Hemolytic anemia following intravenous immunoglobulins in children with PIMS-TS: Two case reports

This is the first case report on two children presenting with immediate and severe hemolytic anemia following the administration of high-dose intravenous immunoglobulins (IVIGs) in the context of pediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS). Hemolytic anemia was described as a significant decrease in hemoglobin and an increase in lactate dehydrogenase after the second administration of high-dose IVIGs was performed. Both patients were found to have AB blood group. One of our patients showed massive pallor, weakness, and inability to walk in association with hemolysis. However, in both cases, the anemia was self-limiting and transfusion of red blood cells was not required: both patients recovered without persistent impact. Nonetheless, we aim to draw attention to this widely unknown adverse effect of IVIG, especially in the context of PIMS-TS. We suggest determining the patient's blood group prior to high-dose IVIG infusion and replacing the second IVIG through high-dose steroids or anticytokine therapy. Using IVIGs containing lower titers of specifically anti-A or anti-B antibodies to avoid isoagglutinin-caused hemolytic anemia is desirable; however, the information is not routinely available

Screening and treatment for tuberculosis in a cohort of unaccompanied minor refugees in Berlin, Germany

INTRODUCTION: In 2015, 4062 unaccompanied minor refugees were registered in Berlin, Germany. According to national policies, basic clinical examination and tuberculosis (TB) screening is a prerequisite to admission to permanent accommodation and schooling for every refugee. This article evaluates the use of an interferon-γ-release-assay (IGRA) during the initial examination and TB screening of 970 unaccompanied minor refugees. RESULTS: IGRA test were obtained during TB screening for 301 (31.0%) of 970 adolescents not previously screened for TB. Positive IGRA results were obtained in 13.9% (42/301). Most of the 42 IGRA-positive refugees originated from Afghanistan or Syria (n?20 and 10 respectively). Two IGRA-positive adolescents were lost to follow-up, 2 were diagnosed with TB and the remaining 38 diagnosed with latent TB infection (LTBI). Demographic features of the 40 patients with positive IGRA result were as follows: 39 male, median age 16.8 years (IQR 16.0-17.2y), none meeting underweight criteria (median BMI 21.3kg/m2). On initial chest X-ray 2/40 participants had signs of active TB, while in 38 active disease was excluded and the diagnosis of latent TB infection (LTBI) made. Active hepatitis B-co-infection was diagnosed in 3/38 patients. All patients with LTBI received Isoniazid and Rifampicin for 3 months without occurrence of severe adverse events. The most frequently observed side effect was transient upper abdominal pain (n = 5). Asymptomatic elevation of liver transaminases was seen in 2 patients. 29 patients completed treatment with no signs of TB disease at the end of chemoprevention and 9 were lost to follow up. CONCLUSION: Screening for TB infection in minor refugees was feasible in our setting with a relatively high rate of TB infection detected. Chemopreventive treatment was tolerated well regardless of underlying hepatitis-B-status. Minor refugees migrating to Germany should be screened for TB infection, instead of TB disease only, regardless of the background TB incidence

Autoantibodies against cytokines: phenocopies of primary immunodeficiencies?

Anti-cytokine autoantibodies may cause immunodeficiency and have been recently recognized as 'autoimmune phenocopies of primary immunodeficiencies' and are found in particular, but not exclusively in adult patients. By blocking the cytokine's biological function, patients with anti-cytokine autoantibodies may present with a similar clinical phenotype as the related inborn genetic disorders. So far, autoantibodies to interferon (IFN)-γ, GM-CSF, to a group of TH-17 cytokines and to IL-6 have been found to be causative or closely associated with susceptibility to infection. This review compares infectious diseases associated with anti-cytokine autoantibodies with primary immunodeficiencies affecting similar cytokines or related pathways

Maintenance of Elective Patient Care at Berlin University Children's Hospital During the COVID-19 Pandemic

Background: In Germany, so far the COVID-19 pandemic evolved in two distinct waves, the first beginning in February and the second in July, 2020. The Berlin University Children's Hospital at Charité (BCH) had to ensure treatment for children not infected and infected with SARS-CoV-2. Prevention of nosocomial SARS-CoV-2 infection of patients and staff was a paramount goal. Pediatric hospitals worldwide discontinued elective treatments and established a centralized admission process. Methods: The response of BCH to the pandemic adapted to emerging evidence. This resulted in centralized admission via one ward exclusively dedicated to children with unclear SARS-CoV-2 status and discontinuation of elective treatment during the first wave, but maintenance of elective care and decentralized admissions during the second wave. We report numbers of patients treated and of nosocomial SARS-CoV-2 infections during the two waves of the pandemic. Results: During the first wave, weekly numbers of inpatient and outpatient cases declined by 37% (p < 0.001) and 29% (p = 0.003), respectively. During the second wave, however, inpatient case numbers were 7% higher (p = 0.06) and outpatient case numbers only 6% lower (p = 0.25), compared to the previous year. Only a minority of inpatients were tested positive for SARS-CoV-2 by RT-PCR (0.47% during the first, 0.63% during the second wave). No nosocomial infection of pediatric patients by SARS-CoV-2 occurred. Conclusion: In contrast to centralized admission via a ward exclusively dedicated to children with unclear SARS-CoV-2 status and discontinuation of elective treatments, maintenance of elective care and decentralized admission allowed the almost normal use of hospital resources, yet without increased risk of nosocomial infections with SARS-CoV-2. By this approach unwanted sequelae of withheld specialized pediatric non-emergency treatment to child and adolescent health may be avoided

Scabies, Periorbital Cellulitis and Recurrent Skin Abscesses due to Panton-Valentine Leukocidin-Positive Staphylococcus aureus Mimic Hyper IgE Syndrome in an Infant

We describe the clinical course of a 2-month-old infant who was evaluated for autosomal dominant Hyper IgE Syndrome based on eczema, periorbital cellulitis, skin abscesses, increased total IgE levels and blood eosinophilia. However, scabies and nasal colonization by Panton-Valentine Leucocidin-positive S. aureus were eventually diagnosed. After specific treatment, the child was asymptomatic

CD70 Deficiency Associated With Chronic Epstein-Barr Virus Infection, Recurrent Airway Infections and Severe Gingivitis in a 24-Year-Old Woman

Most of the few patients with homozygous CD70 deficiency described to date suffered from EBV-related malignancies in early childhood. We present a woman with CD70 deficiency diagnosed in adulthood. She presented in childhood with recurrent airway infections due to encapsulated bacteria, herpes zoster and a fulminant EBV infection followed by chronic EBV infection with mild lymphoproliferation and severe gingivitis/periodontal disease with high EBV viral load in saliva and gingival plaques as an adult. Up to the age of 24 years she developed no malignancy despite constant EBV viremia since primary EBV infection 15 years previously. Immunologic evaluation in childhood showed hypogammaglobulinemia with impaired polysaccharide responsiveness. She has been stable on immunoglobulin substitution with no further severe viral infections and no bacterial airway infections in adulthood. Targeted panel sequencing at the age of 20 years revealed a homozygous CD70 missense mutation (ENST00000245903.3:c.2T>C). CD70 deficiency was confirmed by absent CD70 expression of B cells and activated T cell blasts. The patient finished high school, persues an academic career and has rarely sick days at college. The clinical course of our patient may help to counsel parents of CD70-deficient patients with regard to prognosis and therapeutic options including haematopoetic stem cell transplantation

Severe infections of Panton-Valentine leukocidin positive Staphylococcus aureus in children

Infections caused by Panton-Valentine leukocidin-positive Staphylococcus aureus (PVL-SA) mostly present as recurrent skin abscesses and furunculosis. However, life-threatening infections (eg, necrotizing pneumonia, necrotizing fasciitis, and osteomyelitis) caused by PVL-SA have also been reported.We assessed the clinical phenotype, frequency, clinical implications (surgery, length of treatment in hospitals/intensive care units, and antibiotic treatments), and potential preventability of severe PVL-SA infections in children.Total, 75 children treated for PVL-SA infections in our in- and outpatient units from 2012 to 2017 were included in this retrospective study.Ten out of 75 children contracted severe infections (PVL-methicillin resistant S aureus n = 4) including necrotizing pneumonia (n = 4), necrotizing fasciitis (n = 2), pyomyositis (n = 2; including 1 patient who also had pneumonia), mastoiditis with cerebellitis (n = 1), preorbital cellulitis (n = 1), and recurrent deep furunculosis in an immunosuppressed patient (n = 1). Specific complications of PVL-SA infections were venous thrombosis (n = 2), sepsis (n = 5), respiratory failure (n = 5), and acute respiratory distress syndrome (n = 3). The median duration of hospital stay was 14 days (range 5-52 days). In 6 out of 10 patients a history suggestive for PVL-SA colonization in the patient or close family members before hospital admission was identified.PVL-SA causes severe to life-threatening infections requiring lengthy treatments in hospital in a substantial percentage of symptomatic PVL-SA colonized children. More than 50% of severe infections might be prevented by prompt testing for PVL-SA in individuals with a history of abscesses or furunculosis, followed by decolonization measures

Cross-sectional seroprevalence surveys of SARS-CoV-2 antibodies in children in Germany, June 2020 to May 2021

The rate of SARS-CoV-2 infections in children remains unclear due to many asymptomatic cases. We present a study of cross-sectional seroprevalence surveys of anti-SARS-CoV-2 IgG in 10,358 children recruited in paediatric hospitals across Germany from June 2020 to May 2021. Seropositivity increased from 2.0% (95% CI 1.6, 2.5) to 10.8% (95% CI 8.7, 12.9) in March 2021 with little change up to May 2021. Rates increased by migrant background (2.8%, 4.4% and 7.8% for no, one and two parents born outside Germany). Children under three were initially 3.6 (95% CI 2.3, 5.7) times more likely to be seropositive with levels equalising later. The ratio of seropositive cases per recalled infection decreased from 8.6 to 2.8. Since seropositivity exceeds the rate of recalled infections considerably, serologic testing may provide a more valid estimate of infections, which is required to assess both the spread and the risk for severe outcomes of SARS-CoV-2 infections

Impact of newborn screening for SCID on the management of congenital athymia

BACKGROUND: Newborn screening (NBS) programmes for severe combined immunodeficiency (SCID) facilitate early SCID diagnosis and promote early treatment with haematopoietic stem cell transplantation, resulting in improved clinical outcomes. Infants with congenital athymia are also identified through NBS due to severe T-cell lymphopaenia. With the expanding introduction of NBS programmes, referrals of athymic patients for treatment with thymus transplantation have recently increased at Great Ormond Street Hospital (GOSH), London, United Kingdom. OBJECTIVE: We studied the impact of NBS on timely diagnosis and treatment of athymic infants with thymus transplantation at GOSH. METHODS: We compared the age at referral and complications between athymic infants diagnosed after clinical presentation (N=25) and patients identified through NBS (N=19), referred for thymus transplantation at GOSH between 10/2019 and 02/2023. We assessed whether age at time of treatment influences thymic output at 6 and 12 months after transplantation. RESULTS: Infants referred after NBS identification were significantly younger and had less complications, in particular less infections. All deaths occurred in the non-NBS group, including six patients before and two after thymus transplantation because of pre-existing infections. In the absence of significant co-morbidities or diagnostic uncertainties, timely treatment was more frequently achieved after NBS. Treatment at <4 months of age was associated with higher thymic output at 6- and 12-months post-transplantation. CONCLUSION: NBS contributes to earlier recognition of congenital athymia, promoting referral of athymic patients for thymus transplantation prior to acquiring infections or other complications, and facilitating treatment at younger age, thus playing an important role in improving their outcomes