Serological study of Human Parvovirus (B19) detected among Patients with Thalassemia

Background: Parvovirus B19 is an icosahedral, single-strand DNA, non-enveloped virus. Its DNA genome has 5596 bases and is from the Parvoviridae family. Beta thalassemia, a hereditary illness, causes ruptured red blood cells and acute anemia due to aberrant haemoglobin synthesis. Aim(s): Detect parvovirus (B19) in beta-thalassemia major and study its association with demographic factors like sex, age, place of residence, etc. in specific patient groups. Method(s): From August 2022 to the end of February 2023. This study included the collection of serum samples for the detection of human parvovirus antigen in 60 patients with beta-thalassemia major. The control group consisted of 30 individuals of different ages who did not have beta-thalassemia. All these serum samples are detected for parvovirus antigen by the ELISA method. Result(s): The results of this study showed that the rate of detection of the presence of human parvovirus B19 in the group of patients with beta-thalassemia major was not affected by most of the demographic factors. As there were no statistically significant differences between the study groups in terms of gender, age, in addition to COVID-19 infection, and vaccination against COVID-19. However, the rate of beta-thalassemia major was significantly higher in rural areas than in urban areas (p = 0.040).Copyright © 2021 Muslim OT et al.

Reactivation of Parvovirus B19 Infection: An Uncommon Trigger of Macrophage Activation Syndrome in Adult-Onset Still's Disease.

A 40-year-old woman presented with four weeks of intermittent high-grade fever, cough, and joint pain, and two weeks of a generalized rash. She was found to have adult-onset Still's disease (AOSD) and rapidly developed macrophage activation syndrome (MAS) on the second day of admission. Among infectious etiologies, Epstein-Barr virus and members of the herpes virus family are common triggers of MAS. However, our patient was found to have reactivation/recurrence of parvovirus B19 infection as the cause; this is an uncommon trigger reported infrequently in the medical literature. Despite intensive treatment, the patient passed away.

Hepatotoxicity From Marijuana Gummies

Introduction: We report a case of drug-induced liver injury (DILI) induced by cannabis gummies containing Corydalis Rhizome. Case Description/Methods: A 37-year-old female presented to her primary care clinic with recurrent fevers, night sweats, and myalgias for 7 weeks accompanied by eye redness, brain fog, headache, nausea, and abdominal pain. She denied rashes, tick-bites, cough, dyspnea, chest pain, joint swelling, or genitourinary symptoms. Past medical history was notable for IBS, migraines, and anxiety. She reported edible marijuana use four times a week, rare alcohol use, and denied tobacco use. She denied a family history of liver disease. Physical exam was notable for tachycardia to 110 and scleral injection with the remainder of vitals and exam unremarkable. Initial labs were notable for AST 61, ALT 44 and CRP of 12. CBC, BMP, urinalysis, ESR, blood cultures, blood smear for parasite screen, tests for Lyme disease, Babesia, Tularemia, Anaplasma, Ehrlichia, Rickettsia, EBV, HIV, RPR, ANA, CMV, parvovirus B19, and chest x-ray were all negative. The patient was referred to infectious disease with further testing for West Nile, Leptospira, lymphocytic choriomeningitis virus, and COVID-19 returning negative. Repeat LFTs showed worsening transaminitis with ALT 979 and AST 712, alkaline phosphatase 88, total bilirubin 0.7, and albumin 4.9. Hepatitis workup including hepatitis A, B, and C, HSV, EBV, VZV serologies, AMA, ASMA, antiLKM Ab, acetaminophen level, INR, iron panel, CPK, TSH, and abdominal ultrasound were all normal. It was later discovered that her marijuana gummies contained Corydalis rhizome extract known to be hepatotoxic. Cessation of this drug was strongly advised. She was discharged with hepatology follow-up and underwent a liver biopsy showing patchy periportal and lobular inflammation with extension across the limiting plate, hepatocyte injury and apoptosis, and increased lipofuscin for age compatible with mild to moderate hepatitis. She had complete recovery after cessation of Corydalis-containing gummies. (Figure) Discussion: Our patient consumed '1906 Midnight', an American cannabis brand containing Corydalis rhizopus 100 mg, advertised to improve sleep, pain, and have a liver protective effect. A Korean systematic review on herbal-induced liver injury reported that Corydalis was the 3rd most frequent causative herb, with 36 cases. Although there are several personal accounts on social networking sites and other websites, there are no American-based publications reported on DILI from Corydalis. (Table Presented).

Viral Infections and the Kidney

Viral infections are associated with a number of renal diseases in children resulting in significant morbidity and mortality worldwide. The role of viral infections in the pathogenesis of kidney disease has been largely based on clinical and histologic kidney findings in temporal association with a systemic viral infection and the demonstration of kidney cells infected with viral particles. Viral infections associated with productive viral replication in the kidney of immunocompromised hosts are of particular concern for children. Here, we will discuss the epidemiology, pathogenesis, outcomes, and treatment of the most relevant kidney diseases associated with viral infections in children, excluding those occurring in kidney transplant recipients, which are discussed elsewhere in this textbook (see chap. 84, Renal transplantation: infectious complications). Well-defined associations between a viral infection and kidney disease have been made for the hepatitis B virus (HBV), hepatitis C virus (HCV), human immunodeficiency virus (HIV-1), hantaviruses, and the new coronavirus SARS-CoV-2. In children with immunodeficiency states, herpes viruses, polyomavirus, and adenovirus have been recognized to induce kidney diseases. The roles of other viruses in the pathogenesis of kidney diseases are not clearly defined and remain speculative. With increasing application of molecular techniques, the understanding of the role of viruses in the pathogenesis of kidney diseases is expected to increase. In addition, more specific antiviral treatments and vaccines are currently under development and are expected to improve the outcome of viral-mediated kidney diseases in children. © Springer Nature Switzerland AG 2009, 2016, 2022.

Frequency of Pathological MRI Findings in Suspected Myocarditis during the COVID-19Pandemic

Background: COVID-associated and vaccine-triggered myocarditis in young people have received much attention over the course of the pandemic due to early results of vaccination associated myocarditis. This may have led to an increase in myocarditis suspicions. In this study we wanted to examine the actual amount of COVID-associated myocarditis in ourtertiary center. Method(s): We included all cardiac MRIs performed in our institution for the indication of suspected myocarditis between 2020and 2022. We excluded patients with primary cardiomyopathy. We divided the patients into three groups: Group 1 had noCOVID infection or COVID-vaccine associated with their suspected myocarditis, group 2 had received a COVID vaccination prior to developing symptoms, group 3 had had an acute COVID infection and group 4 had a clinical diagnosis of Pediatric inflammatory multisystem syndrome (PIMS). Result(s): Overall, 28 patients had MRIs for suspected myocarditis performed at our center in the investigated time frame. They were 10 to 18 years of age (mean: 15.1 years). Symptoms included chest pain, fatigue, palpitations and reduction in exercise tolerance. Nineteen patients were in group one, 4 patients had symptoms associated with COVID vaccination, three had acute infection and two had a clinical diagnosis of PIMS. Late gadolinium enhancement (LGE) was found in 7 patients. None of these were in groups 2 or 3. Both patients with PIMS(n = 2) had myocarditis on biopsy but only one on MRI. Myocardial biopsy was performed in 8 patients. They showed myocarditis in 6 patients. Apart from the PIMS cases, none of them were associated with Corona infection or COVID vaccine. Three patients had parvovirus B19 on biopsy and one also had EBV. One of the PIMS patients also had HHV6. Theother four biopsies did not yield any viral DNA on PCR. Conclusion(s): Myocarditis associated with acute COVID infection or vaccination was not found in our cohort. Exercise intolerance or chest pain was not reliable indicators of cardiac causes. Even in the pandemic, coronavirus and COVID-19vaccines are unlikely causes of myocarditis. Most cases were associated with classic cardiotropic viruses. However, in cases of PIMS, cardiac involvement is likely and should be investigated accordingly.

Case report: COVID-19-related acute pericarditis mimicking acute anterior myocardial infarction

Introduction: Coronavirus disease 2019 (COVID-19) was described for the first time in December 2019. Symptoms include cough, fever, myalgia, headache, dyspnea, sore throat, diarrhoea, nausea, vomiting, and loss of smell or taste. Viral-induced myocarditis and pericarditis have been described in developed countries, and SARS-CoV-2 is cardiotropic. Pericarditis can mimic myocardial infarction (MI) in its presentation and ECG findings. Case report: A 46-year-old smoker with no previous medical condition presented with left-sided chest pain, sweating, trouble breathing, palpitations, and left-hand numbness. He denied having reduced effort tolerance, orthopnea, or paroxysmal nocturnal dyspnea. Three weeks earlier, he was infected with Covid-19 category 2A infection. On examination, he is haemodynamically stable, and his respiratory and cardiovascular exams were unremarkable. His ECG showed anterior ST elevation, and the bedside echocardiography showed no hypokinesia or pericardial effusion. High-sensitive cardiac troponin T reached 5000. The emergency team contacted the on-call cardiologist for primary PCI. After analysing the serial ECG and bedside echocardiography, he decided against primary PCI due to acute pericarditis. He was started on intravenous diclofenac acid and colchicine. His pain subsided after 3 days with NSAIDs and colchicine. He was reviewed back in the clinic and had a normal ECG and ECHO. Discussion(s): Pericardial disease caused by COVID-19 has been more common since the pandemic outbreak. Mycobacterium tuberculosis, Borrelia burgdorferi, Parvovirus B19, and Epstein-Barr virus are the most common infecting agents. Most cases of acute pericarditis in developing nations are due to tuberculosis infection. Nearly half of all patients who had previously recovered from COVID-19 infection have now presented with new cardiac MRI findings indicating pericardial involvement. Fibrosis and/or oedema may be linked to persisting active pericarditis following infection resolution, which may lead to short and long-term clinical consequences. Conclusion(s): The ST elevation in post-covid patients does not always signify myocardial infarction. Despite complaints and ECG findings, this could not be an acute myocardial infarction, for which clinicians should have a high index of suspicion.Copyright © 2023

Persistent viral infections and their role in heart disease.

Viral infections are the culprit of many diseases, including inflammation of the heart muscle, known as myocarditis. Acute myocarditis cases have been described in scientific literature, and viruses, such as parvovirus B19, coxsackievirus B3, or more recently, SARS-CoV-2, were the direct cause of cardiac inflammation. If not treated, myocarditis could progress to dilated cardiomyopathy, which permanently impairs the heart and limits a person's lifespan. Accumulated evidence suggests that certain viruses may persist in cardiac tissue after the initial infection, which could open up the door to reactivation under favorable conditions. Whether this chronic infection contributes to, or initiates, cardiac damage over time, remains a pressing issue in the field of virus-induced heart pathology, and it is directly tied to patients' treatment. Previously, large case studies found that a few viruses: parvovirus B19, coxsackievirus, adenovirus, human herpesvirus 6, cytomegalovirus and Epstein-Barr virus, are most commonly found in human endomyocardial biopsy samples derived from patients experiencing cardiac inflammation, or dilated cardiomyopathy. SARS-CoV-2 infection has also been shown to have cardiovascular consequences. This review examines the role of viral persistence in cardiac inflammation and heart disease, and discusses its implications for patients' outcomes.

Type D lymphomatoid papulosis with pityriasis lichenoides et varioliformis acuta-like features in a child with parvovirus infection: a controversial diagnosis in the spectrum of lymphoid proliferations: case report and literature review.

BACKGROUND: Lymphomatoid papulosis (LyP) is a rare condition in pediatrics; LyP histological type D has been reported in only 7 children. The differential diagnosis of LyP in the spectrum of lymphoid proliferation remains controversial. CASE PRESENTATION: A 6-year-old boy presented to Emergency Department with a 3-week history of an erythematous papulo-vesicular itchy eruption over the submandibular regions, trunk and extremities. History, symptoms and laboratory tests were unremarkable. SARS-CoV-2 antigen was negative. The clinical suspicion of pityriasis lichenoides et varioliformis acuta (PLEVA) was posed, and topical steroids were introduced. One week after, he returned with an extensive painful scaly papulo-erythematous rash, with some ulcerated and necrotic lesions, and fever; therefore the child was hospitalized. Biochemical results were within reference limits, except for high level of C-reactive protein, aspartate aminotransferase, alanine transaminase and bilirubin. Due to a persistently high fever, systemic corticosteroid treatment was administered, with a good clinical response and an improvement of the skin lesions. Anti-PVB-19 Immunoglobulin M was detected. Elevated levels of IL-6, IL-10 and IFN-γ were also recorded. Five days post-admission, most of the lesions had cleared, and the child was discharged. Methotrexate was started, with a positive response. At skin biopsy a "PLEVA-like" pattern was apparent, with a dense, wedge shaped lymphoid infiltrate featuring epidermotropism and morphologically comprising pleomorphic and blastic cells. The pattern of infiltration was highlighted by immunohistochemical stains, which prove the process to feature a CD8+/CD30 + phenotype, the latter being intense on larger cells, with antigenic loss. Polymerase chain reaction for T-cell receptor gamma (TCRG) chain clonality assessment documented a monoclonal peak. A diagnosis of LyP type D was favored. CONCLUSION: The reported case encompasses most of the critical features of two separated entities-PLEVA and LyP-thus providing further support to the concept of them representing declinations within a sole spectrum of disease. Studying the role of infectious agents as trigger potential in lymphoproliferative cutaneous disorders and detecting novel markers of disease, such as cytokines, could have a crucial impact on pathogenic disease mechanisms and perspective therapies.

DILATED CARDIOMYOPATHY WITH CARDIOGENIC SHOCK SECONDARY TO COVID-19 INFECTION

SESSION TITLE: Extraordinary Cardiovascular Reports SESSION TYPE: Rapid Fire Case Reports PRESENTED ON: 10/18/2022 01:35 pm - 02:35 pm INTRODUCTION: Acute myocarditis from COVID-19 has been well documented, but there are few cases of COVID -19 patients developing dilated cardiomyopathy (3). We present a case of COVID-19 induced dilated cardiomyopathy leading to cardiogenic shock. CASE PRESENTATION: A 49-year-old African-American female presented to the emergency department (ED) with shortness of breath. She was diagnosed with COVID-19 infection four weeks prior to presentation, and since that time she experienced continuously worsening dyspnea, congestion, and weakness. In the ED, the patient was found to have pulmonary edema and bilateral pleural effusions on chest x-ray, as well as acute kidney injury with a creatinine level of 2.85 mg/dL. An echocardiogram revealed a new diagnosis of dilated cardiomyopathy with reduced ejection fraction of 10-15% with a large left ventricular thrombus. Heparin infusion was initiated and intravenous furosemide was administered for diuresis. Her renal function continued to worsen, which was attributed to cardiorenal syndrome. She became hypotensive and was found to be in cardiogenic shock, which required intensive care unit admission with the initiation of continuous renal replacement therapy (CRRT). The patient improved with CRRT, however her renal function did not recover and she continued to require hemodialysis. She was able to be transferred out of the intensive care unit, and the heparin was bridged to warfarin. Goal-directed medical therapy was initiated for her heart failure. She was eventually discharged home with an external cardioverter-defibrillator vest. A follow-up echocardiogram three months later revealed the left ventricular thrombus had resolved, however, her ejection fraction had improved to only 15-20% despite medication compliance. An implantable cardioverter-defibrillator (ICD) was placed and the patient continues to be followed closely by cardiology. DISCUSSION: Viral infection is a well-documented cause of myocarditis with some patients developing dilated cardiomyopathy (1). Inflammatory dilated cardiomyopathy occurs most commonly in patients infected with Coxsackie B virus, Human Parvovirus B19, Adenovirus, Human Immunodeficiency Virus, Hepatitis C Virus, Cytomegalovirus, Epstein-Barr Virus, and Human Herpes Virus 6 (1). The proposed mechanism of inflammatory cardiomyopathy includes infection of the myocytes, incomplete viral elimination, and persistent retained viral components in the myocytes(2). This may cause direct viral injury or chronic myocardial inflammation leading to remodeling (2). It is documented in the literature that COVID-19 can lead to myocarditis and various types of acute cardiomyopathy (3). However, there have been only a few reported cases of COVID - 19 induced dilated cardiomyopathy (3). CONCLUSIONS: While rarely reported thus far, it should be established that COVID-19 alone can cause dilated cardiomyopathy and lead to heart failure (3). Reference #1: Schultheiss H-P, Baumeier C, Pietsch H, Bock C-T, Poller W, Escher F. Cardiovascular consequences of viral infections: from COVID to other viral diseases. Cardiovascular Research. Published online October 5, 2021. doi:10.1093/cvr/cvab315 Reference #2: Kühl U, Pauschinger M, Seeberg B, et al. Viral Persistence in the Myocardium Is Associated With Progressive Cardiac Dysfunction. Circulation. 2005;(13):1965-1970. doi:10.1161/circulationaha.105.548156 Reference #3: Komiyama M, Hasegawa K, Matsumori A. Dilated Cardiomyopathy Risk in Patients with Coronavirus Disease 2019: How to Identify and Characterise it Early? European Cardiology Review. Published online May 27, 2020. doi:10.15420/ecr.2020.17 DISCLOSURES: No relevant relationships by Amanda Cecchini No relevant relationships by Austin Richardson No relevant relationships by Krupa Solanki

Acute Onset of Remitting Seronegative Symmetrical Synovitis With Pitting Edema (RS3PE) Two Weeks After COVID-19 Vaccination With mRNA-1273 With Possible Activation of Parvovirus B19: A Case Report With Literature Review.

Remitting seronegative symmetrical synovitis with pitting edema (RS3PE) is a rare clinical entity characterized by "remitting," "seronegative," and "symmetrical" synovitis with pitting edema on the dorsum of the hands and feet. Although rheumatic or malignant diseases are diseases that are known to coexist with RS3PE, other factors such as medication, infection, and vaccination have been reported to be associated with RS3PE. Here, we present a case of RS3PE syndrome that satisfied all four diagnostic criteria of RS3PE (pitting edema in the limbs, acute onset, age ≥ 50 years, and/or rheumatoid factor negativity) after mRNA-1273 SARS-CoV-2 vaccination.

Warm Autoimmune Hemolytic Anemia and Pure Red Cell Aplasia during a Severe COVID-19 B.1.1.7 Infection.

Warm autoimmune hemolytic anemia (AIHA) is a rare complication of COVID-19 infection. We report a case of warm AIHA in a patient with COVID-19 pneumonia treated with methylprednisolone and several red blood cell transfusions. Despite treatment of the warm AIHA, the patient's reticulocyte count remained low, and his biochemical markers were suggestive of pure red cell aplasia, which was later attributed to a concurrent parvovirus B19 infection. This case highlights an unusual situation of two separate hematological processes caused by two separate and simultaneous viral infections.

Parvovirus (B19) Infection during Pregnancy: Possible Effect on the Course of Pregnancy and Rare Fetal Outcomes. A Case Report and Literature Review.

Infection caused by human parvovirus B19 (B19) often has mild yet wide-ranging clinical signs, with the course of disease usually defined as benign. Particularly prevalent in the population of young children, the virus is commonly transmitted to the parents, especially to susceptible mothers. During pregnancy, particularly the first and second trimesters, parvovirus infection can lead to pathology of the fetus: anemia, heart failure, hydrops, and disorders of physical and neurological development. In severe cases, the disease can result in fetal demise. This article presents a rare case of manifestation of B19 infection during pregnancy. At the 27th week of gestation, a sudden change in fetal movement occurred in a previously healthy pregnancy. The examination of both fetus and the mother revealed newly formed fetal subdural hematoma of unknown etiology and ventriculomegaly. Following extensive examination to ascertain the origin of fetal pathology, a maternal B19 infection was detected. Due to worsening fetal condition, a planned cesarean section was performed to terminate the pregnancy at 31 weeks of gestation. A preterm male newborn was delivered in a critical condition with congenital B19 infection, hydrocephalus, and severe progressive encephalopathy. The manifestation and the origin of the fetal condition remain partially unclear. The transplacental transmission of maternal B19 infection to the fetus occurs in approximately 30% of cases. The main method for diagnosing B19 infection is Polymerase Chain Reaction (PCR) performed on blood serum. In the absence of clinical manifestations, the early diagnosis of B19 infection is rarely achieved. As a result, the disease left untreated can progress inconspicuously and cause serious complications. Treatment strategies are limited and depend on the condition of the pregnant woman and the fetus. When applicable, intrauterine blood transfusion reduces the risk of fetal mortality. It is crucial to assess the predisposing factors of the infection and evaluate signs of early manifestation, as this may help prevent the progression and poor outcomes of the disease.

Multiple opportunistic infections (pulmonary tuberculosis, Mycobacterium avium complex and parvovirus B19) in a single patient.

INTRODUCTION: HIV infection is a common disease in the South African population. The virus can lead to the development of many opportunistic infections. This case study examines co-infection with three opportunistic infections and the need for clinical suspicion of infections in our HIV population. PATIENT PRESENTATION: A 36-year-old unemployed female residing in Soweto, Johannesburg, presented at Chris Hani Baragwanath Hospital (CHBAH). She was HIV positive, defaulting treatment, with no other comorbidities. She presented to CHBAH with general body weakness, diarrhoea, cough and constitutional symptoms; clinically she appeared pale and chronically ill. A differential diagnosis was made of multiple infections co-inhabiting the patient. MANAGEMENT AND OUTCOME: The patient had blood, sputum, radiological and invasive bone marrow aspiration, and trephine biopsies completed. The investigations revealed that she was co-infected with Mycobacterium tuberculosis (MTB), Mycobacterium avium complex (MAC) and parvovirus B19. The TB and disseminated MAC infection were managed with rifampicin, isoniazid, ethambutol, pyrazinamide and azithromycin, and reinitiation of antiretroviral (ARV) treatment was planned on further follow-up of the ARV drug resistance test. The parvovirus B19 infection was managed with immunoglobulins (Polygam) and steroids (prednisone). She was discharged successfully for further follow-up. CONCLUSION: A thorough history, clinical examination and subsequent targeted investigations are vital to arriving at the correct diagnosis or diagnoses. The case presented above serves to illustrate how three life-threatening opportunistic infections (OIs), all with differing treatments, may present in a single patient. Clinicians caring for immunosuppressed patients need to remain vigilant for the presence of multiple OIs occurring simultaneously.

A case of Parvovirus B19 infection diagnosed as COVID-19 due to false PCR positivity

Although PCR is the most reliable test for the diagnosis of Covid-19 infection, false negative and positive results can also occur. Our case is a 32-year-old laboratory technician who applied with headache and malaise and her first Covid-19 PCR test was negative. It was repeated two days later, and the result was positive. Additional tests were also performed, and Parvovirus IgM antibody was also found to be positive. Four weeks later, while Covid-19 IgM and IgG test results were negative, the Parvovirus B19 IgG and IgM test results were positive. The Covid-19 PCR test was evaluated as false positive. We aimed to emphasize the need to consider other viral infections in the differential diagnosis even under pandemic conditions.

Viral Infections with Rash and Febrile Intoxication Syndrome in Children During the Covid-19 Pandemic in Bulgaria, 2020

Aim: The present study aims to laboratory analyze viral agents causing rash and febrile intoxication syndrome in children aged 1 to 18 years in Bulgaria, in 2020. Materials and Methods: In 2020 there was an increased incidence of measles cases in Europe and on the Balkan Peninsula, against which a measles outbreak was reported 2019-2020 and in Bulgaria (incidence 21, 26 per 100,000). The total of 241 serum samples from children aged 1 to 18 years, hospitalized with fever and rash, were tested in NRL "Measles, Mumps, Rubella", NCIPD. 201 of investigated patients were diagnosed with measles, 24 with "erythema infectious" and 3 with rubella. The study also included 13 serum samples from children diagnosed with varicella, tested in the NRL "Cell cultures, rickettsiae and oncogenic viruses", NCIPD. Differential testing of clinical specimens was performed for panel of four viral agents. Laboratory confirmation of infections was provided by serological method - indirect enzyme-linked immunosorbent assay (indirect EIA test, EUROIMMUN, Germany) for detection of specific viral Ig M antibodies against measles, rubella, parvovirus B19 and varicella, in serum samples. The result was interpreted qualitatively according to the manufacturer’s instruction of the test sets and classified as positive, negative and borderline. Results: The present study included 241 serum samples collected from 241 children with an average age of 6.22 years. They were divided into five age groups. The majority of tested patients were in the age group 1-4 years (88/241;36,51%), followed by those in 5-9 years (56/241;23.24%). Acute infection with fever and rash for at least one of four viral agents was confirmed by ELISA-IgM in 181/241(75%) of cases. The largest proportion of confirmed cases were among children with measles infection - in 165 (68%), followed by children with confirmed chickenpox /varicella- in 9 (4%) and B19V- in and 7 (3%), respectively. No rubella virus infection was laboratory confirmed in any of the children examined. Regarding the age distribution of laboratory confirmed cases, the highest incidence was seen in patients aged between 1 to 4 years (68;28%). Measles affected children mainly between the groups: 1 - 4 years and 5-9 years old. On the other hand, the highest percentage infected with chickenpox and B19V were in the age groups 5-9 and 10-14 years. Conclusion: Conducting a differential laboratory test to monitor respiratory infections with fever and rash in children is important for any health care system. It is crucial for their monitoring, for the preparation of a treatment strategy, as well as for determining the effectiveness of the specific prophylaxis, incl. vaccine. The nature of viral agents and the ability to suppress the spread of respiratory viruses in the dominant circulation of a pathogen should not weaken the attention of health systems to infections, crucial on human pathology, especially pediatrics. © 2021 Academy of Medicine. All rights reserved.

Risk of infections with BCMA-directed immunotherapy in multiple myeloma

Introduction: B cell maturation antigen (BCMA) is a novel target for T cell immunotherapy in MM including bispecific antibody (bsAb) and chimeric antigen receptor therapy (CAR-T). BCMA is critical for survival of the long-lived plasma cell, responsible for generation of protective antibodies. Impaired immune reconstitution, cytopenias, B cell aplasia and hypogammaglobinemia can compound preexisting MM-induced immunosuppression. In the case of bsAb, potential redirection/activation of T regulatory cells can create an immunosuppressive milieu. Herein, we describe the clinically relevant infectious complications observed across different BCMA-directed therapies used across multiple clinical trials at our center. Methods: Infections confirmed by microbiologic or histopathologic evidence were captured from the D1 C1 of bsAb and D 1 of lymphodepleting chemotherapy of autologous BCMA CAR-T therapies. The NCI CTCAE v5 was used to describe the site and grade of infections. Hypogammaglobinemia and severe hypogammaglobinemia were defined as ≤700 mg/dl and ≤400 mg /dl, respectively. Standard antimicrobial prophylaxis included herpes zoster prophylaxis for all MM patients with antibacterial (levofloxacin) / antifungal (fluconazole) during periods of neutropenia and IVIG supplementation as per the treating physician's discretion. PCP prophylaxis was prescribed to CAR T recipient per institutional guidelines. Descriptive statistics and comparisons were performed using two-sample t-test for continuous variables and chi-square goodness of fit test for categorical variables. Results: We identified 62 patients who received BCMA-directed bsAb (n=36) or CAR-T (n=26) between 2019-2021(table 1). The median age was 66 (range 48-84) years with % females and 14.8% of patients belonging to Black race. The median time to bsAb and CAR-T use from diagnosis were 6.6 (range 0.83-15.5) and 2.6 (range 0.35-14.4) years, respectively. The median lines of prior therapy were 6 (range 1-11) with BCMA CAR-T recipients receiving fewer prior lines of therapy (4 vs 6, p=<0.001). The baseline lymphocyte count was higher in the CAR-T (14.71 vs 0.84;p=<0.001). Baseline severe hypogammaglobulinemia and lymphopenia were present in 30% and 26.7% of all patients, respectively. Tocilizumab was used in 40.9% (bsAb -30.8% versus CAR-T 55.6%) patients for CRS. IVIG was used in 25% of patients. The median study duration for bsAb was 4 (range 0.03- 24) months across multiple dose levels. Median follow up among CAR-T recipients was 3.9 (range 0.3 - 22.3) months. Among recipients of bsAb, 41.2% of patients experienced at least one episode of infection vs. 23.1% with CAR-T (p=0.141). The cumulative incidence of infection with bsAb and CAR-T were 22 and 8, respectively. The spectrum of infections with bsAb was predominantly bacterial (64.3% While gram negative infection (Escherichia coli and Klebsiella pneumoniae bacteremia, Proteus mirabilus and Psuedomonas aeroginosa urinary tract infections) were seen in 6 patients, skin infection including cellulitis occurred in 4 patients, with 1 case of necrotizing cellulitis. Bacteremia with rare opportunistic pathogens - Rhizobium radiobacter and recurrent Ochrobacterium anthropi were also observed . Viral infections included rhinovirus, cytomegalovirus, and parvovirus B19 reactivation, and COVID-19. About 50% of infections were ≥ grade 3 with 2 grade 5 events (Pseudomonas aeruginosa bacteremia and COVID-19). In the CAR-T group, we observed more viral infections (66.7% vs 35.7%;p=0.028) and fewer bacterial infections (33.3% vs 64.3%;p=0.028) . Common viral infections included rhinovirus, RSV, and herpes simplex virus reactivation. In this group 25% of infections were ≥grade 3. Conclusion: BCMA-targeted therapies seem to be associated with clinically significant bacterial and viral infections. Repetitive dosing with bsAb therapies could be the reason for the propensity to serious bacterial infections compared to CAR-T recipients and may need novel prophylaxis strategies. (Figure Presented).

Chronic polyarthritis in an adolescent with cutaneous polyarteritis nodosa

Introduction: Polyarteritis nodosa (PAN) is a necrotizing vasculitis of medium/small arteries. It is a rare condition, especially in the pediatric age group. Cutaneous PAN (cPAN) is recognized as a separate entity. It is characterized by disease affecting the skin with no major organ system involvement. Objectives: Chronic polyarthritis is much less observed and can simulate juvenile idiopathic arthritis, which can delay diagnosis, as was the case with this patient. Methods: We report a 14-year-old boy, who presented to us with polyarthritis and myalgia as a first manifestation of cPAN. Results: This 14-year-old male adolescent presented with a history of arthritis in right shoulder, ankles, knees, elbows, fingers and toes, associated with myalgia, with partial improvement after the use of non-hormonal anti-inflammatory drugs. Two months later, he was diagnosed with juvenile idiopathic arthritis. Corticosteroids were prescribed in a dose of 20 mg/day, methotrexate 7.5 mg/week and folic acid. There was no clinical improvement. At this time, he start with fever and the appearance of a painful erythematous lesions in the lower limbs and arms, difficulty in walking, which were progressively getting worse, anorexia and weight loss during this period. He also had a history of oropharyngeal infection prior to beginning of these symptoms. At that time, he was treated with azithromycin for 5 days. As there was no improvement in his clinical condition, he sought the Emergency Room where he was admitted for investigation 3 months after the beginning of his symptoms. On physical examination, we found arthritis in the elbows, knees, ankles and joints of the hands, maculopapular rash in the ankles, muscle atrophy in the arms and legs, palpable and painful nodules on the right leg and right foot. Several laboratory tests were requested. Blood investigations showed anemia, leucocytosis, elevated CRP, ESR and ASLO titres, with normal liver and kidney functions, and normal urine 1. Syphilis, HIV, serology for Mycoplasma pneumoniae, leishmaniasis, Paracoccidioides brasiliensis, Epstein-Barr virus, cytomegalovirus, Zika and Chikungunya viruses, dengue, and parvovirus B19 were negative. HBsAg, hep c were negative. CRP and serology was negative for Coronavirus 19 (Covid-19). Chest Xray, echocardiogram, and ultrasound of the abdomen were normal. Lupus anticoagulant, and FR were negative. Other autoantibodies were negative. p-ANCA and c-ANCA were negative. Myelogram with normal immunophenotyping was found. A skin biopsy was suggestive of PAN showing perivascular lymphomononuclear inflammatory infiltrate, sometimes permeating the vascular wall. The presence of eosinophils and neutrophils with outbreaks of leukocytoclasia was noted, an absence of malignancy was also shown. With infectious, hematological and oncological causes aside, pulse therapy with methylprednisolone was started. After the first infusion, a significant improvement in myalgia and arthritis was observed, in addition to the disappearance of febrile peaks. Then, he started a monthly pulse therapy with cyclophosphamide and methylprednisolone. Four months after start this therapy, we observed improvement of skin lesions and in laboratory exams. Conclusion: Cutaneous PAN is a rare disease, especially in the pediatric age group. Its clinical manifestations are quite varied, making early diagnosis difficult. Joint involvement, when it occurs, is characterized by an acute and oligoarticular pattern in the knees and ankles. Chronic polyarthritis is much less observed and can simulate juvenile idiopathic arthritis, which can delay diagnosis, as was the case with this patient. We must consider the diagnosis of PAN in those patients with chronic polyarthritis, associated with cutaneous vasculitic manifestations and increased ASLO.

A self-limiting symmetrical polyarthritis following COVID-19 infection

Case report-IntroductionWe describe an acute onset self-limiting seronegative non-destructive symmetrical polyarthritis five weeks after laboratory confirmed COVID-19 infection.Case report-Case descriptionA 37-year-old male hospital doctor of presented to the Early Inflammatory Arthritis clinic with a four-week history of acute onset joint pain, swelling and early morning stiffness in excess of two hours. The symptoms began at the left ankle with Achilles' tendonitis but progressed over the following 72 hours to a symmetrical polyarthritis affecting the wrists, proximal interphalangeal joints, shoulders, elbows, and knees.Approximately five weeks prior to the onset of his joint symptoms he had laboratory confirmed SARS-CoV-2 infection with six days of fever, non-productive cough, and fatigue. He did not require hospitalisation.His past medical history was significant for biopsy proven non-alcoholic fatty liver disease. There was no prior history of inflammatory arthritis and no personal or family history of skin psoriasis, inflammatory bowel disease or uveitis. There was no preceding genitourinary or gastrointestinal upset. His family history was significant for a sister with seronegative rheumatoid arthritis for which she was taking sulfasalazine.Examination revealed a normal BMI, synovitis at the wrists and proximal interphalangeal joints without evidence of joint effusion in the large joints. Blood tests revealed elevations in the ESR (83 mm/hour, reference range 0-10 mm/hour) and CRP (25mg/dL, reference range <5mg/dL). Serology was negative for the rheumatoid factor, anti-CCP antibodies, antinuclear antibodies, and an extractable nuclear antigen panel. Radiographs of the affected joints were unremarkable. Serological testing was positive for anti-SARS-CoV-2 IgG antibodies.He was started on oral Prednisolone 20mg daily and an NSAID with good symptomatic response and normalisation of his ESR (5mm/hour) and CRP (<1mg/dL). The course of prednisolone was tapered over a 6-week period and he is still in steroid free remission with normal inflammatory markers at follow up. The patient was given a diagnosis of a post-viral reactive arthritis which was attributed to the preceding COVID-19 illness.Case report-DiscussionPost infectious inflammatory arthritis has been described with many viral infections including: hepatitis virus, parvovirus B19, enterovirus, rubella, alphavirus (including Chikungunya), flavivirus (including Zika), herpes viruses (including Epstein-Barr virus), varicella, cytomegalovirus and human immunodeficiency virus (HIV). Interestingly, viral arthritis has not been reported in influenza and human coronaviruses (including SARS and MERS). Arthralgia was reported in 14.9% of laboratory confirmed COVID-19 cases in China during the early phases of the pandemic but inflammatory arthritis was not well described.The clinical course of the inflammatory arthritis in this case was self-limiting with enthesitis and synovitis resolving within six weeks of onset with the mainstay of treatment being symptomatic relief in the form of non-steroidal anti-inflammatory drugs and corticosteroids.Patient perspective: When I woke up that Tuesday morning with severe joint pains and stiffness, I knew something was not right. It was not like anything I have felt before in terms of my joints, having had sports injuries in the past. It was to the point where I was even struggling to go from sitting to standing. Without Prednisolone, I feel as if I would not have been able to work and may even have been house bound. I was relieved that this inflammatory arthritis did respond to Prednisolone. After six weeks of taking Prednisolone, the condition seemed to settle.Case report-Key learning pointsA self-limiting episode of inflammatory arthritis may occur following COVID-19 infection.

Insights into the knowledge of complex diseases: Environmental infectious/toxic agents as potential etiopathogenetic factors of systemic sclerosis.

Systemic sclerosis (SSc) is a connective tissue disease secondary to three cardinal pathological features: immune-system alterations, diffuse microangiopathy, and fibrosis involving the skin and internal organs. The etiology of SSc remains quite obscure; it may encompass multiple host genetic and environmental -infectious/chemical-factors. The present review focused on the potential role of environmental agents in the etiopathogenesis of SSc based on epidemiological, clinical, and laboratory investigations previously published in the world literature. Among infectious agents, some viruses that may persist and reactivate in infected individuals, namely human cytomegalovirus (HCMV), human herpesvirus-6 (HHV-6), and parvovirus B19 (B19V), and retroviruses have been proposed as potential causative agents of SSc. These viruses share a number of biological activities and consequent pathological alterations, such as endothelial dysfunction and/or fibroblast activation. Moreover, the acute worsening of pre-existing interstitial lung involvement observed in SSc patients with symptomatic SARS-CoV-2 infection might suggest a potential role of this virus in the overall disease outcome. A variety of chemical/occupational agents might be regarded as putative etiological factors of SSc. In this setting, the SSc complicating silica dust exposure represents one of the most promising models of study. Considering the complexity of SSc pathogenesis, none of suggested causative factors may explain the appearance of the whole SSc; it is likely that the disease is the result of a multifactorial and multistep pathogenetic process. A variable combination of potential etiological factors may modulate the appearance of different clinical phenotypes detectable in individual scleroderma patients. The in-deep investigations on the SSc etiopathogenesis may provide useful insights in the broad field of human diseases characterized by diffuse microangiopathy or altered fibrogenesis.

Parvovirus Reactivation in COVID-19.

Anemia is a diagnostic challenge in patients with coronavirus disease 2019 (COVID-19). This is due to the broad differential of etiologies for anemia, which includes bleeding, bone marrow suppression secondary to sepsis, and hemolytic anemia. Here, we present a first-ever case of otherwise unexplained anemia in a patient receiving treatment for COVID-19 secondary to parvovirus B19 reactivation. While parvovirus infections often present as acute states of anemia, this patient developed a case of reactivation secondary to immunosuppression from COVID-19 treatment. This case indicates the importance of assessing for parvovirus infections in COVID-19 patients with otherwise unexplained anemia.