Immunoglobulin Infusion Research Articles

An Unusual Association of Hyper-IgE Syndrome with Celiac Disease: A Case Report

Hyper-IgE syndrome (HIES) is a primary immunodeficiency disorder characterized by eczema, cold abscesses, pneumonia, eosinophilia, and a very high serum IgE concentration. An association with celiac disease is rare. Immunodeficiency and autoimmunity are two manifestations of immune system dysfunction that can be associated with common pathophysiological links. We present the case of a 3-year-old child with psychomotor retardation and a history of recurrent infections who had generalized eczema, failure to thrive, and abdominal distension with hepatosplenomegaly. The patient improved after receiving a monthly intravenous immunoglobulin infusion and a gluten-free diet.

70 Comparative study between PIMS and Kawasaki disease

BackgroundKawasaki disease (kDa) is a multisystemic vasculitis affecting medium and small vessels with a predilection for the coronary arteries. It appears to be very similar to the pediatric multisystemic inflammatory syndrome (PIMS), which is a post-infectious inflammatory condition occurring after SARS-COV2 infection. Although these two entities have clinical and biological similarities, marked differences are identified. The aim of this study is to compare the two conditions in order to highlight the specific criteria of each of these related entities and to describe their demographic, clinical, biological and therapeutic characteristics in our context.MethodSingle center prospective observational study from January 2021 to March 2022 was conducted, comparing children admitted for PIMS on the basis of persistent fever, inflammatory syndrome, and positive COVID-19 IgG serology to patients hospitalized for kDa according to American Heart Association criteria.Results42 cases were recruited, among them 24 PIMS and 18 kDa, with a male predominance. The average age was 5 years for PIMS and 2 years and 7 months for kDa. All had a persistant fever with an average duration of 8 days as reason for consultation. Conjunctivitis was found in 88% of kDa vs 75% of PIMS and cheilitis in 94% of kDa vs 75% of PIMS. Skin rash, extremity involvement, cervical adenopathy were reported in both pathologies with respective percentages of 62.5%, 17.4% and 25% for PIMS vs 61.1%, 33.3% and 33.3% for kDa. Abdominal pain was reported in 54.2% of PIMS patients vs 5.6% of kDa. All patients had an inflammatory syndrome. The mean sedimentation rate was 67 mm at the first h in PIMS and 99 mm at the first h in kDa. The mean CRP was 147 mg/l in PIMS vs 132 mg/l in kDa. Lymphopenia was predominant in PIMS with 33% vs 11% in kDa. Cardiac enzymes were higher in PIMS with 29% of myocarditis and 15% of coronary dilatation vs 16.7% of coronary involvement in kDa. All PIMS patients received immunoglobulin infusion IV-IG, corticosteroid therapy, and an antiplatelet agent, whereas patients with kDa received IV-IG and acetyl salicylic acid in anti-inflammatory doses. Apyrexia was obtained at day 1 of treatment in the majority of patients, whereas 5.6% of kDa had persistent aneurysm.ConclusionPIMS cases predominated over kDa cases during this pandemic period. The distinction between the two entities could be difficult given the clinico-biological similarities. Abdominal pain was significantly more frequent in PIMS patients, whereas lymphopenia and myocarditis were not. The prognosis was better in PIMS.

VACCINE-INDUCED IMMUNE THROMBOTIC THROMBOCYTOPENIA (VITT) BY A THIRD DOSE OF CHADOX1 NCOV-19 (ASTRAZENECA) AFTER BNT162B2 (PFIZER–BIONTECH)

An atypical case of VITT was described resulting from a vaccination schedule where the third booster with ChAdOx1 nCoV-19 (AstraZeneca) was administered. The patient received a complete vaccination schedule with two doses of Pfizer-BioNTech (BNT162b2) without any complications before the third dose. However, the patient has developed an infrequent yet extreme prothrombotic; hypercoagulable state caused by platelet-activating anti-Platelet Factor 4 (PF4) antibodies. This phenomenon is typically triggered by the proximate administration of an adenoviral vector vaccine against COVID-19. The patient's symptoms began ten days after taking the third dose of the ChAdOx1 nCoV-19 vaccine (AstraZeneca). His main complaints when hospitalized were severe headaches and right abdominal pain. The blood tests and MRI scan imaging findings were very characteristic of VITT, and a rare cerebral venous sinus thrombosis was found. Also, a markedly elevated D-dimer and strong positive PF4-dependent enzyme-immunoassay test results were documented. Due to discerning clinical suspicion, this patient was rapidly treated with immunoglobulin infusion for two days and oral steroids for three days. Subsequently, he was anticoagulated with the new oral anticoagulant edoxaban after platelet numbers recovery. In a few days, platelets normalized, and D-dimer levels decreased, while anti- PF4-dependent enzyme-immunoassay test results showed a slow decline. He was discharged taking oral edoxaban without any sequeal.

SARS-CoV-2 antibody response to the second COVID-19 vaccination in neuromuscular disease patients under immune modulating treatment

Einer erfolgreichen Impfung (adäquater Anstieg der Anti-S[Spike]-Protein-Antikörper) gegen SARS-CoV‑2 (engl. severe acute respiratory syndrome coronavirus type 2) wird ein suffizienter Schutz gegen einen schweren Verlauf von COVID-19 (engl. coronavirus disease 2019) zugeschrieben. Bei Patient*innen mit chronisch-inflammatorischen Erkrankungen (engl. „chronic inflammatory diseases“ [CID]) und Immunsuppression ist der Impferfolg weiterhin im wissenschaftlichen Diskurs. Daher evaluierten wir bei Patient*innen mit einer neuromuskulären Erkrankung (NME), die zu regelmäßigen Infusionen von Immunglobulinen in unserer neurologischen Tagesklinik/Ambulanz vorstellig wurden, 2 Wochen nach vollständiger Immunisierung die Antikörpertiter gegen das S1 (S1-Untereinheit des Spike-Proteins) -Antigen von SARS-CoV‑2. Unsere Daten zeigen, dass Patient*innen mit einer chronischen autoimmunen NME und gleichzeitiger immunsuppressiver bzw. immunmodulierender Therapie nach einer Impfung sowohl mit einem mRNA- als auch mit einem Vektorimpfstoff eine Antikörperantwort aufwiesen. Im Vergleich zu gesunden Proband*innen zeigte sich eine vergleichbare Anzahl an Serokonversionen durch die Impfung. Eine Korrelation zwischen Immunglobulindosierung und Impfantwort sowie Infusionsintervall und Impfantwort ließ sich nicht feststellen. Demgegenüber zeigte jedoch insbesondere die Kombination aus Mycophenolatmofetil (MMF) und Prednisolon eine signifikante Reduktion der spezifischen Antikörpersynthese.

Kawasaki disease: a comprehensive review

Introduction and purpose: Kawasaki disease is an acute, self-limited vasculitis of medium arteries, and it affects children under 5 years old. It can lead to coronary artery aneurysms.
 Brief description of the state of knowledge: Pathogenesis of Kawasaki disease is unclear. The diagnosis is based on the clinical findings. The characteristic symptoms are polymorphous skin rashes, conjunctivitis, erythema, dryness, cracking and bleeding of the lips, erythema and swelling of palms and soles and cervical lymphadenopathy. Kawasaki disease is defined as a fever for 5 days accompanied by 4 or more of the diagnostic symptoms described above. The classic diagnosis is based on the exclusion of other diseases too. The diagnosis of incomplete Kawasaki disease is suggested if less than 4 main clinical features are found. It is the most common cause of acquired heart disease in children. Kawasaki disease can lead to coronary artery aneurysm, myocarditis and pericarditis so it is very important to treat this illness correctly. Basic treatment is a single infusion of intravenous immunoglobulin and high-dose aspirin. Recurrent Kawasaki disease (persistent fever after first line treatment with IVIG and aspirin) requires the same treatment as used for the first episode. Corticosteroids and immune-modulating therapies can be used as second and third line options. Quick recognition and early treatment result in a reduction of coronary artery abnormalities.
 Conclusion: This article reviews basic informations, history, epidemiology, pathophysiology, clinical presentation, diagnostic criteria, complications and treatment of Kawasaki disease.

Vaccine-Induced Immune Thrombotic Thrombocytopenia (VITT) by A Third Dose of Chadox1 Ncov-19 (Astrazeneca) After BNT162b2 (Pfizer–BioNTech)

An atypical case of VITT was described resulting from a vaccination schedule where the third booster with ChAdOx1 nCoV-19 (AstraZeneca) was administered. The patient received a complete vaccination schedule with two doses of Pfizer–BioNTech (BNT162b2) without any complications before the third dose. However, the patient has developed an infrequent yet extreme prothrombotic; hypercoagulable state caused by platelet-activating anti-platelet factor 4 (PF4) antibodies. This phenomenon is typically triggered by the proximate administration of an adenoviral vector vaccine against COVID-19. The patient’s symptoms began ten days after taking the third dose of the ChAdOx1 nCoV-19 vaccine (AstraZeneca). His main complaints when hospitalized were severe headaches and right abdominal pain. The blood tests and MRI scan imaging findings were very characteristic of VITT, and a rare cerebral venous sinus thrombosis was found. Also, a markedly elevated D-dimer and strong positive PF4-dependent enzyme- immunoassay test results were documented. Due to discerning clinical suspicion, this patient was rapidly treated with immunoglobulin infusion for two days and oral steroids for three days. Subsequently, he was anticoagulated with the new oral anticoagulant edoxaban after platelet numbers recovery. In a few days, platelets normalized, and D-dimer levels decreased, while anti- PF4-dependent enzyme-immunoassay test results showed a slow decline. He was discharged taking oral edoxaban without any squeal.

Delayed eczematous skin reaction as an adverse drug reaction to immunoglobulin infusions: A case series

BackgroundPompholyx and eczematous reactions are known adverse reactions to intravenous immunoglobulins (IVIg) infusion, but little is known about their clinical characteristics, associated outcomes and management. ObjectiveTo describe IVIg-induced eczematous skin reactions. MethodsWe conducted a retrospective study on cases of delayed skin reactions post-IVIg infusion notified to the French Regional Pharmacovigilance Centre from 1985 to 2020. ResultsA total of 27 patients were identified, of whom 85% were male. IVIg infusions were given in a neurological indication in 82% of cases. Eczematous skin reactions occurred in two-thirds of cases after the first infusion, with a median time to onset of 11 days. Palmoplantar pompholyx was the most common presentation, being seen in 63% of patients. Other eruptions were erythemato-squamous or maculopapular. Eight patients were classified as severely affected and developed extensive lesions (>50% BSA). One third of the 27 patients required hospitalization. All of the severe eczematous reactions involved males receiving high doses of IVIg for neurological diseases. Biopsies of severe cases revealed a common non-specific eczematous pattern. Relapses were frequent and more severe than the initial reaction. Reintroduction of the same IVIg product consistently resulted in relapse, whereas switching IVIg type produced relapse in only 53% of patients. ConclusionWe present the largest retrospective study of delayed skin reactions after IVIg infusions. This side-effect may be severe and have a polymorphic presentation. Relapse occurs frequently but less consistently after IVIg switch.

P810: BONE MARROW FAILURE IN PATIENTS CARRYING VARIANTS ON CARD11 GENE.

Background: An accurate differential diagnosis in children with Marrow Failure (MF) is crucial for the clinical management of the disease. In addition to the classical congenital MF (cMF), the role of Inborn Errors of Immunity (IEI) have been recently highlighted as potential cause of the disease. CARD11 is a membrane protein acting as a key signaling scaffold which controls the antigen-induced lymphocyte activation during the adaptive immune response (NF-kB, JNK and mTOR pathway). Germline CARD11 mutations can result in gain/loss of function of the protein leading to different phenotypes (SCID, BENTA disease, atopy, CVID). Several heterozygous hypomorphic/dominant negative (DN) variants of CARD11 have demonstrated a loss of protein function, exhibiting high penetrance and variable expressivity. In particular, mutations in the GUK (Guanylate Kinase) domain seem to be involved in modulating the self-inactivating capacity of CARD11. No CARD11 variants have ever been described to be associated with MF. Herein, we report 4 patients with MF carrying variants on the CARD11 gene. Aims: To evaluate the clinical/immunological features and genetic profile of patients with MF carrying CARD11 variants and followed in our Centre. Methods: A restrospective review of clinical, immunological and genetic data was performed from patients’ records. Molecular analysis was conducted using Next-Generation Sequencing (NGS), targeted panels including genes involved in both cMF and IEI, or by Whole Exome Sequencing (WES). Filtering of variants was performed according to Mendelian disease segregation and zigosity (OMIM), in silico prediction of pathogenicity (ACMG criteria in “Varsome”), and minor allele frequency (reported in GnomAD). Results: Four children carrying variants in the CARD11 gene presented with MF as initial sign of the disease (n=2) or with immune cytopenias further evolving into MF (n=2). Their clinical/immunological features, genetic profile, treatment and follow-up are reported in Table1. Lymphocytes subsets analysis revealed a deficiency of B memory, Tregs and an increased of HLADR+ T cells in all patients. Two cases showed elevated CD4-CD8- TCR αβ+ T-cells (“double negatives T-cells”). All patients showed autoimmune stigmata and 2 of them also presented autoimmune hepatitis. No patients responded to first-line treatment. One responded to second-line treatment with Mychofenolate-mofetil (MMF) and periodic infusion of immunoglobulins. The remaining 3 patients underwent hematopoietic stem cell transplantation (SCT) from haploidentical-αβCD19 depleted transplant (n=2) or HLA-identical cousin (n=1) (Table1). Image:Summary/Conclusion: This report highlights novel phenotypic characteristics of patients carrying variants in CARD11 such as MF and autoimmune hepatitis, thus widening the clinical spectrum of the disease. This underlines the need for an enlarged molecular analysis in pediatric cases of MF and suggests that, in some patients, immune-mediated destruction of blood and marrow cells cooperate in generating the cytopenia. Three variants detected in our cohort are located in the GUK domain of the gene, close to other reported pathogenic dominant negative mutations leading to haploinsufficiency, suggesting interference with the CARD11’s ability to self-inactivate. Functional study will be necessary to confirm the pathogenic role of such variants. Although treatment with MMF may be considered, SCT represents the only curative option for such patients.

A Systematic Review and Meta-Analysis on the Safety and Efficacy of Second Dose Immunoglobulin Versus High Dose Pulse Methylprednisolone in Refractory Kawasaki Disease

Background: There is limited information available regarding the management of IVIG-refractory Kawasaki Disease (KD). Objective: This study aimed to evaluate the safety and efficacy of a second intravenous immunoglobulin (IVIG) infusion versus intravenous methylprednisolone (IVMP) in patients with IVIG-refractory KD. Methodology: Cochrane Library, PubMed, Medline, Elsevier (Science Direct), Springer Link and BMJ databases were searched from May 1, 2020 to December 31, 2020. We included randomized controlled trials (RCTs) and high-quality prospective and retrospective studies, with population restricted to children 0 months to 18 years, with KD refractory to initial IVIG at 2g/kg, who remained febrile for 24-48 hours after completion of initial IVIG, and who received second-line monotherapy with either a second dose IVIG or IVMP. We conducted a meta-analysis using Review Manager [RevMan] 5.4.1 software. Results: A total of six studies (n=188 patients) were analyzed. The incidence of coronary artery lesions was comparable between a second dose of IVIG and IVMP (RR 0.82, 0.34-1.96, P=0.66) in patients with IVIG-refractory KD. The rate of fever resolution to a second IVIG, compared to IVMP, was not significantly different between groups (RR 0.97, 0.84-1.13, P=0.72). There was a significantly higher incidence of adverse events in the IVMP group (RR 0.42, 0.26-0.57, P=0.0002), but these were all transient and resolved without further treatment. Conclusion: There is no significant difference in the incidence of coronary artery lesions and rate of fever resolution post-retreatment with a second dose of IVIG versus IVMP in IVIG-refractory KD. More adverse events were reported in the IVMP group. Keywords: Mucocutaneous Lymph Node Syndrome, Kawasaki Disease, Refractory Kawasaki Disease, Immunosuppressant, Intravenous Immunoglobulin, Methylprednisolone, Second IVIG Infusion

Clinical presentation and short-term outcomes of multisystemic inflammatory syndrome in children in Lagos, Nigeria during the COVID-19 pandemic: A case series.

SummaryBackgroundMultisystemic inflammatory syndrome in children (MIS-C) has increasingly been documented globally with the progression of the COVID-19 pandemic and a significant proportion of cases have been noted in children of Black descent. There has been a noticeable discrepancy in the presentation and outcomes of COVID-19 infection in sub-Saharan Africa compared to the rest of the world. We documented the demography, clinical features, laboratory and imaging findings, therapeutic management, and short-term outcomes of paediatric patients with MIS-C diagnosed during the COVID-19 pandemic in Lagos, Nigeria.MethodsWe carried out a retrospective review of MIS-C cases seen in nine public and private hospitals in Lagos from July 10, 2020 to July 30, 2021. Data on clinical presentation, laboratory investigations, therapy as well as outcomes at 2 weeks, 6 weeks, 3 months and 6 months were analyzed.Findings28 children and adolescents with median age of 7·5 (IQR 2·3 - 9·4) years were diagnosed with MIS-C. MIS-C was suspected in 24 patients (85·7%) at initial clinical evaluation and mucocutaneous, gastrointestinal and cardiovascular manifestations were identified in 75·0%, 71·4% and 89·3% of patients respectively. Acute kidney injury and aseptic meningitis were noted in 32·1% and 17·9% of patients respectively. Cardiac manifestations at presentation included coronary dilatation and pericardial effusion in 46·4% each, ventricular dysfunction (32·1%), atrioventricular valve regurgitation (25·0%), prolonged QTc interval (40·0%) and first-degree atrioventricular block (16·0%). Therapy included aspirin in 89·3%, steroids in 75·0% and intravenous immunoglobulin (IVIG) infusion in 60·7%. All patients survived and were discharged after a mean of 11·14 (SD 5·65) days. Frequency of coronary dilatation had reduced from 46·4% to 7·1% by 3 months follow up and prolonged QTc interval persisted until the 6 week follow up in 4.5% of patients. Echocardiogram and electrocardiogram findings were normal in all patients assessed at 6 months follow up.InterpretationMIS-C is an important diagnosis in children presenting with prolonged fever during the COVID-19 pandemic. Cardiovascular manifestations occurred in several children with MIS-C and improved by 6 months follow up. Early diagnosis and prompt institution of a combination of antiplatelet therapy, steroids and IVIG appear to be beneficial.FundingNone.

Intravenous immunoglobulin infusion contributes to a high incidence of false reactive screen results for human T-lymphotropic virus

Intravenous immunoglobulin (IVIg) has been increasingly used to treat immunodeficiencies and inflammatory disorders. However, IVIg has also been shown to affect a wide range of laboratory testing, including human T-lymphotropic virus (HTLV) screening. Our laboratory frequently observes false reactive HTLV screens from patients receiving IVIg infusions, however the extent of IVIg contribution to the false reactivity has not been extensively investigated. The objective of this study was to explore the prevalence of HTLV-1/2 infection in patients from the Sydney metropolitan area and evaluate the positive predictive value for HTLV screening test in sera from patients with or without IVIg infusions. HTLV screening test results from sera of 3843 patients referred to Central Sydney Immunology Laboratory between June 2006 and May 2021 were retrospectively analysed. Among 72 (1.9%) sera reactive on screening enzyme-linked immunosorbent assay (ELISA), 62 (86.1%) were from patients receiving IVIg infusions, including 60 collected post-IVIg and two collected pre-IVIg infusions. Only two (3.3%) of the 60 post-IVIg sera were positive on confirmatory western blot. In contrast, in non-IVIg sera, five (50.0%) from the 10 screen-reactive sera were positive on western blot. If positive western blot is used as the reference for determining 'true' HTLV infection, we found the positive predictive value of HTLV screening ELISA in sera collected post-IVIg (3.3%) is considerably lower than that in non-IVIg and pre-IVIg sera (41.7%). The vast majority of false reactive screen results (89.2%) in our study cohort were from sera collected post-IVIg infusion. Our study suggests that the high incidence of falsely reactive results in HTLV screening ELISA could be attributed to IVIg infusion. Hence, collection of sera from patients on IVIg should be avoided and screen-reactive results should be interpreted with greater caution, particularly for patients from non-endemic areas.

Human Metabotropic Glutamate Receptor 5 Antibodies Alter Receptor Levels and Behavior in Mice.

Ophelia syndrome or encephalitis with antibodies against the metabotropic glutamate receptor 5 (mGluR5) manifests with behavioral changes, memory deficits, and anxiety. To study the antibody pathogenicity, mice received continuous cerebroventricular infusion of patients' or controls' immunoglobulin G (IgG) for 14 days, followed by a 15-day washout. The effects on hippocampal mGluR5 clusters were determined by confocal microscopy. Animals infused with patients' IgG, but not controls' IgG, showed memory impairment, increased anxiety, and decreased neuronal surface mGluR5 clusters. After antibody clearance, both behavioral and molecular changes reversed to baseline conditions. These findings support the pathogenicity of these antibodies in anti-mGluR5 encephalitis. ANN NEUROL 2022;92:81-86.

Perioperative Desensitization with IgA- and IgM-Enriched Human Immunoglobulins Allows Safe Lung Transplantation in Patients with Preformed Donor Specific Antibodies

<h3>Purpose</h3> Pretransplant sensitization to human leukocyte antigens (HLA) increases the recipient waiting list time and mortality in lung transplantation. Instead of awaiting crossmatch-negative donors, since 2013, recipients with preformed anti-HLA donor specific antibodies (pfDSA) have been managed peri-transplant at our institution with repeated IgA- and IgM-enriched intravenous immunoglobulin infusions (IgGAM, first infusion: 2gr/kg, then 0.5gr/kg every 4 weeks thereafter to a maximum of 6 months), usually in combination with plasmapheresis (PE) before IgGAM and a single dose of anti-CD20 antibody (375mg/m², Rituximab) after the first IgGAM infusion. This study presents the 8-year results of this protocol in patients transplanted with pfDSA. <h3>Methods</h3> Records of patients transplanted at our institution between 02/2013 and 10/2021 were reviewed. Outcomes were compared between patients with pfDSA (pfDSA group) and those without any early DSA (control group)<i>.</i> Patients without pfDSA who developed DSA only post transplantation (n=219) were excluded from the analysis. Median follow-up was 47 (21-73) months. <h3>Results</h3> Of the 994 transplanted patients, 55 (5%) patients exhibited pfDSA and 721 (73%) did not develop any early DSA. Among these 55 patients, 40 (73%) patients possessed pfDSA against class II HLA antigens and 17 (31%) patients against class I antigens (2 patients against both classes). Twelve (22%) patients showed a positive retrospective CDC crossmatch and 21 (38%) patients developed additional de-novo DSA after transplantation. Forty-four (80%) patients were treated with PE and 45 (82%) patients with Rituximab. At follow-up end, treatment was completed in 45 (82%) patients (still on treatment, n=4; in-hospital deaths, n=2; treatment interrupted earlier as intended by protocol, n=4). In these 45 patients, IgGAM treatment cleared DSA in 33 (73%) patients, with 4 (12%) patients showing the same DSA recurrence. In pfDSA vs. control patients and at 5-year follow-up, respectively, graft survival (%) was 83 vs. 76 (p=0.40) and freedom from chronic lung allograft dysfunction (%) 72 vs. 72 (p=0.62). <h3>Conclusion</h3> In lung transplantation, a treatment protocol based on IgGAM allowed transplanting patients with preformed DSA with good 5-year graft survival similar to control patients.

Fluctuations in quality of life and immune responses during intravenous immunoglobulin infusion cycles

Despite adequate infection prophylaxis, variation in self-reported quality of life (QOL) throughout the intravenous immunoglobulin (IVIG) infusion cycle is a widely reported but infrequently studied phenomenon. To better understand this phenomenon, subjects with humoral immunodeficiency receiving replacement doses of IVIG were studied over 3 infusion cycles. Questionnaire data from 6 time points spread over 3 IVIG infusions cycles (infusion day and 7 days after each infusion) were collected in conjunction with monitoring the blood for number of regulatory T-cells (Treg) and levels of 40 secreted analytes: primarily cytokines, chemokines, and growth factors. At day 7, self-reported well-being increased, and self-reported fatigue decreased, reflecting an overall improvement in QOL 7 days after infusion. Over the same period, percentage of Treg cells in the blood increased (p<0.01). Multiple inflammatory chemokine and cytokine levels increased in the blood by 1 hour after infusion (CCL4 (MIP-1b), CCL3 (MIP-1a), CCL2 (MCP-1), TNF-α, granzyme B, IL-10, IL-1RA, IL-8, IL-6, GM-CSF, and IFN- γ). The largest changes in analytes occurred in subjects initiated on IVIG during the study. A significant decrease in IL-25 (IL-17E) following infusion was seen in most intervals among subjects already receiving regular infusions prior to study entry. These findings reveal several short-term effects of IVIG given in replacement doses to patients with humoral immunodeficiency: QOL consistently improves in the first week of infusion, levels of a collection of monocyte-associated cytokines increase immediately after infusion whereas IL-25 levels decrease, and Treg levels increase. Moreover, patients that are new to IVIG experience more significant fluctuations in cytokine levels than those receiving it regularly.

Multisystem inflammatory syndrome in adults: a\xa0case report\xa0and review of the literature

BackgroundThe current coronavirus disease pandemic has brought recognition of multisystem inflammatory syndrome in adults as a de novo entity, temporally associated with severe acute respiratory syndrome coronavirus 2 viral infection in adults. Hypothesis about its true pathophysiology remains controversial.Case reportThe patient was a 22-year-old African American female presenting to the emergency department with fever, sore throat, and neck swelling for the past 3 days. During her initial emergency department visit, her blood pressure was stable at 110/57 mmHg, temperature of 39.4 °C, and heart rate of 150 beats per minute. While in the emergency department, she received broad-spectrum antibiotics (vancomycin and ceftriaxone) and 30 cc/kg bolus of normal saline. Originally, she was admitted to a telemetry floor. The following night, a rapid response code was called due to hypotension. At that time, her blood pressure was 80/57 mmHg. She appeared comfortable without signs of respiratory distress. She received intravenous fluids and vasopressors, and was transferred to the intensive care unit. The patient had reported a previous coronavirus disease infection a few weeks prior. She was diagnosed and treated for multisystem inflammatory syndrome in adults. Intravenous immunoglobulin infusion was initiated and completed on hospital day 5. She was weaned off vasopressors by day 6, and discharged home on day 11.ConclusionOur case report is an example of the presentation, diagnosis, and management of multisystem inflammatory syndrome. Our research into previous case reports illustrates the wide range of presentations, degree of end organ damage, and treatment modalities. This diagnosis needs to be considered in the presence of recent coronavirus disease infection with new-onset end organ failure, as prompt diagnosis and treatment is crucial for better outcomes.

Recurrence of hepatocellular carcinoma and hepatitis delta infection in a liver transplant recipient: a case report

A 52 years-old caucasian man, with HIV chronic infection, underwent a liver transplantation in 2012 because of end stage liver disease due to HCV/HBV/HDV and HCC. Tacrolimus monotherapy was started as immune-suppression. After transplant, the patient became spontaneously HCV-RNA negative, HBV-HDV recurrence was prevented by tenofovir and anti-HBs immunoglobulins infusion and the patient remained HBsAg neg. In 2018 anti-HBs levels started to decline despite regular immunoglobulin infusion. Frequency and dosage of immunoglobulin infusions were increased but by the end of the year the patient became HBsAg positive with an HDV-RNA >19000 copies/ml; HBV-DNA remained undetectable.

Congenital thrombotic thrombocytopenic purpura simulating alloimmune thrombocytopenia

Congenital thrombotic thrombocytopenic purpura (cTTP) is a thrombotic microangiopathic caused by severely reduced activity of the von Willebrand factor-cleaving protease A Disintegrin And Metalloproteinase with a Thrombospondin type 1 Motif, member 13 (ADAMTS-13), which leads to small-vessel platelet-rich thrombi, thrombocytopenia, and microangiopathic hemolytic anemia (MHA) in the absence of neutralizing antibodies. We describe a case of cTTP in a female neonate presenting initially on the 1st day of life with asymptomatic thrombocytopenia thought to be alloimmune thrombocytopenia, then progressed to severe neonatal jaundice, pallor, and MHA, in whom ADAMTS-13 levels <5%, and the anti-ADAMTS-13 antibody titer was negative confirming the diagnosis of cTTP. The patient initially received intravenous immunoglobulin infusion before documenting MHA. She received fresh frozen plasma infusions which successfully reversed the MHA (by supplying ADAMTS-13) and prevented organ damage in this patient.

Idiopathic purpura fulminans associated with anti-protein S antibodies in children: a multicenter case series and systematic review

AbstractIdiopathic purpura fulminans (IPF) is a rare but severe prothrombotic coagulation disorder that can occur after chickenpox or human herpesvirus 6 (HHV-6) infection. IPF leads to an autoantibody-mediated decrease in the plasma concentration of protein S. We conducted a retrospective multicenter study involving patients with IPF from 13 French pediatric centers and a systematic review of cases in published literature. Eighteen patients were included in our case series, and 34 patients were included as literature review cases. The median age was 4.9 years, and the diagnostic delay after the first signs of viral infection was 7 days. The lower limbs were involved in 49 patients (94%) with typical lesions. In all, 41 patients (78%) had a recent history of varicella-zoster virus infection, and 7 patients (14%) had been infected by HHV-6. Most of the patients received heparin (n = 51; 98%) and fresh frozen plasma transfusions (n = 41; 79%); other treatment options were immunoglobulin infusion, platelet transfusion, corticosteroid therapy, plasmapheresis, and coagulation regulator concentrate infusion. The antithrombin level and platelet count at diagnosis seemed to be associated with severe complications. Given the rarity of this disease, the creation of a prospective international registry is required to consolidate these findings.

Transfusion-Associated Circulatory Overload (Taco) Presentations In Pediatric Patients

Abstract Introduction/Objective Limited literature exists regarding Transfusion Associated Circulatory Overload(TACO) in children. Its clinical expressions compared to those in adults remains to be fully explored. We report two TACO cases in children &amp;lt;18 months of age describing their clinical presentations compared to those in older patients. Methods/Case Report Case series Results (if a Case Study enter NA) Case 1: 1.13 kg 18 day old male neonate (27 weeks premature) with anemia requiring hemotherapy(HT). He received 35 ml aliquot of Red Blood Cells(RBCs) which he tolerated well on postoperative day(POD) 1 after bowel surgery. On POD 2, he was transfused RBCs(18 mls). Within 15 minutes of HT initiation, marked elevations in blood pressure(BP) were noted. Workup for a suspected transfusion reaction(STR) was initiated. Blood Bank studies revealed vital sign value(VSV) changes similarly seen in adults with TACO(Transfusion: 52; 2311, 2012). NT-proBNP levels post HT were markedly elevated (8,000 and 64,000 pg/ml).Case 2: 17 month old(11 kg) female with a three weeks prior history of COVID-19 admitted with fever/dehydration and subsequently diagnosed with multisystem inflammatory syndrome in children (MIS-C). Intravenous immunoglobulin(IVIG) infusion ordered and within 20 minutes of starting IVIG, she developed grunting. STR workup showed post HT BP/temperature elevations/chest X-ray with increased interstitial markings. Of note she had also received 1070 ml of intravenous fluids within 48 hours prior to HT. Elevated NT-proBNP levels pre/post HT were measured(17,121 pg/ml and 19, 824 pg/ml respectively). Symptoms improved with diuretics. Conclusion Children experiencing TACO can clinically manifest similarly as in adults with respect to BP elevations and pulmonary changes. Grunting may be an underappreciated manifestation of TACO in pts &amp;lt; 18 months of age. IVIG infusions used in the treatment of patients with MIS-C may present problematic fluid challenges. Recognition of and mitigation strategies for TACO risk factors in such patients may enhance HT safety in this vulnerable patient population.

Clinical profile of Kawasaki disease in children admitted at a tertiary care hospital of North India and their short-term follow-up.

Aim:The aim of this study was to evaluate presenting symptoms, clinical features, and laboratory tests for the diagnosis of Kawasaki disease (KD) in children and their short-term follow-up at a tertiary care hospital of North India from April 2017 to March 2020.Materials and Methods:A total of 31 children (23 boys and 8 girls) up to 10 years of age were included in this study. The diagnosis of KD was made as per the American Heart Association 2017 guidelines. Clinical features, laboratory parameters, and coronary involvement were compared between the complete and incomplete KD groups.Results:The incidence of complete versus incomplete KD was 19 (61.2%) versus 12 (38.7%) children, respectively. Change in extremities and oral mucosal changes were more encountered in the complete KD group as compared to the incomplete KD group (100% vs. 58.3%, P = 0.004, and 78.9% vs. 33.3%, P = 0.002, respectively). Coronary artery aneurysm was seen in 54% of the patients on echocardiography which was greater in the incomplete KD group (83.3%) as compared to the complete KD group (36.8%). The median time from the onset of symptoms to intravenous immunoglobulin infusion was <10 days in 84.2% of the patients with complete KD versus 41.7% with incomplete KD which was statistically significant. Fifty percent of the children with coronary ectasia and small aneurysm had normal coronaries at follow-up of 6 months.Conclusion:KD is probably underdiagnosed in most developing countries, like that of ours, and requires a high index of suspicion.