Combination Of Intravenous Immunoglobulin Research Articles

Single-cell RNA sequencing uncovers molecular mechanisms of intravenous immunoglobulin plus methylprednisolone in Kawasaki disease: attenuated monocyte-driven inflammation and improved NK cell cytotoxicity.

Intravenous immunoglobulin (IVIG) plus methylprednisolone as initial intensive therapy or additional therapy in Kawasaki disease (KD) has been used in clinical practice. However, its molecular and cellular mechanism is unclear. We performed single-cell analysis on 14 peripheral blood mononuclear cell (PBMC) samples obtained from 7 KD patients who received either IVIG monotherapy or IVIG plus methylprednisolone therapy. This encompassed 4 samples from KD patients collected before and after IVIG treatment, as well as 3 samples from KD patients before and after IVIG plus methylprednisolone therapy. Both IVIG monotherapy and IVIG plus methylprednisolone therapy can increase lymphocyte counts (e.g. CD4+T, CD8+T, and gdT cells) to address lymphopenia. They can also decrease monocyte counts and repress the expression of S100A12, NLRP3, and genes associated with immune-cell migration in monocytes. IVIG combined with methylprednisolone downregulates more monocyte-driven inflammatory pathways than IVIG alone. Additionally, this combination uniquely enhances NK cell cytotoxicity by modulating receptor homeostasis, while significantly upregulating interferon-related genes in CD4+ T cells, CD8+ T cells, and B cells, particularly type I interferons. The combination of IVIG with methylprednisolone attenuated monocyte-driven inflammation and improved NK cell cytotoxicity which might provide clues for pediatricians to consider treatment options for children with KD. Whether the monocyte-driven hyperinflammatory state and NK cell function can be indicators for the clinical choice of IVIG with methylprednisolone therapy in KD needs further investigation.

EFFICACY OF INTRAVENOUS IMMUNOGLOBULIN ALONE ON CORONARY ARTERY LESION REDUCTION IN KAWASAKI DISEASE.

Though Aspirin and intravenous immunoglobulin (IVIG) remain the standard treatments for Kawasaki Disease (KD) to minimize coronary artery damage, the duration and dosage of aspirin are inconsistent across hospitals. However, the lack of multi-center randomized trials prevents definitive answers to the impact of high-dose aspirin. This clinical trial was structured as a prospective, evaluator-blinded, multi-center randomized controlled trial with two parallel arms, aiming to assess the effectiveness of IVIG as a standalone primary therapy of KD in comparison to the combination of IVIG with high-dose aspirin therapy. KD patients were enrolled between September, 2016 and August, 2019. A final cohort of 134 patients were randomly assigned to the standard and test groups with 69 and 65 patients, respectively. The Standard group received IVIG (2 g/kg) along with aspirin (80-100 mg/kg/day) until fever subsided for 48 hours. The test group received IVIG (2 g/kg) alone. Following the initial treatment, both groups received a daily aspirin dose (3-5 mg/kg) for six weeks. The primary outcome measure was the occurrence of coronary artery lesions (CAL) at the 6-8 weeks mark. The secondary outcome is IVIG resistance. The overall rate of CAL in test group decreased from 10.8% at diagnosis to 1.5% and 3.1% at 6 weeks and 6 months, respectively. The CAL rate of standard group declined from 13.0% to 2.9% and 1.4%, with no statistically significant difference (P>0.1) in the frequency of CAL between the two groups. Furthermore, no statistically significant differences were found for treatment (P>0.1) and prevention (P>0.1) effect between the two groups. This marks the first prospective multi-center randomized controlled trial comparing the standard treatment of KD using IVIG plus high-dose aspirin against IVIG alone. Our analysis indicates that addition of high-dose aspirin during initial IVIG treatment is neither statistically significant nor clinically meaningful for CAL reduction. URL: http://www.clinicaltrials.gov ; identifier: NCT02951234. This study represents the first multi-center randomized controlled trial investigating the efficacy of high-dose aspirin or intravenous immunoglobulin (IVIG) during the acute stage of KD. This study assessed the impact of discontinuing high-dose aspirin (80-100 mg/kg/day) on the occurrence of CAL during the acute phase treatment of Kawasaki Disease.No significant differences were observed between high-dose aspirin plus IVIG treatment and IVIG alone treatment in terms of the frequency of abnormal coronary artery abnormalities. Additionally, our analysis revealed no statistically significant differences in either the treatment effect (the number of cases successfully treated) or prevention effect (the prevention of new cases) between these two treatments. Comparison analysis indicated the non-inferiority between two groups with or without high-dose aspirin.Administering the standard 2 g/kg/day IVIG without high-dose aspirin (80-100 mg/kg/day) during the acute phase therapy for KD does not increase the risk of coronary artery lesions, which are a primary cause of morbidity and mortality in KD patients.Addition of high-dose aspirin during initial IVIG treatment is not statistically significant or clinically meaningful.

The first national pediatric immune thrombocytopenia registry in Iran: research protocol and preliminary study results

BackgroundDisease registries are comprehensive databases that record detailed information on patients diagnosed with specific conditions, providing valuable insights into their diagnosis, treatment, and outcomes. This study aims to describe the pilot phase of the national pediatric Immune Thrombocytopenia(ITP) registry (NPITP) in Iran, serving as the inaugural interpretive report.MethodsThis patient-centered software system was implemented as a national program across multiple pediatric centers in Iran. Several focus groups were conducted to establish a minimum data set (MDS) comprising six main classes, 14 sub-classes, and 187 data elements. Following expert consensus on the final data set, a web-based software tool was developed by the dedicated IT team, accessible online and offline via https://disreg.sbmu.ac.ir/q/ITP.html. The registry included children aged between two months and 18 years with a platelet count below 100 × 109/L, based on predefined inclusion criteria.ResultsWithin a four-month period, a total of 60 ITP patients were registered, including 41 (68.3%) newly diagnosed cases, 68 (13.6%) persistent cases, and 14 (23.3%) with chronic ITP. The mean age of the registered patients was 55.93 ± 9.72 months. The most frequently observed bleeding symptoms were petechiae (68.3%), purpura (51.6%), and ecchymosis (13.3%). Among the newly diagnosed patients, 20 (33.3%) received intravenous immunoglobulin (IVIG), 17 (28.3%) were treated with prednisolone, and 17 (28.3%) received combined IVIG and steroid therapy. Of all patients, 40 (66.7%) demonstrated a complete response to treatment, while 16 (26.7%) exhibited a partial response. Four patients (6.7%) remained unresponsive to therapy. Treatment-related complications, such as Cushing’s syndrome, edema, weight gain, hirsutism, and mood disorders, were reported in 10 patients (16.6%). However, the majority of patients (81.7%) did not experience therapy-related complications.ConclusionThe pilot phase of the NPITP registry successfully implemented a web-based software tool for data collection, aiming to enhance the quality of care, facilitate clinical research, and support health service planning in the future.

A Rare Pediatric Case of Allopurinol-Induced Drug Reaction With Eosinophilia and Systemic Symptoms (DRESS) Successfully Treated With Intravenous Immunoglobulins

Allopurinol-induced drug reaction syndrome with eosinophilia and systemic symptoms (A-DRESS) is a well-described condition in adults, whereas it is uncommon among children. We describe a case of A-DRESS in a 16-year-old male with steroid-dependent nephrotic syndrome. He presented a life-threatening clinical course with persisting fever, skin rash, eosinophilia, lymphadenopathy, distributive shock, and herpesvirus 6 detection. The withdrawal of allopurinol and a combination of intravenous immunoglobulins (IVIGs) and systemic corticosteroids led to the patient’s recovery without sequelae. Drug reaction with eosinophilia and systemic symptoms (DRESS) in pediatrics is rare and can present in a severe form. Early diagnosis and timely treatment are critical for prognostic purposes. This report suggests the potentially crucial role of IVIG in the treatment of patients with A-DRESS.

Evaluation of the effectiveness of using prednisolone, tacrolimus, and intravenous immunoglobulin combination therapy on immune-mediated necrotizing myopathy-A non-randomized, observational research.

To recruit immune-mediated necrotizing myopathy (IMNM) patients with extramuscular manifestations who were refractory to initial therapy with either monotherapy with prednisolone or dual therapy with prednisolone and immunosuppressants. These patients subsequently received a combination of prednisolone, tacrolimus, and intravenous immunoglobulin (IVIG), and the efficacy of this treatment regimen was assessed in patients with IMNM. ①Clinical data and treatment measures are as follows: This study enrolled IMNM patients who were treated at the Neurology Department of the First Medical Center of PLA General Hospital from April 2020 to May 2023. These patients received a combination therapy of prednisolone, tacrolimus, and IVIG. ②Observational indicators included manual muscle test for 8 groups of muscles (MMT-8), muscle enzyme levels (creatine kinase (CK), lactate dehydrogenase (LDH), alanine aminotransferase (ALT), aspartate aminotransferase (AST)), and myositis disease activity assessment tool (MDAAT). This study enrolled eight patients. All observational indicators declined after treatment compared to before treatment, and these changes were statistically significant. Moreover, extramuscular manifestations also ameliorated compared to before treatment. The combination therapy of prednisolone, tacrolimus, and IVIG has demonstrated favorable efficacy in IMNM and broadened the treatment options for this disease. However, the results still require further validation by large-scale and randomized controlled studies.

Comparison of the oxidative stress status of children with ITP in two therapies using methylprednisolone and methylprednisolone along with IVIG

Background: Idiopathic thrombocytopenic purpura (ITP) is a rare and autoimmune disorder determined by an abnormal reduction in the number of platelets. The current study aims to evaluate the oxidative stress status of children with ITP in two treatment methods using methylprednisolone and methylprednisolone with intravenous immunoglobulin (IVIG).
 Materials and Methods: This retrospective study was conducted on 60 children with ITP who referred to Baghaei Hospital in Ahvaz in 2021. All the ITP children were equally divided into two groups, 30 receiving methylprednisolone and 30 receiving methylprednisolone and IVIG. The sampling of the patients’ blood was done in two stages before and after the start of treatment. Then, malondialdehyde (MDA), superoxide dismutase (SOD), total antioxidant status (TAS), total oxidative status (TOS), catalase (CAT) and glutathione were measured according to the instructions in the commercial kit. The analyses were performed using SPSS software version 23. P value < 0.05 was significant.
 Results: The number of platelets after treatment in methylprednisolone and methylprednisolone+ IVIG groups was 133.44 ± 18.93 and 158.76 ± 34.76 (×103/µL), respectively. Itas significantly increased compared to that before the treatment (P = 0.04). The amount of TAC in the group receiving methylprednisolone + IVIG and the methylprednisolone group was 1.64 ± 0.18 and 1.26 ± 0.53 nm, respectively; there was a remarkable difference between the two groups (P = 0.001). Also, SOD, CAT and glutathione in the methylprednisolone + IVIG group were remarkably higher than those in the methylprednisolone group (P < 0.05). Finally, the levels of TOS were lower in the methylprednisolone + IVIG group (19.74 ± 9.93 μmol) than in the methylprednisolone group (26.65 ± 10.64 μmol) (P = 0.01).
 Conclusion: A combination of IVIG and methylprednisolone was found to have a greater effect on improving antioxidant status and decreasing the oxidative stress indices of ITP children.

Clinical analysis of 11 cases multisystem inflammatory syndrome associated with SARS-CoV-2 Omicron variant infection in children

Objective: To explore the clinical characteristics, diagnosis, treatment, and follow-up of multisystem inflammatory syndrome in children (MIS-C) related to SARS-CoV-2 Omicron variant infection. Methods: A retrospective analysis was conducted on clinical data of 11 children with MIS-C, who were admitted to the Department of Pediatrics of Peking University First Hospital from December 2022 to January 2023. Clinical characteristics, treatment, and follow-up of MIS-C were summarized in this study. Results: The 11 cases contained 7 boys and 4 girls, with an age of 4.4 (2.0, 5.5) years on admission. All the patients had fever, with a duration of 7(5, 9) days. Other clinical manifestations included rash in 7 cases, conjunctival hyperemia in 5 cases, red lips and raspberry tongue in 3 cases, lymphadenopathy in 3 cases, and swollen fingers and toes in 2 cases. There were 8 cases of digestive symptoms, 8 cases of respiratory symptoms, and 3 cases of nervous system symptoms. Eight patients had multi-system injuries, and one of them had shock presentation. All 11 patients were infected with SARS-CoV-2 Omicron BF.7 variant. The laboratory examination results showed that all cases had elevated inflammatory indicators, abnormal coagulation function and myocardial damage. Six patients had elevated white blood cell counts, 5 cases had liver function abnormalities, 3 cases had kidney function abnormalities, and 8 cases had coronary artery involvement. All 11 patients received anti-infection treatment, of which 3 cases received only 2 g/kg intravenous immunoglobulin (IVIG), while the remaining 8 cases received a combination of IVIG and 2 mg/(kg·d) methylprednisolone. Among the 8 cases with coronary artery disease, 6 cases received low molecular weight heparin anticoagulation therapy. All patients were followed up in 2 weeks after being discharged, and their inflammatory markers had returned to normal by that time. The 8 cases with coronary artery disease and 3 cases with pneumonia showed significant improvement or back to normal at the 4-week follow-up. All patients had no new complications or comorbidities during follow-up of more than 3 months. Conclusions: MIS-C may present with Kawasaki disease-like symptoms, with or without gastrointestinal, neurological, or respiratory symptoms. Elevated inflammatory markers, abnormal coagulation function, and cardiac injury contribute to the diagnosis of MIS-C. IVIG and methylprednisolone were the primary treatments for MIS-C, and a favorable short-term prognosis was observed during a follow-up period of more than 3 months.

Clinical research of multisystem inflammatory syndrome in children

Objective: To analyze the clinical characteristics of children with multisystem inflammatory syndrome (MIS-C) associated with SARS-CoV-2 in China, and to improve the understanding of MIS-C among pediatricians. Methods: Case series study.Collect the clinical characteristics, auxiliary examinations, treatment decisions, and prognosis of 64 patients with MIS-C from 9 hospitals in China from December 2022 to June 2023. Results: Among the 64 MIS-C patients, 36 were boys and 28 were girls, with an onset age being 2.8 (0.3, 14.0) years. All patients suffered from fever, elevated inflammatory indicators, and multiple system involvement. Forty-three patients (67%) were involved in more than 3 systems simultaneously, including skin mucosa 60 cases (94%), blood system 52 cases (89%), circulatory system 54 cases (84%), digestive system 48 cases (75%), and nervous system 24 cases (37%). Common mucocutaneous lesions included rash 54 cases (84%) and conjunctival congestion and (or) lip flushing 45 cases (70%). Hematological abnormalities consisted of coagulation dysfunction 48 cases (75%), thrombocytopenia 9 cases (14%), and lymphopenia 8 cases (13%). Cardiovascular lesions mainly affected cardiac function, of which 11 patients (17%) were accompanied by hypotension or shock, and 7 patients (12%) had coronary artery dilatation.Thirty-six patients (56%) had gastrointestinal symptoms, 23 patients (36%) had neurological symptoms. Forty-five patients (70%) received the initial treatment of intravenous immunoglobulin in combination with glucocorticoids, 5 patients (8%) received the methylprednisolone pulse therapy and 2 patients (3%) treated with biological agents, 7 patients with coronary artery dilation all returned to normal within 6 months. Conclusions: MIS-C patients are mainly characterized by fever, high inflammatory response, and multiple organ damage. The preferred initial treatment is intravenous immunoglobulin combined with glucocorticoids. All patients have a good prognosis.

The Combination of Intravenous Immunoglobulin (IVIG) and Low Does Recombinant Human Thrombopoietin (rhTPO) for the Management of Corticosteroid/IVIG Monotherapy-Resistant Immune Thrombocytopenia in Pregnancy

Introduction Primary immune thrombocytopenia (ITP) is a common autoimmune disease characterized by a low platelet count resulting from antibody-mediated platelet destruction and insufficient platelet production. ITP, with a prevalence of 1 in 1000-10 000 pregnancies, accounts for approximately 3% of all causes of thrombocytopenia in pregnancy and is reported to be the most common cause of thrombocytopenia in the first and early second trimesters. It has been revealed that severe ITP is associated with devastating outcomes. It remains a challenge to manage pregnant patients with ITP. First-line treatment options in pregnant ITP patients currently include corticosteroids and intravenous immunoglobulin (IVIg). However, previous studies reported that the response rate of pregnant ITP patients to corticosteroids was less than 40% and that to IVIg was 38-56%, which was lower than that of nonpregnant ITP patients. The second-line treatment options are limited for pregnant ITP patients. Recombinant human thrombopoietin (rhTPO), a full-length and glycosylated TPO with a molecular weight of 90 000 Daltons developed by 3SBIO (Shenyang, China), has also been approved by the China State Food and Drug Administration as a second-line option for nonpregnant ITP patients. It cannot cross the placenta theoretically with such a large molecular weight, and thus, it has an apparent theoretical advantage over the two TPO mimetics since it would not impact the fetus. A study investigating the application of rhTPO in pregnancy suggested that rhTPO was a potentially effective and well-tolerated treatment option for ITP patients during pregnancy. It might be explained that the development of ITP was associated with increased platelet destruction and impaired platelet production, and the combination of IVIg and TPO mimetics impacts these two targets since IVIg could reduce platelet destruction, whereas TPO mimetics could increase platelet production. Therefore, we conducted a monocenter, single-arm, open-label study to investigate the efficacy and safety of low-dose rhTPO plus IVIg in pregnant corticosteroid/IVIg monotherapy-resistant ITP patients. Methods This study was registered at www.clinicaltrials.gov as NCT05634824.The following criteria were considered: patients have a diagnosis of primary ITP before or first onset during pregnancy; patients ≥ 18 years; patients complicated with bleeding manifestations and/or have a platelet count < 30 × 10^9/L and failed to respond to initial treatment of corticosteroids or intravenous immunoglobulin (IVIg) monotherapy or relapsed during the tapering or discontinuation of corticosteroids. For those patients, the initial combination therapy consisted of rhTPO at an initial dose of 150 U/kg once daily subcutaneously for 28 days and IVIg 400 mg/kg per day for 5 days. If the platelet count was in the range of 30 to 50 × 10^9/L, the combination therapy was repeated. To reduce the risk for thrombocytosis, patients received maintenance therapy consisting of rhTPO at a dose of 150 U/kg per day if the platelet count rose above 50 × 10^9/L, and treatment was discontinued when platelet counts exceeded 100 × 10^9/L. After delivery, the treatment consisted of rhTPO 150 U/kg per day, and the dose was maintained if the platelet count exceeded 30 × 10^9/L. In addition, IVIg 400 mg/kg per day for 5 days was added if the platelet count could not be maintained above 30 × 10^9/L. If patients did not achieve a count of 30 × 10^9/L within 4 weeks, treatment was also discontinued. Results The study included 19 patients with thrombocytopenia during pregnancy who were admitted to Peking University People's Hospital from December 1, 2022, to May 30, 2023, all of whom had failed hormone and IVIG treatment. The median age of those patients was 34 years old (range 20 to 42 years old), and the median platelet count before treatment was 13×10^9/L (range 1-30×10^9/L). The four-week response rate was 63.2% (12/19), and the median response time was 7.5 days (range 5 to 35 days). There were no treatment-related adverse reactions. Conclusions Low-dose rhTPO plus IVIg in pregnant corticosteroid/IVIg monotherapy-resistant ITP patients is effective and safe. These findings suggest that IVIg plus low-dose rhTPO may represent a potential combination therapy for pregnant patients with ITP.

In vitro evaluation of human intravenous immunoglobulin in combination with antimicrobials and human serum against multidrug-resistant isolates of Acinetobacter baumannii.

The high incidence of multidrug-resistant (MDR) Acinetobacter baumannii has been a challenge for health worldwide, due to the reduction of therapeutic options, making the use of antimicrobial combinations necessary for the treatment, such as meropenem, amikacin, and colistin. Antibodies against bacterial species, mainly immunoglobulins G (IgG), are produced for acting as effector mechanisms (neutralization, opsonization, phagocytosis, and complement system activation). Some studies have demonstrated promising results of IgG in combination with antimicrobial preparations against bacterial infections, in which the direct action of IgG has restored the immune system balance. Serious problem caused by the increase of MDR A. baumannii isolates results in a constant search for therapeutic alternatives to defeat these infections. However, this study aims to verify in vitro the phagocytosis rate of the A. baumannii-infected human monocytes, as well as to analyze possible morphological changes induced by intravenous immunoglobulin G (IVIG) with human serum in association with antimicrobials. The phagocytosis rate and bacterial cell binding capacity of IVIG were determined for two A. baumannii isolates submitted to 4mg/mL of human IVIG alone and in combination with different sub-minimum inhibitory concentrations (sub-MICs) of meropenem, amikacin, and colistin and processed for indirect immunofluorescence. Subsequently, these isolates were resubmitted and coupled with human serum and processed for scanning electron microscopy. There was no statistical difference for phagocytosis rates in the isolates tested. Bacterial isolates showed alterations in cell morphology when exposed to IVIG/human serum alone and in combination with antimicrobials such as alteration in shape, wrinkling, membrane depression, and especially cell rupture with extravasation of cytoplasmic material. The isolates visually differed in the IVIG binding to the bacterial cell, with higher fluorescence intensity, which corresponds to the highest IVIG binding, in the isolate more sensitive to meropenem, amikacin, and colistin. No differences between treatments were observed in the IVIG binding to the bacterial cell. The combined action of IVIG with meropenem, amikacin, and colistin against A. baumannii MDR isolates induced several bacterial cell damages. And when associated with human serum, a massive destruction of cells can be observed. These results may suggest the analysis of the use of IgG preparations for the treatment of A. baumannii MDR infections.

Acute necrotizing encephalopathy associated with COVID-19: case series and systematic review.

Acute necrotizing encephalopathy (ANE) is a rare neurological complication related to COVID-19. Here we present a case series of six Chinese cases with ANE associated with COVID-19 and review all reported cases in the literature. A total of six cases with ANE related to COVID-19 were enrolled in this study. Clinical manifestations, neuroimaging data, treatment and outcomes of these patients were analyzed. A literature review was performed in Pubmed and Embase and 25 cases with clinical and neuroimaging data were collected and analyzed. Among our six cases, the age of onset ranged from 15 to 56years, with a male-to-female ratio of nearly 1:1. All patients presented with reduced consciousness. Elevated interleukin 6 in serum and/or cerebrospinal fluid (CSF) was detected in four patients. Two patients improved clinically after intravenous methylprednisolone and intravenous immunoglobulin (IVIG). Based on the literature review, the majority of cases were from Europe and the United States (60%). Two age peaks at 10-20years (20%) and 50-60years (28%) were observed. Two cases were found with a heterozygous Thr585Met mutation. The mortality of ANE caused by COVID-19 was 42%. The use of IVIG in combination with other immunotherapies was related to better outcome (P = 0.041) and both two patients who received Tocilizumab survived. This is the first Chinese case series about ANE associated with COVID-19. Elevated serum and CSF interlukin-6 were found in certain cases. The mortality and morbidity rates remained high although prompt immunotherapy could improve the outcomes.

Combination of intravenous immunoglobulin, oral prednisone, and methotrexate for managing scleromyxedema: case report and literature discussion.

The generalized and sclerodermic form of lichen myxedematosus, known as scleromyxedema (SMX), is a chronic mucinosis that manifests cutaneously and has multiple systemic comorbidities. There are few available treatment options and no established therapeutic guidelines. We describe a 48-year-old man who had intravenous immunoglobulins (IVIg), oral corticosteroids, and methotrexate (MTX) for the treatment of SMX, monoclonal gammopathy, and arthritis. Because of its effectiveness and high level of tolerance, IVIg is the most often used first-line therapy for SMX and has been used for an increasing range of skin conditions. In our instance, better control of skin disease and extracutaneous manifestations was made possible by combining IVIg with oral prednisone and MTX. To the best of our knowledge, this is the first instance of SMX treatment that has combined therapeutic approaches with a favorable safety profile.

MRI of fatal course of acute hemorrhagic leukoencephalitis in a child with SARS-CoV-2 omicron BA 2.0 infection.

We present a pediatric case of acute hemorrhagic leukoencephalitis associated with SARS-CoV-2 Omicron BA 2.0 infection. A previously healthy girl presented with ataxia and diplopia three weeks after the COVID-19 confirmation from a nasopharyngeal swab. Acute and symmetrical motor weakness and drowsiness ensued within the following 3days. She then became spastic tetraplegic. MRI revealed multifocal lesions in the cerebral white matter, basal ganglia, and brainstem, with hemorrhagic changes confirmed with T1-hyperintensity and hypointensity on susceptibility-weighted images. Peripheral areas of decreased diffusion, increased blood flow, and rim contrast enhancement were noted in the majority of lesions. She was treated with a combination of intravenous immunoglobulin and methylprednisolone pulse therapy. Neurological deterioration ensued with coma, ataxic respiratory pattern and decerebrate posture. Repeated MRI performed on day 31 revealed progression of abnormalities, hemorrhages and brain herniation. Despite the administration of plasma exchange, she died two months after admission.

Immune Checkpoint Inhibitors Related New Onset Myasthenia Gravis: Case Series (P4-5.028)

<h3>Objective:</h3> Immune checkpoint inhibitors (ICI), such as cytotoxic lymphocyte-associated protein 4 (CTLA-4) and programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) axis are treatment for several malignancies. Myasthenia gravis (MG) is a rare but life-threatening adverse event of ICI. <h3>Background:</h3> With ICI single agent use, 42 cases of new-onset MG are reported in literature, among those, 14 patients developed severe respiratory failure and required intubation whereas 10 patients died. Combination ICI-induced MG was reported in 7 cases, with at least 2 cases complicated by respiratory failure and 1 death. A better outcome was observed in patients who received intravenous immunoglobulin (IVIG) or plasmapheresis (PLEX) as first-line therapy than in those who received steroids alone (95% vs 63% improvement of MG symptoms). <h3>Design/Methods:</h3> Case series and literature review <h3>Results:</h3> <h3>Case 1:</h3> 87-year-old woman with stage IV adenocarcinoma of colon received pembrolizumab. Ten days after second dose she presented with worsening new onset bilateral ptosis (left&gt;right) and dysphagia, seropositive with acetylcholine receptor antibodies. There was no significant improvement after a course of IVIG in combination with high dose steroids. A trial of pyridostigmine could not be completed due to symptomatic bradycardia and hospice care was started thirty-eight days after first dose of pembrolizumab. <h3>Case 2:</h3> 73-year-old man with metastatic melanoma, received 2 doses of combined ipilimumab and nivolumab. Fifteen days after second dose, he presented with worsening dysphagia, dysarthria, fatigable generalized weakness and shortness of breath, seronegative for MG antibodies. Symptoms improved dramatically with IVIG. His course was complicated by rostral brainstem ischemic stroke and discharged to hospice ninety-four days after the first dose of combined ipilimumab and nivolumab <h3>Conclusions:</h3> Evidence is limited and data from a large cohort of patients is needed to recognize and manage this fatal complication. <b>Disclosure:</b> Dr. Habib has nothing to disclose. Dr. Ahmed has nothing to disclose. Dr. Al-Awwad has nothing to disclose. Sarah Sung, MD has nothing to disclose.

Epidemiological Profile and Management of Kawasaki Syndrome at Rabat Children’s Hospital: A retrospective study from Morocco

Kawasaki disease (KD) is a common pediatric vasculitis with a risk of coronary artery aneurysm. In this report, we review some particularities of KD disease, especially coronary involvement, and highlight its aspects during the COVID-19 epidemic which saw the emergence of a syndrome named multisystem inflammatory syndrome in children (MIS-C). Because of its many similarities with KD, MIS-C is often referred to as Kawasaki-like disease (KLD) or pediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS).We report on a retrospective study on the different epidemiological, clinical, and evolutionary aspects of KD and the coronary involvement resulting from this disease before and after the pandemic. The study is based on the echocardiography records of the P4 Department at Rabat Children’s Hospital, from January 2002 to December 2021. A total of 379 patients were diagnosed with KD during that period. This includes 47 cases that were reported during the first year of the COVID-19 epidemic in Morocco (March 2020). Echocardiography results for our series show that cardiac complications wererelatively more frequent among KD patients during the COVID-19 period, perhaps because they were relatively older (67 months on average) than classic KD patients (37 months on average). However, all patients had a favorable outcome after treatment with a combination of intravenous immunoglobulin (IVIG) and aspirin. The few patients who did not respond to standard treatment received corticosteroids, and no mortality occurred. We conclude that as far as cardiac complications,KD, KLD, and MIS-C are the same core disease that is triggered under different conditions for different age groups.The emergence of the Sars-Cov-2 virus changed the epidemiologic profile of KD but not its treatment. Insights from this study would help in the decision to initiate targeted immunotherapy quickly and reduce the risk factors associated with KD.

Safety and efficacy of pharmacological approaches available for multisystem inflammatory syndrome in children (MIS-C): a systematic review.

To describe the existing pharmacological managements for Multisystem Inflammatory Syndrome in Children (MIS-C) in a systematic way, to identify the available pharmacological managements in MIS-C, evaluate its safety and efficacy and identify the best treatment procedures for practice recommendation. A systematic search using six databases was conducted on August 18, 2021, updated in January 26th 2023. Terminologies that were used in this search are children, MIS-C/PIMS and SARS-CoV-2. A PRISMA flow diagram was used to report the study selection process. Quality analysis was done based on NOS and GRADE tools. Data synthesis was conducted by extracting the information on drugs used, efficacy and side effects. From the 32 articles included, a total of 2331 children with MIS-C were studied. The main pharmacological approaches were immunomodulatory therapy, i.e., intravenous immunoglobulin (IVIG) (77.3%), steroids (60.5%), and a combination of IVIG and steroids (41.3%). IVIG and steroids were found to be potentially effective and safe treatments for MIS-C. Combination of IVIG and steroids was found favorable in severe cases with higher recovery rate. Refractory treatments include second dose of initial treatment and biological response modifier drugs like anakinra, tocilizumab, infliximab. A small number of studies investigating supportive treatment consisted of vasoactive, inotropic and anticoagulation. The mortality rate was 1.28% and only three studies reported side effects from the treatment. Evidence of outcome from GRADE were mostly at moderate, low and very low levels. This review provides preliminary evidence to support the current standard treatment practices in managing MIS-C pharmacologically. However, comprehensive investigation is required using clinical trials to provide stronger outcome evidence.

Hemoperfusion and intravenous immunoglobulins for refractory gastrointestinal involvement in pediatric Henoch-Schönlein purpura: a single-center retrospective cohort study

BackgroundHenoch-Schönlein purpura (HSP) with refractory gastrointestinal (GI) symptoms is always difficult to handle because of its resistance to supportive therapies and glucocorticoid. This study aimed to evaluate the efficacy of hemoperfusion (HP) and intravenous immunoglobulins (IVIG) therapies in this population.MethodsSixty-four HSP patients with refractory GI involvement (R-GI group) and 64 cases with mild GI symptoms (control group) were retrospectively analyzed in our center from March 2016 to October 2019. In R-GI group, 42 cases (subgroup A) were treated with IVIG and steroid, 13 cases (subgroup B) used HP and steroid, 9 cases (subgroup C) executed a combination of IVIG, HP and steroid. Demographic characteristics, clinical features, laboratory indexes and treatment outcomes were recorded. t-test, One-way ANOVA, Mann-Whitney U test, and multivariate logistic regression were used in comparing differences among subgroups and predicting independent risk factors.ResultsCompared with the control group, R-GI cases experienced higher risk of renal involvement (P = 0.000), more steroid exposure (P = 0.000), six times expenses (P = 0.000) and 2.3 times length of hospitalization (P = 0.000). The independent risk factors of R-GI group were elevated neutrophils (OR 1.250 [95% CI 1.130-1.383]) and the percentage of B lymphocytes (OR 1.100 [95% CI 1.026-1.179]) as well as decreased IgG (OR 0.847 [95% CI 0.732-0.98]). In R-GI group, increased age (OR 1.039 [95% CI 1.016-1.062]) and IgM (OR 5.994 [95% CI 1.403-27.611]) were verified to be risk factors of HSP nephritis. All three subgroups could alleviate the symptoms effectively. Compared with those in subgroup A, patients in subgroup B were elder (P = 0.004), had less relapse (P = 0.002), steroid exposure (P = 0.033) and expenses (P = 0.031), more significant decrease of WBC (P = 0.026) after treatment.ConclusionThe HSP with refractory GI involvement had much higher risk of medical burden and renal involvement. Both IVIG and HP therapies could ameliorate refractory GI symptoms efficiently. HP therapy tended to reduce the relapse, costs and steroid exposure in its audiences who were cooperated and with stable hemodynamics, while IVIG had better use in younger children.

A retrospective comparative analysis of factors affecting the decision and outcome of initial intravenous immunoglobulin alone or intravenous immunoglobulin plus methylprednisolone use in children with the multisystem inflammatory syndrome

BackgroundFor children with the multisystem inflammatory syndrome(MIS-C), intravenous immunoglobulins (IVIG) with or without methylprednisolone are the most effective treatment. In this study, IVIG combined with methylprednisolone was compared to IVIG used alone in children with MIS-C.MethodsThis retrospective cohort study was carried out between April 1, 2020, and November 1, 2021. This study covered all children with MIS-C. According to whether they received IVIG alone or IVIG with methylprednisolone as an initial treatment for MIS-C, the patients were split into two groups. The IVIG dosage for the patients in group I was 2 gr/kg, whereas the IVIG dosage for the patients in group II was 2 gr/kg + 2 mg/kg/day of methylprednisolone. These two groups were contrasted in terms of the frequency of fever, length of hospital stay, and admission to the pediatric intensive care unit.ResultsThe study comprised 91 patients who were diagnosed with MIS-C and were under the age of 18. 42 (46.2%) of these patients were in the IVIG alone group (group I), and 49 (53.8%) were in the IVIG + methylprednisolone group (group II). Patients in group II had a severe MIS-C ratio of 36.7%, which was substantially greater than the rate of severe MIS-C patients in group I (9.5%) (p 0.01). When compared to group I (9.5%), the rate of hypotension was considerably higher in group II (30.6%) (p = 0.014). Additionally, patients in group II had considerably higher mean serum levels of C-reactive protein. The incidence of fever recurrence was 26.5% in group II and 33.3% in group I, however the difference was not statistically significant (p > 0.05).ConclusionsThe choice of treatment for patients with MIS-C should be based on an individual evaluation. In MIS-C children with hypotension and/or with an indication for a pediatric intensive care unit, a combination of IVIG and methylprednisolone may be administered. For the treatment modalities of children with MIS-C, however, randomized double-blind studies are necessary.

First-line immunotherapy of neuronal surface antibody-mediated autoimmune encephalitis: Assessment of therapeutic effectiveness and cost-efficiency

ObjectiveTo evaluate the therapeutic effectiveness and cost-efficiency of first-line immunotherapies on neuronal surface antibody-mediated autoimmune encephalitis (AE) based on a real-world observational study in China. MethodsOur study retrospectively collected the clinical and paraclinical data of patients with definite neuronal surface antibody-mediated AE between July 2014 and July 2020. Regular follow-up was performed after administering standard regimens of first-line immunotherapies, including intravenous methylprednisolone (IVMP) and / or intravenous immunoglobulin (IVIG). Therapeutic effectiveness was reflected by modified Rankin Scale scores. The health resource utilization and direct medical costs were extracted to analyze the cost-efficiency. ResultsAmong the 78 eligible patients, 48 (61.5%) were males with a median age of 40 years. More than half (56, 71.8%) were treated with combination therapy, with the rest receiving IVMP and IVIG monotherapy (both of 11, 14.1%). Related objective variables, i.e., sex, onset age, disease course, onset symptoms, antibody types, abnormal paraclinical results, disease severity, and the health insurance, showed insignificant differences on the selection of therapy. Each therapy showed similar short-term (4-week) and long-term (1-year) therapeutic effects. Yet the single or combination of IVIG had a slightly better effectiveness but higher cost than the monotherapy of IVMP. ConclusionThe combination of IVMP and IVIG was used more frequently than either alone, which may be associated with neurologist's personal experience and patient's wishes. Though with similar therapeutic effectiveness, the use of IVMP alone might be a better choice with a better cost-efficiency.

Intravenous Immunoglobulin is Associated with Lower Rates of Reinfection in Solid Organ Recipients with Infection and Secondary Antibody Deficiency: A Multicenter Randomized Clinical Trial

<h3>Purpose</h3> In a multicenter randomized clinical trial we evaluated the safety and efficacy of an intravenous immunoglobulin (IVIG) protocol to decrease the rate of reinfection in solid organ recipients with severe infections and secondary antibody deficiency. <h3>Methods</h3> Distribution: Heart 20, Lung 15, Kidney 5, Liver transplantation 4 were randomized. Patients with post transplant severe infections and secondary antibody deficiency (defined as IgG < 600 mg/dL) were included. IVIG protocol: Two doses of 15 grams (interval between doses 7-15 days) followed by another 3 doses of 20 grams (interval between doses 15-30 days) of a 5% IVIG product. 39 patients that completed the protocol were analysed [IVIG in combination with conventional antimicrobial therapy (n=21) versus conventional antimicrobial therapy alone (n=18)]. Specific antibodies were tested at inclusion in the clinical trial (V1) and 30-45 days after last IVIG dose (last-visit, V7) in a subgroup of patients to assess the kinetics of humoral immunity reconstitution. <h3>Results</h3> The primary outcome measure (rate of reinfection) was significantly lower in patients randomized to receive IVIG as compared with patients receiving only conventional antimicrobial therapy (28.6 vs 66.7%, chi-square test, p=0.017). Mean number of reinfections tended to be lower in IVIG group (0.47, interval 1-3, versus 0.89, interval 1-4, Mann-Whitney test, p=0.056). IVIG recipients tended to have lower IgG levels in V1 but disclosed significantly higher IgG concentrations at distinct visits during follow-up. Significantly higher levels of specific IgG anti-cytomegalovirus, IgG anti-clostridium difficile toxins A and B and IgG1 anti-tetanus toxoid antibodies was demonstrated at V7 in patients who received IVIG as compared with patient that were treated with antimicrobial therapy alone. A significant decrease of serum IL6 and BAFF levels (V1 versus V7) was demostrated in IVIG treated patients. IVIG infusions were well tolerated. <h3>Conclusion</h3> In a multicenter randomized clinical trial we have demonstrated that IVIG is associated with a lower rate of reinfection in solid organ transplantation with severe infection and secondary IgG hypogammaglobulinemia.