LANGERHANS CELL HISTIOCYTOSIS IN A CHILD WITH MULTISYSTEMIC LESIONS ASSOCIATED WITH INFECTED POLIOMYELITIS AND SARS-COV-2, FEATURES OF DIAGNOSTICS. CLINICAL CASE.

Langerhans cell histiocytosis (LCH) is an abnormal clonal proliferation of Langerhans cells. The prognosis varies depending on the form of the disease and organ damage. Any organs and systems can be involved in the pathological process in various combinations. A poor response to standard therapy and an unfavorable prognosis are characteristic of patients with a multisystem form of LCH and involvement of organs at risk. Skin lesions are a classic sign of LCH. Purpose - to describe the complexity and duration of diagnosis of LCH with multisystem damage in a boy aged 2 years and 2 months, infected with poliomyelitis and coronavirus. Clinical case. The first clinical manifestations of LCH in the child debuted with an eczematous-seborrheic rash on the scalp with spread to the limbs and trunk. The child was treated for toxicoderma, hemorrhagic vasculitis at the place of residence for 6 months. The boy lost 1.5 kg of body weight in 1 month. At the time of hospitalization, seborrheic-eczematous rashes on the skin with a hemorrhagic component, trophic-inflammatory changes in the nails of the hands, signs of protein-energy deficiency, stomatitis, gingivitis, hepatosplenomegaly, polyserositis, diabetes insipidus, osteolytic foci of the frontal bones were found. Results of the tests: anemia, thrombocytopenia, hypoproteinemia and hypoalbuminemia, coagulation disorders. The patient had the onset of lower flaccid paraparesis, muscle hypotonia. The boy was diagnosed with a number of infectious complications, including poliomyelitis (a derivative of vaccine poliovirus type 2), COVID-19. The child received LCH-III cytostatic therapy with a positive effect. The research was carried out in accordance with the principles of the Helsinki Declaration. The informed consent of the patient was obtained for conducting the studies.Copyright © 2023 Institute of Physics of the Russian Academy of Sciences. All rights reserved.

Fatal COVID-19 in an infant prompted an early diagnosis of ZNFX1 deficiency in a sibling

Background: NFX1-type zinc finger-containing 1 (ZNFX1) is an interferon-stimulated double-stranded RNA sensor that restricts the replication of RNA viruses in mice. ZNFX1 deficiency in humans is very rare;to date, only fifteen cases have been reported by Vavassori S et al. (10.1016/j.jaci.2021.03.045). The disease presented in all cases as severe viral infections complicated by multisystem inflammation evolved to multiorgan failure with a high mortality rate. Pediatric Allergy and Immunology Section at Queen Rania Children's Hospital in Jordan had confirmed the diagnosis of ZNFX1 deficiency in an infant at his first presentation with severe viral illness based on the positive family history of one sibling death caused by complicated COVID-19 infection. Case presentation: A 12-month-old boy was born to consanguineous parents, full-term, with no NICU admission. He was doing well till the age of four months when he was admitted to the hospital with fever, hypoactivity, and maculopapular skin rash. On admission, he was ill, hypoactive, and febrile, and a physical exam showed hepatosplenomegaly and maculopapular skin rash. His lab showed thrombocytopenia, elevated transaminases, hyperferritinemia, and high CRP;he was treated with broad-spectrum antibiotics, but he continued to deteriorate, and his infectious workup was unrevealing, including COVID-19 PCR. His older sibling died at eight months in 2020 when she got a COVID-19 infection, deceased after rapid deterioration evolved to multiorgan failure. Unfortunately, she had no stored DNA, as she was treated at a peripheral hospital. Based on this presentation and the fatal COVID-19 infection, pediatric immunology service got consulted;we did an immunological workup, which showed normal lymphocyte subsets, Immunoglobulins, and bacterial antibodies. Whole exome sequencing showed a homozygous frameshift mutation in the ZNFX1 gene, protein change defect had detected;p.Tyr555MetfsTer6, and nucleotide change variant: c.1663_1665delTACinsAT. Family screening showed heterozygous for the same variant in both parents and a healthy sibling. The patient was diagnosed with the hemophagocytic lymphohistiocytosis-like disease and treated with steroids, intravenous immunoglobulin, and antimicrobials, he showed complete recovery, and we are going to do bone marrow transplantation as his brother is 8/8 HLA matched.Copyright © 2023 Elsevier Inc.

Bupivacaine-Induced Hepatotoxicity in a Healthy Patient Without Chronic Liver Disease After Shoulder Arthroscopy

Introduction: Bupivacaine is a local anesthetic which has been increasingly used in the post-operative state for pain control. Hepatotoxicity is a rare complication, and few cases are reported in patients with chronic liver disease. We present a case of acute liver injury from bupivacaine use in a healthy patient without prior history of liver disease. Case Description/Methods: A 68-year-old female with a past medical history of primary hypertension and recent nontraumatic complete tear of the right rotator cuff, presents to the hospital with fatigue, loss of appetite, and nausea. She recently underwent an arthroscopy of the right shoulder with repair of the rotator cuff two weeks prior. Her surgery was uncomplicated, and patient was started on bupivacaine ONQ pump infusion at 5 ml/hr for three days for post-operative pain. Further history reveals patient is non-alcoholic without prior liver disease, including cirrhosis. Review of systems is concerning for associated generalized abdominal discomfort. Physical exam demonstrated jaundice with scleral icterus with mild periumbilical tenderness to palpation without hepatosplenomegaly or ascites. Labs demonstrated elevated total bilirubin of 10.2 mg/dL with Alkaline phosphatase, ALT, and AST being 924 U/L, 429 U/L, and 279 U/L, respectively. Imaging studies including CT abdomen and pelvis with contrast, abdominal ultrasound, MRCP, and portal vein doppler were negative. Additional work up for underlying liver disease including acetaminophen and ethanol levels, SARS-CoV2, Hepatitis panel, EBV antigen, and urine toxicology were negative. It was determined patient had bupivacaine induced hepatotoxicity. Patient's health improved with conservative management and she was discharged with instructions for close monitoring of her LFTs. Discussion(s): Bupivacaine is an amino-amide anesthetic which binds to the intracellular portion of voltage-gated sodium channels and prevents depolarization of pain signals. It is metabolized by the liver and thus reports of hepatotoxicity, although rare, occur in patients with underlying liver pathology. Our patient became symptomatic with acute rise in LFTs. An extensive workup for other etiologies of acute liver toxicity was negative. Rapid vascular uptake of the drug is the most common reason for bupivacaine toxicity;and this remains a possibility for the mechanism of toxicity in our patient. A prior case report of bupivacaine hepatotoxicity demonstrated a cholestatic pattern, which is consistent with our findings.

A Case Report of Ivermectin-Induced Liver Failure

Introduction: Ivermectin is an antiparasitic medication that is primarily metabolized by the liver. During the COVID-19 pandemic, researchers demonstrated that Ivermectin successfully inhibited the replication of SARS-COV-2 in vivo, but current research has failed to demonstrate clinical benefit for treatment of COVID-19. Despite this, misinformation campaigns have misled patients to ingest Ivermectin at concentrations meant for domestic animals. Here, we present a case of acute liver failure secondary to the use of Ivermectin. Case Description/Methods: A 61-year-old man with medical history of ischemic cardiomyopathy with last echocardiogram showing ejection fraction at 21%, atrial fibrillation on warfarin for oral anticoagulation, and previously treated Hepatitis C presented with generalized weakness and yellowish discoloration of the skin worsening over the last two weeks. The patient denied significant alcohol use, acetaminophen use, or illicit drugs. He admitted to injecting himself with two doses of weight-based horse ivermectin, for COVID prophylaxis, two weeks prior to his presentation. Physical exam was pertinent for scleral icterus and hepatomegaly with no abdominal tenderness. Initial labs revealed elevated liver chemistries in a mixed pattern (Figure 1). Acute hepatitis panel, HSV, and CMV were negative. Hepatitis C antibodies were positive, but the patient was in sustained virologic response. Full workup for chronic liver disease was unremarkable. Ultrasound revealed hepatosplenomegaly with patent portal and hepatic vasculature. Subsequently, the patient developed hepatic encephalopathy along with his coagulopathy, raising concern for acute hepatic failure. The patient was transferred to the ICU and started on NAcetylcysteine, rifaximin, and supportive care. The patient recovered well and fortunately did not require liver transplant. Discussion(s): While the FDA recommends against the use of Ivermectin for COVID-19, many continue to inappropriately consume it. Ivermectin-induced liver failure is a rare but deadly side effect. Given our patient's rapid onset of symptoms post-self injection of Ivermectin, his liver injury was presumed to be related to Ivermectin. The drug interaction between Ivermectin and warfarin had worsened the patients coagulopathy. Physicians should be aware of the ways Ivermectin overdose may clinically present to avoid delayed treatment. This case demonstrates the detriments of perpetuation of medical misinformation to care.

Differentiating Multisystem Inflammatory Syndrome in Children (MIS-C) and Its Mimics - A Single-Center Experience From a Tropical Setting

OBJECTIVES: Identifying clinical and laboratory indicators that differentiate multisystem inflam-matory syndrome in children (MIS-C) apart from other febrile diseases in a tropical hospital setting. METHOD(S): Review of hospital records done in a tertiary care exclusive children's hospital for children admitted from April, 2020 till June, 2021. Laboratory values, severe acute respiratory syndrome coronavirus (SARS-CoV-2) serological status, and clinical signs and symptoms of patients with MIS-C, and those with similar presentations were analyzed. RESULT(S): 114 children fulfilled the inclusion criteria (age group of 1 mo-18 y) for whom a diagnosis of MIS-C was considered in the emergency room based on the clinical features. Among them, 64 children had the final diagnosis of MIS-C, and the remaining 50 children had confirmatory evidence of infections mimicking MIS-C such as enteric fever, scrub typhus, dengue and appendicitis. CONCLUSION(S): Older age group, presence of muco-cutaneous symptoms, very high C-reactive protein, neutrophilic leukocytosis, abdominal pain and absence of hepatosplenomegaly favor a diagnosis of MIS-C.

Case report: Covid-19 and disseminated tuberculosis coinfection unveiling catastrophic antiphospholipid antibody syndrome: An association or de novo phenomenon

Background: Disseminated infections such as tuberculosis are known to result in a systemic inflammatory response leading to thrombosis, with increasing reported cases of thrombotic event being observed in patients infected with covid-19. This is the first reported case on co-infection with COVID-19 pneumonia and disseminated tuberculosis causing catastrophic antiphospholipid syndrome (CAPS). Method(s): The report highlighted the challenges in the diagnosis and management which include the use of corticosteroid in setting of systemic infections. Another diagnostic dilemma was to explain the cause of myositis by tuberculous or autoimmune. Case Presentation: We report a 26-year- old man with HbE trait thalassemia who reported unintentional weight loss, night sweats for 1 month prior to the diagnosis of covid-19 infection on 10th March 2022. Seven days later, he was hospitalized for suspected perforated appendix. Computed tomography (CT) abdomen revealed hepatosplenomegaly, prostatitis, seminal vesiculitis. Multiple matted abdominal lymph nodes were not amenable for biopsy. Soon, he appeared toxic, dyspneic required non-invasive ventilation with bilateral parotitis. He had raised erythrocyte sedimentation (ESR) 52 mm/hour, C-reactive protein (CRP) 221 mg/dl, lactate dehydrogenase (LDH) 730U/L. Direct Coomb's antibody was positive but did not have any form of haemolysis. Complement 3 (0.45 g/L) and complement 4 (0.1 g/L) levels were low. Serum IgG4, procalcitonin, anti-nuclear antibody, cultures and virology were negative. Sputum for acid fast bacilli (AFB) was positive on Auramine O stain but the Ziehl-Nelson (ZN) stain and tuberculous PCR (GeneXpert) were negative. Diagnosis of disseminated tuberculosis was made but his abdominal pain persisted despite being on anti-tuberculous therapy (ATT), and he had new evidence of splenic infarct. CT angiogram also revealed celiac trunk and superior mesenteric artery thrombosis. Antiphospholipid (aPL) test was positive for lupus anticoagulant, beta 2 glycoprotein 1 and anti-cardiolipin antibodies. Therapeutic anticoagulation and plasma exchange were initiated for probable CAPS followed by intravenous immunoglobulin and corticosteroid. Thereafter, the patient developed severe bilateral pelvic girdle pain with evidence of myositis on the MRI (Figure 2). Serum creatine kinase was never elevated. Anti-PL- 7 and anti Ro-52 were borderline elevated. He recovered well and ambulant before discharged home. Conclusion(s): Our case highlight the complexicity of presentation of CAPS who manifested as multiple arterial thrombosis. The diagnosis of disseminated tuberculosis relied strongly on microbiological, imaging and clinical presentation as histopathological evidence was not feasible. Management challenges were deciding on corticosteroid in disseminated infection and the need for confirmation of persistent positive aPL test and to monitor myositis symptom to help guide decision making. (Figure Presented).

An Unusual case of epstein-barr virus hepatitis mistaken for multisystem inflammatory syndrome in children

Case Report: As COVID-19 infections became more common, children began presenting with multisystem inflammatory syndrome (MIS-C). It can be difficult to distinguish rare presentations of common diseases from MIS-C, especially when there has been a close contact with COVID-19. Epstein-Barr virus (EBV) is a universally common infection with 90% of individuals showing serological signs of past infection. Both MIS-C and EBV can present with similar signs and symptoms. Our case aims to remind the reader to keep in mind uncommon presentations of common viral infections which may mimic MIS-C. Case Presentation: A previously healthy 5-year-old girl presented with persistent fevers for 12 days, associated with stomatitis, vomiting, and diarrhea. Physical exam was significant for a moderately ill-appearance, small (<1 cm) left posterior cervical lymphadenopathy, and soft palate and buccal oral ulcers. Initial labs (see Table) revealed leukocytosis with reactive lymphocytes and cholestatic hepatitis with mild coagulopathy. Although she had no respiratory symptoms, CT chest revealed left upper lobe pneumonia. Abdominal ultrasound showed diffuse hepatosplenomegaly, gallbladder wall thickening, and enlarged epigastric lymph nodes. Echocardiogram showed normal systolic function and coronary arteries without dilation. Extensive viral and bacterial nasal swab and serologic testing, including for SARS-CoV-2 antibodies, was negative. On Day 2, her Monospot was positive, along with EBV viral capsid antigen IgM and IgG with the absence of EBV nuclear antigen IgG. In addition, serum PCR was positive for EBV. Management and Outcome: Due to persistent fevers on Day 3 of broad-spectrum antibiotics, coupled with a close contact with active COVID infection, she was treated with the MIS-C protocol of intravenous immunoglobulin G (IVIG), prednisone, and aspirin. Within a day of IVIG, she improved clinically and fever resolved. By discharge on Day 8, her lab values had begun to normalize. Discussion(s): EBV is known to present in children with typical infective mononucleosis symptoms such as fever, sore throat, and lymphadenopathy. However, these can be lacking which makes the diagnosis challenging. Although hepatitis is a common sequalae of EBV, EBV induced pneumonitis and stomatitis are rare, especially in immunocompetent individuals. While our patient improved after treatment with IVIG, suggesting MIS-C, we still attribute her illness to EBV, as IVIG has been shown to provide antiviral and anti-inflammatory benefit in EBV infections. This case highlights the challenge of recognizing and overtreating rare presentations of common viral infections in the face of an emerging disease such as MIS-C. Significant Laboratory Values [Table presented] Copyright © 2023 Southern Society for Clinical Investigation.

Modified Treatment for Pediatric Multisystemic Histiocytosis during Sars-Cov2 Lockdown. Series of Cases

Purpose: Backbone treatment ofmultisystemic histiocytosis (MS-LCH) is steroids in combination with chemotherapy (vinblastine/vincristine and/or cytarabine). This approach requires a central venous access (CVA) placement because of the possibility of citostatic extravasation and length of treatment. SARS-CoV2 lockdown forced us to adapt standard treatment in order to skip CVA placement, use of available cytostatics, reduce toxicity and hospital visits. We report here our experience using a modified treatment (MT) Methods:Series of 4 pediatric patients (pt) of MS-LCH treated during 2020 with a MT. Induction: Oral Methylprednisone 40 mg/m2 daily for 4weeks, tapering for 2weeks, and subcutaneous/intravenous cytarabine 100 mg/m2/day for 4 days, day 1-14. Evaluation at 6th week. If NAD or ADB, continuation treatment: Methylprednisone 40 mg/m2/day for 5 days every 15 days and subcutaneous/intravenous cytarabine 100 mg/m2/day for 4 days every 3 weeks. Clinical and hematologic evaluation every 3 weeks. We studied the presence of circulating CD207+/CD1a+ cells (cc) by flow cytometry Results:Female 3pt. Identical twins (pt#1,2). Age at diagnosis: 7, 7, 11 and 29 months. Involvement: skin, lymph nodes and hematopoietic (pt#1,2,3,4), ear (pt#2,3,4), bone (pt#3), hepatosplenomegaly (pt#4) All pt achieved ADB after 6 weeks of treatment. Reactivation: 1pt because of non-adherence to treatment. No grade 3/4 toxicity. COVID infection with mild symptoms (pt#1,2). Status: all alive with NAD at 2 years (pt#1,2) and 1 year (pt#3,4) of treatment. All pt started with a low score for cc and increased them with the treatment in negative trend to their clinical status Conclusion(s): This MT was feasible to treat pt with MS-LCH during the SAR-Cov2 lockdown, even those with risk organ involvement.We were able to skip CVA and reduce toxicity. Treatment could be restraining cc migration to the lesions.

DIFFUSE ALVEOLAR HEMORRHAGE SECONDARY TO IMMUNE THROMBOCYTOPENIA FOLLOWING SARS-COV-2 VACCINATION: A CASE REPORT

SESSION TITLE: COVID-Related Critical Care Cases SESSION TYPE: Case Reports PRESENTED ON: 10/19/2022 11:15 am - 12:15 pm INTRODUCTION: We present a case of diffuse alveolar hemorrhage (DAH) secondary to Immune Thrombocytopenia (ITP) temporally related to SARS-CoV-2 (CoV) vaccine. CASE PRESENTATION: An 80-year-old female presented with dyspnea, hemoptysis, diffuse petechiae, and ecchymosis;no focal neurological deficits or hepatosplenomegaly. She had no history of bleeding or autoimmune disorders;no recent respiratory or gastrointestinal infections;but received Moderna CoV vaccine 4 weeks prior to presentation. Chest X-ray (CXR) and CTA of chest demonstrated multifocal bilateral patchy airspace opacities. Initial platelet was 1 x 109/L with normal morphology of platelet and WBC, and no schistocytes. Coagulation panel, LDH, haptoglobin, and bilirubin were all normal. CoV NAAT was negative. Dexamethasone and IVIG for high suspicion of ITP was initiated. Supportive care including platelet transfusion and oxygen via nasal cannula was maintained. Platelets were severely consumed in spite of treatment with platelets undetectable at nadir and rapid decrease of hemoglobin, approximately 6 g/dL, within 24 hours of admission. IgM and IgG plasma platelet autoantibodies returned positive, confirming ITP diagnosis. Additional workup was unremarkable for infections, rheumatologic disorders, and malignancy. Respiratory state rapidly declined with worsening hemoptysis and significant increase of bilateral airspace opacities on repeat CXR, indicative of DAH. Lung protective mechanical ventilation protocol was initiated on day 2 with medically induced deep sedation and paralysis to minimize hemorrhage exacerbation. Rituximab, romiplostim, and nebulized tranexamic acid were added for severe and refractory ITP, which eventually slowed platelet consumption, reduced pulmonary hemorrhage, and stabilized hemoglobin. Platelets recovered above 30 x 109/L on day 9, and subsequent bronchoscopy showed persistent blood on bronchoalveolar lavage. She was successfully extubated after prolonged 14-day intubation. Platelet normalized before discharge. DISCUSSION: Incidence of ITP related to CoV vaccine is approximately 0.8-0.9 case per million vaccinated. Most cases present with superficial bleeding and respond to first-line agents with rapid recovery. GI bleeding and intracranial hemorrhage, but not DAH, have been reported in several cases, requiring third-line agents to promote platelets recovery and achieve hemostasis. We report a case of DAH secondary to ITP following CoV vaccine. Temporal relationship and severe presentation are consistent with other reports of ITP with life-threatening internal bleeding probably secondary to CoV vaccine. CONCLUSIONS: When DAH is suspected, rapid escalation of treatment to include third-line agents is desired. If intubated, lung protective ventilation with paralysis is preferred to minimize further lung injury due to DAH. Reference #1: Lee EJ, Cines DB, Gernsheimer T, et al. Thrombocytopenia following Pfizer and Moderna SARS-CoV-2 vaccination. Am J Hematol. 2021;96(5):534-537. doi:10.1002/ajh.26132 doi:10.1016/J.VACCINE.2021.04.054 Reference #2: Welsh KJ, Baumblatt J, Chege W, Goud R, Nair N. Thrombocytopenia including immune thrombocytopenia after receipt of mRNA COVID-19 vaccines reported to the Vaccine Adverse Event Reporting System (VAERS). Vaccine. 2021;39(25):3329-3332. Reference #3: Tarawneh O, Tarawneh H. Immune thrombocytopenia in a 22-year-old post Covid-19 vaccine. Am J Hematol. 2021;96(5):E133-E134. doi:10.1002/ajh.26106 DISCLOSURES: No relevant relationships by Timothy Barreiro No relevant relationships by Tiewei Cheng No relevant relationships by Zeina El Amil No relevant relationships by Jin Huang No relevant relationships by Sanaullah Khalid

Coronavirus-2019 Disease with Pancytopenia with Leptospirosis and Herpes Simplex Virus Co-infection

Aim and background: COVID-19 pandemic has affected the whole world. Besides COVID, many infections may emerge during the course of the disease. Lymphopenia, use of immunosuppressants underlying comorbidities, and immune dysregulation secondary to SARS-CoV-2 could be the likely cause of the emergence such infections. We hereby describe a case of COVID-19 disease which presented with pancytopenia and was found to have Leptospirosis and Herpes Simplex Virus co-infection. Case summary: A 23-yearold postpartum female with no comorbidities and uneventful obstetric history was referred to our hospital 2 weeks after a full-term normal vaginal delivery. She developed generalized convulsive status epilepticus on the 10th day of her delivery, which was managed elsewhere with anti-epileptic drugs (AEDs). During her hospital stay, RTPCR for COVID-19 turned out to be positive but she remained asymptomatic throughout the course of her illness and seizures remained well-controlled on AEDs. On admission to our hospital, she was fully conscious, alert with no focal neurological deficits. Notable findings on evaluation were pancytopenia with megaloblastic features, bilateral pedal edema, and hepatosplenomegaly. NCCT brain was done which was suggestive of subarachnoid hemorrhage (SAH) along bilateral parietooccipital region for which conservative management was planned. 2D echocardiography was normal. Ultrasonography of abdomen revealed gross splenomegaly and mild hepatomegaly with mesenteric lymphadenopathy. NCCT thorax and abdomen were unremarkable apart from hepatosplenomegaly. In the panel sent for pancytopenia workup, IgM anti-HSV 1 antibodies turned out to be positive in blood. In addition, tropical workup was suggestive of Leptospirosis (IgM antibodies were positive). Workup for tuberculosis was negative. Bone marrow workup revealed features of trilineage hematopoiesis with micronormoblastic maturation consistent with iron deficiency anemia with no evidence of hemophagocytosis. Subsequently, IV acyclovir, IV doxycycline, and iron replacement were added. She improved clinically after these therapies and was subsequently discharged in a stable condition. MRI brain with MR angiography and venography done before discharge showed T1 sulcal hyperintensities along bilateral parietooccipital regions suggestive of SAH which was not progressing (as compared to NCCT brain scan done at admission). On day 60 of telephonic follow-up, patient was doing well and leading normal life without any persistence or emergence of symptoms.

Paediatric Mediastinal Masses: Case Series: Intensivist Perspective

Introduction: Mediastinal masses in the paediatric population pose a challenge for diagnosis and acute management especially when they present with compression of mediastinal structures. Objectives: To study clinical, radiological, and pathological characteristics, treatment, complications, and outcome of patients with mediastinal masses admitted to IPCU with emphasis on respiratory support provided. Materials and methods: Retrospective analysis of medical records of patients admitted with mediastinal masses between 1st July 2020 and 31st October 2021 in PICU at B.J.Wadia Hospital for Children. Results: 10 patients (6 months to 16 years) were included. The common presenting symptoms were breathlessness (90%), orthopnea (44%), cough (40%), fever (40%), and weight loss (20%). One patient had superior vena cava syndrome, 50% had hepato-splenomegaly/lymphadenopathy. One patient was diagnosed outside as a yolk sac tumour and referred. Three patients were wrongly treated as TB before they were referred. The average duration of symptoms before presenting to the hospital was 82.7 days. Airway compression was seen on a CT scan in 6/10 patients. Mechanical ventilation was required in 6 patients and non-invasive ventilation in three. The mean duration of mechanical ventilation was 13.1 days. All the patients required PEEP >7 cm H2O, propped up position, and intermittent desaturations requiring an increase in ventilator settings for a short duration of time or use of paralytics/sedation boluses. Difficult intubation was encountered in 2 patients of whom a smaller size tube was used in 1 patient. Bronchoscopy, LMA insertion was not required in any. Tissue for diagnosis was obtained by CT-guided or USG-guided LN biopsy. 80% needed a mediastinal mass biopsy. During the biopsy, procedural sedation was done using drugs propofol or ketamine which was well tolerated. CT-guided retroperitoneal lymph node biopsy was inconclusive in 1 patient and eventually required open inguinal lymph node biopsy. Final diagnoses included: T cell ALL in 2 patients, AML, classical Hodgkin's lymphoma, neuroblastoma, alveolar rhabdomyosarcoma, yolk sac tumour, teratoma, tuberculosis, in single cases. Definitive diagnosis could not be confirmed in 1 child though blood EBV PCR came positive (viral copies >105 copies/mL) after the child expired. The mean time from symptom onset to diagnosis was 90 days. The mean time from presentation to diagnosis was 7.2 days. The mean duration of IPCU stay was 15.8 days. Patient with yolk sac tumour was COVID-19 positive who later developed peripheral digit gangrene. 7 patients received chemotherapy, 1 patient received AKT and one underwent surgical resection of tumour. Complications encountered were AKI (10%), TLS requiring hemodialysis (10%), and chylothorax (10%). Mortality was 50% of whom 2 did not respond to chemotherapy and 3 had intercurrent events. 5 children were discharged from the unit. Conclusion: At our centre, mediastinal masses are frequently malignant in origin. Though TB is common in our country, not all mediastinal masses are TB. All the effort should be made to obtain microbiological/tissue diagnosis before initiating the treatment. Intubating and ventilating a mediastinal mass is a challenging task and those who require intubation have a poor prognosis. Late diagnosis and associated poor prognosis are glaring, prompting for early intervention to improve outcome.

Hemophagocytic Lymphohistiocytosis after COVID-19 Vaccination: A Case Report

Aim and background: Cases of thrombotic thrombocytopenia induced by coronavirus disease 2019 (COVID-19) vaccines have been reported recently. Herein, we describe hemophagocytic lymphohistiocytosis (HLH) following COVID-19 vaccination. Case report: A 35-year-old male, chronic alcoholic, 3 years into abstinence received first dose Covishield vaccine. He started developing a fever, testicular pain, diminished sensorium requiring invasive ventilation, and decreased urine output 4 days after getting vaccinated. Initial workup for NCCT brain and HRCT chest was normal, tropical fever panel was negative, cultures for blood and endotracheal aspirate were sterile, liver and renal functions showed mild derangement, CSF study was normal. Ultrasound examination of the abdomen revealed mild hepatosplenomegaly, mild testicular swelling, and suprainguinal lymphadenopathy, with no focus of infection. Subsequently, he developed bicytopenia with haemoglobin 9.0 g/dL and platelet counts 50 × 109/L, ferritin 2130 μg/L, triglyceride 353 mg/dL, and decreased fibrinogen 1.41 g/L. Bone marrow as well as lymph node biopsy showed haemophagocytosis with engulfment of neutrophils, lymphocytes, and normoblasts making HLH a likely diagnosis. Soluble CD25 and NK cell function could not be performed. Extensive evaluation was done to look into the etiology of HLH. SARS-CoV-2 reverse transcriptase-polymerase chain reaction (RT-PCR) test was negative. RT-PCR test for Epstein-Barr virus (EBV), influenza A (H1N1, H3N2), influenza B, cytomegalovirus (CMV) performed from endotracheal aspirate (ETA) was negative. Similarly, the RT-PCR test from serum samples for EBV, Parvo B-19, CMV, and from CSF sample for EBV, Parvo B-19, CMV, and HSV-1 was negative. Hepatitis B, C, and HIV serologies were negative. Culture and sensitivity repeated from blood, ETA and urine was sterile. Autoimmune panel including complements levels were negative. Peripheral smear, bone marrow, and lymph node biopsy were normal and did not reveal abnormal or malignant cells. He had persistent fevers to 38.6°C during the first 6 days of his admission, with a rise in his ferritin to 1950 μg/L. The patient received steroids but not etoposide. By the 8th day, his fevers resolved, with improvement in his lethargy and malaise. Two weeks later, his ferritin had reduced to 510 μg/L, platelet count rose to 180 × 109/L, and repeat ultrasound abdomen demonstrated resolution of his splenomegaly. In our patient, there was no clear precipitant of HLH other than the Covishield vaccine. There was no evidence of an infection or malignancy. Due to our patient's clinical stability, resolution of symptoms, and improvement of HLH parameters he did not require HLH specific therapy. It is unclear if he had a pre-existing genetic predisposition to HLH as genetic testing is pending, however, it is unlikely as he has reached the age of 35 and suffered from previous viral infections without developing HLH.

A Case Report of Coronavirus (COVID-19) Disease and Herpesviridae Viral Co-Infections: A Lethal Combination? ABS0138)

Introduction: COVID-19 pandemic has affected the whole world. Besides COVID, other viral infections may emerge during the course of the disease owing to lymphopenia, use of immunosuppressants, underlying comorbidities, and immune dysregulation, which may pose additional threats.1 We hereby describe two cases of COVID- 19 with viral co-infections belonging to the Herpesviridae family with undulating clinical course. Case 1: Cytomegalovirus (CMV) Co-infection: A 55-year-old male, COVID unvaccinated, chronic smoker, overweight and hypertensive was admitted to our ICU with a 1-week history of fever, cough, and breathlessness. SARSCoV- 2 reverse transcriptase-polymerase chain reaction (RT-PCR) test was positive. At admission, he had hypoxaemia (SpO2 86%on room air), respiratory rate 35-40/minute, and ground-glass opacities in chest X-ray involving 50% of bilateral lung parenchyma suggestive of severe COVID-19 pneumonia. He was managed with lung-protective invasive mechanical ventilation, restrictive fluid strategy, 16-18 hour/day proning sessions (4-5), intravenous (IV) remdesivir, IV dexamethasone 6 mg 12 hourly, and enoxaparin thromboprophylaxis. After 2 weeks of ICU stay, weaning was attempted but the weaning attempts failed due to underlying neuromuscular weakness. On examination, bilateral (B/L) cranial nerve palsies, areflexia, and motor power 0/5 in bilateral upper and lower limbs were noticed. possibility of Guillain-Barre syndrome (GBS) was kept and IV immunoglobulin therapy was empirically administered for 5 days with some improvement in power up to 1/5 in upper limbs. On day 35 of hospitalization, he developed pancytopenia along with features of deranged liver function and gut dysfunction. In evaluation, PCR for CMV turned out to be positive in blood. Bone marrow aspiration and biopsy showed hemopoiesis with viral inclusion bodies and hemophagocytosis (HLH) [Figs 1 and 2]. A diagnosis of secondary HLH related to CMV was contemplated and IV ganciclovir was initiated along with steroids. Histological evidence of CMV co-infection was present and moreover, the quantitative viral load of CMV showed a decreasing trend after initiating IV gancyclovir. However, the patient continued to deteriorate and succumbed to his illness in the 8th week of the ICU stay. Case 2: Herpes Simplex Virus (HSV) Co-infection: Twenty-three years postpartum female with no comorbidities and uneventful obstetric history was referred to our hospital two weeks after a full-term normal vaginal delivery. She developed generalized status epilepticus on the 10th day of delivery, which was managed with anti-epileptic drugs (AEDs). During the hospital stay, RTPCR for COVID-19 turned out to be positive but she remained asymptomatic and seizures were well-controlled on AEDs. On admission to our hospital, she was fully conscious and alert with no neurological deficits. Notable findings were pancytopenia with megaloblastic features, B/L pedal edema, and hepatosplenomegaly. NCCT brain revealed mild subarachnoid hemorrhage (SAH) along the bilateral parietooccipital region for which conservative management was planned. 2D echocardiography was normal. Ultrasonography of the abdomen showed gross splenomegaly and mild hepatomegaly with mesenteric lymphadenopathy. NCCT thorax and abdomen were unremarkable apart from hepatosplenomegaly. In pancytopenia workup, IgM anti-HSV-1 antibodies turned out to be positive in blood. In addition, tropical workup was suggestive of Leptospirosis (IgM antibodies positive). Serological evidence was suggestive of acute HSV-1 infection (based on antibody titers). Bone marrow workup had features of trilineage hematopoiesis with micronormoblastic maturation consistent with iron deficiency anemia without any evidence of hemophagocytosis. IV acyclovir, IV doxycycline, and iron replacement were added, after which she improved clinically and was discharged in stable condition. Tables 1 and 2 show a detailed description of these cases. Discussion: Herpesviridae family is the most important group of viruses responsible for persistent vi al infections in humans, of which CMV contributes to 60-90% of infections in adults, especially in developing countries.2 In healthy individuals, these viruses are kept dormant by the body's immune mechanisms but in an immunocompromised population, reactivation from the latent state can occur. SARS-CoV-2 infection predisposes patients to concomitant viral co-infections, owing to T-cell lymphopenia, decreased NK cell number, and use of immunosuppressive medications.3,4 The first case of CMV co-infection was first reported by D'Ardes and co-workers in 2020.5 Since then, many studies have been emerging in this area. In an observational study from France, 38 COVID-19 patients on >7 days of MV were studied for HSV and CMV pulmonary co-infections (by quantitative real-time PCR in tracheal samples) out of which 47% of patients had one of these infections (24% HSV, 5% CMV, 18% both).6 Another study looking for HSV-1 in patients on invasive MV found HSV-1 reactivation between days 11 and 40, which correlated with immunological markers of decreased innate immunity.7 A case series looking for CMV infection (by PCR in plasma or BAL) in COVID-19, also found CMV reactivation between day 7 and 45 of illness. Most of these patients were above 60 years of age and immunosuppressed (HIV, diabetes mellitus, medications).8 Although immunocompromised individuals are more vulnerable, healthy immunocompetent adults who are critically ill or on prolonged MV may also be susceptible to these infections.9-12 This may be explained by a state of immunoparalysis inherent to prolonged critical illness. In case 1, an ICU stay of around 9 weeks complicated with recurrent nosocomial infections, multiple blood product transfusions, and steroid usage could have the likely triggers. Whether viral co-infections are merely bystanders or truly pathogenic is difficult to comment but timely management is essential to avoid end-organ damage (EOD) which may occur directly (by enhanced viral load secondary to compromised host immunity) or indirectly (by inflammatory changes consequent to prolonged cell-mediated immunity required to maintain viral dormancy).2-4,13 It also seems imperative to study if a viral co-infection has a proclivity to develop more severe hematological anomalies (besides the inherent risk of HLH with COVID) as was seen in case 1, in which the patient had a downward spiral of illness with multiorgan dysfunction.14-15 Limitations: Dynamics of PCR trends and virology studies of samples from trachea, gut, and urine could not be analysed in our patients. Conclusion: Viral co-infections can occur in COVID-19 disease as these patients are often immunocompromised and critically ill. A high index of suspicion and prompt management is needed to improve the outcome of patients. Patients with organ dysfunctions especially hematologic abnormalities with bone marrow involvement should be worked up in detail to look for concomitant viral co-infections. In the future, large-scale research is needed to better elucidate the relationship between SARS-CoV-2 and other viral co-infections.

ADULT-ONSET STILL'S DISEASE AND MACROPHAGE ACTIVATION SYNDROME FOLLOWING COVID-19 PNEUMONIA

CASE: A 41-year-old woman with recent COVID-19 pneumonia presented to the hospital with several months of fever, polyarthralgia, and weight loss. She reported waxing and waning shoulder, elbow, wrist, hip, knee, and ankle pain without identifiable triggers. She had no pertinent medical or family history. Vital signs were only notable for fever of 40C which recurred daily. Exam revealed tenderness to palpation of multiple joints;her skin had no rash, purpura, or nodules. Hepatosplenomegaly and axillary lymphadenopathy were noted. Infectious workup was negative for bacterial, viral, fungal, mycobacterial, parasitic, and protozoal infections. Initial studies demonstrated hemoglobin 8.2 mg/dL, lymphopenia, and aspartate transaminase 58 U/L. Flow cytometry, excisional lymph node biopsy, and bone marrow biopsy were negative for lymphoproliferative disease. Rheumatologic workup revealed elevated ferritin, triglycerides, Interleukin-6, soluble Interleukin-2 receptor (sIL-2R), and “C-X-C Motif Chemokine Ligand 9” (CXCL9);extensive rheumatologic serologies were otherwise negative. Her clinical picture was consistent with Macrophage Activation Syndrome (MAS). She also met diagnostic criteria for Adult-Onset Still's Disease (AOSD) given arthralgia, fever, lymphadenopathy, splenomegaly, abnormal liver function test (LFT), and otherwise negative workup. Her presentation suggested COVID-19 triggered AOSD which triggered MAS. We administered intravenous immune globulin (IVIG) and high-dose steroids. She clinically improved and was discharged with oral steroids. She returned to the hospital two months later for fever, arthralgia, and faint, evanescent rash with elevated erythrocyte sedimentation rate, C-reactive protein, ferritin, lactate dehydrogenase, and LFT consistent with an AOSD flare. She received intravenous steroids and Anakinra. Symptoms resolved, and she was discharged with plans to continue Anakinra and oral steroids. At followup, she had resolution of all symptoms. IMPACT/DISCUSSION: COVID-19 has many chronic complications, including triggering of underlying rheumatic disease. This sequence of events suggests that COVID-19 Pneumonia triggered an underlying diagnosis of AOSD. AOSD should be considered in the differential diagnosis of patients with quotidian fever and arthralgia following COVID-19 infection. AOSD is a diagnosis of exclusion and requires ruling out infectious, malignant, and rheumatic etiologies. AOSD may trigger MAS, a dysregulated immune response to underlying inflammation, and should be considered in patients with suspected infection refractory to treatment who have fever, splenomegaly, cytopenias, and elevated ferritin, triglycerides, sIL-2R, and CXCL9. CONCLUSION: COVID-19 has many chronic complications. AOSD may manifest after COVID-19 infection and should be considered in the differential diagnosis of patients with persistent fever and arthralgia. MAS should be suspected in patients with systemic inflammation refractory to treatment. AOSD may cause MAS.

Deep Vein Thrombosis, Septic Pulmonary Emboli and Methicillin-Resistant Staphylococcal Aureus Bacteremia Complicated by a Furuncle in a Child

Staphylococcal aureus infection in children is a major public health problem globally. It causes a varied spectrum of clinical disease including bacteremia, endocarditis, skin and soft tissue infection, pleuro-pulmaonry and osteo-articular infection. Deep vein thrombosis (DVT) is a known complication of staphylococcal infection. We report a case series which included, 10-year old boy developed DVT, septic pulmonary emboli and Methicillin-resistant Staphylococcal aureus (MRSA) bacteremia following a furuculosis and 13 year old girl with thrombosis of internal and external jugular vein, cavernous sinus with pulmonary emboli and MRA bacteremia. Both patients are previously healthy showed complete recovery after aggressive appropriate antibiotics, anticoagulants and supportive care. The high index of suspicion of DVT in MRSA infection is needed, prompt diagnosis and aggressive appropriate therapies improve the outcomes and minimize the complications.

Refractory Acute Disseminated Encephalomyelitis-like Illness Found to be CNS-isolated Hemophagocytic Lymphohistiocytosis due to a Novel PRF1 Mutation

Objective: 5-year-old boy with refractory acute disseminated encephalomyelitis (ADEM) found to have CNS-isolated Hemophagocytic Lymphohistiocytosis (HLH) with PRF1 mutation, c.4422G>A variant, not previously known to be pathogenic. Background: HLH is a hyperinflammatory condition that presents with fever, hepatosplenomegaly and characteristic laboratory findings. HLH can be familial (fHLH) or secondary (sHLH). Mutations in the perforin gene PRF1 have been identified as pathogenic for fHLH and they can also cause isolated CNS-HLH in the absence of systemic HLH. HLH can be triggered by malignancy, infections, or autoimmunity. Viruses are a common trigger and there have been cases of SARS-CoV-2 triggering HLH. Design/Methods: Clinical course, evaluation, management. Results: A 5-year-old boy presented to the emergency department with 3 weeks of headaches, right blurry vision, and emesis. He underwent an extensive evaluation and was diagnosed with ADEM that was thought to be triggered by SARS-CoV-2 after a positive nasal swab. Myelin oligodendrocyte glycoprotein (MOG) antibodies were negative. Patient completed a 5-day course of IV pulse steroids and plasma exchange. In the subsequent months, he was admitted twice due to worsening neuroinflammation and after several courses of IV pulse steroids, PLEX, and IVIG, the CNS inflammation stabilized with rituximab and monthly IVIG. A few months later, his younger brother presented to the emergency department with a similar syndrome. It was found that his parents were cousins, leading to concern for a genetic disorder. Genetic testing revealed a homozygous mutation for PRF1 in both siblings (variant c.4422G>A). Conclusions: This is the first presentation of CNS-isolated HLH triggered by SARS-CoV-2 in the pediatric population. Furthermore, thisis the first report of PRF1 mutation, the variant c.4422G>A, shown to be pathogenic. It highlights the relevance of genetics in pediatric neuroinflammatory disorders. It is possible that as our knowledge in neurogenetics develops, certain genes will be identified as predisposing factors to presentations such as ADEM.

Parotid Abscess in A Case of Acute Lymphoblastic Leukemia

Parotid gland enlargement as a presenting manifestation of acute lymphoblastic leukemia (ALL) is very rare, even though it has been reported in acute myeloid leukemia. Here we present a case of parotid abscess in a case of ALL in the presence of Dengue.

Clinicohaematological Patterns of Anemia and Correlation with Clinical Conditions in Children Aged 5 to 12 Years in Tertiary Care Centre

Objective: To classify the haematological pattern, severity of anemia in children 5-12 years age admitted and to find its correlation with the clinical conditions. Methods Crossectional study of 160 patients in two years was done. Patients satisfying the inclusion criteria were selected for study. Relevant clinical data were recorded in a structured proforma including detailed history was recorded with particular symptoms suggestive of anemia such as weakness and easily fatigability, breathlessness on exertion and pica. A thorough clinical examination of every child was done followed by routine investigations for anemia Results Patients between 7-8 year were found to be the most affected. Anemia was found to be more common in female children as compared to male children (F:M=1.13). Anemia is more common in undernourished child. Most common presenting symptoms were gastrointestinal including vomiting, diarrhea and pain abdomen. Most common sign was Pallor followed by other common signs included signs of dehydration associated with diarrhea, hepatosplenomegaly. microcytic hypochromic anemia was the most common morphological type of anemia and macrocytic anemia was the least common.Thalassemia cases were most common among hemolytic anemias. Iron Deficiency Anemia (Nutritional Anemia) was the most common etiology of anemia. Conclusion Dietary deficits affect children aged 5 to 12, creating financial, emotional, and psychological burden for patients and their families, as well as depleting critical national resources. As a result, screening for these illnesses, as well as early detection of anemia and related problems, is essential.

Cardiac involvement in Pediatric Multisystem Inflammatory Syndrome (PIMS) triggered by pandemic COVID19

Introduction: We want to present the cardiac implication in PMIS, a new and serious SARS COV2 pandemic entity, that has similar characteristics with Kawasaki disease(KD) or Toxic Shock Syndrome and may develop a severe and potential fatal Macrophage Activation Syndrome(MAS), targeting major organs. Methods: During pandemic, 7 patients were admitted into our clinic with prolonged unremitted fever and different clinical onset, 4 female and 3 males, with ages between 4 mo and 16 yo. All patients underwent clinical examination, ECG, serial Echocardiography, abdominal ultrasound, Cardio-pulmonary X ray or CT, complex lab tests. Two tested positive for COVID antibodies. S66 Cardiology in the Young: Volume 32 Supplement 1 Results: Two patients developed incomplete Kawasaki-like disease with slight dilatation of the coronary arteries and thrombocytosis over 1 million/mm3, treated with IGIV and Aspirin. PIMS with severe MAS, a rare complication was present in 5 patients admitted for fever and: diarrhea(1), rash(2), aseptic meningitis(1), encephalitis, seizures and coma(1), ground glass pneumonia(5), generalized purpura(1), appendicitis(2), ascites(1), colonic abscesses(1), arthritis mimicking Systemic Juvenile Arthritis(1), symptoms presented in different combinations, targeting 2 or 3 organs. Hepato-splenomegaly was palpable in all 5. Cardiac involvement was present at the beginning in 2 cases: pericarditis(2), mitral insufficiency(1), mitral and aortic insufficiency(1), and rapidly after admittance in 3 cases: cardiac tamponade and severe hypotension(1), pericarditis( 1), myocarditis(1). Cardiac biomarkers: NT-proBNP and Troponins T and I were elevated in all cases, with more sensitive Troponin I. All 5 patients had: elevated CRP, Ferritin, D-Dimers, liver enzymes, triglycerides, low fibrinogen, falling ESR, leucopenia and thrombocytopenia(one patient with 5000/mm3 thrombocyte), abnormal coagulation. Interleukin 6(IL6) was high in all 7 patients, but in PIMS with MAS, the cytokine storm syndrome, was confirmed by highly elevated soluble IL2 receptor. This patients were promptly treated with IV corticotherapy, anticoagulants, IGIV and antibiotics with favorable evolution. Conclusions: Cardiac tamponade, pericarditis, myocarditis, mitral and aortic insufficiency and Kawasaki-like disease with coronary artery dilatation were found in PIMS patients. Only two cases were positive for COVID Antibodies. Rapid recognition of PIMS and aggressive treatment of MAS prevent fatalities and determined a favorable evolution.

First own experience of intensive care multisystem inflammatory syndrome in children (MIS-C) associated with COVID-19

Introduction: Timeliness of diagnosis and treatment of MIS-C has increased amid the COVID-19 pandemic. Methods: A child was admitted to our clinic (male, 14 years old). He was in contact with a COVID-19 patient 17 days before. Upon admission, the patient complained of a rise in body temperature to 40° C, abdominal pain, vomiting, and diarrhea. Hemorrhagic rash on the skin of the upper and lower extremities, hyperemia of the mucous membrane of the lips and tongue, arterial hypotension were found. Hospitalized at ICU. In laboratory tests: WBC 3.42 × 109/ l, RBC 4 × 1012/ l, HB 111 g/l, HTC 31, PLT 31 × 109/ l, CRP 283 mg/l, PCT 6.66, D-dimer 9.2, LDG 194 U/l, ferritin 989 mcg/l, ALT 54 U/l, GGT 79 IU/l, albumin 32 g/l;proteinuria 0.75 g\l, hematuria. Diagnosis: MIS-C associated with COVID-19. Results: Prescribed: Meropenem 20 mg/kg/d, methylprednisolone 2 mg/kg/d. After 8 h-septic shock. 0.3 μg/kg/min norepinephrine was started. ECG-a violation of repolarization with ST elevation up to 0.3 mm. Echocardiography-a decrease in the left ventricular ejection fraction to 47%, pericardial effusion. Ultrasound examination of the abdominal cavity: hepatosplenomegaly. Dobutamine 3 μg/kg/min was added to the therapy. An increase in PCT up to 19.8 was found. IV IgG 2 g/kg was added to the therapy. On the 3rd day of therapy, regression of all symptoms was obtained. On the 8th day, the child was transferred from the ICU to the pediatric department. On the 12th day he was discharged home. Conclusions: Thus, the timely diagnosis of MIS-C associated with COVID-19 and the appointment of intensive therapy with the inclusion of methylprednisolone and IV IgG allows achieving a positive result in the shortest possible time. Consent to Publish: Written informed consent was obtained from the next of kin.