir/valganciclovir, and the remaining 7 received letermovir for primary prophylaxis. One patient, a 20-kg 6-year-old female receiving 240 mg (12 mg/kg), experienced low-level CMV viremia while on letermovir. No other patients experienced CMV reactivation while on letermovir prophylaxis. In 2 patients, transient mild transaminitis was noted within the first weeks of letermovir therapy, which resolved without intervention, and its relationship to letermovir could not be clearly established. Letermovir administration was feasible and well tolerated as CMV prophylaxis in our small cohort of pediatric patients undergoing HCT. Larger, prospective studies are warranted to confirm the safety and efficacy of letermovir in children. © 2022 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc.

FATAL CASE OF FULMINANT HEPATIC FAILURE DUE TO HERPES SIMPLEX VIRUS REACTIVATION IN SETTING OF IMMUNOSUPPRESSION FROM CHRONIC STEROID AND METHOTREXATE USE: A RARE PRESENTATION

FATAL CASE OF FULMINANT HEPATIC FAILURE DUE TO HERPES SIMPLEX VIRUS REACTIVATION IN SETTING OF IMMUNOSUPPRESSION FROM CHRONIC STEROID AND METHOTREXATE USE: A RARE PRESENTATION

UNDERSTANDING THE NEED FOR A BROAD DIFFERENTIAL DIAGNOSIS: A CASE OF PNEUMONIC TULAREMIA

UNDERSTANDING THE NEED FOR A BROAD DIFFERENTIAL DIAGNOSIS: A CASE OF PNEUMONIC TULAREMIA

S3190 The Great Masquerader: A Case of Syphilitic Hepatitis

Introduction: Syphilis, colloquially termed “the Great Imitator,” is a sexually transmitted infection caused by the spirochete treponema pallidum. Syphilis occurs in multiple stages. Tertiary syphilis occurs years after inoculation and presents with chronic granulomas, cardiovascular, and neurologic manifestations. Syphilitic hepatitis is a rare and often missed diagnosis in patients who have syphilis and who are often are co-infected with HIV or hepatitis B. Case Description/Methods: The diagnosis is made by both clinical presentations and positive serological markers, characteristic transaminitis, with no other alternative cause of hepatobiliary injury identified. Here, we highlight a case of an undomiciled 40-year-old male with HIV (on Genvoya) and chronic hepatitis B, who presented with tachycardia to 107. Physical examination was remarkable for a diffusely spread rash with erythema on the bilateral lower extremities, a small purulent boil on the right shin, left index finger and dry, itchy, distinct raised purple lesions on the scalp, eyebrows, upper and lower extremities, back, and shoulders. Laboratory findings were remarkable for a severely elevated alkaline phosphatase, mild transaminitis, and elevated total bilirubin, with negative pertinent imaging including a right upper quadrant sonogram, CT scan of the abdomen, and MRCP. Extensive additional work-up revealed elevated VDRL titers. Both a skin and liver biopsy were completed. Immunohistochemical stain of shave biopsy of a verrucous plaque on the scalp vertex and an excoriated papule of the left neck highlighted numerous spirochetes. Liver biopsy revealed hepatocellular necrosis with moderate mixed inflammation involving the portal tract and periportal hepatocytes, with immunohistochemical marker for spirochetes negative for organisms. However, given the patient’s clinical history of secondary syphilis involving the skin and lab abnormalities, it raised the differential diagnosis of syphilitic hepatitis (Figure). Discussion: With our case report and extensive research of the literature, we hope to shed light on the importance of certain infections, even those in decline, on the differential. Additionally, contemplation of coexisting infections often helps to contribute to diagnoses not otherwise common. Because of how rarely seen syphilitic hepatitis is, it is often a missed diagnosis, but we are hopeful our case report helps physicians with patients with similar presentations, especially patients with otherwise unexplained high alkaline phosphatase levels.Figure 1.: Skin Findings.

S2449 A Unique Case of Simultaneous Anal Squamous Cell Carcinoma and Esophageal Squamous Cell Carcinoma

Introduction: Anal cancer (AC) is uncommon and comprises only 3% of all digestive system malignancies. It is associated with HPV, tobacco use, and HIV. Esophageal cancer (EC) is the 8th most common cancer and 6th most common cause of death worldwide. Among other associations, HPV and tobacco use has been strongly linked to development of esophageal SCC. Though they have similar risk factors, the literature is limited when it comes to cases of simultaneous anal SCC and esophageal SCC. Case Description/Methods: A 50-year-old male with history of tobacco use presented with dysphagia, dyspnea, and weight loss. His symptoms were progressive with 20 lbs. of weight loss in 3 months. He initially had solid food dysphagia which progressed to liquids and constant regurgitation of food. His cough and dyspnea were acute and worsened 1 week prior to his presentation. He endorsed a bulging growth around his anus that grew over several months. He was found to have a left lower lobe necrotizing pneumonia (NP) on CT scan as well as thickening of the esophagus with liver lesions suspicious for metastatic disease. Labs showed leukocytosis, macrocytic anemia, and a mild transaminitis. He was tested for tuberculosis and HIV which was negative. He underwent an EGD which showed a large, friable, fungating esophageal mass whose biopsies showed SCC. For his anal lesion, he underwent an excisional biopsy which was positive for SCC as well. The patient was treated with antibiotics for his NP with a plan of 6 weeks of therapy followed by repeat imaging to determine if any surgical interventions would be needed. Oncology planned for palliative chemoimmunotherapy once his NP resolved. To improve his dysphagia, a palliative esophageal stent was placed (Figure). Discussion: This patient had both a primary anal SCC and esophageal SCC with his only risk factor being tobacco use. Though both AC and EC commonly metastasizes to the liver, EC is more likely to metastasize. For esophageal SCC, local lymph node invasion typically occurs early since the lymphatics are in the lamina propria rather than beneath the muscularis mucosa. In this case, the patient presented with a NP and though no definitive fistula was noted on imaging, local invasion of esophageal SCC can present with fistulizing disease. Unfortunately, Stage 4 esophageal SCC is incurable though systemic therapies may provide a palliative effect and survival benefit. In this case, an endoscopic esophageal stent was placed for palliation of his dysphagia while awaiting chemoimmunotherapy.Figure 1.: Image A demonstrates the CT scan finding of esophageal wall thickening. Image B is the EGD finding of a large, friable, fungating, circumferential esophageal mass. Image C shows the successful placement of an esophageal stent for palliative treatment of the patient’s dysphagia.